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					IJPD, 2004; Vol I No.3




                                                       Indian Journal for

                             the Practising Doctor

Executive Editor                                              Editor-in-Chief
Bashir Gaash, MD, PhD, DCH                Muzaffar Ahmad,   MD, FAMS,FACP




                   Medical Quiz: Diagnostic dilemma
                   Pregnancy: Diabetes in Pregnancy
                    Endemic Disease: Typhoid Fever
                           Zoonosis : Brucellosis
            Childhood Infections: Acute Respiratory Infection
           Primary Health Care: Burns in the Developing World
               Student’s page: Immunity – An Introduction
              Frequently used drugs: The Forgotten Penicillin
                   Nutrition: Food & Cancer Protection
            Parent/patient education: Asthma, Down’s Syndrome
         Haematology : Adverse Reactions to Blood transfusion
                          Chest Medicine: COPD
                      Genetics: Down’s Syndrome
  Original Research: Immunization Status of Infants in A remote District
       A leaf from the history of Medicine: Discovery of Penicillin
           Special supplement: Drug Use in Renal Impairment




                    Vol I No. 3 (November 2004)
Published from: REGIONAL INSTITUTE OF HEALTH & FAMILY WELFARE, KASHMIR




                                                                                1
IJPD, 2004; Vol I No.3




                      INDIAN JOURNAL OF
                    THE PRACTISING DOCTOR
                                     Volume I; No. 3
                                     November 2004



               (A bimonthly journal for doctors working in
                              peripheries)




         Chief Editor:                                            Executive Editor:
      Dr Muzaffar Ahmad, MD, FACP, FAMS, FIMSA         Dr Bashir Gaash, MD, PhD, DCH.
          Director Health Services, Kashmir.           Principal, RIHFW, Kashmir




                                  Editorial Assistance:
                   Dr Rehana Kausar, MD, Dipl H&FW Dr Farooq Fazilli, MD
                         Dr Manzoor Kadri, MBBS, PG Dipl HIV/AIDS
                                Dr Rubina Shaheen, MD
                            Dr Rohini Bhan, MBBS, PG Dipl RCH
                               Dr Shabnam Bashir, MBBS




                                    Managing Editor:
                                Neelam Bashir, BCA, G.Tech




             Editorial correspondence: P. O. Box: 673 (GPO), Srinagar, Kmr.

                    [Phones: 951954-255042;      Email: gaashb-10@yahoo.co.in]
                           0194-2422987




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IJPD, 2004; Vol I No.3




Contents:
                                    Indian Journal for the Practising Doctor




    •   Medical Quiz III
    •   Ascaris Lumbricoides, 7 (Bashir Gaash)
    •   Lab diagnosis of A. lumbricoides, 12 (WHO)
    •   Typhoid Fever, 14 (M. Yusuf Rathor)
    •   Adverse Reactions to Transfusion, 21 (S M Kadri)
    •   Patient education: Asthma, 30; Down’s Syndrome, 75.
    •   Airborne Infections, 36 (Farooq Fazilli)
    •   Diabetes in Pregnancy, 43 (Rehana Kausar)
    •   Food & Cancer Prevention, 51 (Shabnam Bashir)
    •   Brucellosis, 60 (Smits & Kadri)
    •   Discovery of Penicilin, 66 (Neelam Bashir)
    •   Penicillin, 69 (Rubina Shaheen)
    •   Down’s Syndrome, 73 (B A Qadiri)
    •   Burns in the Developing World, 78.
    •   COPD, 83, (Rohini Bhan)
    •   Immunity – An Introduction, 86 (Ayaz Amin)
    •   Immunization Status of Infants in a Remote District, 88.
                         (Bashir Gaash, Rohini Bhan, Shabnam Bashir)
    •   Special Supplement: Drug use in Renal Impairment (WHO guidelines)




Editorial



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IJPD, 2004; Vol I No.3


          The first two issues of the IJPD met an expectedly warm response. Both the doctors
practicing in the field as well as students, both, have enthusiastically welcomed the issue. This
has encouraged all those involved in the publication of the journal.
          The journal, as promised, carries articles of direct relevance to the practising doctor.
Ascariasis is one of the commonest infestations of the world, and contrary to the popular
belief that it is a mild condition which could be ignored, research shows that roundworm
infestation can prove disastrous, and even a single wandering worm could kill the victim. It
implies that ascariasis should be treated whenever countered.
          We know that water and food form the leading vehicle of infection in the developing
world. Andt providing plenty of safe water, requiring huge monetary inputs, will continue to
be a tall order for some time to come. Accordingly water- & foodborne infections will
continue to haunt our place for a long time. We have included a guest article on typhoid fever
from one of our colleagues currently working in Malaysia. This paper had been presented in
an international seminar on gastrointestinal infections.
          Diabetes in pregnancy is a serious disorder which affects not only the mother but
also the baby and continues its adversity throughout life. With the advent of newer
antibiotics, Penicillin has become a forgotten antibiotic. However, we must remember that
this cheap antibiotic has a place in the treatment which other antibiotics and
chemotherapeutic agents may not be able to fill
          Food provides nutrients, that is a universally known fact. But food can prevent such
serious diseases as cancer is not known to all. For the benefit of doctors working in the field,
we have included an article on the role of non-nutrients on health. This article has been
condensed from an ICMR Bulletin.
          Winter in northern India, particularly Kashmir ,is accompanied by a sharp increase
in burn cases. We have included an article on Burn care which has been condensed from the
British Medical Journal. Some of the articles on common medical and surgical conditions are
carried for the health profession. The one on Chronic Obstructive Pulmonary Disease is
included for the benefit of various health functionaries.
          Brucellosis is a pressing problem for all countries which have adopted animal and
sheep husbandry in a big way. Netherlands is one such country which has brucellosis and at
the same time has a vast body of research-oriented knowledge on such zoonotic diseases. A
guest article on Brucellosis from that country has been included for the benefit of the
practitioner who finds it difficult to diagnose the disease.
          Our own experience shows that doctors generally find it difficult to devise material
for health education. Therefore, while writing articles for the medical profession, we have
included special health education material which the practitioner can use for health
instruction of their patients and family members. In this issue we have carried articles on
asthma, COPD and Mongolism.
          An original paper based on the research of the faculty members of the Institute is put
for its direct relevance to the practitioner working in the field. The current issue carries an
article titled ‘Immunization Status of Infants in a Remote District’ which has already been
published elsewhere.
          A special supplement on the Use of drugs in Renal Impairment has been included
for the benefit of the practising doctor.

November 2004.

                                                            Bashir Gaash
                                                           (Executive Editor)




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IJPD, 2004; Vol I No.3



Contributors:
Henk L Smits, PhD.
Molecular Biologist at the Department of KIT Biomedical Research, Royal Tropical
Institute, Amsterdam, The Netherlands.

M Yusuf Rathor, MD. Associate Professor, General Medicine, International Islamic
University of Malayasia, Malayasia.

Rubina Shaheen: Faculty member, Regional Institute of Health, Kashmir, is a
postgraduate in Microbiology. She taught at the SKIMS before her new appointment.

Rehana Kausar: Faculty Member, Regional Institute of Health, Kashmir, is a
postgraduate from SK Institute of Medical Sciences, Soura, Srinagar. Before joining
RIHFW she has had a stint in the Department of Community Medicine, SK Institute of
Medical Sciences, Srinagar.

Farooq Fazilli: Faculty Member, Regional Institute of Health, Kashmir, is a
postgraduate from the SK Institute of Medical Sciences, Soura, Srinagar. Before
joining the RIHFW, the doctor worked in the Department of Community Medicine, SK
Institute of Medical Sciences, Srinagar.

B A Qadri is a Kashmir-born paediatrician currently working in Kuwait. He has
graduated from the Government Medical College, Srinagar, and got his Fellowship in
Genetics from Ohio.

Ayaz Amin is an Indonesian immunologist currently working in Michigan, USA.

Manzoor A Kadri: Trainer at the Regional Institute of Health, Kashmir, was a teacher
at the Government Medical College, Srinagar (Department of Microbiology) before
joining us.

Rohini Bhan is a trainer at the Regional Institute of Health, Kashmir.

Shabnam Bashir is a medical graduate from the Government Medical College,
Srinagar.

Bashir Gaash; an International Fellow in Tropical Diseases, is a postgraduate in
Social & Preventive Medicine and Health Administration, and currently is the
Principal, Regional Institute of Health & Family Welfare, Kashmir.

Muzaffar Ahmad; MD in general Medicine, has a Fellowship in Emergency Medicine
from USA, and currently is the Director Health Services, Kashmir.




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IJPD, 2004; Vol I No.3




Diagnostic dilemma
Medical Quiz: III



        A mother in England brought her daughter for the 2nd time in the last 24 hours
to hospital, with abdominal pain and frequent passing of a soft stool in the last 2 days.
The 4-year old was fit and well before this illness. She was sent home after she was
assessed at hospital; she was not dehydrated and did not look septic. Two days later
she presented with similar symptoms: headache, lethargy, more abdominal pain,
malaise and a pain in her neck. Her mother said her temperature is going up every
day, and today reached 40C for the first time. She also developed erythematous
papular lesions, which measure about 2 mm in diameter. All members of her family
are healthy and returned from a holiday in Kashmir 6 days ago. There is a 2cm
splenomegaly, with no lymphadenopathy. Her heart rate is 77 beats/min and her
respiratory rate 20/min.

Her lab profile showed:
       Na                             130 mmol/l
       K                              3.9 mmol/l
       Urea                           8.3 mmol/l
       Creatinine                     76 mmol/l
       ALT                            55 iu/l
       Alkaline phosphatase           290 iu/l
       Bilirubin                      35 umol/l
       Hb                             11.3 g/dl
       TLC                            2.2 x 109/l
                      DLC:N           22%
                          L           66%
       Platelets                      90 x 109/l
       Midstream urine                Negative
       Stool                          Negative
       Abdominal ultrasound           Large spleen only

Questions:

        What is the most likely diagnosis?
        Which 2 other tests are required to support the diagnosis?
        What should the treatment be in this case?
                                                          (Answers on page 75)




Ascaris lumbricoides                                               Bashir Gaash


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IJPD, 2004; Vol I No.3


______________________________                             till they reach the trachea, epiglottis,
                                                           and pharynx, and then are swallowed.
        Ascariasis is a very common                        The larvae grow to 2mm and
infestation in Kashmir. Hardly anyone                      physiologically adapt to survive in the
escapes it. However, doctors and                           intestine, where the worms mature and
parents tend to take the infection                         mate, and produce eggs which are
lightly. This essay is to underline the                    passed in stool. The number of eggs
need for prompt treatment of even a                        produced and passed daily can be as
single worm. Giving anthelminthics at                      high as 2 lakh per day. The entire
periodic intervals to high-risk children                   developmental process from ingestion
with heavy burden is not irrational.                       of eggs to the subsequent passage of
_______________________________                            eggs takes 8-12 weeks. During her life
                                                           span, which may extend to 1-2 years,
        Ascariasis is an extremely                         the adult female can pass some 6 crore
common infection; the number of                            or more eggs!
people infected globally with       A.
                    nd
lumbricoides is 2 only to those                            Fertilized egg          Unfertilized egg
infected with the pinworm (Enterobius                      Broadly oval            More oval
                                                           Size: 75 μm long x 50   Size: 90μm x 45μm
vermicularis). Children have the
                                                           μm wide                 long
highest prevalence, which varies with                      Thick     mammilated    Minimally
the socioeconomic status. Ascaris was                      coat, usually bile      mammilated layer
well known in the ancient times;                           stained a golden
Romans called it lumbricus teres. The                      brown.
infestation is more prevalent in moist,
warm climates. In most tropical                                    The female lays eggs in the
countries, the average infection rates                     duodenum which are evacuated with
range up to 45%. Prevalence in                             faeces. Both unfertilized and fertilized
Nigeria, the most populous African                         eggs are passed in stool. Often only
country Even North America is not                          female worms are recovered from the
free; foci of high prevalence among                        intestine. Fertilized eggs passed in
young children still persist in the                        stool become infective within 2 weeks
southeastern United States.                                in warm, moist soil, where they can
                                                           remain viable for months or even
Life cycle                                                 years. The total absence of fertilized
        Every person in the developing                     eggs means that only female worms
world has seen the adult worm and can                      are present in the intestine.
instantly recognize it. Infection is
acquired through ingestion of the                          Clinical features
embryonated eggs from contaminated                                 Infection with A. lumbricoides
soil. On ingestion the eggs hatch in the                   continues to be a major public health
stomach and duodenum, where larvae                         problem in developing countries.
actively penetrate the intestinal wall.                    Though behavioural aspects are behind
Via the hepatic portal circulation, they                   the faeco-oral transmission, there is
are carried to the right heart, and                        evidence       of     an       individual
thence into the pulmonary circulation                      predisposition to infection. In addition,
where they are filtered out by the                         genetic factors account for 30%-50%
capillaries. After about 10 days of                        of the variation in worm burden.
development in lungs, the larvae break
into the alveoli, migrate via the bronchi
Usual time to infective   2-3 weeks in soil; second stage larva in egg



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IJPD, 2004; Vol I No.3


stage
Mode of infection        Ingestion of infective egg
Development       &      Obligatory larval migration through liver and lungs; adults in small intestine.
location in
Human host
Prepatent period         2 months
Normal life span         Up to 1 year or slightly longer
Diagnosis by usual       Bile-stained, mammilated, thick-shelled eggs (45-75x35-50μm) in 1-cell stage in
means                    feces;
                         Infertile eggs (85-95x43-47 μm) have thinner shells & distorted mammilations;
                         Mature or immature adults may be found in feces or may spontaneously migrate out
                         of the anus, mouth, or nares.
Diagnostic problems      Fertile eggs may lose outer mammillated layer (decorticate egs);
                         Infertile eggs may be difficult to recognize; also will not float in usual solution of zinc
                         sulfate (sp gr 1.18) used for concentration.
Clinical notes           Owing to potential migration of adult worms, all infections should be treated.
                         Pulmonary symptoms may be present during larval migration (prior to egg recovery in
                         stool).
                         Eosinophils present but not impressive.

        Ascariasis is an important and                      generally produces no symptoms,
common cause of childhood morbidity;                        pneumonitis occurs with very large
it may even cause mortality from                            number of larvae. Subsequent larval
intestinal obstruction or extra-intestinal                  migrations lead to intense tissue
complications.        Infestation       is                  reactions even with a smaller number
particularly heavy in young children                        of larvae. Pronounced tissue reactions
(probably because of their pica) and                        around the larvae in liver and lungs,
symptoms severe. In older children &                        with infiltration of eosinophils,
adults, worm load is less and infection                     macrophages and epitheloid cells leads
mild or subclinical. In such cases,                         to ascaris pneumonitis, which            is
passage of worm or ova may reveal                           accompanied by allergic dyspnoea, dry
infestation.                                                or productive cough, wheeze, fever,
        Pathogenesis is attributed to                       transient eosinophilia, and an x-ray
         i) the host immune response                        suggestive of viral pneumonia. The
         ii) effects of larval migration                    transient lung infiltrates clear within a
         iii) mechanical effects of the adult               few     weeks.       Sputum       contains
              worms and                                     eosinophils, Charcot-Leyden crystals,
         iv) nutritional deficiencies caused
                                                            and sometimes may even contain
              by the presence of adult
              worms.
                                                            larvae. If needed gastric washings are
                                                            more helpful in detection of larvae.
                                                            Asthma and urticaria may continue
The first symptoms produced are
                                                            during the intestinal phase of
respiratory, due to passage of larvae
                                                            ascariasis.
through the lungs leading to benign
pneumonitis - Loeffler’s syndrome.
                                                            Allergic manifestations (asthma, hives,
Main symptoms in children are
                                                            peripheral eosinophilia) begin with
abdominal pain, loss of appetite and
                                                            the 10-day pulmonary phase but
failure to thrive.
                                                            continue into the intestinal phase.
Loeffler’s pneumonia: Initial passage
                                                            Intestinal manifestations: The main
of larva through liver and lung
                                                            symptoms in children are abdominal
                                                            pain, anorexia and failure to thrive.



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IJPD, 2004; Vol I No.3


Heavy infestation may lead to                respiratory difficulty (stridor, cyanosis,
protrusion of abdomen.                       dyspnoea). It has even caused cardiac
Eosinophilic gastroentritis signifies        arrest. Worms have come out of the
the inflammatory disease characterized       nose or lachrymal duct. They may
by eosinophilic infiltration of the          enter the Eustachian tube and lead to
gastrointestinal tract accompanied by        perforation of the tympanic membrane,
varying abdominal symptoms and               and exit through the ear. Worms have
usually by peripheral eosinophilia.          strayed into paranasal sinuses.
Nutritional complications: In the            3) Migration into lower intestine is the
under-five child heavy burden of             most frequent and most important
worms may lead to severe nutritional         complication. A tangled mass of
impairment. Studies have shown               worms moves from the duodenum to
increased loss of faecal fat and             lodge in the ileocaecal valve,
nitrogen and impaired carbohydrate           especially in the under-fives. This
absorption, which correspond to worm         leads to vomiting, abdominal pain and
load. Lactose malabsorption is               distension, constipation, and partial or
common.The long-term effect of               total obstruction on plain x-ray
impaired       nutrition    is    growth     abdomen. They may enter the
retardation of growth & development.         appendix or Meckel’s diverticulum and
Educational         achievement:      An     lead to obstruction, symptoms & signs
association       between      helminthic    of appendicitis, sometimes with
infection and educational achievement        perforation         &          peritonitis.
has       long      been      recognized.
Antihelminthic treatment has resulted        Intestinal obstruction is the single
in improvement in test scores, learning      most       common        complication
ability, concentration, & eye-hand           accounting for 38%-88% of all
coordination in the affected children.       complications. The complication is
Ascariasis has been shown to be              commoner in young children. Case
associated with lower test scoes in          fatality ranges widely, and may
language, social-, gross motor-, and         exceed 8%.
fine       motor-skills.     Malnutrition
associated with intestinal helminthiasis     4) Pancreatic duct is easily accessed,
is an important contributory factor for      leading to pancreatitis with severe,
increased prevalence of developmental        acute abdominal pain, tenderness, and
disabilities in the developing world.        raised    serum       amylase     levels.
 Wandering worm: Ascaris has a               Pancreatic strictures may occur.
propensity to migrate from its usual         5) Worms can enter the bile duct, the
habitat, duodenum, to other areas.           gall bladder and the intrahepatic biliary
Worm migration is stimulated by              tree. They may cause biliary lithiasis,
fever, general anesthesia, other             acute cholecystitis or acute cholangitis.
abnormal conditions, or the need of the      They may reach the liver parenchyma,
female worm to copulate or                   and cause hepatic ascariasis. They may
postmortem state of the worm.                carry various pathogens on their
1) They may enter the stomach and            surface which may prove disastrous in
lead to vomting or traumatic bleeding.       immuno-compromised host. Liver
Worms may enter a nasogastric tube           abscesses may perforate into the
and                 block              it.   pleural cavity, the lungs and the
2) Worms may ascend the esophagus            pericardium. In one case, 60 adult
and reach epiglottis and thence to           worms were surgically removed from
upper respiratory tract leading to           the liver of a patient suffering from


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IJPD, 2004; Vol I No.3


acute obstructive cholangitis. In             Diagnosis:
endemic areas, ascariasis should be                  In the larval migration phase,
considered in any child with                  diagnosis can be made from detection
hepatobiliary symptoms.                       of larvae in sputum, or more
6) The worm may move to the                   commonly in gastric washings. The
peritoneal cavity through intestinal          typical Loeffler’s syndrome is more
ulcerations. Rarely the worm may              likely to be seen in areas where
itself perforate the intestine. The           transmission is seasonal.
female worm lays eggs which produce
a granulomatous inflammation, and                    In    the   intestinal  phase,
itself dies leading to a large abscess.       diagnosis is made by finding the eggs
Clinically it presents as a tumourlike        or adult worms in the stool. The eggs
mass anywhere in the abdomen.                 are most easily seen on a direct wet
Peritonitis is often fatal since there is     smear or a wet preparation of the
secondary bacterial infection. Post-          concentration sediment.
surgery they may wander into the
peritoneal cavity or come out of the          Burden of ascariasis in developing countries
sutures of the skin wound.                    (1990s)
7) Unusual migrations: Worms may              Population:       2500 million
                                              People infected with ascaris: 1000 million
enter any tube or opening. They have          Daily faecal output with ascaris eggs:
entered nasogastric tubes, T-tubes,                                      2.00 lakh tons
fistulas between intestine & the ureter,      (Average daily output of stool/person, 200g)
sinus tracts in the gluteal region, fistula   Daily discharge of eggs: 2 x 1014 eggs
of ulcerated inguinal hernia, etc. They       (Average 1000 ascaris eggs per gram of stool)
                                              DALYs lost to ascaris:     10.5 million
may pass out from the mouth, nose,
ear, or even eye. They have been found        Adapted from: Coombs I, Crompton, DWT. How much
                                              human helminthiasis is there in the world? J Parasitol
to pass into the placenta and even            85:397-403, 1999
recovered from the intestine of he
delivered baby.                                       Intestinal disease can often be
8) Postmortem migrations: After its           diagnosed from radiographic studies of
death the worm can go to any place it         the gastrointestinal tract, where the
could visit during life. However,             worm displaces the barium and looks
absence of inflammatory changes in            dark. This may be particularly obvious
the visited organ exclude premortem           when two worms are lying parallel
migration.                                    (trolley car lines).

        Inside the intestine, adult                   Specific     symptoms        may
worms when scant usually cause no             indicate the sites involved as bowel
difficulty. However, because of the           obstruction, biliary or pancreatic duct
tendency of the adult worm to migrate,        block, appendicitis, or peritonitis.
even a single worm can cause serious
sequelae.. Wandering worms may                Treatment:
move to any organ of the                       Newer anthelminthics, unlike the
gastrointestinal system (including            older remedies, do not require pre or
liver, biliary tract, gall bladder,           post-treatment purging or fasting. In
pancreatic duct, appendix) or to the          the USA, mebendazole is considered
peritoneal cavity. They may come out          the drug of choice for both children
of the anus, mouth, nose. Unexpected          and adults; other good alternatives
body sites as kidney or pleural cavity        pyrantel pamoate and albendazole are
have been involved.                           not used as commonly. These drugs are


                                                                                                10
IJPD, 2004; Vol I No.3


effective in eliminating the adult worm     that even with proper pretreatment of
but there is no conclusive evidence that    night soil, ascaris eggs retain viability
they are effective in the larval            and infectivity than otrher helminthic
migration phase. For other body sites,      eggs. It has been reorted that upto 90%
surgery is required.                        of ascaris eggs survived sludge
        Worms are easily eliminated         treatment for upto 30 weeks and were
from the intestine, and prognosis is        able to develop motile larvae.
excellent. On the contrary, the
prognosis may be extremely poor in
case of massive larval migration
through the lungs. Prognosis may be
unfavourable if there is perforation or
need for surgery.

        Some        individuals       are
susceptible to heavy infections while
others are not. This too has been seen
that deworming has a greater impact
on the intensity of infection than on its
prevalence       and       that     mass
chemotherapy is likely to be a more
effective    means      of    controlling
morbidity than is selective treatment of           Fertilized egg of A. lumbricoides
heavily infected individuals only.
Targetted approaches (child targeted
treatment) is also as effective and both
these approaches are more cost
effective than the selective approach.

Prevention & Control:
         The ultimate transmission of
ascaris depends on contamination of
the soil by the egg-laden faeces.
Therefore, provision of proper sanitary
facilities, coupled with hygiene                   Unfertilized egg of A. lumbricoides
education, is the best means of
prevention and control. There is no
practical means of killing the eggs in
clay soil under favourable conditions
of warmth and moisture.                     ¤        Both the eggs are still at the
                                            unicellular stage. Eggs are normally at
        In endemic areas where re-
                                            this stage when passed in the stool.
infection rates are high, mass or           Complete development of the larva
targeted treatment plans have been          requires 18 days under favorable
quite successful.                           conditions.

       Human faeces should not be
used for fertilizing crops, and no
vegetable or fruit from such a field
should be eaten raw. It must be noted


                                                                                       11
IJPD, 2004; Vol I No.3


Laboratory diagnosis of ascariasis*

         Helminthic eggs are often easier to find and identify because of their size and their
distinctive morphological features. While direct smears of fresh faeces will often demonstrate
helminth eggs, it is usually more efficient for laboratories to do a simple concentration to
avoid overlooking parasites that may be present in very small numbers.

Direct faecal smears – saline and iodine wet mount preparations
Procedure
1). With a wax pencil or other marker, write the patient’s name or identification number and
the date at the left hand side.
2). Place a drop of saline in the centre of the left half of the slide and place a drop of iodine
solution in the centre of the right half of the slide.

Materials & reagents
       Wooden applicator sticks or matches
       Microscope slides (75x25 mm)
       Coverslips
       Pens or markers for indelible marking
       Dropping bottles containing: Isotonic saline solution (0.85%; 8.5g/l)
       Lugol’s iodine (1% solution)

3). With an applicator stick or match, pick up a small portion of faeces (approximately 2 mg
which is about the size of a match head) and add it to the drop of saline: add a similar portion
to the drop of iodine. Mix the faeces with the drops to form suspensions.
4). Cover each drop with a cover slip by holding the coverslip at an angle, touching the edge
of the drop, and gently lowering the coverslip onto the slide so that air bubbles are not
produced.
5). Examine the preparation with the 10X objective in a systematic manner (either up and
down or laterally) so that the entire coverslip area is observed. When organisms are seen,
switch to higher magnification top see the more detailed morphology of the object in
question. [* Based on the WHO recommendations]
_______________________________




.



                                                                                              12
IJPD, 2004; Vol I No.3


Further reading


Asaulo SO, Holland CV, Jegede JO, Fraser NS. The prevalence and intensity of soil-transmitted
heminthiases in rural communities in Southern Nigeria. Ann Trop Med Parasit, 1992; 86:279-87

Beaver PC, Jung RC, Cupp EW. Clinical Parasitology; Philadelphia: Lea & Febiger, 1984.

Carrera E, Nesheim MC, Crompton DWT. Lactose maldigestion in Ascaris-infected preschool children.
Am J Clin Nutr, 1984; 39: 255-64

Crompton DWT. Ascariasis & childhood malnutrition. Trans Roy Soc Trop Med Hyg, 1992; 86:577-79

Faraj JH. Correspondence. Upper airway obstruction by ascaris worm. Can J anesth, 1993;40:471.

Hakami M, Kharrad M, Mosavy SH. Escape of ascarides through herniorapphy wounds.                  Am J
Proctol;1976: 27:47-8

Holland CV, Asaulo SO. Ascariasis in Nigeria. Parasit Today 1990; 6:143-7

Khuroo MS, Zargar SA. Biliary ascariasis: a common cause of biliary and pancreatic disease in an
endemic area. Gastroenterology 1985;

Khuroo MS, Zargar SA, Mahajan R. Hepatobiliary and pancreatic ascariasis in India. Lancet, 1990:
335:1503-6

Mimpriss TJ. Correspondence. Respiratory obstruction due to roundworm. Br J Anesthes, 1972; 44:413.

Moyes DG, Rogers MA. Respiratory obstruction due to a roundworm. Case Report. Br J Anaethesia;
1971:43:1055

Naravane A, Lindo JF, Williams LA, Gardener MT. Ascaris lumbricoides in the paranasal sinuses of a
Jamaican adult. Trans Roy Soc Trop Med Hyg. 1997; 91:37

Ortega R. Correspondence. An unusual cause of nasogastric tube obstruction. 1992;75:147-8

Shah KN, Desai MP. Ascaris lumbricoides from the right ear. Indian Pediatr. 1969; 6:92-3

Stephenson LS. The contribution of ascaris lumbricoides to malnutrition in children. Semin Respir Infect.
1980;81:221-33

Stephenson LS, Crompton DWT, Latham MC, Schulpen TWJ. Relationship between ascaris infection and
growth of malnourished preschool children in Kenya. Am J Clin Nutr. 1980; 33:1165-72

Tripathy K, Gonzalez F, Lotero H, Bolenos O. Effects of ascaris infection on human nutrition. Am J Trop
Med Hyg. 1971; 20:212-18

Tripathy K, Duque E, Bolanos O, Loreto H. Malabsorption syndromes in ascariasis. 1972; 25:1276-81

Villamizar E, Mendez M, Binilla E, Varon H. Ascaris lumbricoides infestation as a cause of intestinal
obstruction in children: experience with 87 cases. J Ped Surgery. 1996;31:201-4

Wilairatana P, Wilairatna S, Charoenlarp P. Gastric ascariasis associated with upper gastrointestinal
bleeding. Southeast Asian J Trop Med Public Health. 1994; 25:401.

WHO. Bench Aids for the Diagnosis of Intestinal Parasites, 1994, World Health Organization


                                                                                                      13
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    Typhoid Fever                                     Age group: In endemic countries,
                                              typhoid is predominantly a disease of
                                              school children and young adults. In an
             (M Yusouf Rathor)                outbreak of 649 cases in Penang
    ____________________________              (Malayasia) in 1987, 52% of cases were
                                              between the ages of 1-24 years. In
        Typhoid fever is an acute,            Indonesia,     3-19-year-age      group
systemic, febrile illness caused by S.        accounted for 91% of typhoid cases.
typhi, S. paratyphi A, S. paratyphi B                 Typhoid & HIV: In endemic
and occasionally S. typhimurium. Many         regions, the rate of clinical typhoid
clinicians prefer to call it enteric fever.   among the 15-35 year age group is
                                              approximately 25 times higher in HIV
        Typhoid is a worldwide health         positive cases than in the HIV –ve
problem, especially in developing             individuals.
countries, which is attributable to poor
sanitation, poor standards of personal            Pathogenesis
hygiene, and frequent contamination of               Human beings are the only
food. Delay in diagnosis, emergence of        reservoir for S. typhi. The infection is
antibiotic-resistant strains, the lack of     transmitted by faecally-contaminated
availability of a safe, effective and cheap   water and food in endemic areas and by
vaccine are contributing factors.             chronic carriers handling food in
                                              developed countries. The bacteria can
        In developed countries, the           survive several months in soil or water.
infection is acquired from abroad or
from chronic carriers who handle food.                Infection is dose-related - size of
In 1989, a large outbreak occurred in a       the inoculum and the type of vehicle in
New      York    hotel    because    of       which the organisms are ingested will
contamination of orange juice. S typhi        influence both the attack rate and the
was isolated from the stool of an             incubation period. A dose of 109
asymptomatic typhoid carrier who              organisms will induce infection in most
handled orange juice.                         cases, whereas a dose of 103 or less
                                              organisms will rarely produce symptoms
    Epidemiology                              in otherwise healthy individuals.

     Incidence: According to the World                S. typhi virulence is complex
Health Organization, globally some 16         requiring several virulence factors for
million cases occur annually resulting in     full expression of pathogenicity. Host
more than 600,000 deaths. More than           factors, e.g. gastric hypoacidity, may
62% of the global cases occur in Asia, of     increase the attack rate as gastric acid
which, 7 million occur annually in South      kills most of the bacilli that have been
East Asia. Other countries with a high        ingested with food or water.
incidence include Central & South
America, Africa and Papua New Guinea.                The two most important sites
                                              normally affected are the Peyer's patches




                                                                                      14
IJPD, 2004; Vol I No.3


in the small intestine and the gall
bladder.                                              Following recovery, 5 % of
                                              patients become long term (chronic)
Clinical Features                             asymptomatic carriers. The likelihood of
       The average incubation period is       becoming a chronic carrier increases
   10-14 days, (a range of 3 – 60 days        with age, especially in women often
   has been reported). The duration of        associated with cholecystitis and
   illness,    on    an     average,     is   gallstones.
   approximately 4 week (may range
   between 4 to 8 weeks).                     Complications
        First week: The disease                       Gastrointestinal    complications
       classically presents with step-        are the commonest – haemorrhage
       ladder fashion rise in temperature     towards the end of the 2nd week, and
       (40 – 41°C) over 4 to 5 days,          intestinal perforation in 3rd week may
       accompanied by headache, vague         occur in 3-5% of patients. Ileal
       abdominal          pain,        and    perforation, with a mortality of about
       constipation.                          40%, is frequently seen in young men.
       Second week: Between the 7th -
       10th day of illness, mild hepato-             Other complications include
       splenomegally occurs in majority       cardiovascular               insufficiency,
       of patients. Relative bradycardia      myocarditis,       meningitis,      hepatic
       may occur and rose-spots may           involvement       (10%),      cholecystitis,
       be seen.                               thrombophelibitis      and      pulmonary
       Third week: The patient will           embolism,         pneumonia, parotitis,
       appear in the "typhoid state"          thyroiditis,       osteitis,       arthritis,
       which is a state of prolonged          osteomylitis, orchitis and nephritis.
       apathy,     toxaemia,     delirium,    Rarer complications include endotoxic
       disorientation     and/or    coma.     shock,      disseminated      intravascular
       Diarrhoea will then become             coagulation,               encephalopathy,
       apparent. If left untreated by this    myocarditis and paralytic ileus.
       time, there is a high risk (5-10%)
       of intestinal haemorrhage and                  Complications are commoner
       perforation.                           with multi-drug resistant typhoid, and
       Patients with multi-drug resistant     frequency of all complications, except
       typhoid fever (MDR-TF) are             relapse, is reduced by prompt antibiotic
       more toxic at admission and have       therapy.
       a higher risk of life-threatening
       complications such as endotoxic        TYPHOID AND CANCER: A study of cancer
       shock, disseminated intravascular      risk in chronic typhoid and paratyphoid carriers
                                              showed an increased incidence of cancer of gall
       coagulation,       encephalopathy,     bladder, pancreas, colorectum, & lung and
       myocarditis and paralytic ileus.       various other neoplasms.

               The        course       of     Diagnosis
    paratyphoid fever tends to be shorter           Typhoid should be considered in
    and milder than typhoid & onset is              any patient with prolonged
    often abrupt with acute entritis.               unexplained fever in endemic


                                                                                           15
IJPD, 2004; Vol I No.3


        areas and in those with a history             hour             (sensitivity>95%,
        of recent travel to endemic area.             Specificity 75%)
        Prolonged fever,       rose spots,             Typhidot-M, that detects IgM
        relative      bradycardia      and            only     (sensitivity    90%    &
        leucopenia       make      typhoid            specificity 93%)
        strongly suggestive. About 25%                 Typhidot rapid (sensitivity 85%
        of patients show leucopenia and               & Specificity 99%) is a rapid 15
        neutropenia.                                  minute immunochromatographic
        Widal test measures titres of                 test to detect IgM.
        serum       agglutinins     against
        somatic (O) and flagellar (H)          Treatment
        antigens which usually begin to
        appear during the 2nd week. In
                                               Time-tested, Traditional Treatment
        the      absence      of     recent
                                                  Chloramphenicol has been the
        immunization, a high titre of
                                                  antimicrobial gold standard for
        antibody to O antigen > 1:640 is
                                                  treatment of typhoid. Clinical
        suggestive but not specific.
                                                  response is apparent usually within
        Polymerase chain reaction (PCR)
                                                  24 to 48 hrs of treatment. Treatment
        can be performed on peripheral
                                                  is started with a dose of 50 – 75
        mononuclear cells. The test is
                                                  mg/kg bodyweight/day and reduced
        more sensitive than blood culture
                                                  to 30 mg/kg per day once the patient
        alone (92% compared with 50-
                                                  is afebrile. The total course takes
        70%) but requires significant
                                                  some 2 weeks.
        technical expertise.
                                                  Ampicillin/ Amoxillin (750 mg 6
        Several new serologic tests have
                                                  hrly) may be used as an alternative.
        been developed to aid in the
                                                  Trimethoprim-Sulphamethoxazole
        diagnosis of typhoid fever.
                                                  (TMP-SMZ),        2 tablets or IV
                                                  equivalent 12 hrly.
           Definitive      diagnosis   of
    typhoid is by isolation of organisms.
        Blood cultures are positive in 70-     Short course therapy
        80% of cases during the 1st week.               Efficacy          of          both
        Stool and urine cultures are usually   fluoroquinolones and third-generation
        positive (45-75%) during the 2nd-      cephalosporins has been evaluated. (cure
        3rd week.                              rates have been shown to be 90-100%).
        Bone marrow aspirate cultures give     Ceftriaxone has been shown to be the
        the best confirmation (85-95%) and     most effective short-term drug and rivals
        are positive even after brief          Chloramphenicol        in    rapidity    of
        antimicrobial treatment.               defervecenc, and at the same time
                                               relapse rate is less. Ciprofloxin is widely
Immuno-chromatographic           test   for    used in doses of 500mg 12 hrly. Relapse
rapid diagnosis of Typhoid                     responds to same antimicrobials as given
                                               earlier.
Various rapid tests have been developed                 Salicylates should be avoided.
for diagnosing typhoid:                        Role of steroids is controversial.
        Typhidot test that detects
        presence of IgM & IgG in one


                                                                                       16
IJPD, 2004; Vol I No.3


Table I: Treatment of Typhoid Fever using Third-Generation Cephalosporins
                                                                                   Number of
First Author                                        Duration No. of Clinical Cure Patients who
                       Drug              Dose
   (Year)                                            (Days) Patients     (%)       Relapsed
                                                                                      n (%)
Acharya         Chloramphenicol      40-60mg/kg/d     14       23           83           0
(1995)          Ceftriaxone              2g/d         3        23           87           0


Table II: Treatment of Typhoid Fever using Fluoroquinolones
                                                                             Number
                                                                      FCT*
                                                                                of
                                                                     (Days)
                                           Duration No. of Efficacy          Patients MDR-
First Author       Drug           Dose                                Mean
                                            (Days) Patients Rate (%)           who     ST
   (Year)                                                            (SD) or
                                                                             Relapsed
                                                                      range
                                                                              n (%)

Uwaydah               500mg bd              7-10     34      100      4.9          0
        Ciprofloxacin                                                                    43.5%
(1992)                750mg bd              7-10     28      100      5.2        1 (4)

Wallace        Ciprofloxacin 500mg bd         7      20      100       4           0
                                                                                         50%
(1993)         Ceftriaxone 3gm/d              7      22       73      5.2        1 (5)
Alam                       500mg bd          10       35     100      4.2          0
               Ciprofloxacin                                                             52%
(1995)                     500mg bd          14       34     100      4.9        2 (6)
Smith          Ofloxacin   200mg bd           5       22     100      3.4          0
                                                                                         63%
(1994)         Ceftriaxone 3gm/d              3       25      72      8.2        1 (4)
Hien TT                    15mg/kg/d          3      118     100      2.5          0
               Ofloxacin                                                                 91%
(1995)                     10mg/kg/d          5      110     100      3.0        1 (1)
Vinh H                                        2       53      89      4.2          0
               Ofloxacin       15mg/kg/d                                                 86%
(1996)                                        3       47      96      4.4        1 (4)

                                                        Treatment of Typhoid fever in
Managing MDR-TF:                                        Children
     Either oral ciprofloxacin or IV
     Ceftriaxone can achieve a 95%                             Third generation cephalosporins
     cure rate with low relapse and                     have been found to be very safe, but
     carrier rates following clinical                   have to be given parenterally.
     cure of TF
     The         advantages           of                         Quinolones         (ciprofloxacin,
     fluoroquinolones        are low                    oflaxacin, gatifloxacin) are advised to be
     toxicity profiles, its ability to                  avoided in younger children as as they
     penetrate into macrophages (site                   are potentially toxic to the growing plate
     of Salmonella replication), the                    and thus may retard growth. A recent
     low risk of plasmid-mediated                       study, however, showed no evidence of
     resistance and the fact that it can                acute joint toxicity in 326 children, aged
     be given orally.                                   1-14 years, treated with single short
                                                        courses of fluoroquinolones, compared
                                                        to their age-matched controls.


                                                                                                 17
IJPD, 2004; Vol I No.3


                                                     Complications include non-cardiogenic
        Newer drugs that have been                   pulmonary edema, renal failure, and
studied for the treatment of MDR-TF are              encephalitis.
Aztreonam,         Azithromycin      and
Furazolidine. None of them has been              Tick typhus (Mediterranean           spotted
                                                 fever, boutonneuse fever)
well accepted as alternatives and further
studies are awaited.                                     Tick typhus is endemic in southern
                                                 Europe and the Middle East, where it is
Prevention                                       caused by R. conorii, and in southern Africa,
   Environmental Sanitation, sewage              where R. africae is the causative agent. In
   disposal and safe water supplies.             other countries, it is the most common
   Improvement in personal hygiene               imported rickettsial disease .
   Immunization for travelers                            A 5- to 7-day incubation period is
   Eradication of carrier state. (4 weeks        followed by fever and nonspecific
   of    ciprofloxacin,    along     with        symptoms that are generally mild and self-
                                                 limited. A maculopapular rash involving
   cholecystectomy in presence of gall
                                                 palms, soles, and face and an eschar with
   stones).
                                                 regional lymphadenopathy are valuable
   Early diagnosis and treatment.                clues to the diagnosis. Diagnosis is
                                                 confirmed serologically.
Differential Diagnosis
     Differential diagnosis of typhoid                Treatment is as for Rocky Mountain
     includes all infections associated              spotted fever; ciprofloxacin is an
     with prolonged fever such as                    alternative therapy for tick typhus.
       o Rickettsioses
       o Leptospirosis,                          Typhus: Transmitted by the body louse,
       o Infectious Mononucleosis                typhus is both endemic and epidemic in
                                                 mountain regions and highlands of Mexico,
       o Malaria.
                                                 Guatemala, Africa, in the Himalayas and
       o Miliary TB,                             Afghanistan.
       o Viral Hepatitis                                  The infection is caused by R.
     Non-infectious cause – Lymphoma.            prowazeckii through scratching over
                                                 infected faeces of human body louse. The
Rickettsial Infections: Infections caused by     usual incubation period 8- to 12-days is
Rickettsia are vector-borne illnesses that       followed by high fever and other nonspecific
occur worldwide. Rocky Mountain spotted          symptoms.
fever, caused by Rickettsia rickettsii, occurs            Severe headache is common. A
most commonly in North America. It is            maculopapular rash that generally spares the
transmitted by ticks. After an average           palms and soles appears between 4th and 7th
incubation period of 7 days (range, 2 to 14      day and in severe cases may become
days) following a tick bite that may go          hemorrhagic.
unnoticed, fever, malaise, myalgias,                      Hypotension, altered mental status,
headache, and nausea and vomiting develop.       and renal failure are poor prognostic signs.
                                                          Untreated, mortality is as high as
     The typical rash consists of macules on     60% ; in survivors, defervescence occurs in
    the wrists and ankles that appear            2 to 3 weeks, but recovery is prolonged.
    between the second and sixth day,                    The most effective preventive
    subsequently spread to include palms             measure is to eliminate lice.
    and soles, and become hemorrhagic.



                                                                                           18
IJPD, 2004; Vol I No.3


Murine or flea-borne (endemic) typhus,                      The Weil- Felix reaction is the
caused by R. typhi, occurs throughout the          nonspecific agglutination          reaction. A
world, with high endemicity in Central and         fourfold rise in titer is diagnostic.
South America, parts of Africa, Malaysia,                   Doxycilline is the treatment of
Thiland, Myanmar and Australia.                    choice; Chloramphenicol is an alternative.
                                                   Death may occur within 2 weeks of onset of
          Infection results from percutaneous      illness if untreated. Prompt treatment
inoculation or inhalation of infected feces of     significantly reduces mortality. Therapy
the rat flea. Humans are infected when while       should be continued for at least 5 days and
scratching they introduce the faeces of a          for 48 hours after defervecence.
crushed flea which has fed on an infected
rat.                                               Leptospirosis
          Fever 39-40°C, headache ( most
common),         photophobia,     conjunctival              Leptospirosis     is    the      most
suffusion are common but less severe. Neck         widespread zoonotic infection in the world.
rigidity and spasticity suggest meningitis but     It is common in tropical and subtropical
CSF is normal except raised pressure and           climates and is the result of mucous
few lymphocytes.                                   membrane or percutaneous exposure to fresh
          Illness is similar to but much less      water contaminated by the spirochete
severe than that of louse-borne typhus, and        Leptospira interrogans.
mortality is low.                                           Most cases are sporadic, but
                                                   epidemics have been reported. Incubation
Scrub typhus or mite borne typhus:                 period – 2 – 20 days (average 10 days).
Endemic in areas of Asia and nearby Pacific                 Leptospirosis is a typically biphasic
islands, India, and northeastern Australia,        illness: In the first phase, Leptospira are
Pakistan , Myanmar, Thailand, Bangladesh,          present in the blood and CSF. Onset is
Indonesia, the infection is caused by R.           typically abrupt with chills followed by
tsutsumaguch which is transmitted by mites         high spiking temperature , myalgias
(chiggers).                                        (especially thighs & lumber areas) with pain
          Infection leads to fever, headache,      on palpation and headache . Involvement of
and myalgias in 10-14 days; an eschar with         one organ system may predominate, often
regional      lymphadenopathy         and     an   leading to initial misdiagnosis. Examination
erythematous maculopapular rash usually            reveals an acutely ill, febrile patient, with
develop during this time. With treatment,          relative bradycardia .Disturbance of
mortality is low. Temperature continues in a       sensorium in 25% cases,1/2 with icteric
remittent fashion until it falls by lyses on 12-   disease .The most characteristic sign is
18 day. In severe cases patient is prostated       conjunctival suffusion on 3rd or 4th day .
with cough , confusion, and deafness.              Less common findings are pharyngeal
Cardiac failure, renal failure, and                injection, skin rashes and cutaneous
haemorrhage may develop.                           haemorrhages,                 splenomegally,
         Diagnosis is clinical, and serologic      hepatomegally       and    lymphadenopathy.
tests are confirmatory.                            Symptoms resolve in 4 to 7 days, only to be
          Rapid diagnostic tests, such as          followed several days later by second phase.
Rickettsial isolation in cell culture and                   Second       (“Immune”)         phase
immunofluorescence staining of skin                correlates with the appearance of circulating
lesions, are sensitive but are not widely          IgM antibodies. After a relatively
available. With an immunoflorescence test,         asymptomatic period of 1-3 days, fever and
Rickettsia can be can be identified in a skin      earlier symptoms recur and aseptic
biopsy specimen as early as 4 th day of            meningitis      develops . Pleocytosis not
illness.                                           initially present now rapidly develops. CSF
                                                   protein may exceed 1g/L. Xanthochromic


                                                                                              19
IJPD, 2004; Vol I No.3


CSF has been observed in the presence of             eruption in 90 – 100 % of patients of
jaundice.                                            infectious mononucleosis.
         The illness is self-limited, although
treatment does reduce the severity and                    Rarely     autoimmune       hemolytic
duration of symptoms and may prevent the         anemia,        thrombocytopenia,         aseptic
second phase of disease.                         meningitis, hepatitis, G . B syndrome and
         Icteric disease (Weil's syndrome) is    splenic rupture can occur
more severe form of leptospirosis with                    Transmission of EBV requires
hepatic, renal, and vascular involvement,        intimate contact with the saliva of an
and has a 5% to 10% mortality rate.              infected person; less commonly it may be
         Hemorrhagic leptospirosis has also      contracted by blood transfusion. EBV is
been described, with a presentation similar      shed from the oropharynx for up to 18
to other viral hemorrhagic fevers.               months following primary infection.
         Diagnosis: Isolation of leptospires     Asymptomatic shedding of EBV by healthy
from blood or cerebrospinal fluid is             individuals accounts for most of the spread
diagnostic,     but     requires    prolonged    to uninfected members of the population.
incubation. The diagnosis is usually made                  The incubation period,, ranges from
retrospectively by serology. Increased titers    4 to 6 weeks
of leptospiral antibodies( Four fold or                   Clinical diagnosis can be made from
greater rise) are seen after 2 weeks. An IgM     the characteristic triad of fever, pharyngitis,
specific dot- ELISA has been effective in        and lymphadenopathy lasting for 1 to 4
diagnosing leptospirosis in endemic areas.       weeks and atypical lymphocytosis.
         Mild disease responds to oral                    Three fourths of patients present
amoxicillin or doxycycline, whereas more         with absolute lymphocytosis (greater than
severe illness requires intravenous penicillin   10% atypical lymphocytes), normal to
or Ampicillin.                                   moderately elevated white blood cell count,
                                                 and a positive reaction to a "mono spot" test
         Jarisch-Herxheimer reactions have       help in diagnosis. A positive Paul-Bunnell
        occurred with penicillin.                heterophile antibody test result is diagnostic,
                                                 and no further testing is necessary.
Infectious Mononucleosis: Caused by the          Moderate-to-high levels of heterophile
Epstein-Barr virus (EBV), most infections        antibodies are seen during the first month of
are sub clinical and occur before age of 5 or    illness and decrease rapidly after week 4.
through adolescence .                            However "mono spot" test has largely
        EBV, is a member of the herpes           replaced it, because it is rapid, sensitive and
virus family and one of the most common          specific.
human viruses, and most people become                     Clinically infectious mononucleosis
infected with it sometime during their lives.    is a self limited illness in vast majority of
Clinical expression is most often seen in        cases. There is no specific treatment, other
adolescence or young adulthood. Symptoms         than symptomatic. No antiviral drugs or
are fever, sore throat, and lymphadenopathy.     vaccines are available. Acyclovir has been
Posterior and /or anterior cervical              studied with mixed results. The role of
adenopathy is noted in 90 % cases.               corticosteroids remains controversial and are
Hepatomegally is infrequent. Splenomegally       not indicated for usual use. However 60 – 80
which is usually maximal in 2nd or 3rd           mg of prednisolone daily for short periods
week is seen in ½ of patients.                   may be beneficial for patients with severe
                                                 tonsillopharyngitis, thrombocytopenia &
        Administration of Ampicillin             hemolytic anemia. They have also been
    results in a pruritic, maculopapular         reported to decrease the overall length and
                                                 severity of illness, but these reports have not
                                                 been published.


                                                                                              20
IJPD, 2004; Vol I No.3



Miliary Tuberculosis: Results from                        Typhoid is known for its
hematogenous dessimation of Myco                  multisytsem involvement – the common
tuberculosis and chiefly occurs in children       presenting features being fever and
and young adults. It presents with a high         gastrointestinal symptoms.
persistent fever and drenching sweats,
                                                          Some of the features – headache,
marked tachycardia, loss of weight, and
                                                  vomiting, drowsiness, toxicity - and
progressive      anemia        with     hepato
splenomegally. Cough and breathlessness           complications -         as perforation,
only occasionally present with no abnormal        bleeding, sepsis – are widely recognized
physical signs in lungs                           and reported., However, there are some
         Diagnosis: Chest x-ray shows             complications which are only rarely
characteristic           miliary      mottling    reported. One of such infrequently
symmetrically distributed throughout both         recognized and reported complication is
lung fields. Choroidal tubercles may be seen      ascites. Patients present with fever,
on      ophthalmoscopy.         Bacteriological   diffuse tender, distended abdomen with
confirmation is done by culture of sputum,        sluggish bowel habits. Liver function
urine, or bone marrow. Liver biopsy is            tests show some hepatic dysfunction.
diagnostic in difficult cases. Tuberculin test
                                                          Serum albumin may be normal
is usually positive, but a negative test does
                                                  or nor so low as to account for acites.
not rule out miliary TB since sensitivity is
depressed in later stages of illness.             Ultrasonography of the abdomen
         If chemotherapy is not given, death      reveals free fluid. Ascitic tap shows
takes place within days or weeks.                 sterile exudate – caused by generalized
_________________________________                 inflammation of peritoneal serous layer
                                                  (as a part of polyserositis found in
                                                  enteric fever). Most of the times
                                                  presence of ascites is not clinically
                                                  suspected. The signs & symptoms
                                                  including     ascites    responded    to
◙     The     highly     successful     COX2
                                                  ceftriaxone or ciprofoloxacin. (Ed)

inhibitor, rafecoxib, widely used for
                                                  References
osteoarthritis and rheumatoid arthritis,
and studied for use in gut polyposis,             1. Burdzinska J, Nowakoski TK, Pellar J.
has been withdrawn from the market by             Polyserositis in the course of typhoid fever.
Merck, after reports proved that use of           Przegl Epidem 1966; 20: 211-5
this drug for periods exceeding 18                2. Chiu CH, Tsai JR, Ou JT. Typhoid fever in
                                                  children: A 14-year experience. Acta Pediatr
months doubled the risk of myocardial
                                                  Taiwan 2000; 41:28-32
infarction. The drug has been shown to            3. Jagadesh K, Patwari AK, Sarin S. Hepatic
greatly increase the risk of thrombo-             manifestation in typhoid fever. Ind Pedatrics
embolism in chronic users.                        1994; 31: 807-8
                                                  4. Judet O, Roueix E, Verderi D. A classical but
                                                  unknown cause of peritoneal effusion disclosed
                                                  by echography – typhoid fever. J Radiol
                                                  1989;70:419-21
                                                  5. Sinha R, Saha S. Acites – an underreported
                                                  finding in enteric fever. Ind Pediatr 2004;
                                                  41:965-6




                                                                                               21
IJPD, 2004; Vol I No.3


                                                 bank physician consultation. In the USA,
ADVERSE REACTIONS                                the blood bank is required to report any
TO TRANSFUSION                                   death resulting from transfusion to the
                                                 Food and Drug Administration (FDA).
                                                          These reactions may be separated
             S M Kadri                           into reactions that present in proximity to
                                                 the transfusion and those that present at
_________________________
                                                 some time subsequent to the transfusion.
                                                 Suspected post-transfusion disease, which
         Human beings are complex                may present after a considerable time
machineries and blood is not a simple            following transfusion, must also be
fluid; it is a vibrant organ system which        reported to the blood bank. Investigation of
is unique to every individual. Thus              these reports may result in identification of
adverse reactions should be expected             "carrier" donors who are removed from the
with each and every pint of blood that is        donor pool.
transfused. The best recourse is no
transfusion; the next best is transfusion
                                                 FEBRILE REACTIONS
given only sparsely, when no other
choice is left.
                                                         Febrile reactions (chill-fever) to
                                                 blood transfusion are common and are
        Strict testing and cross-matching
                                                 thought to be caused, in some cases, by
is to ensure that no serious reaction
                                                 recipient antibodies to leukocyte
occurs. The most common immediate
                                                 antigens reacting with leukocytes or
adverse sequelae to transfusion of blood
                                                 leukocyte fragments contained in the
and blood components are fever, chills
                                                 transfused component. Such reactions
and urticaria.       The most common
                                                 are most commonly encountered in
potentially serious reactions include
                                                 patients with a history of multiple blood
acute and delayed hemolytic transfusion
                                                 transfusions or pregnancies, both of
reactions and bacterial contamination
                                                 which can stimulate the development of
of blood components, which are
                                                 leukocyte antibodies. Approximately 1
described in some detail below. Less
                                                 out of 8 patients who have such
common severe reactions, such as
                                                 reactions will have similar reactions to
anaphylaxis       due     to     anti-IgA,
                                                 subsequent transfusions. Fever may also
transfusion-related volume overload,
                                                 result from pyrogenic cytokines
acute lung injury, or post-transfusion
                                                 generated during storage of blood
purpura, are managed in consultation
                                                 components.
with the medical staff of the blood bank.

Any adverse reaction to the transfusion of
                                                         Febrile reactions usually present
blood or blood components should be              during transfusion or in the immediate
reported to blood bank personnel as soon as      post-transfusion period and must be
possible.     Speed is essential in such         distinguished from fever related to the
situations because of the possible life-         underlying disease or infection. Thus,
threatening nature of acute transfusion          documentation of a pre-transfusion
reactions. The evaluation of all adverse         baseline temperature is extremely
reactions to transfusion is the responsibility   important. A temperature rise of 1.5° F
of the medical staff of the blood bank and
                                                 (1.0° C) from the baseline is considered
the notification of such a reaction by the
patient-unit serves as a request for blood
                                                 significant. The usual treatment, and


                                                                                           22
IJPD, 2004; Vol I No.3


pre- transfusion prophylaxis, is with an     may also be possible to reinitiate the
antipyretic (non-aspirin containing          blood transfusion. Such a decision must
medication).           Diphenhydramine       be arrived at through consultation
hydrochloride (Benadryl) is not              between the physician reporting the
appropriate for such treatment. In some      reaction and the Blood Bank physician.
patients these reactions present as
severe rigor (shaking chills).               SEVERE ALLERGIC (ANAPHYLACTIC)
                                             REACTIONS
         Fever is also the most frequent
manifestation of acute hemolytic                     In addition to the signs of typical
transfusion reactions. Therefore, it is      milder allergic reactions, anaphylactic
important to rule out this potentially       or anaphylactoid reactions manifest
life-threatening reaction through proper     cardiovascular instability that includes
evaluation. Notification to the blood        hypotension, tachycardia, and loss of
bank of all adverse reactions is             consciousness, cardiac arrhythmia,
necessary to provide the patient with the    shock and cardiac arrest. Respiratory
most appropriate blood component.            involvement with dyspnoea or stridor
                                             may be more pronounced than is usually
ALLERGIC (URTICARIAL)                        seen in typical allergic reactions.
REACTIONS                                    Patients with IgA deficiency who
                                             develop anti-IgA can have anaphylactic
        The appearance of urticaria          reactions. A blood bank physician
during and immediately after the             should be consulted regarding the
transfusion of blood components is seen      evaluation of patients with severe
in approximately 1% of recipients. This      allergic reactions, as well as selection of
reaction is caused by foreign plasma         appropriate blood components for future
proteins. On rare occasions, such            transfusion.
allergic reactions may be associated
with      laryngeal     edema       and      ACUTE HEMOLYTIC REACTIONS
bronchospasm.
                                                     The most dreaded complication
        A mild urticarial reaction is        of blood transfusion is the acute
generally innocuous. If coupled with         hemolytic reaction in which transfused
another sign, such as fever, evaluation      red cells react with circulating antibody
for a hemolytic reaction may be              in the recipient with resultant
indicated.                                   intravascular hemolysis.         Such a
                                             reaction is most likely to occur when a
        If the allergic symptoms, such as    group O patient is ABO-incompatible
urticaria,     are     bothersome,      an   marrow or stem cell transplant with
antihistamine may be administered            sufficient red cell content will likely
before the blood transfusion is restarted.   develop an acute hemolytic reaction.

        In the case of a mild urticarial             Most acute hemolytic reactions
reaction, with no other signs or             are the result of human error, such as
symptoms       attributable    to    blood   the transfusion of properly labeled
transfusion, it is not necessary to submit   blood to the wrong person, improper
post transfusion blood specimens. It         identification of pre-transfusion blood


                                                                                     23
IJPD, 2004; Vol I No.3


samples, or clerical errors occurring         reaction. The onset of hypotension is
within the blood bank.                        during the transfusion, and resolves
 Symptoms of an acute hemolytic               quickly with discontinuation of the
reaction may include                          transfusion. If hypotension persists
    o chills and fever,                       beyond 30 minutes after discontinuing
    o the feeling of heat                     the transfusion, another diagnosis
      along the vein in which                 should     be    strongly     considered.
      the blood is being                      Hypotensive reactions have been
      transfused,                             associated with red cell and platelet
    o pain in the lumbar                      transfusions. Some reactions have been
                                              associated with angiotensin converting
      region,
                                              enzyme (ACE) inhibitor drugs or the
    o constricting pain in the
                                              use of leukocyte reduction filters.
      chest,
    o tachycardia,                            NON-IMMUNE HEMOLYSIS
    o hypotension, and
    o hemoglobinemia with                             Lysis of red cells can occur in
      subsequent                              conditions of         improper storage,
      hemoglobinuria      and                 handling, or transfusion. The clinical
      hyperbilirubinemia.                     signs are usually hemoglobinemia and
                                              hemoglobinuria.                Transient
        Uncontrollable bleeding due to        hemodynamic, pulmonary and renal
disseminated intravascular coagulation may    impairment may occur. Hyperkalemia
be the only sign of a hemolytic transfusion   may occur, particularly in patients with
reaction in an unconscious or anesthetized    renal failure. The most significant
patient. Such a reaction may not be           complications of nonimmune hemolysis
accompanied by hypotension.                   are cardiac arrhythmia due to
                                              hyperkalemia, and renal failure.
HYPOTENSIVE REACTIONS                         Differentiation      of     non-immune
                                              hemolysis from a hemolytic transfusion
        Transfusion             associated    reaction may be impossible unless the
hypotension is defined as hypotension         contents of the blood bags are available
occurring during transfusion in the           for study. Therefore, the blood bag
absence of signs or symptoms of other         together with attached tubing and
transfusion reactions such as fever,          intravenous fluids should be saved for
chills, dyspnoea, urticaria, or flushing.     further investigations.
A drop of at least 10 mm Hg in systolic
or diastolic arterial blood pressure from     POST-TRANSFUSION PURPURA
the pre-transfusion baseline is typical of
a hypotensive reaction. However, if the               Post-transfusion purpura (PTP)
immediate       pre-transfusion     blood     presents as thrombocytopenia typically
pressure is elevated from the patient’s       5 to 21 days after transfusion. In PTP,
typical blood pressure, and the arterial      the patient makes an allo-antibody in
pressure does not fall below the              response to platelet antigens in the
patient’s usual blood pressure, it should     transfused blood that for a period of
not be considered a hypotensive               time causes destruction of autologous


                                                                                     24
IJPD, 2004; Vol I No.3


antigen-negative platelets. The signs        slowly.    Symptomatic patients may
and symptoms are thrombocytopenia            manifest fever and leukocytosis thus
that is frequently profound, purpura, or     appearing to have an occult infection.
bleeding. Febrile reactions have been
reported retrospectively with the                    Delayed hemolytic reactions
implicated        transfusion.      The      occur in patients who have developed
thrombocytopenia is self-limited in          antibodies from previous transfusion or
PTP, with recovery occurring within 7-       pregnancy but, at the time of pre-
48 days. PTP must be differentiated          transfusion testing, the antibody in
from the far more common allo-               question is too weak to be detected by
immunization to platelet antigens. This      standard procedures.         Subsequent
may be problematic when the patient          transfusion with red cells having the
has     an    underlying     cause    of     corresponding antigen results in an
thrombocytopenia. Consultation with a        anamnestic antibody response and
blood bank physician is recommended          hemolysis of transfused red cells.
in evaluating such patients.
                                                     Notify the blood bank at the time
         Platelet transfusion is of very     the reaction is suspected, to allow
little value in PTP; however, therapeutic    prompt investigation. Care must be
plasma exchange may be beneficial.           taken that subsequently transfused red
Since autologous platelets do not            cells lack the antigen corresponding to
survive in circulation, there is no          the patient's antibody.
expectation that transfused platelets
regardless of antigen matching will do       GRAFT vs HOST DISEASE (GVHD)
any better. Platelet transfusion should be
reserved for patients with active                    GVHD is associated with bone
bleeding.                                    marrow transplantation. Transfusion
                                             associated GVHD occurs when viable T
DELAYED HEMOLYTIC                            lymphocytes in blood components are
REACTION                                     transfused engraft and react against the
                                             recipient's tissues and the recipient is
        Not all hemolytic reactions          unable to reject the donor lymphocytes
occur during or shortly after blood          because of immunodeficiency, severe
transfusion. The so-called "delayed"         immunosuppression, or shared HLA
hemolytic reaction commonly occurs           antigens. It typically presents 3-4 weeks
about 4-8 days after blood transfusion,      after transfusion with rash, fever,
but may develop up to one month later.       diarrhea, pancytopenia and liver
The most common signs of such a              dysfunction. Transfusion associated
reaction are a falling hematocrit (a         GVHD carries a very poor prognosis.
manifestation    of    extra     vascular    Irradiation is the recommended method
destruction of the transfused red blood      of preventing this complication. The
cells) and a positive direct antiglobulin    blood bank must be appraised of the
(Coomb’s) test (DAT). There may also         immune status, or diagnosis, of the
be hemoglobinuria and a mild elevation       patient so that cellular components
of the serum bilirubin. Many delayed         intended       for      transfusion    of
hemolytic reactions will go undetected       immunocompromised patients and
because the red cell destruction occurs      blood components from designated


                                                                                    25
IJPD, 2004; Vol I No.3


donors will be irradiated. Irradiation of    TRANSFUSION RELATED
blood red cell containing components         ACUTE LUNG INJURY
decreases the red cell survival and          (TRALI)
increases the potassium of the                        TRALI is a rare though under-
component. There is no apparent effect       recognized complication of transfusion
on platelet survival. Fresh Frozen           manifested by abrupt onset of non-
Plasma (FFP) and cryoprecipitated            cardiogenic pulmonary edema. Severe
AHG (CRYO) need not be irradiated            cases may require assisted ventilation
because these components do not              with high FIO2. Most cases of TRALI
contain enough viable lymphocytes to         resolve within 72 hours although
cause GVHD.                                  fatalities may occur in approximately
                                             10% of cases. TRALI has been
BACTERIAL CONTAMINATION OF                   associated with the presence of
BLOOD COMPONENTS                             antibodies in the donor plasma reactive
                                             to recipient leukocyte antigens or with
        Bacterial contamination occurs       the production of inflammatory
when a small number of bacteria enter a      mediators during storage of cellular
blood component during collection or         blood components. Prompt notification
processing. During storage, bacteria         of the blood bank when TRALI is
may proliferate, resulting in a large        suspected will assist in evaluation and
number of organisms, and possible            appropriate blood component selection
endotoxin, being given with the              for future transfusions.
transfusion. Bacterial contamination is
rare, but difficult to detect prior to       IF A TRANSFUSION REACTION IS
transfusion. The organisms that              SUSPECTED
contaminate red blood cells are often
Yersinia and Pseudomonas, which grow         Stop the transfusion immediately!
at 4° C and metabolize citrate.
                                             Disconnect the intravenous line from the
Autologous blood may be contaminated
                                             needle. Attach a new IV set and prime with
with bacteria, particularly if the patient   saline, or flush the line with the normal
had an active infection at the time of       saline used to initiate the transfusion and
donation. Organisms that contaminate         reconnect the line. Open the line to a slow
platelets are typically Gram negative        drip. In certain cases, such as a mild
rods and Gram positive cocci.                urticarial reaction or the presence of
Symptoms that indicate bacterial             repeated chill-fever reactions, it may be
contamination include hypotension,           possible to restart the blood transfusion
shock, fever and chills, nausea and          after evaluation and treatment of the
                                             patient. To reinitiate the transfusion using
vomiting, and respiratory distress. These
                                             new IV tubing set, enter the second port to
symptoms may also indicate a                 reduce the chance of bacterial
hemolytic       transfusion      reaction.   contamination.
Suspected transfusion reactions due to
bacterial contamination should be            Seek medical attention immed- iately
reported promptly to the blood bank.
Diagnosis is established by Gram stain       Check to ensure that the patient name and
and blood culture of both the blood          registration number on the blood bag label
component and the recipient.                 matches exactly with information on the
                                             patient's identification



                                                                                       26
IJPD, 2004; Vol I No.3


DO NOT BYPASS THIS STEP BY ASSUMING                    The necessary specimens, blood
THAT THE PATIENT'S TRUE IDENTITY IS
KNOWN.
                                               bag and attached tubing should be sent
                                               to the Blood Bank unless the Blood
        Do not discard the unit of blood       Bank physician, after review of the
that has been discontinued because it may      clinical information, believes the
be necessary for the investigation of the      transfusion can be restarted. The latter
transfusion reaction.                          may apply to patients who might
                                               manifest urticarial reactions or repeated
                                               chill-fever reactions.
When a Reaction Occurs!
                                                       Additional blood specimens may
        Notify Blood Bank personnel            be requested, depending on the
that a transfusion reaction has occurred       serological findings. The venipuncture
and briefly describe the nature of the         to obtain these blood specimens must
reaction. Delay the transfusion of             not be traumatic. Small lumen catheters
additional units until the possibility of      should not be used to collect blood
serological incompatibility has been           specimens for a transfusion reaction
investigated.                                  investigation. If red cells are hemolyzed
                                               during the venipuncture or collection,
         Consult a Blood Bank physician        the serum will turn pink and it may be
if there is an urgent need for transfusion.    erroneously concluded that intravascular
Initiate the Transfusion Reaction Report       hemolysis has occurred.
Form after Blood Bank personnel have
been notified of a transfusion reaction.               The IV tubing used to transfuse
It is essential that this form be filled out   the blood components should be
completely, including the unit numbers         clamped and sent without the needle
of all blood transfused. The form will         attached. A urine sample is not required
serve as a written request for                 for the routine evaluation of a
investigation of the reaction by a Blood       transfusion reaction, but may be
Bank physician.                                requested by the Blood Bank physician
                                               in the course of further assessment.
        In the case of a suspected
hemolytic transfusion reaction (not                    Patient care personnel will be
urticaria alone), the following items          notified by telephone of significant
should be submitted promptly to the            findings of the reaction evaluation as
Blood Bank:                                    soon as possible. A written report of the
                                               investigation, on the Blood Transfusion
    o   Completed Transfusion Reaction         Reaction Form, will be returned to the
        Form (all copies),
                                               patient care unit at a later date for
    o   Post transfusion blood specimens       inclusion in the patient's chart.
        and

    o   Incriminated unit(s) of blood and
        attached tubing.




                                                                                      27
IJPD, 2004; Vol I No.3


TREATMENT OF TRANSFUSION                   corresponding to the offending antibody
REACTIONS                                  may be necessary to compensate for the
                                           transfused cells that have been removed
The following guidelines should be         from the circulation.
tailored to suit individual cases.
                                           ALLERGIC TRANSFUSION REACTIONS
ACUTE HEMOLYTIC REACTIONS

                                           Antihistamines Give 50-100 mg orally
Diuretic therapy:                          or intravenously. If urticaria develops
                                           slowly, antihistamines may be given
        Initially,  give    40-80    mg    orally. Pediatric dose: 1-2 mg/kg im or
Frusomide (Lasix) intravenously. This      iv; 25-50 mg per average dose. Routine
dose can be repeated once. Lack of         use     of     an    antihistaminic  as
response to frusomide in 2-3 hours         premedication for all transfusions,
indicates the presence of acute renal      regardless of a history of allergic
failure. Pediatric dose: 1-2 mg/kg/dose.   reactions, is discouraged.
May repeat once at 2-4 mg/kg.
                                           Aminophylline for wheezing, at a dose
Water loading:                             of 125-250 mg iv slowly over a period
                                           of about 5 minutes. Pediatric dose: 3
        The patient should be hydrated     mg/kg/dose in iv drip over a period of
to maintain urinary output of at least     20 minutes.
100 ml/hr. Infuse a loading dose of
0.9% sodium chloride or 5% dextrose in     Epinephrine for severe, acute reactions
0.45% sodium chloride. Chart hourly        including     laryngeal    edema      or
urine output. Maintain the urine output    bronchospasm. Give 0.1-0.5 mg (0.1-0.5
by administering intravenous fluid at      ml     of      a    1:1000     solution)
100 ml/hour until the urine is free of     subcutaneously. Subcutaneous dose may
hemoglobin. If the patient's urinary       be repeated at 10-15 minute intervals.
output does not increase with this         The total subcutaneous dose in a 24-
hydration, any additional fluids should    hour period, with rare exceptions,
be infused with caution. Pediatric         should not exceed 5 mg. Pediatric dose:
patients should receive a smaller          0.03 mL/M2 (0.03 mg/M2 of a 1:1000
loading volume of fluid in proportion to   solution) given subcutaneously. A
their body surface area.                   single pediatric dose should not exceed
                                           0.3 mg.
        Treat shock and disseminated
intravascular     coagulation    with      FEBRILE TRANSFUSION REACTIONS
appropriate measures if and when they
appear.                                          Premedicate the patient with
                                           acetaminophen or other antipyretic
DELAYED HEMOLYTIC TRANSFUSION
                                           agents when previous reactions have
REACTIONS
                                           been extremely bothersome. Pediatric
        Specific treatment generally is    dose: 10 mg/kg to a maximum of 600
not necessary. Supplemental transfusion    mg. Aspirin will adversely affect the
of    blood     lacking   the   antigen    patient's platelet function, so non-aspirin
                                           antipyretic agents are preferable.


                                                                                   28
IJPD, 2004; Vol I No.3


Severe shaking chills (rigors) can be                        contraindications to the use of these
controlled by the sedative effect of                         drugs. In general, transfusion of
antihistaminic (25-50 mg given im or                         granulocytes should be terminated only
iv). Some prefer an opiate as Demerol                        for such complications as severe flank
which may cause acute respiratory                            pain, chest pain, hemoglobinemia and
arrest. An opiate antagonist should be                       hemoglobinuria,           hypotension,
immediately available.                                       laryngospasm, or acute pulmonary
                                                             injury.
        For patients with a history of
severe repeated well-documented febrile                      POSTTRANSFUSION DISEASES
reactions, transfusion with leukocyte-                       All cases of suspected posttransfusion
poor components may be indicated to                          disease     transmission     encountered
reduce the transfused load of white                          among inpatients or outpatients, in any
blood      cells.    Leukocyte-reduced                       context, must be reported to the Blood
components are transfused routinely to                       Bank so that they can be investigated.
patients with hematologic malignancy                         This way blood donors who are thought
and to patients receiving outpatient                         to be infectious can be excluded from
transfusion.                                                 the list of eligible donors. Because of
                                                             the risk of posttransfusion infection, the
SEPSIS DUE TO BACTERIAL                                      benefits     associated    with     blood
CONTAMINATION OF DONOR BLOOD                                 transfusion must always be weighed
                                                             against possible risks. In addition
        Treatment of septic shock                            patients must be informed of the risks of
includes: terminating the suspected                          transfusion and of alternative strategies.
transfusion immediately, cardiovascular                      Under extremely rare circumstances it
and respiratory support, blood culture of                    may be necessary to transfuse blood or a
the patient, and administration of broad                     blood component to a patient before all
spectrum antibiotics including anti-                         the screening tests for disease
pseudomonas coverage if the blood                            transmission have been completed. In
component involved is red blood cells.                       such situations, the physician treating
                                                             the patient should be made aware of the
PREMEDICATION FOR RECIPIENTS OF                              available options by Blood Bank
GRANULOCYTES
                                                             medical staff and will be informed of
                                                             the test results as soon as they are
        It is suggested that patients
                                                             available.
receiving granulocytes who have a
history of febrile reactions to blood
                                                             ****************************
components      be    pretreated  with
antipyretic agents if there are no
_________________________________
◙        Studies have shown that fast foods when consumed regularly lead to obesity.                      Public
consciousness in the UK has led to mounting pressure on fast food manufacturers to alter the composition
of such foods which are generally high-salt, high-calorie snacks, and fast-food joints to serve such healthy
foods as salads, organic milk and juices.
         Two school girls in New York have filed suits against the world-famous fast-food giant, McDonalds,
claiming their food made them overweight and sick.
         Our place long known for traditional food habits is adopting fast-food style to its detriment. It is the
need of the hour to make our youngsters aware of the dangers of fast-food culture.




                                                                                                             29
IJPD, 2004; Vol I No.3


Patient Education                                attack.

                                                          Some of the differences in
Asthma                                           diagnoses are undoubtedly attributable to the
                                                 greater propensity of women to seek medical
                                                 attention for any condition. The differences
                                                 may also be related to the fact that asthma in
         Asthma is a chronic airway disease      men is often misdiagnosed as some other
that involves episodic attacks of breathing      respiratory condition, such as chronic
difficulty, wheezing, coughing, or tightness     obstructive lung disease or emphysema.
in the chest. Just what triggers these attacks   Even so, there is now some intriguing
varies from one person to another, but           evidence that at least some of the
allergies probably account for the majority      explanation for women’s susceptibility lies
of symptoms in people with susceptible           in hormonal differences. Also, women
airways. Other influences can include cold       frequently have conditions (such as arthritis,
air, respiratory infections (including colds),   menstrual cramps, and headaches) that lead
smoke and environmental pollutants, sudden       them to use aspirin and other anti-
changes in temperature or humidity, and          inflammatory drugs which, in rare cases,
strenuous exercise. Only rarely is asthma        may trigger asthma attacks. In addition,
attributed to emotional or psychological         women may be exposed more frequently
distress, although for many years this was       than men to certain inhaled allergens, such
considered one of the prime triggers.            as the mites that grow in house dust and
                                                 other indoor pollutants. Despite the many
         During an asthma attack the muscles     strides made in sharing household duties, a
tighten around the tubes inside and leading      woman allergic to dust mites still is much
to the lungs (the bronchi), and the lining of    more likely to be the one who does the
the tubes becomes swollen and inflamed.          vacuuming than a man with similar
Often thick mucus accumulates in the             susceptibilities.
airways as well. In all cases airflow is
restricted, and emptying the lungs of air                 There is no evidence that asthma
becomes particularly difficult. These attacks    attacks become more severe or more
can last anywhere from several minutes to        frequent during pregnancy, but asthma can
several days. Although severely restricted       pose particular problems for a woman
airflow can be life-threatening, in most cases   expecting a baby. This is because restricted
the attacks are mild or moderate. In fact, by    airflow to the mother can potentially deprive
avoiding triggers and using appropriate          the fetus of oxygen. During pregnancy many
medications, most people with asthma can         women who do not have asthma notice
lead active, healthy lives.                      changes in breathing patterns or difficulty
                                                 breathing because the growing uterus
        Asthma has become increasingly           changes the shape of the chest cavity. In
common in early childhood, affecting as          pregnant women with asthma, these body
many as 10 percent of all children, probably     changes can make asthma attacks more
because of a rise in both outdoor and indoor     difficult to control than normal. Still, most
pollution. Up to the age of 10, boys are         women with asthma can expect to stay
twice as likely as girls to have asthma, but     healthy and have healthy babies if they
by the preteen years the numbers even out.       continue to take their medications under the
By age 20, as well as throughout the             supervision of a clinician who is aware of
remainder of life, women are about 3 times       their pregnancy.
more likely than men to be diagnosed with
asthma. They are also more likely to be
hospitalized for asthma and to die of an


                                                                                            30
IJPD, 2004; Vol I No.3


Who is likely to develop asthma?                 How is the condition evaluated?

         The susceptibility to asthma appears             Usually asthma is diagnosed by a
to be inherited, and people with allergies are   clinician only after several attacks have
particularly likely to develop it at some        occurred. Various tests including pulmonary
point. Among the allergens that trigger          function tests can help differentiate asthma
attacks in people with susceptible airways       from other respiratory diseases. Once
are dust mites, molds, pollens, animal           asthma has been diagnosed, the clinician
dander, and certain foods. As much as 8          may suggest seeing an allergist, who can do
percent of the population is also allergic to    skin tests to see if there are any identifiable
food additives called sulfites (whitening        allergens underlying the attacks. The
agents), and they may experience an almost       clinician may also suggest keeping a diary to
immediate asthma attack after eating foods       help determine if the attacks can be linked to
containing these chemicals. Sulfites are         any particular substances or situations.
often found in dried fruits and vegetables,
wine, beer, potatoes, dehydrated seafood         How is asthma treated?
soups, baking mixes, fruit drinks, and
certain soft drinks.                                     Active asthma attacks are usually
                                                 treated with a short-acting bronchodilator,
        Susceptible people exposed to large      such as albuterol, which opens the airways
amounts of smoke (whether from cigarettes        by relaxing smooth muscle. Corticosteroid
or wood-burning stoves), gasoline fumes,         medication in an inhaler or in oral form,
fresh paint, and other environmental             such as prednisolone or prednisone, reduces
pollutants may have frequent attacks of          inflammation, which is a key mechanism of
asthma.                                          asthma attacks. Because it takes at least 6
                                                 hours for corticosteroids to take effect even
What are the symptoms?                           if inhaled, bronchodilators are used to
                                                 provide immediate relief of symptoms.
        The classic symptoms of an asthma
attack are wheezing (noisy breathing),                    Once the attack is under control, the
coughing (especially at night), tightness in     physician may prescribe maintenance
the chest, shortness of breath, and labored      medications, such as cromolyn, which
breathing. Symptoms may begin upon               reduce the chances that the airways will
exposure to the offending trigger or may         become inflamed. Corticosteroids are
develop slowly over many hours. Often            usually continued on a maintenance basis, in
attacks develop in the middle of the night.      the inhalable form; long-term treatment with
                                                 oral preparations is avoided if possible
        In a severe attack breathing             because they are associated with adverse
becomes rapid and shallow, heartbeat             side effects.
quickens, and the skin pales or takes on a
bluish cast. It may be necessary to use                   Many asthma medications are
accessory neck and abdominal muscles in          available in aerosol form and can be inhaled
order to support breathing. Sometimes a          into the lungs in specific amounts through a
person with longstanding asthma becomes          device called a metered-dose inhaler. The
barrel-chested as the chest expands to           medications are also available as tablets and
accommodate enlarged lungs -the body’s           syrups. The aerosol inhalers fit inside a
way of compensating for constricted              purse and should be carried at all times to
airways.                                         stave       off      emergency       attacks.
                                                 Bronchodilators are also available in a
                                                 solution for use in an electric nebulizer,
                                                 which produces a mist that the patient


                                                                                             31
IJPD, 2004; Vol I No.3


breathes through a hand-held inhaler               How can asthma be prevented?
attached by tubing to the machine. The mist                Although the underlying physical
may provide added relief at home during            cause of asthma cannot be prevented,
prolonged attacks. Bronchodilators can also        minimizing the frequency of asthma
be taken systemically if necessary. Nose
                                                   attacks boils down to eliminating or
sprays can help dry up the stuffy or runny
nose which often accompanies allergic
                                                   reducing exposure to anything known to
asthma.                                            trigger them. This is not always easy and
                                                   is sometimes impossible, in which case
        Although some asthma medications           the only recourse is heavy reliance on
are available over the counter, the condition      medications. The many asthma attacks
should be evaluated by a clinician before          that develop for no apparent reason
these are tried.                                   obviously cannot be prevented either.
                                                   Anyone who suspects certain allergens
         Most asthma drugs are considered          or environmental sources can try one or
safe for use during pregnancy. If antibiotics      more of the following tactics.
are prescribed to treat the upper respiratory
infections that can trigger asthma,
tetracycline or sulfa drugs should be avoided
                                                   Minimize dust and other household
because of adverse effects on the fetus.           allergens
Corticosteroids used in inhaled form are
preferred over oral forms during pregnancy,                Ordinary household dust consists
since relatively little drug can reach the fetus   of a number of different materials that
through this route. But because severe             trigger asthma attacks, including the
asthma attacks can be life-threatening to the      feces of dust mites and cockroaches, pet
pregnant woman and so potentially                  dander, and microscopic fabric fibers.
damaging to the fetus, systemic steroids are       Frequent dusting and vacuuming can
considered an appropriate tradeoff for             minimize dust exposure over the long
pregnant women with severe asthma, even            run, but often these well-intentioned
though their safety for the fetus has not yet
                                                   efforts only stir some of the lighter-
been proved or disproved.
                                                   weight particles into the air, where they
         In the past, people with known            are readily inhaled. For this reason,
allergies received desensitization shots to        someone other than the allergic person
reduce susceptibility to allergens. Today,         should be assigned these dust-busting
however,      allergists  often    advocate        tasks and the allergic person should stay
eliminating or reducing exposure to the            out of the room for at least half an hour
allergen as a first course of action, partly       after cleaning.
because desensitization shots must be taken
quite frequently, are not always effective,                An alternative is to invest in a
and are uncomfortable and expensive.               double-filtered vacuum cleaner or, better
                                                   yet,     a    so-called   high-efficiency
        Anyone with asthma needs to be
under the regular care of a clinician. This is     particulate arresting (HEPA) vacuum
because it often takes a good deal of trial        cleaner. HEPA air cleaners are a good
and error before the right combination of          investment for the bedroom, if not the
medications and preventive steps can be            whole house, because so much time is
determined.                                        spent in that room during sleep. Many
                                                   allergists also recommend more extreme
                                                   measures such as ripping out carpeting,



                                                                                         32
IJPD, 2004; Vol I No.3


eliminating all stuffed and upholstered      conditioned or filtered air. At all times of
furniture, and removing books and dust-      the year, shampoos and skin creams
catching knickknacks, but not all people     should be checked to make sure they do
are willing or able to take these steps      not contain extracts of cottonseed,
(nor do they necessarily help). Perhaps a    flaxseed, or other natural substances that
more practical alternative is to cover the   are sometimes allergenic. Those allergic
affected       person’s    mattress   and    to mold and dust mites in particular may
pillowcase with airtight rubber covers,      want to invest in a dehumidifier, since
wipe these down with water on a weekly       humidity above 20 percent encourages
basis, wash bedding frequently in very       the growth of these organisms. Adding a
hot water, and keep the bedroom in           few drops of chlorine bleach to cut
particular as dust-free as possible. If      flower arrangements and changing the
there is a forced-air heating system in      water daily can also help prevent mold.
the home (which disperses dust even          Also, because soil and water can foster
more than other heating systems), it         the growth of molds, it is a good idea to
should be equipped with an effective air     keep indoor plants to a minimum. If
filter to trap offending particles.          there is a humidifier in the home, it
                                             needs to be cleaned regularly to prevent
        Various steps can be taken           the growth of molds and other allergens.
against specific allergens found in dust.
If dust mites are the problem, for           Exercise with care
example, agents lethal to the mites,
called acaricides, can be applied to                 Even though exercise often
carpeting although these are probably        triggers asthma attacks, there is no
not safe for use in the home of a            reason people with asthma should have
pregnant woman. A cockroach problem          to forgo an activity so important to
may be reduced by having the house or        health and well-being. In fact, regular
apartment fumigated regularly by an          exercise that develops lung capacity is
exterminator. As for animal dander, the      generally recommended. Just what steps
best solution is clearly to avoid owning a   need to be taken to keep exercise safe,
dog, cat, or other furry pet and to avoid    however, will vary with the individual.
long stays at homes inhabited by these
animals. If this is impossible, having               If exercise itself triggers attacks,
someone who is not allergic wash the pet     it is often sufficient to inhale a
on a weekly basis can be a significant       bronchodilator before beginning the
help.                                        exercise. If cold or rapid temperature
                                             changes trigger attacks, it is best to
Avoid molds and pollens                      restrict exercise to places with warm,
                                             humidified air (such as swimming pools
        Because     many       of    these   or gymnasiums). If it is necessary to
substances are prevalent only during         walk in the cold air, problems can be
certain seasons, the best tactic for those   reduced by wearing a warm scarf or
unable to exile themselves temporarily       mask around the mouth and nose and
to another climate may be to stay            breathing through the nose in order to
indoors as much as possible, preferably      warm, filter, and humidify the air before
in a home, car, or office with air-          it reaches the lungs. If pollen plays a role



                                                                                      33
IJPD, 2004; Vol I No.3


as well as exercise, it makes sense to        Administration (FDA) recently banned
exercise indoors during allergy season.       the use of these agents on fresh fruits
                                              and vegetables and made it mandatory
Be wary of aspirin and other anti-            for manufacturers to include a notice on
inflammatory drugs                            labels if detectable amounts of sulfites
                                              are present in a food.
        Because many drugs used to
reduce pain seem to promote asthma            Consider getting a flu shot
attacks, anyone with asthma should use
these drugs with caution until she is                 If asthma is triggered by
certain they do not pose a problem for        respiratory infections, it is a good idea to
her. Aspirin (acetylsalicylic acid), which    have a flu vaccination every year. Other
is sold under a variety of brand names, is    household members might also consider
a common culprit. Other analgesics that       getting shots, to minimize the chances
often cause problems are ibuprofen and        that they will bring an infection home.
other non-steroidal anti-inflammatory         Also, if at all possible, contact with
drugs (NSAIDs).                               people who have viral infections
                                              (including colds) should be avoided.
Avoid smoke and other pollutants
                                              *********************************
         Anyone with asthma should cut        Expected breakup of 135 cases of
out cigarettes and steer clear of other       TB under RNTCP
people’s smoke whether it is secondhand       New smear-positive: New smear-negative
                                                           [ 50 : 50]
smoke from a cigarette or smoke from a
woodstove, burning leaves, or an              New smear-positive (CAT I): Retreatment smear-
industrial chimney. It is also advisable to                                    positive (CAT II)
                                                                [50 : 25 (initially)]
stay inside during pollution or ozone
alerts in urban areas and to avoid            New smear-positive: Extra-pulmonary
breathing fumes from fresh paint,                           [50 : 10]
turpentine, insecticides, deodorants,         Non-seriously ill smear-negative: Seriously ill
chlorine, cleaning fluid, and other           smear-negative
irritants.                                                         [40 : 10]

                                              Non-seriously ill extra-pulmonary: Seriously ill
Eliminate foods that cause problems                                           extra-pulmonary
                                                                      [8 : 2]
        If the problem is a solitary food
such as peanuts, this is relatively easy to   Treatment    Smear       Smear       Extra         Total
avoid. It can be quite an ordeal,             Category     positive    negative    Pulm.
however, when the allergy is to eggs,
milk, or flour ingredients that are often     I               50          10           2          62
                                                           Seriously   Seriously   Seriously
hidden in processed foods or foods                             ill         ill         ill
prepared in restaurants. Anyone who           II              25          Nil         Nil         25
reacts to sulfites needs to be particularly                    0          40          8           48
                                              III
careful in restaurants and should                             75          50          10         135
                                              Tota;
routinely check all labels on packaged
foods eaten at home. The Food and Drug



                                                                                                 34
IJPD, 2004; Vol I No.3



Airborne infections                           influnzae,    S.     pneumoniae       and
                                              Staphylococci . All these are sensitive to
Epidemiology & Control                        anti bacterials like Co-trimoxazole,
                                              which is a safe, effective and cheap
                                              therapy and if started early and provided
                  Farooq Fazilli              adequately, can save many lives.
_______________________________
                                              Deaths from ARI occur because:
                                                        o Children do not come for
                Acute           respiratory
                                                          treatment at all.
infections (ARI) range, in spectrum,
                                                        o Children       come       for
from mild colds & coughs to life-
                                                          treatment, but too late.
threatening pneumonias. ARI is the most
                                                        o Children       come       for
common cause of morbidity and
                                                          treatment     but     receive
mortality among young children; of the
                                                          inadequate treatment.
estimated 15 million deaths in Indian
children under 5 years of age, 1/3rd are
                                              What is ARI ?
due to ARI. Among these, 1 million
                                              ARI is an acute infection of any part of
deaths are due to result of measles and
                                              respiratory tract & related structures
diphtheria both vaccine preventable
                                              including paranasal sinuses, middle ear,
diseases. Hospital-based statistics shows
                                              and pleural cavity. For qualifying as
that 13% inpatients pediatric deaths are
                                              ARI, the duration of acute illness must
attributable to pneumonia. ARI is more
                                              be less than 30 days except in the case of
common in urban than in rural areas. On
                                              acute suppurative otitis media (ASOM)
an average, a child in an urban area gets
                                              where duration may be less than14 days.
5-9 episodes of ARI annually during the
first 5 years of life, each episode lasting   Classification of ARI
for a mean duration of 7-9 days. In rural           1. Upper respiratory tract infections
areas, the annual incidence per child is                 (AURI) include: common cold,
1-3 episodes. Estimatedly, one in every                  pharyngitis, laryngitis, tracheitis,
30—50 episodes of cough develop into                     epiglotitis and otitis media .
pneumonia and without treatment 10—                 2. Lower respiratory tract infections
20% will die. Vaccine preventable                        (ALRI) include:          bronchitis,
                                                         bronchiolitis, and pneumonias.
diseases like measles, whooping cough
& diphtheria together account for 15-
                                              Mode of presentation
25% of all deaths. Without adequate
treatment, the child may die within 4-5               Children     with      pneumonia
days of the onset of illness. Morbidity is    generally present with symptoms of
equal in both developing and developed        cough or/ and difficult breathing. For
countries, but the mortality is 30 times      practical purposes, the cases are
greater in the developing countries.          classified as: no pneumonia, pneumonia,
                                              severe pneumonia, and very severe
                                              illness. Acute lower respiratory tract
       In 50-60% of children, the             infection (e. g. pneumonia) is a serious
causative agents in lower respiratory         life threatening illness with high
tract infection (LRTI) are bacterial          mortality . This mortality can be reduced
agents – the common bacteria being H.         by timely diagnosis, adequate and


                                                                                          35
IJPD, 2004; Vol I No.3


effective management with relatively        Chest in-drawing means inward
cheap and effective antibiotics and good    movement of lower chest wall
nutrition, health education as well as      /(intercostal   &    subcostal)   while
good hygiene.                               breathing in (inspiratory indrawing).
                                            Look for the chest in- drawing when the
Clinical assessment                         child is quite/calm or sleeping. Crying
 History taking:                            may mask chest indrawings.
Ask about
   • Age,                                           In children below 2 months of
   •    If coughing, for how long?          age, presence of any of the following
   • About feeding; is child able to        indicates severe disease:
       drink?                                •    Fever (38oC or more)
   • Did the child has antecedent history    •    Convulsions
       of measles ?                          •    Abnormal sleepy or difficult to wake
   • History of diarrhea / and or fever,     •    Stridor in calm child
   • Drowsiness and seizers                  •    Wheezing
   • Convulsions                             •    Not feeding
   • Fast breathing ,chest in-drawing        •    Tachypnea
       and abnormal sounds like stridor,     •    Chest indrawing
       grunting                              •    Altered sensorium
                                             •    Central cyanosis
  look / listen for:                         •    Grunting
    o Whether the child is calm,             •    Apnoeic spells or
    o How many breaths/m,                    •    Distended abdomen.
    o Chest in-drawing,
    o Stridor, wheeze,                              Such children should be referred
    o Drowsy,                                    to hospital for admission and
    o Febrile, hypothermia,                      treatment with injectable antibiotic
    o Severe malnutrition                        like gentamycin, ampicillin or any
                                                 other feasible antibiotic. Supportive
                                                 care must be continued.
Physical examination
                                                 Management
Fast breathing: Count the respiratory
rate for one minute. Expose the chest             A) No Pneumonia:
and abdomen before the counting. Use             Home care should be given to the
the second-hand of wrist watch. Count            children with common cold, cough
the respiratory rate by looking at               and fever (ie children with no
abdominal/lower chest wall movements.            pneumonia). These children do not
Count only when the baby is quite and            require treatment with antibiotics
calm or sleeping.
                .                                because
                                                   •    Majority are viral, where
Fast breathing is considered if:                        antibiotic is not effective.
Respiratory rate is
                                                   •    May produce side effects with
60 or more in a 2 month old child                       no clinical effects.
50 or more in 2-12 months child                        • May       produce      resistance
40 or more in 12 -60 months child                         strains.


                                                                                       36
IJPD, 2004; Vol I No.3


         •   Unnecessary financial loss.             breathing. The children in the age group
                                                     of 2 months to 5 years should be treated
                                                     as follows:
Mothers should do the following:
  •   Continue feeding as before. If the             Table IV: Dose Frequency and Rate of
      child is unwilling to take food, give          Administration of Antibiotics in Severe
      small quantities frequently.                   Pneumonia.
  •   Continue breast-feeding in breast-fed
      children.                                   Antibiotics                          Interval    Mode
                                                  First 48 hours
  •   Give enough fluids orally.                                       Dose
  •   Give Paracetamol for fever.
  •   If nose is blocked with nasal               Benzyl Penicillin    50000           6 hrly      IM
      secretions, then clean the nose with        Or Ampicillin Or     IU/Kg           6 hrly      IM
      normal saline drops.                        Chloramphenicol      50 mg/Kg        6hrly       IM
                                                                       25 mg/Kg
  •   Do not use medicated nasal drops
      which may be harmful.
  •   For cough and cold may give honey,          If condition improves, continue for next 3 days
      ginger, tulsi etc. but not to the baby
                                                  Procaine             50000/kg        Once        IM
      below two months of age.
                                                  penicillin Or        (max 4 lakh)    daily
  •   Mothers should be aware about the                                50 mg /kg                   Oral
      danger signs of pneumonia like;             Ampicillin Or        dose            6           Oral
      breathlessness, intercostals recession,                          25 mg/kg        hourly
                                                  Chloramphenicol
      convulsions and irritability etc. so that                        dose            6
      she brings the child immediately for                                             hourly
      the treatment.
                                                  If there is no improvement over the next 3 days
B) Pneumonia;                                            Change to chloramphenicol          IM,         if
        In developing countries, bacterial               Ampicillin was started initially
pneumonia like streptococcal pneumonia
and Hemophilus influenzae type b are                     Change to Cloxacillin 25 mg /kg/dose 6hrly
most common in the age group of 2                        IM with Gentamycin 2.5mgm /kg/dose
months to 5 years, followed by viral                     8hrly IM, if chloramphenicol was started
                                                         initially
pneumonia. The former organisms are
sensitive to Co-trimoxazole, which is the                If    condition    improves,           continue
drug of choice for the treatment of                      chloramphenicol only
pneumonia.       The      efficacy      of
                                                  Symptomatic treatment for fever and wheeze if
Cotrimoxazole is similar to ampicillin            required.
and procaine penicillin and cure rate is
about 95%. At the same time,                      Regulate fluid and food intake.
cotrimoxazole is also less expensive and          On discharge advise the mother to continue home
cost- effective.                                  treatment.

        The children suffering from
pneumonia should be given treatment as                       Treatment with antibiotics should
in table:                                            be continued for at least 5 days.
                                                     Continue treatment for at least 3 days
Severe pneumonia:                                    after the child recovers.
       In severe pneumonia, there is
chest indrawing in addition to fast


                                                                                                        37
IJPD, 2004; Vol I No.3


                         Table II: Antibiotic Dosage in Pneumonia



                                                            Amoxicillin thrice Procaine
         Age / weight        Co-trimoxazole           twice Daily orally       penicillin
                             daily orally.
                                                           Tb.                        IM              once
                             †Ad.Tb            Pd      Tb* syrup                      daily
                             Syrup**                       250mg               5ml

         <2 months           ¼         1        2.5ml         ¼          2.5ml        200000 IU
         <5Kg
         2—12 months         ½         2        5ml           ½          5ml          400000 IU
         6—9 Kg

         1—5 yrs             1         3        7.5ml         1          10ml         800000 IU
         10—19 Kg


                 †Ad.Tb. Sulphamethoxazole 400mg & Trimethoprim 80 mg
                 *Pediatric tablet: Sulphamethoxazole 100mg & Trimethoprim 20 mg
                **Pediatric syrup. Each TSF (5ml) Sulphamethoxazole 200mg & Trimethoprim 40 mg



     •  Cotrimoxazole should not be                   If cloxacillin and gentamycin are started,
        given to premature babies and in              they should be continued at least for 3
        cases of neonatal jaundice.                   weeks.
     • Less than two months child with
        rapid breathing and drowsiness                Very severe illness:
        should be treated as a                                The child is too sick if s/he is not
        case of severe disease/pneumonia              able to drink/feed, is having convulsions,
     • The tablets are crushed and                    is sleepy, and is having stridor when
        mixed with water. The mixture                 calm with severe chest indrawing and
        should be given to the child                  severe malnutrition. It may be because
         with a spoon.                                of meningitis, encephalitis, and severe
     • Cotrimoxazole should be given                  pneumonia etc. thus there is need of
        for 48 hours initially followed by            appropriate diagnosis and treatment. If
        the re-assessment of the child.               there is difficulty in diagnosis and
     • If there is improvement, continue              treatment, the children should be
        same treatment for further 3                  referred to FRU.
        days; and
     • If there is no improvement or the                       The child with very severe illness
        condition deteriorates, the                   must be treated in a hospital with
        child should be brought for                   facilities of oxygen and intensive care
     revaluation and new treatment                    as well as invasive facilities.
     started as per the
        type of pneumonia.


                                                                                                 38
     IJPD, 2004; Vol I No.3


Antibiotics  In all such cases the drug of
                 Dosage                             Route   Wheezing
                                Frequency
          choice is chloramphenicol IM.
                                    Age< 7d-                        Wheezing is referred to high-
                                    7days 2month            pitch whistling sounds audible without
Inj. Benzyl         50000           12    6 hrly    IV/IM
penicillin If
           or                                               auscultation by the stethoscope. About
                the IU/Kg/dose
                     condition      hrly
                                 improves after    48
                                                            30-50 % of all children suffer from one
     hours:
Inj. Ampicillin     50mgm/Kg/dose 12      8 hrly IV/IM
          o Change IM chloramphenicol to oral               or more bouts of wheezy chest during
and                                hrly
Inj. gentamycin chloramphenicol, and continue to
                    2.5                                     the first decade of life, causing
                complete 10 days’ course. 8 hrly
                    mgm/Kg/dose    12            IV/IM      considerable anxiety to the parents.
                                   hrly                     Wheezing is due to the obstruction of
                                                            flow of air in the small air ways, which
                If the condition does not improve           might be due to inflammation caused by
                /or deteriorates after 48 hours             infection as in pneumonia or allergy as
          o     Change over from chloramphenicol            in bronchial asthma. Pressure from
                to IM cloxacillin and gentamycin            outside the bronchi may also be
                IM.                                         responsible in some cases. Thus, all that
          o     On improvement continue for 3               wheezes is not asthma.
                weeks.
                                                               Causes:
     Treatment of a childless than 2                               I.   Wheeze associated with lower
     months                                                             respiratory      tract    infection
                                                                        (WLRI).
                                                                  II.   Bronchiolitis
             Cough, running nose and fever                       III.   Bronchial asthma
     are not the usual features in young                        IV.     Tropical eosinophilia
     infants with pneumonia. There may be                         V.    Loeffler’s syndrome
     only fast breathing/ indrawing of chest.                   VI.     Hypersensitivity pneumonitis
     The pneumonia is always severe in the                      VII.    Rare causes like inhaled foreign
     young infant and the low birth weight                              bodies
     baby may die from cold stress/                            VIII.    Pressure from large mediastinal
     hypothermia even in hot climate. In such                           nodes
                                                                 IX.    Pressure from anomalous left
     conditions, it is very difficult to
                                                                        pulmonary artery
     differentiate between severe pneumonia,                      X.    Cystic fibrosis of the lungs
     septicemia,     and    meningitis.   But                    XI.    Pulmonary hemosiderosis
     whatever it may be, treatment is same.                     XII.    Tuberculous lymph glands
                                                               XIII.    Mediastinal cysts and tumors
              These     children  must     be
     hospitalized and treated with injectable               Presentation
     benzyl penicillin or injection penicillin                 Wheezing child may present as:
     and gentamycin. Here chloramphenicol                   o    Wheezing without associated
     is not the drug of choice.                                  respiratory distress.
                                                            o    Wheezing        with  respiratory
          •     ►Maintain the body temperature.                  distress.
          •     Treat associated complications if           o    Recurrent wheezing.
                any.
          •     Continue exclusive breast feeding           Management
                and home care.                              I.  Management of wheezing without
                                                                associated respiratory distress.


                                                                                                        39
IJPD, 2004; Vol I No.3


      Give oral salbutamol in the                        If there is fast breathing but no
      following doses:                         respiratory distress, treat for pneumonia,
   1. Child less than 10 Kg body weight,       give oral SBM
                                                         If No respiratory distress and no
      give 1 mg 8 hourly orally after
                                               fast breathing then treat for ‘no pneumonia’,
      food.                                    cough or cold; give oral SBM.
   2. Child weighing 11-19 Kg, give 2
      mg 8 hourly orally after food.           Dosage of oral salbutamol (Oral salbutamol
   3. Salbutamol is given only for few         three times daily)
      days.                                    Age /weight           2mg tablet   4      mg.
II. Management           of      wheezing                                         tablet
      associated      with     respiratory     2 months upto 12      ½            ¼
      distress and recurrent wheezing.         months (<10 Kg)       ***          ***
                                               12 months upto 5      1            ½
                                               years (10-19 kg)      ***          ***
    Here rapidly acting bronchodilators
are required to be given as follows:
                                               Advice to mothers
 Rapid-acting bronchodilator
                                                      Mothers play a key role in the
   Nebulized         In the dose of 0.5ml
 salbutamol         SBM plus 2.0ml of          management of illnesses in infants and
 (5mg/ml)           sterile    water    may    children. Majority of cases of pneumonia
                    repeat after 20 minutes.   are to be treated at home, therefore
 Subcutaneous       `In the dose of            mothers must be advised on:
 Epinephrine        0.01ml/kg          body    o   How to give antibiotics to the child in
 (Adrenaline)       weight, may repeat             proper dosages.
 1:1000=0.1%        after 20 minutes           o   Continue adequate feeding including
 Subcutaneous       `0.1 mgm/Kg body wt.           breast –feeding in small quantities and
 terbutaline        may be repeated after          at frequent intervals, as the child may
                    30      minutes    upto        not be willing to take feed.
                    maximum of 3 times         o   Mothers should know and understand
                    (total 0.3 mgm)                the signs whether the child is improving
                                                   or worsening.
                                               o   Danger signs should be explained to the
        Wait for 30 minutes after the last         mother so that she immediately
dose of administration; if the child               recognizes the worsening condition of
responds well, treat at home with oral             the child and brings her for treatment;
salbutamol. If there is no improvement,            failure to do so may cost the child her
refer the child for hospitalization.               life.
                                                   Various danger signs are:
Children with Recurrent Wheezing                   - Difficult and rapid breathing.
(Asthma)                                           - Chest indrawings
  Give rapid acting bronchodilator as              - Refusal of feeds.
mentioned above.                                   - Eating and drinking poorly
  Asses the child’s condition 30 minutes              excessive sleeping/ drowsiness.
later:                                             - Convulsions.
        If respiratory distress or any             - Cyanosis.
danger sign is present, treat for severe
pneumonia or severe disease (refer)            Precautions to be taken by the mother:
                                                  Keep young infants warm and away
                                                  from the draught.


                                                                                         40
IJPD, 2004; Vol I No.3


    Exclusive breast feeding upto 6                  media is a common cause of fever
    months                                           among children.
    Complete       immunization      on
    scheduled dates                                  Treatment:
    Prophylactic Vit. A
    Hand-washing before feeding and                         Fever and infection in children
    touching the child especially young              are not synonymous; antimicrobial
    infants.                                         agents should not be used as
    Smoke- and dust-free environment.                antipyretics and empirical trails of
                                                     medication should thus be avoided.

Mothers of sick children are themselves of poor              Fever with temperatures less than
health and anemic, so they should be advised about   39º C in healthy children usually does
their nutrition and birth spacing. Counsel them to
adopt birth spacing in the interest of her and her
                                                     not require treatment. However, as the
child’s health.                                      temperatures become higher, patients
                                                     tend to become more uncomfortable and
                                                     administration of antipyretics often
                                                     makes patient feel better. Other than
Fever                                                providing        symptomatic        relief
       Fever is defined as an elevation              antipyretics do not change the course of
of body temperature in response to any               the infectious disease. Hyper-pyrexia
pathological stimulus.                               (>41º C) indicates greater risk of severe
                                                     infection, hypothalamic disorders, or
        American College of Emergency                CNS hemorrhage, and should always be
Physicians has published a clinical                  treated with antipyretics.
policy on febrile illness in children that
chooses a rectal temperature of ≥38◦c                        Aspirin, acetaminophen and
(100.4◦F) as the most widely used                    ibuprofen are inhibitors of hypothalamic
definition of fever.                                 cyclo-oxigenase, thus inhibiting PGE-2
                                                     synthesis. These all drugs are equally
        Fever is a sign that the body is             effective antipyretics. Acetaminophen
fighting an infection. The main reason to            10-15 mg/kg orally every 4 hours is not
treat the child is to make him or her feel           associated with significant adverse
better. When the child is achy and fussy,            affects; however prolonged use may be
he/she may need some medicine.                       associated with renal injury and massive
                                                     overdose may be hepatotoxic. Ibuprofen,
         Common cold, pharyngitis, acute             5-10 mg /kg orally every 6-8 hours may
 otitis media, mastoiditis and pneumonia             cause dyspepsia, gastrointestinal bleed,
 are the usual acute respiratory illnesses           reduced renal blood flow, and rarely
 leading to fever in children. These are             aseptic meningitis & aplastic anemia.
 often viral in etiology. Throat should
 always be examined to exclude                       Treat fever
 follicular tonsillitis and diphtheria.                if Fever is high (≥39°C), give
 Other important area to be examined is              Paracetamol
 ear, where acute supparative otitis                   If fever is not high (38-39°C), advise
                                                     the mother to give more fluids



                                                                                            41
IJPD, 2004; Vol I No.3


  If fever continues for more than five                  Microorganisms, which as part of
days, refer the patient to a hospital for        their evolution chose to be human
further assessment.                              pathogens, have adapted themselves to
  Fever alone is not the reason to give          thrive and multiply more efficiently at a
an antibiotic except in a young infant           temperature of 37C° - ie the human
(age < 2 months)                                 body’s normal internal temperature.
                                                 When they invade the body with the
                                                 expectation of finding an optimal
Paracetamol dosage                               temperature, the body increases its
                                                 temperature (fever) so as to deprive
Age or weight    100 mg tablet   500 mg tablet   them of such cozy atmosphere. Thus
                                                 fever is the body’s defence to microbial
2 months up 1                    ¼               invasion.
to 3 years
(6-14 Kg)                                                Body has its own mechanisms of
3 years up to 1 ½                ½               fighting which require boost only when
5 years (15-                                     in danger of being overwhelmed. Most
19 Kg)                                           of the times our body can ward off the
                                                 invading microorganisms on its own.
Other ways to help the child feel                         Reducing    fever    by    giving
better                                           antipyretics for all fevers is simply to
                                                 over-drugging children. It is only when
    •   Give the child plenty to drink to        the temperature exceeds 104°, the
        prevent dehydration and help the         patient is in discomfort, or when there is
        body cool itself.                        previous history of febrile convulsions,
    •   Keep the child still and quiet.          should pharmacologic antipyresis be a
    •   Keep the room temperature at             part of the drug regimen.
        about 70°F to 74°F.
    •   Dress the child in light cotton                  Parents should be advised to
        pajamas so that body heat can            offer lukewarm sponging or bathing as a
                                                 good alternative. Also, the patient
        escape.
                                                 should sufficiently be hydrated orally (if
    •   If the child is chilled, put on an       needed, intravenously) to provide
        extra blanket but remove it when         enough water for perspiration and
        the chills stop.                         evaporation.

*******************************                          When    advised,      antipyretics
                                                 should be prescribed in full dose and at
                                                 recommended intervals. The dose of
                                                 paracetamol is 325 per dose every 4
                                                 hourly, with a maximum of 5-6 doses in
                                                 24 hours. The dose of ibuprofen is
                                                 200mg/400 mg every 6-8 hourly.

                                                         Appropriate antibiotic theray is
                                                 the mainstay of treatment in bacterial
                                                 infections. In viral infections temperature
                                                 is symptomatic.(Ed)




                                                                                         42
IJPD, 2004; Vol I No.3



DIABETES IN                                            intensive approach to the diabetic
                                                       pregnancy has become the standard. A
PREGNANCY                                              true shift in the therapeutic paradigm
                                                       has occurred. Whereas simple maternal
                                                       and fetal survival used to be the primary
                  Rehana Kausar                        goal in the diabetic pregnancy, today’s
_________________________________                      chief concern is to approximate the
                                                       clinical outcomes of non-diabetic
        Before insulin was discovered,                 pregnancy.
patients of reproductive age group
usually died within 1-2 years of onset of                      An essential concept that has
illness and pregnancy was very rare.                   evolved from years of epidemiologic
Despite the immediate improvements in                  observation is the differential effect of
maternal survival that occurred when                   diabetic control during preconception
insulin became available, perinatal                    and the early first trimester (which
outcome remained poor. Pregnancy in                    practically encompasses the period of
the diabetic woman was complicated by                  organogenesis) from that during the final
a high rate of fetal malformations,                    two trimesters. Glycemic control in the
sudden fetal death in late pregnancy,                  early phase primarily affects the risk of
pre-eclampsia and eclampsia, death from                fetal congenital malformations, whereas
prematurity and fetal injury and death                 maternal gestational outcomes , the risk
from macrosomia. During the past three                 of fetal macrosomia (and its attendant
decades, a great deal has been learned                 obstetric complications) and much of the
about the important relationship between               risk of perinatal complications are
maternal glycemic control before and                   influenced by the latter phase.
during pregnancy and fetal outcome. The
perinatal mortality has simultaneously
improved as an improved and an

Table 1: White Classification of Diabetes During Pregnancy
     Class                                             Description
      A           Abnormal glucose tolerance test
                  (asymptomatic ; normal glucose levels achieved with diet only)

      B           Adult onset diabetes (age > 20) and short disease duration (<10 yrs)
      C           Youth onset diabetes ( age 1-19) or relatively long disease duration (10-19 yrs)
      D           Childhood onset (age <10 ) , very long disease duration (>20yrs) , or evidence of
                  background retinopathy
       E          Any diabetes with evidence of vascular disease in the pelvis
                  (diagnosed by plain radiograph)
      F           Any diabetes with the presence of renal disease
      R           Any diabetes with the presence of retinopathy
      RF          Any diabetes with the presence of both renal disease and proliferative retinopathy
      G           Any diabetes with history of multiple failures during pregnancy
      H           Any diabetes with atherosclerotic heart disease
      T           Any diabetes post-renal transplantation




                                                                                                 43
IJPD, 2004; Vol I No.3


Classification
                                            Epidemiology
        The White Classification of                 The incidence of diabetes
Diabetic Pregnancy is given below.          mellitus in pregnancy is less than 0.5%.
Although this classification is widely      Many surveys report an incidence of pre-
used, it makes no attempt to take into      gestational diabetes of 2 per 1000
account the degree of glycemic control      pregnancies.
during or before pregnancy. Many
centres prefer to use a simpler             Screening
classification   which places diabetes              Despite more than 30 years of
primarily in the context of pregnancy (ie   research, there is lack of consensus
as a pre-existing condition) or one that    regarding the optimal approach to
was acquired during gestation (table 2)     screening for gestational diabetes. The
.Patients with either type I or type II     best time for diabetes screening is
diabetes have pre-gestational diabetes.     between 24 and 28 weeks’ gestation
Those women with diabetes diagnosed         because peripheral insulin resistance and
during pregnancy itself have gestational    insulin response to a glucose load start to
diabetes                                    increase at that time. While some
                                            advocate screening for all expectant
Table 2: Alternative Classification of      mothers, others reserve it for potential
        Diabetes in Pregnancy
                                            candidates. Such patients include those
Overt diabetes                              with

  Type I diabetes                                  Family history of diabetes
       Complicated by retinopathy                  Marked obesity
       Complicated by nephropathy                  Prior gestational diabetes
       Complicated by coronary heart               Glucosuria
           disease                                 History    of    poor    obstetric
  Type II diabetes                                 outcome
       Complicated by retinopathy                  Having a previous birth of a
       Complicated by nephropathy                  macrosomic baby
       Complicated by coronary artery              Age over 30
           disease                                 Presence of polyhydramnios or
  Gestational diabetes                             recurrent vaginal candidiasis in
       Diet controlled                             present pregnancy
       Insulin requiring




                                                                                    44
IJPD, 2004; Vol I No.3


           Criteria for diagnosis of gestational diabetes with 100 gm of oral glucose
           tolerance test
           Time                     Whole blood(mg%)            Plasma (g%)
                                                                ``
           Fasting                              90                       105
           1hour                               165                       190
           2hours                              145                       165
           3hours                              125                       145

                                                                 if any two or more
                                                                values are elevated ,
                                                                  the GTT must be
                                                                considered abnormal

           Criteria for diagnosis of impaired glucose tolerance and diabetes with 75 g
           (WHO) oral glucose
           Time               Normal             Impaired glucose Diabetes
                                                 tolerance
           Fasting                   <105             105-<140             >140
           2 hour post               <160            160 to<200            >200
           glucose



        Evaluation for diabetes may be            100g test is used without the preceding
done in one or two steps. In the two step         50g test. .The WHO (1985) recommends
procedure, a 50gm oral             glucose        the 75g 2-hour oral glucose tolerance
challenge test is followed by a diagnostic        test ie the one step diagnostic procedure
100g oral glucose test if results exceed a        and this approach is often used in
predetermined         plasma       glucose        Europe. The criteria are the same as
concentration. Plasma glucose is                  those of non-pregnant individuals, with
measured 1 hour after a 50g load without          the important modification that impaired
regard to the time of the day or time of          glucose tolerance (2-hour plasma
last meal. A cut-off value of 140mg is            glucose>140mg)          be treated in
used. In the one step test, the diagnostic        pregnancy as diabetes.
    ___________________________________________________________

                                                Pre-gestational diabetes

                                                        In diabetic women with fair to
                                                good glycemic control, fertility is well
                                                maintained. As a result, pregnancy occurs
                                                commonly in women of child bearing age.
                                                Generally speaking, the fetal risks
                                                associated with both types of diabetes are
                                                similar. However, the maternal risks are
                                                more closely aligned with the presence of
                                                end-organ complications, which tend to be


                                                                                         45
IJPD, 2004; Vol I No.3


associated with the established duration of           in the case of fetal malformations,
diabetes. For this reason, and because of             maternal HbA1 at the end of first
their absolute lack of endogenous insulin             trimester is positively correlated with
production (which predisposes them to                 this risk. The exact explanation for the
ketosis and more erratic glycemic control),           effects     of   diabetes    on    fetal
women with type 1 pre-gestational                     complications      is    unclear     but
diabetes tend to have more difficult                  presumably involves several factors
courses.                                              e.g       hyperosmolarity,      ketosis,
                                                      disruption of glycolysis, DNA
Effects on the fetus: The abnormal                    glycosylation, inhibition of various
metabolic milieu of the diabetic pregnancy            growth factors, the generation of free
has substantial deleterious effects on the            radicals,      altered     myoinositol
fetus. The diabetic pregnancy is associated           metabolism, cell membrane lipid
with multiple potential complications for             peroxidation        and       decreased
the fetus-neonate, which directly or                  prostaglandin concentration.
indirectly result from the maternal
metabolic derangements:                           Table 3: Congenital abnormalities found
                                                  more frequently in infants of mothers with pre-
    Congenital anomalies (6-8%): The
                                                  gestational diabetes
    incidence of congenital malformations
    is 2-4 times more than the expected           cardiac                   gastrointestinal
    frequency. There is a substantial             transposition of the      anal/rectal atresia
    positive correlation between the              great vessels
    degree of maternal hyperglycemia              atrial septal defects
    present at conception and /or first           ventricular septal
                                                  defects
    trimester . Overall the rate of               spinal /central nervous   genitourinary
    congenital      malformations      may        system                    renal agenesis
    approach 10% when no specific                 spina bifida              cystic kidney
    preconception glycemic goals are              anencephaly               ureteral duplex
    attained. The various congenital              hydrocephalus
                                                  other
    malformations are listed in table 3.          caudal regression
    Early intensive diabetes management           syndrome
    has been shown to be advantageous for         situs inversus
    fetal and maternal health and also very
    cost-effective.                                   Hyperinsulinemia and macrosomia:
                                                      Poor glycemic control spurs fetal
                                                      growth during the second and third
Early detection of fetal anomalies                    trimesters,   as    excess     nutrients
Estimation of glycosylated hemoglobin A               (glucose, aminoacids, free fatty acids)
(HbA1c) before 14 weeks can predict affection
                                                      are delivered to the fetus. Excess
of the fetus. Mothers with Hba1c values
<=8.5% have got least chance of severe
                                                      glucose from the maternal circulation
malformations . Chances increase if value rises       stimulates fetal beta-cells, leading to
to 9.5% or more. Maternal serum alpha                 increased      anabolic       processes,
protein level at 16 weeks and a detailed USG          including the deposition of excess
at 20 weeks are recommended.                          calories as fetal fat. This fetal fat is
    Early pregnancy loss: The risk of                 deposited in the insulin dependent
    spontaneous abortions is increased. As


                                                                                                  46
IJPD, 2004; Vol I No.3


    tissues e.g liver, intra-abdominal, and               Maternal Effects
    thigh adipose stores.                                        In patients with pregestational
      Birth injuries are associated with                  diabetes, the progressive insulin resistance
      prolonged labour and shoulder                       of pregnancy results in increased insulin
      dystocia, due to an oversized baby.                 requirements, typically 2-3 fold their
      The injuries include shoulder                       prepregnancy dose. The increase in insulin
      dystocia, brachial plexus injury                    requirements is directly related to the
      (Erb’s palsy), fractures of the                     maternal weight gain in pregnancy.
      clavicle and humerus, cerebral                      Diabetic women are also more prone to
      injury, and increased requirements                  hypoglycemia and ketosis in pregnancy.
      for both cesarean and forceps
      delivery.                                              Hypertensive disorders: The incidence
      Late fetal demise: Stillbirth rate in                  of pregnancy-induced hypertension in
      diabetic pregnancy is reported to be                   pre-gestational diabetes is 15% ie two
      0-4% with good diabetic control.                       to four fold higher than in normal
      These fetal deaths are without any                     pregnancies. In more advanced
      identifiable cause such as placental                   diabetes, the incidence is 30%.
      insufficiency, abruption, fetal growth                 Hypertensive disorders are more
      restriction and oligo-hydramnios.                      common when glycemic control is
      These infants are typically large for                  poor.
      age and die before labour, usually at                  Preterm labour complicates 10-30% of
      35 weeks or later. It may be due to                    pre-gestational diabetic pregnancies
      impaired placental oxygen transfer                     and this rate also increases with
      due to placental vasculopathy, fetal                   worsening severity of disease, elevated
      acidosis, and villous hydrops.                         plasma glucose levels and presence of
                                                             uro-genital infections.
Neonatal complications include:                              Hydramnios is seen in 16% of all
                                                             diabetic        pregnancies,       with
         Respiratory distress syndrome                       comparatively higher rates in pre-
         Neonatal hypoglycemia                               gestational diabetes. Increased fetal
         Neonatal hypocalcemia                               urinary flow, and altered amniotic
         Polycythemia                                        fluid osmolarity have been postulated
         Neonatal hyperbilirubinemia                         in the patho-physiology.
         Cardiac hypertrophy                                 Pyelonephritis is reported in 4% of
                                                             diabetic pregnancies.
                                                             Cesarean section is two times more
                                                             common in diabetic mothers than their
The risk of future type 1 diabetes in the off-spring of      non-diabetic counterparts, mainly due
mothers with type 1 diabetes is 1.3%; for those              to increased rates of macrosomia.
having fathers with this type is 6%. There is a              Vascular changes such as retinopathy,
greater genetic predisposition in type 2 diabetes,           nephropathy, coronary artery disease,
with the risk being approximately 15% with one               and neuropathy may be worsened
affected parent and as high as 60% to 75% when               during pregnancy.
both parents are affected.




                                                                                                   47
IJPD, 2004; Vol I No.3


Management                                         acting insulin the usual ratio is 2:1 0f
1. Preconceptional screening: The theme            N:R (NPH:regular) before breakfast
   of diabetic control in pregnancy is to          and 1:1 before supper.
   approximate the non-diabetic state; ie      4. If the blood glucose level is high and
   to lower blood glucose levels into a            ketones are present, the patient
   range as close to normal as possible.           requires more insulin. If ketones are
   Such care requires the joint efforts of         present and blood glucose is normal,
   an obstetrician, internist, diabetologist       the patient requires extra calories,
   and neonatologist. It is imperative that        particularly before bedtime.
   all women with pre-gestational              5. The diet should contain 30-35 kcal/kg,
   diabetes attain strict glycemic control         consisting of three meals and a
   as soon as possible upon discovery of           bedtime snack, comprising 50-60%
   pregnancy if such control is not                carbohydrates, and less than 30% fat,
   achieved during the preconception               with adequate amount of dietary fibre.
   phase. This may require a brief             6. A graded exercise programme should
   hospitalization     to     assess     the       be considered because it improves
   effectiveness of therapy. Treatment             insulin sensitivity and glucose levels in
   options for women with diabetes                 both pregnant and non-pregnant
   during pregnancy include a variety of           patients.
   insulin combinations. The most              7. Antenatal visits should be scheduled
   common        combinations        include       every 1-2 weeks during gestation to
   mixtures of intermediate-insulin, such          ensure proper glycemic control
   as NPH or lente with short-acting               throughout pregnancy. This is more
   insulin (Regular insulin).                      important in the last trimester of
2. There is frequent change in insulin             pregnancy because insulin resistance
   need in pregnancy and changes in                increases and most of the insulin
   dosage should be made in small                  dosage adjustments are required.
   increments at a time. Glycemic goals        8. HbA1c levels as an index of recent
   are shown in table 4. Frequent blood            glycemic control should be monitored
   sugar estimation should be done. The            every 4-6 weeks.
   aim is to maintain blood sugar within       9. Blood pressure and urinary albumin
   normal     range     without     causing        excretion should be monitored closely
   troublesome      hypoglycemia.       Oral   10. A retinal evaluation should be done in
   hypoglycemics are not used in                   every trimester in those without known
   pregnancy as they can cause fetal               eye disease and every 1 to2 months in
   teratogenesis. Changes in insulin               those with established retinopathy.
   dosage should be made at no more            11. Sonogaphic evaluation of the fetus is
   frequent intervals than every 3 to 4            done to rule out any congenital
   days, so that trends in glycemia are            abnormalities and to detect fetal
   addressed.                                      macrosomia or growth retardation.
3. For patients receiving two injections       12. Fetal well-being is assessed from 32
   daily , two thirds of the dose should be        weeks onwards. This is done by
   given in the morning before breakfast,          various methods including fetal heart
   with the remainder being given before           rate testing, non-stress test or
   the evening meal. For patients taking a         contraction stress test        and the
   mixture of intermediate- and short-



                                                                                         48
IJPD, 2004; Vol I No.3


    biophysical score. These should be             An intravenous drip with 5% dextrose
    done bi-weekly between 26-36 weeks.            is started with 10 units of soluble
13. It is essential to obtain accurate dates       insulin. An infusion rate of 100-125
    in diabetic pregnancies; USG should            ml/hr (1-1.25 units/hr) will maintain a
    be performed in first trimester before         glucose level of 100mg/dl. Blood
    macrosomia becomes established.                glucose levels are measured hourly
14. Alfa-fetoprotein concentrations should         using dextrostix and insulin dosage is
    be monitored between 16-21 weeks.              adjusted accordingly. If the labour fails
15. Timing of delivery: A universal                to start within 6-8 hours or progress of
    guideline has not been formulated. The         labor is unsatisfactory, cesarean
    possibility of fetal demise in a               section should be performed.
    potentially hostile environment needs      19. Procedure for cesarean: Cesarean is
    to be weighed against the risk of              scheduled for morning. On the day of
    potential premature lung development.          operation, breakfast and insulin-dose
    But the fact that majority of fetal            are omitted. A 5% dextrose drip is
    deaths occur in the last two weeks of          started. The maintenance of dextrose
    pregnancy,      the    termination    of       and insulin dosage are the same as
    pregnancy should be done after 37              mentioned      above.     The    insulin
    completed      weeks.     If    adequate       requirement falls suddenly after
    glycemic control is achieved and the           delivery and after the omission of the
    pregnancy has been otherwise                   drip, pre-pregnant dose of insulin is
    uncomplicated, there is little reason to       given. Epidural or spinal anaesthesia is
    alter the natural course of pregnancy.         administered.
    In these situations a vaginal delivery
    should be planned. However, many           Table 4.  Glycemic goals for       intensive
    experts still recommend elective           management of diabetes during pregnancy
    induction between 36 to 38 weeks.
                                                 Criteria              Goals (mg/dl)
16. Women whose pregnancies are                                Preconception     2nd and 3rd
    complicated by poor glycemic control                          and first       trimester
    or who have other high-risk                                  trimester
    characteristics, should be delivered       Preprandial         70-110           60-90
    once fetal lung maturation has been          glucose
    achieved.                                  Postprandial        <140             <120
17. Early delivery, usually by cesarean, is      glucose
    recommended in the situation of a            at 2 hrs
    macrosomic infant. Generally, fetal
    weight more than 4500g is a strong
    indication for a cesarean delivery, and    GESTATIONAL DIABETES
    should be considered for fetuses           MELLITUS (GDM)
    weighing 4000 to 4500g.
18. Methods for normal delivery: Prior                Diabetes     diagnosed     during
    to the day of induction, the usual dose    pregnancy is called gestational diabetes
    of insulin is administered. No             mellitus. This category includes both
    breakfast is given. Induction is done by   diabetes that first appears during
    low rupture of membranes. Oxytocin         pregnancy and that which is first
    drip is started, if not contraindicated.   recognized during pregnancy. GDM is 10


                                                                                           49
IJPD, 2004; Vol I No.3


times more common than pre-gestational                 blood sugar <90 mg/dl and
diabetes. Its diagnosis is made routinely by           postprandial      levels    below120
oral GTT as described above. Specific risk             mg/dl.
categories have been described as above.               Initially a diet consisting of 30-32
Treatment consists of diet and exercise; a             kcal/kg per day is recommended
few patients will require insulin. GDM is              for the non-obese woman with
associated with significant risks to both              GDM. In an obese woman further
mother and fetus, although most series                 restriction, as low as 25kcal/kg per
have shown no increase in congenital                   day, is warranted.
malformations. There is no increase in                 Diet should contain 50-60%
rates of early fetal demise and risk of                carbohydrate, and less than 30%
congenital malformations; presumably                   fat      and       adequate     fiber
because hyperglycemia has not become                   (25gm/1000kcal).
established till late second trimester - well          Daily caloric intake should be
after the period of organogenesis. The                 divided equally between three
woman with GDM is at risk of recurrence                meals and one or two snacks. A
in later pregnancies and for type 2 diabetes           bedtime snack is important to
in later life. Many believe that GDM is                prevent fasting ketosis.
and type 2 diabetes mellitus are nothing               Insulin therapy is needed for
more than variations of the same general               women who are not able to
disease process or an unmasking of type 2              maintain their plasma glucose at or
diabetes in pregnancy. Recurrence rates                below 105mg/dl or their 2 hr
between 20-50 % have been reported in                  postprandial glucose at or below
future pregnancies.                                    120mg/dl.
                                                       Others recommend the use of
Complications of GDM:                                  insulin using the 1-hr postprandial
1. Fetal macrosomia                                    glucose reading of less than
2. Traumatic delivery                                  140mg/dl as threshold.
3. Neonatal complications related to
   hyperglycemia (hypoglycemia,
   hypocalcemia, hypomagnesemia,
   polycythemia, hyperbilirubinemia)            *******************************
   increased perinatal mortality

Pathogenesis: Like type 2 diabetes, GDM
is marked by a variable combination of
decreased      insulin  production    and       ◙     Studies across 25 countries have
decreased insulin action due to peripheral      shown that involvement in bullying (as
insulin resistance.                             a bully or a victim) is associated with
                                                negative social adjustment in later life.
Management:                                     This manifests as poorer relationships
     Treatment goals are similar to             with classmates, with bullies resorting
     patients with type 2 diabetes. Oral
                                                to alcohol abuse and weapon carrying.
     hypoglycemics are contraindicated.
     About 20% patients will require
     insulin. During 2nd and 3d
     trimesters maintain preprandial


                                                                                         50
IJPD, 2004; Vol I No.3



Food & Cancer Prevention                       Chemoprevention is considered as a
                                               strategy to block or reverse carcinogenesis
                                               from the very early stages. It has been
            Shabnam Bashir                     suggested that chemoprevention should be
_________________________________              considered as an inexpensive, cost
                                               effective and easily applicable approach to
        Cancer is a multi-factorial, multi-    cancer control.
faceted and multi-mechanistic disease
                                                        In 1981 Doll and Peto attempted the
requiring a multi-dimensional approach
                                               first    relative    quantification   of    the
for its treatment, control and prevention.     environmental contributions of a variety of
Cancer involves fundamental biological         factors such as diets, alcohol, tobacco,
processes concerning disorganized cell         occupation and radiation. Diet is not only a
replication, cell death and disorganization    source of antimutagens/ anticarcinogens but
of organ structure. For India, the annual      also a source of mutagens. The carcinogens in
estimate of cancer for the year 2001 was       the diet may be exogenous in origin or formed
9.8 lakh, while the annual mortality in        as a result of the interaction of components of
2000 was 7 lakh. The incidence of cancer       foods endogenously eg heterocyclic amines.
is on the rise, with multiple risk factors
                                                        Doll and Peto also estimated the
that involve an interplay between genetic      contribution of diet, and identified some
and environmental components. Diet is a        specific agents to have preventive influences
major environmental risk factor. The           on cancer. Throughout the 1930s and 1940s,
contribution of diet and nutrition status to   the modifying effects of diet on cancer
cancer risk and conversely to the              induced in animals by chemicals were very
prevention and treatment of cancer has         well    demonstrated.    Many     hypotheses
been a major focus of research as well as      proposed centered on nutritional deficiencies,
public health policy.                          which were believed to be provoked by
                                               carcinogenic compounds.
         Several epidemiological studies
                                               CHEMOPREVENTERS (Phytochemicals)
highlighted the role of vegetables and
fruits in reducing the risk of cancer in a
variety of organs and tissues. Nutrients               Cereals, vegetables, fruits, pulses,
which show modulatory effects in               spices and other plant foods contain many
experimental         cancers       include     micro- constituents other than vitamins
macronutrients such as fat, carbohydrates,     and minerals that are known to be
proteins, fibre and micronutrients such as     biologically active (Table I). The
vitamins - folic acid, riboflavin, β-          chemopreventers belong to over 25 classes
carotene, retinol, α-tocopherol, vitamin       of chemicals. They are safe and have low
B12 and minerals such as selenium, zinc,       or no toxicity.
magnesium and calcium. Recently,
however, the focus and emphasis has            Nutritive Chemo-preventers
shifted to a number of non-nutritional
components in our diet which possess                  A number of micronutrients in diet
anticarcinogenic     and     antimutagenic     have cancer preventive properties. These
properties. These are also known as            include vitamins A, C and E, β-carotene,
bioactive compounds or chemopreventers.        selenium and calcium. Most of      these
 Table I. Food sources of phytochemicals.



                                                                                           51
IJPD, 2004; Vol I No.3




Phytochemicals                                    Food source

Fiber (macronutrients)          Cereals (grains) fruits and vegetables
Caroterioids                    Yellow/orange vegetables. fruits and dark-green leafy vegetables
Allium compounds                Qnion, garlic, chives, leeks
Dithiolthiones/
glucosinolates                  Cruciferous vegetables
Isothiocyanates                 Cruciferous vegetables
Terpenoids                      Oil of citrus fruit peel
Phytoestrogens                  Cereals, pulses. sorghum. millets, soyabeans, fruits and berries
Protease inhibitors             Cereals. barley, wheat. oats. rye, soyabeans, kidneybeans and chick peas
Phytic acid                     Cereals, nuts, seeds, seasame seeds, lima beans, peanuts, and soyabeans
Flavonoids                      Fruits and vegetables
Phenolic compounds              Fruits, vegetables and tea
Plant sterols                   Vegetables
Saponins                        Soyabeans, yam and colacasia
                                                        binds to bile acid and shortens the
agents are antioxidants. Epidemiological                intestinal transit time. Bile acids are
studies have shown that the incidence of                believed to be one of the factors involved
certain forms of cancer is highest in people            in colon carcinogenesis by regulating gene
with a low dietary intake of the above                  expression II. The prevalence of colon
nutrients.                                              cancer in India is much lower as compared
                                                        to Western population, probably because
Non-nutritive chemo-preventers                          of higher unprocessed cereal intake with
                                                        more fibre.
        There are many non-nutrients in
diet with plausible cancer preventive                   Vegetables
effects. During the past few years,
research on the relationship between diet                       Green leafy vegetables, beans of
and cancer has shown that cereals,                      all varieties, cruciferous vegetables
vegetables, fruits, and certain beverages               namely cabbage, brussels sprouts,
contain a variety of potential cancer                   cauliflower and broccoli are rich in anti-
preventing substances.                                  carcinogens. Umbelliferae vegetables like
                                                        carrots, celery, parsnips, alliums namely
Sources of Non-nutritive Chemo-                         onions, garlic and chives, solanaceaous
preventers                                              vegetables like potato, tomato and brinjal
                                                        have significant levels of cancer protecting
Cereals                                                 non-nutrients .

        Cereals like wheat, rice, maize,                Fruits
millet, sorghum are principle constituents
of food. They provide protein, vitamins,                       All the citrus fruits, grapes, apples,
trace elements and varying amounts of                   strawberries, plums, pineapple, melons
non-starch polysaccharide (NSP)/dietary                 have high levels of protective phyto-
fibre. Although dietary fibre is not a                  chemicals. All the other fruits and dried
supplier of calories or essential nutrients, it         fruits also possess some amounts of
is important for intestinal functioning. The            anticancer agents.
dietary fibre lowers the intestinal pH,


                                                                                                           52
IJPD, 2004; Vol I No.3


Spice                                             cholesterolaemic, hypoglycaemic, anti-
        Spices and condiments which are a         inflammatory and antimicrobial properties.
part of the Indian diet have chemical             Turmeric, cloves, ginger, thyme, mustard
constituents which have antioxidant, anti-         and cinnamon have been reported to have
mutagenic       and       anti-carcinogenic       antioxidant and anti-mutagenic properties.
properties. Some of them have many
other beneficial effects like        hypo-        *********************************




Table II.    Nonnutrient chemopreventers - Mechanism of action

Category                                        Mechanism

Inhibitors of carcinogen formation              Inhibit formation of carcinogen eg
Caffeic acid, ferulic acid                      nitrosamines formation

Blocking agents Isothiocyanates,
diallylsulphide, ellagic acid, ferulic acid,    Inhibit the activity of enzymes (cytochrom P
dithiocarbamates                                450) which convert procarcinogens to
                                                carcinogens
Inducing agents
Isothiocyanates. sulpharaphane d-limonene,      Stimulate enzymatic system which are
terpenoids, curcumin                            involved in detoxification of carcinogens

Trapping agents Ellagic acid. N-
acetylcysteine                                  Physically react with carcinogens and
                                                detoxify them
Suppressing agents/ selenium, soya products
Isotlavones, phytoestrogens, epigallocatechin   Suppress different steps in metabolic
gallate (EGCG)                                  pathways required for tumour development




                                                                                            53
IJPD, 2004; Vol I No.3
Mechanisms of Action of Chemo-           Turmeric as Anticancer Agent
preventers                                       Among the spices, turmeric is
        The mechanism of action of       the most extensively used for its
chemo-preventers is complex. It          colour, taste and flavour. It is also
appears that most chemopreventers act    added to foods as a preservative. In
primarily as antioxidants, anti-         traditional medicine, turmeric has been
mutagens, immuno-modulators and          used as a potent anti-inflammatory
anticarcinogens" (Table II).             agent, carminative and antiseptic
        Broadly, the chemo-preventers    agent. Curcumin, the active principle
may act through detoxification           in turmeric, has strong antioxidant and
mechanism or by antimutagenic            anti-inflammatory potency. The NIN
processes at both the initiation and     studies on turmeric consisted of its in
promotion steps of carcinogenesis.       vivo and in vitro evaluation as a
                                         potential chemo-preventive agent. Its
Detoxificants                            potent anti-mutagenic effects were
        These phyto-chemicals induce     demonstrated against well known
drug metabolizing enzymes in the body    carcinogens. In order to understand the
and act by detoxifying the harmful       underlying mechanisms. experiments
substances capable of producing          were conducted to study the levels of
harmful effects. The anti-neoplastic     tissue      xenobiotic      metabolising
effects of inducing and inhibiting       enzymes in animals fed turmeric
agents in foods focus on specific        through diet. The results suggested that
mono-oxygenases like the aryl            there was stimulation of detoxifying
hydrocarbon hydroxylase (AHH),           enzymes        glutathione-S-transferases
uridine diphosphate - glucuronyl         (GSTs)       and     UDP      glucuronyl
transferase (UDPGT), and glutathione     transferases (UDPGT). Although drug
S-transferases I.                        metabolising enzymes are important in
                                         the carcinogen activation/deactivation
Antimutagens                             pathway, the propensity of DNA to
       Carcinogens bind to the cell      bind itself to the toxic metabolites of
macromolecules namely, DNA, RNA          carcinogens is equally important.
and proteins, and result in mutagenic    Turmeric/curcumin feeding to rats for
events leading to cell transformation    4 weeks prior to carcinogen exposure
and    neoplastic    changes.   Some     decreased the binding of liver DNA to
phytochemicals prevent these changes     the carcinogen benzo(a)pyrene.
from occurring either by directly
binding to the carcinogens/ their               As     oral     cancers   occur
metabolites or by metabolizing toxic     commonly in India, the effects of
xenobiotics. These are known as          curcumin and turmeric were assessed
antimutagens/ anticarcinogens.           in experimental tumourigenesis. Cheek
                                         pouches of certain animals were
        At the National Institute of     painted with the carcinogen, dimethyl-
Nutrition (NIN), Hyderabad, extensive    benanthracene (DMBA) with or
research has been carried out on some    without turmeric/ curcumin for
of the non-nutritive chemo-preventers    induction or retardation of tumours
such as garlic, onion, turmeric, green   along with feeding turmeric/ curcumin
leafy vegetables (spinach, amaranth)     through diet. At the end of 14 weeks, it
and cabbage. Some results of the NIN     was found that the animals .given
studies are highlighted here.            turmeric/ curcumin through diet or
                                         painted with curcumin had a lower
                                         percentage of microscopic tumours as



                                                                               54
IJPD, 2004; Vol I No.3
compared to controls which did not         that it was effectively counteracted
receive turmeric through diet. In          suggesting that in addition to anti-
animals which received curcumin,           initiating, detoxifying and antioxidant
most of the tumours did not go beyond      activities, curcumin also has the ability
grade I. The binding of tissue DNA to      to repair DNA.
carcinogen was found to be
significantly   reduced      in    the     Turmeric as antimutagen in humans
experimental       groups        given
turmeric/curcumin either through diet              Anti-mutagenicity effect of
or locally painted. These findings         turmeric was evaluated in human
suggest that turmeric/curcumin may         smokers who are known to excrete
act as anti-proliferators and anti-        mutagens. The excretion of urinary
promoters.                                 mutagens was reduced at the end of 15
                                           days of turmeric ingestion (1.5 g/day
Turmeric anti-initiator or anti-           orally for 30 days). The liver and
promoter                                   kidney function tests were not altered.
                                           A clinical trial in reverse-smokers who
        To know exactly at what stage      are at a high risk of palatal cancers in a
turmeric acts, tumours were induced        specific areas of Andhra Pradesh
by benzo(a)pyrine in mice which were       showed that turmeric administration
simultaneously fed turmeric/curcumin       (Ig/day for 9 months) had a significant
during the various stages of               impact on the regression of
carcinogenesis. While turmeric and         precancerous lesions such as red and
curcumin treatment during initiation       white patches over the palatal regions,
inhibited papillomas by 67 and 50%         and decreased the micronuclei and
respectively, the inhibition was 50 to     DNA adducts in oral epithelial cells
100% post-initiation. While turmeric       which are markers for genomic
can act in the both phases (initiation &   damage.
postinitiation), curcumin can act only
in post-initiation process..               Turmeric /curcumin as antioxidant

Curcumin on DNA repair                            Turmeric and curcumin have
                                           been shown to be antioxidants. Studies
        DNA repair is one of the           in the animal model where oxidant
important mechanisms of protecting         damage was induced by paracetamol
the system from the onslaught of           and DMBA showed that the levels of
genotoxic agents. Therefore, the effect    TBARS and SGOT and SGPT were
of curcumin was studied on the single      reduced in liver of carcinogen-treated
strand breaks (ssb) in the DNA of          rats, demonstrating its antioxidant
yeast,   Saccharomyces      cerevisiae,    property.
exposed to UV radiation, 8-
methoxypsoralen and benzo(a)pyrene.        Effect of cooking oil on
The single strand breaks in DNA were       turmeric/curcumin
found to be reduced in yeast cells in
the presence of curcumin.                          As turmeric in the Indian culinary
                                           practices is usually boiled or fried, it was
       Studies to assess the repair        considered essential to assess its anti-
                                           mutagenic properties after heating or
capacity of curcumin against DNA
                                           frying. A short term assay was used to
damage induced by carcinogens in           measure the genotoxic response to a
lymphocytes of smoking and non-            commonly present food mutagen,            4-
smoking men and in women, showed           nitroquinoline oxide in E.coli, PQ37. In



                                                                                    55
IJPD, 2004; Vol I No.3
the presence of boiled or fried curcumin,         endogenously present mutagens could
this response was decreased indicating            be countered by protective substances.
that cooking conditions are unlikely to destroy   Enhancement in the levels of tissue
the antimutagenic property of turmeric.
                                                  detoxification enzymes could be
                                                  another important mechanism through
Turmeric as a functional food                     which these dietary agents could
                                                  confer their protective effects. Garlic at
        In view of its wide spectrum of           0.1 and 0.5% and onion 1 and 5% were
action, turmeric is an ideal functional           fed through diet in these experiments.
food for prevention of cancer.                    These quantities of alliums can be
Toxicological studies on turmeric have            easily consumed through diet.
indicated that curcumin taken orally in
doses of 40-1800 mg/day for 1 to 3
months does not produce toxic effects.            Mustard
From mutagenicity and other studies,
the protective consumption levels can                     Mustard is a spice used for
be extrapolated for humans. A daily               flavouring and as a source of edible oil
intake of 0.5 to 1.0 g can be consumed            in India. The leaves of this plant are
without any adverse effect.                       consumed as vegetable. Mustard
                                                  belongs to cruciferous family, other
                                                  members of which are cabbage,
Alliums                                           broccoli, cauliflower, etc. The active
                                                  principle of mustard is dithiolthione.
        Among the vegetables, those               NIN studies have shown that mustard
belonging to the allium family have               has antimutagenic property. In rats fed
received increased attention in recent            10% mustard powder-containing diet,
times. Onion and garlic are commonly              significant reduction in the activity of
consumed through the diet. They                   carcinogen activation enzyme, aryl
contain sulphur compounds like                    hydrocarbon        hydroxylase       and
diallyl-sulphide and diallyl-disulphide.          stimulation in the activities of
Wistar rats fed garlic- (0.1,0.5, 1 %) or         carcinogen-detoxification      enzymes
onion- (1 and 5%) containing diet for             namely UDPGT and glutathione-S-
one month when exposed to either                  transferases were observed.
B(a)P or 3MC showed reduction in the
excretion of urinary mutagens,
                                                  Vegetables
Effect on drug metabolising enzymes
                                                  Induction of Protective Enzymes by
        Stimulation of activity of liver          Vegetables
cytosolic glutathione S-transferase                       Induction       of       hepatic
enzyme was seen on garlic feeding.                microsomal and cytosolic xenobiotic
The activity of the antioxidant enzyme            metabolising enzymes by commonly
quinone reductase in the liver and lung           consumed vegetables such as spinach,
microsomes was elevated in animals                amaranth, gogll, cabbage etc was
fed garlic containing diets. In onion fed         studied in rats fed at 20% level.
rats there was stimulation in the GST             Stimulation of the microsomal aryl
and GSTMu activity in the stomach                 hydrocarbon        hydroxylase      was
and liver tissues.                                observed only in animals fed gogu,
                                                  while the activities of UDP glucuronyl
        The reduction in the excretion            transferase      and      glutathione-S-
of carcinogen derived mutagens in                 transferase were significantly elevated
garlic/onion fed rats suggested that              in    the    groups     fed     cabbage.
                                                  Benzopyrene binding to hepatic DNA


                                                                                         56
IJPD, 2004; Vol I No.3
in vivo, a measure of carcinogen           b) Epidemiological
activation, tended to decrease in the              Epidemiological           studies
groups fed gogll, onion and mustard.       indicate that fruits and vegetables have
                                           health-promoting factors particularly
Other Evidences for Non-nutrients          against cardiovascular diseases and
as Chemopreventers                         cancer. Possible plant nutrients
a) Experimental                            providing this protection include
         Phenolic compounds in grains,     micronutrient       and     non-nutrient
fruits and vegetables, lignans, and        components of the diet. According to
flavonoids          have        shown      National Nutrition Monitoring Bureau
chemopreventive         effects     in     (NNMB) surveys in 10 states of India,
experimental animals. These have been      there is poor consumption of green
shown to exert antimutagenic activity.     leafy vegetables and poor intake of
Turmeric and curcumin have been            micronutrients.
shown to inhibit tumours in skin,
breast, oral cavity and forestomach in             Oral cancer is one of the ten
initiation and promotion models in         most common cancers in the world and
many species including mice, rats and      in India accounts for a third of all
hamsters.                                  cancers. A case control study was
                                           conducted by the NIN to examine the
        Diallyl-sulphide (DAS), an         role of diet in oral and oropharyngeal
active component present in garlic, has    cancers. Dietary intakes and nutrient
been shown to inhibit DNA carcinogen       estimates were obtained through diet
adduct formation in rat tissue. It was     history collected by oral questionnaire.
found to reduce forestomach tumour         The results suggested poor dietary
frequency in hamster buccal pouch and      intake of vegetables and fruits coupled
rat oesophagus. Garlic oil has been        with low estimated intake of
shown to inhibit promotion of              micronutrients.
chemically-induced skin cancers.
                                                   Cancer of the colon and rectum
        Isothiocyanates, present in        is the fourth most common cancer and
cruciferrous vegetables, have been         cause of death from cancer, throughout
shown to block tumours induced by          the        world.       Cross-sectional
chemical carcinogens. Tumours of the       comparisons, case control studies and
mammary gland, digestive system, and       trends in food intake show high rates
nitrosamine-induced lung tumours           of colorectal cancer in populations
have been shown to occur at reduced        consuming diets high in meat and fat
frequency in laboratory animals fed        and low in fibre and vegetables. In
thiocyanates prior to carcinogen           prospective    cohort     studies,   an
exposure.                                  association between consumption of
                                           vegetables and fruits with reduced risk
        Short     term     tests    and    of lung, oesophagus, stomach and
experiments on animals are used to         pancreatic cancer was observed .
establish the anti-genotoxic potential
of phyto-chemicals and unequivocal                 An epidemiological study was
evidence is available to demonstrate       conducted in Jiangsu province, China,
the anticancer property of these agents.   where gastric cancer is low and in
However epidemiological studies need       Yangzhong which is a high risk area
to be conducted to establish the diet-     for gastric cancer using a questionnaire
cancer relationship in humans.             and adjusting for ecological and life-
                                           style factors and age and sex. The



                                                                                 57
IJPD, 2004; Vol I No.3
study reports that allium vegetables         administration of spirulina for a year
were consumed in .the low risk area          resulted in complete regression of
more      frequently,   with     high        leukoplakia    in     45%.     Similar
consumption of raw vegetables, fruits,       observations on chemoprevention have
tomatoes, kidney beans and soyabean          been noted in China where a high
products. The results suggest that           prevalence of oesophageal and
frequent consumption of allium               stomach cancers exists. Intervention
vegetables, in addition to other             trials using antioxidants in various
anticancer foods may be a factor for         doses and combinations have yielded
low mortality due to gastric cancer in       inconsistent results for protection
the low risk area.                           against lung cancer in smokers,
                                             invasive cervical cancer, oesophageal
        From several reports it emerges      and gastric cancers and colorectal
that, assessment of individual nutrient      polyps.
intake, as opposed to fruit and
vegetable consumption, does not                       Dietary Modification Studies
increase the protective association of       Women's Health Initiative (WHI) 10
these components. However, changes           year trial was started in 1993 to assess
in the diet that would increase              the effect of diet low in fat and high in
consumption of fruits and vegetables         fruits, vegetables and fibre on cancer
would be beneficial as such a diet is        incidence among more than 50,000
unequivocally associated with cancer         post menopau'sal women. Women's
protection. Based on available               Intervention Nutrition Study (WINS) is
information, it seems prudent to             a 5 year clinical trial designed to test
advocate a diet rich in fruits and           whether dietary fat reduction will
vegetables, rather than consumption of       reduce breast cancer recurrence and
a specific nutrient or non-nutrient in       increase survival among 2000 women
order to decrease the risk of                breast cancer patients. Can dietary
developing cancer of organs such as          intervention with increased fruit and
colon, stomach, oesophageal, breast          vegetable consumption provide the key
and prostrate.                               answer? A recent study has
                                             demonstrated that a group of healthy
        An       interventional      trial   individuals who consumed increased
supplementing micronutrients such as         quantities of fruits and vegetables for 2
vitamin A, riboflavin, zinc and              weeks had elevated plasma levels of
selenium to a group of reverse smokers       antioxidant nutrients as compared to
indicated that the cocktail of nutrients     basal values; the levels of a tocopherol
given as a prescriptive approach could       and retinol did not show elevation.
result in regression of pre-neoplastic
lesions in the oral cavity. The nutrients            In another recent study, a group
also prevented the deterioration of          of subjects on normal diet, except
lesions and the appearance of new            vegetables high in carotenoids for 2
lesions in the non lesion group.             weeks, were supplemented with tomato
Similarly       in      tobacco-chewers      juice (weeks 3 and 4), carrot juice
administration of beta-carotene and          (weeks 5 and 6) or spinach (weeks 7
vitamin A lead to disappearance of           and 8). The supplementation resulted
leukoplakia. Biomarkers such as DNA          in a significant decrease in the
adducts     and     micronuclei     were     endogenous levels of strand breaks in
significantly reduced in the treated         lymphocytes DNA as measured by
groups. In another intervention study        comet assay; oxidative damage was
on tobacco-chewers in Kerala,                significantly reduced by carrot juice.



                                                                                   58
IJPD, 2004; Vol I No.3
High intake of cruciferous vegetables          turmeric have established. its anti-
associated with reduced risk for               carcinogenic potential in animals. In
colorectal cancer have been shown to           humans, turmeric and curcumin reduced
induce GST in human plasma and                 urinary mutagens excretion by smokers,
                                               and the precancerous lesions in reverse
lymphocytes following consumption of
                                               smokers.
brussel,s sprouts. This stimulation has
been shown in plasma GST-α and                          Evidence from epidemiological
rectal GST-α and GST–α in humans               studies indicates that diets high in fruits
after one week of consuming brussels           and vegetables with phytonutrients and
sprouts. This is supported by another          low in certain types of fat, along with
intervention study in fried meat               moderate caloric intake and fibre-rich food
consumers in whom a two-fold                   are associated with reduced cancer risk.
reduction. in urinary mutagenicity was         Results from clinical trials with nutrients/
observed.                                      nonnutrients as supplements have not
        In a dietary-intervention study,       given conclusive evidence for protective
                                               effects against cancer. It is important to
a group of subjects with non-
                                               realize that a supplement of any nutrient or
melanoma skin cancer was placed on
                                               nutrients against the backdrop of a poor
low fat diets for 2 years. The incidence       diet can hardly be expected to produce the
of both premalignant lesions (actinic          desired outcome. A more appropriate
keratoses) as well as skin cancer per se       approach should be a food based one,
was      reduced     significanty.    An       rather than nutrient-based. Beside the
intervention     study     is   currently      protective effects of nutrients and non-
underway to investigate the effect of          nutrients their synergistic effect is also an
wheat bran fibre. However, in studies          important point to be considered.
of this kind a double blind regimen is         Therefore, dietary preventive measures or
not possible where the intervention            promotion of healthy dietary habits and
comprises a diet high in fibre and low         life styles, though demanding, are perhaps
                                               the right answer for cancer prevention.
in fat. Cancer as an unambiguous end
point needs prolonged duration of              (Condensed from ICMR Bulletin)
study.

Conclusions

         Prescriptive and proscriptive
approaches for cancer prevention in
relation to diet are important to reduce the
incidence of cancer particularly that of the
aero-digestive system and cervical cancer
in India. The current focus is on cost-
effective health care strategies of which
dietary change is one. Beside the nutrients,
the non-nutrient components of diet are
gaining importance in studies pertaining to
diet-cancer relationship. Plant foods
including vegetables, fruits and spices
possess phyto-chemicals which have
antioxidant activity. Spices such as
turmeric, onion and garlic were shown to
be potent antimutagens in in vitro and in
vivo conditions. These were also shown to
induce the drug metabolizing enzymes
involved in detoxification of harmful
substances in the tissues. Studies on


                                                                                         59
IJPD, 2004; Vol I No.3
                                               widespread in India. Although the
                                               evolution of disease caused by B.
                                               abortus often follows a milder pattern,
Brucellosis                                    serious complications may occur as
                                               well.
Henk L. Smits & Manzoor Kadri
                                               Epidemiology.        Brucellosis is an
_______________________________                important     disease     of     farmers,
                                               veterinarians and butchers. They may
                                               contract the disease when working
Brucellosis is a severe zoonotic disease       with infected animals and animal
that leads to considerable morbidity and
                                               products.     Brucellosis     is     also
loss of man-days across the globe and thus
perpetuates poverty. Brucellosis presents      transmitted through the ingestion of
as an acute or persistent febrile illness      unpasteurized raw milk and dairy
with a diversity of clinical manifestations.   products. Dairy products prepared
Untreated patients may develop severe          from unpasteurized milk such as soft
complications and suffer from prolonged        cheeses, yoghurts and ice-creams, may
disability. Early diagnosis and prompt         contain high concentration of the
treatment with a full course of                bacteria and consumption of these is an
appropriate antibiotics is essential to        important cause of brucellosis.4
prevent relapse. For early diagnosis,          Brucellosis is common in rural areas
alertness of the physician with awareness      because farmers live in close contact
of many non-specific presentations is
                                               with their animals and often consume
essential.      Brucellosis cannot be
diagnosed      with     certainty   without    fresh unpasteurized dairy. However,
laboratory testing. The Rose Bengal test       the vending of dairy products may also
may be used as a simple and rapid              bring the disease to urban areas.
screening test but should be confirmed
with the serum agglutination test or           Clinical aspects. Human brucellosis
ELISA.                                         usually manifests as an acute or sub-
                                               acute febrile illness, which may persist
Introduction. Brucellosis is endemic           and progress to a chronically
in all states of India and is a significant    incapacitating disease with severe
and increasing veterinarian and public         complications. The intermittent or
health problem.1 As it is a particularly       remittent fever may be accompanied
severe disease that often is overlooked        by malaise, anorexia and prostration.
or misdiagnosed, it requires close             Complaints may persist for weeks or
attention by the practitioner.2,3              months in the absence of specific
                                               treatment. Typically, no or few
                                               objective signs are apparent that
        Brucellosis is a bacterial             specifically point to brucellosis. Thus,
disease caused by gram-negative                to the unaware physician, the diagnosis
coccobacillae, of which Brucella               of brucellosis can be problematic.
abortus, B. melitensis and B. suis are
pathogenic for man. Of main concern                   Brucellosis is acute in about
in India are B. melitensis and B.              half the cases, with an incubation
abortus. B. melitensis is transmitted          period of two to three weeks. In the
mainly by goats and sheep, and is the          other half, the onset is insidious,
most virulent strain for man; it causes        developing over a period of weeks to
severe and prolonged disease with a            months. Fever, chills, sweats, aches,
high risk of disability. B. abortus is the     lack of energy, joint and back pain,
dominant species in cattle and is              headache and loss of appetite are


                                                                                     60
IJPD, 2004; Vol I No.3
observed in majority of the patients.5         indicative. The liver is commonly
Arthritis, constipation, abdominal pain        involved in brucellosis even though
and sleep disturbance are seen in about        liver function tests are normal or only
half of them. Cough, testicular pain           slightly    elevated.    Orchitis    and
(from epididymo-orchitis), rash, ill-          epididymitis are the most frequent
appearance, pallor, vaginal bleeding,          genitourinary complications in men
hepatomegaly,             splenomegaly,        and may be confused with testicular
lymphadenopathy are somewhat less              cancer or tuberculosis. Infection during
common. Other symptoms such as                 pregnancy carries the risk of abortion
diarrhoea, jaundice, central nervous           or intrauterine transmission to the
system abnormalities, cardiac murmurs          infant. Meningitis and meningo-
and pneumonia are rare. Although               encephalitis are the most common
symptoms and signs often occur in              complications seen in neurobrucellosis.
various combinations, one study                The central nervous system is affected
reported fever as the only sign in 44%         in about 5% of the cases of B.
of patients with a positive blood              melitensis infection and often occurs at
culture for B. melitensis and fever with       a late stage as the main presenting
arthritis in another 42%.6 Arthritis           manifestation. It should be noted that
may affect all major joints including          brucellosis may affect essentially any
hip, back, knee, sacroiliac and knee.          organ at any site and that the list of
Sometimes more than one joint is               rare and unusual complications is
affected.                                      much longer than those mentioned
                                               here.     Complications       of     the
         To a doctor with no suspicion,        cardiovascular system are rare but
brucellosis is a typical example of a          important as they have a high degree of
difficult-to-diagnose disease. It may          mortality. Other examples of rare
present as a very mild, self-limiting          complications are those of skin and
affliction to a chronic incapacitating
                                               eyes.
disease. The patient may present as mild
fever or debilitating psychosis. It is very
difficult for a doctor to diagnose it in a             Laboratory diagnosis. Culture
non-endemic area; s/he needs a high            from the blood of a patient provides
degree of suspicion. In endemic areas, it is   definite proof of brucellosis but is too
relatively easier to diagnose. In the          slow to provide a quick diagnosis.7 For
hyperendemic areas, as Mediterranean           this reason, one often resorts to
region & the Gulf, practitioners take every    serological testing.8 The classical Rose
case of prolonged fever as brucellosis         Bengal test is often used as a rapid
unless proved otherwise. (Ed)
                                               screening test. This test is performed
                                               by mixing on a glass plate a drop of
         Acute brucellosis may progress        reagent with an equal volume of serum
to a more persistent disease. Persistent       and agglutination is read after 2 or 4
infections often are localised to one          minutes. The sensitivity of Rose
specific organ or site. Osteoarticular,        Bengal is very high (>99%) but the
gastrointestinal,          hepatobiliary,      specificity is disappointingly low.
respiratory,               genitourinary       Therefore, a positive test result should
complications are observed. Bone and           be confirmed with a more specific test
joint complications are the most               such as the serum agglutination test
frequent complications. These include          (SAT) also known as Wright’s SAT is
sacroiliitis, spondylitis, peripheral          performed by mixing serial dilutions of
arthritis, osteomyelitis and bursitis.         serum, usually 1:20 through 1:2,560, with
Complaints of back pain with radiation         Brucella antigen in test tubes or in ELISA
down to the legs and refusal of                plates. After overnight incubation,
children to walk or carry loads are            agglutination is read either by the unaided


                                                                                       61
IJPD, 2004; Vol I No.3
eye or under a binocular. As a guide,            of spontaneous improvement. In all
agglutination at titres of 1:160 or above is     cases it is important that the patient
considered of diagnostic value as long as        finishes the full course of medication
the patient has signs and symptoms of            because the risk of incomplete
disease. In endemic areas the diagnostic
                                                 recovery and relapse is otherwise
threshold value will have to be set at least
                                                 considerably increased.13 The standard
one titre step higher (1:320) to provide a
sufficiently high specificity as many            treatment of uncomplicated cases in
asymptomatic individuals will have titres        adults and children 8 years of age and
equal to the lower threshold level of 1:160.     older is 100 mg doxycycline twice a
Under endemic conditions titres of 1:320         day for 6 weeks plus 1 g streptomycin
and above in general provide conclusive          daily for 2 to 3 weeks. Instead of
evidence for brucellosis. Lower titres are       streptomycin, rifampicin may be given
inconclusive and land the clinician in a         in combination with doxycycline (200
diagnostic dilemma. The use of the higher        mg/day orally for 6 weeks) at a dose of
threshold level thus restricts the sensitivity   600-900 mg for 6 weeks. Treatment of
and clinical importance of the test.
                                                 complications such as spondylitis and
                                                 osteomyelitis, neurobrucellosis and
        Sometimes SAT is performed
                                                 brucella endocarditis may require
in the presence of reducing agent,
                                                 prolonged therapy ie for at least 8
which destroys the agglutinating
                                                 weeks. The optimal therapy for
activity of immunoglobulin M (IgM)
                                                 brucellosis during pregnancy has not
leaving IgG intact. This 2-ME (2-
                                                 been established. Co-trimoxazole has
mercaptoethanol) test is used to
                                                 been used successfully. Alternatively,
increase the specificity of the reaction
                                                 rifampicin for at least 45 days may be
by looking at IgG only, which is
                                                 used. The optimal therapy for infants
important in patients with a more
                                                 and children less than 8 years of age
persistent infection.
                                                 remains to be established as well. As
                                                 for pregnant women doxycycline is
        In brucellosis, specific IgM
                                                 contraindicated because of possible
antibodies dominate during the acute
                                                 permanent staining of deciduous teeth
phase of the disease. Specific IgG
                                                 and inhibition of bone growth of the
antibodies are present in the serum of
                                                 baby. Suggested therapies include
patients at a more persistent phase and
                                                 trimethoprim-sulfamethoxazole
in the serum of relapsing patients.
                                                 (TMP/SMZ) 8/40 mg/kg/day twice
ELISA is used to discriminate between
                                                 daily orally for 6 weeks plus
the presence of specific IgM and IgG
                                                 streptomycin 30 mg/kg/day once daily
antibodies and to roughly assess the
                                                 intramuscularly for 3 weeks or
stage of illness. SAT and the 2-ME test
                                                 gentamycin 5 mg/kg/day once daily
also may be used for this purpose but
                                                 intravenously or intramuscularly for 7
are less accurate.
                                                 to 10 days. Another alternative is
                                                 TMP/SMZ        plus     rifampicin  15
Treatment. Uncomplicated acute
                                                 mg/kg/day orally for 6 weeks.
brucellosis almost invariably responds
well    to      appropriate    antibiotic
          11,12                                  Brucellosis in Jammu & Kashmir
treatment.       In those patients with
                                                 and prospects. Brucellosis has not
complications, additional treatment,
                                                 been studied in any detail in the State
including in some cases surgical
                                                 of Jammu & Kashmir. Rearing of
intervention will be necessary. To
                                                 sheep and cattle is common among
prevent disease progression and the
                                                 villagers in the State and most villagers
development        of     complications,
                                                 live in close contact with their animals
treatment should start as early as
                                                 or handle animal products regularly.
possible also in patients showing signs


                                                                                       62
IJPD, 2004; Vol I No.3
Veterinary services are not high grade;      flow assay is very high and a positive
most of the live stock remains               test result is highly consistent with
unexamined       and       unimmunized.      active brucellosis.17 The use of this test
Consequently, most of the animals,           will provide clinicians with a means to
flesh or milch, remain ill. There are no     confirm the diagnosis of brucellosis at
abattoirs, and slaughtered animals are       first presentation of the patient and to
not examined pre- or post-mortem. In         start treatment immediately.
addition, the consumption of raw dairy
is common practice. In the absence of        Conclusions
effective measures to control and
prevent brucellosis such as vaccination         •   Brucellosis is a severe and
of livestock, farm sanitation and food              debilitating febrile illness.
hygiene brucellosis could be easily             •   It is very deceptive disease;
transmitted to the human population.                physicians should be aware of the
In the absence of laboratory testing,               diverse and non-specific clinical
many patients with febrile illness are              manifestations.
classified by practitioners, registered as      •   Laboratory testing is indispensable
well as unregistered, as pyrexia of                 for diagnosis.
unknown origin (PUO), some of whom              •   The Rose Bengal test is a rapid
could very well be suffering from                   and simple screening test but
brucellosis. Serum agglutination test               should be confirmed with a more
(Wright) has often detected presence of             specific test.
brucellosis in patients admitted to the         •   A high titre in the SAT (Wright’s
SMHS       hospital     as         PUO.14           test) is consistent with brucellosis;
Retrospective examination with SAT                  a low titre at or around the
of 3,532 cases of PUO referred for                  threshold value suggests but does
diagnosis to the Department of Clinical             not prove brucellosis.
Microbiology, Government Medical                •   Uncomplicated               brucellosis
College, Srinagar, revealed a serum                 responds well to antibiotic
prevalence of 0.8% at a threshold value             treatment.
of 1:16015.                                     •   Early diagnosis and prompt
                                                    treatment is essential to prevent
        To improve the diagnosis of                 complications and relapse.
brucellosis the authors intend to
                                                •   Use of the Brucella IgM/IgG flow
examine the clinical utility of the
                                                    assay will allow physicians to
Brucella IgM/IgG flow assay as a
                                                    diagnosis and treat patients with
point-of-care test for brucellosis in
                                                    brucellosis promptly.
hospitals and health care centres. The
Brucella IgM/IgG flow assay is a
simplified version of ELISA and is
simply performed by the addition of a
drop of serum and some running fluid
to the sample well of a plastic assay
device. The test result is read after 10-
15 minutes by visual inspection for
staining of the detection line.16 The
Brucella IgM/IgG flow assay is easy to
perform and to read and may be
performed by a nurse or a medical
assistant.   The     sensitivity      and
specificity of the Brucella IgM/IgG



                                                                                       63
IJPD, 2004; Vol I No.3


Dr. S. Manzoor Kadri, from the Regional Institute of Health, Kashmir, and Dr. H.L. Smits, a molecular biologist at the department of
KIT Biomedical Research of the Royal Tropical Institute in Amsterdam, The Netherlands, are investigating the clinical utility of a
simple and rapid “point-of care” test, the Brucella IgM/IgG flow assay, for use by general practitioners to improve the diagnosis and
treatment of patients with clinical suspicion of brucellosis. The Brucella IgM/IgG flow assay was developed at the Royal Tropical
Institute and studies performed in Spain and Turkey showed a high sensitivity and specificity. The study also will be used to
determine the main risk factors for brucellosis. (Ed)


Bibliography

1.    Renukaradhya GJ, Isloor S, Rajasekhar M. Epidemiology, zoonotic aspects, vaccination and
      control/eradication of brucellosis in India. Vet Microbiol. 2002;90:183-195.
2.    Thakur SD, Kumar R, Thapliyal DC. Human brucellosis: review of an under-diagnosed animal
      transmitted disease. J Commun Dis. 2002;34:287-301.
3.    Al-Eissa Y, al-Zamil F, al-Mugeiren M, al-Rasheed S, al-Sanie A, al-Mazyad A. Childhood
      brucellosis: a deceptive infectious disease. Scand J Infect Dis. 1991;23:129-33.
4.    Bikas C, Jelastopulu E, Leotsinidis M, Kondakis X. Epidemiology of human brucellosis in a rural area
      of north-western Peloponnese in Greece.Eur J Epidemiol. 2003;18:267-74.
5.    Gur A, Geyik MF, Dikici B, Nas K, Cevik R, Sarac J, Hosoglu S. Complications of brucellosis in
      different age groups: a study of 283 cases in southeastern Anatolia of Turkey. Yonsei Med J.
      2003;44:33-44.
6.    Memish Z, Mah MW, Al Mahmoud S, Al Shaalan M, Khan MY. Brucella bacteraemia: clinical and
      laboratory observations in 160 patients. J Infect. 2000;40:59-63.
7.    Al Dahouk S, Tomaso H, Nockler K, Neubauer H, Frangoulidis D. Laboratory-based diagnosis of
      brucellosis--a review of the literature. Part I: Techniques for direct detection and identification of
      Brucella spp. Clin Lab. 2003;49:487-505.
8.    Al Dahouk S, Tomaso H, Nockler K, Neubauer H, Frangoulidis D. Laboratory-based diagnosis of
      brucellosis--a review of the literature. Part II: serological tests for brucellosis. Clin Lab. 2003;49:577-
      589.
9.    Barroso Garcia P, Rodriguez-Contreras Pelayo R, Gil Extremera B, Maldonado Martin A, Guijarro
      Huertas G, Martin Salguero A, Parron Carreno T. Study of 1,595 brucellosis cases in the Almeria
      province (1972-1998) based on epidemiological data from disease reporting. Rev Clin Esp.
      2002;202:577-82.
10.   Martin Moreno S, Guinea Esquerdo L, Carrero Gonzalez P, Visedo Orden R, Garcia Carbajosa S,
      Calvo del Olmo T, Reverte Cejudo D. Diagnosis of brucellosis in an endemic area. Evaluation of
      routine diagnostic tests. Med Clin (Barc). 1992;98:481-5.
11.   Solera J, Martinez-Alfaro E, Espinosa A. Recognition and optimum treatment of brucellosis. Drugs.
      1997;53:245-56.
12.   Solera J. Treatment of human brucellosis. J Med Liban. 2000;48:255-63.
13.   Solera J, Martinez-Alfaro E, Espinosa A, Castillejos ML, Geijo P, Rodriguez-Zapata M. Multivariate
      model for predicting relapse in human brucellosis. J Infect. 1998;36:85-92.
14.   Kadri SM, Tanvir M, Chowdhary ND,Hassan G, Gash B. Pancytopenia in a patient with brucellosis
      admitted as a case of pyrexia of unknown origin (PUO) in Kashmir - A case report. JK Practioner
      2003;10:222-223.
15.   Kadri SM, Rukhsana A, Laharwal MA, Tanvir M. Seroprevalence of brucellosis in Kashmir (India)
      among patients with pyrexia of unknown origin. J Indian Med Assoc 2000;98:170-171.
16.   Smits HL, Abdoel TH, Solera J, Clavijo E, Diaz R Immunochromatographic Brucella-specific
      immunoglobulin M and G lateral flow assays for rapid serodiagnosis of human brucellosis. Clin Diagn
      Lab Immunol. 2003;10:1141-1146.
17.   Irmak H, Buzgan T, Evirgen O, Akdeniz H, Demiroz AP, Abdoel TH, Smits HL Use of the Brucella
      IgM and IgG flow assays in the serodiagnosis of human brucellosis in an area endemic for brucellosis.
      Am J Trop Med Hyg. 2004;70:688-694.




                                                                                                                                     64
IJPD, 2004; Vol I No.3


A leaf from the history of medicine

Fleming
[Sir Alexander Fleming]

        Fleming (1881-1955) was a
British bacteriologist and Nobel laureate,
best known for his discovery of
penicillin. Born in Lochfield, Ayr (now
part of Strathclyde), Scotland, Fleming
had a brief military career before a small                Discovery of Penicillin
legacy enabled him to begin studying         The research of Alexander Fleming in 1928 led
                                             to the accidental discovery of penicillin, the life-
medicine in 1901 at St Mary’s Hospital       saving antibiotic derived from the mould
Medical School of the University of          Penicillium notatum. Penicillin is effective
London. He remained associated with St       against a wide range of disease-causing bacteria
Mary’s throughout his career, ending as      and acts by killing bacteria directly or by
Director of what (from 1948) was called      inhibiting their growth.
the    Wright-Fleming       Institute   of
Pathology and Research. (The Institute               In 1928, Fleming observed that a
was      originally     the    Inoculation   mould (later identified as Penicillium
Department of St Mary’s Hospital and         notatum) lysed colonies of the bacteria
was under the direction of Sir Almroth       staphylococci, a common cause of
Wright, with whom Fleming worked             wound infections. His paper describing
closely).                                    this phenomenon mentioned the
                                             potential clinical importance of the
        In addition to a number of           substance, but he was unable to obtain
routine contributions to bacteriology and    penicillin in a sufficiently pure form to
chemotherapy, Fleming made two               produce reliable results in patients with
important observations about antibiotic      infections, and he abandoned his work in
substances. In 1921, he noticed that his     this area in the early 1930s. It was taken
own nasal secretions lysed (dissolved) a     up again in World War II by a group at
colony of common bacteria on a Petri         Oxford University, including the
dish. He named the active substance          pathologist Howard Florey and the
lysozyme and discovered that it was also     chemist Ernst Chain. This group
contained in other body fluids and in        succeeded in producing small amounts
some plants. Lysozyme had no clinical        of penicillin and in demonstrating its
application, however, as it was difficult    effectiveness against a number of
to obtain in concentrated amounts and        bacterial diseases. Industrial production
was ineffective against disease-causing      methods were developed in the United
bacteria.                                    States during the War.

                                                    Fleming, who was knighted in
                                             1944, shared the 1945 Nobel Prize for
                                             Medicine or Physiology with Florey and
                                             Chain. Primarily through the publicity


                                                                                             65
IJPD, 2004; Vol I No.3


activities of Wright, Fleming received       promising. In 1939 Florey and the
most of the popular acclaim for              German-born British biochemist Ernst
penicillin’s discovery.                      Boris Chain isolated the active agent,
                                             penicillin, from a fraction of the mould
Chain      [Ernst Boris Chain]               and formulated procedures for extraction
                                             and production. With British industries
        Chain (1906-1979), was a             affected by World War II, Florey took
German-born        British    biochemist,    his process to the United States, where
pathologist, and Nobel laureate, born in     private and government laboratories
Berlin and educated at the University of     produced sufficient quantities to combat
Berlin. Because he was Jewish, he left       bacterial infection in wounded soldiers.
Germany for England after Hitler's           For his work he was knighted in 1944,
accession to power in 1933. He engaged       shared the Nobel Prize for Physiology or
in research on enzymes at the                Medicine in 1945 with Chain and
Universities of Cambridge and Oxford,        Fleming, was elected president of the
where he collaborated with the               Royal Society in 1960, and was created a
Australian pathologist Sir Howard            life peer in 1965.
Walter Florey in the investigation of
antibiotic substances produced by            Penicillin
moulds. By 1941, this investigation had
resulted in the small-scale production of            Penicillin is a widely known
penicillin. After 1950, Chain worked at      antibiotic derived from     the    mould
the Higher Institute of Health in Rome,      Penicillium notatum. The action of this
and in 1961 he became Professor of           antibiotic was first observed in 1928 by
Biochemistry at the University of            the British bacteriologist Sir Alexander
London. Chain shared the 1945 Nobel          Fleming, but it was another ten years
Prize for Physiology or Medicine with        before penicillin was concentrated and
Florey and the British bacteriologist Sir    studied by the British biochemist Ernst
Alexander Fleming.                           Chain, the Australian pathologist Sir
                                             Howard Florey, and other scientists.
Florey
[Sir Howard Walter, Baron]

        Florey (1898-1968) was an
Australian pathologist, co-discoverer of
penicillin, and Nobel laureate. Born in
Adelaide, Australia, and educated in
medicine at the University of Adelaide,
he later studied and taught in England. In                   Penicillium Mould
1935 he was appointed director of the        Penicillin is an important antibiotic derived from
Dunn School of Pathology, University of      the mould Penicillium notatum pictured here. It
Oxford. Florey studied naturally             is effective against a wide range of disease-
occurring antibacterials, of which the       causing bacteria, which it kills directly or by
                                             inhibiting their growth.
Penicillium mould discovered by
Alexander Fleming seemed the most


                                                                                           66
IJPD, 2004; Vol I No.3


        Penicillin acts both by    killing    killed by penicillin, but also inhibits
bacteria and by inhibiting their growth.      enterococci and most gram-negative
It does not kill organisms in the resting     bacilli.
stage but only those that are growing
and reproducing (ie the actively growing      DOSAGES
microbes). It is effective against a wide
range of pathogenic micro-organisms,
                                              The strength and dosage of penicillin are
including pneumococci, streptococci,
                                              measured in terms of international units.
gonococci,        meningococci,        the
                                              Each of these units is equal to 0.0006 g
clostridium of tetanus, and the syphilis
                                              of the crystalline fraction of penicillin
spirochaete. The drug has been
                                              called penicillin G. In the early days of
successfully employed to treat such
                                              penicillin therapy, the drug was
deadly diseases as subacute bacterial
                                              administered every three hours in small
endocarditis, septicaemia, gas gangrene,
                                              doses. More recently a preparation called
gonorrhoea, and scarlet fever. Toxic
                                              benzathine penicillin G has been
symptoms produced by penicillin are
                                              produced that provides detectable levels
limited largely to allergic reactions
                                              of antibiotic for as long as four weeks
which can be determined by scratch tests
                                              after a single intramuscular injection. It
before administration of the drug.
                                              is useful for treatment of syphilis and
                                              strep throat. Bacterial resistance to
SEMI-SYNTHETIC PENICILLIN
                                              penicillin has increased over the years,
                                              causing a need for alternative drugs and
        Despite the effectiveness             increases in penicillin dosage.
displayed by penicillin in curing a wide
range of diseases, infections caused by       _________________________________
certain strains of staphylococci could not
be cured by the antibiotic as a result of
the ability of the organism to produce an
enzyme, penicillinase, capable of             With the advent of new antibiotics,
destroying the antibiotic. In addition,       penicillin has fallen from grace in our
enterococci and many gram-negative            place for three simple reasons:
bacilli known to cause respiratory and
urinary-tract infections were found to be     1) Newer antibiotics are more
intrinsically-resistant to the action of      fashionable; since penicillin has been
penicillin.      Appropriate      chemical    around for long and is still one of the
treatment of a biological precursor to        cheapest available, parents feel that it is
penicillin, isolated from bacterial           inferior to other costlier antimicrobials,
cultures, resulted in the formation of a
number of so-called semi-synthetic            2) Practitioners either don’t want to take
penicillins. The most important of these      chance or have lost faith in penicillin.
are     methicillin     and     ampicillin.
Methicillin is remarkably effective           3) Retailers don’t stock and sell
against            penicillinase-producing    penicillin, mainly because it is too cheap
staphylococci                          and    to deal in. (Ed)
ampicillin/amoxycillin are not only
active against all organisms normally


                                                                                      67
IJPD, 2004; Vol I No.3



Penicillins                                  Benzylpenicillin
             Rubina Shaheen
                                             Availability: Injection (Powder         for
________________________________             solution), benzylpenicillin sodium,
                                             600-mg vial (1 million units),
                                             3-g vial (5 million units)
        Benzylpenicillin remains an
important and useful antibiotic but it is    Uses: Benzylpenicillin is useful for
inactivated by bacterial beta-lactamases.    pneumonia; throat infections; otitis
It is effective for many streptococcal,      media; Lyme disease in children;
(including pneumococcal), gonococcal         streptococcal                endocarditis;
and meningococcal infections and also        meningococcal meningitis; necrotizing
for anthrax, diphtheria, gas gangrene,       enterocolitis;    necrotizing     fasciitis;
leptospirosis, tetanus and treatment of      leptospirosis; neurosyphilis; anthrax;
Lyme disease in children. Pneumococci,       actinomycosis; brain abscess; gas
meningococci and gonococci often have        gangrene; cellulitis; osteomyelitis
decreased sensitivity to penicillin and
benzylpenicillin is no longer the first      Contra-indications:              Penicillin
choice for pneumococcal meningitis.          hypersensitivity; avoid intrathecal route.
Benzylpenicillin is given by injection as
it is inactivated by gastric acid and        Precautions: History of allergy; renal
absorption from the intestinal tract is      failure; heart failure; pregnancy and
low.                                         breastfeeding; interactions.

        Depot preparations are used          Dose:
when therapeutic concentrations need to      i) Mild to moderate infections due to
be sustained for several hours.              sensitive organisms, by intramuscular
Benzathine benzylpenicillin or procaine      injection or by slow intravenous
benzylpenicillin provides a tissue depot     injection or by intravenous infusion ,
from which the drug is slowly absorbed       ADULT: 0.6-2.4 g daily in 2-4 divided
over a period of 12 hours to several         doses, with higher doses in severe
days. They are the preferred choice for              infections and duration of
the treatment of syphilis                    treatment depending on disease;
or yaws.                                     CHILD 1 month to 12 years, 100 mg/kg
                                             daily in 4 divided doses, with higher
        Phenoxymethylpenicillin         is   doses in severe infections. (Infant 1 to 4
suitable for oral administration; it has a   weeks, 75 mg/kg daily in 3 divided
similar spectrum of activity but is less     doses; neonate 50 mg/kg daily in 2
effective than benzylpenicillin. It should   divided doses)
not be used for                              ii)    Bacterial endocarditis, by slow
serious infections because absorption        intravenous injection or by intravenous
can be unpredictable and plasma              infusion, ADULT up to 7.2 g daily in 6
concentrations variable.                     divided doses
                                             iii) Meningococcal meningitis, by slow
                                             intravenous injection or by intravenous


                                                                                      68
IJPD, 2004; Vol I No.3


infusion, ADULT up to 14.4 g daily in         spirochaete infections, probably due to
divided doses; premature infant and           release of endotoxins);
neonate 100 mg/kg daily in 2 divided          .     Inflammation,      phlebitis   or
doses; infant 150 mg/kg daily in 3            thrombophlebitis at injection sites
divided doses; CHILD 1 month to 12
years, 180-300 mg/kg daily in 4-6
divided doses                                 Benzathine
iv) Suspected meningococcal disease
(before transfer to hospital), by             benzylpenicillin
intramuscular injection or by slow
intravenous injection , ADULT and
CHILD over 10 years, 1.2 g; CHILD 1           Availibility: Injection (Powder for
to 9 years, 600 mg; CHILD under 1 year,       solution for injection), benzathine
300 mg                                        benzylpenicillin, 1.8-g vial (equivalent
v) Neurosyphilis, by slow intravenous         to benzylpenicillin 1.44 g, 2.4 million
injection , ADULT 1.8-2.4 g every 4           units)
hours for 2 weeks.
vi) Congenital syphilis, by intramuscular     Uses:      Streptococcal     pharyngitis;
injection or by slow intravenous              diphtheria carrier state; syphilis and
injection , CHILD up to 2 years, 30           other treponemal infections (yaws, pinta,
mg/kg daily in 2 divided doses for 10         bejel); rheumatic fever prophylaxis.
days; CHILD over 2 years, 120-180
mg/kg (to a maximum of 1.44 g) daily in       Contra-indications:             Penicillin
divided doses for 14 days                     hypersensitivity; intravascular injection;
                                              neurosyphilis
 (Reconstitution & administration is
done according to manufacturer' s             Precautions: History of allergy; renal
directions)                                   failure; pregnancy and breastfeeding;
                                              interactions.
Adverse-effects:
. Hypersensitivity reactions including        Dose:
urticaria, fever, joint pains, rashes,        i) Streptococcal pharyngitis; primary
angioedema,        anaphylaxis,     serum     prophylaxis of rheumatic fever, by deep
sickness-like     reactions,   haemolytic     intramuscular injection , ADULT and
anaemia, interstitial                         CHILD over 30 kg body-weight, 900 mg
nephritis;                                    as a single dose; CHILD under 30 kg
. Diarrhoea, antibiotic-associated colitis;   body-weight, 450-675 mg as a single
.Neutropenia,           thrombocytopenia,     dose
coagulation disorders, central nervous        ii) Secondary prophylaxis of rheumatic
system toxicity, including convulsions,       fever, by deep intramuscular injection ,
coma, and encephalopathy (associated          ADULT and CHILD over 30 kg body-
with high dosage, or severe renal             weight, 900 mg once every 3-4 weeks;
failure);                                     CHILD under 30 kg body-weight, 450
. Electrolyte disturbances;                   mg once every 3-4 weeks
.Jarisch-Herxheimer reaction (during
treatment for syphilis and other



                                                                                     69
IJPD, 2004; Vol I No.3


iii) Early syphilis, by deep intramuscular         i) Inhibition of bacterial cell wall synthesis:
injection , ADULT 1.8 g as a single                Penicillins exert their bactericidal activity
dose, divided between 2 sites                      primarily by inhibiting bacterial cell wall
iv) Late syphilis, by deep intramuscular           synthesis. This they do probably by binding
injection , ADULT 1.8 g, divided                   to penicillin-binding proteins (enzymes as
between two sites, once weekly for 3               transpeptidases, carboxypeptidases, &
consecutive weeks                                  endopeptidases which play important role in
v) Congenital syphilis (where no                   formation and maintenance of cell wall
evidence of CSF involvement), by deep              structure). More specifically they inhibit the
intramuscular injection , CHILD up to 2            transpeptidation stage – ie the last stage of
years, 37.5 mg/kg as a single dose                 transpeptidation in cell-wall formation, by
vi) Yaws, pinta, and bejel, by deep                acting as the structural analogue of the
intramuscular injection , ADULT 900                concerned enzymes. Therefore, the cell wall
mg as a single dose; CHILD 450 mg as a             formed is defective in structure and can not
single dose                                        sustain the cell which dies. Other
                                                   mechanisms also are operative.
 (Reconstitution & administration is
done according to manufacturer' s                  ii) Penicillin-induced bacterial autolytic effect:
directions)                                        Inhibition, by penicillin, of various enzymes
                                                   which normally would facilitate cell wall
Adverse-effects:                                   expansion leads to inhibition of cell-wall
. Hypersensitivity reactions including             synthesis, resulting in autolysis of bacteria
urticaria, fever, joint pains, rashes,             from increased osmotic pressure. This
angioedema,        anaphylaxis,      serum         autolysis is cell-cycle dependent, and occurs
sickness-like     reaction,      haemolytic        mostly when the cell is actively dividing (Ed)
anaemia, interstitial nephritis;
.    Neutropenia,       thrombocytopenia,
coagulation disorders and central
                                                   Procaine benzylpenicillin
nervous system toxicity (associated with
high dosage or severe renal failure);              Availability: Injection (Powder for
                                                   solution     for    injection),    procaine
. Jarisch-Herxheimer reaction (during              benzylpenicillin 1-g vial (1 million
treatment for syphilis and other                   units), 3-g vial (3 million units)
spirochaete infections, probably due to
release of endotoxins);                            Uses: Syphilis; anthrax; childhood
. Rarely, non-allergic (embolic-toxic)             pneumonia; diphtheria carrier state;
reactions; pain and inflammation at                cellulitis; mouth infections; bites
injection site

Mechanism of action:                               Contra-indications:
                                                   . Hypersensitivity to               penicillins;
Penicillins are bactericidal agents that inhibit   intravascular injection
bacterial cell wall synthesis & induce a
bacterial autolytic effect.                        Precautions: History of allergy; renal
                                                   failure; interactions.



                                                                                                 70
IJPD, 2004; Vol I No.3


Dose:                                         Phenoxymethylpenicillin
i) Infections due to sensitive organisms,
by deep intramuscular injection ,
ADULT 0.6 to 1.2 g daily
                                              Availability: Tablets, phenoxy-
ii) Pneumonia, by deep intramuscular
                                              methylpenicillin (as potassium salt) 250
injection , CHILD 50 mg/kg daily for 10
                                              mg.
days
                                                            Oral suspension (Powder
                                              for oral suspension), phenoxy-
iii) Syphilis, by deep intramuscular
                                              methylpenicillin (as potassium salt) 250
injection , ADULT 1.2 g daily for 10 to
                                              mg/5 ml
15 days, or up to 3 weeks in late syphilis
iv) Congenital syphilis, by deep
                                              Uses: Streptococcal pharyngitis; otitis
intramuscular injection , CHILD up to 2
                                              media; erysipelas; mouth infections;
years, 50 mg/kg daily for 10 days
                                              secondary prophylaxis of rheumatic
                                              fever; post-splenectomy prophylaxis.
(Reconstitution & administration are
done according to manufacturer's
                                              Contra-indications: Hypersensitivity to
directions)
                                              penicillins; serious infections.
Adverse-effects:
                                              Precautions:      History     of allergy;
                                              pregnancy         and        breastfeeding;
. Hypersensitivity reactions including
                                              interactions.
urticaria, fever, joint pains, rashes,
angioedema,         anaphylaxis,     serum
                                              Dose:
sickness-like      reaction,    haemolytic
                                              i) Infections due to sensitive organisms,
anaemia,      interstitial   nephritis;   .
                                              by mouth , ADULT 500-750 mg every 6
Neutropenia,             thrombocytopenia,
                                              hours; CHILD up to 1 year, 62.5 mg
coagulation disorders and central
                                              every 6 hours; CHILD 1-5 years, 125 mg
nervous system toxicity (associated with
                                              every 6 hours; CHILD 6-12 years, 250
high doses and severe renal failure);
                                              mg every 6 hours
                                              ii) Secondary prophylaxis of rheumatic
. Jarisch-Herxheimer reaction (during
                                              fever, by mouth , ADULT 500 mg twice
treatment for syphilis and other
                                              daily; CHILD 1-5 years, 125 mg twice
spirochaete infections, probably due to
                                              daily; CHILD 6-12 years, 250 mg twice
release of endotoxins);
                                              daily
. Rarely, non-allergic (embolic-toxic)        Patient Advice: Phenoxymethylpenicillin
reactions;                                    should be taken at least 30 minutes before or
                                              2 hours after food
. Pain and inflammation at injection site
                                              Adverse-effects:
                                              Hypersensitivity reactions including
                                              urticaria, joint pain, rash, angioedema,
                                              anaphylaxis; nausea and diarrhoea.




                                                                                        71
IJPD, 2004; Vol I No.3


                                                       Several hypothesis have been
Down’s Syndrome                                advanced to account for this increase,
                                               including the idea that older women are less
         _______Bashir Gaash                   likely to spontaneously abort a trisome
                                               pregnancy. Direct studies of the frequency
                                               of chromosomal abnormalities in sperm &
                                               egg cells indicate that the pattern is in fact
       Trisomy 21 is seen in                   due to an increase in non-disjunction among
approximately 1 of every 800 live births,      older mothers. Since all of a female’s oocytes
making it the most common aneuploid            are formed during her embryonic
condition compatible with survival to          development, an ovum of a 45 year old
term. Although this condition was first        woman is also 45 years old. This long period
described by Hohn Langdon Down in              of suspension in prophase I (before being
                                               shed in ovulation) may impair disjunction.
1866, and it took another hundred years
                                               Despite studies on the effect of various
to find out that it was caused by the          environmental factors on chromosome,
presence of an extra copy of                   maternal age has emerged as the only
chromosome 21.                                 known consistently correlated factor.
                                                       In spite of the strong correlation of
Prevalence: General population: 1 in 1000      maternal age with nondisjunction of
conceptions                                    chromosome almost 3/4th           of Downs
     Maternal age 35 years: 1 in 250           children are born to mothers younger than
     Maternal age 48: 1 in 11                  35 years. This is because 90% of children are
                                               borne bt women of that age group.
       Advanced maternal & paternal                    The effect of paternal age is minor;
age, both, are risk factors. Increasing        this is because spermatocytes, unlike
maternal age is associated with higher         oocytes, are generated throughout the life of
                                               the male.
disjunction rate during meiosis I.
However, this does not mean that
mothers below 35 years will not deliver        Clinical features
a Downs baby. In fact, most babies (70-                There is considerable variation in
80%) with Downs are born to mothers            the appearance of patients, however,
under 35 years of age. This is because         there is a constellation of features that
non-disjunction occurs sporadically at         make the diagnosis easier.
any age.
                                               Facial features:
                                                       A low nasal root,
Trisomies, nondisjunction, & maternal age.
                                                       Upslanting palpebral fissures,
The prevalence of Downs syndrome among
                                                       Small ears (which are sometimes
offsprings varies with maternal age. Among             over-folded),
mothers younger than 30 of age, the risk is            Flattened maxillary and malar
less than 1/1000. It increases to                      region,
approximately 1/400 at age 35 years, 1/100             Round cheeks,
at age 40, and approximately 1/25 after age            Corners of the mouth sometimes
45. Most other trisomies, including those in           down-turned.
which the fetus does not survive to term,      Neck: Short neck with the skin redundant
also increase in prevalence as maternal age            at the nape of the neck, especially
increases. This risk is one of the primary             in newborns.
indications for prenatal diagnosis among       Occiput: Flat
women older than 35 years of age.              Hands & feet: Broad & short;



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         About 50% have a deep flexion           2) Intellect: Enriched environments have
crease across their palms (simian crease)        been shown to significantly improve
         Decreased muscle tone (hypotonia)       their intellectual function.
is consistently present, and helps in            3) Sterility: Male patients are almost
diagnosis.
                                                 always sterile; 40% of females patients
                                                 fail to ovulate. A female with Downs has
Prognosis & Complications                        a 50% risk of producing a gamete with
1) About 3% develop obstruction / atresia
                                                 two copies of chromosome 21 (which
of duodenum, esophagus or anus.
2) Respiratory infections are quite common.      would then produce a trisomic zygote).
3) Risk of developing leukemia is 15-20          However, approximately 3/4ths of
times higher than in the general population.     trisomy        21      conceptions   are
4) Approximately 40% are born with               spontaneously aborted.
structural heart defects:
         Most common is an atrio-                         Because     reproduction     is     so
ventricular canal (because inter-arterial and    uncommon, nearly all cases of trisomy are
inter-ventricular septa fail to fuse normally    regarded as new mutations. Approximately
during fetal development). This leads to         95% of trisomy are caused by non-
blood flow from left to right side of heart      disjunction, with most of the remainder
which results in pulmonary hypertension.         being caused by chromosome translocations.
         Another common cardiac defect is        In 90% to 95% of trisomy 21 cases, the extra
ventricular septal defect.                       chromosome is contributed by the mother.
5) Mental retardation is moderate to severe      Mosaicism, in which only some cells of the
(IQ between 25 to 60 in most). Downs             body have extra chromosome, is seen in 2-
syndrome is the most common genetic              4% cases of trisomy. It results in milder
disorder causing mental retardation. In the      clinical    expression     of    abnormality.
USA, Down’s accounts for 10% of mental           Mosaicism, affecting primarily the germ line
retardation.                                     of a parent can lead to multiple recurrences
6) Conductive hearing loss (sometimes            of the disease in offsprings. Therefore
         neural)                                 recurrence risk in mothers under 30 years of
7) Hypothyroidism is common, especially          age is 1% ie 10 times the expected risk in this
         during                   adolescence.   age group.
8) Various eye abnormalities
                                                     Other trisomies:
Prognosis:                                               Edwards syndrome (Trisomy 18;
                                                     47,XY,+18) is the 2nd most common
1) Survival: Survival rates are
                                                     autosomal trisomy (prevalence 1/6000
significantly decreased because of so
                                                     live births). However, only 5% of such
many medical problems. As recently as                pregnancies survive to term, the vast
early 1960s, only a half of them would               majority end in still birth with
survive their 5th birthday. Congenital               congenital anomalies.
heart defects are the most important                     Clinically, such babies suffer
single cause of death. Because of                    prenatal growth deficiency [low
modern treatment (including corrective               gestational age (LGA), lighter for dates],
surgery,     antibiotic    treatment,   &            characteristic facies (small ears with
treatment      of      leukemia),     now            unraveled helix, small mouth that is hard
approximately 80% of the children with               to open), short sternum, characteristic
Down’s syndrome will survive till their              over-lapping fingers with clenched fists,
                                                     and short big toes.
10th birthday and about half the patients
would survive till 50 years.


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    Most of them have major anomalies;               correction of this condition should be
    congenital heart defects especially              done before 1st birthday; afterwards,
    VSD are most common, followed by                 pulmonary hypertension has been
    omphalocele, diaphragmatic hernia,               present too long for surgery to be
    and spina bifida. Mortality rate is very
                                                     successful. Therefore, now it is
    high, and mere 5% reach their first
    birthday.
                                                     recommended that an echocardiogram
                                                     be performed during newborn period.
        Patau syndrome (Trisomy 13;                  2) Eye problems especially strabismus
    47,XY,+13) leads to oro-facial clefts,           are often present, therefore eyes should
    microphthalmia, and polydactyly.                 be       regularly     examined.       In
    Malformations of CNS, CVS and                    asymptomatic                    children,
    kidney are common.                               ophthalmologic examination before the
        The condition is less common than            4th birthday is recommended to
    Edwards syndrome, but, again, only               evaluate visual acuity.
    5% are born alive and 95% of them                3) Hypothyroidism is common
    die before completing their first year.          especially in adolescent period.
                                                     Therefore, thyroid profile should be
                                                     done on annual basis.
Anticipatory                                         4) Sensori-neural & conductive
                                                     hearing loss, both, seen in children
        Guidance:                                    with Downs. Hearing test should be
                                                     done at 6-8 months of age and as
       A new approach for the care                   needed afterward.
and treatment of patients with Downs                 5) Older patients with instability of the
syndrome (and other genetic &                        first & second vertebrae may get spinal
chromosomal disorders), anticipatory                 cord injuries. Imaging studies are
guidance, sets guidelines which if                   recommended in children with
followed strictly by the primary care                neurological symptoms and in those
physician, would help to prevent                     planning to participate in athletic
further disability or illness and                    activities.
improve survival.                                    6) Children should be referred to
1) Evaluation of heart defects: Atrio-               appropriate preschool programmes
ventricular canals are the most                      (where available) to provide for
common congenital heart defects seen                 developmental disabilities.
in the neonates with Downs. Sugical



1. A karyotype will establish whether the condition is the result of a true trisomy or a
translocation. If the latter is the case, the recurrence risk in future pregnancies is greatly
elevated. A karyotype will also help to establish whether the patient is a mosaic. This may
help to predict and explain the severity of expression of the disorder.
 2. The risk ranking varies with many factors (chances of occurrence/recurrence):
         25 year old female with one previous Down syndrome child (approximately 1%)
         25 year old male carrier of a 21/14 translocation (1% - 2%)
         45 year old female with no family history (approximately 3%)
         25 year old female carrier of a 21/14 translocation (10%-15%).




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Patient Guidance

Downs Syndrome
       Down's Syndrome is a congenital malformation accompanied by moderate to
severe mental underdevelopment. It is caused by a genetic abnormality, specifically in
the 21st chromosome.

  INCIDENCE AND DIAGNOSIS


       The overall incidence of Down’s syndrome is approximately 1 in 800 births,
but the risk increases with rising age of the mother. Prenatal tests such as
amniocentesis and chorionic villus sampling can be used to detect the chromosomal
abnormality causing Down’s syndrome. In addition, maternal blood tests can suggest
the presence of a foetus with Down’s syndrome when levels of a protein, alpha-
foetoprotein, are lower than usual, or when levels of the female sex hormone oestriol
(a form of oestrogen) and human chorionic gonadotrophin (a pituitary hormone that
controls the sex hormones) are abnormal.

        Individuals with Down’s syndrome are often short in stature and have a small,
round head with a high, flattened forehead and fissured, dry lips and tongue. A typical
feature is a fold of skin, the epicanthic fold, on the inner corner of each eye. The
palms show a single transverse crease and the soles have a straight crease from the
heel to the space between the first and second toes.

  CAUSES


        The chromosomal abnormality involved in most cases of Down’s syndrome is
trisomy-21, or the presence of three copies of the 21st chromosome. As a result, the
affected person has 47 chromosomes in all body cells instead of the normal 46,
although how this causes the condition’s symptoms is not yet known. Scientists
assume that the reason for the abnormal chromosomal assortment is the fertilization of
an ovum with 24 chromosomes by a sperm with a normal assortment of 23, but they
have also found that the sperm can carry the extra chromosome as well. The abnormal
ovum or sperm is derived from a germ cell in which the pair of 21st chromosomes
holds together and passes into the same sperm or ovum instead of separating. In the
type of Down’s syndrome called translocation, the extra chromosome-21 material is
attached to one of the other chromosomes; when some, but not all, of the body’s cells
carry an extra chromosome 21, the condition is a type of Down’s syndrome called
mosaicism.

  OUTLOOK


        Congenital heart disease, usually in the form of endocardial cushion defects,
affects around 40 per cent of babies with Down’s syndrome. Septal defects and


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Fallot’s tetralogy also occur. Many of these heart defects can be corrected surgically;
babies should be screened by echocardiography soon after birth as the defects may
well be difficult to detect. In the absence of a congenital heart defect, however, the
majority of children can expect to live into their sixth decade.

       Sensory problems include hearing impairments, which occur in many children
with Down’s syndrome. Annual audiometry and specialist consultation is
recommended. Visual impairment owing to refractive errors or strabismus (squint) is
also common and should be checked annually. Cataracts often develop but are usually
outside the visual axis.

        Although Down’s syndrome itself is not yet amenable to medical treatment,
medical care of the accompanying disorders and infections results in an almost normal
lifespan. In the past, many children with Down’s syndrome were institutionalized, but
this rarely happens today. Most children with Down’s syndrome take part in school
activities and curricula, and most adults hold a job.

         Unlike the cretins, Downs syndrome children are alert and happy, take interest
in life, and love music. Because of this vivacity, in the past they have sometimes been
termed ‘cheerful idiots’. Given a conducive & congenial atmosphere they can be
helped to pass life almost normally.

Answers to quiz III:

The child is suffering from typhoid fever. Repeated stool culture and widal test could help in
diagnosis. Management includes antibiotics, hydration (if needed iv fluids) and personal
hygiene.

         S. typhi only infects humans, and causes typhoid fever when an individual eats
contaminated food. S typhi can survive for a long time, even in frozen and dried foods. After
an incubation period of usually 10-14 days, vague influenza like illness with fever, malise,
pains and headache develops. The fever persists for a week and the child will become ill with
vomiting, abdominal pain, diarrhoea and cough. Older children and adults may get
constipation. The affected child looks septic and confused, and has a high temperature. There
will be tachycardia and tachypnea, but later on, as the disease progresses, bradycardia may
evolve and chest signs will appear. There is generalized tenderness in the abdomen, which is
also distended. There may be meningeal signs and hepatosplenomegaly in many cases.
Sometimes perforation of gut may occur, especially in the 2nd or 3rd week. This is usually
associated with sudden deterioration, hypotension, tachycardia, abdominal pain and rigidity.
The blood culture is positive in more than 2/3 of patients in the first week, but only in half of
these patients will the stool sample be positive. The Widal test may be helpful; an O antibody
of more than 4-fold will indicate infection with S. typhibut a high H-antibody will indicate
previous infection or vaccination. Anaemia, hyponatremia and thrombocytopenia occur in his
illness.

         Supportive treatment with careful electrolyte and fluid balance is more important than
trying to treat the infection with antibiotics. Chloramphenicol, co-trimoxazole and amoxicillin
are very effective in treating S typhi. Ceftriaxone and ciprofloxacin are used more frequently
these days as species of S. typhi become more resistant to other antibiotics. The duration of
illness varies from 7-14 days with the introduction of antibiotics. (Also see page 14-20)



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Burns                                       incidence of injuries during the festival
                                            period. Fire is also used in homicide
With    special     reference   to   the    and suicide.
developing world*
_______________________________             Problems in management

        Developing countries have a                  Burn       management          in
high incidence of burn injuries,            developing countries is riddled with
creating a formidable health problem.       difficulties. Lack of government
High population density, illiteracy, and    initiative and low literacy rates
poverty are the main demographic            preclude       effective        prevention
factors associated with a high risk of      programmes.        Many        uneducated
burn injury. The exact number of burns      households       are      fraught     with
is difficult to determine: judicious        superstition, taboo, weird religious
extrapolation suggests that India, with     rituals, and faith in alternative systems
a population of over 1 billion, has 7 to    of “medicine” which complicates
8 lakh burn admissions annually. The        management.
high incidence makes burn an endemic
health hazard. A multitude of social,                Most burn centres are situated
economic and cultural factors interact,     in large cities and are inadequate for
thereby complicating the management,        the high incidence of injuries.
reporting, and prevention of burns.         Resuscitation is often delayed as
                                            patients have to travel long distances
Epidemiology                                and transport facilities are poor, many
                                            burn centres are also plagued with lack
        The epidemiology of burn            of resources, lack of operating time
injuries is different from that in the      and shortage of blood. Generally there
developed world. Most burn injuries         are no dedicated burn surgeons, and
are sustained by women aged 16-35           surgeons without formal training in
years. Women of this age group tend to      burn management are involved in burn
be engaged in cooking, and most work        care. Burn nursing is also not a
at floor level and relatively unsafe        recognized concept. These conditions
kitchens and wear loose fitting clothes     make excisional surgery impossible for
such as saris, dupattas, and ghararas,      a large percentage of patients. There is
etc. Children and elderly people are at     generally no coordination between
relatively less risk because many           district hospitals and tertiary centres.
house-hold still exist as joint families,
and the system safe guards these age        Burn management problems in developing
                                            countries
groups to some extent.
                                                    High incidence of burns
                                                    Lack of prevention programme
        The commonest mode of burn                  Inadequate burn care facilities
injury is a flame burn. Most such                   Lack of resources
incidents are related to malfunctioning             Lack of trained staff
kerosene pressure stoves. These are                 Poor infrastructure and
cheap contraptions without safety                   coordination
features, and burns occur when carbon               Social problems
deposits block the kerosene vapour
outlets. Unsupervised and careless
handling of fire-crackers during the
festival of Diwali leads to an increased


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IJPD, 2004; Vol I No.3


Strategies for effective burn care         explosive chemicals, and firecrackers.
in developing countries                    A national body of burn professionals
                                           should be constituted to educate all
        The   approach   to  burn          healthcare staff involved in burn care.
management has to be radically
different from that in the Western         Providing treatment
countries.
                                                   To provide optimal burn care to
Strategies for burn management in          a large population with limited
developing countries                       resources, it is imperative to strengthen
        Effective prevention programmes    existing infrastructure. A few regional
        Burn as national health agenda     burn centres should be developed to
        Central registry of burns          provide tertiary management and
        Create a professional burn group   training to burn care staff. General
        Adequate safety legislation
                                           surgeons working in district hospitals
        Induct district Hospital and
        primary health centers             should form the nucleus of the burn-
        Encourage patient management at    care service and decide on referral
        home                               procedures.
        Cost effective treatment
        procedures                         Cost effective burn treatments to
        Develop regional centers of        conserve scarce resource
        excellence                         Parkland formula for fluid resuscitation -
                                           It is cost effective and ensures proper
Prevention programmes                      compliance

        Prevention programmes should               It is not possible to keep
be directed at behavioural and             referral patients at burn centres for six
environmental changes which can            to eight weeks of treatment; they can
easily adopted into lifestyle. The         be discharged after two to three weeks
programmes need to be executed with        of stabilization. Such patients can then
patience, persistence, and precision       be treated at district hospitals or at
training high risk groups.                 home with the help of primary health
                                           centres. Thus, primary health centres
        Depending on the population of     can act as liaison between burn
the country, burns prevention could be     patients and district hospital. The
national programmes. This can ensure       incidence of burn wound septicemia
sufficient funds are available and lead    with     domiciliary     treatment     is
to proper coordination of district,        remarkable low. These patients can be
regional and tertiary care centres. It     readmitted as necessary for blood
could also provide for compulsory          transfusion, treating septicemia and
reporting of all burn admissions to a      skin grafting.
central registry and these data could be
used to evaluate strategies and            Conservative burn wound
prevention programmes. There should        management
be adequate provision by law to set          This involves using closed dressing,
manufacturing standards for heating        eschar separation, and skin grafting.
and electrical equipment, fire safety      This takes the pressure off operating
standards for high rise buildings, and     facilities and provides comparable
procedures       for     storage     and   results of surgery.
transportation of hazardous materials,


                                                                                  78
IJPD, 2004; Vol I No.3


        Certain well-effected and cost-            Disaster plan
effective treatment procedures need to
be adopted to conserve resources; these                    An organized disaster plan can
include using Parkland formula for                 reduce loss of property, social disruption,
                                                   and suffering. A disaster plan should
resuscitation pursuing conservative
                                                   specially be tailored for a particular region
burn wound management and using                    and nature of fire disaster. Ultimately, a
amnion as a biological dressing.                   coordination system must be developed
                                                   that includes medical and public safety
Amnion as a biological dressing                    organization, law and order agencies, and
This is easily available, is free of cost, and     transport agencies.
can be comfortably preserved for a week
                                                   First aid at the site of burn disaster
                                                   Quantitative assessment of burns
Burn disaster                                      Qualitative assessment of burns
                                                   Commence intravenous resuscitation
       A disaster is a situation that is           Catheterization
unpredictable, massive, and poses an               Analgesia Hospital transfer
immediate threat to public health. A
burn disaster is “an event resulting in                    The communication lines from
mass burn casualties and severe loss of            the central command should be fast
human lives and material from a                    and multilingual. It should be able to
known           thermal         agent”.            advise workers at the disaster site,
                                                   direct     transport  agencies,    and
Characteristics of a burn disaster                 simultaneously relay the information
Large number of patient with extensive             to surrounding hospitals. All the
burn injuries                                      regional and distant hospitals must be
Immediate care and Assistance may not be           incorporated in a multi-tier system as
adequate                                           the number of cases may overwhelm
A high incidence of serious associated             local facilities.
injuries
Site of the disaster is not always accessible
                                                            Hospitals play a pivotal role in
Response time may be prolonged
Local infrastructure may                           providing trained staff. All doctors
                                                   and nurses, irrespective of their
       Disaster normally exceeds the               specialties and whether they are
resources of healthcare facilities.                included in the plan, should be
                                                   educated about the basics of burn care.
       Disaster management involves                With a burn specialist at the core, the
coordinating the activities of various             hospital disaster management team
health disciplines to prevent disaster,            also includes a respiratory physician
and help in rehabilitation of victims.             and an anesthetist. There should be
                                                   prompt and judicious deployment of
Factors to be considered while developing a        staff. Teams of psychologists should
disaster plan                                      manage panic among disaster victims
Unpredictability                                   and their relatives both at the disaster
Time (day night during festivities, etc)
                                                   site and at hospitals. Accurate triage
Area (City, non –urban, accessibility etc,)
Characteristics (explosion, building fire, toxic   by clinicians experienced in burns
fumes etc)                                         must guide the flow of patients from
Type of building (dwelling, hotel, office etc)     the site to the inner circle of healthcare
Type of trauma burn, associated injury,            facilities (primary and secondary care
inhalational injury
                                                   hospitals) and then to the outer circle
Number of people injured
Degree of preparedness to manage disaster          (tertiary care hospitals and burn
                                                   centres).


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        Transportation    needs    are      Group I – Minor burns (<10% of
guided by the number of victims, their      total surface area in children; <20%
condition, the nature of the fire           in adults ) to non-critical areas.
disaster,       and      geographical       Assigned to – Out patient care, dressing,
consideration. Possible modes of            tetanus prophylaxis.
transport include ambulances, local
transport vehicles, military vehicles,      Group II – Minor burns of critical
helicopters, fixed wing aircraft, and
                                            sites (face, hands genital)
rescue boats.
                                            Assigned to – Short hospital stay, special
Principles of disaster management
                                            wound care or operation.

Prevention                                  Group III- Major burns (20-60%)
Effective multidisciplinary response        Assigned to – Admission to burn unit,
Disaster profiles                           intravenous resuscitation.
Mobilization of workforce resources
Disease patterns                            Group IV – Extensive burns
Local community or national involvement
Risk assessment
                                            (>60%)
phase                                       Assigned to – Lower priority to transfer.
Reconstructive Post- emergency phase
                                            Group V – Minor burns with
Managing disaster                           inhalation injury or associated
                                            injury
        Immediate care is provided by       Assigned to - Oxygen, incubation, transfer
people present at the scene of the          to intensive care unit.
disaster, who may be survivors or
passers- by. These first responders are
later guided by trained healthcare                 The patients in groups III and
workers who arrive at the site. On site     V are evacuated first, followed by
management includes first aid, patient      group IV. Group II cases are evacuated
triage and ambulance-staging with a         at the end. Group I cases are either
basic aim of maximal use of resources.      discharged after first aid or asked to
                                            make their own way to the nearest
Triage                                      primary care centre

        Triage is the cornerstone of        Further treatment
effective burn disaster management
and is done at the disaster site by staff           Initial care is in the line of
with knowledge of burn treatment.           ABC of resuscitation. An adequate
Triage takes into consideration the         airway and respiration must be
total number of patients, bed               ensured. All patients except those with
availability,    and      transportation    minor burns must receive fluid
capacity.                                   resuscitation based on a simple
                                            formula. Wounds should be covered
        Triage should be prognostic,        with a sterile sheet until they are
and patients should be categorized on       dressed. Dressing should be simple
the basis of age, extent of burn, sit of    with only antimicrobial pads and
burns and presence of inhalation            Gamgee tissue. Effort should be made
injury:                                     to detect and treat associated injuries.


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Secondary triage may also be done at            centres. The success of such a plan lies
this time. If necessary, seriously              in accurate triage at every level, so that
injured patients can be sent to centres         all centres are used optimally and best
of higher level while less serious              possible treatment is delivered to all
patients who reach the tertiary centres         according to the severity of injury;
are referred back to primary care               with minimum delay.


                                                (Adapted from the British Medical Journal)




World Health Organisation…………
           Classification of depth of burn

           First degree (superficial) burns: The tissue damage is restricted to
           the epidermis and upper dermis. Nerve endings in the dermis
           become hypersensitive and the burn surface is painful. Blister
           formation is common. If the burn remains free from contamination,
           healing without scarring takes place in 7 days.

           Second degree (dermal) burns: The lowest layer of the epidermis,
           the germinal layer, derives support and nourishment from the
           dermis. Portions of the germinal layer remain viable within the
           dermis and are able to re-epithelialize the wound. A deeper burn
           penetrates into the dermis and fewer epidermal elements survive.
           The amount of residual scarring correlates with the density of
           surviving epidermal elements. Healing of deep dermal burns may
           take longer than 21 days and usually occurs with such severe
           scarring that skin grafting is recommended. Because vessels and
           nerve endings of the dermis are damaged, dermal burns appear
           paler and are less painful than superficial burns.

           Third degree (full-thickness) burns: Full thickness burns destroy
           all epidermal and dermal structures. The coagulated protein gives
           the burn a white appearance, and neither circulation nor sensation
           are present. After separation of the dead eschar, healing proceeds
           very slowly from the wound edge. Skin grafting is always
           required, unless the area is very small. Severe scarring is
           inevitable.

           Mixed depth: Burns are frequently of mixed depth. Estimate the
           average depthby the appearance and the presence of sensation.
           Resuscitation is based on the total of 2nd and 3rd degree burns and
           local treatment on the burn thickness at any specific site.




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Chronic Obstetric                            •   While the COPD death rate for
                                                 females more than doubled between
Pulmonary Disease                                1980 and 2000, and the number of
                                                 deaths for females surpassed the
            Rohini Bhan                          number for males in 2000, the overall
__________________________                       age-adjusted death rate for COPD
                                                 remained higher for males in 2000.
        Chronic Obstructive Pulmonary            The age-adjusted COPD death rate
Disease (COPD) is a slowly                       was about 46 percent higher in males
                                                 than females and 63 percent higher in
progressive disease of the airways that
                                                 whites than blacks.
is characterized by a gradual loss of
                                             •   COPD is the fourth leading cause of
lung function. What can be grouped               death in the U.S. and is projected to be
under the term varies from country to            the third leading cause of death for
country. In the U.S., the term COPD              both males and females by the year
includes chronic bronchitis, chronic             2020.
obstructive bronchitis, or emphysema,        c) Hospitalizations
or combinations of these conditions. It             From 1995 to 2000, the trend in
represents the fourth leading cause of       COPD hospitalization rates was about
death in the U.S.                            the same for males and females.
                                             However, the rates were slightly higher
        The symptoms of COPD can             among blacks than whites during this
range from chronic cough and sputum          same period. In 2000, the COPD
production to severe, disabling,             hospitalization rates were 31.5 and
shortness of breath. In some                 36.0 per 10,000 population for whites
individuals, chronic cough and sputum        and blacks, respectively.
production are the first signs that they
are at risk for developing the airflow       d) Emergency Department Visits and
obstruction and shortness of breath          Hospitalizations
characteristic of COPD. In others,               • About 1.5 million emergency
shortness of breath may be the first                department visits by adults 25
indication of the disease.                          and older were made for COPD
                                                    in 2000.
Epidemiology:                                    • More emergency department
Distribution:                                       visits for COPD were made by
                                                    adult females than adult males
                                                    (898,000 vs. 651,000).
a) Prevalence:
                                                 • About 726,000 hospitalizations
•   12.1 million adults ages 25 and older           for COPD occurred in 2000.
    reported being diagnosed with COPD              More females than males were
    in 2001.                                        hospitalized     for    COPD
•   About 24 million adults have evidence           (404,000 vs. 322,000).
    of impaired lung function indicating     e) Costs of COPD
    that COPD is under-diagnosed.                     The cost of COPD to the nation in
•   The prevalence of self-reported COPD     2002 was estimated to be $32.1 billion.
    is higher in females than males and in   Direct medical services accounted for
    whites than blacks.                      $18.0 billion, and indirect cost of
b) Mortality                                 morbidity and premature mortality was
•   About 119,000 adults ages 25 and         $14.1 billion. Medicare expenses for
    older died from COPD in 2000.            COPD beneficiaries were nearly 2.5 times
                                             that of the expenditures for all other
                                             patients.


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Costs of COPD in the US:                      they have COPD because they have
 ¡The total estimated cost of COPD in         minimal or no symptoms. Therefore,
2002 was $32.1 billion.                       COPD may be under-diagnosed.
          $18 billion direct costs
          $14.1 billion indirect costs                In the developed world, the
                                              most important risk factor for COPD
EMPHYSEMA                                     by far is cigarette smoking. Pipe, cigar,
        In 2001, the prevalence of            other types of tobacco smoking, and
emphysema was appreciably higher for          passive exposure to cigarette smoke
the 65 and older age group than the 45-       are also risk factors. Other documented
64 age group for each race-sex group.         causes of COPD include occupational
The prevalence was higher in males            dusts and chemicals. Outdoor air
than females and in whites than blacks.       pollution adds to the total burden of
The                                           inhaled particles in the lungs, but its
prevalence was highest in white males         role in causing COPD is uncertain. The
and lowest in black females. Over the         most important measure for preventing
past two decades, prevalence of               COPD – and for stopping disease
emphysema has consistently been               progression – is avoidance of smoking.
higher for the 65 and above age group.
                                              The most important risk factor for COPD
CHRONIC BRONCHITIS                            by far is cigarette smoking. Pipe, cigar,
         In 2001, the prevalence of           other types of tobacco smoking, and
chronic bronchitis was lowest among           passive exposure to cigarette smoke are
the 25-44 age group. Across age               also risk factors. Thus, the most important
groups, females had higher rates than         measure for preventing COPD – and for
males for both races. Among the 25-44         stopping disease progression – is
and 65 and older age groups,                  avoidance of smoking.
prevalence was higher
for whites than blacks for each sex                   The diagnosis of COPD is
group. For the 45-64 age group,               confirmed by the presence of airway
chronic bronchitis was higher among           bstruction on testing with spirometry.
females, and black females in
particular, had the highest prevalence                There is no known cure for
for this age group.                           COPD at the present time. Treatment is
                                              usually supportive and designed to
In 1997, the survey questions used to         relieve symptoms and improve quality
determine the prevalence of COPD in the       of life. Patients with COPD require
developed world changed. Prior to 1997,       emergency treatment and sometimes
the prevalence was based on individuals       ospitalizations during periods of
who had, or knew someone in the family        exacerbations of their disease
who     had,    chronic    bronchitis or
emphysema during the past 12 months.                  With continued exposure to
The new survey asks, “During the past 12
                                              cigarettes or noxious particles, the
months, have you been told by a doctor or
other health professional that you have       disease progresses and individuals with
chronic bronchitis?”; and “Have you ever      COPD increasingly lose their ability to
been told by a doctor or other health         breathe. Acute infections or certain
professional that you have emphysema?”        weather conditions may temporarily
Based on these questions, during 2001,        worsen symptoms (exacerbations),
12.1 million U.S. adults 25 years and older   occasionally where hospitalization may
reported having COPD (figure 1). In           be required.
addition, millions may be unaware that



                                                                                      83
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Immunity: An                               ii)     Microbes that penetrate the
                                           epithelium are met with macrophages
Introduction                               and related cells that have receptors for
                                           cell-surface molecules found on many
                  Ayaz Amin                microbial agents. These interactions
                                           may lead to phagocytosis of the
_______________________________            pathogen, activation of the macrophage
                                           so that it can destroy the agent and to
Over the last decades, body of             the induction of an inflammatory
knowledge on immunology has grown          response that recruits other cell types,
by leaps and bounds. The newer jargon      including neutrophils, to the site.
is quite unfamiliar to some who had        iii) Microbial pathogens may also be
qualified decades back and could not       recognized by components of the
keep in touch. The purpose of this         complement system leading to the
series is also to acquaint those with a    enhanced phagocytosis of the agent
limited background in immunology           and in some instances to its lysis as
with the current understanding of our      well as to independent activation of
immune system. Medical students also       inflammatory responses.
will find the section beneficial.          iv) The innate immune system also
                                           acts to recruit antigen-specific immune
        The immune system is a             responses, not only by attracting cells
remarkable defense mechanism of the        of the immune system to the site of the
bosy. It provides the means to make        infection, but also through the uptake
rapid,    specific,    and    protective   of antigen by dendritic cells that
responses      against    the    myriad    transport antigen to lymphoid tissue
potentially pathogenic microorganisms      where primary immune responses are
that inhabit the world in which we live.   initiated. Dendritic cells also produce
The tragic example of severe               cytokines that can regulate the quality
immunodeficiencies, as seen in both        of the immune response so that it is
genetically determined diseases and in     most appropriate to combating the
acquired immunodeficiency syndrome         pathogen.
(AIDS), graphically illustrates the
central role the                immune     Primary Responses
response plays in protection against
microbial infection. The immune                  Primary immune responses are
system also has a role in the rejection    initiated when a foreign antigenic
of tumors and may exert important          substance interacts with antigen-
effects in regulating other bodily         specific lymphocytes under appropriate
systems.                                   circumstances. The response generally
                                           consists of the production of antibody
Innate Immunity                            molecules specific for the antigenic
                                           determinants      of    the    antigen
       Most                pathogenic      (immunogen) and of the expansion and
microorganisms attempting to infect an     differentiation of antigen-specific
individual have to face powerful           helper and effector T-lymphocytes.
nonspecific defenses.                      The latter include cells that
i)   The epithelium provides both a        produce cytokines and killer T cells,
physical barrier to the entry of           capable of lysing infected cells.
microbes and produces a variety of         Generally, the combination of the
antimicrobial factors.                     innate immune response and the


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primary response are sufficient to          discriminated by the immune system is
eradicate or to control the microbe.        enormous.
Indeed, the most effective function of
the immune system is to mount a             Tolerance to self-antigen
response that eliminates the infectious
agent from the body.                               One of the most important
                                            features of the immune system is its
Secondary     Responses             and     ability to discriminate between
Immunologic Memory                          antigenic determinants expressed on
                                            foreign substances, such as pathogenic
       As a consequence of the initial      microbes, and potential antigenic
encounter with antigen, the immunized       determinants expressed by the tissues
individual develops a state of              of the host. The capacity of the system
immunologic memory. If the same (or         to ignore host antigens is an active
a closely related) microorganism is         process involving the elimination or
encountered again, a secondary              inactivation of cells that could
response is made. This generally            recognize self-antigens through a
consists of an antibody response that is    process     designated    immunologic
more rapid, greater in magnitude, and       tolerance.
composed of antibodies that bind to the
antigen with greater affinity and are       Autoimmune Diseases
more effective in clearing the microbe
from the body. A more rapid and more               Failures     in      establishing
effective T-cell response also ensues.      immunologic tolerance or unusual
One effect is that an initial infection     presentations of self-antigens can give
with a microorganism initiates a state      rise to tissue-damaging immune
of immunity in which the individual is      responses directed against antigenic
protected against a second infection. In    determinants on host molecules. These
the majority of situations, protection is   can result in autoimmune diseases. It is
provided by high-affinity antibody          now recognized that a range of
molecules that rapidly clear the re-        extremely important diseases are
introduced microbe. This is the basis of    caused by autoimmune responses or
vaccination; the great power of             have major autoimmune components,
vaccines is illustrated by the              including         systemic         lupus
elimination of smallpox from the world      erythematosus, rheumatoid arthritis,
and by the complete control of polio in     insulin-dependent diabetes mellitus,
the Western world.                          multiple sclerosis, myasthenia gravis,
                                            and regional enteritis. Efforts to treat
Specificity of immune response              these diseases by modulating the
                                            autoimmune response are a major
       The immune response is highly        theme of contemporary medicine.
specific. Primary immunization with a
given       microorganism        evokes
antibodies and T cells that are specific    AIDS: A virus the immune system
for the antigenic determinants found on     fails to eliminate
that microorganism but that fail to
recognize (or recognize only poorly)               Immune      responses     against
antigenic determinants expressed by         infectious agents do not always lead to
unrelated microbes. Indeed, the range       elimination of the pathogen. In some
of antigenic specificities that can be      instances, a chronic infection ensues in


                                                                                 85
IJPD, 2004; Vol I No.3


which the immune system adopts a           of immunity. It is their response that
variety of strategies to limit damage      orchestrates the effector limbs of the
caused by the organism or by the           immune system. Cells that interact
immune response. One of the most           with lymphocytes play critical parts
notable infectious diseases in which       both in the presentation of antigen and
the immune response generally fails to     in the mediation of immunologic
eliminate the organism is AIDS,            functions. These                    cells
caused by the human immuno-                include dendritic cells, and the closely
deficiency virus (HIV). In this            related Langerhans cells, Monocyte
instance, the principal infected cells     /macrophages, natural killer (NK)
are those of the immune system itself,     cells,    neutrophils,    mast     cells,
leading to an eventual state in which      basophils, and eosinophils. In addition,
the individual can no longer mount         a series of specialized epithelial and
protective immune responses against        stromal cells provide the anatomic
other microbial pathogens.                 environment in which immunity
                                           occurs, often by secreting critical
Major Principles of Immunity               factors that regulate migration, growth,
                                           and/or gene activation in cells of the
   The major principles of the             immune system. Such
immune response are:                       cells also play direct roles in the
                                           induction and effector phases of the
    1. Elimination of many microbial       response.
agents through the nonspecific
protective   mechanisms of the                           The cells of the immune
innate immune system                       system are found in peripheral
                                           organized tissues, such as the spleen,
    2. Highly specific recognition of      lymph nodes, Peyer’s patches of the
foreign antigens coupled with potent       intestine, and tonsils, where primary
mechanisms for      elimination    of      immune responses generally occur. A
microbes bearing such antigens             substantial portion of the lymphocytes
                                           and macrophages comprise a re-
    3.    A vast universe of distinct      circulating pool of cells found in the
antigenic     specificities   and   a      blood and lymph, as well as in the
comparably vast capacity      for the      lymph nodes and spleen, providing the
recognition of these antigens              means to deliver immuno-competent
                                           cells to sites where they are needed and
    4. The capacity of the system to       to allow immunity that is initiated
display immunologic memory                 locally to become generalized.
                                           Activated lymphocytes acquire the
    5. Tolerance of self-antigens          capacity to enter non-lymphoid tissues
                                           where they can express effector
                                           functions      and     eradicate   local
CELLS OF THE IMMUNE SYSTEM AND             infections.
THEIR SPECIFIC RECEPTORS AND
PRODUCTS
                                                   Some memory lymphocytes are
     The immune system consists of a       "on patrol" in the tissues, scanning for
wide range of distinct cell types, each    reintroduction of their specific
with important roles. The lymphocytes      antigens. Lymphocytes are also found
occupy central stage because they are      in the central lymphoid organs,
the cells that determine the specificity   thymus, and bone marrow, where they


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undergo the developmental steps that       created in the genes encoding antigen-
equip them to mediate the responses of     specific receptors, it seems virtually
the mature immune system.                  certain that the number of distinct
                                           combining sites on lymphocyte
             Individual    lymphocytes     receptors of an adult human can be
are specialized in that they are           measured in the millions.
committed to respond to a limited set
of structurally related antigens. This                  Lymphocytes differ from
commitment exists before the first         each other not only in the specificity of
contact of the immune system with a        their receptors but also in their
given antigen. It is expressed by the      functions. There are two broad classes
presence on the lymphocyte’s surface       of lymphocytes:        the            B-
membrane of receptors specific for         lymphocytes, which are precursors of
determinants (epitopes) of the antigen.    antibody-secreting cells, and the T-
Each     lymphocyte      possesses     a   (thymus-derived) lymphocytes. T-
population of receptors, all of which      lymphocytes express important helper
have identical combining sites. One        functions, such as the ability to aid in
set, or clone, of lymphocytes differs      the development of specific types of
from another clone in the structure of     immune responses, including the
the combining region of its receptors      production of antibody by B cells and
and thus in the epitopes that it can       the increase in the microbicidal activity
recognize. The ability of an organism      of macrophages. Other T-lymphocytes
to respond to virtually any non-self       are involved in direct effector
antigen is achieved by the existence of    functions, such as the lysis of virus-
a very large number of different           infected cells or certain neoplastic
lymphocytes, each bearing receptors        cells.   Specialized     T-lymphocytes
specific for a distinct epitope. As a      (regulatory T cells) have the capacity
consequence, lymphocytes are an            to suppress specific immune responses.
enormously heterogeneous group of
cells. Based on reasonable assumptions     ******************************
as to the range of diversity that can be




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IJPD, 2004; Vol I No.3



Immunization Status of Infants in a Remote District of
Kashmir
                   Bashir Gaash, Rohini Bhan, Shabnam Bashir
________________________________

        Immunization is a simple and cost-effective measure for preventing death and
disability in infants and young children. Yet, despite the international emphasis,
universal immunization has not been attained in most of the developing countries.(1)
The underlying reasons for this failure have generally been non-availability of
vaccine, breakdown of cold-chain, complacency of the staff, socio-economic disorder,
or an unfavourable public attitude.

        India, too, is according high priority to immunization, however, results remain
far from satisfactory and regional imbalances are quite sharp.(2) . Jammu & Kashmir
State generally, and its backward areas especially, are considered poor performers.
However, no authentic data is available to substantiate or refute this belief. Kargil,
being the most backward district of the State, was therefore taken up for an appraisal
survey to determine the current status of immunization among the infants .

Subjects, methodology & Setting:

        Kargil, located 203 km north of Srinagar and situated at an altitude of 7000 m
above the sea-level, is very sparsely populated. The land is hilly, terrain very difficult,
climate chilly, & weather inclement, and the only road linking it to rest of the world
remains closed for more than 8 months a year. The adverse geo-climatic features,
along with rampant illiteracy, conservatism, and frequent cross-border shelling, make
the district a highly vulnerable area amenable to disruption of health services. In the
current survey, which covered the 3 most populated blocks (Kargil, Sankoo & Drass),
a total of 538 children between the ages of 12 and 23 months were evaluated for their
immunization status.

Results show that only 65% of infants received full primary immunization, with rural
areas fairing worse (62%) than the urban areas (72%). Coverage rates were similar in
boys and girls. Antigen-wise, the highest coverage (92.5%) was seen for BCG, and
the poorest (65%) for measles vaccine. The attrition from the first to third dose of
DPT & OPV (from 89% to 83%) was remarkable; drop-out rates from the 3rd priming
dose (83%) to booster (31%) at 16-24 months were far more steep. Some 7.5% of the
infants remained completely un-immunized, while 28.5% were only partially primed.
(Table I).

Discussion:

        In the year 1998-99, the 2nd National Family Health Survey (NFHS-II) (3) was
undertaken by the International Institute for Population Sciences, Mumbai, to provide
information on the immunization status of infants. However, Kargil had been left out
of the J & K State.

        Our study showed a higher coverage in Kargil than the State-average found
in the NFHS-II and other surveys (3,4,5)(Table II). The coverage for BCG, DPT 3 &


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OPV3 was far higher in Kargil than what the Rapid Household Survey (MOHFW,
Government of India, 1999) found in District Baramulla. By inference, thus,
performance in Kargil - the most backward district of the State - was higher than the
districts with a better geo-demographic and socio-economic background. This
suggests that, educational backwardness, poverty, and conservatism,  the hallmarks
of Kargil  don’t necessarily keep populations from taking the advantages of the
available health care facilities. A comparative analysis of the official immunization
statistics of Kargil & Leh in 1998-99, too, revealed a much poorer performance in
Leh despite a better topography, more income, and higher literacy.

        The fact that immunization coverage among infants from socio-economically
better families and of highly educated mothers was lower than in their less privileged
counterparts suggests negative attitude of educated mothers towards immunization of
their infants.
        Despite a higher comparative performance revealed in our study, the pattern of
steadily decreasing proportion of infants from the 1st priming to 3rd dose, and a
further remarkable attrition for booster dose at 16-24 months (Fig 2), was similar to
that found elsewhere in the State. This indicates that the enthusiasm of the parents
generated with the birth of the child is not maintained, which, in turn, suggests lack of
sustained health education activity by the concerned health workers.

        Comparative analysis of the evaluated figures reveals that the actual coverage
for all antigens was lower than that conveyed officially. The NFHS-II also found a
consistent overestimation in the official statistics of the J & K State (6). Gross
exaggeration of immunization coverage in official data is found even at the national
level (Table IV), as has been pointed out by the WHO-Unicef evaluation studies. This
suggests that policy-makers & planners should not rely heavily on the officially-
quoted figures, and that well-designed evaluation studies by independent agencies
may be required annually to assess the actual coverage.




Table I.    Proportion of 12-23 month old children found to be actually covered* in             various
            evaluation studies.

       Name of the Survey               Total sample         Rural       Urban        Male       Female
                                              %                %            %          %            %
      Current Study (Kargil)                 65.1             62.1         72.2       66.3        63.0

           MICS¤ (J&K)                       54.9             50.7         72.9       58.4        50.3
           NFHS-II€ (J&K)                    56.7             53.4         73.1       61.4        50.0

            RHS¥ (J&K)                       41.8               -           -         65.7        60.8


* Children who had received BCG, 3 doses of DPT & OPV each, & measles vaccine were considered to be fully
immunized..
         ¤ MICS: Multiple Indicator Cluster Survey, 2000. Department of Women & Child Development,
                  Govt of India & Unicef.
         € NFHS-II: National Family Health Survey, 1998-99. International Institute for Population
                  Sciences, Mumbai & ORC USA.
         ¥ RHS: Rapid Household Survey, Phase II, 1999. Ministry of Health & Family Welfare, Govt of
                  India.




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Table II. Immunization Coverage by Vaccine (Percent of Children Aged 12-23 months covered)
             Comparison of State-level Evaluation Figures with Those in Kargil Study

                  Vaccine                        Current Study              MICS      NFHS-II              RHS
                Year of Survey                        2000-01               1999      1998-99             1998-99

 Geo-demographic area                       Kargil District              J&K        J&K                J&K
 represented
               BCG                                     92.6                 89.6          85.7                 84.7

                    DPT1                               88.9                 83.7          85.7                  -

                    DPT2                               84.0                 78.7          83.6                  -

                    DPT3                               83.0                 68.4          72.3                 63.4

                    OPV1                               88.9                 93.7          88.3                  -

                    OPV2                               84.0                 91.6          85.4                  -

                    OPV3                               83.0                 82.0          74.3                 61.3

                   Measles                             65.1                 65.5          68.9                 63.2

                 All Vaccines                          65.1                 54.9          56.7                 41.8

                   None                                7.4                  6.3        10.4                    5.0



Table III: Vaccine Coverage in India (Percent Achievement of Targets):
           Comparison of official and evaluation figures(1999 & 2000)

     Vaccine             Official figures    Evaluation          Official figures         Evaluation figures
                                              figures
                                (1999)      MICS (1999)            (2000 - 01)       WHO-Unicef Evaluation
                                                                                        Study (2001)

         BCG                     99              68                    99                        73

      DPT1                        -              64                     -                         -

      DPT3                       93              47                    94                        64

         Pol3                    93              59                    89                        70

     Measles                     89              50                    89                        56
     Vaccine




Bibliography:

    1.     WHO. Vaccines & Biologicals. WHO Vaccine-Preventable Diseases Monitoring System.
           Global Summary 2002. Geneva
    2.     Central Bureau of Health Intelligence: Health Information of India, 2000 & 2001.
           Directorate General of Health Services (MOHFW), Government of India, June 26, 2003.
    3.     International Institute for Population Sciences. National Family Health Survey – 1998-99
           (NFHS-II). International Institute for Population Sciences, Mumbai, & ORC Macro,
           Calverton; October 2002; pg 128-31
    4.     Department of Women & Child Development(Government of India) & United Nations
           Childrens’ Fund. Multiple Indicator Cluster Survey. (MICS-2000); November 2001; pg 45
    5.     Ministry of Health & Family Welfare, Government of India. Rapid Household Survey –
           RCH Project (Phase-II), 1999. Society for Applied Research in Humanities, New Delhi; pg
           29-31
    6.     Ministry of Health & Family Welfare, Government of India. Evaluation of          Routine
           Immunization 1997-98. New Delhi : Department of Family Welfare, MOHFW, Govt of India.



                                                                                                                      90
IJPD, 2004; Vol I No.3




Special Supplement

                              Drug Use in
                         Renal impairment




                                       91
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                         92
IJPD, 2004; Vol I No.3




Drug Use in Renal impairment

       Reduced renal function may cause problems with drug therapy for the
following reasons:

1. The failure to excrete a drug or its metabolites may produce toxicity.

2. The sensitivity to some drugs is increased even if the renal elimination is unimpaired.

3. The tolerance to adverse effects may be impaired.

4. The efficacy of some drugs may diminish.

       The dosage of many drugs must be adjusted in patients with renal impairment
to avoid adverse reactions and to ensure efficacy. The level of renal function below
which the dose of a drug must be reduced depends on how toxic it is and whether it is
eliminated entirely by renal excretion or is partly metabolized to inactive metabolites.

       In general, all patients with renal impairment are given a loading dose which is
the same as the usual dose for a patient with normal renal function. Maintenance
doses are adjusted to the clinical situation. The maintenance dose of a drug can be
reduced either by reducing the individual dose leaving the normal interval between
doses unchanged or by increasing the interval between doses without changing the
dose. The interval extension method may provide the benefits of convenience and
decreased cost, while the dose reduction method provides more constant plasma
concentration.

        In general, all patients with renal impairment are given a loading dose which
is the same as the usual dose for a patient with normal renal function. Maintenance
doses are adjusted to the clinical situation. The maintenance dose of a drug can be
reduced either by reducing the individual dose leaving the normal interval between
doses unchanged or by increasing the interval between doses without changing the
dose. The interval extension method may provide the benefits of convenience and
decreased cost, while the dose reduction method provides more constant plasma
concentration
       In the following table drugs are listed in alphabetical order. The table includes
only drugs for which specific information is available. Many drugs should be used


                                                                                             93
IJPD, 2004; Vol I No.3


with caution in renal impairment but no specific advice on dose adjustment is
available; it is therefore important to also refer to the individual drug entries. The
recommendations are given for various levels of renal function as estimated by the
glomerular filtration rate (GFR), usually measured by the creatinine clearance. The
serum-creatinine concentration can be used instead as a measure of renal function but
it is only a rough guide unless corrected for age, sex and weight by special
nomograms.



Renal impairment is usually divided into three grades:

        mild - GFR 20-50 ml/minute or approximate serum creatinine 150-300
                     micromol/litre

        moderate - GFR 10-20 ml/minute or serum creatinine 300-700 micromol/litre

        severe - GFR <10 ml/minute or serum creatinine >700 micromol/litre


When using the dosage guidelines the following must be considered:

    •   Drug prescribing should be kept to a minimum.

    •   Nephrotoxic drugs should, if possible, be avoided in all patients with renal
        disease because the nephrotoxicity is more likely to be serious.

    •   It is advisable to determine renal function not only before but also during the
        period of treatment and adjust the maintenance dose as necessary.

    •   Renal function (GFR, creatinine clearance) declines with age so that by the
        age of 80, it is half that in healthy young subjects. When prescribing for the
        elderly, assume at least a mild degree of renal impairment.

    •   Uraemic patients should be observed carefully for unexpected drug toxicity. In
        these patients the complexity of clinical status as well as other variables for
        example altered absorption, protein binding or metabolism, or liver function,
        and other drug therapy precludes use of fixed drug dosage and an
        individualized approach is required.




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Table of drugs to be avoided or used with caution in renal impairment

            Drug             Degree of                   Comment
                            impairment
Abacavir                  Severe          Avoid

Acetazolamide             Mild            Avoid; metabolic acidosis

Acetylsalicylic acid      Severe          Avoid; sodium and water retention;
                                          deterioration in renal function;
                                          increased risk of gastrointestinal
                                          bleeding
Aciclovir                 Mild            Reduce intravenous dose
                          Moderate to     Reduce dose
                          severe

Alcuronium                Severe          Prolonged duration of block


Alcuronium                Severe          Prolonged duration of block


Allopurinol               Moderate        100-200 mg daily; increased toxicity;
                                          rashes

                          Severe          100 mg on alternate days (maximum
                                          100 mg daily)
Aluminium hydroxide       Severe          Aluminium is absorbed and may
                                          accumulate.
                                          NOTE. Absorption of aluminium from
                                          aluminium salts is increased by citrates
                                          which are contained in many
                                          effervescent
                                          preparations (such as effervescent
                                          analgesics)
Amiloride                 Mild            Monitor plasma potassium;
                                           high risk of hyperkalaemia in renal
                                          impairment;
                                          amiloride excreted by kidney
                                          unchanged
                          Moderate        Avoid

Amoxicillin                Severe         Reduce dose; rashes more common




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IJPD, 2004; Vol I No.3


Amoxicillin + Clavulanic   Moderate to   Reduce dose
acid                       severe


Amphotericin               Mild          Use only if no alternative;
                                         nephrotoxicity may be reduced with
                                         use of complexes


Ampicillin                 Severe        Reduce dose; rashes more common


Atenolol                   Moderate      Reduce dose (excreted unchanged)

                           Severe        Start with small dose;
                                          higher plasma concentrations after oral
                                         administration;
                                         may reduce renal blood flow and
                                         dversely affect renal function
Azathioprine               Severe        Reduce dose




Benzathine                 Severe        Neurotoxicity-
benzylpenicillin                         high doses may cause convulsions

Benzylpenicillin            Severe       Maximum 6 g daily;
                                         neurotoxicity-
                                         high doses may cause convulsions
Bleomycin                  Moderate      Reduce dose


Captopril                                Use with caution and monitor response;
                           Mild to       initial dose 12.5 mg twice daily.
                           moderate      Hyperkalaemia and other adverse
                                         effects more common
Carbamazepine                            Manufacturer advises caution


Ceftazidime                Mild          Reduce dose


Ceftriaxone                Severe        Reduce dose;
                                         also monitor plasma concentration if
                                         both severe renal and hepatic
                                         impairment
Chlorambucil               Moderate      Use with caution and monitor response;
                                         increased risk of myelo-suppression


                                                                              96
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Chloramphenicol          Severe        Avoid unless no alternative;
                                       dose-related depression of
                                       aematopoiesis

Chloroquine              Mild to       Reduce dose
                         moderate

                         Severe        Avoid

Chlorphenamine           Severe        Dose reduction may be required


Chlorpromazine           Severe        Start with small doses;
                                       increased cerebral sensitivity


                                       Monitor kidney function-
Ciclosporin                            dose dependent increase in serum
                                       creatinine and urea during first few
                                       weeks may necessitate dose reduction
                                        (exclude rejection if kidney
                                       transplant)
Cimetidine                             600-800 mg daily;
                         Mild to       occasional risk of confusion
                         moderate

                         Severe        400 mg daily

Ciprofloxacin            Moderate      Use half normal dose


Cisplatin                 Mild         Avoid if possible;
                                       nephrotoxic and neurotoxic

Clindamycin                            Plasma half-life prolonged-
                                       may need dose reduction

Clonazepam               Severe        Start with small doses;
                                       increased cerebral

Cloxacillin              Severe        Reduce dose



Codeine                  Moderate to   Reduce dose or avoid;
                         severe        increased and prolonged effect;
                                       increased cerebral sensitivity
Colchicine               Moderate      Reduce dose



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                         Severe        Avoid or reduce dose if no alternative

Cyclophosphamide                       Reduce dose


Dacarbazine              Mild to       Dose reduction may be required
                         moderate

                         Severe        Avoid
Daunorubicin             Mild to       Reduce Dose
                         moderate

Deferoxamine                           Metal complexes excreted by kidneys
                                       (in
                                       severe renal impairment dialysis
                                       increases
                                       rate of elimination)
Desmopressin                           Antidiuretic effect may be reduced


Dextromethorphan         Moderate to   Reduce dose or avoid;
                         severe        increased and prolonged effect;
                                       increased cerebral sensitivity

Diatrizoates             Mild          Reduce dose and avoid dehydration;
                                       nephrotoxic


Diazepam                 Severe        Start with small doses;
                                       increased cerebral sensitivity literature



Didanosine               Mild          Reduce dose;
                                       consult manufacturer's

Diethylcarbamazine       Moderate to   Reduce dose;
                         severe        plasma half life prolonged and urinary
                                       excretion considerably reduced
Digoxin                  Mild          Reduce dose;
                                       toxicity increased by electrolyte
                                       disturbances

Dimercaprol                            Discontinue or use with extreme
                                       caution if impairment develops during
                                       treatment




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IJPD, 2004; Vol I No.3


Eflornithine                        Reduce dose


Ephedrine                Severe     Avoid;
                                    increased CNS toxicity

Ergometrine              Severe     Manufacturer advises avoid


Ergotamine               Moderate   Avoid;
                                    nausea and vomiting;
                                    risk of renal vasoconstriction
Erythromycin             Severe     Maximum 1.5 g daily (ototoxicity)


Ethambutol                          Reduce dose;
                         Mild       if creatinine clearance less than 30 ml /
                                    minute monitor plasma-ethambutol
                                    concentration;
                                    optic nerve damage
Fluconazole              Mild to    Usual initial dose then halve
                         moderate   subsequent
                                     doses
Flucytosine                         Reduce dose and monitor plasma-
                                    flucytosine concentration-
                                    consult manufacturer' s literature
Fluphenazine             Severe     Start with small doses;
                                    increased cerebral sensitivity

Furosemide               Moderate   May need high doses;
                                    deafness may follow rapid i/v injection




Gentamicin                Mild      Reduce dose; monitor plasma
                                    concentrations;

Glibenclamide            Severe     Avoid



Haloperidol              Severe     Start with small doses;
                                    increased cerebral sensitivity


Heparin                  Severe     Risk of bleeding increased




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IJPD, 2004; Vol I No.3




Hydralazine                              Reduce dose if creatinine clearance less
                                         than 30 ml/minute
Hydrochlorothiazide        Moderate      Avoid; ineffective


Ibuprofen                                Use lowest effective dose and monitor
                           Mild          renal
                                          function;
                                         sodium and water retention;
                                         deterioration in renal function possibly
                                         leading to renal failure
                           Moderate to
                           severe        Avoid

Imipenem + Cilastatin      Mild          Reduce dose

Reduce dose

Insulin                    Severe        May need dose reduction;
                                         Insulin requirements fall;
                                         compensatory response to
                                         hypoglycaemia is impaired
Iohexol                    Moderate to   Increased risk of nephrotoxicity;
                           severe        Avoid dehydration

Iopanoic acid              Mild to       Maximum 3 g
                           moderate
                           Severe        Avoid

Isoniazid                  Severe        Maximum 200 mg daily;
                                         Peripheral neuropathy

Lamivudine                 Mild          Reduce dose;
                                         consult manufacturer's literature


Lithium                    Mild          Avoid if possible or reduce dose and
                                         monitor
                                         plasma concentration carefully
                           Moderate
                                         Avoid

Lopinavir with Ritonavir                 Avoid oral solution due to propylene
                                         glycol
                                         content;
                                         use capsules with caution in severe
                                         impairment
Magnesium hydroxide        Moderate      Avoid or reduce dose;
                                         increased risk of toxicity


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IJPD, 2004; Vol I No.3


Magnesium sulfate        Moderate      Avoid or reduce dose; increased risk of
                                                               toxicity


Mannitol                               Avoid unless test dose produces
                                       diuretic
                                       response
Meglumine iotroxate      Moderate to   Increased risk of nephrotoxicity;
                         severe        Avoid dehydration


Mercaptopurine           Moderate      Reduce dose



Metformin                Mild          Avoid;
                                       increased risk of lactic acidosis

Methotrexate             Mild          Reduce dose; accumulates; nephrotoxic

                         Moderate      Avoid

Methyldopa               Moderate      Start with small dose;
                                       increased sensitivity to hypotensive and
                                       sedative effect
Metoclopramide           Severe        Avoid or use small dose;
                                       increased risk of extrapyramidal
                                       reactions
Morphine                 Moderate to   Reduce dose or avoid;
                         severe        increased and prolonged effect;
                                       increased cerebral
                                       sensitivity
Nalidixic acid           Moderate to   Use half normal dose;
                         severe        ineffective in renal failure because
                                       concentration in urine is inadequate
Nelfinavir                             No information available-
                                       Manufacturer advises caution

Neostigmine              Moderate      May need dose reduction


Nevirapine                              No information available-
                                       Manufacturer advises avoid
Nitrofurantoin           Mild          Avoid;
                                       peripheral neuropathy; ineffective
                                       because of inadequate urine
                                       concentrations
Ofloxacin                Mild          Usual initial dose, then use half normal
                                       dose



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IJPD, 2004; Vol I No.3




                            Moderate
                                           Usual initial dose, then 100 mg every
                                           24 hours


Penicillamine               Mild           Avoid if possible or reduce dose;
                                           nephrotoxic



Pentamidine isetionate      Mild           Reduce dose;
                                           consult manufacturer' s literature
Pentavalent antimony        Moderate       Increased adverse effects
compounds                   Severe         Avoid



Pethidine                    Moderate to   Reduce dose or avoid;
                            severe         increased and prolonged effect;
                                           increased cerebral sensitivity
Phenobarbital               Severe         Avoid large doses


Polyvidone-iodine           Severe         Avoid regular application to inflamed
                                           or                         broken
                                           mucosa
Potassium chloride          Moderate       Avoid routine use;
                                           high risk of hyperkalaemia

Prazosin                    Moderate to    Initially 500 micrograms daily;
                            severe         increased with
                                           caution
Procainamide                Mild           Avoid or reduce dose



Procaine benzylpenicillin   Severe         Neurotoxicity-
                                           high doses may cause convulsions

Procarbazine                Severe         Avoid


Proguanil                  Mild            100 mg once daily
                         > Moderate        50 mg on alternate days
               >           Severe          50 mg once weekly;
                                           increased risk of haematological
                                           toxicity




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IJPD, 2004; Vol I No.3


Propranolol                            Start with small dose;
                         Severe        higher plasma concentrations after oral
                                       administration;
                                       may reduce renal blood flow and
                                       adversely affect
                                       renal function in severe impairment
Propylthiouracil         Mild to       Use three-quarters normal dose
                         moderate

                         Severe        Use half normal dose

Pyridostigmine           Moderate      Reduce dose; excreted by kidney


Quinine                                Reduce parenteral maintenance dose
                                       for                        malaria
                                       treatment
Saquinavir               Severe        Dose adjustment possibly required


Sodium chloride          Severe        Avoid



Sodium hydrogen          Severe        Avoid;
carbonate                              specialized role in some forms of renal
                                       disease


Sodium nitroprusside     Moderate      Avoid prolonged use


Spironolactone                         Monitor plasma K+ ;
                         Mild          high risk of hyperkalaemia in renal
                                       impairment
                         Moderate
                                       Avoid
Stavudine                Mild          20 mg twice daily (15 mg if body
                                       weight less than 60 kg)

                         Moderate to   20 mg once daily (15 mg if body
                         severe        weight less
                                                              than 60 kg)
Streptomycin             Mild          Reduce dose; monitor plasma
                                       concentrations

Sulfadiazine             Severe        Avoid; high risk of crystalluria


Sulfamethoxazole +       Mild          Use half normal dose if creatinine


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IJPD, 2004; Vol I No.3


Trimethoprim                        clearance                          15-30
                                    ml/minute;
                                    avoid if creatinine clearance less than
                                    15 ml/minute and plasma-
                                    sulfamethoxazole concentration cannot
                                    be monitored

Sulfasalazine            Moderate   Risk of toxicity including crystalluria
                                       - ensure high fluid intake

                         Severe        Avoid

Trimethoprim             Moderate   Reduce dose


Valproic acid            Mild to    Reduce dose
                         moderate
                         Severe
                                    Alter dosage according to free serum
                                    valproic acid concentration
Vancomycin                          Reduce dose-
                         Mild       monitor plasma-vancomycin
                                    concentration and renal function
                                    regularly
Vecuronium               Severe     Reduce dose;
                                    duration of block possibly prolonged

Warfarin                 Severe     Avoid


Zidovudine               Severe     Reduce dose;
                                    manufacturer advises oral dose of 300-
                                    400 mg daily




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