Malaria in Pregnancy

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					Malaria in Pregnancy



   Prof.Surendra Nath Panda, M.S.
   Department of Obstetrics & Gynaecology
       M.K.C.G.MEDICAL COLLEGE
       BERHAMPUR, ORISSA, INDIA
Malaria Menance
  World wide 103 countries with 2.5 billion people,
   developing countries worst affected.
  40 % of world’s population in shadow of Malaria.
  Deaths- Under estimated/Unknown,1.1 to 2.7
   million per year
  Gender related mortality - Females more
  Malaria in Pregnancy: -
      Mutually aggravating
      Mortality is double

      Primigravidae - 60-70%

      Highest prevalence in second half.

      Plasmodium Falciparum – More common.


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Malaria in Pregnancy :                        Sinister Coincidence
 Malaria and pregnancy are mutually aggravating conditions.
 The physiological changes of pregnancy and the
  pathological changes due to malaria have a synergistic
  effect on the course of each other, thus making life difficult
  for the mother, the child and the treating physician.
 P. falciparum malaria can run a turbulent and dramatic
  course in pregnant women.
 The non- immune, primigravidae are usually the most
  affected.
 In areas where malaria is endemic, 20-40% of all babies
  born may have a low birth weight.



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Malaria in Pregnancy :                            Double Trouble
More common.
     Malaria is more common in pregnancy compared to the
      general population probably due to Immuno suppression
      and loss of acquired immunity to malaria.
More atypical.
     In pregnancy, malaria tends to be more atypical in
      presentation probably due to the hormonal ,
      immunological and haematological changes of
      pregnancy.
More severe.
     Probably for the same reason, the parasitemia tends to
      be 10 times higher and as a result, all the complications
      of falciparum malaria are more common in pregnancy
      compared to the non-pregnant population.
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Malaria in Pregnancy :                                Double Trouble
 More fatal
      P. falciparum malaria in pregnancy being more severe, the mortality
       is also double (13 % ) compared to the non-pregnant population
       (6.5%).
 Selective treatment
      Some anti malarials are contra indicated in pregnancy and some
       may cause severe adverse effects.
      Therefore the treatment may become difficult, particularly in cases
       of severe P. falciparum malaria.
 Other problems
      Management of complications of malaria may be difficult due to the
       various physiological changes of pregnancy.
      Careful attention has to be paid towards fluid management,
       temperature control, etc.
      Decisions regarding induction of labour may be difficult and
       complex.
      Foetal loss, IUGR, and premature labour are common.


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Pathology of Malaria in Pregnancy
P. falciparum malaria can run a very turbulent
 course in pregnancy, particularly the first and
 second pregnancies.
These complications are more common and
 severe in hyperendemic areas for falciparum
 malaria.
Physiologic changes of pregnancy contribute to the
 aggravation of malarial infection.
   Changes in the hormonal milieu,
   Increase in the body fluid volume,

   Decrease in haemoglobin level and other changes add
    to the severity.

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Pathology of Malaria in Pregnancy
There is a generalised immunosuppression in
 pregnancy with reduction in gamma globulin
 synthesis and inhibition of reticulo endothelial
 system, resulting in
   Decrease in the levels of anti malarial antibodies and
    loss of acquired immunity to malaria.
   This makes the pregnant woman more prone for malarial
    infection and the parasitemia tends to be much higher.




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Changes in Placenta
Placenta is the preferred site of sequestration and
 development of malarial parasite.
Intervillous spaces are filled with parasites and
 macrophages, interfering with oxygen and nutrient
 transport to the foetus.
Villous hypertrophy and fibrinoid necrosis of villi
 (complete or partial) have been observed.
All the placental tissues exhibit malarial pigments
 (with or even without parasites).



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Clinical features
 Atypical manifestations of malaria are more common in
   pregnancy, particularly in the 2nd half of pregnancy.
 Fever :
      Patient may have different patterns of fever - from afebrile to
       continuous fever, low grade to hyper pyrexia.
      In 2nd half of pregnancy, there may be more frequent paroxysms
       due to Immunosuppression.
 Anemia :
      In developing countries, where malaria is most common, anemia is
       a common feature of pregnancy.
      Malnutrition and helminthiasis are the commonest causes of
       anemia.
      In such a situation, malaria will compound the problem.
      Anemia may even be the presenting feature of malaria and therefore
       all cases of anemia should be tested for M.P.
       Anemia as a presenting feature is more common in partially
       immune multigravidae living in hyper endemic areas.

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Clinical features
 Atypical manifestations of malaria are more common in
   pregnancy, particularly in the 2nd half of pregnancy.
 Splenomegaly :
      Enlargement of the spleen may be variable. It may be absent or
       small in 2nd half of pregnancy.
      A pre-existing enlarged spleen may regress in size in pregnancy.
 Complications :
      Complications tend to be more common and more severe in
       pregnancy.
      A patient may present with complications of malaria or they may
       develop suddenly.
      Acute pulmonary edema, hypoglycemia and anemia are more
       common in pregnancy.
      Jaundice, convulsions, altered sensorium, coma, vomiting /
       diarrhoea and other complications may be seen.
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Complications of Malaria in Pregnancy
 Anemia:
Malaria can cause or aggravate anaemia due to:
      Hemolysis of parasitised red blood cells.
      Increased demands of pregnancy.
      Profound hemolysis can aggravate folate deficiency.
Anemia due to malaria is more common and
 severe between 16-29 weeks.
It can develop suddenly, in case of severe malaria
 with high grades of parasitemia.
 Pre existing iron and folate deficiency can exacerbate the
  anemia of malaria and vice versa.


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Complications of Malaria in Pregnancy
Anemia:
Anaemia increases perinatal mortality and
 maternal morbidity and mortality.
It also increases the risk of pulmonary oedema.
 Risk of post-partum haemorrhage is also higher.
Significant anemia (Haemoglobin < 7-8 g%) may
 have to be treated with blood transfusion.
In view of the increased fluid volume in pregnancy,
 it is better to transfuse packed cells than whole
 blood.
Rapid transfusion, particularly whole blood, may
 cause pulmonary oedema.

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Complications of Malaria in Pregnancy
Acute pulmonary oedema:
 Acute pulmonary oedema is also a more common
  complication of malaria in pregnancy compared to the non-
  pregnant population.
 It may be the presenting feature or can develop suddenly
  after several days. It is more common in 2nd and 3rd
  trimesters.
 It can develop suddenly in immediate post-partum period.
  This is due to
      Auto transfusion of placental blood with high proportion of
       parasitised RBC’s
      Sudden increase in peripheral vascular resistance after delivery.
 It is aggravated by pre existing anaemia and hemodynamic
  changes of pregnancy.
 Acute pulmonary oedema carries a very high mortality.
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Complications of Malaria in Pregnancy
Hypoglycaemia:
This is another complication of malaria that is
 peculiarly more common in pregnancy.
The following factors contribute to hypoglycemia:
     Increased demands of hypercatabolic state and infecting
      parasites.
     Hypoglycaemic response to starvation.
     Increased response of pancreatic islets to secretory
      stimuli (like quinine) leads to hyperinsulinemia and
      hypoglycemia..


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Complications of Malaria in Pregnancy
Hypoglycaemia:
Hypoglycaemia in these patients can remain
 asymptomatic and may not be detected, because:
     all the symptoms of hypoglycemia are also caused by
      malaria viz. tachycardia, sweating, giddiness etc.
     Some patients may have abnormal behaviour,
      convulsions, altered sensorium, sudden loss of
      consciousness etc.
     These symptoms of hypoglycemia may be easily
      confused with cerebral malaria.
     Therefore, in all pregnant women with falciparum
      malaria, particularly those receiving quinine, blood sugar
      should be monitored every 4-6 hours.

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Complications of Malaria in Pregnancy
Hypoglycaemia:

Hypoglycaemia can be recurrent and
 therefore constant monitoring is needed.
In some, it can be associated with lactic
 acidosis and in such cases mortality is very
 high.
Maternal hypoglycemia can cause foetal
 distress without any signs.


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Complications of Malaria in Pregnancy
Immunosuppression:
Immunosuppression in pregnancy poses special
 problems.
It makes malaria more common and more severe.
 And to add to the woes, malaria itself suppresses
 immune response.
Hormonal changes of pregnancy, reduced
 synthesis of immunoglobulins, reduced function of
 reticulo endothelial system are the causes for
 Immunosuppression in pregnancy.



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Complications of Malaria in Pregnancy
Immunosuppression:
This results in loss of acquired immunity to malaria,
 making the pregnant more prone for malaria.
 Malaria becomes more severe with higher
 parasitemia.
Patient may have more frequent paroxysms of
 fever and frequent relapses.
Secondary infections (U.T.I. and pneumonias) and
 algid malaria (septicaemic shock) are more
 common in pregnancy due to Immunosuppression.


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Risks for the foetus
Malaria in pregnancy is detrimental to the foetus
 due to: -
   high grades of fever,
   placental insufficiency,

   hypoglycaemia,

   anaemia and other complications.

Both P. vivax and P. falciparum malaria can pose
 problems for the foetus, with the latter being more
 serious.



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Risks for the foetus
The prenatal and neonatal mortality may vary from
 15 to 70%.
   In one study, mortality due to P. vivax malaria during
    pregnancy was 15.7% while that due to P. falciparum
    was 33%.
   Spontaneous abortion, pre mature birth, still birth,
    placental insufficiency and I.U.G.R. (temporary /
    chronic), low birth weight, foetal distress are the different
    problems observed in the growing foetus.
   Transplacental spread of the infection to the foetus can
    result in congenital malaria.



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Risks for the foetus                  Congenital malaria:
It is very rare and occurs in < 5% of affected
 pregnancies. Placental barrier and matenal Ig G
 antibodies which cross the placenta may protect
 the foetus to some extent.
However, it is much more common in non-immune
 population and the incidence goes up during
 epidemics of malaria.
Fetal plasma Quinine and Chloroquine levels are
 about one third of simultaneous maternal levels
 and this subtherapeutic drug level does not cure
 the infection in the foetus.

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Risks for the foetus                  Congenital malaria:
All four species can cause congenital malaria, but
 it is proportionately more with P. malariae.
The new born child can manifest with fever,
 irritability, feeding problems, hepato splenomegaly,
 anaemia, jaundice etc.
The diagnosis can be confirmed by a smear for
 M.P. from cord blood or heel prick, anytime within
 a week after birth (or even later if post-partum,
 mosquito-borne infection is not likely).
Differential diagnoses include Rh. incompatibility,
 infections with C.M.V., Herpes, Rubella,
 Toxoplasmosis, and syphilis.

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Diagnosis
High level of awareness
Peripheral blood smear




Antigen detection techniques : (PfHPR-2)
Fluorescent staining
PCR based assay
Antibody test
Placental blood smear
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Indicators of Poor Prognosis
   Hyper parasitemia: - 5% erythrocytes infested.
   Peripheral schizotaemia.
   Leucocytosis 12,000/ cmm.
   Hb 7.1 gm%.
   PCV 20 %.
   Blood urea 60 mg / dL
   Creatinine 3 mg / dL.,
   Blood glucose 40 mg / dL.
   High lactate and low sugar in CSF.
   Low antithrombin III level.
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Management of Malaria in Pregnancy

 Management of malaria in pregnancy
  involves the following three aspects and
  equal importance should be attached to
  all the three.
  1. Treatment of malaria
  2. Management of complications
  3. Management of labour



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Treatment of Malaria in Pregnancy
Should Be Energetic, Anticipatory and Careful.
Energetic:
 Don't waste any time.
 It is better to admit all cases of P. falciparum
  malaria.
 Assess severity-
    General condition, pallor, jaundice, B.P.,
     temperature, haemoglobin, Parasite count,
     S.G.P.T., S .bilirubin, S.creatinine, Blood sugar.

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Treatment of Malaria in Pregnancy
Should Be Energetic, Anticipatory and Careful.
Anticipatory:
 Malaria in pregnancy can cause sudden and
  dramatic complications. Therefore, one should
  always be looking for any complications by regular
  monitoring.
 Monitor maternal and foetal vital parameters 2
  hourly.
 R.B.S. 4-6 hourly; haemoglobin and parasite
  count 12 hourly; S. creatinine; S. bilirubin and
  Intake / Output chart daily.

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 Treatment of Malaria in Pregnancy
Should Be Energetic, Anticipatory and Careful.
Careful:
 The physiologic changes of pregnancy pose special
  problems in management of malaria.
 In addition, certain drugs are contra indicated in pregnancy
  or may cause more severe adverse effects. All these
  factors should be taken into consideration while treating
  these patients.
 Choose drugs according to severity of the disease/
  sensitivity pattern in the locality.
 Avoid drugs that are contra indicated
 Avoid over / under dosing of drugs
 Avoid fluid overload / dehydration
 Maintain adequate intake of calories.

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 Treatment of Malaria in Pregnancy
 Choice of Anti malarials in pregnancy

 All trimesters:
   First line - Chloroquine; Quinine;
   Second line - Artesunate / Artemether / Arteether
 2nd / 3rd trimester: with caution
   Pyrimethamine + sulphadoxine; Mefloquine
 Contra indicated:
   Primaquine; Tetracycline; Doxycycline; Halofantrine




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Treatment of Malaria in Pregnancy
 Dose of Anti malarials

 Chloroquine:
    600mg (base) start, 300mg after 6 hours, 24 hours & 48 hours
 Quinine:
    IV - 20mg/kg infusion over 4 hours, repeat 8 hourly. Maintenance:
     10mg over 4 hours, 8 hourly. Follow with oral medication after
     clinically stable.
    Oral – 600mg 8hourly ( maximum 2 gm / day) for 7 days.
 Artesunate:
    Oral-100mg BD on day 1, then 50mg BD for 4-6 days (Total dose
     10mg/kg).
    IM / IV-120mg on Day 1 followed by 60mg daily for 4 days. In
     severe cases an additional dose of 60mg after 6 hours on Day 1.

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 Treatment of Malaria in Pregnancy
  Dose of Anti malarials

 Artemether:
    Six amp (480mg) IM in 5 / 3 days. 1x2x1+1x1x4 OR 1x2x3.
 Arteether:
    One amp (150mg) IM / day for3 consecutive days.
 Pyrimethamine 25mg+sulphadoxine 500mg tablets:
    Three tablets single dose.
 Mefloquine:
    15mg / kg body wt., up to 1 Gm in a single dose. OR
    Tablets of 250mg, 3 tab start, then 2 tab after 6-8 hours. With body
     wt >60kg, a third dose of 1 tab after 6-8 hours.



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Management of complications
 Acute Pulmonary Oedema:
      Careful fluid management; back rest; oxygen; diuretics; ventilation if
       needed.
 Hypoglycaemia:
      25-50% Dextrose, 50-100 ml I.V., followed by 10% dextrose
       continuous infusion.
      If fluid overload is a problem, then Inj. Glucagon 0.5-1 mg can be
       given intra muscularly.
      Blood sugar should be monitored every 4-6 hours for recurrent
       hypoglycemia.
 Anemia:
      Packed cells should be transfused if haemoglobin is <5 g%.
 Renal failure:
      Renal failure could be pre-renal due to unrecognised dehydration or
       renal due to severe parasitemia.
      Treatment involves careful fluid management, diuretics, and dialysis
       if needed.

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Management of complications
 Septicaemic shock:
      Secondary bacterial infections like urinary tract infection, pneumonia
       etc. are more common in pregnancy associated with malaria.
      Some of these patients may develop septicaemic shock, the so
       called 'algid malaria'.
      Treatment involves administration of 3rd generation cephalosporins,
       fluid replacement, monitoring of vital parameters and intake and
       output.
 Exchange transfusion:
      Exchange transfusion is indicated in cases of severe falciparum
       malaria to reduce the parasite load. Patient’s blood is removed and
       it is replaced with packed cells.
      It is especially useful in cases of very high parasitemia (helps in
       clearing) and impending pulmonary oedema (helps to reduce fluid
       load).

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Management of Labour
Anaemia, hypoglycaemia, pulmonary oedema, and
 secondary infections due to malaria in pregnancy
 lead to problems for both the mother and the
 foetus.
Severe falciparum malaria in term pregnancy
 carries a very high mortality.
Maternal and foetal distress may go unrecognised
 in these patients.
Therefore, careful monitoring of maternal and
 foetal parameters is extremely important.
Pregnant women with severe malaria are better
 managed in an intensive care unit.
   2:54 AM   02-11-02   Malaria in Pregnancy - Prof.S.N.Panda   34
Management of Labour
Falciparum malaria induces uterine contractions,
 resulting in premature labour. The frequency and
 intensity of contractions appear to be related to the
 height of the fever.
Fetal distress is common and often unrecognised.
 Therefore only monitoring of uterine contractions
 and fetal heart rate may reveal asymptomatic
 labour and foetal distress.
All efforts should be made to rapidly bring the
 temperature under control,
   By tepid sponging (cold sponging causes cutaneous
    vasoconstriction and can result in core hyperpyrexia).
   Anti pyretics like paracetamol etc.

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Management of Labour
 Careful fluid management is also very important.
  Dehydration as well as fluid overload should be avoided,
  because both could be detrimental to the mother and/or the
  foetus.
 In cases of very high parasitemia, exchange transfusion
  may have to be carried out.
 If the situation demands, induction of labour may have to be
  considered.
 Once the patient is in labour, foetal or matenal distress may
  indicate the need to shorten the 2nd stage by forceps or
  vacuum extraction.
 If needed, even caesarean section must be considered.


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Treatment of Vivax Malaria in Pregnancy
Radical cure
 Use of Primaquine & Proguanil are not safe in pregnancy
  and also in lactating mothers.
 Therefore to prevent the relapse of vivax malaria,
  suppressive chemoprophylaxis with Chloroquine is
  recommended.
 Tablet Chloroquine 300 mg (base) weekly should be
  administered to all such patients until stoppage of lactation.
 At that point, a complete treatment with full therapeutic
  dose of Chloroquine and Primaquine (7.5mg b.I.d. or 15mg
  daily, for 14 days) should be administered.
 However in case of resistance, Primaquine or Proguanil
  may be given with caution in 2nd half of pregnancy.

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Chemoprophylaxis in Pregnancy
 Malaria being potentially fatal to both the mother and the
  foetus, this should be an important part of antenatal care in
  areas of high transmission.
      All pregnant women, who remain in the malarious area during their
       pregnancy, should be protected with chemoprophylaxis.
 Choice of anti malarials for chemo prophylaxis:
      Chloroquine being the safest drug in pregnancy, should be the first
       choice.
      However, its use may be restricted due to the wide spread
       resistance to this drug.
      In areas with known resistance to Chloroquine
           Pyrimethamine + Sulpha, Mefloquine or Proguanil can be used.
           But these drugs should be started only after 1st trimester only.



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Chemoprophylaxis in Pregnancy                                     DOSAGE –

Chloroquine: - 300mg base, administered once
 every week.
Pyrimethamine-25mg + Sulphadoxine-500mg: -
 One tablet once weekly.
Mefloquine: -250mg weekly.
     Dose may have to be increased in the last trimester, in
      view of the accelerated clearance of the drug.
Proguanil: - 150-200mg / day.




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              FOR A HEALTHY MOTHER AND
                   A HEALTHY BABY




2:54 AM   02-11-02   Malaria in Pregnancy - Prof.S.N.Panda   40

				
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Description: World wide 103 countries with 2.5 billion people, developing countries worst affected. 40 % of world’s population in shadow of Malaria. Deaths- Under estimated/Unknown,1.1 to 2.7 million per year. Malaria and pregnancy are mutually aggravating conditions. The physiological changes of pregnancy and the pathological changes due to malaria have a synergistic effect on the course of each other, thus making life difficult for the mother, the child and the treating physician. P. falciparum malaria can run a turbulent and dramatic course in pregnant women. In areas where malaria is endemic, 20-40% of all babies born may have a low birth weight. Malaria is more common in pregnancy compared to the general population probably due to Immuno suppression and loss of acquired immunity to malaria. In pregnancy, malaria tends to be more atypical in presentation probably due to the hormonal , immunological and haematological changes of pregnancy.