hiv by niusheng11

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									AIDS and Opportunistic
      Infections



      April 13, 2010

    Silvia N. J. Moreno
                                 History of AIDS
• 1981: PCP and Kaposi’s sarcoma reported by doctors in NY and Los Angeles. CDC reports in MMW
 a strange killer pneumonia spreading among gay men. Is was designated as GRID (Gay-Related
 Immune Deficiency).
• 1982-1985: Cases of AIDS in 1982 began to be reported by fourteen nations. In 1982 CDC received
 its first report of "AIDS in a person with hemophilia (from a blood transfusion), and in
  infants born to mothers with AIDS.”
• 1983: Dr. Montagnier announced the
 isolation of LAV retrovirus
 (lymphadenopathy-associated virus),
 which later was identified as the cause
  of AIDS. 33 countries reported cases.
• 1984: Dr. Robert Gallo of the NCI
 isolated HTLV-III retrovirus ( Human
 T-cell lymphotropic virus III). It was later
 determined that LAV and HTLV-III were the same virus
• 1985: AIDS awareness was brought to the public's consciousness,
 Rock Hudson, died of AIDS shortly after making it public thus becoming the first major public figure to
 announce that he had AIDS. An HIV blood test was brought to large companies to make it available
 in large scale.
                           History of AIDS
• 1986: President Reagan makes his first mention of the word “AIDS”
  publicly and request the Surgeon General C. Everett Koop to
  prepare a report which was released in October 1986. He followed
  with a brochure: “Understanding AIDS” that was sent to 107 million
  households. It warned that “AIDS is one of the most serious
  health problems that has ever faced the American public”. It
  discussed risk behaviors.
• 1987: AZT (also known
  as Retrovir®, zidovudine,
  or ZDV) -- GlaxoSmithKline
  -- became the first anti-HIV
  drug (a Nucleoside
  Reverse Transcriptase
  Inhibitor) approved by
  the FDA. Reverse transcriptase is the
  enzyme that HIV uses to make a DNA
  copy of its RNA. This is necessary for the
  production of the viral double-stranded
  DNA which is integrated into the genetic
  material of the infected cell. AZT is used
  in combination with at least two other
  anti-HIV drugs.
                          History of AIDS
 • 1987: A touch of a Princess: On March
 20, 1987 princess Diana changed the public
 perception of AIDS at the opening of a special
 ward at London’s Middlesex Hospital. She
 was seen not wearing gloves and shaking
 hands with people with AIDS.

               1990: Death of Ryan White, a nineteen year old, white,
               heterosexual, teenager from Indiana died because of
               AIDS which he contracted from blood products, as part
               of his treatment for hemophilia.


• In August of 1990, President George H.W. Bush signed the the Ryan White
 Comprehensive AIDS Resources Emergency (CARE) Act into law.
• The bill authorized $881 million in relief funds to the 16 cities hardest hit by the
 epidemic. Congress only appropriated $350 million.
• President Bush also signed the Americans with
 Disabilities Act (ADA) in 1990 to protect people with HIV/AIDS from discrimination.
                                      History of AIDS
1999: Origin of HIV-1 Discovered. A research
 team from UAB lead by Dr Beatrice Hahn identified a
 subspecies of chimpanzee (Pan troglodytes troglodytes) native to
 West-Central Africa as the natural reservoir for HIV-1. Viruses
 related to HIV-1 had previously been found in chimpanzees and
 were given the designation SIVcpz (for Simian Immunodeficiency
 Virus). P. T. troglodytes has been the source of three
 independent cross-species transmission events.
 Both HIV-1 (chimpanzees) and HIV-2 (sooty mangabeys)
 originated in Africa.
 Why the epidemic arose in the mid-20th century is not
 clear.




                                                         Pan troglodytes sub-especies and distribution
                                                         1. Pan troglodytes verus
                                                         2. P. t. vellerosus
     People in some African nations                      3. P. t. troglodytes
     contract the virus by eating                        4. P. t. schweinfurthii
     'bushmeat'
The Nobel Prize in Physiology or Medicine for 2008 with one half
to Harald zur Hausen for his discovery of “human papilloma
viruses causing cervical cancer” and the other half jointly to
Françoise Barré-Sinoussi and Luc Montagnier for their discovery
of “human immunodeficiency virus.”
Four's a crowd. The Nobel Assembly surprised many by not
sharing the award with pioneering AIDS researcher Robert Gallo.
               Global summary of the AIDS epidemic,
                         December 2008
                                       Total                                  34.4 million [31.1 – 35.8 million]
Number of people living
                                       Adults                                 31.3 million [29.2 – 33.7 million]
with HIV in 2008                       Women                                  15.7 million [14.2 – 17.2 million]
                                       Children under 15 years                2.1 million [1.2 – 2.49 million]


                                       Total                                  2.7 million [2.4 – 3.0 million]
People newly infected
                                       Adults                                 2.3 million [2.0 – 2.5 million]
with HIV in 2008                       Children under 15 years                430 000 [240 000 – 610 000]


AIDS deaths                            Total                                  2.0 million [1.7 – 2.4 million]
                                       Adults                                 1.7 million [1.4 – 2.1 million]
in 2008
                                       Children under 15 years                280 000 [150 000 – 410 000]


  At the end of 2007, the CDC estimates that there were 571,378 people living with HIV/AIDS in the 39 states
  and dependent areas that have a history of confidential name-based HIV reporting, based on reported
  diagnoses and deaths.
  However, the total number of people living in the USA with HIV/AIDS is thought to be around 1.1 million.
               HIV infection and AIDS
• AIDS is caused by Human Immunodeficiency Virus (HIV)
 which is found in all cases of the disease.
• The primary targets of HIV are activated CD4+ T4 helper
 lymphocytes but the virus can also infect several other cell
 types including macrophages. It is the loss of T4 helper
 lymphocytes that leads to immunosuppression in the patient
 and the consequent opportunistic
 infections.

• HIV is a lentivirus (slow virus), a class of
  retrovirus. These viruses take a long
 time to cause overt disease.
• Most lentiviruses target cells of the
 immune system so disease is
 manifested as immunodeficiency.
                              Life-cycle of HIV-1
• The cell primary receptor is the CD4
  molecule.
• Entry into the cytoplasm initiates the
  disassemble of the HIV core.
• The uncoated HIV-1 reverse transcribes
  its genomic RNA in the cytoplasm into a
  DNA copy which is transported into the
  nucleus for integration into host
  chromosomes.
• The provirus is transcribed by the cell’s
  RNA polymerase II machinery.
• Viral mRNA enters the cytoplasm and
  uses the host's cellular machinery to
  manufacture virus proteins.
• The viral components then gather at the
  cell membrane and immature viruses bud
  off the cell.
• Core proteins are produced as part of long
  polypeptides, which must be cut into
  smaller fragments by a protease to form
  functional proteins.
Figure 1 from BMC Medicine 2008, 6:31
     What are the symptoms of AIDS?
Early symptoms
Some people have flu like illness within a month or two
after exposure to the virus
They may have fever, headache, malaise and enlarged
lymph nodes
These symptoms usually disappear within a week

More persistent and severe symptoms may not surface
for a decade or more after HIV first enters the body in
adults:
          Diarrhea for more than one month
          Dry mouth and skin rushes
          Severe headache
          Dry cough

AIDS: this term applies to the most advanced stages of HIV infection.
All HIV-infected people who have fewer than 200 CD4+ T cells
            Opportunistic Infections
   Most AIDS-defining conditions are opportunistic infections, which
   rarely cause harm in healthy individuals. In people with AIDS, these
   infections are often severe

Bacteria:
• Mycobacterium Avium Complex
• Mycobacterium Tuberculosis
Viruses:
• Varicella-Zoster Virus                              Fungi:
• Herpes Simplex Virus                                • Pneumocystis carinii
• Cytomegalovirus                                       Pneumonia
Protozoa:                                             • Candidiasis
• Coccidiosis (Cryptosporidiosis,
  Cyclosporiasis, and Isosporiasis)                   • Aspergillosis
• Toxoplasmosis                                       • Cryptococcosis
• Leishmaniasis (not in the U.S.,
  but in Southern Europe and in
                                                      • Histoplasmosis
  many other parts of the world)                      • Coccidioidomycosis
• Chagas                                              • Microsporidiosis
• Malaria
Opportunistic Infections
  Why do AIDS patients show
infections with a special set of
  (opportunistic) pathogens?

 What do the AIDS associated
      infections share?
• Usually benign but persistent infections
• Protection against the disease is mediated
 by the cellular arm of the immune system
• No vaccination
                          AIDS treatment
            Antiretroviral treatment: more than 20 drugs
            approved. HAART: highly active
antiretroviral
Therapy combines three or more anti-HIV medications daily.
Anti-HIV medications do not cure HIV infection.
Four classes of Anti-HIV drugs approved by the U.S.
Food and Drug Administration (FDA):
1. Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs):Efavirenz (Sustiva) binds to and block the
action of reverse transcriptase.
2. Nucleoside Reverse Transcriptase Inhibitors
(NRTIs): zidovudine (Retrovir), tenofovir DF (Viread),
and stavudine (Zerit), are nucleotide analogues.
They inhibit reproduction of the virus.                  Core proteins of HIV-1 are produced as part of
                                                         long polypeptides that are cut into smaller
3. Protease Inhibitors (PIs): lopinavir/ritonavir        pieces by protease to create functional and
(Kaletra)                                                mature proteins. Protease inhibitors bind to the
                                                         active site, where protein cleavage occurs. With
4. Fusion Inhibitors: enfuvirtide (Fuzeon), are          the inhibition of protease, new viral particles
newer treatments that work by blocking HIV entry         cannot mature and do not become infectious.
                                                         This figure is Fig. 3 from Nature Medicine,
into cells                                               2003, 9:867
HAART resulted in further declines in rates of
  PCP and other opportunistic infections
                                   Yearly opportunistic
                                   infection rates per 1,000
                                   person-years, CDC Adult
                                   and Adolescent
                                   Spectrum of Disease
                                   Project, 1994–2001.
                                   CMV, cytomegalovirus;
                                   HAART, highly active
                                   antiretroviral therapy; KS,
                                   Kaposi's sarcoma; MAC,
                                   Mycobacterium avium
                                   complex; PCP,
                                   Pneumocystis pneumonia.
                                   Data are standardized to the
                                   population of AIDS cases reported
                                   nationally in the same year by age,
                                   sex, race, HIV exposure mode,
                                   country of origin, and CD4+
                                   lymphocyte count.
                                   Emerging Inf. Dis. 10:1713
                                Opportunistic infections:
                                 Pneumocystis carinii
                                                • First identified in 1909 in a
                                                  trypanosome-infected animal lung
They can be stained by a                        • Was long thought to be a protozoan
number of tissue stains, like                     but molecular phylogeny identifies
this silver stain showing the                     it as fungus
typical black cup-shaped
appearance makes them                           • The number of cases exploded in
stand out against a paler                         the 1980s as PCP became one of the
background.                                       hallmark manifestations of AIDS
                                                • Ubiquitous organism in the
                                                  environment
                                                • Most important transmission route
                                                  is airborne
                                                • Subclinical infection during
                                                  childhood which is usually well
                                                  contained

                                          Cases of PCP reported to the CDC in the pre-AIDS era compared with the
                                          AIDS era. Horizontal bars at the top indicate the period during which
                                          prophylaxis to prevent PCP and HAART were available. The arrow
                                          indicates the time of publication of guidelines by the US Public Health
                                          Service for prevention of PCP in (HIV)–infected patients. JAMA 2001, Vol.
                                          286:2450
                       Pneumocystis pneumonia

                                                                               • P. carinni causes clinically apparent
                                                                                pneumonia virtually exclusively in
                                                                                immunosuppresed patiens.
                                                                               • Seen in patients with CD4 counts
Chest radiograph of a patient with     Hematoxylin-eosin–stained                below 200
PCP demonstrating diffuse
bilateral infiltrates. JAMA 2001,
                                       section of lung from an HIV-
                                       infected patient with PCP. An
                                                                               • Fever, nonproductive cough, chest
Vol. 286:2450                          acellular eosinophilic exudate           tightness, shortness of breath
                                       characteristic of PCP can be seen
                                       filling the alveoli. JAMA 2001, Vol.
                                                                               • Diagnosis by x-ray (but 20%
                                       286:2450                                 undetected), or better by detection of
                                                                                organisms in induced sputum or
                                                                                bronchial lavage
                                                                               • Chemoprophylaxis has been
                                                                                successful. Sulfa drugs for treatment
                                     Detection of human-derived P carinii by    and prophylaxis
                                     immunofluorescence using monoclonal
                                     antibodies. JAMA 2001, Vol. 286:2450
                                 Cell Biology of Pneumocystis carinii
                                                                              Electron micrograph
• Four morphological                                                          illustrates both cysts
                                                                              (white arrowheads)
 forms: trophozoites,
                                                                              and trophozoites
 cysts, precysts, and                                                         (black arrowheads).
 sporozoites (intracysts                                                      Kovacs, J. A. et al. JAMA
 bodies).                                                                     2001;286:2450-2460.


•      Trophozoites are
    pleomorphic and form
    clusters. Their cytoplasm
    is poor in organelles.
• Trophozoites interact with
  the surface of
  pneumocytes.
  Attachment to host cells                   Thin section showing several
  is required for survival.                  trophozoites. A thick surface
                                             coat is evident, especially in
• The cyst is the diagnostic                 cross sections of the surface
  form.                                      projections
                                             (arrows). N, nucleus; T,
                                             trophozoite. Bar = 200 nm.
    Copyright restrictions may apply.
                                             Mem. Inst. Osw. Cruz 100: 903
         Cryptosporidia and cryptosporidiosis
• Apicomplexan parasite described in 1907 by Tyzzer in gastric gland of mice
 Cryptosporidia (hidden sporocst)
• Pathogenic significance unclear until 1955-Slavin described infection in
 turkeys (C. meleagridis)
     • Low mortality but severe diarrhea
     • 1970s infections in intestines of calves
     • 1976 infections reported in two human patients-severe watery diarrhea
     • 1982-present-mortalities in AIDS patients and worldwide infections in
      both immunocompromised and immunocompetent people

                                                       • C. parvum has caused a
                                                         series of massive
                                                         waterborne outbreaks in
                                                         the US
                                                       • Infection with C. parvum
                                                         results in severe diarrhea,
                                                         which can be life-
                                                         threatening in AIDS
                                                         patients and malnourished
                                                         children
                     Milwaukee skyline 1993
C. parvum has high attack rates
Year   Location            People      People     Cause
                           exposed     infected
1984   Braun Station, TX   5900        2006       Sewage
                                                  contaminated well

1987   Carrollton, GA      32,400      12,960     Treatment
                                                  deficiencies

1991   PA                  NA          551        Treatment
                                                  deficiencies

1992   Jackson, OR         160,000     15,000     Treatment
                                                  deficiencies

1993   Milwaukee, WI       1,600,000   403,000    Treatment
                                                  deficiencies
    Cryptosporidium parvum life cycle
                                            Sporozoites attach to epithelial cells
Oocysts excyst in                           where they become enclosed within a PV.
the intestine
releasing                                                                             Trophozoites
sporozoites.                                                                          undergo asexual
                                                                                      reproduction by
                                                                                      merogony
                                                                                      (endopolygeny).



                                                                               Two types of meronts:
                                                                               Type I meront form 8
                                                                               merozoites released from
                                                                               the PV when mature.
                                                                               Type II meront form 4
                                                                               merozoites which do not
                                                                               undergo further merogony
Zygote undergo asexual development                                             but produce sexual
producing a sporulated oocyst with 4                                           stages (microgamont
sporozoites. Most oocysts are thick walled and   Monoxenous life cycle: all    and macrogamont)
are excreted with feces. Some are thin-walled    stages (asexual and sexual)
and excyst within the same host.                 occur within one host.
           Cryptosporidium parvum




Electron microscopy shows their intracellular but extra-cytoplasmic location
within parasitophorous vacuoles formed by a continuous covering of
microvillous membranes. El: attachment zone; Fo: feeder organelle; Ec:
electron dense collar; Fl: fibrous layer of the attachment organelle; Pv:
parasitophorous vacuole
  Transmission electron micrographs showing the
  invasion process of C. parvum into the host cell.




C. parvum attaches to a host cell. The
microvilli of the host cell elongate along     C. parvum is completely covered with the membrane
both sides of the parasite (arrows). A dense   derived from the microvilli.
band (DB) is found under the host cell         Each parasite is in a parasitophorous vacuole (PV)
membrane. From J. Parasitol. 2005,             formed by the microvilli. Membranes surrounding the
91:1034                                        parasites are composed of double layers. The microvilli
                                               (MV) between 2 parasites show remarkable elongation.
                                               DB, dense band. From J. Parasitol. 2005, 91:1034
 Cryptosporidium induces actin
  polymerization in the host cell
                                     • As we have seen before
                                       T. gondii invasion
                                       depends only on
                                       parasite actin (there is
                                       no difference in
                                       infection rate between
                                       normal host cells and
                                       those with reduced actin
                                       polymerization (SCAR-
                                       WA)
   Filamentous actin is found
   directly under the site of
                                     • For Cryptosporidium
   parasite infection.                 however there is clear
Figure 1 from Infect. Immun. 2000,     dependence on host
   68:2315                             actin
       Cryptosporidium parvum




Oocysts: Lb: lipid body; Ow: oocyst wall;
Pv: parasitophorous vacuole; Sp:
sporozoite; fo: deeder organelle;
                      Clinical symptoms
• Incubation period: 2-14 days
• Watery and profuse diarrhea, abdominal cramps,
 nausea, vomiting, weight loss and low-grade fever.
• Self-limited disease in immuno-competent individuals
• Prolonged duration in immuno-compromised host.
 Degree of immunodeficiency correlates with severity:
    – Self-resolving disease
   – Chronic diarrhea over months (<50 CD4 count)
   – Fulminate diarrhea
• Malabsorption can contribute to the wasting syndrome in
 AIDS patients.
• Bile duct infection can produce jaundice.
          Prevalence:
           Non-AIDS: 4.9% (developed countries); 7.9% (underdeveloped
          countries)
          AIDS: 14% (developed countries); 24% (Underdeveloped countries.
          Mortality: 80%
                          Pathogenesis
Histopathological changes: relatively nonspecific

Enteric infections:
         • mild to severe villous atrophy
         • increased crypt size
         • inflammation: cellular infiltrated in lamina propria (neutrophils
          and plasma cells; occasionally macrophages and lymphocytes)
Respiratory infections:
         • Cellular infiltrates with neutrophils and plasma cells in the sub-
          epithelial lamina propria together with deciliation, hyperplasty
                                     or hyperthrophy of the
                                     respiratory epithelium




                                  In histological sections parasite appears as
                                  small basophilic bodies apparently
                                  attached to the surface of the cells,
                                  sometimes giving the microvillous brush
                                  border a spotted granular appearance
                                     DIAGNOSIS
• Detection of endogenous developmental stages: Most stages are basophilic and stain well
  with hematoxylin and eosin or giemsa stains.
• TEM helps to confirm the identity of the organisms
• Scanning electron microscopy may be used to confirm infections.
• Finding oocyst in fecal material. Other body fluids such as bile, sputum, respiratory aspirates
  may be examined
• Immunolabeling techniques have been developed to detect
  oocysts. Concentration procedures to improve sensitivity:
  centrifugation, filtration.
• Immunoserology: specific
  antibodies against C. parvum

            The modified acid-fast
            methods produce                                     Oocysts of Cryptosporidium parvum labeled in an
            bright red oocysts                                  indirect immunofluorescence assay (IFA) with
            against a background                                monoclonal antibody 8F4 to the inner oocyst wall. The
                                                                IFA is still the most commonly used technique to assay
            of blue-green fecal                                 for oocysts in environmental samples.
            debris and yeasts
Metabolic differences with other
   apicomplexan parasites
•   Cryptosporidium is quite divergent from the
    other Apicomplexa
•   It lacks a plastid
•   It has a highly simplified mitochondrion
    which does no longer perform oxidative
    phosphorylation
•   It has lost many of its biosynthetic enzyme
    genes and depends almost completely of
    host cell derived nutrients
Chemotherapy of cryptosporidiosis
                         Latest drug to be used- a
                         nitrothiazole benzamide
                         with broad antimicrobial
                         spectrum

                         Parasite is highly
                         resistant to
                         chemotherapy

                         Drugs with modest
                         activity: Paramomycin,
                         nitaxosanide



                 Chemical structures for nitazoxanide (a) and its first
                 metabolite in human plasma, tizoxanide (b)
                 Giles et al., Trends in Parasitology, 18, 95-97,
                 2002..
       Cryptosporidium is highly
                     drug resistant
     Drugs with broad activity against apicomplexans that fail in C.
        parvum:
     • Antifolates (pyrimethamnine, sulfonamides)
     • Macrolide antibiotics (clyndamycin, azithromycin)
     • Atovaquone

     Drugs with modest activity:
     • Paramomycin, nitaxosanide




Two possible explanations for the drug resistance:
1) Drugs do not reach the parasite because it lives in a specialized
    compartment
2) The drugs used against other Apicomplexa are metabolically
    inappropriate
       Cryptosporidium parvum transmission
Fecal-oral spread of oocysts
Fecal contamination of drinking water sources is an
    important vehicle for transmission of oocyst. Also
    contamination of recreational water
Large scale outbreaks have been associated with
    contamination of community drinking water
Zoonotic transmission: General lack of host specificity
    of C. parvum: animal-to-human or animal-to-animal.
    Bovine genotype (gt II).
Contaminated food: unpasteurized milk, offal and
    sausages, foods prepared in
    untreated water or foods grown in soil fertilized in
    animal/human waste
Person-to-person through direct or indirect contact,
    possibly including
    sexual activities. Human genotype of C. parvum (C.
    hominis)
 Prevention and control
 Hygiene/disinfection-prevention of oocyst
transmission-difficult
• Oocyst very stable in aqueous solution; 3 months at 20oC
and 1 year at 46oC
• Infectivity lost upon heating (65oC, 30 min) or desiccated
for 4h or snap freezing
          • Disinfecting agents-only 5 effective over short
          exposure periods
          • 50% ammonia (30 min, 25oC)
          • 288 mg/ml hydrogen peroxide (30 min)
          • 10% formalin 1-7 days (< 87%)
          • Glutaraldehyde (2%, 30 min, 37oC)
          • Exspor (chlorine dioxide-based sterilant-Alcide
          Co)- 30 min, 22 oC
          • Oocide (two phase product producing ammonia-
          Antec Int. Ltd.)- 5%, 30 min, 22 oC
          • Oozone (especially for water treatment- 2.5 mg/ml
          at 22 oC)
            CYCLOSPOROSIS and RASPBERRIES

                                                                   Multiple foodborne outbreaks,
                                                                   thousands in US and Canada
                                                                   since 1990:
                                                                    Before 1996: mostly overseas
                                                                   and 3 small US outbreaks
                                                                   May 1996: 55 events (all had
                                                                   raspberries served) of
                                                                   outbreaks in US and Canada
                                                                   1465 cases, 978 confirmed.
                                                                   Spring 1997: 41 events, 1012
                                                                   cases. Again the only common
   ATLANTA-Guatemalan raspberries have been fingered as            food consumed in all events
the delectable vehicle of this springユs outbreaks of Cyclospora    was raspberries from
cayetanensis. And while the epidemiologic links to the caviar of   Guatemala
fruit accumulated, a cousin berry was exonerated. Despite much
scuttlebutt, the strawberry got a clean bill of health….           May 1998: Ontario, Canada,
                                                                   315 cases
                    Cyclospora cayetanesis
• Countries initially identified as having endemic
  cyclosporiasis: Haiti, Guatemala, Peru and Nepal
• Infection most common in HIV/AIDS patients.
• Also important in travelers
• Large, multi-state food-borne outbreaks of
  Cyclospora infection in the USA and Canada during
  the 1990s.
• Cyclospora infects enterocytes of the small bowel.
• The main symptom is watery diarrhea, loss of
  appetite, weight loss, abdominal bloating and
  cramping, nausea, fatigue and low grade fever.
• In the immunocompromised patient, severe diarrhea
  can last up to 4 months or longer even if treated thus
  producing a disease syndrome that is debilitating and
  life threatening                                         Duodenal biopsy showing immature
                                                           schizonts (broad arrow) and merozoites
• Extra-intestinal infection appears to be more common     (arrow) in a parasitophorous vacuole of
                                                           C. cahetanesis in surface enterocytes.
  in AIDS patients                                         (HE STAIN)
Cyclospora
cayetanesis life cycle
• The oocyst is passed in stools but is
 not infective.
• Sporulation occurs after days or
 weeks (22°C to 32°C), to form
 two sporocysts, each containing two
 sporozoites.
• Fresh produce and water can serve
 as vehicles for transmission and the
 sporulated oocysts are ingested.
• The oocysts excyst in the
 gastrointestinal tract, releasing
 sporozoites which invade the
 epithelial cells of the small intestine.
 Inside the cells they undergo
 asexual multiplication and sexual
 development to mature into oocysts,
 which will be shed in stools.
                      The relative sizes of various microbes.




Giardia lamblia cyst (length from 8 to 19  and
averages 11-12 ), a Cyclospora cayetanensis
oocyst (8-10 ), and a Cryptosporidium parvum
oocyst (4.5  × 5 ). The virus is not drawn to
scale. The Cyclospora oocyst shown is fully
sporulated it has 2 internal sporocysts, each with 2
sporozoites. Whereas oocysts of Cryptosporidium,
are fully sporulated and infectious when excreted,
Cyclospora oocysts sporulate in the environment,
days to weeks after excretion. Giardia, which is not
a coccidian parasite, does not have sporocysts or
sporozoites. (Figure courtesy of Dennis D.
Juranek.)
                EPIDEMIOLOGICAL DATA
        • Co-infection with leishmaniasis and HIV has been
          reported in 34 countries in Africa, Asia, Europe, and
          South America. The impact of this health problem is
          increasingly severe.
        • In southern Europe, up to 70% of adult cases of
          visceral leishmaniasis are associated with HIV
          infection.
        • Users of injecting drugs are the most seriously
          affected group. Analysis of trends is facilitated by use
          of a geographical information system to map and
          monitor patterns of co-infection.

Source:Communicable Disease Surveillance and response.Who
http://www.lynx.who.ch/ctd/html/leisepidat.html
                         LEISHMANIASIS-HIV
Leishmania/HIV co-infection is emerging as a new disease:
• Important epidemiological changes: Humans become
  reservoirs: Co-infected patients harbor a high number of Leishmania in
 their blood. This increases the risk of future epidemics.
• Atypical manifestations of Leishmaniasis: Leishmania/HIV co-
 infections modify the traditional patterns of zoonotic VL.
VL is the clinical form most frequently associated with HIV/AIDS specially in
  south-western Europe (some CL have been reported):
The geographical distribution of VL and AIDS is increasing because:
• the spread of AIDS in suburban and rural areas of the world,
• the spread of VL from rural to suburban areas.
• In southwestern Europe up to 70% of all adult cases of VL are related to
  HIV/AIDS.

• While the incidence of leishmania/HIV co-infection is increasing en
  eastern Africa and India, the incidence in Europe has diminished thanks
  to HAART.
                                   TRANSMISSION




The diagram suggests a few possible paths of leishmaniasis infection. Female sandflies,
vectors for parasites of the genus Leishmania, disseminate to humans mainly from animals.
Infected dogs, both symptomatic and asymptomatic, have traditionally been reported to be
the reservoir of this disease; foxes, jackals, wolves, raccoons, sloths, hyraxes, rats, and other
rodents have been reported as reservoirs. In HIV-Leishmania coinfection, intravenous drug
users seem to be human reservoirs.
Reports of transmission of leishmaniasis via needle-sharing are increasing.
         LEISHMANIA/HIV CO-INFECTION
• Among immunosuppressed individuals quickly evolve to a full
 clinical presentation of severe leishmaniasis.
• VL quickly accelerates the onset of AIDS and shortens the life
 expectancy of HIV-infected people.
• HIV spurs the spread of VL. AIDS increases the risk of VL by 100-
 1000 times in endemic areas. HIV infection reactivates latent
 leishmaniasis.
• This combination produces cumulative deficiency of the immune
 response because Leishmania parasites and HIV destroy the same
 cells, increasing disease severity and consequences. Leishmania
 and HIV invade and replicate in macrophages.
• VL is considered a major contributor to a fatal outcome in co-infected
 patients.
• Leishmaniasis can be transmitted directly person to person through
 the sharing of needles, as is the case among intravenous drug users.
     HIV modifies the clinical presentation of
     leishmaniasis in the co-infected patient

Major characteristics for HIV-associated leishmaniasis, all related to
 the immunologic impairment caused by the virus:
(1) Parasitic dissemination, to the skin in DCL, or throughout the
 reticuloendothelial system in visceral and visceralizing syndromes
(2) Atypical locations
(3) Chronic and relapsing course, with each patient typically
 experiencing two or three relapses despite proper treatment
(4) Poor response to standard therapy.


General treatment of leishmaniasis is indicated for each clinical presentation,
 although localized cutaneous lesions may benefit from topical and/or
 intralesional therapy as well.

								
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