Transcript C. parvum

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.
People in some African nations
contract the virus by eating
'bushmeat'
Pan troglodytes sub-especies and distribution
1. Pan troglodytes verus
2. P. t. vellerosus
3. P. t. troglodytes
4. P. t. schweinfurthii
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
Number of people living
with HIV in 2008
Total
Adults
Women
Children under 15 years
34.4 million [31.1 – 35.8 million]
31.3 million [29.2 – 33.7 million]
15.7 million [14.2 – 17.2 million]
2.1 million [1.2 – 2.49 million]
People newly infected
with HIV in 2008
Total
Adults
Children under 15 years
2.7 million [2.4 – 3.0 million]
2.3 million [2.0 – 2.5 million]
430 000 [240 000 – 610 000]
AIDS deaths
in 2008
Total
Adults
Children under 15 years
2.0 million [1.7 – 2.4 million]
1.7 million [1.4 – 2.1 million]
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
• Herpes Simplex Virus
• Cytomegalovirus
Protozoa:
• Coccidiosis (Cryptosporidiosis,
Cyclosporiasis, and Isosporiasis)
• Toxoplasmosis
• Leishmaniasis (not in the U.S.,
but in Southern Europe and in
many other parts of the world)
• Chagas
• Malaria
Fungi:
• Pneumocystis carinii
Pneumonia
• Candidiasis
• Aspergillosis
• Cryptococcosis
• Histoplasmosis
• Coccidioidomycosis
• Microsporidiosis
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.
3. Protease Inhibitors (PIs): lopinavir/ritonavir
(Kaletra)
4. Fusion Inhibitors: enfuvirtide (Fuzeon), are
newer treatments that work by blocking HIV entry
into cells
Core proteins of HIV-1 are produced as part of
long polypeptides that are cut into smaller
pieces by protease to create functional and
mature proteins. Protease inhibitors bind to the
active site, where protein cleavage occurs. With
the inhibition of protease, new viral particles
cannot mature and do not become infectious.
This figure is Fig. 3 from Nature Medicine,
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
They can be stained by a
number of tissue stains, like
this silver stain showing the
typical black cup-shaped
appearance makes them
stand out against a paler
background.
trypanosome-infected animal lung
• Was long thought to be a protozoan
but molecular phylogeny identifies
it as fungus
• The number of cases exploded in
the 1980s as PCP became one of the
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
Chest radiograph of a patient with
PCP demonstrating diffuse
bilateral infiltrates. JAMA 2001,
Vol. 286:2450
• P. carinni causes clinically apparent
Hematoxylin-eosin–stained
section of lung from an HIVinfected patient with PCP. An
acellular eosinophilic exudate
characteristic of PCP can be seen
filling the alveoli. JAMA 2001, Vol.
286:2450
Detection of human-derived P carinii by
immunofluorescence using monoclonal
antibodies. JAMA 2001, Vol. 286:2450
pneumonia virtually exclusively in
immunosuppresed patiens.
• Seen in patients with CD4 counts
below 200
• Fever, nonproductive cough, chest
tightness, shortness of breath
• Diagnosis by x-ray (but 20%
undetected), or better by detection of
organisms in induced sputum or
bronchial lavage
• Chemoprophylaxis has been
successful. Sulfa drugs for treatment
and prophylaxis
Cell Biology of Pneumocystis carinii
Electron micrograph
illustrates both cysts
(white arrowheads)
and trophozoites
(black arrowheads).
• Four morphological
forms: trophozoites,
cysts, precysts, and
sporozoites (intracysts
bodies).
Kovacs, J. A. et al. JAMA
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
is required for survival.
• The cyst is the diagnostic
form.
Copyright restrictions may apply.
Thin section showing several
trophozoites. A thick surface
coat is evident, especially in
cross sections of the surface
projections
(arrows). N, nucleus; T,
trophozoite. Bar = 200 nm.
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
Milwaukee skyline 1993
• C. parvum has caused a
series of massive
waterborne outbreaks in
the US
• Infection with C. parvum
results in severe diarrhea,
which can be lifethreatening in AIDS
patients and malnourished
children
C. parvum has high attack rates
Year
Location
People
exposed
People
infected
Cause
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
Oocysts excyst in
the intestine
releasing
sporozoites.
Sporozoites attach to epithelial cells
where they become enclosed within a PV.
Zygote undergo asexual development
producing a sporulated oocyst with 4
sporozoites. Most oocysts are thick walled and
are excreted with feces. Some are thin-walled
and excyst within the same host.
Trophozoites
undergo asexual
reproduction by
merogony
(endopolygeny).
Monoxenous life cycle: all
stages (asexual and sexual)
occur within one host.
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
but produce sexual
stages (microgamont
and macrogamont)
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
both sides of the parasite (arrows). A dense
band (DB) is found under the host cell
membrane. From J. Parasitol. 2005,
91:1034
C. parvum is completely covered with the membrane
derived from the microvilli.
Each parasite is in a parasitophorous vacuole (PV)
formed by the microvilli. Membranes surrounding the
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
Filamentous actin is found
directly under the site of
parasite infection.
Figure 1 from Infect. Immun. 2000,
68:2315
• 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 (SCARWA)
• For Cryptosporidium
however there is clear
dependence on host
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 subepithelial 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
bright red oocysts
against a background
of blue-green fecal
debris and yeasts
Oocysts of Cryptosporidium parvum labeled in an
indirect immunofluorescence assay (IFA) with
monoclonal antibody 8F4 to the inner oocyst wall. The
IFA is still the most commonly used technique to assay
for oocysts in environmental samples.
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 ammoniaAntec Int. Ltd.)- 5%, 30 min, 22 oC
• Oozone (especially for water treatment- 2.5 mg/ml
at 22 oC)
CYCLOSPOROSIS and RASPBERRIES
ATLANTA-Guatemalan raspberries have been fingered as
the delectable vehicle of this springﾕs outbreaks of Cyclospora
cayetanensis. And while the epidemiologic links to the caviar of
fruit accumulated, a cousin berry was exonerated. Despite much
scuttlebutt, the strawberry got a clean bill of health….
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
food consumed in all events
was raspberries from
Guatemala
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
• Extra-intestinal infection appears to be more common
in AIDS patients
Duodenal biopsy showing immature
schizonts (broad arrow) and merozoites
(arrow) in a parasitophorous vacuole of
C. cahetanesis in surface enterocytes.
(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 coinfections 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 1001000 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.