Transcript KALA AZAR

SYNONYMS
kala azar, black fever, sandfly
disease, Dum-Dum fever and
.espundia
Leishmania throughout the ages…
 one of the first and most important clinical
descriptions was made in 1756 by Alexander
Russell following an examination of a Turkish
patient. The disease, then commonly known
as "Aleppo boil"
 In 1901, Leishman identified certain
organisms in smears taken from the spleen of
a patient who had died from "dum-dum
fever"
 in 1903 Captain Donovan described them as
being new.
 Pre-Incan pottery from Ecuador and Peru also
show individuals with facial deformities and skin
lesions
Introduction
 Leishmaniasis is a parasitic disease transmitted by
the bite of sand flies.
 Found in parts of at least 88 countries including the
Middle East
 Three main forms of leishmaniasis
• Cutaneous: involving the skin at the site of a sandfly bite
• Visceral: involving liver, spleen, and bone marrow
• Mucocutaneous: involving mucous membranes of the mouth and nose
after spread from a nearby cutaneous lesion (very rare)
 Different species of Leishmania cause different forms of
disease
LEISHMANIASIS
Leishmania donovani (complex) (VL)
Leishmania tropica (CL)
Leishmania major (CL)
Leishmania aethiopica (CL)
Leishmania mexicana (Complex) (CL)
Leishmania brazilliensis (complex) (MCL)
Leishmania peruriana
Introduction
 In the Middle East L. major and L. tropica are the most
common species
• L. major causes skin infection
• L. tropica causes skin and visceral infection and rarely causes
mucocutaneous infection
Leishmaniasis in the Middle East
 90% of cutaneous leishmaniasis occurs in Afghanistan,
Iran, Saudi Arabia, Syria, Brazil and Peru
• 8,779 cases were reported in Iraq in 1992
• Sore is commonly called the Baghdad boil
• At least 20 cases of cutaneous leishmaniasis were reported in
Americans from Desert Storm
 90% of all visceral leishmaniasis occurs in Bangladesh,
Brazil, India, and the Sudan
• 2893 cases were reported in Iraq in 2001
• 12 visceral leish cases were reported in Americans in Desert
Storm
 90% of mucocutaneous leishmaniasis occurs in Bolivia,
Brazil and Peru
• Rarely associated with L tropica which is found in Middle East
The Parasite
 Phylum
Sarcomastigophora
 Order
Kinetoplastida
 Family
Trypanosomatidae
 Genus
Leishmania
Morphology
Digenetic Life Cycle
 Promasitogte
 Amastigote
 Insect
 Mammalian stage
 Motile
 Non-motile
 Midgut
 Intracellular
Promastigote
Amastigote
 A macrophage
filled with
Leishmania
amastigotes.
The vector
 The insect vector of leishmaniasis, the phlebotomine sandfly, is found
throughout the world's inter-tropical and temperate regions.
 The female sandfly lays its eggs in the burrows of certain rodents, in the
bark of old trees, in ruined buildings, in cracks in house walls, in animal
shelters and in household rubbish, as it is in such environments that the
larvae will find the organic matter, heat and humidity which are necessary
for their development.
In its search for blood (usually in the evening and at night), the female
sandfly covers a radius of a few to several hundred metres around its
habitat.
Cutaneous forms
 Cutaneous forms of the disease normally
produce skin ulcers on the exposed parts of
the body such as the face, arms and legs.
The disease can produce a large number of
lesions - sometimes up to 200 - causing
serious disability and invariably leaving the
patient permanently scarred, a stigma which
can cause serious social prejudice.
Mucocutaneous forms
 In mucocutaneous forms of leishmaniasis,
lesions can lead to partial or total destruction
of the mucous membranes of the nose,
mouth and throat cavities and surrounding
tissues.
These disabling and degrading forms of
leishmaniasis can result in victims being
humiliated and cast out from society.
Visceral Leishmaniasis
 Most severe form of the disease, may be fatal if left untreated
 Usually associated with fever, weight loss, and an enlarged spleen
and liver
 Anemia (low RBC), leukopenia (low WBC), and thrombocytopenia
(low platelets) are common
 Lymphadenopathy may be present
 Visceral disease from the Middle East is usually milder with less
specific findings than visceral leishmaniasis from other areas of the
world
Diagnosis
 For Visceral Leishmaniasis:
 enzyme liked immunosorbent assay (ELISA)
 direct agglutination test (DAT)
 indirect fluorescent antibody test (IFAT)
Diagnosis
 n patients with VL, smears or cultures of
material from splenic, bone marrow, or
lymph node aspirations are usually
diagnostic.
 In experienced hands, splenic aspiration
has a higher diagnostic sensitivity.
LABORATORY FINDINGS
 Laboratory findings associated with
classic kala-azar include anemia
 (hemoglobin 5–8 g/dL),
 thrombocytopenia,
 leukopenia (2,000–3,000 cells/μL),
 elevated hepatic transaminase levels,
 and hyperglobulinemia (>5 g/dL) that is
mostly immunoglobulin G (IgG).
Treatment
 The pentavalent antimony compounds (sodium
stibogluconate [Pentostam], and meglumine




antimoniate have been the mainstay of
antileishmanial chemotherapy for >40 yr.
Cure rates with this regimen of 80–100% for VL
lower initial cure rates have been noted recently in
regions where clinical resistance to antimony
therapy is common.
Relapses are common in patients who do not have
an effective antileishmanial cellular immune
response.
Adverse effects of antimony therapy
Treatment
 Liposomal amphotericin B (3 mg/kg on days 1–5,
and again on day 10) has been shown to be highly
effective, with a 90–100% cure rate for VL.
 Liposomal amphotericin B is approved by the Food
and Drug Administration for treatment of VL and
should be considered for 1st line therapy in the
United States.
 Parenteral treatment of VL with the aminoglycoside
paromomycin (aminosidine) has efficacy (95%)
similar to that of amphotericin B in India.
 Recombinant human interferon-γ has been
successfully used as an adjunct to antimony therapy
in the treatment of refractory cases of ML and VL
Treatment
 March 2002- 1st oral drug for visceral
leishmaniasis registered (milefosine)
 currently used in India
 safe and effective  up to 98% cure rate
 mild side-effects  vomiting and diarrhea
 does not require refrigeration
 Other drugs- sitamaquine and aminosidine