Dr.Alaa jumaa

1. KALA AZAR Dr.Alaa jumaa

2. SYNONYMS kala azar, black fever, sandfly disease, Dum-Dum fever and espundia.

3. 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.

4. Pre-Incan pottery from Ecuador and Peru also show individuals with facial deformities and skin lesions

5. 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 Leishmaniacause different forms of disease

6. Leishmaniadonovani (complex) (VL) Leishmaniatropica (CL) Leishmania major (CL) Leishmaniaaethiopica (CL) Leishmaniamexicana (Complex) (CL) Leishmaniabrazilliensis (complex) (MCL) Leishmaniaperuriana Leishmaniasis

7. Introduction • In the Middle East L. major and L. tropica are the most common species • L. major causes skin infection • L. tropicacauses skin and visceral infection and rarely causes mucocutaneousinfection

8. Leishmaniasis in the Middle East • 90% of cutaneousleishmaniasis 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 cutaneousleishmaniasis 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 mucocutaneousleishmaniasis occurs in Bolivia, Brazil and Peru • Rarely associated with L tropica which is found in Middle East

9. Phylum Order Family Genus Sarcomastigophora Kinetoplastida Trypanosomatidae Leishmania The Parasite

10. Promasitogte Insect Motile Midgut Amastigote Mammalian stage Non-motile Intracellular Morphology Digenetic Life Cycle

11. Promastigote

12. Amastigote

13. A macrophage filled with Leishmaniaamastigotes.

14. The vector • The insect vector of leishmaniasis, the phlebotominesandfly, 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.

17. 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.

20. 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.

22. 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

24. Diagnosis • For Visceral Leishmaniasis: • enzyme liked immunosorbent assay (ELISA) • direct agglutination test (DAT) • indirect fluorescent antibody test (IFAT)

25. 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.

26. 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).

27. Treatment • The pentavalent antimony compounds (sodium stibogluconate [Pentostam], and meglumineantimoniate 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

28. 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

29. 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