Visceral Leshmaniasis/ Kala- azar disease.pptx

This is a presentation of a tropical disease VL

1. VISCERAL LEISHMANIASIS Presenter: Olympia Godbless Machange Moderator: Prof. Billy Ngasala

2. Introduction Leishmaniasis is a parasitic disease caused by protozoan parasites of the genus Leishmania which are spread by phlebotomine sand flies. The genus Leishmania is named after Sir William Leishman who discovered the flagellate protozoon causing kala-azar, the Indian visceral leishmaniasis . All members of the genus Leishmania are obligate intracellular parasites that pass their life cycle in two hosts, the mammalian host and the insect vector, female sandfly . In human and other mammalian hosts, they multiply within macrophages, in which they occur exclusively in the amastigote form, having an ovoid body containing a nucleus and kinetoplast . In the sandfly , they occur in the promastigote form, with a spindle shaped body and a single flagellum arising from the anterior end.

3. Visceral Leishmaniasis (VL) Visceral leishmaniasis  ( VL ), also known as  kala-azar  "black sickness") or " black fever ", is the most severe form of leishmaniasis . VL is the second-largest parasitic killer in the world (after malaria), responsible for an estimated 20,000 to 30,000 deaths each year worldwide. It is also the emerging problem of HIV/VL co-infection Usually occurs two to eight months after being bitten by the Phlebotomine sandfly

4. VL cont … Two species of  Leishmania  are known to give rise to the visceral form of the disease. L. donovani species commonly found in East Africa and the Indian subcontinent L . infantum ( also known as  L. chagasi ) species found in Europe, North Africa, and Latin America (is the most severe, systemic form that is usually fatal unless treated). Post-kala-azar dermal leishmaniasis (PKDL by L. donovani ) is a skin manifestation that occurs in otherwise healthy people after treatment of visceral leishmaniasis .

5. Classificatio n Kingdom : Protista Phylum: Sarcomastigophora Subphylum: Mastigophora Class: Kinetoplastidea Order: Trypanosomatida Genus: Leishmania Species: L. donovani , L. infantum

6. Morphology https://www.slideshare.net/ssuser7af4ca/morphology-and-life-cycle-of-leishmania-donovani The parasite exists in two forms: Amastigote form ; In humans and other mammals. Promastigote form ; In sandfly and artificial culture

7. Amastigote form No flagellum, Round or oval in shape 2-4 µm in length Seen in reticuloendothelial cell of vertebrate host Nucleus situated in the middle or along the sides of the cell wall and kinetoplast lies at the right angle to the nucleus Axoneme is delicate filament extending from the kinetoplast to the margin of the body and represents the root of the flagellum.

8. Promastigote form Flagella stage, s een in digestive tract of sandfly . Spindle shaped measures 15-20 µm in length and 1-2 µm in breadth . There is no undulating membrane. Nucleus is situated centrally and kinetoplast lies transversely near the anterior end The flagellum is single delicate and measures 15-28 micro meter A vacuole is present near the root of the flagellum

9. Life cycle Life cycle of Leishmania donovani Sandfly feeding on infected person ingests amastigotes. In the stomach of the sand-fly, the amastigote becomes promastigote, which multiplies by binary fission. Promastigotes accumulate in pharynx and block the passage . When the sandfly bites a person the promastigotes get deposited in the puncture wound then phagocytosed by macrophage. In which they multiply, distending the cell causing the macrophage to ruptures , releasing the amastigotes, some of which are phagocytosed by other macrophages . Amastigotes in peripheral blood and skin are ingested by sandflies while feeding, to repeat the cycle

10. Life cycle

11. Pathogenesis V isceral leishmaniasis (Kala-azar) is a reticuloendotheliosis resulting from the invasion of the reticuloendothelial system by L.donovani . Affects several internal organs (usually spleen, liver, and bone marrow) and can be life threatening. The incubation period is usually from 2 to 6 months, though occasionally it may be as short as 10 days or as long as two years. Parasitized macrophages disseminate the infection to all parts of the body. In the spleen, liver and bone marrow particularly, the amastigotes multiply enormously in the fixed macrophages to produce a ‘blockade’ of the reticuloendothelial system. This leads to a marked proliferation of the reticuloendothelial tissue in these organs.

12. Pathogenesis cont … The spleen is the organ most affected. Lymphocytic infiltration is scanty , but plasma cells are numerous. The liver is enlarged. The Kupffer cells and vascular endothelial cells are heavily parasitized , but hepatocytes are not affected. Liver function is therefore not seriously affected , though prothrombin production is commonly decreased. The sinusoidal capillaries are dilated and engorged. Some degree of fatty degeneration is seen. The cut surface may show a nutmeg appearance.

13. Pathogenesis cont … Hepatosplenomegally A liver showing nutmeg appearance https:// pictures.doccheck.com/com/photo/18827-nutmeg-liver https:// www.slideserve.com/jana/leishmaniasis

14. Pathogenesis cont … The bone marrow is heavily infiltrated with parasitized macrophages which may crowd out the haemopoietic tissues. Anaemia occurs as a result of infiltration of the bone marrow as well as by the increased destruction of erythrocytes due to hypersplenism . Autoantibodies to red cells may contribute to haemolysis . Leucopenia , with marked neutorpenia , and thrombocytopenia are frequently seen. Polyclonal hypergammaglobulinaemia is a common finding May produce immunodeficiency due to extensive damage to the reticuloendothelial system

15. Clinical symptoms The onset is typically insidious. The clinical illness begins with fever, which may be continuous, remittent or irregular. Splenomegaly starts early and is progressive and massive. Hepatomegaly and lymphadenopathy also occur but are not so prominent. Pallor ( caused by severe anemia ) , leucopenia (low white blood cell count), and weight loss. The skin becomes dry, rough arid darkly pigmented, hair becomes thin and brittle. Epistaxis and bleeding gums are common jaundice and fluid buildup in the abdomen.

16. Clinical symptoms cont … Most untreated patients die in about 2 years due to some intercurrent disease such as dysentery or tuberculosis. Other signs and symptoms include respiratory problems or gastrointestinal disturbances such as vomiting and diarrhea; in severe cases there is malnutrition and lower limb edema , which may progress to anasarca (extreme generalized edema). About 10 to 20% of patients who recover develop post kala-azar dermal leishmaniasis (PKDL). The dermal lesions usually develop about a year or two after recovery from the systemic illness

17. Diagnosis Microscopically using Giemsa staining technique Specimen: Material aspirated from the spleen, bone marrow or an enlarged lymph node ( Splenic aspirates higher sensitivity than for specimens) Peripheral blood monocytes and less commonly in neutrophils (buffy coat preparations). Patients co-infected with HIV, amastigotes are frequently found in blood monocytes and neutrophils in buffy coat preparations and also in aspirates from enlarged lymph nodes and also in atypical sites (such as the gastrointestinal tract ).

18. Diagnosis Testing for leishmanial antibodies using antigen known to detect local parasite strains. In visceral leishmaniasis , specific antibody as well as non-specific polyclonal Ig G and Ig M are produced. Technique used is Direct agglutination test (DAT) and rK39 dipstick to detect anti-rK39 antibody.

19. Diagnosis Testing for leishmanial antigen in urine Katex test to detect leishmanial antigen in urine of patients with VL A urine sample is first boiled for 5 minutes to inactivate substances capable of causing false positive reactions with the latex reagent. After allowing the urine to cool to ambient temperature, 50µl of sample is mixed with 1 drop of the latex reagent. Results are read after mixing for 2 minutes. Agglutination indicates a positive test for VL .

20. Treatment Visceral disease always requires treatment. The standard treatment is the pentavalent antimonial sodium stibogluconate ( Pentostam ) given intravenously 600 mg daily for 6 days. The aminoglycoside antibiotic aminosidine ( paromomycin ) is useful, given alone or with antimonials . An alternative is pentamidine 4 mg/kg/ day given IM for 10 days. If this also does not succeed , amphotericin 0.25 to 1 mg/kg/day may be given as slow infusion for up to 8 weeks. By using liposomal amphotericin, higher doses can be given, improving the cure, without toxicity. Meltefosine ( Impavido ) is an effective oral treatment.

21. Epidemiology An estimated 700 000 to 1 million new cases occur annually. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Is found in countries of the tropics, subtropics, and southern Europe but not found in Australia or the Pacific islands. The disease affects some of the poorest people and is associated with malnutrition , population displacement , poor housing , a weak immune system and lack of financial resources . It is also linked to environmental changes such as deforestation, building of dams, irrigation schemes and urbanization.

22. Epidemiology cont … Only a small fraction of those infected by parasites causing leishmaniasis will eventually develop the disease . Visceral leishmaniasis  (VL), is fatal if left untreated in over 95% of cases. Most cases occur in Brazil, East Africa and in India. An estimated 50 000 to 90 000 new cases of VL occur worldwide annually It remains one of the top parasitic diseases with outbreak and mortality potential . In 2020, more than 90% of new cases reported to WHO occurred in 10 countries: Brazil, China, Ethiopia, Eritrea, India, Kenya, Somalia, South Sudan, Sudan and Yemen.

23. Distribution of visceral leishmaniasis worldwide L ocation of the main endemic foci : (1) Chinese (2) Central Asian, (3) Mediterranean, (4) Indian and (5) East African foci Credit: Jean-Louis Koeck : https :// www.researchgate.net/figure/Distribution-of-visceral-leishmaniasis-worldwide-and-location-of-the-main-endemic-foci_fig1_47334865

24. Prevention & Control The best way for people to prevent infection is to protect themselves from sand fly bites Personal protection from sandfly bites by : Avoid outdoor activities, especially from dusk to dawn, when sand flies are most active . Minimize the amount of exposed (uncovered) skin, wear long-sleeved shirts, long pants, and socks Using insect repellants Avoiding endemic areas especially at times when sandflies are most active. Use of insecticide impregnated bed nets and curtains.

25. Prevention & Control cont … When indoors: Stay in well-screened or air-conditioned areas. Keep in mind that sand flies are much smaller than mosquitoes and therefore can get through smaller holes. Vector control by the use of light traps, sticky paper traps, or residual insecticide spraying of houses Early detection and treatment of infected persons , especially in areas where humans are the only or important reservoirs of infection.

26. Prevention and control cont … Destruction of stray dogs and infected domestic dogs in areas where dogs are the main reservoir hosts. Elimination and control of rodents in areas where these are sources of human infections. Whenever possible, siting human dwellings away from the habitats of animal reservoir hosts where sandflies are known to breed, e.g. rodent burrows or rocks where hydraxes live.

27. References Textbook of medical parasitology, sixth edition CK Jayaram Paniker Manson’s Tropical Diseases, 22 nd edition, Edited by Gordon & C.Cook , W.B Saunders London Medical Parasitology Second edition by Dr. Arora District Laboratory Practice in Tropical Countries. Second Edition by Monica Cheesbrough . 2009 Burza S, Croft SL, Boelaert M. Leishmaniasis . Lancet. 2018;392(10151):951–70. CDC - Leishmaniasis [Internet]. [cited 2022 Apr 22]. Available from: https:// www.cdc.gov/parasites/leishmaniasis/index.html Leishmaniasis [Internet]. [cited 2022 Apr 24]. Available from: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis Distribution of visceral leishmaniasis worldwide and location of the... | Download Scientific Diagram [Internet]. [cited 2022 Apr 24]. Available from: https://www.researchgate.net/figure/Distribution-of-visceral-leishmaniasis-worldwide-and-location-of-the-main-endemic-foci_fig1_47334865

28. Thank you