Leishmaniasis 

Definition: Chronic inflammatory disease of skin, mucous membranes or viscera caused by obligate intracellular Kinetoplastid protozoal parasites (Leishmania species) transmitted through infected sand fly.

-  Leishmania infections like with other intracellular organism (including mycobacteria, histoplasma, toxoplasma and tryprosoma) is exacerbated by AIDS. 

-  Different leishmania parasites in new and old world appeared to show tropism related to temperature, because parasites that cause visceral disease grow at 37% in vitro whereas parasite that cause multiple diseases grow only at 34 ⁰c. 

-  Leishmania are phagocytosed by macrophage and acidity within phagolysosome induces them to transform into amastigote from promatigate by losing flagella. 

-  Leishmania amastigote are the only protozoal parasites that survive and reproduce in macrophage phagolysosomes, which have a PH of 4.5. Amastigotes are protected from the intravascular acid by a proton -transforming ATPase which maintains the intracellular parasite PH at 6.5 

-  Leishmania parasites have two glycocongugates, which appeared important in their virulence. The first is lipophosphoglycans that are glycolipids & bind C3b and iC3b.  Organisms resist  lysis by complement C5-9   but are  phagocytosed by macrophages through complement receptors CR1 and CR3

-  Lipophosphoglycans may also protect the parasite within phagolysosomes by supplying oxygen radical and by inhibiting lysosmal enzymes. 

- Like M. laprae severity of disease is determined by host immune response. 

 Parasites specific to CD+T-cells of TH1 class may secrete interferon gamma which along with TNF-α secreted by other macrophages activates phagocytes to kill the parasites through toxic metabolites of oxygen or nitric acid (or both). In contrast, down regulation of the immune response that lead to anergy and progressive diseases may be caused by parasite specific CD4+T cells of T helper class 2 that secrete IL-4 which inhibits macrophages activation by interferon gamma and inhibits secretion of TNF α .

Morphology:

-   Visceral leishmaniasis (L.donovanni & L.chagasi) macrophages of RES are invaded so hepatosplenomegly, lymphadenopathy, pancytopenia, fever & weight loss, hyperpigmentation of the skin (kalazar, black fever) glomerulonephritis (mesangioproliferative) and in advanced cases amyloid deposits. 

Cutaneous leishmaniasis 

Localized single ulcer on exposed skin (slowly expanding and irregular borders, usually heals within 6 months by involution. The lesion is granulomatous.

Diffuse cutaneous leishmaniasis

Lesions of diffuse cutaneous leishmaniasis resembles lepromatous leprosy nodules. The lesions do not ulcerate but contain vast aggregates of foamy macrophages filled with leishmania.  The patients are usually anergic not only to Leshmania but also to other skin antigens and the disease respond poorly to therapy.    

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.