Introduction - Leishmania is a genus of flagellate protozoa responsible for leishmaniasis. - The disease is transmitted by the female sandfly ( Phlebotomus spe
Introduction - Leishmania is a genus of flagellate protozoa responsible for leishmaniasis. - The disease is transmitted by the female sandfly ( Phlebotomus species in the Old World and Lutzomyia species in the New World). - It is an obligate intracellular parasite , completing its life cycle in two hosts: Definitive host: Humans, dogs, and other mammals. - Vector: Female sandfly. - Infective form: Metacyclic promastigote. Epidemiology - Global Distribution: Leishmaniasis is widespread in the tropics and subtropics, including:Central and South America, parts of North America, Central and Southeast Asia, India, China, the Mediterranean region, and Africa. - Risk Factors: Affects low socio-economic groups. - Poor housing, overcrowding, poor ventilation, and organic material accumulation inside houses increase transmission risk. Types of Leishmaniasis - Visceral Leishmaniasis (Kala-azar): Caused by L. donovani complex . - Affects internal organs, mainly the liver, spleen, and bone marrow. - Cutaneous Leishmaniasis: Caused by L. tropica complex, L. aethiopica, L. major, and L. mexicana complex . - Characterized by skin ulcers. - Mucocutaneous Leishmaniasis: Caused by L. braziliensis complex . - Affects mucous membranes of the nose, mouth, and throat. Leishmania donovani: Visceral Leishmaniasis (Kala-azar) Morphology - Exists in two forms : Amastigote form (Leishman-Donovan [LD] bodies) – found inside macrophages of the reticuloendothelial system. - Promastigote form – found in the sandfly vector and in artificial culture. Life Cycle 1. Transmission to Humans - Humans acquire the infection through the bite of an infected female sandfly . - Other transmission routes:Vertical (mother-to-fetus). - Blood transfusion. - Laboratory inoculation (accidental). 2. Infection in Humans - Promastigotes enter the wound via sandfly bite. - Phagocytosed by macrophages, monocytes, and polymorphonuclear leukocytes . - Transform into amastigotes within the macrophages. - Multiply by binary fission , eventually lysing the macrophages. - Spread to spleen, liver, bone marrow, lymph nodes, and intestinal mucosa . 3. Transmission to Sandfly - When a sandfly bites an infected person, it ingests amastigotes . - In the sandfly's midgut , amastigotes transform into promastigotes . - Multiply by longitudinal binary fission , forming rosettes . - Migrate to the pharynx and hypostome , where they accumulate and block passage. - When the sandfly bites another person, infective promastigotes are regurgitated into the wound. 4. Extrinsic Period (In Vector) - Takes about 10 days for promastigotes to develop in the sandfly before transmission. Pathogenesis and Organ Involvement - L. donovani infects the reticuloendothelial system (RES) , leading to widespread infection. - Spleen :Most affected organ, massive splenomegaly . - Soft, friable, dark chocolate/red cut surface due to engorged vascular spaces. - Microscopically, reticulum cells contain numerous LD bodies . - Liver :Enlarged liver with Kupffer cell parasitization. - Hepatocytes are not affected . - Nutmeg appearance on cut section. - Bone Marrow : Suppression of hematopoiesis due to infiltration with infected macrophages. - Causes pancytopenia (anemia, leukopenia, thrombocytopenia). Clinical Features of Kala-azar - Incubation Period : 2–6 months (can range from 10 days to 2 years). - Symptoms :Insidious onset of irregular, remittent fever . - Progressive massive splenomegaly (hallmark sign). - Hepatomegaly (less prominent than spleen). - Lymphadenopathy (not always present). - Severe anemia due to bone marrow suppression and hypersplenism. - Darkening of skin ("Kala-azar" means "black fever"). - Cachexia, weight loss, and emaciation . - Bleeding tendencies (epistaxis, gum bleeding). - Fatality in untreated cases within 2 years due to opportunistic infections. Post-Kala-azar Dermal Leishmaniasis (PKDL) - Occurs 1–2 years after recovery from visceral leishmaniasis. - Seen mainly in India and East Africa . - Types of Skin Lesions : Depigmented macules – resemble tuberculoid leprosy. - Erythematous patches – occur on the face in a butterfly distribution . - Nodular lesions – non-ulcerative granulomatous nodules. - Parasites can be demonstrated in lesions . Diagnosis of Visceral Leishmaniasis 1. Microscopy (Gold Standard) - Demonstration of amastigotes (LD bodies) in smears from: Peripheral blood - Bone marrow aspirate - Splenic aspirate (most sensitive but risky due to bleeding complications) - Enlarged lymph node aspirate - Staining: Leishman, Giemsa, or Wright’s stain . 2. Culture - Novy-MacNeal-Nicolle (NNN) medium for promastigotes. 3. Serological Tests - rK39 Antigen Test (rapid diagnostic test). - ELISA for leishmanial antibodies. 4. Molecular Tests - PCR (high sensitivity). 5. Leishmanin Skin Test (Montenegro Test) - Delayed hypersensitivity test (negative in active cases, positive in healed cases). Treatment of Visceral Leishmaniasis - First-line Drugs Sodium stibogluconate or Meglumine antimonate (20 mg/kg IV/IM for 20–30 days). - Second-line Drugs Amphotericin B (IV) : 0.75–1.0 mg/kg on alternate days (total 15 doses). - Liposomal Amphotericin B : 3 mg/kg daily. - Miltefosine (Oral) : 25 kg: 50 mg twice daily for 28 days. - Paromomycin (IM): 11 mg/kg daily for 21 days. - PKDL Treatment – same as visceral leishmaniasis. Prophylaxis - Early detection and treatment to prevent spread. - Vector control :Insecticide spraying. - Personal protective measures (bed nets, insect repellents). - Destruction of animal reservoirs (dogs, rodents). - No vaccine available .