LEISHMANIA 1. INTRODUCTION & BASIC FACTS What is Leishmania? - Flagellate protozoan parasite - Causes leishmaniasis (including Kala-azar) - Obligate intracellul
LEISHMANIA 1. INTRODUCTION & BASIC FACTS What is Leishmania? - Flagellate protozoan parasite - Causes leishmaniasis (including Kala-azar) - Obligate intracellular parasite - Requires TWO hosts to complete life cycle Key Classifications: - Definitive hosts: Humans, dogs, other mammals - Vector: Female sandfly (Phlebotomus & Lutzomyia species) - Infective form: Metacyclic promastigote 2. GLOBAL DISTRIBUTION & EPIDEMIOLOGY Geographic Distribution: - Tropical and subtropical regions worldwide - Central & South America, North America (parts) - Central & Southeast Asia, India, China - Mediterranean region, Africa Risk Factors: - Low socioeconomic status - Overcrowding and poor ventilation - Accumulation of organic material in houses - Poor sanitation 3. CLINICAL TYPES OF LEISHMANIASIS A. VISCERAL LEISHMANIASIS (Kala-azar) - Causative agent: L. donovani complex - Organs affected: Liver, spleen, bone marrow - Most severe form B. CUTANEOUS LEISHMANIASIS - Causative agents: L. tropica, L. major, L. aethiopica, L. mexicana complex - Affects: Skin only - Forms ulcerative lesions C. MUCOCUTANEOUS LEISHMANIASIS - Causative agent: L. braziliensis complex - Affects: Skin and mucous membranes - Can cause facial disfigurement 4. MORPHOLOGY - TWO FORMS A. AMASTIGOTE FORM (LD Body) - Location: Inside human/mammalian cells - Shape: Oval, small (2-4 μm) - Features: No external flagellum - Nucleus and kinetoplast visible - Found in macrophages - Also called Leishman-Donovan (LD) body B. PROMASTIGOTE FORM - Location: In sandfly and culture - Shape: Elongated (15-25 μm) - Features: Long anterior flagellum - Motile - Infective metacyclic form 5. LIFE CYCLE - STEP BY STEP STAGE 1: INFECTION OF HUMAN - Transmission: Infected female sandfly bites human - Inoculation: Promastigotes injected into skin wound - Phagocytosis: Promastigotes engulfed by macrophages - Transformation: Promastigotes → Amastigotes inside cells - Multiplication: Amastigotes multiply by binary fission - Cell rupture: Infected macrophages burst, releasing amastigotes - Spread: Released amastigotes infect new macrophages STAGE 2: INFECTION OF SANDFLY - Blood meal: Sandfly feeds on infected human - Ingestion: Amastigotes enter sandfly's midgut - Transformation: Amastigotes → Promastigotes in midgut - Multiplication: Promastigotes multiply rapidly - Migration: Parasites migrate to pharynx and proboscis - Blockage: Parasites block sandfly's feeding apparatus - Transmission: Next bite releases infective promastigotes Extrinsic incubation period: 10 days in sandfly 6. VISCERAL LEISHMANIASIS (KALA-AZAR) - DETAILED A. PATHOGENESIS - Primary process: Reticuloendothelial system (RES) blockade - Mechanism: Massive multiplication in fixed macrophages - Result: RES dysfunction and organ damage B. ORGAN INVOLVEMENT LIVER - Enlargement: Hepatomegaly - Cells affected: Küpffer cells, vascular endothelial cells - Hepatocytes: NOT affected - Appearance: "Nutmeg" cut surface - Function: Mostly preserved (slight ↓ prothrombin) SPLEEN - Most affected organ - Massive enlargement: Splenomegaly - Consistency: Soft and friable - Color: Red/chocolate on cut section - Microscopy: Reticulum cells loaded with LD bodies BONE MARROW - Heavy infiltration with parasitized macrophages - Result: Crowding of hematopoietic tissue - Consequence: Severe anemia (Hb 5-10 g/dL) C. CLINICAL FEATURES - Onset: Insidious - Fever: Continuous, remittent, or irregular - Splenomegaly: Early, progressive, massive - Hepatomegaly: Present but less prominent - Skin changes: Dry, rough, darkly pigmented - Hair changes: Thin and brittle - General: Cachexia, anemia, weight loss - Bleeding: Epistaxis, gum bleeding - Prognosis: Death in ~2 years if untreated D. INCUBATION PERIOD - Usual: 2-6 months - Range: 10 days to 2 years 7. POST KALA-AZAR DERMAL LEISHMANIASIS (PKDL) A. BASIC FACTS - Occurrence: 3-10% of visceral leishmaniasis patients - Timing: 1-2 years after recovery - Geographic: Mainly India and East Africa - Nature: Non-ulcerative skin lesions B. LESION TYPES - Depigmented macules: Trunk/extremities, resemble leprosy - Erythematous patches: Face, butterfly distribution - Nodular lesions: Painless, yellowish-pink, granulomatous 8. CUTANEOUS LEISHMANIASIS A. OLD WORLD CUTANEOUS LEISHMANIASIS Type 1: Anthroponotic Urban Type (L. tropica) - Vector: P. sargenti - Lesions: Painless, dry, ulcerating - Names: Oriental sore, Delhi boil - Healing: Spontaneous in ~1 year - Scars: Disfiguring Type 2: Zoonotic Rural Type (L. major) - Vector: P. papatasi - Lesions: Moist, inflamed, often multiple - Reservoirs: Gerbils, rats, rodents - Healing: Faster than L. tropica Type 3: Diffuse Cutaneous (L. aethiopica) - Vector: P. longipes - Location: Ethiopia, Kenya highlands - Lesions: Non-ulcerative, diffuse, nodular - Immunity: Low humoral and cell-mediated - Duration: Years to lifetime - Treatment: Difficult B. LEISHMANIASIS RECIDIVANS - Immunity: High cell-mediated immunity - Pattern: Chronic, alternating activity/healing - Appearance: Central scar with peripheral activity - Parasites: Very scanty - Leishmanin test: Strongly positive C. NEW WORLD LEISHMANIASIS - Agents: L. braziliensis & L. mexicana complexes - Vector: Lutzomyia species - Reservoirs: Sylvatic rodents, domestic animals - Location: Skin and mucous membranes 9. IMMUNITY A. VISCERAL LEISHMANIASIS - Cell-mediated immunity: Markedly suppressed - Result: Unrestricted parasite multiplication - Recovery: CMI returns ~6 weeks post-treatment - Antibodies: Overproduction of IgG and IgM - Immune complexes: Present in serum B. CUTANEOUS LEISHMANIASIS - Generally: Good cell-mediated immunity - Protection: Against reinfection - Exception: Diffuse cutaneous form (poor immunity) 10. DIAGNOSIS A. MICROSCOPY (Gold Standard) Specimens: - Bone marrow aspirate - Splenic aspirate - Lymph node aspirate - Peripheral blood - Skin lesion scraping (for cutaneous) Stains: Leishman, Giemsa, Wright's stain Identification: Look for LD bodies in macrophages B. CULTURE - Medium: NNN (Novy-MacNeal-Nicolle) medium - Growth: Promastigotes at 22-24°C C. SEROLOGY - Tests: ELISA, IFA, DAT (Direct Agglutination Test) - Usefulness: Visceral leishmaniasis D. MOLECULAR METHODS - PCR: Highly sensitive and specific - Advantage: Can identify species E. LEISHMANIN SKIN TEST (Montenegro Test) - Positive: Past infection or cutaneous leishmaniasis - Negative: Active visceral leishmaniasis - Use: Epidemiological surveys F. BLOOD PICTURE - Anemia: Severe (Hb 5-10 g/dL) - WBC: Leukopenia - Platelets: Thrombocytopenia - ESR: Elevated 11. TREATMENT A. VISCERAL LEISHMANIASIS First-line Drugs: - Pentavalent Antimonials (SbV) Sodium stibogluconate (100 mg SbV/mL) - Meglumine antimonate (85 mg SbV/mL) - Dose: 20 mg/kg IV/IM for 20-30 days - Amphotericin B (first-line in Bihar, India) Dose: 0.75-1.0 mg/kg alternate days, 15 infusions - Liposomal form: 3 mg/kg daily (preferred) - Miltefosine (oral) Dose: 50 mg daily ( 25 kg) - Duration: 28 days - Paromomycin Dose: 11 mg/kg IM daily for 21 days B. CUTANEOUS LEISHMANIASIS - Mild cases: May heal spontaneously - Treatment: Same drugs as visceral (shorter duration) - Local therapy: Heat application, intralesional antimony C. PKDL TREATMENT - Same as visceral leishmaniasis 12. PREVENTION & CONTROL A. VECTOR CONTROL - Insecticidal spraying: Reduce sandfly population - Environmental management: Remove breeding sites - Personal protection: Bed nets, repellents, protective clothing B. RESERVOIR CONTROL - Zoonotic forms: Control animal reservoirs - Case management: Early detection and treatment C. PERSONAL PROTECTION - Clothing: Thick, full-coverage clothing - Bed nets: Fine mesh (sandflies are small) - Repellents: DEET-based repellents - Environment: Keep surroundings clean D. VACCINATION - Status: No vaccine currently available - Research: Ongoing vaccine development 13. IMPORTANT EXAM POINTS Key Differentiating Features: - Visceral: Internal organs, fever, splenomegaly - Cutaneous: Skin lesions, usually self-healing - Mucocutan