TRYPANOSOMA OVERVIEW - Type : Protozoan parasite (hemoflagellate) - Kingdom : Protista - Phylum : Sarcomastigophora - Class : Zoomastigophora - Order : Kinetopl
TRYPANOSOMA OVERVIEW - Type : Protozoan parasite (hemoflagellate) - Kingdom : Protista - Phylum : Sarcomastigophora - Class : Zoomastigophora - Order : Kinetoplastida - Family : Trypanosomatidae GENERAL CHARACTERISTICS - Elongated, motile parasites with undulating membrane - Single flagellum arising from kinetoplast - Kinetoplast contains mitochondrial DNA - Polymorphic (different forms in different hosts) - Obligate parasites requiring two hosts for complete life cycle MAIN SPECIES AND DISEASES 1. T. brucei gambiense → West African Sleeping Sickness (WASS) 2. T. brucei rhodesiense → East African Sleeping Sickness (EASS) 3. T. cruzi → Chagas Disease (American Trypanosomiasis) --- AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS) CAUSATIVE AGENTS T. brucei gambiense and T. brucei rhodesiense MORPHOLOGY - Length : 15-30 μm - Width : 1.5-3.5 μm - Shape : Elongated with pointed ends - Flagellum : Single, arising from kinetoplast - Undulating membrane : Present along body length - Nucleus : Central, oval - Kinetoplast : Near posterior end LIFE CYCLE - SIMPLE STEPS IN HUMAN HOST: - Infection : Metacyclic trypomastigotes injected by tsetse fly bite - Multiplication : Parasites multiply in lymphatic system - Blood invasion : Transform into slender blood trypomastigotes - Tissue invasion : Spread to various organs including CNS - Antigenic variation : Change surface proteins every 7-10 days IN TSETSE FLY VECTOR: - Ingestion : Fly takes blood meal containing trypomastigotes - Midgut development : Transform into procyclic trypomastigotes - Migration : Move to salivary glands - Transformation : Become epimastigotes, then metacyclic trypomastigotes - Transmission : Ready for injection into new host Total cycle time : 3 weeks in vector COMPARISON: T.b. gambiense vs T.b. rhodesiense PATHOGENESIS AND CLINICAL FEATURES STAGE I DISEASE (Systemic - No CNS involvement) Signs & Symptoms: - Painless chancre at bite site (trypanosomal chancre) - Intermittent fever and chills - Rash - Anemia and weight loss - Headache - Hepatosplenomegaly - Lymphadenopathy (especially posterior cervical - Winterbottom's sign ) - Myocarditis (common in T.b. rhodesiense) Laboratory findings: - Anemia - Moderate leucocytosis - Thrombocytopenia - High immunoglobulin M (IgM) levels STAGE II DISEASE (CNS involvement - "Sleeping Sickness") Signs & Symptoms: - Increasing headache - Mental dullness and apathy - Daytime sleepiness - Behavioral changes - Progressive coma - Death from asthenia (weakness) Histopathology: - Chronic meningoencephalitis - Lymphocytes, plasma cells, and morula cells in meninges - Morula cells contain mulberry-shaped IgA masses - Perivascular cuffing of brain vessels - Neuronal degeneration - Microglial proliferation CSF changes: - Raised intracranial pressure - Pleocytosis (increased WBC) - Raised protein levels DIAGNOSIS Non-specific findings: - Anemia and monocytosis - Raised ESR (due to increased gamma globulins) - Reversed albumin:globulin ratio - Increased CSF pressure, cells, and proteins Specific diagnosis: Demonstration of trypanosomes in: - Peripheral blood - Bone marrow - Lymph node aspirate - CSF - Chancre fluid Methods: - Microscopy : Wet mount, Giemsa stain - Culture : Special media - Molecular : PCR - Imaging : CT (cerebral edema), MRI (white matter enhancement) TREATMENT STAGE I DISEASE: - T.b. gambiense : Pentamidine (3-4 mg/kg IM daily × 7-10 days) - T.b. rhodesiense : Suramin (20 mg/kg IV, 5 injections at 5-7 day intervals) Note: Suramin doesn't cross blood-brain barrier but is nephrotoxic STAGE II DISEASE: - T.b. gambiense : Eflornithine - T.b. rhodesiense : Melarsoprol (Mel-B) 2-3 mg/kg/day (max 40mg) × 3-4 days Note: Melarsoprol crosses blood-brain barrier --- AMERICAN TRYPANOSOMIASIS (CHAGAS DISEASE) CAUSATIVE AGENT Trypanosoma cruzi HOSTS AND VECTORS - Definitive host : Humans - Vector : Reduviid bugs (triatomine bugs) - "kissing bugs" - Reservoir hosts : Armadillo, cats, dogs, pigs MORPHOLOGY - Similar to T. brucei but smaller - Amastigote form : Oval, 2-4 μm (intracellular) - Trypomastigote form : C-shaped, 20 μm (in blood) - Epimastigote form : In vector gut LIFE CYCLE - SIMPLE STEPS IN HUMAN HOST: - Infection : Metacyclic trypomastigotes from bug feces enter through skin/mucosa - Cell invasion : Parasites enter cells and transform to amastigotes - Multiplication : Amastigotes multiply in cells - Transformation : Become trypomastigotes and rupture cells - Blood circulation : Trypomastigotes in bloodstream - Tissue invasion : Invade heart, digestive tract, nervous system IN REDUVIID BUG: - Ingestion : Bug takes blood meal with trypomastigotes - Gut development : Transform to epimastigotes in midgut - Multiplication : Epimastigotes multiply - Transformation : Become metacyclic trypomastigotes - Excretion : Passed in feces during feeding INFECTION CYCLES - Sylvatic cycle : Wild animals (armadillos, opossums) - Peridomestic cycle : Domestic animals (dogs, cats) - Domestic cycle : Humans CLINICAL FEATURES ACUTE CHAGAS DISEASE (1-4 months) - Incubation period : 1-2 weeks - Age group : Often children under 2 years - Chagoma : Subcutaneous lesion at inoculation site - Romana's sign : Unilateral, painless periocular edema (classical finding) - Generalized symptoms : Fever, lymphadenopathy, hepatosplenomegaly - Complications : Acute myocarditis, meningoencephalitis - Resolution : Symptoms resolve in 4-8 weeks → asymptomatic phase CHRONIC CHAGAS DISEASE (Years to decades later) - Age group : Adults and older children - Pathophysiology : Inflammatory response, cellular destruction, fibrosis - Target organs : Heart, esophagus, colon - Manifestations :Cardiac myopathy - Megaesophagus - Megacolon CONGENITAL INFECTION - Possible in both acute and chronic phases - Causes myocardial and neurological damage in fetus DIAGNOSIS - Direct : Demonstration of T. cruzi in blood or tissues - Serology : Antibody detection - Microscopy : Peripheral blood film examination TREATMENT - No highly effective treatment available - Drugs used : Nifurtimox : 8-10 mg/kg (adults), 15 mg/kg (children) - Benznidazole : 5-10 mg/day × 60 days - Dosing : 4 divided doses daily for 90-120 days (Nifurtimox) - Limitation : Kill only extracellular forms, not intracellular --- ANTIGENIC VARIATION (Important Concept) MECHANISM - Trypanosomes change their surface glycoproteins - VSG (Variant Surface Glycoprotein) or VSSA (Variant Surface Specific Antigens) - Cyclical fluctuation every 7-10 days - Single trypanosome has 1,000+ VSG genes - Helps evade host immune response --- PREVENTION AND CONTROL For African Trypanosomiasis: - Vector control (tsetse fly elimination) - Protective clothing - Insect repellents - Clearing of vegetation around settlements - Mass screening and treatment For Chagas Disease: - Vector control (improving housing conditions) - Insecticides - Screening blood donors - Education about the disease --- KEY EXAMINATION POINTS - Distinguish between the three main species - Know the complete life cycles - Understand antigenic variation - Clinical staging of African trypanosomiasis - Romana's sign and Winterbottom's sign - Treatment differences for each stage and species - Diagnostic methods - Vectors and reservoirs for each species --- MEMORY AIDS - WASS : West African Sleeping Sickness = T.b. g ambiense = G lossina p alpalis - EASS : East African Sleeping Sickness = T.b. r hodesiense = r apid course - Romana's sign : R omana = R eduviid bug = R ight or left eye swelling - Winterbottom's sign : W inter = W est African = W -shaped lymph nodes (posterior cervical) - Pentamidine : P entamidine for p alpalis (T.b. gambiense) - Suramin : S uramin for s avanna (T.b. rhodesiense - found in East African savanna)