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2 Subspecies
- Trypanosoma brucei gambiense (W + C Africa) â slow, chronic, > 95% of human cases
- Trypanosoma brucei rhodesiense (E + S Africa) â rapid, acute, sometimes fatal in weeks
Vector + Reservoir
- Tsetse fly (Glossina spp.) â both subspecies
- Reservoirs:
- T. b. gambiense: humans primary (anthroponotic)
- T. b. rhodesiense: cattle + wild animals (zoonotic)
Epidemiology (WHO 2024)
- ~ 800-1000 reported cases/yr globally (mostly DRC)
- WHO 2030 elimination of T. b. gambiense as public health problem (near)
- 2024 trends: declining incidence
Clinical (2 Stages)
Stage 1: Hemolymphatic (Early)
- Inoculation chancre at tsetse bite site (transient, often missed)
- Fever (intermittent)
- LAP (Winterbottomâs sign = posterior cervical LAP â pathognomonic for T. b. gambiense)
- Hepatosplenomegaly
- Anemia + thrombocytopenia
- Itching, rash
- Lasts months (gambiense) to weeks (rhodesiense)
Stage 2: Meningoencephalitic (Late / CNS)
- Sleep disturbances (gives âsleeping sicknessâ name): hypersomnia daytime, insomnia night, sleep cycle reversal
- Behavioral changes, apathy, depression, psychosis
- Movement disorders (extrapyramidal + cerebellar)
- Progressive neurological decline â coma â death without treatment
- Months (gambiense) to weeks (rhodesiense)
Diagnosis
- Card Agglutination Test for Trypanosomiasis (CATT) â screening for T. b. gambiense
- Thick + thin blood smears, lymph node aspirate, CSF microscopy â direct visualization of trypomastigotes
- CSF examination for staging:
- Stage 2 if CSF WBC > 5 cells/µL or trypanosomes present
- PCR + immunoassays â emerging
- Card test for HAT (now widely available POC test)
Treatment (2024 Update)
T. b. gambiense (W + C Africa)
- Stage 1: Fexinidazole (oral, 10 days) â replaces pentamidine in most settings
- Alternative: pentamidine IM Ã 7d
- Stage 2: Fexinidazole (oral, 10 days) â replaces NECT (nifurtimox-eflornithine combination therapy)
- NECT (10-day eflornithine + 10-day nifurtimox) still in use some settings
- Acoziborole (single-dose oral) â Phase 3 success 2024, regulatory submission ongoing; will revolutionize
T. b. rhodesiense (E + S Africa)
- Stage 1: Suramin IV (no oral alternative yet)
- Stage 2: Melarsoprol IV (arsenic-based, very toxic 5% encephalopathy mortality but reduces in disease)
- Fexinidazole + acoziborole being trialed for rhodesiense
Prevention
- Tsetse fly avoidance (long clothing, light colors, repellent)
- Vector control (traps, insecticide-treated targets, drug-impregnated cattle)
- Surveillance + active case finding + treatment
1ïžâ£ Microbiology + Life Cycle
Trypanosoma brucei
- Trypomastigote: extracellular flagellated form in blood/CSF
- Epimastigote: in tsetse fly
- Surface variant glycoprotein (VSG) â antigenic variation â continuous evasion â fever periods
Antigenic Variation
1000 different VSG genes
- Switch every few days
- Wave of parasitemia â IgM response â switch â new wave
- Drives chronic relapsing fever
Life Cycle
- Tsetse bite â trypomastigotes injected
- Multiply in blood + lymph (Stage 1)
- Cross blood-brain barrier â CNS (Stage 2)
- Tsetse takes blood meal â trypomastigotes ingested
- Transform to epimastigotes in tsetse â multiply â re-enter human
2ïžâ£ Clinical Features
Inoculation Chancre
- 5-15 days post-tsetse bite
- Painful indurated nodule at bite site
- Transient (1-3 weeks)
- More common with T. b. rhodesiense
Stage 1: Hemolymphatic
T. b. gambiense (Chronic)
- Months-years duration
- Intermittent fever
- Winterbottomâs sign: posterior cervical LAP â pathognomonic
- Hepatosplenomegaly
- Generalized LAP
- Anemia + thrombocytopenia
- Pruritus
- Cardiac involvement uncommon
T. b. rhodesiense (Acute)
- Weeks duration
- High intermittent fever
- LAP less prominent
- Myocarditis prominent
- Hepatosplenomegaly
- Sometimes hemorrhagic complications
Stage 2: Meningoencephalitic
Sleep Disturbances
- Reversal of sleep-wake cycle
- Daytime hypersomnia, nighttime insomnia
- Pathognomonic for HAT
Other CNS Features
- Mental status changes: apathy, depression, psychosis
- Movement disorders: tremor, ataxia, chorea, parkinsonism
- Speech changes
- Cranial nerve palsies
- Seizures
- Coma â death without treatment
Differential
- Malaria (always rule out first)
- HIV
- Viral / bacterial meningitis
- Encephalitis (other causes)
- Other CNS protozoal infections
3ïžâ£ Diagnosis
Screening (Asymptomatic in Endemic)
- CATT (Card Agglutination Test for Trypanosomiasis) â T. b. gambiense
- Reactive â confirmatory testing
Direct Microscopy
- Thick + thin blood smears (Giemsa)
- Trypomastigotes have undulating membrane + flagellum
- Better sensitivity in T. b. rhodesiense (higher parasitemia)
- T. b. gambiense often low parasitemia â multiple smears + concentration
Lymph Node Aspirate
- Posterior cervical LN
- High sensitivity for T. b. gambiense
- Microscopy for trypomastigotes
Cerebrospinal Fluid (CSF)
- Lumbar puncture for staging (essential for treatment selection)
- Stage 2 if: WBC > 5 cells/µL or trypomastigotes present
- Increased protein
- IgM elevated
- Direct microscopy for trypomastigotes
PCR
- Sensitive
- Species + subspecies identification
- Reference labs
Card Test for HAT (Combo)
- POC test (2017+)
- Antibody detection
- Used in active surveillance
Other Tests
- ELISA, immunofluorescence
- Loop-mediated isothermal amplification (LAMP)
4ïžâ£ Treatment
T. b. gambiense Treatment Algorithm (2024)
Stage 1 (Hemolymphatic, CSF normal)
- Fexinidazole PO 10 days (preferred 2019 WHO + 2024)
- Day 1-4: 1800 mg PO bid
- Day 5-10: 1200 mg PO bid
- Take with food (better absorption)
- Alternative: Pentamidine 4 mg/kg IM/IV daily à 7d (older, side effects)
Stage 2 (CNS Involvement)
- Fexinidazole PO 10 days â increasingly first-line
- Alternative: NECT (Nifurtimox-Eflornithine Combination Therapy)
- Eflornithine 400 mg/kg/d IV Ã 7 days
- Nifurtimox 15 mg/kg/d PO Ã 10 days
- WHO previous standard
- Effective but requires IV access + monitoring
Acoziborole (2024 Breakthrough)
- Single-dose oral ~ 480 mg
- Phase 3 trial 2024: efficacy + safety profile excellent
- Regulatory submission EMA + WHO 2024+
- Will revolutionize HAT treatment
T. b. rhodesiense Treatment
Stage 1
- Suramin IV (no oral alternative yet)
- 1 g IV at days 1, 3, 5, 14, 21
- Side effects: nephrotoxicity, infusion reactions
Stage 2
- Melarsoprol IV (arsenic-based)
- 2.2 mg/kg IV daily à 10 days
- Severe toxicity: encephalopathy (5% mortality), peripheral neuropathy, dermatitis
- âReactive encephalopathyâ 2-5% in 1st week
- High historical use but progressively replaced
- Fexinidazole + acoziborole being trialed for rhodesiense (efficacy promising)
Treatment Considerations
- Lumbar puncture before treatment for staging
- Post-treatment LP at 6 months to confirm cure (CSF normalization)
- Pregnancy: fexinidazole safe in 2nd-3rd trimester (1st trimester avoid)
- Pediatric: weight-based fexinidazole
Supportive Care
- Hospitalization for severe + Stage 2
- Anticonvulsants for seizures
- Glucose monitoring
- Fluid + electrolyte management
5ïžâ£ Prevention + Public Health
Personal Protection
- Light-colored clothing (tsetse attracted to dark + blue)
- Long sleeves + pants
- DEET repellent
- Avoiding tsetse habitats (riverside vegetation, savanna)
Vector Control
- Tsetse traps + insecticide-treated targets
- Sequential aerial spraying historical
- Sterile insect technique (SIT) â Zanzibar success story
- Drug-impregnated cattle (zoonotic rhodesiense control)
Surveillance + Case Detection
- Active surveillance â mobile teams in endemic villages
- CATT screening + microscopy
- Treat detected cases â reduces reservoir
WHO 2030 Elimination Targets
- T. b. gambiense: elimination as public health problem (< 1 case per 10,000 in endemic foci) â near
- T. b. rhodesiense: zoonotic control
- 2020s: dramatic case reduction (~ 800-1000/yr from 30,000+ early 2000s)
No Vaccine
- Antigenic variation (VSG) makes vaccine difficult
- Research ongoing but no candidates near clinical use