African Trypanosomiasis (Sleeping Sickness)
Summary
Human African Trypanosomiasis (HAT), commonly known as sleeping sickness, is a parasitic disease caused by Trypanosoma brucei protozoa and transmitted by the tsetse fly in sub-Saharan Africa. Two subspecies cause distinct clinical syndromes: T. b. gambiense (West and Central Africa, 97% of cases, chronic progression) and T. b. rhodesiense (East Africa, 3% of cases, acute severe disease). The disease progresses through haemolymphatic (Stage 1) and meningoencephalitic (Stage 2) phases. Without treatment, HAT is invariably fatal; with appropriate treatment, cure rates exceed 95%. Early diagnosis before CNS involvement is critical for optimal outcomes.
Key Facts
- Prevalence: Less than 1000 reported cases annually (significant historical burden now controlled)
- Vector: Tsetse fly (Glossina species) — endemic only to sub-Saharan Africa
- Two forms: T. b. gambiense (97%, chronic) and T. b. rhodesiense (3%, acute)
- Mortality: 100% if untreated; less than 5% with appropriate treatment
- Key distinction: Stage 1 (peripheral) vs Stage 2 (CNS) — determines treatment
- Diagnosis: Parasite detection in blood, lymph, or CSF
Clinical Pearls
The Chancre: A painless trypanosomal chancre at the bite site appears 5-15 days after infection and is more common in T. b. rhodesiense. It is often missed but is pathognomonic when present.
Winterbottom's Sign: Posterior cervical lymphadenopathy (Winterbottom's sign) is classically associated with T. b. gambiense and was historically used by slave traders to detect infected individuals.
Sleep Reversal: The "sleeping sickness" name comes from disruption of the sleep-wake cycle — patients are somnolent during the day and sleepless at night, not simply excessive sleeping.
Why This Matters Clinically
HAT is fatal without treatment but curable with appropriate therapy. Stage determination is critical as Stage 2 disease requires CSF-penetrating drugs with more toxicity. Travellers to endemic areas and migrants from Africa may present in non-endemic countries, making clinical recognition important globally.
Incidence & Prevalence
- Annual reported cases: Less than 1000 (down from 300,000 in 1998)
- At-risk population: 65 million in 36 sub-Saharan African countries
- T. b. gambiense: 97% of cases; endemic in West and Central Africa
- T. b. rhodesiense: 3% of cases; endemic in East and Southern Africa
- Trend: WHO targeting elimination as a public health problem
Demographics
| Factor | Details |
|---|---|
| Geography | Sub-Saharan Africa only (tsetse fly habitat) |
| Age | All ages; occupational exposure in adults |
| Sex | Equal; males may have higher occupational exposure |
| Occupation | Farmers, hunters, fishermen in endemic areas |
Risk Factors
Non-Modifiable:
- Living in or travelling to endemic areas
- Proximity to tsetse fly habitats (riverine, woodland)
Modifiable:
| Risk Factor | Relative Risk |
|---|---|
| Occupational exposure (farming, hunting) | 3-5x |
| Lack of protective clothing | 2x |
| Poor vector control | 2-3x |
Mechanism
Step 1: Tsetse Fly Bite and Inoculation
- Infected tsetse fly (Glossina spp.) injects metacyclic trypomastigotes
- Local multiplication at inoculation site (chancre formation)
- Trypanosomes divide extracellularly
Step 2: Haemolymphatic Stage (Stage 1)
- Parasites spread via lymphatics and bloodstream
- Dissemination to lymph nodes, spleen, liver
- Intermittent waves of parasitaemia (antigenic variation)
- Immune evasion through variant surface glycoprotein (VSG) switching
Step 3: Meningoencephalitic Stage (Stage 2)
- Trypanosomes cross blood-brain barrier
- CNS invasion with perivascular inflammation
- Disruption of circadian rhythm (sleep-wake disturbance)
- Progressive encephalopathy
Step 4: Death (if untreated)
- Progressive cachexia and immunosuppression
- Opportunistic infections
- Coma and death
Classification
| Form | Subspecies | Geography | Clinical Course |
|---|---|---|---|
| West African | T. b. gambiense | West/Central Africa | Chronic (months-years); human reservoir |
| East African | T. b. rhodesiense | East/Southern Africa | Acute (weeks-months); zoonotic (cattle) |
Stages
| Stage | Definition | CSF Findings |
|---|---|---|
| Stage 1 | Haemolymphatic; no CNS involvement | Normal CSF |
| Stage 2 | Meningoencephalitic; CNS involvement | WCC greater than 5/µL or trypanosomes in CSF |
Symptoms
Incubation Period:
Stage 1 (Haemolymphatic):
Stage 2 (Meningoencephalitic):
Signs
Red Flags
[!CAUTION] Red Flags — Urgent specialist input required if:
- Confusion, personality change, or altered consciousness (Stage 2)
- Seizures or focal neurological signs
- Sleep-wake cycle reversal
- Rapid deterioration (suggests T. b. rhodesiense)
- Treatment failure or relapse
Structured Approach
General:
- Vital signs (fever pattern)
- Nutritional status (cachexia in advanced disease)
- Level of consciousness
Lymph Node Examination:
- Posterior cervical (Winterbottom's sign)
- Generalised lymphadenopathy
Skin:
- Inspect for chancre at possible bite sites
- Pruritus, rash
Abdominal:
- Hepatosplenomegaly
Neurological:
- Conscious level and orientation
- Sleep pattern history (crucial)
- Tremor, ataxia, movement disorders
- Reflexes, tone
Special Tests
| Test | Technique | Positive Finding | Sensitivity/Specificity |
|---|---|---|---|
| Winterbottom's sign | Palpate posterior cervical nodes | Enlarged, rubbery nodes | Classic for gambiense |
| Kerandel's sign | Apply pressure; delayed pain response | Pain seconds after stimulus | Suggestive |
| Sleep history | Detailed history of sleep-wake pattern | Day somnolence, night insomnia | Stage 2 indicator |
First-Line (In Endemic Areas)
- Card Agglutination Test (CATT) — Serological screening for T. b. gambiense
- Thick and thin blood films — Direct parasite visualisation
- Lymph node aspirate — Chancre or enlarged nodes; wet preparation microscopy
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| FBC | Anaemia, thrombocytopenia, leukopenia | Assess severity |
| ESR/CRP | Elevated | Inflammatory response |
| LFTs | May be mildly deranged | Baseline |
| Thick blood film | Trypomastigotes (motile) | Diagnosis |
| Lymph node aspirate | Trypanosomes | Diagnosis |
Lumbar Puncture (Essential for Staging)
| Parameter | Stage 1 | Stage 2 |
|---|---|---|
| WCC | ≤5/µL | >/µL |
| Protein | Normal | Elevated |
| Trypanosomes | Absent | May be present |
| IgM | Normal | Elevated |
Imaging
| Modality | Findings | Indication |
|---|---|---|
| CT/MRI Brain | Cerebral oedema, white matter changes (late) | If neurological symptoms |
| Chest X-ray | Exclude concurrent infections | Baseline |
Diagnostic Criteria
- Definitive diagnosis: Identification of trypanosomes in blood, lymph node aspirate, chancre fluid, or CSF
- Stage 2 diagnosis: CSF WCC greater than 5/µL OR trypanosomes in CSF
Management Algorithm
SUSPECTED AFRICAN TRYPANOSOMIASIS
↓
┌─────────────────────────────────────────┐
│ CONFIRM DIAGNOSIS │
│ Blood film, lymph node aspirate, CATT │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ IDENTIFY SUBSPECIES │
├─────────────────────────────────────────┤
│ T. b. gambiense (West/Central Africa) │
│ T. b. rhodesiense (East Africa) │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ LUMBAR PUNCTURE (STAGING) │
├─────────────────────────────────────────┤
│ Stage 1: CSF WCC ≤5, no parasites │
│ Stage 2: CSF WCC >5 or parasites │
└─────────────────────────────────────────┘
↓
┌─────────────────────────────────────────┐
│ TREATMENT SELECTION │
├─────────────────────────────────────────┤
│ GAMBIENSE STAGE 1: Pentamidine or │
│ Fexinidazole │
│ GAMBIENSE STAGE 2: Fexinidazole or │
│ NECT │
│ RHODESIENSE STAGE 1: Suramin │
│ RHODESIENSE STAGE 2: Melarsoprol │
└─────────────────────────────────────────┘
Acute/Emergency Management
- Manage seizures if present
- Supportive care for coma
- Do not delay specific treatment once diagnosis confirmed
Conservative Management
- Nutritional support
- Vector control measures (insecticide-treated screens)
- Surveillance in endemic areas
Medical Management
T. b. gambiense:
| Stage | Drug | Dose | Duration |
|---|---|---|---|
| Stage 1 | Pentamidine | 4mg/kg IM daily | 7 days |
| Stage 1 or early Stage 2 | Fexinidazole | 1800mg PO daily x4 days, then 1200mg daily x6 days | 10 days |
| Stage 2 | NECT (Nifurtimox + Eflornithine) | Eflornithine 400mg/kg/day IV in 2 doses x7d + Nifurtimox 15mg/kg/day PO in 3 doses x10d | 10 days |
T. b. rhodesiense:
| Stage | Drug | Dose | Duration |
|---|---|---|---|
| Stage 1 | Suramin | Test dose 4-5mg/kg IV, then 20mg/kg IV weekly | 5 doses |
| Stage 2 | Melarsoprol | 2.2mg/kg IV daily | 10 days |
[!WARNING] Melarsoprol Toxicity: Melarsoprol (arsenical compound) causes encephalopathic syndrome in 5-10% of patients with 50% mortality. Reserve for T. b. rhodesiense Stage 2 only.
Surgical Management
- Not applicable
Disposition
- Admit: All confirmed cases for treatment initiation and monitoring
- Follow-up: Lumbar puncture at 6, 12, and 24 months post-treatment to confirm cure (CSF normalisation)
Immediate
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Seizures | 10-20% (Stage 2) | Generalised tonic-clonic | Benzodiazepines, anticonvulsants |
| Drug reactions | Variable | Anaphylaxis (suramin), encephalopathy (melarsoprol) | Supportive, steroids |
Early (Treatment-Related)
- Melarsoprol encephalopathy: 5-10%; 50% mortality — steroids, supportive care
- Jarisch-Herxheimer reaction: Fever, rigors after treatment initiation
- Pentamidine hypotension and hypoglycaemia: Monitor glucose
Late
- Relapse: 5-10% — repeat treatment with alternative regimen
- Neurological sequelae: Cognitive impairment, movement disorders
- Death: If untreated or treatment fails
Natural History
- Stage 1: Weeks (rhodesiense) to months/years (gambiense)
- Stage 2: Progressive decline over months
- Untreated: 100% mortality
- Spontaneous cure: Extremely rare
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| Stage 1 cure rate | Greater than 95% |
| Stage 2 cure rate (gambiense) | 90-95% with NECT/fexinidazole |
| Stage 2 cure rate (rhodesiense) | 90% with melarsoprol |
| Mortality with treatment | Less than 5% |
Prognostic Factors
Good Prognosis:
- Early diagnosis (Stage 1)
- T. b. gambiense (chronic course)
- Prompt treatment
Poor Prognosis:
- Late presentation (Stage 2)
- T. b. rhodesiense (acute course)
- Melarsoprol encephalopathy
- Relapse
Key Guidelines
- WHO Guidelines (2019) — Control and surveillance of human African trypanosomiasis. WHO HAT
- CDC Guidelines — Traveller's Health: African Trypanosomiasis.
- MSF Protocols — Treatment of sleeping sickness in endemic areas.
Landmark Trials
NECT Development Studies (2009) — Nifurtimox-Eflornithine Combination
- Demonstrated NECT non-inferior to eflornithine monotherapy with simpler regimen
- Clinical Impact: NECT became first-line for gambiense Stage 2
Fexinidazole Trials (2018) — Oral treatment for HAT
- First oral-only treatment effective for Stage 1 and early Stage 2 gambiense
- Clinical Impact: Simplified treatment, reduced hospitalisation
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| NECT for gambiense Stage 2 | 1b | RCTs, WHO recommendation |
| Fexinidazole | 1b | Phase III trials |
| Pentamidine for Stage 1 | 2a | Historical studies, WHO recommendation |
| Melarsoprol for rhodesiense Stage 2 | 2a | Only effective option |
What is African Trypanosomiasis?
African trypanosomiasis, also called sleeping sickness, is an infection caused by tiny parasites called trypanosomes. These parasites are spread by the bite of the tsetse fly, which is only found in parts of Africa. The disease gets its name because it disrupts your sleep pattern — you may feel very sleepy during the day but unable to sleep at night.
Why does it matter?
Without treatment, sleeping sickness is always fatal. The parasites first cause fever, swollen glands, and fatigue. Later, they can travel to the brain, causing confusion, personality changes, and eventually coma. The good news is that with the right treatment, most people recover completely.
How is it treated?
- Early stage (Stage 1): Injections or tablets for about 7-10 days. This usually cures the infection.
- Late stage (Stage 2): More intensive treatment is needed because the parasites have reached the brain. This requires hospitalisation.
- Follow-up: After treatment, you will need regular check-ups including lumbar punctures to make sure the infection is truly gone.
What to expect
- Diagnosis requires blood tests and often a lumbar puncture (spinal tap)
- Treatment requires hospitalisation, especially for late-stage disease
- Most people recover fully if treated early
- Follow-up appointments are essential to detect any relapse
When to seek help
See a doctor immediately if you have:
- Been to Africa and have unexplained fevers
- A sore at a fly bite that lasts more than a few days
- Swollen glands in your neck
- Problems sleeping or unusual sleepiness during the day
- Confusion or personality changes
Primary Guidelines
- World Health Organization. Control and surveillance of human African trypanosomiasis: report of a WHO expert committee. WHO Technical Report Series 984. 2013.
Key Trials
- Priotto G, et al. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet. 2009;374(9683):56-64. PMID: 19559476
- Mesu VKBK, et al. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018;391(10116):144-154. PMID: 29113731
- Kennedy PGE. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol. 2013;12(2):186-94. PMID: 23260189
Further Resources
- WHO HAT Programme: who.int/trypanosomiasis_african
- CDC Sleeping Sickness: cdc.gov/parasites/sleepingsickness
- DNDi HAT Programme: dndi.org
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.