Human African trypanosomiasis (sleeping sickness): comprehensive epidemiology, staging, diagnosis and treatment

Learning outcomes

• Differentiate gambiense and rhodesiense HAT by geography, reservoir, tempo, parasitaemia and clinical pattern.
• Explain tsetse transmission, antigenic variation and CNS invasion.
• Recognise haemolymphatic and meningoencephalitic stages.
• Plan specimen collection, microscopy, concentration tests, molecular tests and CSF staging.
• Understand why treatment is species- and stage-specific and why specialist supervision is essential.
• Provide follow-up, contact investigation and vector-control counselling.

Species, geography and reservoirs

American trypanosomiasis (Chagas disease, T. cruzi) is a different infection transmitted mainly by triatomine bugs in the Americas; it should not be confused with HAT.

Vector and life cycle

1. An infected tsetse takes a blood meal and inoculates metacyclic trypomastigotes into skin.
2. Parasites multiply extracellularly in lymph and blood. They periodically change variant surface glycoproteins, escaping antibody responses and creating waves of fever.
3. Parasites disseminate into lymphatics and tissues; later they cross the blood–brain barrier and multiply in CSF and CNS tissue.
4. A second tsetse ingests bloodstream forms. In the fly gut they transform, multiply and migrate to salivary glands, where infective metacyclic forms develop.

Rare transmission routes include congenital infection, contaminated blood, laboratory exposure and sexual transmission. A history of travel to a tsetse region is more useful than a patient’s ethnic label or passport.

Pathophysiology

• Antigenic variation: recurring surface-antigen changes produce waves of parasitaemia and fever.
• Immune activation: cytokines, immune complexes and polyclonal B-cell activation contribute to lymphadenopathy, anaemia, thrombocytopenia, pruritus and hypergammaglobulinaemia.
• Vascular/cardiac disease: rhodesiense infection can cause myocarditis, arrhythmias, pericarditis, hypotension and sudden deterioration.
• Neuroinvasion: inflammation and parasite growth in CNS tissue cause sleep–wake reversal, endocrine changes, movement disorders, psychiatric change, seizures and coma.
• Systemic wasting: prolonged infection causes weight loss, fever, malnutrition and susceptibility to secondary infection.

Clinical stages and features

Inoculation chancre

A painful, erythematous nodule at the bite site may enlarge, ulcerate and heal over one to three weeks. It is more often recognised in rhodesiense disease. Absence of a chancre does not exclude HAT because the bite may be unnoticed or the lesion may have healed before presentation.

Haemolymphatic disease

• Intermittent fever, rigors, headache and profound malaise.
• Pruritus, rash, facial oedema and weight loss.
• Posterior cervical lymphadenopathy (Winterbottom sign), especially in gambiense disease.
• Hepatosplenomegaly, anaemia, thrombocytopenia, oedema and arthralgia.
• Rhodesiense disease: abrupt high fever, high parasitaemia, chancre, myocarditis, shock and rapid organ dysfunction.

Meningoencephalitic disease

• Daytime somnolence and inability to remain awake, followed by nocturnal insomnia.
• Personality change, irritability, apathy, confusion, hallucinations or psychosis.
• Ataxia, tremor, dysarthria, hyperreflexia, abnormal movements, rigidity or weakness.
• Endocrine/autonomic features, headache, cranial-nerve abnormalities and incontinence.
• Seizures, coma and death if untreated.

Focused history and examination

Ask about residence/travel in endemic districts, farming, fishing, hunting, game-park work, riverine exposure, livestock, tsetse bites, chancre, recurrent fever, lymph-node swelling and new sleep or behaviour changes. Ask relatives whether the patient sleeps during conversations, stays awake at night, has become apathetic or has lost work skills.

Examine skin and bite sites, nodes, fever, pallor, jaundice, oedema, hepatosplenomegaly, cardiac rhythm, murmurs, heart failure, hydration, mental state, gait, coordination, cranial nerves, tone, reflexes, sensation and meningeal signs. A normal neurological examination does not exclude early CNS invasion.

Diagnosis: practical algorithm

1. Raise suspicion: compatible exposure plus fever, node, chancre or neurological symptoms.
2. Collect specimens before treatment if safe: chancre fluid, lymph-node aspirate and blood for thick/thin films and concentration methods.
3. Confirm the parasite: examine immediately or send to a reference laboratory. Molecular testing/PCR can help when available.
4. Use screening correctly: CATT and related tests are primarily gambiense screening tools; they do not replace parasite confirmation and are not reliable stand-alone tests for rhodesiense.
5. Stage: perform lumbar puncture after confirmation unless contraindicated. CSF white-cell count, protein and direct examination for trypanosomes determine CNS involvement under the applicable protocol.
6. Assess safety: FBC, renal/liver tests, glucose, ECG, pregnancy test and HIV testing according to consent and local policy.

Differential diagnosis

Malaria, relapsing fever, visceral leishmaniasis, tuberculosis, HIV, bacterial endocarditis, lymphoma, viral encephalitis, meningitis, autoimmune disease, drug intoxication, psychiatric illness and other causes of movement/sleep disorders. HAT and malaria may coexist.

Treatment principles

HAT treatment is potentially toxic and is selected by subspecies, stage, age, weight, pregnancy, renal function and the current WHO/UCG programme protocol. Recent WHO guidance expanded fexinidazole for selected rhodesiense disease, but eligibility must be checked at a referral centre.

• Do not copy a regimen from an old textbook without checking current WHO/UCG guidance.
• Treat seizures, anaemia, myocarditis, dehydration, malnutrition and bacterial co-infection.
• Observe the patient during parenteral treatment and ensure access to renal, neurological and haematological monitoring.

Drug toxicity and monitoring

Follow-up

Neurological recovery may be slow. Document baseline cognition, sleep, gait, speech, reflexes and functional status. Follow the national programme’s scheduled blood/CSF surveillance because relapse can occur. Return urgently for recurrent fever, somnolence, personality change, ataxia, tremor or seizures. Record species, stage, drug, dates, adverse events and contacts for surveillance.

Prevention and control

• Wear long sleeves/trousers and avoid dark contrasting clothing in tsetse areas.
• Avoid resting close to dense riverside vegetation; inspect vehicles before travel.
• Use traps, targets and insecticide-based vector programmes where available.
• Early detection and treatment interrupt human transmission; rhodesiense control also requires attention to livestock/wildlife reservoirs.
• No routinely available vaccine or reliable traveller chemoprophylaxis exists.

Exam and OSCE pearls

• Winterbottom nodes are suggestive, not mandatory, for gambiense HAT.
• Rhodesiense is more acute, more parasitaemic and more often visible in blood.
• Sleeping sickness refers to CNS disease and sleep–wake reversal, not ordinary fatigue.
• Species and stage determine the drug; lumbar puncture is a treatment decision, not a ceremonial test.
• Melarsoprol can cause fatal reactive encephalopathy and should never be used casually.

References

• SlideShare: Trypanosomiasis.
• Uganda Clinical Guidelines: INF035.
• WHO guidelines for treatment of human African trypanosomiasis (2024).
• CDC clinical care of HAT.

Safety note: This is educational material. Confirm species/stage, eligibility, dose and monitoring requirements with the current national sleeping-sickness programme.