Human african trypanosomiasis (sleeping sickness)


Human african trypanosomiasis (HAT) is a zoonosis caused by protozoa (trypanosomes), transmitted to humans through the bite of a tsetse fly (Glossina). Transmission by contaminated blood transfusion and transplacental transmission are also possible.

The disease is found only in sub-Saharan Africa. There are two forms: Trypanosoma brucei gambiense HAT in western and central Africa and Trypanosoma brucei rhodesiense HAT in eastern and southern Africa.

Clinical features

Inoculation may be followed by an immediate local reaction (trypanosomal chancre). This chancre arises in about 50% of all rhodesiense but rarely in gambiense.

Gambiense HAT

– Incubation lasts from a few days to several years.
– The first stage (haemolymphatic stage) corresponds to the haematogenous and lymphatic dissemination of the parasite. Signs include intermittent fever, joint pain, lymphadenopathy (firm, mobile, painless lymph nodes, mainly cervical), hepatosplenomegaly and skin signs (facial oedema, pruritus).
– The second stage (meningoencephalitic stage) corresponds to the invasion of the central nervous system. Signs of the haemolymphatic stage recede or disappear and varying neurological signs progressively develop: sensory disturbances (deep hyperaesthesia), psychiatric disorders (apathy or agitation), disturbance of the sleep cycle (with daytime somnolence alternating with insomnia at night), impaired motor functions (paralysis, seizures, tics) and neuroendocrine disorders (amenorrhoea, impotence).
– In the absence of treatment: cachexia, lethargy, coma and death.

Rhodesiense HAT

The first stage is the same as above, but the incubation period is shorter (< 3 weeks), the disease evolves more rapidly and symptoms are more severe. Patients often die of myocarditis in 3 to 6 months without having developed signs of the meningo-encephalitic stage.


In practice, gambiense and rhodesiense HAT can be difficult to differentiate: e.g., there exist cases of acute gambiense infection and others of chronic rhodesiense infection.

Laboratory

– Diagnosis involves 3 steps for gambiense HAT (screening test, diagnostic confirmation and stage determination) and 2 steps for rhodesiense HAT (diagnostic confirmation and stage determination).

– The recommended screening test for T.b. gambiense infection is the CATT (Card Agglutination Test for Trypanosomiasis). It detects the presence of specific antibodies in the patient’s blood or serum.

– Diagnostic confirmation: presence of trypanosomes in lymph node aspirates or in blood using concentration techniques: capillary tube centrifugation technique (Woo test), quantitative buffy coat (QBC), mini-anion exchange centrifugation technique (mAEC).

– Stage determination: detection of trypanosomes (after centrifugation) and white cell count in the cerebrospinal fluid (lumbar puncture):
• Haemolymphatic stage: no trypanosomes AND ≤ 5 white cells/mm3
• Meningoencephalitic stage: evidence of trypanosomes OR > 5 white cells/mm3

Treatment (except in pregnant women)

– Due to the toxicity of trypanocides, detection of the parasite is essential before initiating treatment. In the absence of parasitological confirmation, treatment may nevertheless be justified in certain cases: very strong clinical suspicion, patients in life-threatening condition, strong serological suspicion (CATT 1:16 positive) in a population where the disease is highly prevalent (> 2%).
– Several treatment regimens exist. Check national recommendations and local resistance levels.
– Treatment must be administered under close medical supervision. Patients receiving pentamidine can be treated as outpatients but those receiving suramin, eflornithine (with or without nifurtimox) or melarsoprol should be hospitalised.
– After treatment, patients should be checked every 6 months (clinical examination, lumbar puncture and examination for trypanosomes) over 24 months, to look for relapse.

Haemolymphatic stage (Stage I)

Gambiense HAT

pentamidine isetionate deep IM
Children and adults: 4 mg/kg once daily for 7 to 10 days
Patients should receive a source of glucose (meal, sweet tea) one hour before injection (risk of hypoglycaemia); they should remain supine during administration and one hour after injection (risk of hypotension).

Rhodesiense HAT

suramin slow IV
Children and adults:
D1: test dose of 4 to 5 mg/kg
D3, D10, D17, D24, D31: 20 mg/kg (max. 1 g par injection)
Suramin may cause anaphylactic reactions, a test dose is recommended prior to starting treatment. In the event of an anaphylactic reaction after the test dose, the patients must not be given suramin again.

Meningoencephalitic stage (Stage II)

Before administrating trypanocides, the priority is to improve the patient’s general condition (rehydration, treatment of malaria, intestinal worms, malnutrition, bacterial infections). It is nonetheless recommended not to postpone the trypanocidal treatment for more than 10 days.

Gambiense HAT

– First choice: nifurtimox-eflornithine combination therapy (NECT)
nifurtimox PO
Children and adults: 5 mg/kg 3 times daily for 10 days
eflornithine IV infusion over 2 hours
Children and adults: 200 mg/kg every 12 hours for 7 days

The catheter must be handled with great attention to avoid local or general bacterial infections: thoroughly disinfect the insertion site, ensure secure catheter fixation, protect the insertion site with a sterile dressing, systematically change the catheter every 48 hours or earlier in case of signs of phlebitis.

– Second choice:
eflornithine IV infusion over 2 hours
Children under 12 years: 150 mg/kg every 6 hours for 14 days
Children 12 years and over and adults: 100 mg/kg every 6 hours for 14 days

– In the event of a relapse after NECT or eflornithine:
melarsoprol slow IV
Children and adults: 2.2 mg/kg once daily for 10 days
Melarsoprol is highly toxic: reactive encephalopathy (coma, or recurrent or prolonged seizures) in 5 to 10% of treated patients, fatal in around 50% of cases; peripheral neuropathy, invasive diarrhoea, severe skin rash, phlebitis, etc.
Prednisolone PO (1 mg/kg once daily) is frequently combined throughout the duration of treatment.

Rhodesiense HAT

melarsoprol slow IV
Children and adults: 2.2 mg/kg once daily for 10 days
Prednisolone PO (1 mg/kg once daily) is frequently combined throughout the duration of treatment.

Treatment in pregnant women

All trypanocides are potentially toxic for the mother and the foetus (risk of miscarriage, malformation, etc.). However, due to the life-threatening risk for the mother and the risk of mother-to-child transmission, treatment must be initiated as follows:

Haemolymphatic stage:
pentamidine for gambiense HAT as of the second trimester and suramin for rhodesiense HAT.

Meningoencephalitic stage:
Treatment depends on the mother's condition:
– If in immediately life-threatening condition: treatment with NECT or eflornithine cannot be deferred until after delivery.
– If not immediately life-threatening condition: pentamidine for gambiense HAT and suramin for rhodesiense HAT. Treatment with NECT or eflornithine is to be administered after delivery.

Prevention and control

– Individual protection against tsetse fly bites: long sleeves and trousers, repellents, keeping away from risk areas (e.g. near rivers).
– Disease control: mass screening and treatment of patients (T.b. gambiense), trypanocide treatment of cattle (T.b. rhodesiense), vector control using tsetse fly traps or insecticides.