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Diagnosis

Definitive diagnosis rests on the observation of trypanosomes by microscopy.

In T. b. rhodesiense infection, the identification of suspected cases relies on the clinical presentation and a history of exposure. The level of parasitemia is relatively high, particularly in the first stage of disease, and trypanosomes can be found in blood. In centrifuged blood, the parasite sediments just above the white blood cells, and examination of buffy coat will increase sensitivity. Slides stained with Giemsa can be used, but it is easiest to find the parasite by microscopic examination of fresh wet preparations, because the trypanosomes are motile. Delay between sampling and microscopy should be minimized, because trypanosomes will lose motility within a few hours. Parasites can also be found in fluid expressed in trypanosomal chancres and in lymph node aspirates. Serologic testing is not used for the diagnosis of T. b. rhodesiense infection.

Detecting trypanosomes in T. b. gambiense infection is more difficult. The card agglutination test for trypanosomiasis/T. b. gambiense (CATT) is a serologic screening test used for population screening in endemic areas of Africa. It is not available in the United States. The test is insufficiently specific for confirmation of infection but can be helpful in identifying suspect cases. Parasitologic confirmation rests upon microscopic examination of chancre fluid or lymph node aspirate. The yield in lymph node examination varies from about 40% to 80%. Trypanosomes can also be found in blood, however, the yield is low, and concentration techniques (e.g., centrifugation followed by buffy coat examination, mini-anion exchange centrifugation technique, or microhematocrit centrifugation technique) are helpful. Serial examinations on consecutive days may be needed.

Staging for both T. b. gambiense and T. b. rhodesiense (i.e., assessment of neurological infection) is performed by microscopic examination of CSF collected by lumbar puncture on a wet preparation looking for motile trypomastigotes and WBCs. Patients with five or fewer WBCs per microliter and no trypomastigotes are considered to be in the first stage, and those with more than five WBCs per microliter or trypomastigotes are in the second stage. Other indications of second stage disease include elevated protein and an increase in nonspecific IgM in CSF.

Diagnostic assistance for African trypanosomiasis is available through DPDx.

Treatment

<em>Trypanosoma brucei</em> ssp. in a thin blood smear stained with Giemsa.

Trypanosoma brucei ssp. in a thin blood smear stained with Giemsa.

Antitrypanosomal treatment is indicated for all persons diagnosed with African trypanosomiasis. Choice of therapy depends on the infecting subspecies of the parasite and on the disease stage. The first line drugs for both first and second stage disease are highly effective. Pentamidine is used to treat first stage T. b. gambiense infection. It is generally well-tolerated but may cause adverse reactions such as hypotension, hypoglycemia, injection site pain, diarrhea, nausea and vomiting. Suramin is also effective in treating the first stages of both T. b. gambiense and T. b. rhodesiense but is recommended to be only used to treat the first stage of T. b. rhodesiense because of the risk of severe adverse reactions in patients co-infected with onchocerciasis, which can occur in T. b. gambiense-endemic areas. Adverse reactions to suramin treatment in patients with T. b. rhodesiense trypanosomiasis are frequent, but usually mild and reversible. These include drug rash, nephrotoxicity, and peripheral neuropathy. In rare instances, suramin administration results in a hypersensitivity reaction, and, for this reason, a small test dose is usually given prior to the full first dose.

Second stage T. b. gambiense is treated with nifurtimox-eflornithine combination therapy (NECT). The combination regimen appears to be more effective and less toxic than eflornithine monotherapy. Adverse events with eflornithine include fever, pruritus, hypertension, nausea, vomiting, diarrhea, abdominal pain, headaches, myelosuppression and more rarely, seizures. Eflornithine is not effective against T. b. rhodesiense and it is not recommended for treating the East African form of the disease. Melarsoprol, an organoarsenic compound, is the only drug available for treating second stage T. b. rhodesiense. Adverse reactions to melarsoprol can be severe and life-threatening. An encephalopathic reaction occurs in 5–10% of patients with a case-fatality rate of approximately 50% when it occurs. Prednisone or prednisolone is often given to patients who are being treated with melarsoprol to reduce the risk of encephalopathy. Other adverse reactions observed with melarsoprol include gastrointestinal and skin reactions, pyrexia, and peripheral neuropathy. Intravenous injections of melarsoprol are painful and can cause phlebitis.

The 2019 WHO interim guidelines for the treatment of human West African trypanosomiasis provide recommendations about treatment with fexinidazole, a recently approved new medicine for the treatment of gambiense trypanosomiasis. It is recommended and adapted for use in rural health facilities in Africa. Fexinidazole is not available and is not recommended for use in the United States. There is no test of cure for African trypanosomiasis. After treatment, patients should be closely followed for 24 months and monitored for relapse. Recurrence of symptoms will require examination of body fluids, including CSF, to detect the presence of trypanosomes.

Standard Treatment of African Trypanosomiasis by Form and Stage

Ref	Species	First-line Treatment	Dosage	Alternative Treatment and Dosage	Comments
1.	T. b. gambiense, first stage	Pentamidine*	4 mg/kg/day IM or IV (diluted in saline in 2-hour infusions) x 7 days.
2.	T. b. gambiense, second stage	Nifurtimox^- eflornithine† combination therapy (NECT)	Nifurtimox 15 mg/kg per day orally in three doses x 10 days, and eflornithine 400 mg/kg/day IV in two 2-hour infusions (each dose diluted in 250 mL of water for injection) x 7 days. See Comments column for dosage in children.	NECT long (10 days of nifurtimox 15 mg/kg/day orally in three doses, and eflornithine 400 mg/kg per day IV in four 2-hour infusions, each dose diluted in 100 mL of water for injection) × 14 days. See Comments column for dosage in children. ‡ Elfornithine 400mg/kg/day IV in four 2-hour infusions (each dose diluted in 100mL of water for injection) x 14 days. Treatment for relapse is with melarsoprol 2.2 mg/kg per day IV × 10 days.	Eflornithine in children weighing <10 kg: dilute in 50 mL of water for injection. Children weighing 10–25 kg: dilute in 100 mL of water for injection. If water for injection is unavailable, eflornithine can be diluted in 5% dextrose or saline. Eflornithine might not be effective in immunosuppressed patients because it is trypanostatic and not trypanocidal.
3.	*T. b. rhodesiense, first stage*	Suramin	Test dose of 4–5 mg/kg (day 0) slowly IV, then 20 mg/kg IV (max 1 gm/injection) over several hours on days 1, 3, 7, 14, and 21. See comments for dosage in children.	Pentamidine 4 mg/kg per day IM or IV (diluted in saline, in 2-hour infusions) × 7 days.	Suramin in children (test dose): 2 mg/kg; maximum, 100 mg Suramin in children (treatment dose): 10–20 mg/kg, maximum 1 gm In case of renal toxicity, consider alternative treatment schedules adjusting the daily dose and the interval between doses.
4.	T. b. rhodesiense, second stage	Melarsoprol	2.2 mg/kg per day (max 180–200 mg/day) IV × 10 days.		Corticosteroid pretreatment should be considered as it can reduce the risk of encephalopathic reaction to melarsoprol.

References for Table:

1.

Human African trypanosomiasis. Büscher P, Cecchi G, Jamonneau V, Priotto G. Lancet. 2017 Nov 25;390(10110):2397–2409. doi: 10.1016/S0140-6736(17)31510-6. Epub 2017 Jun 30. Review. PubMed PMID: 28673422.

WHO interim guidelines for the treatment of gambiense human African trypanosomiasis. Geneva: World Health Organization; 2019.

Control and surveillance of human African trypanosomiasis: report of a WHO expert committee. Geneva: World Health Organization; 2013.

2.

WHO interim guidelines for the treatment of gambiense human African trypanosomiasis. Geneva: World Health Organization; 2019.

Control and surveillance of human African trypanosomiasis: report of a WHO expert committee. Geneva: World Health Organization; 2013.

Communication with Dr. Gerardo Priotto

3.

Control and surveillance of human African trypanosomiasis: report of a WHO expert committee. Geneva: World Health Organization; 2013.

4.

Efficacy of 10-day melarsoprol schedule 2 years after treatment for late-stage gambiense sleeping sickness. Schmid C, Nkunku S, Merolle A, Vounatsou P, Burri C. Lancet 2004; 364:789–90.

Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage Rhodesiense sleeping sickness. Kuepfer I, Schmid C, Allan M, Edielu A, Haary EP, Kakembo A, Kibona S, Blum J, Burri C. PLoS Negl Trop Dis. 2012 Aug;6(8).

Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II). Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, Manthelot CR, Nangouma A, Doua F, Asumu PN, Simarro PP, Burri C. J Infect Dis. 2005 Jun 1;191(11):1922–31.

Control and surveillance of human African trypanosomiasis: report of a WHO expert committee. Geneva: World Health Organization; 2013.

* Pentamidine is available for human use in the United States.

† Eflornithine is available for human use in the United States through CDC.

^ Nifurtimox is commercially available in the United States.

‡ Eflornithine may be given as monotherapy for second-stage gambiense HAT when NECT is not feasible because nifurtimox is unavailable or contraindicated. NECT or NECT long is preferred over eflornithine monotherapy when both drugs are available and not contraindicated.

NOTE: For treatment advice and to obtain suramin, melarsoprol, or eflornithine, physicians should contact CDC’s Division of Parasitic Diseases and Malaria (404-718-4745; parasites@cdc.gov).

Eflornithine

Data on the use of eflornithine in pregnant women are limited, and risk to the embryo-fetus is unknown. Eflornithine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether eflornithine is excreted in breast milk. Eflornithine should be used with caution in breast-feeding women.

The safety of eflornithine in children has not been established by FDA but combined nifurtimox-eflornithine (NECT) has been used successfully by WHO in endemic settings in children. Eflornithine is not approved by FDA for use in pediatric patients but it is available from CDC with an individual IND from FDA. Eflornithine is listed for the treatment of 2^nd stage African trypanosomiasis in Trypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children.WHO 2019 interim guidelines for T. b. gambiense have eflornithine dosing recommendations for children as small as 5kg.

Pentamidine

Pentamidine is in pregnancy category C. Data on the use of pentamidine in pregnant women are limited, and risk to the embryo-fetus is unknown. Pentamidine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether pentamidine is excreted in breast milk. The World Health Organization (WHO) classifies pentamidine as compatible with breast-feeding, although data on the use of pentamidine during lactation are limited. Pentamidine should be used during lactation only if the potential benefit of therapy to the mother justifies the potential risk to the infant.

Intravenous and intramuscular pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

Page last reviewed: July 8, 2022

Content source: Global Health, Division of Parasitic Diseases and Malaria

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Diagnosis

References for Table:

1.

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4.

Eflornithine

Pentamidine