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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

References for Table:
1.

Human African trypanosomiasisexternal icon. 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.external icon Geneva: World Health Organization; 2019.

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

2.

Human African trypanosomiasisexternal icon. 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.external icon Geneva: World Health Organization; 2019.

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

Communication with Dr. Gerardo Priotto

3.

Human African trypanosomiasisexternal icon. 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.

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

4.

Human African trypanosomiasisexternal icon. 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.

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 committeeexternal icon. 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.

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

Pentamidine

Page last reviewed: July 28, 2021