Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 35-01: African Trypanosomiasis (Sleeping Sickness) + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Exposure to tsetse flies; chancre at bite site uncommon Hemolymphatic disease: Irregular fever, headache, joint pain, rash, edema, lymphadenopathy Meningoencephalitic disease: somnolence, severe headache, progressing to coma Trypanosomes in blood or lymph node aspirates; positive serologic tests Trypanosomes and increased white cells and protein in cerebrospinal fluid (CSF) +++ General Considerations ++ African trypanosomiasis is caused by the hemoflagellates Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense T b gambiense causes West African trypanosomiasis and is transmitted in the moist sub-Saharan savannas and forests of west and central Africa Organisms are transmitted by bites of tsetse flies (Glossina species), which inhabit shaded areas along rivers Humans are the principal mammalian host, but domestic animals can be infected Trypanosomes ingested in a blood meal undergo a developmental period of 18–35 days in the fly When the fly feeds again on a new mammalian host, the infective stage is injected +++ Demographics ++ The number of reported cases increased from the 1960s to1990s, and has since decreased greatly, although cases are reported from over 20 countries Total incidence has been estimated at about < 5000 cases per year, the large majority due to T b gambiense, with the largest number in the Democratic Republic of the Congo Infections are rare among travelers + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Chancres at the site of the bite are uncommon Patient may be asymptomatic for months before hemolymphatic disease develops Hemolymphatic disease progresses to meningoencephalitic disease, which leads to coma and death +++ Hemolymphatic disease ++ Fever, headache, myalgias, arthralgias, weight loss, and lymphadenopathy Discrete, nontender, rubbery nodes, referred to as Winterbottom sign when in a posterior cervical distribution Mild splenomegaly Transient edema Pruritic erythematous rash Febrile episodes may be broken by afebrile periods of up to several weeks +++ Meningoencephalitic disease ++ Somnolence, irritability, personality changes Severe headache Parkinsonian symptoms +++ Differential Diagnosis ++ T b rhodesiense infection Malaria Influenza and pneumonia Tuberculosis Infectious mononucleosis Leukemia or lymphoma HIV Arbovirus encephalitis Wilson disease Psychosis due to other causes, eg, neurosyphilis + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ During the hemolymphatic stage, detection of parasites in Giemsa-stained blood smears is difficult Serial specimens should be examined, since parasitemias vary greatly over time Meningoencephalitic (or second stage) disease is defined by the World Health Organization as CSF showing at least 5 mononuclear cells per mcL, elevated protein, or trypanosomes Concentration techniques can aid identification of parasites in blood or CSF Serologic tests are positive The simple card agglutination test for trypanosomes (CATT) Has excellent sensitivity and specificity Can be performed in the field However, the diagnosis should be confirmed by identification of the parasites Field-applicable immunochromatographic lateral flow rapid diagnostic tests that are lower cost and simpler to produce than CATT are available; combining tests improves sensitivity and specificity Molecular diagnostic tests, including PCR and field-friendly loop-mediated isothermal amplification (LAMP) are available but not yet standardized or routinely available + Treatment Download Section PDF Listen +++ +++ Medications ++ Pentamidine 4 mg/kg intramuscularly or intravenously every day or every other day for 7 days Used to treat infection that does not involve the CNS Side effects include immediate hypotension; tachycardia; gastrointestinal symptoms during administration; sterile abscesses; and pancreatic (hypoglycemia), liver, and kidney abnormalities Eflornithine Alternative to pentamidine 100 mg/kg/day intravenously every 6 hours for 14 days Combination of intravenous eflornithine (400 mg/kg/day in two doses for 7 days) and oral nifurtimox (15 mg/kg/day in three doses for 10 days) Treatment of choice for CNS infection; advanced infection defined as CNS leukocytes > 100/mcL) Has improved efficacy and less toxicity than older regimens Eflornithine, though less toxic than older trypanocidal drugs, can cause gastrointestinal symptoms, bone marrow suppression, seizures, and alopecia Melarsoprol is alternative agent Fexinidazole Recommended for patients 6 years of age and older, with body weight at least 20 kg, and a CSF leukocyte count < 100/mcL As efficacious and safe as eflornithine plus nifurtimox when administered orally over 10 days Approved by the WHO for both early and CNS infection and will likely replace other therapies for all but advanced CNS disease Adverse events include Headache Nausea Vomiting Insomnia Anxiety Weakness Tremor Decreased appetite + Outcome Download Section PDF Listen +++ +++ Prevention ++ Individual prevention should include Wearing neutral-colored clothes with long sleeves and pants Insect repellents Using mosquito nets while sleeping Control programs focusing on vector elimination and treatment of infected persons and animals have shown good success but suffer from limited resources + References Download Section PDF Listen +++ + +Aksoy S et al. Human African trypanosomiasis control: achievements and challenges. PLoS Negl Trop Dis. 2017 Apr 20;11(4):e0005454. [PubMed: 28426685] + +Büscher P et al. Human African trypanosomiasis. Lancet. 2017 Nov 25;390(10110):2397–409. [PubMed: 28673422] + +Deeks ED. Fexinidazole: first global approval. Drugs. 2019 Feb;79(2):215–20. [PubMed: 30635838] + +Lumbala C et al. Prospective evaluation of a rapid diagnostic test for Trypanosoma brucei gambiense infection developed using recombinant antigens. PLoS Negl Trop Dis. 2018 Mar 28;12(3):e0006386. [PubMed: 29590116] + +Mesu VKBK et al. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018 Jan 13;391(10116):144–54. [PubMed: 29113731]