Guidelines Summary
WHO interim guidelines for the treatment of gambiense human African trypanosomiasis. Geneva: World Health Organization;2019. Licence: CC BY-NC-SA 3.0 IGO.
Executive Summary from the Guideline:
Human African trypanosomiasis (HAT), or sleeping sickness, is a parasitic infection that is almost invariably fatal unless treated. It is a neglected tropical disease that occurs insub-Saharan Africa.
The infection is transmitted to humans through the bite of an infected tsetse fly. The parasite multiplies in the lymph and blood, causing unspecific symptoms and signs(first-stage or haemo-lymphatic stage) and, over time, crosses the blood–brain barrier to infect the central nervous system (second-stage or meningo-encephalitic stage). Brain involvement causes various neurological disturbances, including sleep disorders (hence the name “sleeping sickness”), progression to coma and, ultimately, death.
The disease has 2 forms: the slowly progressing form (gambiense HAT), caused by infection with Trypanosoma brucei gambiense, found in western and central Africa (currently 98% of cases); and the faster progressing form (rhodesiense HAT), caused by infection with T brucei rhodesiense, in eastern and southern Africa (responsible for the remainder of cases). All age groups and both sexes are at risk of both forms of HAT, although prevalence is higher in adults than in children.
The incidence of the disease is declining in response to intensive surveillance andncontrol in endemic areas. As a result, HAT is among the neglected tropical diseases targeted by the World Health Organization (WHO) for elimination. WHO maintains exhaustive records of all declared cases; in 2018, a historically low number of cases(< 1000) was reported.
The remarkable progress in the control of gambiense HAT has relied on case-finding and curative treatment, a strategy that interrupts transmission by depleting the reservoir ofparasites in humans. This has been combined occasionally with vector control activities.The subject of these guidelines, therefore, is of utmost importance for the continuation of progress to eliminate HAT.
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African trypanosomiasis (sleeping sickness). Human trypanosomes blood smear.
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Trypanosoma life cycle. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).
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Trypanosoma brucei in a thin blood smear stained with Giemsa. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).
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Geographical distribution of human African trypanosomiasis. Courtesy of PLoS Neglected Tropical Diseases [Franco JR, Cecchi G, Paone M, et al. The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020. PLoS Negl Trop Dis. 2022 Jan 18;16(1):e0010047. Online at: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010047.]
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The cases of Human African Trypanosomiasis (HAT) have decreased annually from 2000 to 2020. Courtesy of PLoS Neglected Tropical Diseases [Franco JR, Cecchi G, Paone M, et al. The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020. PLoS Negl Trop Dis. 2022 Jan 18;16(1):e0010047. Online at: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010047.]
Tables
Type of Trypanosomiasis |
Medications |
|
Stage 1 (Early or Hemolymphatic Stage) |
Stage 2 (Late or Neurologic Stage) |
|
East African trypanosomiasis (caused by Trypanosoma brucei rhodesiense) |
Suramin 4-5 mg/kg IV test dose, then 20 mg/kg (maximum 1 g/dose) IV on Days 1, 3, 7, 14, 21 |
Melarsoprol 2.2 mg/kg/day (maximum 180-200 mg) IV for 10 days |
West African trypanosomiasis (caused by Trypanosoma brucei gambiense) |
Pentamidine isethionate 4 mg/kg/day IM for 10 days or Suramin 4-5 mg/kg IV test dose, then 20 mg/kg (maximum 1 g/dose) IV on Days 1, 3, 7, 14, 21 or Fexinidazole 20 to < 35 kg: 1200 mg PO qd on Days 1-4, then 600 mg qd on Days 5-10 Fexinidazole 35 kg or greater: 1800 mg PO qd on Days 1-4, then 1200 mg qd on Days 5-10 |
Nifurtimox-Eflornithine Combination Therapy (NECT): Nifurtimox 5 mg/kg PO q8h for 10 days AND Eflornithine 200 mg/kg IV q12h for 7 days or Eflornithine 400 mg/kg/day IV in 2 divided doses for 14 days or Melarsoprol IV for 10 days or Fexinidazole PO for 10 days |
