Photo: Swiss TPH (Trypanosoma brucei)

Human African Tryponosomiasis

African sleeping sickness can only be tackled in a combined effort. Since decades Swiss TPH has been developing unique methods aimed at studying the effect of compounds on the fatal parasites directly.  In the last ten years, researchers at Swiss TPH identified several dozen highly active compounds, some with complete new properties. The most promising candidate compounds were selected for further preclinical analysis.

From Laboratory to Field

While new compounds are being sought in the laboratories, other Swiss TPH staff often find themselves dealing with the realities of everyday life in the field: clinical research in remote locations with arduous journeys, extremely limited medical care and logistical difficulties on site. Despite of all these challenges, a clinical trial must meet the highest possible standards.

Eradication of West African Sleeping Sickness?

Experts of Swiss TPH have evaluated and modelled various scenarios for halting the spread of West African Sleeping Sickness. The models show that, in addition to the introduction of new drugs, tsetse fly populations should be destroyed in a targeted manner, diagnosis improved and the active monitoring of disease outbreaks reinforced.

A Swiss TPH Success Story

West African sleeping sickness is a prime example of a neglected disease. It occurs in the most remote regions of sub-Saharan Africa, and primarily affects the poorest in society. The protozoan parasite Trypanosoma brucei gambiense that causes the disease is transferred to humans via the tsetse fly.

Following the initial stage of the disease with non-specific pain, fever, skin rashes and swelling, the parasite passes through the blood-brain barrier and attack the brain. Severe psychiatric disorders, sleeplessness and impaired speech, body coordination and food intake ultimately result in death. The WHO has set a target of putting an end to the transmission of the disease by 2020.

Study team discussing the procedure, Kwamouth DRC

Milestone in the Fight Against Sleeping Sickness

In December 2023, the European Medicines Agency adopted a positive opinion on fexinidazole for the treatment of sleeping sickness T.b. rhodesiense, which occurs in eastern and southern Africa. The positive opinion followed a clinical trial conducted by the HAT-r-ACC consortium, of which Swiss TPH is a member. This is an important milestone in the fight against this acute and deadly form of the neglected tropical disease. Read more

Fexinidazole against Human African Trypanosomiasis

In November 2018, the European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion of fexinidazole, the first all-oral treatment that has been shown to be efficacious for both stages of sleeping sickness. This approval is a result of clinical trials led by the non-profit research and development organization DNDi and an application submitted by Sanofi. Swiss TPH contributed extensively to the development of this novel drug. Fexinidazole is the first all-oral treatment that works both for the early stage as well as the second stage of the disease in which the parasites have crossed the blood-brain barrier, causing patients to suffer from neuropsychiatric symptoms. Read more

Drug Discovery in Collaboration with DNDi

The Drugs for Neglected Diseases initiative (DNDi) can be viewed as a virtual non-profit pharmaceutical company with technical support from a range of partners in industry, universities, foundations and the public sector. We collaborate with DNDi in the area of drug discovery by contributing in vitro assays for the parasites and cytotoxicity assessment as well as rodent models of infection for African trypanosomes.

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Selected projects at this location:

Antillón M et al. Health economic evaluation of strategies to eliminate gambiense human African trypanosomiasis in the Mandoul disease focus of Chad. PLoS Negl Trop Dis. 2023;17(7):e0011396. DOI: 10.1371/journal.pntd.0011396

Mesu V.K.B.K et al. Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial. Lancet Infect Dis. 2023;23(4):463-470. DOI: 10.1016/S1473-3099(22)00660-0

Antillón M et al. Cost-effectiveness of sleeping sickness elimination campaigns in five settings of the Democratic Republic of Congo. Nat Commun. 2022;13:1051. DOI: 10.1038/s41467-022-28598-w

Bernhard S, Kaiser M, Burri C, Mäser P. Fexinidazole for human African trypanosomiasis, the fruit of a successful public-private partnership. Diseases. 2022;10(4):90. DOI: 10.3390/diseases10040090

Koester D.C et al. Discovery of novel quinoline-based proteasome inhibitors for human African trypanosomiasis (HAT). J Med Chem. 2022;65:11776−11787. DOI: 10.1021/acs.jmedchem.2c00791

Mesu V.K.B.K et al. Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial. Lancet Glob Health. 2022;10(11):e1665-e1674. DOI: 10.1016/S2214-109X(22)00338-2

Mudji J et al. Mental distress and health-related quality of life in gambiense human African trypanosomiasis: a case-control study in the Democratic Republic of Congo. Trans R Soc Trop Med Hyg. 2022;116(11):1022-1031. DOI: 10.1093/trstmh/trac035