Control of HAT has been one of the region’s great success stories. Infection with trypanosomes – principally Trypanosoma brucei gambiense, a single-celled parasite transmitted by the tsetse fly – can lead to lethargy and potentially death. In recent decades, however, cases have been reduced by more than 90% through more effective treatments and vector control.

A major advance has been the development of a new drug for HAT, fexinidazole, by the Drugs for Neglected Diseases initiative (DNDi) and its partners. Fexinidazole is an oral drug, so much easier to administer than current treatments for severe disease, which require use of intravenous drug infusions. The FEX-g-HAT project, awarded in 2019, aims to accelerate the introduction of fexinidazole by engaging with health systems and health workers in affected countries to raise awareness of the drug and WHO recommendations on its use, to train health workers on its administration, and to support the development of national health policies.

Launched in 2019, the HAT-r-ACC study is assessing whether fexinidazole is also effective against Trypanosoma brucei rhodesiense, which causes a more acute form of HAT and is found mainly in East Africa. Fexinidazole is being assessed as an alternative to a toxic arsenic-based drug (melarsopol) and a less toxic but difficult-to-administer drug (suramin).

The HAT-r-ACC study is assessing whether a new treatment is effective against a type of sleeping sickness mainly found in East Africa. What are the advantages of this new treatment? 

Sleeping sickness or human African trypanosomiasis is a serious parasitic infection prevalent in sub-Saharan Africa that is usually fatal if untreated. The first fully oral treatment, fexinidazole, was recently developed and is now in use for the most common form of the disease in Central and West Africa, caused by Trypanosoma brucei gambiense. 

This new treatment is now being tested by DNDi and partners* against the less common but more acute form of the disease, caused by Trypanosoma brucei rhodesiense, which is prevalent in East African countries. This form of the disease is still being treated with very toxic drugs, especially the advanced neurological form of the disease, which can be cured only with an arsenic derivative, melarsoprol, which causes death in one in 20 patients. We expect that this new treatment will be highly effective, less toxic, easier to administer, and avoid the need for painful lumbar puncture, which is currently used to determine the disease stage.

What comes next?

The HAT-r-ACC partners expect to complete the clinical trial by September 2022 as planned. A second ethnographic survey is planned in Malawi. Our activities with communities and the continuous training of peripheral health staff will facilitate early diagnosis and improve disease control.

As the infection also affects cattle and wild game, eradication of the disease is not possible, but we expect that this project will contribute towards the WHO roadmap target of eliminating T. b. rhodesiense sleeping sickness as a public health problem and facilitating future access for patients to a highly effective and safe treatment.

What progress was made in 2019?

The core activity of the HAT-r-ACC project is a clinical trial, which started in Rumphi Hospital in Malawi in October 2019. Soon after the start, an outbreak of sleeping sickness occurred in the area, allowing the team to enrol 26 patients up to July 2020 and enabling the project to advance several months ahead of the planned enrolment rate. Opening of a second site, at Lwala Hospital in Uganda, was delayed due to COVID-19 pandemic-related restrictions.

Beyond the clinical trial, the project aims to raise community awareness of the disease. This component started with an ethnographic survey in Uganda that led to the preparation of a comprehensive and community-focused communication plan that will be developed in the months to come.