The first time I had patients with sleeping sickness was in Uganda in 1989. I worked for Doctors Without Borders (MSF) as a doctor in refugee camps who were crossing the border from South Sudan fleeing war. We had to transfer some patients affected by this terrible parasitic disease to another MSF project on the other side of the Nile, where good medicines were not available.
Human African trypanosomiasis (HAT) – its scientific name – is transmitted through the bite of infected tsetse flies and subsequently leads to sleep disorders and neuropsychiatric symptoms such as disinhibition, aggression or psychosis. If left untreated, it is almost always fatal.
The TAH devastated entire regions of sub-Saharan Africa in the first half of the 20th century. It is an example of a neglected disease that affects communities too poor to be of interest to for-profit pharmaceutical research.
For a doctor, knowing that he can kill his patient is the worst dilemma
Transmission is facilitated by wars, conflicts and forced relocations. In 1995, in Angola, during the civil war, we were the first to enter the newly liberated town of N'dalatando. Sleeping sickness spread unhindered there and our Doctors Without Borders team was able to treat thousands of infected people. At the beginning, we could see that the only drug that could have cured advanced patients, melarsoprol, had no reserves and urgently needed to mobilize production. This arsenic derivative is administered by intravenous injection and is so toxic that it can cause death in one in 20 patients.
I think of the stories of my African colleagues who were afraid of having to prescribe melarsoprol: they knew that their patients would die without medication, but it was impossible to predict which of them would react to the arsenic and die, not from it disease, but rather the treatment. Too many patients were lost, some young and apparently healthy, whose deaths caused incomprehension and anger among their families. For a doctor, knowing that he can kill his patient is the worst dilemma.
It was this particular trauma that led MSF, together with research institutes in endemic countries, to create a non-profit research organization, the Drugs for Neglected Diseases Initiative (DNDi), which was founded in 2003 and which I joined in 2009. During its 20 years, DNDi has been working intensively on sleeping sickness, in collaboration with researchers in sub-Saharan Africa and the Sanofi Foundation, in close collaboration with the World Health Organization (WHO). With success: We have succeeded in developing new, effective medications that are well tolerated and accessible to those who need them. In 2018, the European Medicines Agency (EMA) issued a positive opinion on fexinidazole for the most common form of the disease found in Central and West Africa, caused by Trypanosoma brucei gambiense, which was quickly registered in the Democratic Republic of Congo. and is used to treat most forms of TAH.
Fexinidazole (oral tablets effective in all stages of the disease) can be taken at home for 10 days. It is safe and effective and represents a big change from the past.
A few days ago a new significant step was taken: the EMA gave its favorable opinion on the extension of the indication of fexinidazole against a rarer (about 7% of cases) but more virulent form of the disease caused by Trypanosoma brucei rhodesiense and in the East Africa is endemic. We finally have a safe and effective drug for both forms of HAT, which will lead to a significant reduction in the use of melarsoprol. The EMA's support also paves the way for WHO to distribute the tablets donated by Sanofi.
The EMA made its decision based on clinical trials coordinated by DNDi and carried out in Malawi and Uganda by national health workers with the support of several European institutions.
We do not know what impact climate change could have if it were to potentially expand to areas that were previously free of sleeping sickness.
What should be highlighted here is the central role of the European & Developing Countries Clinical Trials Partnership (EDCTP), a European Union program that finances clinical trials in sub-Saharan Africa. Supporting our clinical trial was a bold and wise decision in clinical research: Rhodesian variant is a neglected and rare disease.
We do not know what impact climate change could have if it were to potentially spread to areas that were previously free of the disease. Last year, Ethiopia recorded its first five cases of Rhodesia since the 1970s. An unusual drought brought people and livestock closer to the tsetse fly's habitat. Three people died (one due to side effects of treatment and two before diagnosis).
This European support made it possible to train doctors, health workers and laboratory technicians in Malawi and Uganda in clinical research and to equip and modernize health infrastructure in remote regions. This research paves the way for the registration and use of this new drug in the endemic countries of East Africa. But our work continues. We are developing a new molecule called acoziborole that is effective and even easier to administer in a single dose, allowing the possibility of almost complete elimination of the disease.
The therapeutic progress is immense for patients. It has been almost 35 years since I first encountered this terrible disease in Uganda, and now we can dream of a near future where all detected patients will be cured quickly and without complications.
This success can be replicated in other neglected diseases, such as leishmaniasis, a widespread endemic parasitic disease; or Chagas disease, which chronically affects about six million people, mainly in Latin America. We have proven that it is possible to bring the benefits of science to those who need them, regardless of their income or where they live.
Olaf Valverde is leader of the HAT clinical project of the Drugs for Neglected Diseases Initiative (DNDi).
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