African Trypanosomiasis - History

History

The condition has been present in Africa since at least the 14th century, and probably for thousands of years before then. Because of a lack of travel between indigenous people, sleeping sickness in humans had been limited to isolated pockets. This changed once Arab slave traders entered central Africa from the east, following the Congo River, bringing parasites along. Gambian sleeping sickness travelled up the Congo River, then further eastwards. In 1901, a devastating epidemic erupted in Uganda, killing more than 250,000 people, including about two-thirds of the population in the affected lakeshore areas. According to The Cambridge History of Africa, "It has been estimated that up to half the people died of sleeping-sickness and smallpox in the lands on either bank of the lower river Congo."

The causative agent and vector were identified in 1903 by David Bruce, and the differentiation between the subspecies of the protozoa made in 1910. The first effective treatment, atoxyl, an arsenic-based drug developed by Paul Ehrlich and Kiyoshi Shiga, was introduced in 1910, but blindness was a serious side effect. Numerous drugs designed to treat the disease have been introduced since then.

Suramin was introduced in 1920 to treat the first stage of the disease. By 1922, Suramin was generally combined with tryparsamide (another pentavalent organoarsenic drug) in the treatment of the second stage of the gambiense form. It was used during the grand epidemic in West and Central Africa in millions of people and was the mainstay of therapy until 1969.

Pentamidine, a highly effective drug for the first stage of the disease, has been used since 1939. During the 1950s, it was widely used as a prophylactic agent in western Africa, leading to a sharp decline in infection rates. At the time, eradication of the disease was thought to be at hand.

The organoarsenical melarsoprol (Arsobal) developed in the 1940s is effective for patients with second-stage sleeping sickness. However, 3-10% of those injected have reactive encephalopathy (convulsions, progressive coma, or psychotic reactions), and 10-70% of such cases result in death; it can cause brain damage in those who survive the encephalopathy. However, due to its effectiveness, melarsoprol is still used today. Resistance to melarsoprol is increasing, and combination therapy with nifurtimox is currently under research.

Eflornithine (difluoromethylornithine or DFMO), the most modern treatment, was developed in the 1970s by Albert Sjoerdsmanot and underwent clinical trials in the 1980s. The drug was approved by the United States Food and Drug Administration in 1990, but Aventis, the company responsible for its manufacture, halted production in 1999. In 2001, however, Aventis, in association with Médecins Sans Frontières and the World Health Organization, signed a long-term agreement to manufacture and donate the drug.