Human African trypanosomiasis

The history of sleeping sickness

Towards systematic control

Initially patients were systematically isolated in sleeping sickness centres or "lazarets". On the heavily infested shores of Lake Victoria in Uganda and German East Africa (Tanzania) the whole population was evacuated to 3 to 25 km from the water front to break the contact with the fly. This was completed by 1907 and by that time the number of patients in Uganda had gone down from 30.000 in 1905 to 1500. As an emergency solution the evacuation strategy was quite successful however on the long term the uninhabited areas offered ideal grounds for game and tsetse to regenerate and it ended with further expansion of the tsetse infested zones.

The next approach towards control was tsetse control. Since ages people in Sudan have been using gourds filled with blood as bait to protect their cattle from tsetse bites. First systematic application of tsetse trapping by a colonial administration was in 1911 on the island Principe where from 1910 till 1914 tsetse were successfully eradicated by means of some three hundred fieldworkers carrying black cloths coated with birdlime on their back.

Vector control was used especially in East Africa. Bush clearing was practised at extensive scale and since the thirties a number of tsetse traps were developed and applied for research as well as control. The Chorley trap of 1933 was designed to mimic a human being

Reservoir host control, game destruction, strongly recommended by Bruce, was practised in Zimbabwe (Rhodesia), Uganda and Southern Sudan between 1920 and 1940. It resulted in a significant decline of the tsetse populations without however reaching the point of extermination. When by the 1940’s hunting activities slowed down game and tsetse recovered rapidly again.

World War II had brought DDT and by 1949 insecticide spraying was introduced against tsetse. It rapidly took over from traps and hand catching. In East Africa from the fifties till early seventies armies of ground sprayers of the tsetse control programmes covered annually large parts of the endemic areas.

Jamot (1879-1937) was the founder of the principle of systematic case detection and treatment: a highly logic control system for T.b. gambiense control: systematic case detection and treatment with as ultimate objective the elimination of the parasite reservoir. Jamot's three basic principles expressed by his nine "postulates" were: (i) case detection and treatment by mobile teams which should cover the highest possible percentage of the population at risk (ii) using specially trained personnel and (iii) absolute autonomy of the sleeping sickness services in technical, administrative and budgetary matters. The mobile teams used gland palpation and gland puncture for diagnosis, together with "atoxylisation" of each positive case. Jamot was a typical military man with great self-discipline, highly devoted and systematic. He started in the ex-Oubangi-Chari in 1917-1919 and after long opposition from his superiors in Paris he obtained in 1926 authorisation to establish a special service in Cameroon with the spectacular result that prevalence levels declined from up to 60% in 1919 to only 0.2-4.1% in 1930. Tragically an ambitious younger colleague of him had deliberately used overdoses of tryparsamide. The result was blindness of 700 people. Jamot received the blame for it and was dismissed from his service in 1931. He organised four more years of successful campaigns in French West Africa and returned embittered to France where he died in 1937 Jamot’s vertical approach for T.b. gambiensen control however had proven itself and the example was followed methodically by workers like Muraz, Richet, Labusquière and others. The British, Belgian and Portuguese services introduced it in Ghana, Nigeria, Cameroon, Congo DR and Angola. By the late sixties the overall percentage of new T.b. gambiense cases had fallen below 0.01% . Had initial hopes been directed towards eliminating the reservoir of infection, eradication was not achieved. Apparently there was a residual level of incidence, the "zéro épidémiologique" due either to diagnostic failures, drug resistance or perhaps the existence of an additional parasite reservoir in animal hosts.

Friedheim (1899-1989) medical pathologist and microbiologist searched for compounds that would not affect the optic nerve or brain parenchyma whilst retaining adequate trypanocidal properties. He was one of those rare scientists who personally carried out the chemical design, the laboratory evaluation as well as the clinical trials in the field. Melarsen oxide which he developed was very effective but still too toxic. Friedheim then had the paradoxical idea to blend melarsen oxide with the arsenicals antagonist British Anti- Lewisite (BAL), a substance developed during World War II against the arsenic gas lewisite. As expected BAL weakened indeed the trypanocidal properties considerably but more than that reduced its toxicity. The combined molecule melarsoprol, introduced in 1949 became, and still is, the most widely applied trypanocidal drug for the treatment of late stage human trypanosomiasis. It was the first effective drug for late stage T.b. rhodesiense disease.