Human African trypanosomiasis

The history of sleeping sickness

Scientific missions

In 1899 Mott published his classic paper on the histopathology of the brain from autopsies done on two Congolese patients shipped to Manson in London for observation and treatment. He described infiltrations of mononuclears in the perivascular space of the brain vessels including large abnormal plasma cells later known as the "morula cells of Mott". At that time the cause of the disease was unknown. It would take another four years before Sleeping Sickness became known as due to an infection with trypanosomes.

The first time that a trypanosome infection was found in man was by Forde in the Gambia in 1901. He found parasites in the blood of a European suffering from recurrent fevers. Dutton identified them a few months later as trypanosomes. In his publication in 1902 Dutton proposed as species name Trypanosoma gambiense. Until then trypanosomes had been reported to occur in trout’s (Valentin, 1841) and frogs (Gluge, 1842) and Gruby defined the genus as "Trypanosoma" in 1843.

Between 1900 and 1915 Portuguese, British, French, German and Belgian scientific teams were sent out to Africa. They were to investigate the cause, the spread of the disease and the severity of the problem in the respective colonies. From then onwards sleeping sickness became part of the domains of biological and medical science.1

In 1902, a year after the finding of trypanosomes in human blood, Dutton and Todd, from the Liverpool School, were sent to Senegambia to further investigate trypanosome infections. They used a haematocrit centrifugation technique for the detection of trypanosomes in the blood that was essentially similar as the one in current use.2 The patients they had found infected (seven out of one thousand) seemed to suffer from fever and only minor symptoms. “Trypanosoma fever" as it was called was considered to be "a mild tropical infection". The link with sleeping sickness remained to be made.

The Royal Society in London sent a Sleeping Sickness Commission to East Africa in 1902. The group consisted of Christy, epidemiologist, Low, clinician and Castellani, an Italian bacteriologist. They travelled from Mombassa to Kisumu by train from where Christy continued the journey to Entebbe on foot. Christy's distribution maps for Sleeping Sickness and filariasis showed that SS occurred only not far from the Lake Victoria and filariasis was found everywhere.

Castellani initially suspected a streptococcus as the cause of the disease. He adopted in 1903 a new method for cerebrospinal fluid (CSF) examination by centrifugation of 10 ml and then examining the deposit. Using this technique he found trypanosomes in the CSF and reported 20 positive results out of 34 sleeping sickness patients. Probably encouraged by Bruce who had joined the Royal SS Commission to Uganda later in 1903, Castellani proposed trypanosomes as causative organism of Sleeping Sickness. On the basis of supposed morphological differences with Dutton's T. gambiense, Castellani, proposed that on morpholical grounds that the trypanosomes he had seen were different than T .gambiense and proposed the name T. ugandensis.

Bruce had in 1895 in Zululand identified T. brucei as the cause of cattle trypanosomiasis (nagana) and tsetse (G.morsitans) as the vector. Bruce and colleagues pursued Castellani's hypothesis. On the basis of detailed morphological examinations concluded that the trypanosomes of Uganda and T.gambiense were identical. Sleeping sickness and "Trypanosoma fever" had been brought together as one and the same disease.

Finally it was Bruce and his colleagues who in 1903 provided conclusive evidence that sleeping sickness was transmitted via Glossina palpalis, (now G. fuscipes).

Kleine in German East Africa demonstrated in 1909 that T.b. brucei during their passage in the fly, go through a cycle of development before becoming infective. Kleine took part in the German research mission initially under Robert Koch. Koch had a strong suspicion that crocodiles acted as reservoir hosts for the human pathogenic trypanosomes and that the polymorphism of the parasite represented "male and female" trypanosomes.

In 1905 Thomas in Liverpool had discovered the trypanocidal properties of atoxyl, an organic arsenical developed by Béchamp in 1863 for anaemia and skin diseases. Thomas considered it safe for use in sleeping sickness after having injected himself with high doses intravenously. That same year, Koch in Tanzania and Kopke from Lisbon started using it in patients. It appeared effective against parasitaemia but results against central nervous system infections were unpredictable. Treatment courses of one to two years were needed and toxic side effects on the optic nerve occurred. Nevertheless it meant a great relief at least for 30% of the patients and a valuable tool for reducing man-to-man transmission. Fifteen years later in 1919 Jacobs and Heidelberger of the Rockefeller University discovered tryparsamide a considerably less toxic and more effective compound.

From the discovery of a trypanosome infection in man in 1901 until the introduction of an anti-trypanosomal drug in 1905 were only four years of research on sleeping sickness. No doubt a remarkably productive four years when the cause was found, the vector identified and the first trypanocidal drug had become available.

1The six most significant missions in chronological order were: Angola by Bettencourt et al (1901-02) , Uganda Royal Society of London by Low/Christy/Castellani/Bruce (1902-03), Congo King Leopold II sent Dutton/Todd/Christy (1903-05), French Congo Service de Santé militaire by Martin/Leboeuf/Roubeaud (1906-08), German East Africa by Koch/Kleine/Beck (1906-07)..

2Later, during their survey in the Congo Dutton decided to use gland punctures instead because the latter technique was easier and faster. As a result the more sensitive haematocrit centrifugation was abolished and remained forgotten for almost sixty years.