History of sleeping sickness in East Africa

Abstract

The history of human sleeping sickness in East Africa is characterized by the appearance of disease epidemics interspersed by long periods of endemicity. Despite the presence of the tsetse fly in large areas of East Africa, these epidemics tend to occur multiply in specific regions or foci rather than spreading over vast areas. Many theories have been proposed to explain this phenomenon, but recent molecular approaches and detailed analyses of epidemics have highlighted the stability of human-infective trypanosome strains within these foci. The new molecular data, taken alongside the history and biology of human sleeping sickness, are beginning to highlight the important factors involved in the generation of epidemics. Specific, human-infective trypanosome strains may be associated with each focus, which, in the presence of the right conditions, can be responsible for the generation of an epidemic. Changes in agricultural practice, favoring the presence of tsetse flies, and the important contribution of domestic animals as a reservoir for the parasite are key factors in the maintenance of such epidemics. This review examines the contribution of molecular and genetic data to our understanding of the epidemiology and history of human sleeping sickness in East Africa.

FIG. 1

Human sleeping sickness foci in East Africa (data are from references , , and and other specific reports detailed below. Specific details of epidemics and references are given for numbered foci. Focus 1, Busoga focus (Uganda and Kenya), epidemics, 1900 (18, 21), 1942 (82), 1953 to 1960 (107), and 1964, in Alego, Kenya, (4, 141); 1976 to 1983 (1, 46); and 1988 to 1992 in Tororo District (36, 38, 62, 63, 86). Focus 2, Lambwe Valley focus (Kenya), epidemics, 1960 (2, 8, 40, 137, 141) and 1980 (23, 46, 48, 88, 97). Focus 3, Gilo River focus (Ethiopia), epidemic, 1970 (7, 48, 68). Focus 4, Gambela focus (Ethiopia), epidemic, 1967 (7, 48, 68). Focus 5, Kasulu focus (Tanzania), epidemics, 1930s and 1957 to 1960 (4, 5, 74, 78). Focus 6, Tabora focus (Tanzania), epidemics, 1930s and 1957 to 1960 (4, 5, 74, 78). Focus 7, Rungwa River focus (Tanzania), epidemic, 1920 to 1921 (74, 77, 83). Focus 8, Maswa focus (Tanzania), epidemic, 1920 (29, 39). Focus 9, Matandu River focus (Tanzania), epidemic 1925 (96). Focus 10, North Luangwa Valley focus (Zambia), epidemic 1970 (20). Focus 11, South Luangwa Valley focus (Zambia), epidemic, 1970 (100). Focus 12, Kafue River focus (Zambia), epidemic, 1960 to 1968 (41). Focus 13, Okavango Swamp focus (Botswana), epidemics, 1939 to 1942 and 1957 to 1971 (28, 48, 96). Focus 14, South Malawi focus (Malawi and Mozambique), epidemic, 1912 (43, 96). Focus 15, West Nile (T. b. gambiense) focus (Uganda), epidemic, 1930 (30, 37). Focus 16, Southern Sudan, recent epidemic, 1997 onward (73).

FIG. 2

Relationship between human- and non-human-infective isolates collected during the 1988 to 1990 human sleeping sickness epidemic in the Tororo District of Uganda. A dendrogram depicts the results of a molecular fingerprinting approach based on RFLP analysis with repetitive DNA probes. The banding patterns generated by this molecular fingerprinting approach were compared in pairwise combinations, and a similarity matrix which records levels of similarities and differences in the presence and absence of bands between T. brucei isolates was constructed. The resulting matrix was analyzed by cluster analysis (58) and is depicted in the figure. The names (e.g., TIRA 44) refer to the name of the isolate. Strains identified as + either were isolated from humans or tested positive for human serum resistance (i.e., human-infective strains); strains identified as − were isolated from cattle and were sensitive to human serum (i.e., non-human-infective strains). Details of isolates can be found elsewhere (references to 64). The dendrogram shows that non-human-infective (T. b. brucei) and human-infective (T. b. rhodesiense) isolates, collected during the 1988 to 1990 epidemic in Tororo (Busoga focus), form clearly distinct groups. The strains responsible for human disease in the Luangwa Valley focus, Zambia, are quite unrelated. Human-infective strains from West Africa (T. b. gambiense) are included for comparison.

FIG. 3

Dynamics of transmission during the 1988 to 1990 human sleeping sickness epidemic in Tororo, Uganda. p1h and p1c are the probabilities of tsetse flies feeding on, respectively, humans or cattle (calculated from the analysis of tsetse fly blood means). p2h and p2c are the probabilities of either humans or cattle (respectively) being infected with human sleeping sickness trypanosomes. p2h is taken from the frequency of infected humans in the population (0.6%), and p2c is calculated from the frequency of T. brucei-infected cattle (5%) multiplied by the proportion of T. brucei which are human infective (23%). The product of p1 and p2 (p3) is the probability of a fly picking up human-infective parasites from either humans (p3h) or cattle (p3c). In this epidemic, a fly harboring human-infective trypanosomes is five times more likely (p3c = 0.0026) to have picked up that infection from domestic cattle than from an infected person (p3h = 0.0005).

FIG. 4

Map of the Busoga focus in Uganda and Kenya.