Sir David Bruce's elucidation of the aetiology of nagana--exactly one hundred years ago.

Surgeon-Captain David Bruce (1855-1931) (ANONYMOUS, 1931a, 1931b, 1932; HAMERTON, 1932; J. R. B., 1932) was posted to Pietermaritzburg, Natal, South Africa, for military field service in 1894. At the time, cattle (and also horses) were dying in hundreds from a disease the origin(s) of which was obscure; the Zulus gave it the name nagana (MACARTHUR, 1955). As a result, the country was faced with ruin, and grave economic stress affected the indigenous stock-raisers and white settlers (TULLOCH, 1955). On the initiative of the Governor of Natal and High-Commissioner of Zululand. Sir Walter Hely-Hutchinion (who had lately served as ‘LieutenantGovernor of Malta whilst Bruce was solving the Malta [undulant] fever problem), Bruce was ordered to proceed on secondment from Natal to Zululand in an attempt to discern the aetiology of this mysterious disease; nagana and (tsetse) fly disease of travellers and hunters were, at that time, considered separate entities (BRUCE, 1915; ANONYMOUS, 1932, J. R. B., 1932). The inhabitants of this region of Africa had been seriously bothered by the disease for at least a century (SIKGER & UNDERWOOD, 1962), and perhaps since 1742 (ANONYMOUS, 1931a). David Livingstone (1813-1873) was familiar with it on the banks of the Zambesi in 1847 (LIVINGSTONE, 1858; COOK, 1994); he described the disease in 1847 (LIVINGSTONE, 1857) and produced an accurate diagram of Glossina morsitans. Many local residents (some of them of European origin) were of the opinion that it was caused by the bite of the tsetse fly (which elaborated a poison within itself) (BRUCE, 1915; ANONYMOUS, 1931a; MACARTHUR, 1955), death of the animal following some 10 d after this event. An alternative theory (apparently held by most Zulus) was that game animals harboured the disease, and that it was transmitted to cattle by food and water contaminated by them-perhaps faecally (MACARTHUR, 1955). [We now know that b&h theories possessed an eiemen<of truth (ROBERTSON. 1955).1 Livingstone was fullv convinced that the disease did ‘nbt affectman; he and hk party lived in a heavily infected area for 2 months without ill effect. This strongly suggests that human strains of Typanosoma b&i [sic] (now T. brucei) were not at that time present in this part of Africa. Bruce and his wife Mary (herself a brilliant laboratory worker) (TULLOCH, 1955), set off on a long trek to Ubombo Hill (650 m [2000 feet] above sea level) in northern Zululand, by mule and ox wagon, to take up their challenge on 27 October 1894 (BRUCE, 1915). However, from notes written at Pietermaritzburg before they set off, it is clear that Bruce was already intellectually involved in the problem, for he made an attempt to infect animals by injecting into them watery and alcoholic tsetse fly extracts. Following his work which unravelled the cause of Malta (undulant) fever, Bruce felt that a bacterium was the most likely candidate. Furthermore, he had spent the year 1888 in Robert Koch’s institution in Berlin-‘a Mecca for budding bacteriologists’ (J. R. B., 1932; VELLA, 1973). At Ubombo Hill, where they arrived on 24 November 1894, the Brutes took over a wattle and daub hut (Fig. 1) which had belonged to a ‘squatter’ married to a ?uiu woman (MACARTHUR, 1955; TOUBERT et al., 1993). His work beean bv undertaking daily blood examinaiions (includini cell-counts) on ‘; ‘brown cow’. Each examination revealed micrococci and slender poorly-staining bacilli; however, on rhe sixth day he recorded in his notes: ‘also Haematozoa’ (MACARTHUR, 1955). Bruce had very little knowledge of trypanosomes and ‘at first thought that the wriggling object might possibly be a small filaria’ (BRUCE, 1915). The observation was repeated on a ‘black and white cow’. Healthy calves were shown to develop nagana when taken down to the low country (ROBERTSON, 1955); their blood also contained ‘Haematozoa’-in one case numbering 10 000 per mm3. Whilst in the low country, 2 of the Bruce? dogs-pointers-were bitten by tsetse flies; shortly after return to the hill, both developed acute, fatal nagana with ‘Haematozoa’ in their blood; one of them, ‘John Keats’, apparently had 4 organisms (‘wriggling about like little snakes’) per erythrocyte. When the splenic pulp and blood of this dog were cultured, they were shown to be bacteriologically sterile. Bruce also examined large numbers of healthy cattle, and noted that ‘Haematozoa’ were invariably absent. Within 2 months, and probably a mere 5-6 weeks (TULLOCH, 1955) of his arrival in Zululand, Bruce seems to have clearly established a positive correlation between nagana and blood ‘Haematozoa’, and furthermore that the ‘organism’ was responsible for both nagana and tsetse -fly disease JANONYMOUS, 1932: HAMERTON. 1932: ROBERTSON. i955; TULLO~H, 1955; VELLA, 1973). Heiecorded these observations in his Preliminary Report on the Tsetse Fly Disease or Nagana, in Zululand (BRUCE, 1895); this was later expanded in the Further Report on the Tsetse Fly Disease or Nagana, in Zululand (BRUCE,, 1896). Later! in 1915, he described this work in considerable detail m 4 Croonian lectures delivered to the Royal College of Physicians (BRUCE, 1915). At this exciting point in the saga, Bruce was recalled, on 26 Tanuarv 1895. to Natal (BRUCE. 1915: MACARTHUR, i955);howev&, on reaching Pie;ermaritzburg he discovered that there had been no compelling reason for this order. Following communications between the Governor and the War Office (who were seemingly pretty uncooperative), the Brutes were able to return to Ubombo on 8 September 1895; when they arrived, 7 months had, however, been wasted. Bruce was by this time fully convinced that ‘Haematozoa’ were causatively related to nagana, but this had to be confirmed scientifically. Therefore, he infected healthy animals by inoculating blood of diseased ones. A minor set back came when a dog fed on coagulated, infected blood developed na-