African animal trypanosomiasis (AAT) affects the livestock of 12.3 million Somalis and constrains their development and wellbeing. There is missing data on AAT in the country after the civil war of the 1990s. Therefore, this study has aimed to assess the prevalence of Trypanosoma spp. in 614 blood samples from cattle (n = 202), goats (n = 206) and sheep (n = 206) in Afgoye and Jowhar districts, Somalia using parasitological and molecular methods. Twenty-one out of 614 (3.4%; 95% CI: 2.1–5.2%) and 101/614 (16.4%; 95% CI: 13.6–19.6%) ruminants were positive for Trypanosoma spp. by buffy coat technique (BCT) and internal transcribed spacer 1 (ITS1)-polymerase chain reaction (PCR), respectively. Using ITS1-PCR, the highest prevalence was observed in cattle (23.8%; 95% CI: 18.4–30.1%) followed by goats (17.5%; 95% CI: 12.9–23.3%) and sheep (8.3%; 95% CI: 5.1–12.9%). A total of 74/101 (73.3%; 95% CI: 63.5–81.6%) ruminants were shown coinfection with at least two Trypanosome species. The four T. brucei-positive samples have tested negative for T. b. rhodesiense, by the human-serum-resistance-associated-PCR. Trypanosoma evansi, T. godfreyi, T. vivax, T. brucei, T. simiae and T. congolense were the Trypanosoma species found in this study. This is the first study on the molecular detection of Trypanosoma sp. in ruminants in Somalia. Further investigations and control measures are needed to manage Trypanosomiasis spreading in the country. Studies should also focus on the detection of T. b. rhodesiense in the country.

The period 1875–1925 was remarkable in the history of parasitology mainly for the elucidation of the life cycles of parasites causing important parasitic diseases and the incrimination of vectors in their transmission. These discoveries were made by a small number of scientists working in the tropics a number of whom were Scots. Sir Patrick Manson, the discoverer of the mosquito transmission of filarial worms, was instrumental in directly or indirectly encouraging other Scots including Douglas Argyll-Robertson, David Blacklock, David Bruce, David Cunningham, Robert Leiper, William Leishman, George Low, Muriel Robertson and Ronald Ross, who all made significant discoveries across a wide spectrum of tropical diseases. Among these, William Leishman, Robert Leiper and Muriel Robertson were all graduates of the University of Glasgow and their achievements in the fields of leishmaniasis, schistosomiasis, dracunculiasis and African sleeping sickness, together with subsequent developments in these fields, are the subjects of the ten papers in this Special Issue of Parasitology.

The period 1875–1925 was remarkable in the history of parasitology partly because of the number of significant discoveries made, especially the elucidation of important life cycles, and partly because of the achievements of the clinicians and scientists who made these discoveries. What is remarkable is that so many of these individuals were Scots. Preeminent in this pantheon was Patrick Manson, who not only discovered the mosquito transmission of filarial worms but was instrumental in directly encouraging others to make significant discoveries in the fields of malaria, Guinea worm disease (dracunculiasis), onchocerciasis, loiasis and schistosomiasis and, indirectly, sleeping sickness and leishmaniasis. This chapter describes and discusses the contributions made by Douglas Argyll-Robertson, Donald Blacklock, David Bruce, David Cunningham, Robert Leiper, William Leishman, George Low, Patrick Manson, Muriel Robertson and Ronald Ross together with short biographical notes.

Trypanosomiasis is caused by Trypanosoma species which affect both human and animal populations and pose a major threat to developing countries. The incidence of animal trypanosomiasis is on the rise. Surra is a type of animal trypanosomiasis, caused by Trypanosoma evansi, and has been included in priority list B of significant diseases by the World Organization of Animal Health (OIE). Control of surra has been a challenge due to the lack of effective drugs and vaccines and emergence of resistance towards existing drugs. Our laboratory has previously implicated Heat shock protein 90 (Hsp90) from protozoan parasites as a potential drug target and successfully demonstrated efficacy of an Hsp90 inhibitor in cell culture as well as a pre-clinical mouse model of trypanosomiasis. This article explores the role of Hsp90 in the Trypanosoma life cycle and its potential as a drug target. It appears plausible that the repertoire of Hsp90 inhibitors available in academia and industry may have value for treatment of surra and other animal trypanosomiasis.

The aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3′-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase) in vitro by using mice experimentally infected with Trypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In the in vivo trials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg−1) and pentostatin (2 mg kg−1) was 100% effective in the T. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3′-deoxyadenosine with deoxycoformycin has a curative effect on mice infected with T. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.

The paper examines the possible contributions to be made by Geographic Information Systems (GIS) to studies on human and animal trypanosomiasis in Africa. The epidemiological characteristics of trypanosomiasis are reviewed in the light of the formula for the basic reproductive rate or number of vector-borne diseases. The paper then describes how important biological characteristics of the vectors of trypanosomiasis in West Africa may be monitored using data from the NOAA series of meteorological satellites. This will lead to an understanding of the spatial distribution of both vectors and disease. An alternative, statistical approach to understanding the spatial distribution of tsetse, based on linear discriminant analysis, is illustrated with the example of Glossina morsitans in Zimbabwe, Kenya and Tanzania. In the case of Zimbabwe, a single climatic variable, the maximum of the mean monthly temperature, correctly predicts the pre-rinderpest distribution of tsetse over 82% of the country; additional climatic and vegetation variables do not improve considerably on this figure. In the cases of Kenya and Tanzania, however, another variable, the maximum of the mean monthly Normalized Difference Vegetation Index, is the single most important variable, giving correct predictions over 69 % of the area; the other climatic and vegetation variables improve this to 82 % overall. Such statistical analyses can guide field work towards the correct biological interpretation of the distributional limits of vectors and may also be used to make predictions about the impact of global change on vector ranges. Examples are given of the areas of Zimbabwe which would become climatically suitable for tsetse given mean temperature increases of 1, 2 and 3 °Centigrade. Five possible causes for sleeping sickness outbreaks are given, illustrated by the analysis of field data or from the output of mathematical models. One cause is abiotic (variation in rainfall), three are biotic (variation in vectorial potential, host immunity, or parasite virulence) and one is historical (the impact of explorers, colonizers and dictators). The implications for disease monitoring, in order to anticipate sleeping sickness outbreaks, are briefly discussed. It is concluded that present data are inadequate to distinguish between these hypotheses. The idea that sleeping sickness outbreaks are periodic (i.e. cyclical) is only barely supported by hard data. Hence it is even difficult to conclude whether the major cause of sleeping sickness outbreaks is biotic (which, in model situations, tends to produce cyclical epidemics) or abiotic. The conclusions emphasize that until we understand more about the variation in space and time of tsetse and trypanosomiasis distribution and abundance we shall not be in a position to benefit from the advances made by GIS. The potential is there, however, to re-introduce the spatial and temporal elements into epidemiological studies that are currently often neglected.

Objective. Glycogen synthase kinase 3 (GSK-3) is a promising target for the treatment of various human diseases such as type 2 diabetes, Alzheimer's disease and inflammation. Successful inhibition of the homologues of this kinase in Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani makes the kinase an attractive target for the treatment of malaria, trypanosomiasis and leishmaniasis, respectively. The aim of this work was to compare the binding sites of the GSK-3 kinases of different parasites and to analyse them as possible targets for therapeutic compounds. Methods. Both a sequence alignment and homology models of the structure of 21 different GSK-3 homologues belonging to mammals, insects, pathogenic fungi, nematodes, trematodes and protozoa have been analysed, 17 of them being studied for the first time. Results. The structure of the kinases and, in particular, their binding sites, were found to be rather conserved, possessing small insertions or deletions and conserved amino acid substitutions. Nevertheless, the kinases of most species of parasite did have some amino acid differences from the human kinase, which could be exploited for the design of selective drugs. Conclusion. Comparison of the human and parasite GSK-3 ATP binding site models has shown that the development of selective drugs affecting parasite GSK-3 is possible. Known inhibitors of human GSK-3 can also be used as starting scaffolds for the search for drugs acting against parasitic diseases.

African sleeping sickness is a parasitic disease transmitted through the bites of tsetse flies of the genus Glossina. We constructed mechanistic models for the basic reproduction number, R0, of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively the causative agents of West and East African human sleeping sickness. We present global sensitivity analyses of these models that rank the importance of the biological parameters that may explain variation in R0, using parameter ranges based on literature, field data and expertize out of Uganda. For West African sleeping sickness, our results indicate that the proportion of bloodmeals taken from humans by Glossina fuscipes fuscipes is the most important factor, suggesting that differences in the exposure of humans to tsetse are fundamental to the distribution of T. b. gambiense. The second ranked parameter for T. b. gambiense and the highest ranked for T. b. rhodesiense was the proportion of Glossina refractory to infection. This finding underlines the possible implications of recent work showing that nutritionally stressed tsetse are more susceptible to trypanosome infection, and provides broad support for control strategies in development that are aimed at increasing refractoriness in tsetse flies. We note though that for T. b. rhodesiense the population parameters for tsetse – species composition, survival and abundance – were ranked almost as highly as the proportion refractory, and that the model assumed regular treatment of livestock with trypanocides as an established practice in the areas of Uganda experiencing East African sleeping sickness.

For over 50 years it has been known that there are considerable differences in the severity and rate of progression of both Trypanosoma brucei rhodesiense and T. b. gambiense infection between individuals. Yet research into the factors, whether parasite or host, which control virulence in Human African trypanosomiasis is in its infancy. In this paper we review the clinical evidence for virulence variation and the epidemiological and experimental data that give clues as to the mechanisms involved. Evidence will be presented for both asymptomatic forms of T. b. gambiense infection and low virulence forms of T. b. rhodesiense infection in humans. While in both cases the mechanisms remain to be elucidated, the overall infection virulence phenotype is determined by both parasite and host genotype.

Anti-trypanosomiasis vaccination still remains the best theoretical option in the fight against a disease that is continuously hovering between its wildlife reservoir and its reservoir in man and livestock. While antigentic variation of the parasite surface coat has been considered the major obstacle in the development of a functional vaccine, recent research into the biology of B cells has indicated that the problems might go further than that. This paper reviews past and current attempts to design both anti-trypanosome vaccines, as well as vaccines directed towards the inhibition of infection-associated pathology.

An incomplete ring of electric nets was placed around oxen which were either uninfected, infected with Trypanosoma vivax, or infected with T. congolense. The numbers of fed and unfed Glossina pallidipes caught on the nets were used to estimate the attractiveness of the oxen to tsetse, and the feeding success of the tsetse on the oxen. Oxen infected with T. congolense attracted more G. pallidipes than the other groups of oxen. Taking into consideration daily variation in the abundance or activity of the flies, oxen infected with T. congolense were about 70% more attractive to G. pallidipes than were uninfected oxen or oxen infected with T. vivax. The latter two groups mostly attracted high numbers of G. pallidipes on days when the flies were especially abundant or active. The feeding success of G. pallidipes declined with increase in the rate at which oxen made anti-fly movements. Taking this movement rate into consideration, the feeding success of G. pallidipes on oxen infected with T. congolense was approximately 60% greater than on uninfected oxen or oxen infected with T. vivax. It is suggested that vasodilation induced by T. congolense may account for the difference in feeding success. The level of parasitaemia of T. congolense or T. vivax was not found to affect either the attractiveness of oxen or the feeding success on oxen. There was significant daily variation in the mean fat content of male G. pallidipes caught around the oxen but no effect of mean daily fat content on the proportion of males that fed. The mean haematin content of fed male G. pallidipes was positively correlated with the packed cell volume of the ox on which they fed.

Maintaining the puparial stage of successive generations of a population of tsetse 3 °C lower than normal reduced the numbers of rickettsia-like organisms (RLO) carried by emerging flies. The susceptibility of these flies to midgut infection with Trypanosoma congolense was also significantly reduced compared with control flies held at normal temperature. These results support the view that the relationship between RLO and susceptibility is quantitative – teneral flies with heavier RLO infections being more susceptible to trypanosome infection.

Rickettsia-like organisms (RLO) from tsetse midguts and mosquito cell cultures showed high levels of endochitinase activity. A line of Glossina morsitans morsitans highly susceptible to midgut trypanosome infection and with high incidence of RLO infection showed significantly greater chitinolytic activity than G. austeni which had low RLO incidence and were correspondingly refractory to midgut infection. Midgut infection rates of Trypanosoma brucei rhodesiense in G. m. morsitans showed a dose-related increase when flies were fed N-acetyl-D-glucosamine (GlcNAc) in the infective meal and for 4 subsequent days. A model is proposed for susceptibility to trypanosome infection based on the generation of GlcNAc by RLO endochitinase activity in tsetse pupae inhibiting midgut lectin in teneral flies.

The immune status of a host infected with Trypanosoma spp. or Leishmania spp. can play an important role in successful chemotherapy. In animal models, treatment of African trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. An intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. Similarly, an efficient cell-mediated immune response is required for maximal efficacy of pentavalent antimonials in the treatment of leishmaniasis. However, the potential relationship between parasite-induced or acquired immunosuppression and effective chemotherapy has been poorly studied. Macrophages which have been activated by bacterial cell wall components or gamma-interferon are known to display increased activity against Leishmania donovani or Trypanosoma cruzi. In experimental and clinical visceral leishmaniasis, use of macrophage activators together with pentavalent antimonials has lowered the dose of antimony required to cure the infection.

Efficient, cyclical transmission of trypanosomes through tsetse flies is central to maintenance of human sleeping sickness and nagana across sub-Saharan Africa. Infection rates in tsetse are normally very low as most parasites ingested with the fly bloodmeal die in the fly gut, displaying the characteristics of apoptotic cells. Here we show that a range of antioxidants (glutathione, cysteine, N-acetyl-cysteine, ascorbic acid and uric acid), when added to the insect bloodmeal, can dramatically inhibit cell death of Trypanosoma brucei brucei in tsetse. Both L- and D-cysteine invoked similar effects suggesting that inhibition of trypanosome death is not dependent on protein synthesis. The present work suggests that antioxidants reduce the midgut environment protecting trypanosomes from cell death induced by reactive oxygen species.

A feeding system, draught cows, disease/work interactions and animal power introduction in a farming system, four areas of recent research on draught ruminants which are important to future development of animal power, are reviewed. A new feeding system for draught animals is described which enables food requirements and the effects of work on live weight and milk production to be calculated.

Recent data on the energy cost of walking are appraised. Research on working cows, mainly in Ethiopia, has shown that undernutrition has a greater effect on milk yield than work, which has a transient effect. The length of the post-partum anoestrous period increases with decrease in body condition. Body-weight loss increases with increasing work load. It is suggested that dairy cows delay conception by 1 day for every day of work done. Work has little effect on food intake or digestive parameters. Although it is associated with an overall increase in food intake of cows, even of un-supplemented forage diets, the increase is not sufficient to meet all the extra energy needs for work. Food intake of both working and non-working cows increases during lactation.

Disease limits the working capacity of draught animals and work can exacerbate disease. These effects were investigated using Trypanosoma evansi in Indonesia and T. congolense in The Gambia. In both studies, infected animals were able to do much less work than non-infected ones and the severity of the effect depended greatly on the strain of trypanosome used. In general, increasing the plane of nutrition did not ameliorate the effects of the disease, nor in the Gambian study did it prevent loss of appetite in infected animals.

The technical and agronomic innovations necessary for the introduction of animal power into an inland valley region of central Nigeria are described and some of the sociological implications discussed.

Thirty-two N'Dama bulls aged 3 to 4 years were used to study the interactions between work, trypanosomosis and nutrition. The bulls were randomly allocated to two treatments, working (W) and non-working (N). Half in each treatment were placed on an andropogon hay basal diet (B), the other half on a better quality groundnut hay diet (H). Five days a week, four pairs of animals in the BW group and and four pairs in the HW group pulled weighted sledges four times around a 2056-m track. Loads were set to ensure energy expenditure was equivalent to 1·4 times maintenance. After 4 weeks all 32 bulls were injected intradermally with 104 Trypanosoma congolense organisms. The trial continued for a further 8 weeks.

Trypanosome infection caused a significant (P < 0·001) decline in packed cell volume (PCV), and the anaemia was more severe (P < 0·05) in working animals; three pairs in the HW group and two pairs in the BW group were withdrawn because PCV fell below 17%. Diet had no effect on PCV or parasitaemia. Infection caused a decline in food intake (P < 0·001) but with significant interactions between diet and work. Intake patterns were similar in the BN and BW groups whilst the HW animals consumed significantly more groundnut hay compared with the HN group (P < 0·01). However, nutrition had no significant effect on lap times or the team's ability to work under trypanosomosis challenge. Post-infection, diet was the dominant factor determining weight change, HN and HW animals weighed significantly more than BN and BW animals (P < 0·01) and the interaction between period, diet and work demonstrated that BWhad the lowest weights in the latter stages of the trial (P < 0·05).

The results suggest that supplementation with better quality forages confers no benefit to an animal infected with trypanosomes. Nor can trypanotolerant cattle sustain long periods of work if subiected to a primary challenge of trypanosomes.

The effect of growth retardation, resulting from feed restriction for a prolonged period, on the course of infection with Trypanosoma vivax was studied. Twelve male castrated West Africa Dwarf goats were subjected to a restricted feeding reghen of 55 g pelleted lucerne (Medicago safiva)/kg body weight0·75 per d for on average 17 weeks. Twelve other animals were fed on pelleted lucerne ad libitum, resulting in a normal growth pattern. After this period, all animals were fed on pelleted lucerne ad libitum, and six animatn of each previous feeding regimen treatment were infected with Trypanosoma viva. The other animals served as controls. In week 2 and 4 post infection (pi) energy and N balaoces were measured. In the week before infection and daring infection blood biochemical and clinlcal variables were measured. At 2 weeks before, and 4 weeks after infection, a liver biopsy was taken for measurement of triacylglycerol. Iofection caused intermittent fever and anaemia. The first peak of fever persisted longer in iofected anlmaln with normal growth than in infected animals with retarded growth. Gross energy and metabolizable energy intake, and energy retention were reduced ininfected animals. Metabolizable energy requirements for mainteoaoce were increased by infection. Plasma non-esterified fatty acids (NEFA) and glucose concentratioos were increased in infected animals, whereas serum triiodothyronine and thyroxine coocentratioos were decreased.Plasma urea concentration and liver triacylglycerol were uoaffected. No interaction of growth retardation with infection with respect to blood biochemical variables was found, apart from plasma NEFA in week 2 pi. N retention was not significantly affected by treatments. In conclusion, minor indications were found for an interaction between growth retardation, as applied in the present study, and trypaommiasis infection in West Africao Dwarf goats with respect to energy and N metabolism.

The influence of types of roughage, barley straw (diet B) versus lucerne hay (diet L), on the patho-physiology of a T. congolense infection was compared in eight pairs of Scottish Blackface male twin lambs. One animal of each twin pair was infected and the other used as a pair-fed control. Voluntary food intake, body weight, digestive function, various blood haematological and biochemical measurements were made.

Voluntary organic matter intake decreased significantly after the T. congolense infection, the decrease being greater in the diet L group than in the diet B group lambs (P < 0·01). The apparent digestibility coefficients of crude protein and organic matter were significantly lower in the infected lambs (P < 0·01). Mean retention time of the roughage through the digestive tract in the animals given barley straw was significantly longer (P < 0·05) due to a lower rumen outflow rate constant (P < 0·01). Infection resulted in longer mean retention times (P < 0·01).

Packed cell volume (PCV) was significantly lower before infection in the animals given diet B (P < 0·01). After infection, diet (P < 0·01) and infection (P < 0·01) had an additive effect on PCV. The anaemia was both macrocytic (P < 0·05) and hypochromic (P < 0·01).

Diet B resulted in higher plasma cholesterol (P < 0·05), but lower plasma urea (P < 0·01) and albumin (P < 0·01) concentrations before infection than diet L. The T. congolense infection significantly lowered plasma cholesterol (P < 0·01) and increased plasma urea (P < 0·01) concentrations compared with the uninfected controls. Plasma albumin concentrations decreased, but were more affected by nutrition (P < 0·01) than by infection (P < 0·05).

It ivas concluded that the patho-physiological effects of the T. congolense infection in the Scottish Blackface lambs were affected by the type of roughage offered, but that these effects were additive rather than interactive to the effects of infection.