Sleeping sickness, caused by Trypanosoma brucei spp., has become resurgent in sub-Saharan Africa. Moreover, there is an alarming increase in treatment failures with melarsoprol, the principal agent used against late-stage sleeping sickness. In T. brucei , the uptake of melarsoprol as well as diamidines is thought to be mediated by the P2 aminopurine transporter, and loss of P2 function has been implicated in resistance to these agents. The trypanosomal gene TbAT1 has been found to encode a P2-type transporter when expressed in yeast. Here we investigate the role of TbAT1 in drug uptake and drug resistance in T. brucei by genetic knockout of TbAT1. Tbat1 -null trypanosomes were deficient in P2-type adenosine transport and lacked adenosine-sensitive transport of pentamidine and melaminophenyl arsenicals. However, the null mutants were only slightly resistant to melaminophenyl arsenicals and pentamidine, while resistance to other diamidines such as diminazene was more pronounced. Nevertheless, the reduction in drug sensitivity might be of clinical significance, since mice infected with tbat1 -null trypanosomes could not be cured with 2 mg of melarsoprol/kg of body weight for four consecutive days, whereas mice infected with the parental line were all cured by using this protocol. Two additional pentamidine transporters, HAPT1 and LAPT1, were still present in the null mutant, and evidence is presented that HAPT1 may be responsible for the residual uptake of melaminophenyl arsenicals. High-level arsenical resistance therefore appears to involve the loss of more than one transporter.

Human African trypanosomiasis or ‘sleeping sickness’ is a neglected tropical disease caused by the parasite Trypanosoma brucei. A decade of intense international cooperation has brought the inciden...

Brucellosis remains a neglected zoonotic disease among agro-pastoral communities where unprocessed milk and milk products are consumed. A cross-sectional study was carried out in Kiboga district to determine the seroprevalence and risk factors associated with human brucellosis in communities where livestock rearing in a common practice. A total of 235 participants were involved in the study. Blood samples from the participants were collected and screened for Brucella using Serum Agglutination Test and Rose Bengal Plate Test. A questionnaire was used to collect data on socio-demographic characteristics and human brucellosis related risk factors. Human Brucella seroprevalence was at 17.0 % (n = 235). The prevalence was highest among males (20.5 %, n = 78) and the elderly - above 60 years (22.2 %, n = 18). Residence in rural areas (OR 3.16, 95 % CI: 1.16–8.56), consuming locally processed milk products (OR 2.54, 95 % CI: 1.12–5.78) and being single (OR 2.44, 95 % CI: 1.05–5.68), were associated with increased risk of brucellosis. Human brucellosis seroprevalence was high at 17 %, this was parallel with animal brucellosis prevalence that has been reported to range from 10.2 % to 25.7 % in cattle in the region. The participants were from communities known to habitually consume raw milk and milk products, know to process milk products using bare hands which are major risk factors for brucellosis in humans. This also explains why consumption of unpasteurized milk products was associated with the occurrence of brucellosis in study area. This strengthened the argument that humans get infected through consumption of contaminated animal products as reported in other earlier studies. Males and elderly being more affected because of traditional roles of these groups they play in livestock care and management. The single were also to be more associated to brucellosis, due to the fact that this group consume milk and milk products more as it is readily available in the informal markets as highly nutritious fast foods in this community as also observed in USA. Brucellosis is highly prevalent in Kiboga district, and therefore, an important public health problem. The transmission risk was aggravated by consumption of unpasteurized milk products, residing in rural settings and being single. There is a need to initiate screening, treat infected humans early, and educate the public about risk factors and appropriate preventive measures of brucellosis.