African trypanosomiasis

African trypanosomiasis remains a serious health concern across large areas of sub-Saharan Africa, despite several decades of research. As well as causing sleeping sickness in humans, trypanosomes are responsible for significant disease in livestock. The combination of human and livestock disease makes these parasites a serious impediment to agricultural and economic advancement in the affected areas, an impact that combines with the obvious health concerns to create a problem that seriously impinges at several levels upon human wellbeing. Despite this seemingly pessimistic summary, significant strides have been made in our understanding of the interactions between the host and the parasite that drive disease and shape the course of infections. This volume will attempt to summarise recent significant findings, outlining the holistic way in which our understanding is progressing, encompassing human and livestock disease, disease determinants in both the host and the parasite, and the potential that is arising for novel therapeutics from the often neglected member of the lifecycle, the tsetse fly. Given the emerging drug resistance in both human and livestock licensed trypanocidal drugs and the fact that a vaccine is unlikely for African trypanosomes, understanding the disease process and the key host–parasite interactions that influence this is an obvious route by which novel interventions may be developed. An obvious first step in this process is to comprehend what occurs in the mammalian host when it is infected with trypanosomes. A crucial component that has contributed significantly to our knowledge of what influences the outcome of trypanosome infection has been the development over the decades of a multi-faceted rodent model of disease. Although not the ‘natural host’ of trypanosome infections, Stefan Magez and Guy Caljon (1) review key insights that the rodent model has enabled, and which would have been extremely difficult if not impossible without this tractable system. These include how the trypanosome interacts and is affected by both the humoral and innate immune responses, how human-infective trypanosomes are able to avoid lysis by human serum (which has the innate ability to kill all other species of African trypanosome – this work was first pioneered in the mouse), and the influence of tsetse saliva on the immune response at the bite site. Boniface Namangala (2) expands on these themes and outlines the impact of trypanosome infection upon lymphocyte responses. While the rodent model has undoubtedly hugely enriched our knowledge of immunopathogenesis in trypanosomiasis, complementary studies in natural hosts are a key component in confirming translation of any findings. Bruno Bucheton, Annette MacLeod and Vincent Jamonneau (3) describe recent data from sleeping sickness patients. These findings indicate that the classically described progression of Trypanosoma brucei gambiense infection leading through Stage 1 disease (haemolymphatic) to Stage 2 symptoms (neurological) and then death is too simplistic. They describe the diversity of disease presentation and progression observed, discuss the probability of ‘trypanotolerance’ (whereby the genetics of the host plays a role in susceptibility or otherwise to trypanosome infections, i.e., trypanotolerant hosts remain infected but do not display the serious clinical signs displayed by susceptible counterparts) in humans, and review what is currently known about possible host factors that may contribute to this. While a significant amount of research has much improved our understanding from the mammalian host’s perspective, a significant factor in disease pathology is obviously supplied by the parasite. Genetic variation in Correspondence: Annette MacLeod, Wellcome Trust Centre for Molecular Parasitology, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, 464 Bearsden Rd, Glasgow G61 1QH, UK (e-mail: [email protected]). Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen# OnlineOpen_Terms. Received: 12 May 2011 Accepted for publication: 13 May 2011 Parasite Immunology, 2011, 33, 421–422 DOI: 10.1111/j.1365-3024.2011.01302.x