Focus–Specific Clinical Profiles in Human African Trypanosomiasis Caused by Trypanosoma brucei rhodesiense.

Background: Diverse clinical features have been reported in human African trypanosomiasis (HAT) foci caused by Trypanosoma brucei rhodesiense (T.b.rhodesiense) giving rise to the hypothesis that HAT manifests as a chronic disease in South-East African countries and increased in virulence towards the North. Such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. Our molecular tools allow us to study the role of host and parasite genotypes, but obtaining matched extensive clinical data from a large cohort of HAT patients has previously proved problematic. Methods/Principal Findings: We present a retrospective cohort study providing detailed clinical profiles of 275 HAT patients recruited in two northern foci (Uganda) and one southern focus (Malawi) in East Africa. Characteristic clinical signs and symptoms of T.b.rhodesiense infection were recorded and the degree of neurological dysfunction determined on admission. Clinical observations were mapped by patient estimated post-infection time. We have identified common presenting symptoms in T.b.rhodesiense infection; however, marked differences in disease progression and severity were identified between foci. HAT was characterised as a chronic haemo-lymphatic stage infection in Malawi, and as an acute disease with marked neurological impairment in Uganda. Within Uganda, a more rapid progression to meningo-encephaltic stage of infection was observed in one focus (Soroti) where HAT was characterised by early onset neurodysfunction; however, severe neuropathology was more frequently observed in patients in a second focus (Tororo). Conclusions/Significance: We have established focus-specific HAT clinical phenotypes showing dramatic variations in disease severity and rate of stage progression both between northern and southern East African foci and between Ugandan foci. Understanding the contribution of host and parasite factors in causing such clinical diversity in T.b.rhodesiense HAT has much relevance for both improvement of disease management and the identification of new drug therapy. Author Summary: T. b. gambiense and T. b. rhodesiense cause human African trypanosomiasis (HAT). These parasite subspecies differ in their rate of progression to central nervous system (CNS) infection, and consequently to coma and death. Variation in disease progression and severity has also been documented between northern and southern East African T.b. rhodesiense HAT. However, it is unknown if this is caused by differences in patient susceptibility to infection, genetic variation in parasite virulence, or both, as despite the existence of good molecular tools, previous studies have involved limited numbers of HAT cases. In this paper we present extensive clinical data on T. b. rhodesiense cases and describe robust clinical profiles for three disease foci. Common presenting symptoms were identified. We also describe marked differences in disease progression and severity both between Ugandan and Malawi foci, and between two Ugandan foci (Tororo and Soroti) giving rise to three foci-specific clinical phenotypes ranging from a chronic haemo-lymphatic stage infection in Malawi, to rapid disease progression and neurological dysfunction in Soroti and severe neuropathology in Tororo cases. Most importantly, we have now established clinical focus-specific phenotypes that will be available to supplement host and parasite genetics studies to determine their contribution to HAT disease virulence. [ABSTRACT FROM AUTHOR]