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

Abstract

BackgroundDiverse 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 FindingsWe 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/SignificanceWe 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.

Human African trypanosomiasis in endemic populations and travellers

“…The black line divides the endemic regions of T. b. gambiense and T.b. rhodesiense HAT (61%) and somnolence (58%) dominated in other foci [27]. In the second stage, fever has less frequently been observed in most studies (14-37%) [27,29,30,33], and fever is only moderate, rarely (4-9%) exceeding 38.4°C [33].…”

“…rhodesiense HAT (61%) and somnolence (58%) dominated in other foci [27]. In the second stage, fever has less frequently been observed in most studies (14-37%) [27,29,30,33], and fever is only moderate, rarely (4-9%) exceeding 38.4°C [33]. Pruritus, sleeping disorders, reduced consciousness, or neurological signs and symptoms such as tremor, abnormal movements or walking disabilities may predominate in some foci.…”

“…rhodesiense HAT is classically described as an acute disease progressing to second stage within a few weeks and death within 6 months [26]. The clinical presentation is similar, but trypanosomal chancres are more frequently seen (5-26%) [27][28][29][30][31], the localisation of enlarged lymph nodes is rather submandibular, axillary and inguinal than nuchal, and oedemas are more frequently observed [28,32]. However, recent descriptions of the clinical presentation show a high variability in different foci [27,33], possibly due to different strains [34].…”

Capacity and Policy Change in Managing Human African Trypanosomiasis in Endemic Rural Districts of Eastern Zambia

“…Unfortunately, as indicated on the similarity in clinical symptoms of HAT with febrile diseases, detection of HAT in its early stage is not easily achievable in rural settings of Africa [11,12]. Increase in rapid diagnostic tests has made microscopy redundant hence eliminating the opportunity of making incidental diagnoses.…”

Development and evaluation of lateral flow test for the detection of trypanosomes in tsetse flies

“…Also the HAT cases caused by T.b. rhodesiense in Malawi are subacute as most people infected present themselves passively to district hospitals mostly in second stage of the disease (MacLean et al, 2010). The case fatality rates are very high due to this fact (Chisi et al, 2011).…”