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Focus-specific clinical profiles in human African Trypanosomiasis caused by Trypanosoma brucei rhodesiense
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 4, Iss 12, p e906 (2010)
- Publication Year :
- 2010
-
Abstract
- 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.<br />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.
- Subjects :
- Male
Trypanosoma brucei rhodesiense
Malawi
Disease
Severity of Illness Index
Cohort Studies
0302 clinical medicine
African trypanosomiasis
Uganda
Child
Aged, 80 and over
0303 health sciences
Geography
lcsh:Public aspects of medicine
Meningoencephalitis
Middle Aged
3. Good health
Infectious Diseases
Child, Preschool
Disease Progression
Female
Cohort study
Research Article
Adult
Infectious Diseases/Epidemiology and Control of Infectious Diseases
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
030231 tropical medicine
Biology
03 medical and health sciences
Young Adult
parasitic diseases
medicine
Humans
030304 developmental biology
Aged
Retrospective Studies
Public Health, Environmental and Occupational Health
Infectious Diseases/Protozoal Infections
Infant
Retrospective cohort study
lcsh:RA1-1270
medicine.disease
biology.organism_classification
Trypanosomiasis, African
Infectious Diseases/Neglected Tropical Diseases
Immunology
Trypanosoma
Trypanosomiasis
Subjects
Details
- ISSN :
- 19352735
- Volume :
- 4
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS neglected tropical diseases
- Accession number :
- edsair.doi.dedup.....a48bfbc3f769ad30fc427be094e335cf