Electrocardiographic changes in African trypanosomiasis caused by Trypanosoma brucei rhodesiense

Jones, Ian G.; Lowenthal, M; Buyst, H

doi:10.1016/0035-9203(75)90194-7

Cited by 19 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Less is known in T.b. rhodesiense HAT, however, there is some evidence for ECG alterations during infection [54], histological examinations have shown myocardinal degeneration and interstitial haemorrhage [55], and infectious perimyocarditis can be more severe which can lead to a fatal outcome [55], [56]. Indeed, in some studies, cardiac involvement is thought to cause death before neurological deterioration manifests [40], [41].…”

Section: Discussionmentioning

confidence: 99%

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

MacLean

Odiit²,

Chisi

et al. 2010

PLoS Negl Trop Dis

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

MacLean

Odiit²,

Chisi

et al. 2010

PLoS Negl Trop Dis

View full text Add to dashboard Cite

show abstract

“…Gastrointestinal (nausea, vomiting, diarrhoea) and skin reactions (pruritus) are common; severe complications like exfoliative dermatitis occur in < 1% of cases (53). Cardiac failure is common during treatment and can be a frequent cause of death (152), but it is still unclear whether this is due to an adverse drug reaction or the well-known cardiac involvement of HAT itself (153)(154)(155). Other adverse reactions that have been reported occasionally are peripheral motor (palsy) or sensorial (paresthesia) neuropathy, renal dysfunction (proteinuria and hypertension) and hepatotoxicity (elevated liver enzymes, bilirubinaemia) (142).…”

Section: Second-stage Rhodesiense Human African Trypanosomiasis: Melamentioning

confidence: 99%

“…A major recent advance in the spatial analysis of HAT was the preparation of the Atlas of human African trypanosomiasis (153)(154)(155). This required extensive work with WHO Member States to obtain all potential data and to locate cases geographically, which was an essential initial step (156), and to present them spatially.…”

Section: Geographical Distribution and Population At Riskmentioning

confidence: 99%

6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

et al. 2015

View full text Add to dashboard Cite

From a whole-organism high throughput screen of approximately 87000 compounds against Trypanosoma brucei brucei, we recently identified eight new unique compounds for the treatment of human African trypanosomiasis. In an effort to understand the structure−activity relationships around these compounds, we report for the first time our results on a new class of trypanocides, the pyrazine carboxamides. Attracted by the low molecular weight (270 g•mol −1 ) of our starting hit (9) and its potency (0.49 μM), the SAR around the core was explored, leading to compounds having an EC 50 as low as 25 nM against T. b. brucei and being more than 1500 times less toxic against mammalian L6 and HEK293 cell lines. The most potent compounds in the series were exquisitely selective for T. brucei over a panel of other protozoan parasites, showing an excellent correlation with the human infective parasite Trypanosoma brucei rhodesiense, the most potent compound (65) having an EC 50 of 24 nM. The compounds are highly drug-like and are able to penetrate the CNS, their only limitation currently being their rate of microsomal metabolism. To that effect, efforts to identify potential metabolites of selected compounds are also reported.

show abstract

“…Compared to T.b. gambiense HAT, thyroid dysfunction, adrenal insufficiency and hypogonadism are more frequently found and myocarditis is more severe and may even be fatal [35][36][37]. Liver involvement with hepatomegaly is usually moderate, but jaundice, hyperbilirubinaemia, and ascites have been observed [38].…”

Section: Endemic Countriesmentioning

confidence: 99%