Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

Abstract

BackgroundIn Human African Trypanosomiasis, neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The aims of the study were to assess the frequency and characteristics of electrocardiographic findings in the first stage of HAT, to compare these findings to those of second stage patients and healthy controls and to assess any potential effects of different therapeutic antiparasitic compounds with respect to ECG changes after treatment.MethodsFour hundred and six patients with first stage HAT were recruited in the Democratic Republic of Congo, Angola and Sudan between 2002 and 2007 in a series of clinical trials comparing the efficacy and safety of the experimental treatment DB289 to the standard first stage treatment, pentamidine. These ECGs were compared to the ECGs of healthy volunteers (n = 61) and to those of second stage HAT patients (n = 56).ResultsIn first and second stage HAT, a prolonged QTc interval, repolarization changes and low voltage were significantly more frequent than in healthy controls. Treatment in first stage was associated with repolarization changes in both the DB289 and the pentamidine group to a similar extent. The QTc interval did not change during treatment.ConclusionsCardiac involvement in HAT, as demonstrated by ECG alterations, appears early in the evolution of the disease. The prolongation of the QTC interval comprises a risk of fatal arrhythmias if new drugs with an additional potential of QTC prolongation will be used. During treatment ECG abnormalities such as repolarization changes consistent with peri-myocarditis occur frequently and appear to be associated with the disease stage, but not with a specific drug.

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

“…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.…”

“…In the first application of this type, data from the Atlas were combined with spatially explicit population layers to generate current, evidence-based estimates of populations at risk (155). The risk was characterized into low, moderate and high, and the population in each category was quantified.…”

“…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).…”

Human African trypanosomiasis in endemic populations and travellers

“…gambiense HAT and increases to 70% in the second stage [18]. However, it rarely leads to relevant clinical heart failure [19,20].…”

Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke

“…Major ECG alterations have been found in more than half of HAT patients in the first stage and in approximately twothirds in the second stage [89]. A recent prospective case-control study analyzed the ECG data of first-and second-stage HAT patients compared with healthy controls [89].…”