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.
Highlights
Human African Trypanosomiasis (HAT) or sleeping sickness evolves in two stages, the first or early stage and the second or late stage which is characterized by invasion of the central nervous system (CNS) by trypanosomes
Cardiac involvement plays an important role in American trypanosomiasis (Chagas’ disease); in the African form, cardiac involvement has been suggested but has never been studied systematically in the first stage of the disease
Cardiac involvement has been observed in up to 73% of HAT patients in post mortem histological studies [2,3]. Those findings are supported by the recent study of Blum et al [4] that showed cardiac alterations in 71% of second stage HAT patients, but are in contrast to previous studies, where ECG findings were reported in only 35–48% of the patients [5,6,7]
Summary
Human African Trypanosomiasis (HAT) or sleeping sickness evolves in two stages, the first or early (hemo-lymphatic) stage and the second or late (meningo-encephalitic) stage which is characterized by invasion of the central nervous system (CNS) by trypanosomes. Cardiac involvement has been observed in up to 73% of HAT patients in post mortem histological studies [2,3] Those findings are supported by the recent study of Blum et al [4] that showed cardiac alterations in 71% of second stage HAT patients, but are in contrast to previous studies, where ECG findings were reported in only 35–48% of the patients [5,6,7]. The latter studies included both first and secondstage HAT patients. 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
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