Date Published: February 17, 2009
Publisher: Public Library of Science
Author(s): Johannes A. Blum, Caecilia Schmid, Christian Burri, Christoph Hatz, Carol Olson, Blaise Fungula, Leon Kazumba, Patrick Mangoni, Florent Mbo, Kambau Deo, Alain Mpanya, Amadeo Dala, Jose R. Franco, Gabriele Pohlig, Michael J. Zellweger, Marleen Boelaert
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.
Partial Text: 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. Neuropsychiatric disturbances are the most prominent and best documented features of the disease . Cardiac involvement plays an important role in American trypanosomiasis (Chagas’ disease); however, 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 ,. Those findings are supported by the recent study of Blum et al 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 –. The latter studies included both first and second-stage HAT patients. A low prevalence of ECG findings in first stage disease could explain this discrepancy. Thus, cardiac involvement, as documented by ECG findings, may parallel CNS involvement and ECG findings could be used as additional tool for assessing the advancement of the disease.
Patient baseline characteristics are summarized in Table 1. Age and gender distribution were similar among the disease stages, the HAT treatment groups and the healthy controls, respectively. Pyrimethamine-sulfadoxine (SP) was given as first line malaria treatment prior to HAT treatment in all centers with the exception of CNPP Kinshasa, where quinine was used as standard malaria treatment due to the high level of SP resistance in Kinshasa.
To our knowledge this is the first study comparing ECG data of first and second stage HAT patients and also healthy controls. This study comprises ECG recordings of 523 participants, the largest number of patients to date in a population with HAT.