title: Cardiac alterations in human African trypanosomiasis (T.b. gambiense) with respect to the disease stage and antiparasitic treatment.
abstract: BACKGROUND
  In 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.
  
  
  METHODS
  Four 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).
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Cardiac 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.
authors.affiliation: Swiss Tropical Institute, Basel, Switzerland.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Blum
authors.forename: Caecilia
authors.initials: C
authors.lastname: Schmid
authors.forename: Christian
authors.initials: C
authors.lastname: Burri
authors.forename: Christoph
authors.initials: C
authors.lastname: Hatz
authors.forename: Carol
authors.initials: C
authors.lastname: Olson
authors.forename: Blaise
authors.initials: B
authors.lastname: Fungula
authors.forename: Leon
authors.initials: L
authors.lastname: Kazumba
authors.forename: Patrick
authors.initials: P
authors.lastname: Mangoni
authors.forename: Florent
authors.initials: F
authors.lastname: Mbo
authors.forename: Kambau
authors.initials: K
authors.lastname: Deo
authors.forename: Alain
authors.initials: A
authors.lastname: Mpanya
authors.forename: Amadeo
authors.initials: A
authors.lastname: Dala
authors.forename: Jose R
authors.initials: JR
authors.lastname: Franco
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pohlig
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zellweger
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000209:etiology; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000209:etiology*; D006801:Humans; D008297:Male; D014344:Trypanocidal Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D014344:Trypanocidal Agents