Early antiparasitic treatment prevents progression of Chagas disease: Results of a long-term cardiological follow-up study in a pediatric population

Background Chagas disease (CD), a parasitic disease caused by Trypanosoma cruzi . Parasite persistence is crucial in the development and progression of Chagas cardiomyopathy that occurs in 30% of untreated patients. Methods and findings A cohort of 95 CD treated children, with at least 6 years post-treatment follow up, was evaluated. Median after treatmeant follow-up was 10 years. At the time of the last visit a group of non infected subjects were also included as a control for cardiological studies. During follow-up, the majority of treated subjects 59/61 (96%) achieved negative parasitemia by qPCR at the end of treatment. A decrease in T. cruzi antibodies titers were observed and seroconversion by two conventional serology tests (IHA, ELISA) occurred in 53/95 (56%). Holter showed alterations in 3/95 (3%) of treated patients: isolated ventricular extrasystoles and nocturnal sinus bradycardia (one patient); asymptomatic and vagal related 1st and 2nd degree AV block (one patient); and complete right bundle branch block (cRBBB) (one patient). Only the last one is probably related to CD involvement. 2D speckle tracking echocardiography was conducted in 79/95 (83%) patients and no alterations in myocardial contractility were observed. In the non infected group Holter evaluations showed similar non pathological results in 3/28 (10%) of subjects: isolated ventricular premature beats (2 patients); asymptomatic 2nd degree AV block with Wenckebach sequences during night time (one patient). 2D speckle tracking echocardiography was conducted in 25/28 (89%) with no alterations. Conclusions After long term follow-up of a cohort of treated children for CD, a good parasiticidal treatment effect and a low incidence of cardiological lesions, related to Chagas disease, were observed. These results suggest a protective effect of treatment on the development of cardiological lesions and strengthen the recommendation of early diagnosis and treatment of infected children. Trial registration [ClinicalTrials.gov][1] [NCT04090489][2]. Author summary If left untreated, CD evolves into a chronic oligosymptomatic infection that can progress to cardiac complications in 30% of patients after several years. It is known that the main early marker of cardiac involvement are alterations in the conduction system. There are few studies of long-term after treatment cardiological evolution which have assessed the clinical effectiveness of treatment. The rationale for CD treatment is to avoid the development of cardiological complications. The parasiticidal effect of treatment has been demonstrated but its clinical effectiveness in preventing cardiac involvement requires long term follow-up. In our long term follow-up study of treated children, we observed the preventive effect on cardiac lesions by treatment with benznidazole or nifurtimox. This intensifies the need for early diagnosis and treatment to prevent the development of long term complications observed in CD. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04090489 ### Funding Statement Part of this work was supported by DNDi. DNDi received financial support for this work from UK aid, UK and Fundacion Mundo Sano, Argentina; and for its overall mission from Medecins sans Frontieres (MSF) and the Swiss Agency for Development and Cooperation (SDC), Switzerland. The donors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: HOSPITAL DE NINOS RICARDO GUTIERREZ COMITE DE ETICA EN INVESTIGACION All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Individual participant data will be available (including data dictionaries). All of the individual participant data collected during the trial, after de-identification, will be shared. Study protocol, statistical analysis plan, informed consent form, clinical study report and analytic code will be available, too. It will be available beginning 9 months and ending 36 months following article publication. Information will be shared with investigators whose proposed use of the data has been approved by an independent review committee (learned intermediary) identified for this purpose. It would be used for individual participant data meta-analysis. After 36 months the data will be available in our service's data warehouse but without investigator support other than deposited metadata. * Bz : benznidazole CD : Chagas disease cRBBB : complete right bundle branch block ECG : electrocardiogram Nf : nifurtimox STE : speckle-tracking 2D echocardiogram [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04090489&atom=%2Fmedrxiv%2Fearly%2F2020%2F07%2F03%2F2020.06.30.20143370.atom