Longitudinal follow up of serological response in children treated for Chagas disease

Moscatelli, Guillermo; Moroni, Samanta; Bournissen, Facundo García; González, Nicolás; Ballering, Griselda; Schijman, Alejandro G.; Corral, Ricardo S.; Bisio, Margarita; Freilij, Héctor; Altcheh, Jaime

doi:10.1371/journal.pntd.0007668

Cited by 31 publications

(54 citation statements)

References 32 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A decrease in antibody titres with clearance of T . cruzi in blood seems to precede complete reversion of serological response to negative and may indicate an evolution towards cure from a clinical point of view [ 24 ]. In contrast, follow-up of patients in the chronic phase of Chagas disease has shown that antibody titres remain stable if no antitrypanosomal treatment is received [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO)

Altcheh

Castro²,

Dib

et al. 2021

PLoS Negl Trop Dis

Self Cite

View full text Add to dashboard Cite

Nifurtimox is a recommended treatment for Chagas disease, but data from treated children are limited. We investigated the efficacy, safety and tolerability of nifurtimox administered as divisible, dispersible 30 mg and 120 mg tablets in children with Chagas disease. In this blinded, controlled study conducted January 2016–July 2018, 330 patients aged <18 years from 25 medical centres across three South American countries were randomised 2:1 to nifurtimox 10–20 mg/kg/day (aged <12 years) or 8–10 mg/kg/day (aged ≥12 years) for 60 days (n = 219), or for 30 days plus placebo for 30 days (n = 111) (ClinicalTrials.gov NCT02625974). The primary outcome was anti-Trypanosoma cruzi serological response (negative seroconversion or seroreduction ≥20% in mean optical density from baseline determined by two conventional enzyme-linked immunosorbent assays) at 12 months in the 60-day treatment group versus historical placebo controls. Nifurtimox for 60 days achieved negative seroconversion (n = 10) and seroreduction (n = 62) in 72 patients (serological response 32.9%; 95% confidence interval [CI] 26.4%, 39.3%, of all treated patients), confirming superiority relative to the upper 95% CI of 16% for controls. In patients aged <8 months, 10/12 treated for 60 days (83.3%) and 5/7 treated for 30 days (71.4%) achieved negative seroconversion. Overall serological response was lower for 30-day than for 60-day nifurtimox (between-treatment difference 14.0% [95% CI 3.7%, 24.2%]). The frequency of T. cruzi-positive quantitative polymerase chain reactions decreased substantially from baseline levels (60-day regimen 53.4% versus 1.4%; 30-day regimen 51.4% versus 4.5%). Study drug-related treatment-emergent adverse events (TEAEs), which were observed in 62 patients (28.3%) treated for 60 days and 29 patients (26.1%) treated for 30 days, were generally mild or moderate and resolved without sequelae; 4.2% of all TEAEs led to nifurtimox discontinuation. Age- and weight-adjusted nifurtimox for 60 days achieved a serological response at 12 months post-treatment that was superior to historical placebo, was well tolerated and had a favourable safety profile in children with Chagas disease. Although, at 1 year serological follow-up, efficacy of the shorter nifurtimox treatment was not comparable to the 60-day treatment regimen for the overall study population, further long-term follow-up of the patients will provide important information about the progress of serological conversion in children treated with nifurtimox, as well as the potential efficacy difference between the two regimens over time.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Significant reductions in anti- T . cruzi antibody concentration (i.e., seroreduction) measured by conventional serology after antitrypanosomal treatment seem to be predictive of subsequent negative seroconversion [ 22 – 24 ].…”

Section: Methodsmentioning

confidence: 99%

Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO)

Altcheh

Castro²,

Dib

et al. 2021

PLoS Negl Trop Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Parasitic negativization occurs in the majority of treated newborns. Long-term follow-up studies are necessary to assess the relationship of treatment to rates of subsequent clinical events in infants [88,89,90,91,92].…”

Section: Anti-trypanosomal Treatment During the Acute Phasementioning

confidence: 99%

WHF IASC Roadmap on Chagas Disease

Echeverría

Marcus

Novick

et al. 2020

View full text Add to dashboard Cite

Background: Chagas Disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality associated with the disease, the social and economic burdens on individuals and society are substantial. Often called the 'silent killer', Chagas disease is characterized by a long, asymptomatic phase in affected indivi duals. A pproximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure. Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American S ociety of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment Echeverría et al: WHF IASC Roadmap on Chagas Disease Art. 26, page 2 of 31 of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care professionals working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation. Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of 'roadblocks' in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy. Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease.

show abstract

“…The cardiac presentations of Chagas disease can be highly variable in pediatrics and limited data are available regarding the cardiac status of children in the U.S. with Chagas disease. Data from endemic countries shows cardiac presentations in neonates and infants with congenital Chagas disease, to adolescents showing pathologic and non-pathologic electrocardiographic changes, and even some adolescents with signs of cardiomyopathy [12][13][14][15][16][17][18][19][20]. Congenital Chagas disease is typically asymptomatic, but can present with heart failure, electrocardiogram (EKG) changes or myocarditis.…”

mentioning

confidence: 99%

“…A metanalysis found that EKG changes in children and adolescents are found just as frequently as in adults but with more rapid time to death and more diagnostic di culty [15]. The most common ndings are right bundle branch block, atrioventricular block and left anterior fascicular block [15,19,21]. A study in Mexico looked at 37 cases of Chagas disease in adolescents under 18 and found that 25 of them already had cardiac pathology consistent with Chagas disease cardiomyopathy [12].…”

mentioning

confidence: 99%

Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

Malhotra

Masood

Giglio

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundChagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S.MethodsWe prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience.ResultsOf 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture.ConclusionsPediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

show abstract

Longitudinal follow up of serological response in children treated for Chagas disease

Cited by 31 publications

References 32 publications

Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO)

Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO)

WHF IASC Roadmap on Chagas Disease

Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States

Contact Info

Product

Resources

About