Estimation of the morbidity and mortality of congenital Chagas disease: a systematic review and meta-analysis

Abstract

AbstractChagas disease is caused by the parasite Trypanosoma cruzi which can be transmitted from mother to baby during pregnancy. There is no consensus on the proportion of infected infants that become symptomatic for congenital Chagas disease (cCD). The objective of this systematic review is to determine the burden of cCD.Articles from journal inception to 2020 reporting morbidity and mortality associated with cCD were retrieved from academic search databases. Observational studies, randomized-control trials, and studies of babies diagnosed with cCD were included. Studies were excluded if they were case reports or series, without original data, case-control without cCD incidence estimates, and/or did not report number of participants. Two reviewers screened articles for inclusion. To determine pooled proportion of symptomatic infants with cCD, individual symptoms, and case-fatality, random effects meta-analysis was performed.We identified 4,531 records and reviewed 4,301, including 47 articles in the narrative summary and analysis. 28.3% (95% confidence interval (CI) = 19.0%, 38.5%); of cCD infants were symptomatic and 2.2% of infants died (95% CI = 1.3%, 3.5%). The proportion of infected infants with hepatosplenomegaly was 12.5%, preterm birth 6.0%, low birth weight 5.8%, anemia 4.9%, and jaundice 4.7%. Although most studies did not include a comparison group of non-infected infants, the proportion of infants with cCD symptomatic at birth are comparable to those with congenital toxoplasmosis (10.0%-30.0%) and congenital cytomegalovirus (10.0%-15.0%).We conclude that cCD burden appears significant, but more studies comparing infected mother-infant dyads to non-infected ones are needed to determine an association of this burden to cCD infection.Author summaryChagas disease is caused by the parasite Trypanosoma cruzi, which can be passed from mother to infant. It is estimated that one million women of reproductive age are infected with T. cruzi. Prior to our work, the proportion of infants infected with T. cruzi congenitally presenting with clinical symptoms was unknown. After systematically searching for and identifying studies that collected information on infants with congenital Chagas disease, we summarized and analyzed 47 studies. Our pooled analysis of these studies estimated that 28.3% of infants with congenital Chagas disease were symptomatic and 2.2% died. Prior work has shown that transmission of T. cruzi from mother to child occurs in 5% of cases. Other studies have shown that this transmission is preventable through treatment of women prior to conception, and infants can be cured if shown to be infected at birth. Our estimated proportion of 28.3% of infants diagnosed with cCD at birth presenting with clinical symptoms are comparable to infants diagnosed with congenital toxoplasmosis presenting with clinical symptoms (10.0%-30.0%) and congenital cytomegalovirus (10.0%-15.0%). More studies comparing infected mother-infant dyads to non-infected mother-infant dyads are needed to determine an association of this burden to cCD infection.