Prevalence of Maternal Chagas Disease and Vertical Transmission Rates in Bolivia: A Systematic Review and Meta-Analysis

ABSTRACT.

Bolivia has one of the highest burdens of Chagas disease in the world. Vertical transmission from mother to infant accounts for a growing number of cases. We performed a systematic review of articles assessing the prevalence of Chagas disease in pregnant women and rates of vertical transmission to infants in Bolivia. Studies were not excluded based on year of publication or language. Random-effects analyses were performed to estimate a pooled prevalence of maternal Chagas disease and pooled vertical transmission rate. Our search yielded 21 articles describing over 400,000 cases of Chagas disease among pregnant women in Bolivia. The reported prevalence of maternal Chagas disease ranged from 17.3% to 64.5%, with a pooled prevalence of 33.0% (95% CI, 27.4–38.7%). The prevalence of maternal Chagas disease trended down over time (P = 0.006), decreasing by approximately 25% to 30% over the last 40 years. Vertical transmission rates ranged from 2.0% to 13% with a pooled average of 6.2% (95% CI, 4.4–7.5%); rates did not significantly change over time. Our study is the first systematic review and meta-analysis of Chagas disease maternal prevalence and vertical transmission in Bolivia. Our findings indicate that maternal Chagas disease has fallen in prevalence but still affects 20% to 30% of pregnant women and poses a considerable risk of vertical transmission. Pregnant women and infants are an important target for public health interventions to limit the mortality and morbidity of Chagas disease and to reduce intergenerational spread.

INTRODUCTION

The WHO estimates that between 6 million and 7 million people worldwide are infected by Trypanosoma cruzi, the protozoan parasite that causes Chagas disease.¹ Endemic to 21 countries in Latin America, Chagas disease is considered a neglected tropical disease and is associated with significant morbidity and mortality.² Although local public health initiatives have made significant strides in reducing vector and blood-borne transmission over the last few decades, Chagas disease remains a common infection among pregnant women and poses a risk of vertical transmission to infants.^3–5 Vertical transmission accounts for over 15,000 cases annually and represents a growing proportion of new cases of Chagas disease.^4,5 The risk of vertical transmission among infected mothers is estimated at 5% to 10%.⁵

Bolivia is a region where T. cruzi is endemic and has the highest prevalence rate of Chagas disease in the world.⁶ Over 600,000 people in Bolivia are estimated to have Chagas disease, and approximately a third of these are women of child-bearing age.¹ These women act as a reservoir for infection and may perpetuate the multigenerational spread of disease, particularly given migration between areas where the disease is endemic and nonendemic.^6,7

We performed a systematic review of articles assessing the prevalence of Chagas disease in women and vertical transmission rates to infants in Bolivia. We aimed to assess trends in maternal prevalence and vertical transmission rates in the existing literature, which spans almost 40 years.

MATERIALS AND METHODS

Search strategy and study selection.

A systematic review of the existing literature was performed in the following databases: PubMed, LILACS, and Scielo. Searches were designed to identify studies that reported the prevalence of T. cruzi infection among pregnant women, the rate of vertical transmission to infants, or both. The last search was performed in 2023. The review protocol was designed a priori but not registered. Studies were compiled for further review in Covidence, which removed duplicate studies. Two reviewers screened studies by title and abstract and removed irrelevant studies; conflicts were resolved through discussion. Next, full-text articles were screened for inclusion by using eligibility criteria determined a priori (Table 1). Our review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and were not excluded by publication date or language.⁸

Table 1.

Inclusion and exclusion criteria for literature search

Parameters	Inclusion Criteria	Exclusion Criteria
Patient population	Women residing in Bolivia who are currently pregnant or have given birth within the last month; infants under 6 months of age residing in Bolivia with T. cruzi-seropositive mothers	Women who are of childbearing age but are not currently pregnant or have not given birth within the last month Women or infants who do not reside in Bolivia
Intervention or exposure	Diagnosis of Chagas disease (T. cruzi seropositivity)	Inconclusive or negative test results for Chagas disease
Comparison	Women residing in Bolivia who are currently pregnant or have given birth within the last month who do not have Chagas disease; infants residing in Bolivia with T. cruzi-seropositive mothers who do not have Chagas disease
Outcome	Maternal prevalence of Chagas disease Rate of vertical transmission of T. cruzi to infants
Setting	Any publication date, medical setting, or language	Studies taking place outside of Bolivia
Type of study design	Interventional or observational studies, including cohort studies, case control studies, or randomized controlled trials	Animal studies, systematic reviews, case series, editorials, letters, commentaries, or articles without full text available

Data extraction.

Data extracted for each study included study period, setting, maternal sample size, prevalence of maternal Chagas disease, infant sample size, and vertical transmission rate. Study data were extracted manually by two reviewers; conflicts were resolved through discussion.

Study assessment.

The risk of bias in individual studies was assessed using the Joanna Briggs Institute Checklist for Analytical Cross Sectional Studies (Supplemental Material). Studies were evaluated by one reviewer.

Statistics.

Data analysis was performed in Stata (v. 17). The prevalence of maternal Chagas disease was defined as the number of pregnant women with T. cruzi infection divided by the total number of pregnant women evaluated. The rate of vertical transmission was defined as the number of congenitally infected infants divided by the total number of infants born to infected mothers and screened for Chagas disease. Two-way scatter plots were used to illustrate temporal trends in maternal Chagas disease prevalence and vertical transmission rates, with articles organized chronologically by publication date. Plots included linear prediction plots with 95% CI, with analytical weighting for sample size. Linear regressions with analytical weighting for sample size were performed to assess trends in maternal prevalence and vertical transmission rates over time. For the meta-analysis, random-effects analyses were used to estimate a pooled prevalence of maternal Chagas disease and pooled T. cruzi vertical transmission rate with 95% CI.

RESULTS

Study selection.

Our search yielded a total of 236 articles (Figure 1). On title and abstract screening, 92 were determined to be irrelevant. After screening with full-text review, a total of 21 articles were included in our final analysis. Of these, 20 described maternal Chagas disease prevalence, and 17 described vertical transmission rates. Publication dates ranged from 1985 to 2022, with studies performed between 1979 and 2021. Four articles were available exclusively in Spanish.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram.

Study characteristics and findings.

Our search yielded a total of 21 articles describing over 400,000 cases of Chagas disease among pregnant women in Bolivia. The most common setting was maternity hospitals in the city of Santa Cruz, followed by Tarija and Cochabamba. For studies that included study sites in multiple countries, only data for Bolivian participants were included in our analysis. The median study size was 1,696 women and their infants (interquartile range, 526–5,485).

Among the 20 articles reporting Chagas disease in pregnant women, maternal prevalence ranged from 17.3% to 64.5%. Maternal prevalence of Chagas disease significantly decreased over the 37-year span of these studies (P = 0.006) (Figure 2). Before 2000, the reported prevalence of maternal Chagas disease ranged from 51% to 54%; after 2015, reported prevalence ranged from 21.5% to 26.9%. The pooled prevalence of maternal Chagas disease was 33.0% (95 CI, 27.4–38.7%) (Figure 3). The I² (a statistic estimating the percentage of variance attributable to heterogeneity) was 100%, indicating high levels of heterogeneity.

Figure 2.

Reported prevalence of maternal Chagas disease in Bolivia by study.

Figure 3.

Forest plot of reported maternal Chagas disease prevalence in Bolivia by study.

Among the 17 articles reporting vertical transmission of T. cruzi in Bolivia, vertical transmission rates ranged from 2.0% to 13% (Figure 4). There was a trend towards decreasing transmission rates over time, but this did not reach statistical significance. The pooled vertical transmission rate was 6.2% (95% CI, 4.6–7.7%) (Figure 5). The I² was 100%, indicating high levels of heterogeneity.

Figure 4.

Reported T. cruzi vertical transmission rate in Bolivia by study.

Figure 5.

Forest plot of reported T. cruzi vertical transmission rates in Bolivia by study.

Risk of bias.

The risk of bias in the included publications was primarily low to moderate, as assessed by the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies (Supplemental Table S1). The most common limitations were lack of detailed description of the study subjects or lack of clear inclusion criteria (Supplemental Table S2).

DISCUSSION

Our study is the first systematic review and meta-analysis of Chagas disease in Bolivia. The 21 studies in our review demonstrated that the reported prevalence of maternal Chagas disease in Bolivia decreased by approximately 25% to 30% over the last 40 years. Recent studies since 2015 suggest that the current prevalence of maternal Chagas disease falls between 20% and 30%. Our findings are consistent with other studies showing reduced prevalence rates of Chagas disease in Latin American countries where the disease is endemic over the last few decades.⁶ A recent study estimated that the overall prevalence of Chagas disease in Bolivia decreased by 30% from 1990 to 2019, suggesting that prevalence reductions in pregnant women are similar to that of the general population.⁶

The reported rate of T. cruzi vertical transmission to infants ranged from 2.0% to 13%, and rates did not change significantly over time. The weighted average was 6.2%, which is similar to the pooled transmission rate of 5.0% calculated in a recent international meta-analysis for countries where the disease is endemic.⁷ Variation in reported vertical transmission rates was likely affected in part by changing diagnostic modalities for congenital Chagas disease. Historically, diagnosis of congenital Chagas disease relied on a micromethod that involved microscopic examination of infant venous blood or umbilical cord blood for parasites.¹⁰ This method relies on the expertise of skilled personnel and detects fewer than half of congenital infections.^10–12 Over the last 10 years, quantitative polymerase chain reaction has emerged as a more sensitive diagnostic modality and has been implemented in some Bolivian maternity hospitals.¹³

The decreasing prevalence of Chagas disease observed in our study reflects the initiatives and actions in Bolivia by the Ministry of Health, the Pan American Health Organization, various public health agencies, and nongovernmental organizations that combat Chagas disease. The National Chagas Program was implemented in Bolivia in 2004 and led to reduced vector circulation through housing improvements and intensified fumigation of areas of endemicity. In addition, national insurance reforms such as the Universal Maternal and Infant Insurance implemented in 2003 and the Single Health System implemented in 2019 have expanded access to health care resources, including diagnostic testing and treatment options.³ Despite these improvements, Bolivia continues to have the highest global prevalence rate of Chagas disease, at approximately 5,000 cases per 100,000 people, a rate over three times higher than that of the next leading country.⁶ Bolivia also has the highest age-adjusted disability-adjusted life-year rate due to Chagas disease of any country, highlighting that Chagas disease remains a key public health challenge.⁶

Our study has several limitations. First, there was significant heterogeneity in the study designs, including diagnostic methods of T. cruzi infection, follow-up lengths, and sample sizes. As many studies provided limited demographic information on study subjects, such as age, ethnicity, and residence in urban or rural locations, we could not assess how closely the studied population reflected the general population in Bolivia. It is also possible that the existing literature overestimates the prevalence or transmission rates of Chagas disease because of publication bias.

In summary, although the prevalence of maternal Chagas disease has diminished in the last few decades, it remains a very common maternal infection affecting 20% to 30% of pregnant women. Our findings highlight the need for universal screening of pregnant women and affordable and accessible treatment options. Targeting pregnant women offers the opportunity to prevent T. cruzi transmission in future pregnancies and to reduce the risk of developing irreversible sequelae such as Chagas cardiomyopathy, which carries high morbidity and mortality.⁴ Notably, antiparasitic treatment with benznidazole or nifurtimox is more effective and best tolerated at younger ages, and infants under 1 year of age have a cure rate exceeding 90%.⁵ Therefore, both pregnant women and infants remain an important target for public health interventions to limit the intergenerational spread of Chagas disease.

Note: Supplemental material appears at www.ajtmh.org.