SEARCH

SEARCH BY CITATION

Keywords:

  • Chagas disease;
  • Trypanosoma cruzi ;
  • congenital infection;
  • pregnant women;
  • systematic review;
  • Brazil
  • maladie de Chagas;
  • Trypanosoma cruzi ;
  • infection congénitale;
  • femmes enceintes;
  • revue systématique;
  • Brésil
  • enfermedad de Chagas;
  • Trypanosoma cruzi ;
  • infección congénita;
  • mujeres embarazadas;
  • revisión sistemática;
  • Brasil

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objective

To estimate the prevalence of Chagas disease in pregnant women and the risk of congenital transmission of Trypanosoma cruzi infection in Brazil, through a systematic review and meta-analysis.

Methods

We searched electronic databases, grey literature and reference lists of included publications to identify epidemiological studies on the prevalence of Chagas disease in pregnant women and on the congenital transmission rate of T. cruzi infection in Brazil published between January 1980 and June 2013. Pooled estimates and 95% confidence intervals (95% CIs) were calculated using fixed- and random-effects models.

Results

Sixteen articles were included – 12 studies on the prevalence of Chagas disease in pregnant women (549 359 pregnant women) and nine on congenital transmission rates (1687 children born to infected mothers). Prevalence of Chagas disease in pregnant women ranged from 0.1% to 8.5%, and congenital transmission rates from 0% to 5.2%. The pooled prevalence of Chagas disease among pregnant women across studies was 1.1% (95% CI: 0.6–2.0); the pooled congenital transmission rate was 1.7% (95% CI: 0.9–3.1). In 2010, 34 629 pregnant women were estimated to be infected with T. cruzi, and 312–1073 children born (mean: 589 cases) with congenital infection.

Conclusion

Congenital Chagas disease is a neglected public health problem in Brazil. Systematic congenital Chagas disease control programs through routine prenatal screening for T. cruzi should be widely implemented in Brazil's endemic areas, to identify infected pregnant women and newborns at risk of congenital infection.

Objectif

Estimer la prévalence de la maladie de Chagas chez les femmes enceintes et le risque de transmission congénitale de Trypanosoma cruzi au Brésil, à l'aide d'une revue systématique et méta-analyse.

Méthodes

Nous avons recherché dans des bases de données électroniques, dans la littérature grise et dans les listes de références des publications incluses pour identifier les études épidémiologiques sur la prévalence de la maladie de Chagas chez les femmes enceintes et sur le taux de transmissions congénitales de l'infection à T. cruzi au Brésil, publiées entre janvier 1980 et juin 2013. Les estimations poolées et les intervalles de confiance à 95% (IC95%) ont été calculés en utilisant des modèles à effets aléatoires et fixes.

Résultats

16 articles ont été inclus: 12 études sur la prévalence de la maladie de Chagas chez les femmes enceintes (549 359 femmes enceintes) et 9 sur les taux de transmissions congénitales (1687 enfants nés de mères infectées). La prévalence de la maladie de Chagas chez les femmes enceintes variait de 0,1% à 8,5% et les taux de transmissions congénitales de 0% à 5,2%. La prévalence poolée de la maladie de Chagas chez les femmes enceintes dans toutes les études était de 1,1% (IC95%: 0,6–2,0), le taux de transmissions congénitales poolé était de 1,7% (IC95%: 0,9 à 3,1). En 2010, il était estimé que 34 629 femmes enceintes étaient infectées par T. cruzi et 312 à 1 073 (moyenne: 589 cas) enfants sont nés avec une infection congénitale.

Conclusion

La maladie de Chagas congénitale est un problème de santé publique négligé au Brésil. Des programmes de contrôle systématique de la maladie de Chagas congénitale par le dépistage prénatal de routine de T. cruzi devraient être largement implémentés dans les zones endémiques du Brésil pour identifier les femmes enceintes infectées et les nouveau-nés à risque d'infection congénitale.

Objetivo

Calcular la prevalencia de la enfermedad de Chagas en mujeres embarazadas y el riesgo de transmisión congénita de la infección por Trypanosoma cruzi en Brasil, mediante una revisión sistemática y meta-análisis.

Métodos

Hemos realizado una búsqueda en bases de datos electrónicas, literatura gris y las listas de referencias de las publicaciones incluidas, para identificar estudios epidemiológicos sobre la prevalencia de la enfermedad de Chagas en mujeres embarazadas y sobre las tasas de transmisión congénita de la infección por T. cruzi en Brasil, publicados entre Enero de 1980 y Junio del 2013. Los cálculos de datos agrupados en intervalos de confianza del 95% (IC 95%) se realizaron utilizando modelos de efectos fijos y aleatorios.

Resultados

Se incluyeron 16 artículos – 12 estudios sobre la prevalencia de la enfermedad de Chagas en mujeres embarazadas (549,359 mujeres embarazadas) y 9 con tasas de transmisión congénita (1,687 niños nacidos de madres infectadas). La prevalencia de la enfermedad de Chagas entre mujeres embarazadas estaba entre un 0.1% y un 8.5%, y las tasas de transmisión congénita entre el 0% y el 5.2%. La prevalencia de la enfermedad de Chagas en mujeres embarazadas, calculada a partir de los datos agrupados de todos los estudios era del 1.1% (IC 95%: 0.6–2.0); la tasa de transmisión congénita a partir de datos agrupados era del 1.7% (IC 95%: 0.9–3.1). En el 2010, se calculó que 34,629 mujeres embarazadas estaban infectadas con T. cruzi, y entre 312 a 1,073 bebés nacidos (media: 589 casos) con infección congénita.

Conclusiones

La enfermedad de Chagas congénita es un problema de salud pública olvidado en Brasil. Los programas de control sistemático de la enfermedad de Chagas congénita mediante el cribado prenatal rutinario de T. cruzi deberían implementarse ampliamente en áreas endémicas del Brasil, con el fin de identificar a las mujeres embarazadas y a los recién nacidos en riesgo de infección congénita.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Chagas disease (American trypanosomiasis), caused by the protozoan parasite Trypanosoma cruzi, is endemic in 21 Latin American countries, where an estimated 8–10 million people are infected (PAHO 2006; WHO 2012). In Brazil, there are about 2.9–7.2 million people living with Chagas disease (Martins-Melo et al. 2014), causing about 6000 deaths annually (Martins-Melo et al. 2012a,b,c). Chagas disease has become a global emerging problem due to large-scale international migration of Latin Americans to non-endemic countries, particularly to the USA, Canada, Europe, Australia and Japan (Schmunis & Yadon 2010).

Trypanosoma cruzi is transmitted by infected faeces of blood-sucking triatomine bugs, blood transfusion, organ transplantation, consumption of contaminated food or drink and from mother to child (Rassi et al. 2010; WHO 2012). With the control of vector and blood-borne transmission in most endemic areas, congenital transmission has increased in importance (Gurtler et al. 2003; Howard et al. 2014).

Prevalence of T. cruzi infection in pregnant women ranges from 1% to 40%, (Torrico et al. 2004, 2005; Salas et al. 2007; Carlier & Truyens 2010), and about 1.8 million women of childbearing age are infected in Latin America (PAHO 2006). Congenital transmission rates of T. cruzi infection range from 0% to 28.6% (Howard et al. 2014). Recent estimates indicate that about 14 400 newborns are congenitally infected annually in Latin America (PAHO 2006), and 2000 in North America (Buekens et al. 2008). The transmission can be repeated at each pregnancy and during the entire fertile period of a woman's life (Carlier & Torrico 2003). While most cases are asymptomatic, congenital T. cruzi infection may result in preterm birth, low birth weight, stillbirths and clinical manifestations of the disease at birth (Bittencourt 1976, 1992; Carlier & Torrico 2003; Torrico et al. 2006). As congenital transmission cannot be prevented, early diagnosis and treatment of congenital cases are high priorities in congenital Chagas disease control programs (Bern et al. 2009; Carlier et al. 2011).

There are no systematic estimates of burden of Chagas disease in pregnant women and transmission of congenital infection for most endemic areas (Gurtler et al. 2003). In Brazil, prevalence data on Chagas disease in pregnant women are limited, and risk of congenital transmission in most endemic and non-endemic areas is unknown. This study aimed to estimate the prevalence of Chagas disease in pregnant women and the risk of congenital transmission of T. cruzi infection in Brazil, through a systematic review and meta-analysis.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Search strategy

We conducted a systematic literature review to identify relevant publications about prevalence of Chagas disease in pregnant women and congenital transmission of T. cruzi infection in Brazil. We searched the electronic databases PubMed, Web of Science, Scopus, Science Direct, LILACS and SciELO for reports published between 1 January 1980 and 30 June 2013. The search terms used were as follows: ‘Chagas disease’, Trypanosoma cruzi, ‘pregnant women’, ‘congenital transmission’, ‘vertical transmission’, ‘prevalence’ and ‘Brazil’. There were no restrictions on language of publication. Reference lists of review articles and other documents were hand-searched for additional relevant studies. Furthermore, we screened journals not indexed in electronic databases, abstracts from congresses of tropical and infectious disease societies, reports of control programs and grey literature. Our analyses were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Liberati et al. 2009).

Selection criteria

We included all types of observational studies from Brazil that reported prevalence of Chagas disease in pregnant women and/or congenital transmission rate of T. cruzi infection. We further included only studies in which the diagnosis of infection by T. cruzi in pregnant women was carried out by combination of two or more conventional serological tests. For children born from infected mothers, we included studies if diagnosis of congenital infection was made using one or combination of the following diagnostic methods: direct parasitological examination; serological tests performed on children after 6–9 months of age; polymerase chain reaction (PCR), xenodiagnosis and hemoculture (Howard et al. 2014). Studies with no detailed description of sampling, case reports, anecdotal evidence and reviews were excluded. Duplicated studies using the same data were identified, and the most recent and/or more complete data were included.

Data extraction

From each article included, the following data were extracted: author names, publication year, study period, study sites, sampling method and sample size, study setting (population/community based or hospital based), age group, number of T. cruzi cases in pregnant women or children, diagnostic methods used, follow-up/time of diagnosis of congenital infection, origin of the blood sample for diagnostic screening (venous blood, umbilical cord and peripheral/capillary blood dried on filter paper), and prevalence of disease in pregnant women and/or congenital transmission rate (or data needed to calculate them) with their respective 95% confidence intervals (95% CI). The 95% CI were directly extracted from articles, when available, or calculated using an exact binomial method. Searches and data extraction were performed by a single investigator (FRM). Disagreements were resolved by consensus between the authors or through consultation with the corresponding author of relevant studies.

Statistical analysis

Pooled estimates with their 95% CI were calculated using the fixed- and random-effects models (Hedges & Vevea 1998). Prevalence of Chagas disease in pregnant women was defined as the number of cases of pregnant women with T. cruzi infection divided by the total of pregnant women evaluated. Congenital transmission rate was defined as the number of congenitally infected children divided by number of children born to infected mothers. In order to minimise bias caused by small sample size, in the quantitative analysis we excluded studies with a sample size <10 children born to infected mothers. Heterogeneity between studies was assessed using the Cochran's Q test (reported as χ2 and P values) and I2 statistic. Heterogeneity was considered statistically significant at a P value <0.10. I2 values of >25%, 50% and 75% show low, moderate and high heterogeneity, respectively (Higgins & Thompson 2002; Higgins et al. 2003). When significant heterogeneity was absent, the pooled estimates were calculated using a fixed-effects model; otherwise, a random-effects model was used. Publication bias was assessed using Begg's funnel plots and Egger's regression test (Egger et al. 1997). If significant publication bias was found, the Duvall and Tweedie's trim and fill method was performed by adding studies that appeared to be hypothetically missing (Duval & Tweedie 2000). Adjusted pooled estimates were computed after the addition of potential missing studies.

Subgroup analyses were performed to investigate potential sources of heterogeneity among studies and included the following variables: Brazil's five geographical regions, maternal age group (<20, 20–29 and >30 years), study period (1980–1989, 1990–1999 and after 2000), sample size, study type, urban/rural area, diagnostic method and origin of the blood sample for diagnostic screening. If a study did not report the year of data collection, the publication year was used.

We also estimated the expected number of women of childbearing age, pregnant women and children born with T. cruzi infection using data on the general population and women of childbearing age (10–49 years) from the 2010 National Demographic Census of the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística – IBGE; http://tabnet.datasus.gov.br/cgi/deftohtm.exe?ibge/cnv/popuf.def); live births in Brazil in 2010 obtained from the Information System on Live Births (Sistema de Informação sobre Nascidos Vivos – SINASC; http://tabnet.datasus.gov.br/cgi/deftohtm.exe?sinasc/cnv/nvuf.def); and the estimated birth rate in 2010. The number of pregnant women was estimated using the total population multiplied by the birth rate, adding a correction of 10% due to losses resulting from abortion, stillbirths and underreporting (http://nutricao.saude.gov.br/calculo_bvg.php). To estimate the potential number of pregnant women and women of childbearing age with T. cruzi infection in Brazil and regions in 2010, we applied the result of the estimated pooled prevalence of Chagas disease in pregnant women at national level, extrapolating to the women of childbearing age population and estimated pregnant women. To estimate the expected number of children born with congenital infection in 2010, we used the estimated pooled congenital transmission rate at national level. Potential geographic and temporal variations and effects of the parasite were not considered for calculation. In addition, we assumed that congenital transmission rate was not modified by mother's age, as most of women of childbearing age are in the indeterminate or chronic phases, and levels of parasitemia are low.

Data were analysed using Stata software, version 11.2 (StataCorp LP, College Station, TX, USA) and Comprehensive Meta-Analysis software, version 2.0 (Biostat, Englewood, NJ, USA). Thematic maps presenting the study sites and prevalence/transmission rate estimates for Brazilian states were created using ArcGIS software, version 9.3 (Environmental Systems Research Institute, Redlands, CA, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Literature search

We identified a total of 621 records. After removal of duplicates and initial screening, 33 articles were reviewed in full (Figure 1). After exclusion of not eligible articles and inclusion of additional articles identified by manual search of reference lists, 16 publications were eligible for analysis (Bittencourt 1984; Arteaga-Fernandez et al. 1987; Vaz et al. 1990; Medina-Lopes 1992; Mota 1993; Santos et al. 1995; Gontijo et al. 1998a,b, 2009; Nisida et al. 1999; Reiche et al. 2000; Rassi et al. 2004; Figueiró-Filho et al. 2007; Botelho et al. 2008; Araújo et al. 2009; Gomes Filho et al. 2009). These included 21 studies: 12 on prevalence of Chagas disease in pregnant women (Bittencourt 1984; Vaz et al. 1990; Santos et al. 1995; Gontijo et al. 1998a,b, 2009; Reiche et al. 2000; Figueiró-Filho et al. 2007; Botelho et al. 2008; Araújo et al. 2009; Gomes Filho et al. 2009) and nine on congenital transmission of T. cruzi infection (Bittencourt 1984; Arteaga-Fernandez et al. 1987; Medina-Lopes 1992; Mota 1993; Gontijo et al. 1998a, 2009; Nisida et al. 1999; Rassi et al. 2004; Araújo et al. 2009) (Figure 1).

image

Figure 1. Flow chart showing selection of studies for inclusion in this systematic review.

Download figure to PowerPoint

Study characteristics

Characteristics of studies for both target groups are summarised in Tables 1 and 2. The 12 studies on prevalence of Chagas disease in pregnant women included a total of 549 359 pregnant women, with 3033 cases of T. cruzi infection. Sample size ranged from 351 to 272 335 (mean: 45 780; median: 2141) and observed prevalence of Chagas disease in pregnant women from 0.1% to 8.5% among studies. The studies were conducted between 1981 and 2007 in seven Brazilian states. Most data were collected in the south-east region (41.7%), in the 1980s and after 2000 (41.7%) (Table 1).

Table 1. Studies on prevalence of Chagas disease in pregnant women in Brazil
Authors/publication yearStudy periodStudy site (locality, city or municipality)StateRegionStudy setting/sample typeAreaSerological testBlood sample origin (screening)Age group (years)Sample sizeCasesPrevalence (%)a95% CI
  1. Studies are presented in order of publication year and author. 95% CI, 95% confidence intervals calculated using exact binomial method; IFA, indirect immunofluorescence assay; ELISA, enzyme-linked immunosorbent assay; IHA, indirect haemagglutination assay. NA, information not available.

  2. a

    Number of cases of pregnant women with T. cruzi infection, divided by total of pregnant women evaluated (multiplied by 100).

  3. b

    Serological test used for diagnostic screening.

  4. c

    Indirect estimate by neonatal screening (prevalence of Chagas disease in post-partum women).

Bittencourt (1984)January 1981 to August 1982Salvador (02 maternity hospitals)BahiaNortheastHospital basedUrban/ruralELISAb; IFAbVenous bloodNA26512268.57.5–9.6
Vaz et al. (1990)April to October 1988São Paulo (08 health centres)São PauloSoutheastHealthcare serviceUrbanIFAb; IHAbVenous blood14–46481142.91.6–4.8
Santos et al. (1995)November 1990 to June 1991SalvadorBahiaNortheastPopulation/Community basedUrbanIFA; IHAbVenous blood<20–>301024242.31.5–3.5
Gontijo et al. (1998a)cMarch to May 1997Statewide (407 municipalities)Minas GeraisSoutheastPopulation/Community basedUrban/ruralELISAb; IFA; IHACapillary blood dried on filter paperNA18 4141750.9 (0.1–33.0 among municipalities)0.8–1.1
Gontijo et al. (1998b) (1)July 1995 to June 1997Belo Horizonte (maternity hospital)Minas GeraisSoutheastHospital basedUrban/ruralIFAb; IHAbUmbilical cord bloodNA1631231.40.9–2.1
Gontijo et al. (1998b) (2)July 1995 to June 1997Uberaba (maternity hospital)Minas GeraisSoutheastHospital basedUrban/ruralIFAb; IHAbUmbilical cord bloodNA1266544.33.2–5.5
Reiche et al. (2000)June 1996 to June 1998Londrina (ambulatory obstetric)ParanáSouthHospital based/Healthcare serviceUrban/ruralELISAb; IFAbVenous blood12–581164110.90.5–1.7
Figueiró-Filho et al. (2007)November 2002 to October 2003Statewide (78 municipalities)Mato Grosso do SulCentral-WestPopulation/Community basedUrban/ruralELISAb; IFA; IHAPeripheral blood on filter paper11–4932 512430.10.0–0.2
Botelho et al. (2008)January 2004 to December 2007Statewide (78 municipalities)Mato Grosso do SulCentral-WestPopulation/Community basedUrban/ruralELISAb; IFA; IHAPeripheral blood on filter paper9–54153 8575120.30.30–0.36
Araújo et al. (2009)2004Pelotas (03 hospitals)Rio Grande do SulSouthHospital basedUrban/ruralELISAb; IFA; IHA; TESA-BlotUmbilical cord bloodNA35110.30.0–1.6
Gomes Filho et al. (2009)September 2003 to May 2008Statewide (245 municipalities)GoiásCentral-WestPopulation/Community basedUrban/ruralELISAb; IFA; IHAPeripheral blood on filter paperNA272 33514180.50.49–0.55
Gontijo et al. (2009)cAugust 2005 to October 2006Statewide (853 municipalities)Minas GeraisSoutheastPopulation/Community basedUrban/ruralELISAb; IFA; IHACapillary blood dried on filter paperNA63 6735320.8 (0.1–23.0 among municipalities)0.77–0.91
Table 2. Studies on congenital transmission rate of T. cruzi infection in Brazil.
Authors/publication yearStudy periodStudy site (locality, city or municipality)StateRegionStudy setting/sample typeAreaDiagnostic methodBlood sample origin (screening)Follow-up time/diagnosisSample sizeCasesTransmission rate (%)a95% CI
  1. Studies are presented in order of publication year and author. 95% CI: 95% confidence intervals calculated using exact binomial method. IFA, indirect immunofluorescence assay; ELISA, enzyme-linked immunosorbent assay; IHA, indirect hemagglutination; CFR, complement fixation reaction; QBC, quantitative buffy coat; PCR, polymerase chain reaction; NA, information not available.

  2. a

    Number of congenitally infected children divided by number of children born to infected mothers (multiplied by 100).

  3. †Vectorial and transfusional transmission excluded, but not discarded transmission by breastfeeding.

Bittencourt 1984January 1981 to August 1982Salvador (02 maternity hospitals)BahiaNortheastHospital-basedUrban/ruralParasitological (microhematocrit); xenodiagnosisPeripheral blood (heel puncture)Birth18631.60.3–4.6
Arteaga-Fernandes et al. 1987NASão Paulo (01 hospital)São PauloSoutheastHospital-basedUrbanSerological (CFR, IHA, IFA); xenodiagnosisNABirth, >6 months12943.10.8–7.7
Medina-Lopes 1992NABrasíliaDistrito FederalCentral-WestHospital-based NAParasitological (Strout method); xenodiagnosisUmbilical cord blood/peripheral blood0–5 days, until 4 years17821.10.1–4.0
Mota 19931983–1990Belo Horizonte (01 hospital)Minas GeraisSoutheastHospital-basedNAParasitological; serological (CFR, IFA), xenodiagnosisNABirth to 5 years6423.10.4–10.8
Gontijo et al. 1998aMarch to May 1997Statewide (407 municipalities)Minas GeraisSoutheastPopulation/Community-basedUrban/ruralSerological (ELISA/IFA/IHA)Capillary blood dried on filter paper5–7 days, 6–12 months17531.70.3–4.9
Nisida et al. 1999NASão Paulo (03 obstetric clinics)São PauloSoutheastHospital-basedUrban/ruralParasitological (microhematocrit, QBC); serological (ELISA, TESA-blot); xenodiagnosis; immunohistochemistryVenous blood/umbilical cord bloodBirth, 1 month, >6 months5835.21.1–14.4
Rassi et al. 20041975–2004GoiâniaGoiásCentral-WestHospital-basedNASerological (CFR, IHA, IFA, ELISA); xenodiagnosisVenous bloodRetrospective (3 months –40 years old)a27820.70.1–2.6
Araújo et al. 20092004Pelotas (03 hospitals)Rio Grande do SulSouthHospital-basedUrban/RuralSerological (ELISA, IFA, IHÁ, TESA-Blot)Umbilical cord bloodBirth, >6 months100.00.0–97.5
Gontijo et al. 2009August 2005 to October 2006Statewide (853 municipalities)Minas Gerais SoutheastPopulation/Community-basedUrban/RuralSerological (ELISA, IHA, IFA, ELISA), PCR, haemocultureCapillary blood dried on filter paper5–7 days, 3 months, 6–9 months54110.20.0–1.0

Figure 2(a) shows the geographical distribution of study sites for studies on prevalence in pregnant women. These were concentrated in the Southeast and Central-West regions. Some states (such as Minas Gerais, Goiás and Mato Grosso do Sul) contain a large number of study sites, while there are no data available from many other states (Figure 2a). Not a single study was identified from the North region. Available data for municipalities in the states of Goiás (all 245 municipalities) (Gomes Filho et al. 2009) and Mato Grosso do Sul (all 78 municipalities) (Figueiró-Filho et al. 2007; Botelho et al. 2008) are derived from prenatal screening programs, while most of the data of Minas Gerais were derived from surveys based on neonatal screening conducted on state level in 1997 (407 municipalities) (Gontijo et al. 1998a) and 2005 (all 853 municipalities) (Gontijo et al. 2009) (Figure 2a, Table 1).

image

Figure 2. Distribution of study sites in Brazil: (a) prevalence of Chagas disease in pregnant women; (b) congenital transmission rate of T. cruzi.

Download figure to PowerPoint

The nine selected studies on congenital transmission of T. cruzi infection included a total of 1610 children born to infected mothers and 20 cases of congenital transmission. Congenital transmission rates ranged from 0% to 5.2% among studies (Table 2). Sample size ranged from 1 to 541 children born to infected mothers (mean: 179; median: 175), while the number of diagnosed congenital cases ranged from 0 to 4 children. Studies were conducted between 1975 and 2006 in six Brazilian states. Most data were collected in the south east region (55.6%), in the period 1980–1989 (44.4%) (Table 2). Most samples were hospital based (77.8%), using peripheral blood for diagnostic screening (33.3%) (Table 2). Most study sites were in the south east region, especially in the state of Minas Gerais (Figure 2b, Table 2).

Prevalence of Chagas disease in pregnant women

Pooled prevalence of Chagas disease in pregnant women from the 12 studies was 1.1% (95% CI: 0.6–2.0) (Table 3), with high level of heterogeneity (I2: 95%, P < 0.001), which remained even after analysis of estimates by subgroups (Table 3). There was no evidence of significant publication bias (Egger's test, P = 0.15). Prevalence estimates for the study period ranged from 5.2% (95% CI: 1.8–14.2) in 1980–1989, 1.7% (95% CI: 0.8–3.3) in 1990–1999, to 0.4% (95% CI: 0.2–0.6) after 2000. The highest estimated regional prevalence was observed in the north east region (4.6%, 95% CI: 1.3–15.3) (Table 3). Among the states with available data, the highest estimated prevalence was observed in Bahia (4.6%, 95% CI: 1.3–15.3) and São Paulo states (2.9%, 95% CI: 1.7–4.9) (Figure 3a).

Table 3. Pooled estimates of the prevalence of Chagas disease in pregnant women, stratified by subgroups
CharacteristicsNumber of studiesRangeaPooled Chagas disease prevalenceHeterogeneity
CasePregnant womenPrevalence (%)95% ICI2 (%)P-value (Cochran's Q)Model
  1. We calculated pooled proportions with a fixed- or random-effects model. We used the I² statistic and Cochran's Q to estimate heterogeneity between studies. 95% CI: 95% confidence intervals.

  2. a

    Observed prevalence in studies.

  3. b

    Standardisation of age groups utilised in some studies.

Overall prevalence120.1–8.53033549 3591.10.6–2.099.5<0.001Random
Study period
1980–1989022.9–8.524031325.21.8–14.293.9<0.001Random
1990–1999050.9–4.328723 4991.70.8–3.396.1<0.001Random
>2000050.1–0.82506522 7280.40.2–0.698.7<0.001Random
Age group (years)b
<20040.0–1.88050 8010.20.0–1.191.5<0.001Random
21–30040.1–0.9239102 5820.30.2–0.581.50.001Random
>30040.3–8.022534 6641.40.4–4.797.1<0.001Random
Region of Brazil
North-east022.3–8.525036754.61.3–15.397.4<0.001Random
South-east050.8–4.379885 4651.71.0–2.997.5<0.001Random
Central-west030.1–0.51973458 7040.30.2–0.598.6<0.001Random
South020.3–0.91215150.80.3–1.924.70.249Fixed
Survey area
Urban022.3–2.93815052.51.9–3.50.00.514Fixed
Urban/Rural100.1–8.52995547 8540.90.5–1.899.6<0.001Random
Sample size
<1000020.3–2.9158321.10.1–9.880.50.023Random
1000–10 000050.9–8.533877362.71.2–.5.997.3<0.001Random
>10 000050.1–0.92680540 7910.50.3–0.798.9<0.001Random
Serological test
IFA/IHA041.4–4.311544022.61.5–4.386.2<0.001Random
ELISA/IFA020.9–8.523738152.90.3–22.198.1<0.001Random
ELISA/IFA/IHA060.1–0.92681541 1420.50.3–0.798.6<0.001Random
Study setting/sample type
Population/Community based060.1–2.32704541 8150.60.4–0.998.8<0.001Random
Hospital based040.3–8.530458992.71.1–6.796.8<0.001Random
Healthcare services020.9–2.92516451.70.6–5.087.40.005Random
Blood sample (screening)
Venous blood040.9–8.527553202.81.0–7.796.9<0.001Random
Peripheral blood/capillary blood dried on filter paper050.1–0.92680540 7910.50.3–0.798.9<0.001Random
Umbilical cord blood030.3–4.37832481.70.6–4.992.3<0.001Random
image

Figure 3. Estimates of (a) prevalence of Chagas disease in pregnant women, and (b) congenital transmission rate of T. cruzi infection by states.

Download figure to PowerPoint

Information on the age distribution was available in four studies. The highest prevalence was found in pregnant women >30 years (1.4%, 95% CI: 0.4–4.7) (Table 3).

Congenital transmission rate

In quantitative analysis, eight studies were included in the meta-analysis. One study was excluded due to sample size <10 children (Araújo et al. 2009). Pooled congenital T. cruzi transmission rate among studies was 1.7% (95% CI: 0.9–3.1), with low degree and significant heterogeneity (I2: 44.5%, P = 0.08) (Table 4). Evidence of significant publication bias was found (Egger's test, P = 0.02). Duval and Tweedie's trim and fill method (random effect) imputed one hypothetically missing study, with an adjusted congenital transmission rate of 2.0% (95% CI: 1.0–3.9). Congenital transmission estimates for the study period varied between 2.0% (95% CI: 1.0–3.6) in 1980–1989, 2.3% (95% CI: 1.2–4.6) in 1990–1999 and 0.2% (95% CI: 0.0–1.3) after 2000 (Table 4). The highest estimation of regional congenital transmission rate was observed in the Southeast region (2.1%, 95% CI: 0.9–5.0) (Table 4). The states of São Paulo (3.9%; 95% CI: 1.8–7.9) and Minas Gerais (1.2%; 95% CI: 0.3–4.7) had the highest estimates (Figure 3b). Estimates were higher in studies performed in urban areas (3.1%, 95% CI: 1.2–8.0), hospital-based samples (2.2%, 95% CI: 1.4–3.6) and sample sizes of <100 children born to infected mothers (3.5%, 95% CI: 1.8–9.8) (Table 4).

Table 4. Pooled estimates of the congenital transmission rate of T. cruzi infection, stratified by subgroups.
CharacteristicsNumber of studiesRangeaPooled congenital T. cruzi transmission rateHeterogeneity
CaseSample sizeInfection rate (%)95% ICI2 (%)P-value (Cochran's Q)Model
  1. We calculated pooled transmission rates with a fixed- or random-effects model. We used the I² statistic and Cochran's Q to estimate heterogeneity between studies. 95% CI: 95% confidence intervals. NA, information not available.

  2. a

    Observed congenital transmission rate in studies.

Overall transmission rate080.2–5.22016091.70.9–3.144.50.082Random
Study period
1980–1989040.7–3.1116572.01.1–3.613.30.326Fixed
1990–1999031.1–5.284112.31.2–4.639.80.190Fixed
>20000115410.20.0–.1.30.01
Region of Brazil
North-east0131861.60.5–4.90.01
South-east050.2–5.2139672.10.9–5.056.70.055Random
Central-west020.7–1.144560.90.3–2.40.00.654Fixed
Study area
Urban0141293.11.2–8.00.00.514
Urban/Rural040.2–5.2109601.60.5–4.565.40.034Random
NA030.7–3.165201.40.6–3.212.90.317Fixed
Sample size
<100023.1–5.251223.51.8–9.80.00.573Fixed
100–200041.1–3.1126681.91.1–.3.30.00.647Fixed
>200020.2–0.738190.50.1–1.419.10.266Fixed
Diagnostic method
Serological0131751.70.6–5.20.01.0
Parasitological/xenodiagnosis021.1–1.653641.40.6–3.30.00.690Fixed
Parasitological/serological/xenodiagnosis023.1–5.251224.21.8–9.80.00.573Fixed
Serological/xenodiagnosis020.7–3.164071.60.4–6.665.50.089Random
Hemoculture/serological/PCR0115410.20.0–1.30.01.0
Study setting/sample type
Population/Community based020.2–1.747160.70.1–5.573.30.053Random
Hospital based060.7–5.2168932.21.4–3.625.70.241Fixed
Blood sample (screening)
Venous blood01022780.70.2–2.80.01.0Fixed
Peripheral blood/capillary blood dried on filter paper030.2–1.7079021.20.6–2.552.20.124Fixed
Umbilical cord blood/peripheral blood01021781.10.3–4.10.01.0
Umbilical cord blood/venous blood0103585.21.1–14.40.01.0
NA023.1–3.1061933.11.4–6.70.00.993Fixed

Number of pregnant women and children born with T. cruzi infection

In 2010, the estimated number of women of childbearing age infected with T. cruzi in Brazil was 683 217 (95% CI: 372 664–1 242 213), with an expected number of 34 629 infected pregnant women (Table 5). Considering the estimated pooled congenital transmission rate, there was an expected number of 589 (95% CI: 312–1073) newborns with congenitally acquired T. cruzi infection in Brazil in 2010 (Table 5). The incidence was estimated at 18.7 congenital cases per 100 000 live births (95% CI: 9.9–34.1).

Table 5. Estimated number of women of childbearing age, pregnant women and newborns infected by T. cruzi in Brazil and regions, 2010.
RegionNumber of women of childbearing age (10–49 year-olds)aEstimated number of women of childbearing age infected with T. cruzi (95% IC)bNumber of live births recordedcEstimated numbers of pregnant women infected/newborns from infected mothersbExpected number of newborns infected with T. cruzid
Lower limitMiddle limitUpper limit
  1. 95% CI, 95% confidence intervals. Estimated number of pregnant women in 2010: total population × birthrate + 10% (losses resulting of underreporting and abortions) or total of live births +10%.

  2. a

    Data obtained from 2010 National Demographic Census (IBGE).

  3. b

    Estimated using the result of pooled estimated prevalence of Chagas disease in pregnant women at national level (1.1%; 95% CI: 0.6–2.0).

  4. c

    Data obtained from SINASC.

  5. d

    Estimated using the estimated pooled congenital transmission rate of T. cruzi infection at national level (1.7%; 95% CI: 0.9–3.1).

North5 206 85457 275 (31 241–104 137)306 42237083363115
North-east17 476 138192 238 (104 857–349 523)841 16010 17892173316
South-east2 597 7400285 751 (155 864–519 548)1 123 59313 595122231421
South8 735 41896 090 (52 413–174 708)369 90544764076139
Central-west4 714 82751 863 (28 289–94 297)220 7882672244583
Brazil62 110 637683 217 (372 664–1 242 213)2 861 86834 6293125891073

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

This systematic review provides a comprehensive overview of the prevalence of Chagas disease in pregnant women and of the congenital transmission rate of T. cruzi infection in Brazil, over a period of more than three decades. The data indicate an increasing urbanisation of the disease, higher prevalence in women with more advanced age, and considerable regional and temporal variations of congenital transmission risk.

With the development of national programs in recent decades, focusing on systematic entomological surveillance and screening of blood donors, control of vector and blood-borne transmission was achieved in most endemic areas (Gurtler et al. 2003; Ramos Jr et al. 2010; Martins-Melo et al. 2012a). Consequently, congenital transmission has an increasing epidemiological importance (Reiche et al. 1996; Brazilian Ministry of Health 2005; Ostermayer et al. 2005; Andrade & Gontijo 2008; Bern et al. 2009). In Argentina, it has been estimated that congenital cases are at least 10 times more frequent than acute cases by vector transmission (Gurtler et al. 2003).

In this context, the higher prevalence in pregnant women at more advanced age (>30 years) reflects the trend of ageing of patients with chronic Chagas disease, after successful control of vector and blood-borne transmission in the last decades (Martins-Melo et al. 2012a,c, 2014). A national seroprevalence survey conducted in Brazil's rural areas (2001–2008), including about 105 000 children aged 0–5 years (Ostermayer et al. 2011), has found a prevalence of 0.03% (32 confirmed cases) – 0.02% (20) with probable congenital transmission, mostly from Rio Grande do Sul state, and only 0.01% (11) with probable vector transmission (Ostermayer et al. 2011). Currently, about 60–90% of Brazil's population infected with T. cruzi is living in urban areas (Dias 2007; Martins-Melo et al. 2014). As a result, congenital transmission, as confirmed by our study, has been an increasing problem of urban centres.

Latin American urbanisation and migratory movements from endemic to non-endemic countries, including women of reproductive age, also have changed transmission dynamics (Schmunis & Yadon 2010; Dias 2013). Migration of women of childbearing age to non-endemic countries is partially responsible for spread of Chagas disease worldwide through congenital transmission (Schmunis & Yadon 2010). For example, congenital cases in non-endemic countries have been reported from Spain, USA Sweden, Switzerland and Japan (Pehrson et al. 1981; Jackson et al. 2009; CDC 2012; Merino et al. 2013; Imai et al. 2014).

It can be assumed that congenital transmission will continue being a public health problem in Latin American countries for years (and in countries receiving migrants from endemic areas), despite the decline of prevalence of Chagas disease over the past decades. As long as a significant proportion of women of childbearing age are still seropositive for T. cruzi, congenital transmission will occur (Gontijo et al. 2009; Raimundo et al. 2010).

The prevalence of Chagas disease in pregnant women among studies ranged from 0.1% (Mato Grosso do Sul state, 2002–2003) (Figueiró-Filho et al. 2007) to 8.5% (Salvador city, 1981–1982) (Bittencourt 1984), and congenital transmission rate from 0% (Pelotas city, 2004) (Araújo et al. 2009) to 5.2% (São Paulo city, 1999) (Nisida et al. 1999). The observed and pooled congenital transmission rates are lower than in other Latin American endemic countries: 0.75–17% in Argentina; 3.4–11% in Bolivia; 0.49–19% in Chile; 1.44–10% in Paraguay; and 0.13–1.57% in Uruguay (Yadon & Schmunis 2009; Howard et al. 2014), and non-endemic countries (children born to immigrant Latin American pregnant women): 0–28.6% in Spain, and 25% in Switzerland (Howard et al. 2014). These variations may be caused by the degree of parasitemia of the infected mother, differing parasite strains, exposure to vector-borne re-infections during pregnancy, occurrence of acute form of the disease during pregnancy, different origins of the population studied (Latin American immigrants in non-endemic countries), maternal age, as well as different diagnostic techniques and study designs (Bittencourt 1992; Andrade et al. 1994; Gurtler et al. 2003; Hermann et al. 2004; Moretti et al. 2005; Torrico et al. 2006; Salas et al. 2007; Yadon & Schmunis 2009; Carlier & Truyens 2010; Howard et al. 2014).

The Brazilian Consensus on Chagas disease and the World Health Organization (WHO) reinforce the need for implementation of routine screening programs for Chagas disease in pregnant women and newborns at risk (Brazilian Ministry of Health 2005; Gontijo et al. 2009; Carlier et al. 2011). In fact, screening pregnant women at risk is a cost-effective intervention, not only for early diagnosis of congenital Chagas disease, but also for improvement in quality of life and prognosis for patients (Billot et al. 2005; Sicuri et al. 2011; Alonso-Vega et al. 2013). High cure rates of specific treatment of congenital cases justify the efforts needed to detect infection by T. cruzi in mothers and their newborns (Gontijo et al. 2009). However, these recommendations are neglected in most endemic and non-endemic countries receiving Latin American immigrants (Buekens et al. 2008; Pinto et al. 2011; Imai et al. 2014). In Brazil, only the states of Goiás and Mato Grosso do Sul have established systematic prenatal screening programs in all municipalities (Figueiró-Filho et al. 2007; Botelho et al. 2008; Gomes Filho et al. 2009). Specific antiparasitic treatment is mandatory in all congenital cases, but is not recommended during pregnancy, due to toxicity and teratogenic risks of available drugs (benznidazole and nifurtimox) (Brazilian Ministry of Health 2005; Gontijo et al. 2009; Carlier et al. 2011).

There are several factors limiting the estimation of prevalence of Chagas disease in pregnant women and congenital transmission rate in Brazil (Martins-Melo et al. 2012a, 2014). First, only acute forms of the disease are subject to compulsory notification, and contemporary data on the prevalence of Chagas disease on national or regional level are scarce (Camargo et al. 1984; Martins-Melo et al. 2014). Second, systematic control programs on congenital Chagas transmission through prenatal and neonatal screening are not routinely established at national level, nor in most endemic areas (Gurtler et al. 2003). Lastly, as most children with congenital infection are asymptomatic (Oliveira et al. 2010), the number of congenital cases is still underestimated.

There were only a small number of relevant studies included, with a clear geographic focus. Consequently, the included studies may reflect the situation in some areas or regions in Brazil, but due to the lack of data from other regions not the reality of the entire country. Furthermore, the studies were conducted during a period of about 30 years (1980–2013). This long time period was necessary because of limited data availability in some areas of Brazil. Thus, prevalence figures should be interpreted and compared with care, especially in those areas where due to the lack of more recent studies, current data were not available. Other limitations of our analysis refer to differences in diagnostic techniques used, different settings and populations, case definitions and methods used to detect infection in children born to infected mothers.

We assumed that the estimated prevalence can be generalised to the general population of women of childbearing age and that the prevalence and transmission rates did not vary between regions, period and mother's age. While there is evidence that the prevalence of Chagas disease was different over decades and among regions, this assumption was applied for the sake of simplicity (Yadon & Schmunis 2009; Martins-Melo et al. 2014). Thus, the numbers presented provide a general overview of the burden of congenital Chagas disease, indicating the importance of this mode of transmission (Yadon & Schmunis 2009).

There is a need to implement public health programs directed to congenital transmission at national and regional levels. Chagas disease in Brazil and some other endemic countries is suffering from the so-called curse of success, where reduction in public health importance also reduces public and political interest and budgets (Massad 2008). Clearly, the potential re-emergence of vector transmission and the importance of congenital transmission in the maintenance of Chagas disease in Brazil are underestimated by policy makers.

Adequate access to health services and social assistance should be guaranteed for the large number of individuals affected by chronic Chagas disease (Ramos et al. 2010; Martins-Melo et al. 2012a). Most infected pregnant women present in the chronic phase of the disease, especially in the indeterminate form. This reinforces the need for the introduction of compulsory notification also of chronic forms of Chagas disease (Martins-Melo et al. 2012a).

In conclusion, our findings show that congenital Chagas disease is an important but neglected health problem in Brazil, with significant regional differences. Systematic implementation of surveillance and control of congenital Chagas disease is needed, including routine screening of infection by T. cruzi in pregnant women and newborns, early case detection, prompt treatment and follow-up of children with congenital infection. Epidemiological data on the extension of maternal and congenital T. cruzi infection are lacking from many endemic areas.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

We thank the Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil) for granting a PhD Scholarship to FRM and Master Scholarship to MSL. JH is research fellow at the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil).

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
  • Alonso-Vega C, Billot C & Torrico F (2013) Achievements and challenges upon the implementation of a program for national control of congenital Chagas in Bolivia: results 2004–2009. PLoS Neglected Tropical Diseases 7, e2304.
  • Andrade AQ & Gontijo ED (2008) Neonatal screening for congenital Chagas infection: application of latent class analysis for diagnostic test evaluation. Revista da Sociedade Brasileira de Medicina Tropical 41, 615620.
  • Andrade ALSS, Zicker F & Martelli CMT (1994) An epidemiological approach to study congenital Chagas’ disease. Cadernos de Saúde Pública 10(Suppl. 2), 345351.
  • Araújo AB, Castagno VD, Gallina T & Berne ME (2009) Prevalence of Chagas disease among pregnant women in the southern region of Rio Grande do Sul. Revista da Sociedade Brasileira de Medicina Tropical 42, 732733.
  • Arteaga-Fernandez E, Pereira Barretto AC, Ianni BM et al. (1987) Incidence of congenital transmission of Chagas’ disease. Arquivos Brasileiros de Cardiologia 49, 4749.
  • Bern C, Verastegui M, Gilman RH et al. (2009) Congenital Trypanosoma cruzi transmission in Santa Cruz, Bolivia. Clinical Infectious Diseases 49, 16671674.
  • Billot C, Torrico F & Carlier Y (2005) Cost effectiveness study of a control program of congenital Chagas disease in Bolivia. Revista da Sociedade Brasileira de Medicina Tropical 38(Suppl. 2), 108113.
  • Bittencourt AL (1976) Congenital Chagas disease. American Journal of Diseases of Children 130, 97103.
  • Bittencourt AL (1984) Congenital Chagas’ disease in Bahia. Revista Baiana de Saúde Pública 11, 165208.
  • Bittencourt AL (1992) Possible risk factors for vertical transmission of Chagas disease. Revista do Instituto de Medicina Tropical de São Paulo 34, 403408.
  • Botelho CAO, Tomaz CAB, Cunha RV et al. (2008) [Prevalence of diseases screened by a pregnancy protection program of the State of Mato Grosso do Sul, Brazil, 2004–2007]. Revista de Patologia Tropical 37, 341353.
  • Brazilian Ministry of Health (2005) Brazilian Consensus on Chagas disease. Revista da Sociedade Brasileira de Medicina Tropical 38(Suppl. 3), 129.
  • Buekens P, Almendares YCarlier, Y, et al. (2008) Mother-to-child transmission of Chagas’ disease in North America: why don't we do more? Maternal and Child Health Journal 12, 283286.
  • Camargo ME, Silva GR, Castilho EA & Silveira AC (1984) Serological survey of the prevalence of Chagas’ infection in Brazil, 1975/1980. Revista do Instituto de Medicina Tropical de São Paulo 26, 192204.
  • Carlier Y & Torrico F (2003) Congenital infection with Trypanosoma cruzi: from mechanisms of transmission to strategies for diagnosis and control. Revista da Sociedade Brasileira de Medicina Tropical 36, 767771.
  • Carlier Y & Truyens C (2010) Maternal-fetal transmission of Trypanosoma cruzi. In: American trypanosomiasis – Chagas disease. One hundred years of research (eds J Telleria & M Tibayrenc) Elsevier, London, UK, pp. 539581.
  • Carlier Y, Torrico F, Sosa-Estani S et al. (2011) Congenital Chagas disease: recommendations for diagnosis, treatment and control of new-borns, siblings and pregnant women. PLoS Neglected Tropical Diseases 5, e1250.
  • CDC (2012) Congenital transmission of Chagas disease – Virginia, 2010. Morbidity and Mortality Weekly Report (MMWR) 61, 477479.
  • Dias JCP (2007) Globalization, inequity and Chagas disease. Cadernos de Saúde Pública 23(Suppl 1), S13S22.
  • Dias JCP (2013) Human chagas disease and migration in the context of globalization: some particular aspects. Journal of Tropical Medicine 2013, 789758.
  • Duval S & Tweedie R (2000) Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56, 455463.
  • Egger M, Smith GD, Schneider M & Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 315, 629634.
  • Figueiró-Filho EA, Senefonte FRA, Lopes AHA et al. (2007) Frequency of HIV-1, rubella, syphilis, toxoplasmosis, cytomegalovirus, simple herpes virus, hepatitis B, hepatitis C, Chagas disease and HTLV I/II infection in pregnant women of State of Mato Grosso do Sul. Revista da Sociedade Brasileira de Medicina Tropical 40, 181187.
  • Gomes Filho C, Macedo Filho JV, Gomes MM & Luquetti AO (2009) Expanded prenatal screening: the mommy test. Vita et Sanitas 03, 101109.
  • Gontijo ED, Andrade GQM, Jannuzzi JH et al. (1998a) Doença de Chagas congênita-inquérito sorológico em Minas Gerais-modelo e proposta. Revista da Sociedade Brasileira de Medicina Tropical 31 (Suppl. 3), 5354.
  • Gontijo ED, Sousa HM, Dias JCP et al. (1998b) Doença de Chagas congênita: estudo transversal em hospitais universitários de Belo Horizonte e Uberaba. Revista da Sociedade Brasileira de Medicina Tropical 31(Suppl. 3), 2526.
  • Gontijo ED, Andrade GMQ, Santos SE et al. (2009) Neonatal screening program for the infection by Trypanosoma cruzi in Minas Gerais, Brazil: congenital transmission and tracking of the endemic areas. Epidemiologia e Serviços de Saúde 18, 243254.
  • Gurtler RE, Segura EL & Cohen JE (2003) Congenital transmission of Trypanosoma cruzi infection in Argentina. Emerging Infectious Diseases 9, 2932.
  • Hedges LV & Vevea JL (1998) Fixed-and random-effects models in meta-analysis. Psychological Methods 3, 486504.
  • Hermann E, Truyens C, Alonso-Vega C et al. (2004) Congenital transmission of Trypanosoma cruzi is associated with maternal enhanced parasitemia and decreased production of interferon- gamma in response to parasite antigens. The Journal of Infectious Diseases 189, 12741281.
  • Higgins JP & Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 21, 15391558.
  • Higgins JP, Thompson SG, Deeks JJ & Altman DG (2003) Measuring inconsistency in meta-analyses. British Medical Journal 327, 557560.
  • Howard E, Xiong X, Carlier Y, Sosa-Estani S & Buekens P (2014) Frequency of the congenital transmission of Trypanosoma cruzi: a systematic review and meta-analysis. BJOG: An International Journal of Obstetrics & Gynaecology 121, 2223.
  • Imai K, Maeda T, Sayama Y et al. (2014) Mother-to-child transmission of congenital Chagas disease, Japan. Emerging Infectious Diseases 20, 146148.
  • Jackson Y, Myers C, Diana A et al. (2009) Congenital transmission of Chagas disease in Latin American immigrants in Switzerland. Emerging Infectious Diseases 15, 601603.
  • Liberati A, Altman DG & Tetzlaff J (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Annals of Internal Medicine 151, 6594.
  • Martins-Melo FR, Alencar CH, Ramos AN Jr & Heukelbach J (2012a) Epidemiology of mortality related to Chagas’ disease in Brazil, 1999–2007. PLoS Neglected Tropical Diseases 6, e1508.
  • Martins-Melo FR, Ramos AN Jr, Alencar CH, Lange W & Heukelbach J (2012b) Mortality of Chagas’ disease in Brazil: spatial patterns and definition of high-risk areas. Tropical Medicine & International Health 17, 10661075.
  • Martins-Melo FR, Ramos AN Jr, Alencar CH & Heukelbach J (2012c) Multiple causes of death related to Chagas’ disease in Brazil, 1999 to 2007. Revista da Sociedade Brasileira de Medicina Tropical 45, 591596.
  • Martins-Melo FR, Ramos AN Jr, Alencar CH & Heukelbach J (2014) Prevalence of Chagas disease in Brazil: a systematic review and meta-analysis. Acta Tropica 130, 167174.
  • Massad E (2008) The elimination of Chagas’ disease from Brazil. Epidemiology & Infection 136, 11531164.
  • Medina-Lopes MD (1992) Transmissão materno-infantil da doença de Chagas: incidência da forma congênita e da adquirida durante aleitamento. Revista da Sociedade Brasileira de Medicina Tropical 25(Suppl. 3), 99.
  • Merino FJ, Martínez-Ruiz R, Olabarrieta I et al. (2013) Control of Chagas disease in pregnant Latin-American women and her children. Revista Española de Quimioterapia 26, 253260.
  • Moretti E, Basso B, Castro I et al. (2005) Chagas’ disease: study of congenital transmission in cases of acute maternal infection. Revista da Sociedade Brasileira de Medicina Tropical 38, 5355.
  • Mota CCC (1993) Significado diagnóstico e conduta na doença de Chagas congênita. Revista da Sociedade Brasileira de Medicina Tropical 26(Suppl. 2), 7677.
  • Nisida IV, Amato Neto V, Braz LM, Duarte MI & Umezawa ES (1999) A survey of congenital Chagas’ disease, carried out at three health institutions in Sao Paulo City, Brazil. Revista do Instituto de Medicina Tropical de São Paulo 41, 305311.
  • Oliveira I, Torrico F, Muñoz J & Gascon J (2010) Congenital transmission of Chagas disease: a clinical approach. Expert Review of Anti-Infective Therapy 8, 945956.
  • Ostermayer AL, Ferreira AW, Oliveira RA et al. (2005) Congenital transmission of Trypanosoma cruzi in Brazil: estimation of prevalence based on preliminary data of national serological surveys in children under 5 years old and other sources. Revista da Sociedade Brasileira de Medicina Tropical 38(Suppl. 2), 2426.
  • Ostermayer AL, Passos AD, Silveira AC, Ferreira AW, Macedo V & Prata AR (2011) The national survey of seroprevalence for evaluation of the control of Chagas disease in Brazil (2001–2008). Revista da Sociedade Brasileira de Medicina Tropical 44(Suppl. 2), 108121.
  • Pan American Health Organization (2006) Estimación cuantitativa de la enfermedad de Chagas en las Americas. Pan American Health Organization, Washington, DC, USA. Available: http://www.bvsops.org.uy/pdf/chagas19.pdf. Accessed: June 15, 2013.
  • Pehrson PO, Wahlgren M & Begtsson E (1981) Asymptomatic congenital Chagas’ disease in a 5-year-old-child. Scandinavian Journal of Infectious Diseases 13, 307308.
  • Pinto AYN, Valente VC, Valente SAS & Figueiras ACM (2011) Congenital Chagas disease due to acute maternal Trypanosoma cruzi infection transmitted by the oral route. Revista Pan-Amazônica de Saúde 2, 8994.
  • Raimundo SM, Massad E & Yang HM (2010) Modelling congenital transmission of Chagas’ disease. Biosystems 99, 215222.
  • Ramos AN Jr, Martins-Melo FR, Barbosa JC & Heukelbach J (2010) The role of operational research and the challenges for integration of care and control of Chagas disease in the Brazilian Unified Health System. Revista da Sociedade Brasileira de Medicina Tropical 43(Suppl. 2), 1217.
  • Rassi A, Amato Neto V, Rassi GG et al. (2004) A retrospective search for maternal transmission of Chagas infection from patients in the chronic phase. Revista da Sociedade Brasileira de Medicina Tropical 37, 485489.
  • Rassi A Jr, Rassi A & Marin-Neto JA (2010) Chagas disease. The Lancet 375, 13881402.
  • Reiche EMV, Inouye MMZ, Bonametti AM & Jankevicius JV (1996) Congenital Chagas’ disease: epidemiology, laboratorial diagnosis, prognosis and treatment. Jounal de Pediatria 72, 125132.
  • Reiche EMV, Morimoto HK, Farias GN et al. (2000) Prevalence of American trypanosomiasis, syphilis, toxoplasmosis, rubella, hepatitis B, hepatitis C, human immunodeficiency virus infection, assayed through serological tests among pregnant patients, from 1996 to 1998, of the Hospital Universitário Regional Norte do Paraná (Londrina State University, Paraná, Brazil). Revista da Sociedade Brasileira de Medicina Tropical 33, 519527.
  • Salas NA, Cot M, Schneider D et al. (2007) Risk factors and consequences of congenital Chagas disease in Yacuiba, south Bolivia. Tropical Medicine & International Health 12, 14981505.
  • Santos JI, Lopes MAA, Deliège-Vasconcelos E et al. (1995) Seroprevalence of HIV, HTLV-I/II and other perinatally-transmitted pathogens in Salvador, Bahia. Revista do Instituto de Medicina Tropical de Sao Paulo 37, 343348.
  • Schmunis GA & Yadon ZE (2010) Chagas disease: a Latin American health problem becoming a world health problem. Acta Tropica 115, 1421.
  • Sicuri E, Munoz J, Pinazo MJ et al. (2011) Economic evaluation of Chagas disease screening of pregnant Latin American women and of their infants in a non-endemic area. Acta Tropica 118, 110117.
  • Torrico F, Alonso-Vega C, Suarez E et al. (2004) Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected new-borns in Bolivia. The American Journal of Tropical Medicine and Hygiene 70, 201209.
  • Torrico F, Alonso-Veja C, Suarez E et al. (2005) Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia. Revista da Sociedade Brasileira de Medicina Tropical 38(Suppl. 2), 1720.
  • Torrico F, Vega CA, Suarez E et al. (2006) Are maternal re-infections with Trypanosoma cruzi associated with higher morbidity and mortality of congenital Chagas disease? Tropical Medicine & International Health 2, 628635.
  • Vaz AJ, Guerra EM, Ferratto LCC, Toledo LAS & Azevedo Neto RS (1990) Positive sorology of syphilis, toxoplasmosis and Chagas’ disease in pregnant women on their first visit to State Health Centres in a metropolitan area, Brazil. Revista de Saúde Pública 24, 373379.
  • World Health Organization (2012) Chagas’ disease (American trypanosomiasis) fact sheet (revised in August 2012). Weekly Epidemiological Record 87, 519522.
  • Yadon ZE & Schmunis GA (2009) Congenital Chagas disease: estimating the potential risk in the United States. The American Journal of Tropical Medicine and Hygiene 81, 927933.