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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.
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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.