Neglected Tropical Diseases (NTD) are found in 149 countries with different populations, economies and health systems, according to a report of the World Health Organization (WHO) of 2011.¹ One of the most important NTD is Chagas’ Disease. Among the most affected countries are the developing ones and the population that is most affected by this disease is the low-income people, who are invisible and have no political voice.²

Trypanossoma cruzi is a protozoanthe that is the etiologic agent of Chagas’ Disease – also known as american trypanosomiasis. There are 6 forms of contamination:^2-4 1. by the excrement of blood-sucking insects of Triatominae family contaminated with the T cruzi which penetrates skin fissures of the individual after being bit by the infected insect; 2. by oral transmission, through the ingestion of contaminated food; 3. by blood transfusion; 4. by organ transplantation; 5. by vertical transmission (mother-child); e 6. by laboratories incidents.

It is estimated that there has been a decrease in prevalence - of 17 millions of contaminated individuals, in 1980, to 6 millions, in 2009 - after supranational and governmental actions in many countries.⁵ WHO leads a global initiative to eradicate NTDs and established a goal for eradication of the transmission of Chagas’ Disease by blood transfusion until 2015 and by intra-domiciliary pathway until 2020. It considers the control of the transmitter well succeeded in many countries of Latin America, including Brazil.¹ In the same document, WHO pointed the necessity to sustain the control of oral and congenital transmission.

The United Nations Organization indicates, in the 2030 Agenda,⁶ the need to control this disease as follows: “by 2030, end the epidemics of AIDS, tuberculosis, malaria and NTD and combat hepatitis, water-borne diseases and other communicable diseases” (item 3.3 of the 2030 Agenda). As a consequence, the NDT was included in the center of political discussions.

According to estimations of 2010 of WHO,³ in Brazil there would be 1,156,821 people contaminated with Chagas’ Disease (0.61% of population); women in childbearing age (15 to 44 years old) would sum up to 119,298 infected individuals. The same document³ registered the possibility of 571 cases of congenital transmission of Chagas’ (incidence of 0.020 of 100 live births), however there is an estimation of 25,474,365 people in risk of contamination by this disease, that indicates underreporting. In addition, oral contamination was not considered in this estimation. The congenital contamination pathway seems to be relevant, mostly in Amazon and in Brazil.

The estimation of prevalence of T cruzi in Brazil, in 2020, in the population aged 25 or more was between 1,365,585 and 3,213,142 cases; 30% of these patients developed the cardiac form, 10% developed the digestive form and 60% stayed in the indeterminate form.^4,7 Among the population of infected people pregnant women are found and for this reason WHO recommends the screening of the pregnant women at risk of Chagas’ Disease, as well as their children, to avoid and treat congenital form.³

Between 2019 and 2020, according to the epidemiologic bulletin on Chagas’ Disease, of the Ministry of Health, 146 new acute cases were identified, with 2% of mortality (3/146 cases) – all cases were identified in the state of Pará – and six percent of the cases were diagnosed in pregnant women.⁷ A decrease in the registration of new cases during Covid19 was observed (reduction of 47% of the suspect cases and 63% of the confirmed cases), indicating underreporting.⁷ The bulletin of 2022 describes that 1.0 to 2.4% of the total population of Brazil was infected by T cruzi. It reflects a high rate of morbimortality to the public system of health; therefore, changes are necessary to detect new cases:⁸ since 2020 the chronic form of Chagas has been classified as a disease of compulsory notification in Brazil.^7,9 Until then, just the acute form was a disease of compulsory notification.

The importance of the treatment of childbearing women is clear in papers which show that treated mothers with trypanocide medication do not transmit the congenital form to their children.^10,11 The treatment is advocated in the 2nd Brazilian Consensus of Chagas’ Disease, of the Brazilian Society of Tropical Medicine.¹² The etiologic treatment should not be administered in pregnant women for teratogenicity has been observed in experimental animals, however in acute and severe cases the medical decision for the use of medication should be based on the risk-benefit ratio.^4,13

In the beginning of gestation, women with ventricular dysfunction of classes I and II end up without intercurrences. Nevertheless, the ones with classes III and IV dysfunctions can develop a severe case and the risk of mortality is around 25 and 50%.⁴ Furthermore, patients with heart failure and cardiac arrhythmia require special care and the avoidance of gestation is recommended.^4,13 The indeterminate form of the disease apparently does not increase the risk of mortality, but its reactivation during pregnancy can cause complications.

According to the Brazilian Ministry of Health, all pregnant women without the previous serological analysis and with the presence of the risk factors should be tested.¹⁴ Considering the evidence of under registration of cases and the hypothesis of maternal death in the pregnancy-puerperal cycle due to Chagas’ Disease in absence of diagnosis and adequate medical assistance, the aim of this paper is to review the literature on maternal mortality by Chagas’ Disease.

A systematic and integrative review of literature was conducted to identify publications about maternal mortality and Chagas’ Disease on the following websites: Medline, BVS, Bireme, Lilacs, Scielo, PubMed, and Science Direct. The search was performed in the period of January 2019 until December 2021. Furthermore, other researches were done in the site of the Ministry of Health of Brazil, National Committee of Incorporation of Technologies into Public System of Health (NCIT), WHO and of Brazilian Society of Cardiology (SBC), aiming to find all documents that describe consensus and public policies. The data of the System of Information about Mortality (SIM) were also used in the epidemiologic analyses.

The keywords used to search for studies were doença de Chagas and mortalidade materna, Chagas’ Disease and maternal mortality. All papers, master’s degree and PhD thesis, consensus, epidemiologic bulletins and manuals were considered for the revision process, in English, in Portuguese, and in Spanish.

No paper, master’s degree and PhD thesis, epidemiologic bulletins, WHO documents, consensus or manuals were excluded from the preliminary analysis, independently of the year of publication.

In the preliminary search using the keywords, 22 papers were found in the LILACS, Medline and Bireme; 17 papers in the PubMed; 1 paper in the Scielo and 1,286 papers in the Science Direct websites. After reading the titles and abstracts, just the papers with descriptions about maternal mortality of Brazilian women were selected.

Documents and data of the Ministry of Health of Brazil, NCIT, WHO, SIM and SBC were also compiled for the description of results.

All documents used in the revision are described in Table 1 and a brief explanation is in the Central Figure. It was difficult to find scientific evidence on the relevance of Chagas’ Disease in maternal mortality because of the lack of publications about this theme.

Table 1

Title	Authors/ Institucion	Year	Type of publication
Mortalidade materna no Brasil	Ministry of Health	2020	Epidemiologic bulletin
Mortalidade proporcional por grupos de causas em mulheres no Brasil em 2010 e 2019	Ministry of Health	2021	Epidemiologic bulletin
Boletim epidemiológico da Doença de Chagas	Ministry of Health	2021	Epidemiologic bulletin
Mortalidade materna no Brasil, 2009 a 2020	Ministry of Health	2022	Epidemiologic bulletin
Boletim epidemiológico – Territorialização e vulnerabilidade para doença de Chagas crônica	Ministry of Health	2022	Epidemiologic bulletin
Manual dos comitês de mortalidade materna	Ministry of Health	2009	Manual
Gestação de alto risco	Ministry of Health	2012	Technical manual
Protocolo clínico e diretrizes terapêuticas doença de Chagas – relatório de recomendação	Ministry of Health / NCIT	2018	Technical manual
Manual de gestação de alto risco	Ministry of Health	2022	Technical manual
Diretrizes da Sociedade Brasileira de Cardiologia para gravidez na mulher portadora de cardiopatia – 2009	Tedoldi CL, Freire CMV, Bub TF et al.	2009	Consensus of SBC
Posicionamento da Sociedade Brasileira de Cardiologia para gravidez e planejamento familiar na mulher portadora de cardiopatia – 2020	Avila WS, Alexandre ERG, de Castro ML, de Lucena AJG, Marques-Santos C, et al.	2020	Consensus of SBC
Diretriz da SBC sobre diagnóstico e tratamento de pacientes com cardiomiopatia da Doença de Chagas – 2023	Marin-Neto JA, Rassi A Jr, Oliveira GMM, Correia LCL, Ramos Júnior AN, Luquetti AO, Hasslocher-Moreno AM, et al.	2023	Consensus of SBC
Doença de Chagas no ciclo grávido-puerperal	Chuster M, Ezagui D.	1985	Book
Transmissão materno-infantil da Doença de Chagas	Medina-Lopes MD	1983	Master’s degree thesis
Repercussões da doença de Chagas materna no concepto da gestação ao nascimento	Mota, CCC	1986	Master’s degree thesis
Mulheres gestantes em pré-natal no Distrito Federal – Brasil: estudo do binômio mãe-filho para a frequência de infecção por Trypanosoma cruzi	Nobre TF.	2018	Master’s degree thesis
Sobre a transmissão transplacentária da infecção chagásica humana	Rezende CL, Canelas ZB, Pelegrino J.	1954	Scientific paper
Doença de Chagas e gravidez	Oliveira FC, Lopes ER, Alonso MT, Salum R, Bilharinho MR, Chapadeiro E.	1968	Scientific paper
Doença de Chagas na gestação	Magalhães JM Netto.	1988	Scientific paper
Morte materna em hospital de referência	Mattar R, Vigorito NM, Stavale JN, Camano L.	1990	Scientific paper
Mortalidade materna por cardiopatia	Feitosa HN, Moron AF, Born D, Almeida PA.	1991	Scientific paper
Prevalência das arritmias cardíacas em portadoras de doença de Chagas, sem cardiopatia aparente, durante e após a gravidez	Achá RES, Rezende MTO, Heredia RAG, da Silva AC, Rezende ES, Souza CAO.	2002	Scientific paper
Pregnancy in patients with heart disease: experience with 1.000 cases	Ávila WS, Rossi EG, Ramires JAF, Grimberg M, Bartolotto MRL, Zugaib M et al.	2003	Scientific paper
Morte por doenças infecciosas em mulheres: ocorrências no ciclo gravídico-puerperal	Laurenti R, Jorge MHPM, Gotlieb SLD.	2009	Scientific paper
Triagem neonatal da infecção pelo Trypanosoma cruzi em Minas Gerais, Brasil: transmissão congênita e mapeamento das áreas endêmicas	Gontijo ED, Andrade GMQ, Santos SE, Galvão LMC, Moreira DF, Pinto FS et al.	2009	Scientific paper
Epidemiology of mortality related to Chagas Disease in Brazil, 1999-2007	Martins-Melo FR, Alencar CH, Ramos AN Jr, Heukelbach J.	2012	Scientific paper
Immunosuppression and Chagas Disease: a management challenge	Pinazo MJ, Espinosa G, Cortes-Lletget C, Posada EJ, Aldasoro E, Oliveira I, et al.	2013	Scientific paper
Systematic review: prevalence of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in Brazil: a systematic review and meta-analysis	Martins-Melo FR, Lima MS, Ramos AN Jr, Alencar CH, Heukelbach J.	2014	Scientific paper
Reactivation of Chagas Disease: implications for global health	Perez CJ, Lymbery AJ, Thompson RCA.	2015	Scientific paper
Chagas disease: review of needs, neglect, and obstacles to treatment access in Latin America	Pinheiro E, Brum-Soares L, Reis R e Cubides JC.	2017	Scientific paper

NCIT: National Committee of Incorporation of Technologies into Public System of Health; SBC: Sociedade Brasileira de Cardiologia.

Few publications were found about the impact of Chagas’ Disease in the maternal mortality rates in Brazil. The disease and the maternal mortality for Chagas’ are underreported according to this review.

Many data are estimations of the number of infected people and how it would impact the society in case the rate of infection persists to be between 1 to 2.4% of the Brazilian population. More studies are necessary to identify the disease in pregnant women to prevent mortality.

The obligatory screening is done in pregnant women at risk of contamination, without previous serology.¹⁴ The risk factors that indicate serology are: 1. lives or have lived, in any period of time, with people diagnosed with Chagas’ Disease; 2. lives in a place with blood-sucking insects or animal reservoirs where an infection for T cruzi has been found; 3. lives or have lived in an area where the transmission or epidemiologic history has been confirmed; 4. has received blood transfusion or any kind of blood component before 1992; 5. has lived in any period of time in houses which favors the proliferation of the insect vector of the disease; and 6. has relatives of habitual coexistence that have been diagnosed, specially a mother, with confirmed infection.¹⁴

With the screening recommended by the Ministry of Health the identification of the pregnant women infected with the disease that move from one state to another should be possible, taking into account that the impact of migration in the spread of infectious diseases is well known.

Because of the high impact of Chagas’ Disease in the society, the Ministry of Health developed strategies for the screening of the disease in its chronicle form.⁸Moreover, it created a vulnerability index for chronic Chagas’ Disease (Índice de vulnerabilidade para doença de Chagas crônica – Índice DCC, in Portuguese) (Figure 2). These actions are in the structuring phase to establish the monitoring system in the entire territory.

Figure 2

The vulnerability index for chronic Chagas’ Disease and the effective establishment of the monitoring system in Brasil⁸ should result in improvement in the health services for pregnant women and in reduction of the total number of deaths.

In one of the studies half of the deaths of pregnant women (6:12) occurred in the absence of prenatal assistance.¹⁶ The data described shows also that the prevalence and incidence of Chagas’ Disease in pregnant and puerperal women are underrated and, as a consequence, so are the reports of maternal deaths.

The pregnant women with Chagas, even those classified in the indeterminate form, need a high-risk prenatal and puerperium follow-up. This follow-up should be done by a multidisciplinary team, including an obstetrician and a cardiologist. The reason for this recommendation is that, besides the cardiac alterations caused by the pregnancy, the chagasic infection in the indeterminate form can also impact and produce alterations in the cardiac function.²⁵ To verify the indeterminate form, it is necessary to evaluate the cardiac function, however, this is not done routinely.

The reactivation of the chagasic infection can occur during treatments with immunosuppressors or coinfection situations (other parasites or microorganisms).^40,41 The immunosuppression caused by pregnancy can reactivate the infeccion,⁴² causing cardiac dysfunction.

Regarding the screening of pregnant women, it was evaluated the cost-benefit of the screening of mothers and their babies (congenital infection) in USA, comparing with the health costs of the treatment of people without and with delayed diagnosis of Chagas' Disease.⁴³ Estimating a prevalence of 0.0131 of Chagas' among Hispanic women in the endemic areas and a cohort of 480,000 births/years, the screening during gestation could result in saving of 636 millions of dollars for each birth year.⁴³ The universal screening could save 426 millions of dollars for each birth year, with a prevalence of 0.06% and 4 million births in the USA.⁴³

Despite the favorable results, the underestimation of the total follow-up costs during the entire treatment of mothers and children is probable (annual checkups and other procedures). However, the data is really important since the implementation of the screening can impact the number of infected people in future generations and saving costs.

More studies are necessary to identify the disease in pregnant women to prevent mortality in this group – the disease and maternal mortality are underreported.

Maternal death is a serious violation of women's human rights because, in many cases, it can be prevented. The evidences found in this review shows the urgency for adopting measures to do the screening of pregnant women, identify Chagas' and provide the adequate treatment; the creation of an assistance program designed for chagasic pregnant women is necessary. This assistance must be followed throughout the puerperium, in order to decrease the indirect maternal mortality in this group.