Despite being in constant rise, congenital Chagas disease is still neglected

Publicação: 13 de September de 2018

Mother-to-child transmission currently occurs in 5% in the Cone-Sul and 1,5% in Central Brazil

In Brazil, only two States carry out the screening of pregnant women by “Mother’s Test Program”, coordinated by APAE [Association of Parents and Friends of Special Children] and by their respective Health departments

For infectious disease and public health researcher, Dr. Ana Yecê das Neves Pinto, congenital Chagas disease is neglected because the diagnosis during pregnancy is not carried out and, consequently, children born to infected mothers are rarely screened, even in the classic areas of occurrence of the disease in phase chronic. Still according to her, this also happens due to the decrease of public policies prevention actions on the subject, since there is a false sense of control with elimination of transmission of Trypanosoma cruzi by Triatoma infestans vector. “In the Amazon, for example, where there are still foci of transmission of high morbidity acute phase, the prenatal screening is not applied with mandatory and this implies potential risk of pregnant women with high parasitemia of transmitting the disease to their children”, she points.

In Argentina, the study to detect the disease in the pregnant mother is mandatory, but due to lack of monitoring it is estimated that after giving birth just one out of three children who became infected with T. cruzi this way is acknowledged. In Brazil, only two States, Mato Grosso do Sul and Goiás, perform the screening of all pregnant women as part of the “Mother Test Program”, coordinated by the Association of parents and friends of special children (APAE) and by the respective Health Departments. According to the researcher and professor at the Universidade Federal de Goiás (UFG), specialist in the subject, Dr. Alejandro Luquetti, the procedure has already allowed to detect more than 3 thousand infected pregnant women. “The experience in the state of Goiás, with the Department of health and the APAE has been excellent, with a coverage of over 90% of the pregnant women in the state, since 2005. We know precisely where infected mothers are”, he celebrates while regretting that not all of them seek medical attention or bring their children for examination to rule out vertical transmission (mother to child). Chagas disease mother to child transmission is currently one of the main routes of infection in countries where vector transmission has been controlled, with surveillance, by improving housing standards and by applying the screening blood donation candidates in hemocenters (blood banks), such as Argentina, Brazil, Chile, Honduras, Paraguay, Nicaragua and Uruguay.

However, congenital Chagas disease represents one of the fields where additional efforts should be concentrated. Dr. Luquetti points out that the main transmission mechanisms, in order of importance, are (1)vector (including oral – insects and/or their droppings in food), (2)transfusion and (3)congenital. “Once controlled the first two, as some of these countries have done, vertical transmission remains as the most important”, he explains.

The impact of mother-to-child transmission

In accordance to Dr. Ana Yecê, disregarding the binomial child and only considering the child, the impact of Chagas disease transmission in relation to other major congenital infections is slightly larger than that of toxoplasmosis and Cytomegalovirus, however, it is lower if compared to herpes virus, congenital syphilis, rubella and zika virus. However, considering the mother-child binomial, the complexity of Chagas’ disease is greater, since among women, cytomegalovirus, toxoplasmosis, herpesvirus, rubella and even zika virus are aggravated by low morbidity and are most often, asymptomatic. Speaking of Chagas disease, however, for both mother and fetus, this means a possibility of serious illness, with particular emphasis on the acute phase, added to the fact that the only drug available for treatment has a considerably toxic potential and its effectiveness is questionable during the chronic phases. “Conclusively, from a mother-to-child perspective, Chagas disease, if compared to other potential vertical transmission infections, presents the greater impact on the health of exposed populations,” he explains.

The size of Brazil’s problem

To Dr. Ana Yecê, the difficulty in establishing the size of the problem relies on failures of prenatal screening (traceback) in the regions where the predominant disease is in its chronic phase, as well as the absence of this procedure in places where the predominant disease is in its acute phase, in transmission of greater morbidity, as happens in the Amazon. Besides this, she cites the lack of clarity in the indications given by experts regarding information about mother-to-child transmission and consequent postponement of treatment beginning. “For example, the presence of passive antibodies in the child may induce diagnostic errors during the first months of life. This postpones the beginning of an asymptomatic child’s treatment, considering there is no way to differentiate which antibodies were inherited from the mother and which are the child’s own antibodies”, he says.

The specialist is categorical in emphasizing that public policies that allow wide and unrestricted access to prenatal diagnosis of any potential vertical transmission, including Chagas disease, must be quickly implemented. “Similarly, encouraging the tracking of silent infectious for women in fertile age groups, could be strategically linked to haemovigilance programs in the Country”, she says.

Dr. Luquetti recalls that since the are no measures to avoid vertical transmission, since the factors that favor it are unknown, the only effective measure is etiological treatment of girls or young women, which is difficult to implement. Still according to him, mother-to-child Chagas disease transmission has always existed, but it is now clearer due to the infected mother’s early diagnostic.

The Pan American Health Organization (PAHO) recommends universal screening for Chagas disease for pregnant women, parasite screening for newborns or serological study after seven months of age, which if positive is a formal indication for etiological treatment, curable in all cases. It is also encouraging to treat women after giving birth and diagnose and treat children of other women who had positive results.

According to the II Brazilian Consensus on Chagas disease, Latin America is estimated to have over 15 congenital cases of Chagas disease every year, while recent estimates point to 8,668 children infected by vertical transmission. Still according to the document, congenital Chagas diseases in Brazil is considered an acute disease, therefore, of obligatory notification. However, specific surveillance in pregnant women or exposed/infected children has not been established in the country. On the other hand, anti T.  cruzi treatment for infected women in fertile age groups, who are not pregnant, can be an effective strategy to reduce vertical transmission for future generations. Vertical transmission can happen every pregnancy, throughout the fertile period of a woman’s life.

Prevention measures

– In areas where products potentially involved in transmissions are eaten: washing, sanitizing and obedience to the recommended handling of “raw” food.

– Use of conservatives as global prevention;

– Effective hemovigilance among candidates for blood, tissue or organ donation.

Importance of prenatal care

Essentially, tracking infected mothers who are unaware of morbid conditions for all potential infections of vertical transmission. This way, if the mother’s condition is known, the prenatal care can be fit, aiming to detect early risk situations to the baby, which will be, therefore, duly accompanied with the opportunity for early diagnostic and complication prevention.

“The excellent tolerance of babies to the drugs used for treatment and the early diagnostic opportunity in phase similar to acute phase, make the chances of cure very high in these babies”, says Dr. Ana Yecê.

International Evidence

It is estimated that Brazil will have 3 million infected people by 2020, approximately 950 thousand with the chronic heart form and 410 thousand with the digestive form, according to analysis published in the II Brazilian Consensus in Chagas Disease in 2015. These numbers reinforce the burden of disease in the country and the challenges to achieve control. The experiences from the State of Goiás has clearly demonstrated that Chagas disease is a relatively common event among women tested after 2003. In this same sense, Latin-American evidences, especially in Argentina, reinforce this way of transmission as a public health issue and its impact on population control. In fact, the treatment of children with benznidazole is highly effective in eliminating the infection by T. cruzi.

According to Professor at the Community Health Department at the Ceara Federal University Medical School, Dr. Alberto Novaes Ramos Junior, also a specialist in the theme, from a premise that congenital infection could indefinitely support Chagas disease transmission, its importance is acknowledged even considering scenarios in countries where there is no vector-borne transmission. “Despite existing few studies about the economic impact of Chagas disease and the interventions to reduce morbidity and mortality, especially regarding economic assessments of the maternal tracking programs, there are important indicators that support intervention. In fact, the screening of pregnant women has already proved cost-effective in other countries with lower disease burden, such as Spain and the United States of America. In Spain, costs of a tracking system for Latin-American women was estimated. They used two analytical perspectives: one for the cost of mothers and other for the cost of children. In the Spanish study, it was found in a compelling way that a screening programme was in fact cost-effective in a wide range of screening costs according to different probability of maternal prevalence and mother-to-child transmission”, he adds. Another more recent study published in June 2018 assessed costs related to maternal screening and testing of exposed children, as well as the treatment of Chagas disease in the United States [Stillwaggon and Perez-Zetune V, Bialek, Mr. Montgomery SP. Congenital Chagas Disease in the United States: Cost Savings through Maternal Screening. Am J Trop Med Hyg. Jun 2018 98 (6): 1733-1742.] “The analytical decision-making model used in this study sought to recognize the cheaper option, comparing costs of tests and treatment, as needed, for mothers and babies with social costs in lives of people without access to tests and the consequent morbidity and mortality due to the lack of treatment or delayed treatment” he explains.

The study revealed that performing maternal screening, infant testing, and treatment of Chagas’ disease in the United States together accounted for cost savings for all congenital transmission rates above 0.001% and for all maternal prevalence levels above 0.06%, if compared to the absence of a screening program. Recently approved diagnostic methods allow universal screening to reduce costs in settings with maternal prevalence as low as 0.008%. The value of social economy through life due to the screening and treatment summed approximately USD 634 million for each year of birth cohort. The authors concluded that the benefits of universal screening for T. cruzi as part of routine prenatal testing outweighs the costs of the actions of the attention program for all births in the United States.

The Brazil is implementing epidemiological surveillance through notification of chronic cases of the disease, in addition to the acute cases already established, what would be appropriate, therefore, the adoption of these procedures for serological screening to integrate these people diagnosed to the unified health system (SUS).

“We emphasize that Chagas disease is historically one of the most neglected diseases, with diagnostic restriction to millions of people, a restriction that widens when considering access to treatment (less than 20% of people who need in fact have access). Its elevated burden in Brazil (the largest of neglected diseases) [Malik-Melo FR, Lamb M, Ramos AN Jr, J, Ribeiro Heukelbach ALP, Werneck GL. The burden of Neglected Tropical Diseases in Brazil, 1990-2016: A subnational analysis from the Global Burden of Disease Study 2016. PLoS Negl Trop Dis. 2018 Jun 4;12 (6) 0006559.: e0006559. –] reinforces the required response to the problem in Brazil”, says Dr. Novaes.

From the American standpoint, since 2010, the Member States of the Pan American Health Organization (PAHO) have committed to the eliminate mother-to-child transmission (EMTCT) of HIV and syphilis in the region, and the goals were established for 2015 on CD50.R12 Resolution. These commitments were renewed and expanded in 2016 in the plan of action for the prevention and control of HIV and sexually transmitted infections (2016-2021), contributing to the end of AIDS and sexually transmitted infections (STI) as problems of public health in the Americas in Resolution CD55.R5. The action plan widens the EMTCT initiative (now called “EMTCT Plus”), leveraging the platform of maternal and child health (MCH) to include the elimination of other communicable preventable diseases in the Americas, such as hepatitis B and Chagas disease (the latter, mainly in endemic countries). The goal of the EMTCT Plus initiative is to achieve and maintain the elimination of mother-to-child transmission of HIV, syphilis, Chagas disease and perinatal hepatitis B as a public health threat. It covers principles and action lines for the Universal Access to Health Care and Universal Health Coverage Strategy, based on lessons learned from the PAHO Strategy and Action Plan for the EMTCT of HIV and congenital syphilis. [EMTCT Plus. Framework for elimination of mother-to-child transmission of HIV, Syphilis, Hepatitis B, and Chagas. PAHO, PAHO/CHA/17-009, 2017]