The CUIDA Chagas Project: towards the elimination of congenital transmission of Chagas disease in Bolivia, Brazil, Colombia, and Paraguay

ABSTRACT Background: Mother-to-child transmission of Chagas disease (CD) has become a relevant problem in both endemic and non-endemic areas. Methods: Description of the CUIDA Chagas Project - Communities United for Innovation, Development and Attention for Chagas disease'. Results: Through innovative and strategic research, this project will provide improved diagnostic and treatment options as well as replicable implementation models that are adaptable to different contexts. Conclusions: By integrating test, treat and care actions for CD into primary health care practices, the burden of CD on people and health systems may be significantly reduced.

Chagas disease. The use of serology to establish drug efficacy. Value and limitations

Presented at the "Consultative Meeting on the Strategic and Operational Aspects for the Clinical Development of Trypanocidal Drugs for Chagas Disease, 23-24 April 2007, Buenos Aires, Argentina.", sponsored by TDR, WHO.

Proportional mortality ratio due to chagas disease is five times higher for the state of Goias than the rest of Brazil

Mortality data due to Chagas disease for the endemic State of Goias, Brazil, was retrieved from the National System of Information on Mortality, between 2006 and 2011. A total of 29,041 deaths were attributed to Chagas disease in the country, of which 4,293 (14.8%) occurred in the State of Goias. The proportion of deaths attributable to Chagas disease was 0,4% for the country overall and 2.4% for State of Goias. Seventy-two percent of the records were from individuals over 60 years of age, and heart disease was the main cause of death in 80.3%. Chagas disease is a major cause of death in Goias and, proportionally, 5.3 times higher than for the rest of the country.

Detecção de doenças transmissíveis em gestantes no Estado de Goiás: o teste da mamãe / Detection of transmissible diseases in pregnant women in the State of Goias, Brazil. Maternal screening

Neste trabalho é descrita a triagem de doenças infecciosas em gestantes do estado de Goiás para detecção de agravos que podem ser transmitidos durante a gravidez e causar sequelas na criança. A triagem é realizada por meio de programa da Secretaria Estadual da Saúde em parceria com a Associação de Pais e Amigos dos Excepcionais (APAE) e as Secretarias Municipais de Saúde. A experiência da APAE na detecção de algumas doenças congênitas por teste simples em papel filtro foi aproveitada e seu uso expandido para a detecção de doenças infecciosas/transmissíveis. De setembro de 2003 até junho de 2009 foram examinadas amostras de 348.037 gestantes. Implantada progressivamente a partir de dois municípios, a triagem para doenças infecciosas está disponível em 245 dos 246 municípios do estado de Goiás. Os agravos triados foram: sífilis, HIV/Aids, toxoplasmose, rubéola, hepatites B e C, infecção pelo Trypanosoma cruzi, HTLV e citomegalovirose. A triagem foi realizada em papel filtro por testes imunoenzimáticos (ELISA) para cada marcador e os resultados positivos foram confirmados por coleta de sangue venoso, cujo soro foi encaminhado a diferentes centros de referência. Foram identificadas 11.061 gestantes com resultados positivos. A confirmação após os testes com soro foi obtida em 10.496 (94,9%) amostras com as seguintes prevalências: sífilis: 4.028 (1,2%); toxoplasmose: 2.320 (0,7%), anticorpos anti-T. cruzi: 1.768 (0,5%); hepatite B: 956 (0,3%); HIV: 469 (0,1%), hepatite C: 334 (0,1%), HTLV: 312 (0,1%), rubéola: 181(0,05%) e fase aguda de citomegalovirose: 128 (0,04%). Os resultados foram encaminhados ao pré-natalista e ao núcleo de vigilância epidemiológica municipal.

II Consenso Brasileiro em Doença de Chagas, 2015 / Brazilian Consensus on Chagas Disease, 2015

A doença de Chagas é uma condição crônica negligenciada com elevada carga de morbimortalidade e impacto dos pontos de vista psicológico, social e econômico. Representa um importante problema de saúde pública no Brasil, com diferentes cenários regionais. Este documento traduz a sistematização das evidências que compõe o Consenso Brasileiro de Doença de Chagas. O objetivo foi sistematizar estratégias de diagnóstico, tratamento, prevenção e controle da doença de Chagas no país, de modo a refletir as evidências científicas disponíveis. Sua construção fundamentou-se na articulação e contribuição estratégica de especialistas brasileiros com conhecimento, experiência e atualização sobre diferentes aspectos da doença. Representa o resultado da estreita colaboração entre a Sociedade Brasileira de Medicina Tropical e o Ministério da Saúde. Espera-se com este documento fortalecer o desenvolvimento de ações integradas para enfrentamento da doença no país com foco em epidemiologia, gestão, atenção integral (incluindo famílias e comunidades), comunicação, informação, educação e pesquisas.

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

Congenital transmission of Trypanosoma cruzi in central Brazil. A study of 1,211 individuals born to infected mothers

Transmission of Trypanosoma cruzi during pregnancy is estimated to occur in less than 20% of infected mothers; however, the etiopathogenesis is not completely understood. The Centre for Studies on Chagas Disease provides confirmation of T. cruzi infection for individuals living in central Brazil. In this retrospective hospital-based study, all requests for diagnosis of T. cruzi infection in individuals less than 21 years old from 1994-2014 were searched. We end with 1,211 individuals and their respective infected mothers. Congenital transmission of infection was confirmed in 24 individuals (2%) in central Brazil, an area where the main T. cruzi lineage circulating in humans is TcII. This low prevalence of congenital Chagas disease is discussed in relation to recent findings in the south region of Brazil, where TcV is the main lineage and congenital transmission has a higher prevalence (approximately 5%), similar to frequencies reported in Argentina, Paraguay and Bolivia. This is the first report to show geographical differences in the rates of congenital transmission of T. cruzi and the relationship between the prevalence of congenital transmission and the type of Tc prevalent in each region.

Congenital Chagas disease: an update

Congenital infection with Trypanosoma cruzi is a global problem, occurring on average in 5% of children born from chronically infected mothers in endemic areas, with variations depending on the region. This presentation aims to focus on and update epidemiological data, research methods, involved factors, control strategy and possible prevention of congenital infection with T. cruzi. Considering that etiological treatment of the child is always effective if performed before one year of age, the diagnosis of infection in pregnant women and their newborns has to become the standard of care and integrated into the surveillance programs of syphilis and human immunodeficiency virus. In addition to the standard tests, polymerase chain reaction performed on blood of neonates of infected mothers one month after birth might improve the diagnosis of congenital infection. Recent data bring out that its transmission can be prevented through treatment of infected women before they become pregnant. The role of parasite genotypes and host genetic factors in parasite transmission and development of infection in foetuses/neonates has to be more investigated in order to better estimate the risk factors and impact on health of congenital infection with T. cruzi.

Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.

Current epidemiological profile of Chagasic megaesophagus in Central Brazil

Introduction Chagasic megaesophagus (CM) is the most common digestive manifestation of Chagas disease in Brazil, and the State of Goiás is one of the most affected regions. In recent decades, the Hospital das Clínicas (HC)/Universidade Federal de Goiás (UFG) has been a reference center for the study and treatment of CM. The objective of this study was to characterize the current epidemiological profile of patients with CM observed at the HC of the UFG from 1998 to 2010. Methods In total, 939 patient records were analyzed, and age, gender, place of birth, serology, symptoms and radiological classification according to Rezende et al. were analyzed. Results The median patient age was 55 years. Male patients were more (54%) prevalent than female patients. The prevalence of younger patients (less than 31 years of age) was 4.2%, but 82.1% of the younger patients were from State of Bahia. Patients older than 40 years were the majority (85.5%). The radiological groups were distributed as follows: Group I (35.9%), Group II (32.9%), Group III (17%) and Group IV (14.2%). Conclusions Compared with previous studies by the same group in 1975, 1994 and 1995, the number of younger patients decreased, and the frequency curve has shifted to older patients. .

Performance levels of four Latin American laboratories for the serodiagnosis of Chagas disease in Mexican sera samples

In nearly all of the previous multicentre studies evaluating serological tests for Trypanosoma cruzi infection, sera samples from Central or South American countries have been used preferentially. In this work we compared the reliability of the serological tests using Mexican sera samples that were evaluated in four independent laboratories. This included a reference laboratory in Brazil and three participant laboratories, including one in Central America and two in Mexico. The kappa index between Brazilian and Honduran laboratories reached 1.0 and the index for the Mexican laboratories reached 0.94. Another finding of this study was that the source of antigen did not affect the performance of the serological tests.

Diagnosis of Chagas disease: what has been achieved? What remains to be done with regard to diagnosis and follow up studies?

In the acute phase and in the chronic forms of Chagas disease, the etiological diagnosis may be performed by detection of the parasite using direct or indirect parasitological methods and by the presence of antibodies in the serum by way of serological tests. Several techniques are easily available, ranging from the simplest wet smear preparation to immuno-enzymatic assays with recombinant antigens that will meet most diagnostic needs. Other tests under evaluation include a molecular test using polymerase chain reaction, which has shown promising results and may be used as a confirmatory test both in the acute and chronic phases of the disease. Better rapid tests are needed for diagnosis, some of which are already under evaluation. Additionally, there is a need for tools that can identify patients cured shortly after specific treatment. Other needs include a marker for prognosis and early diagnosis of congenital transmission.

Gastric and transverse colonic volvulus in patient with chagasic megagastria and megacolon

In edemic regions for Chagas disease as in central part of Brazil digestive manifestations are common and colonic volvulus is a possible complication. Sigmoid volvulus is the most frequent type. Aim - report an uncommon case of volvulus is a possible complication. Sigmoid volvulus is the most frequent type / O volvo colônico é frequente nas regiões endêmicas da doença de Chagas em que o megacólon é manifestação comum. O sigmóide é o segmento mais acometido e a literatura é escassa sobre o padrão do volvo no megacólon chagásico...

Busca retrospectiva da transmissão maternal da infecção chagásica em pacientes na fase crônica / A retrospective search for maternal transmission of Chagas infection from patients in the chronic phase

Avaliamos a transmissão maternal do Trypanosoma cruzi em 278 filhos de 145 mães com a doença crônica causada por esse protozoário, nascidos após o estabelecimento do diagnóstico materno. Usamos, nas mães e nos filhos, provas sorológicas como base do objetivo do estudo. Verificamos que ocorreram apenas duas veiculações pela modalidade citada (2/278 = 0,7 por cento). Como houve amamentação, não foi possível diferenciar, nesses casos, a transmissão congênita da adquirida pelo leite, mas, de qualquer forma, processou-se transmissão maternal, que constitui uma das modalidades alternativas de infecção pelo Trypanosoma cruzi. A metodologia empregada é mais uma dentre as diversas propostas para aquilatar a prevalência desse tipo de propagação do Trypanosoma cruzi. Ao lado da constatação fundamental, registramos fatos relacionados com a gestação, parto, puerpério, abortamento, prematuridade, nati-neomortalidade e aleitamento materno, que podem representar subsídios para melhores interpretações sobre o assunto.

Impacto do controle químico extensivo de Triatoma infestans sobre a incidência de casos agudos e a prevalência de doença de Chagas. O exemplo de Montalvânia, Minas Gerais / The impact of the extensive chemical control of Triatoma infestans on the incidence of acute cases and the prevalence of human Chagas disease. The example of Montalvânia, Minas Gerais State

A partir da emergência de um surto de casos agudos de doença de Chagas em Montalvânia, norte de Minas Gerais, Brasil, e da implantação do controle triatomínico com inseticidas, verifica-se pronta e conseqüente desaparição dos casos e redução da incidência da infecção no Município. É mostrada a evolução da implantação e do controle do Triatoma infestans em Montalvânia e a evolução da sorologia praticada na população em geral, ao longo dos últimos trinta anos.

Parasite persistence in treated chagasic patients revealed by xenodiagnosis and polymerase chain reaction

Polymerase chain reaction (PCR) was compared with xenodiagnosis performed 20 years after trypanocidal chemotherapy to investigate parasite clearance. Eighty-five seropositive individuals for Chagas disease presenting a positive xenodiagnosis were treated with specific drugs; 37 in the acute phase and 48 in the chronic phase. Fifteen chronic assymptomatic patients received a placebo. Treatment in the acute phase led to PCR negative results in 73 percent of the cases, while xenodiagnosis was negative in 86 percent. In the chronic phase, PCR was negative in 65 percent of the patients and 83 percent led to xenodiagnosis negative results. Regarding the untreated group (placebo), 73 percent gave negative results by xenodiagnosis, of which 36 percent were positive by PCR. Individuals that were considered seronegative (n=10), presented unequivocally negative results in the PCR demonstrating the elimination of parasite DNA. Seventeen individuals had their antibodies titers decreased to such a level that the final results were considered as doubtful and 16 of them presented negative PCR. The molecular method represents a clear advantage over conventional techniques to demonstrate persistent infections in Chagas disease patients that underwent chemotherapy