Chagas disease as a mechanistic model for testing a novel hypothesis

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.

Acute Chagas disease outbreak associated with oral transmission

Seven individuals living in a town in the Southwest of Bahia developed sudden signs of cardiac and systemic impairment, with lethality of 28.6%. Serological tests were positive at least in one test in the five patients examined. Forty percent of the Triatoma sordida mynphs found inside or around Trypanosoma cruzi were found by blood culturig in there out five cases the homes of these cases were positive for Trypanosoma cruzi. Transmission probably occurred through consumption of water contaminated with triatomine feces. These findings emphasize the necessity to evaluation the importance of vectors like Triatoma sordida in maintaining the endemicity of this disease.

Further evidence of spontaneous cure in human Chagas disease

An acute case of Chagas disease was studied in 1944, with clinical and laboratory follow-up until 2007, in Bambuí, Minas Gerais, Brazil. A five-year-old girl living in a rural hut that was highly infested with Triatoma infestans presented a febrile clinical condition compatible with the acute form of trypanosomiasis. She presented a positive thick blood smear, but never again showed serological and/or parasitological evidence of Trypanosoma cruzi infection, on several occasions. This patient never received any specific treatment and, to this day, she remains completely asymptomatic, with normal findings from clinical, electrocardiographic, X-ray and echocardiographic examinations.

Mother-child transmission of Chagas disease: could coinfection with human immunodeficiency virus increase the risk?

A study was conducted on all newborns from mothers with Chagas disease who were attended at Hospital Donación F. Santojanni between January 1, 2001, and August 31, 2007. Each child was investigated for the presence of Trypanosoma cruzi parasitemia through direct examination of blood under the microscope using the buffy coat method on three occasions during the first six months of life. Serological tests were then performed. Ninety-four children born to mothers infected with Trypanosoma cruzi were attended over the study period. Three of these children were born to mothers coinfected with the human immunodeficiency virus. Vertical transmission of Chagas disease was diagnosed in 13 children, in all cases by identifying parasitemia. The overall Chagas disease transmission rate was 13.8% (13/94). It was 100% (3/3) among the children born to mothers with HIV infection and 10.9% (10/91) among children born to mothers without HIV [Difference = 0.89; CI95 = 0.82-0.95; p = 0.0021]. We concluded that coinfection with HIV could increase the risk of vertical transmission of Chagas disease.

Entomological surveillance of Chagas disease in Berilo municipality, Jequitinhonha Valley, State of Minas Gerais, Brazil

This study aimed to evaluate the Chagas Disease Control Program which has operated since 1982 in the municipality of Berilo in the Jequitinhonha Valley, Minas Gerais, Brazil, based on evaluation of 5,242 domiciliary units (DUs) and 7,807 outbuildings over an eight-year period of epidemiological surveillance implanted in 1997. A total of 391 triatomines (280 Panstrongylus megistus and 111 Triatoma pseudomaculata) were captured, indicating the continued predominance of the former species. However, Triatoma pseudomaculata is clearly becoming more important in this region, with intradomiciliary colonies being detected in recent years. Entomological parameters, such as dispersion (17%) and intradomiciliary infestation (0.15%) indices, are compatible with the results of the epidemiological surveillance. The majority of DUs were of construction type A (plaster over bricks) or C (plaster over adobe). Twenty-five percent of the inhabitants of the DUs infested by triatomines were reactive in ELISA, IHA and IIF tests for Trypanosoma cruzi antigens.

Chagas disease in the State of Pernambuco, Brazil: analysis of admissions and mortality time series

INTRODUCTION: A time series study of admissions, deaths and acute cases was conducted in order to evaluate the context of Chagas disease in Pernambuco. METHODS: Data reported to the Information Technology Department of the Brazilian National Health Service between 1980 and 2008 was collected for regions and Federal Units of Brazil; and microregions and municipalities of Pernambuco. Rates (per 100,000 inhabitants) of hospitalization, mortality and acute cases were calculated using a national hospital database (SIH), a national mortality database (SIM) and the national Information System for Notifiable Diseases (SINAN), respectively. RESULTS: The national average for Chagas disease admissions was 0.99 from 1995 to 2008. Pernambuco obtained a mean of 0.39 in the same period, with the highest rates being concentrated in the interior of the state. The state obtained a mean mortality rate of 1.56 between 1980 and 2007, which was lower than the national average (3.66). The mortality rate has tended to decline nationally, while it has remained relatively unchanged in Pernambuco. Interpolating national rates of admissions and deaths, mortality rates were higher than hospitalization rates between 1995 and 2007. The same occurred in Pernambuco, except for 2003. Between 2001 and 2006, rates for acute cases were 0.56 and 0.21 for Brazil and Pernambuco, respectively. CONCLUSIONS: Although a decrease in Chagas mortality has occurred in Brazil, the disease remains a serious public health problem, especially in the Northeast region. It is thus essential that medical care, prevention and control regarding Chagas disease be maintained and improved.

Serological survey for Chagas disease in the rural areas of Manaus, Coari, and Tefé in the Western Brazilian Amazon

INTRODUCTION: Deforestation, uncontrolled forest, human population migration from endemic areas, and the large number of reservoirs and wild vectors naturally infected by Trypanosoma cruzi promote the endemicity of Chagas disease in the Amazon region. METHODS: We conducted an initial serological survey (ELISA) in a sample of 1,263 persons; 1,095 (86.7%) were natives of the State of Amazonas, 666 (52.7%) were male, and 948 (75.1%) were over 20 years old. Serum samples that were found to be reactive, indeterminate, or inconclusive by indirect immunofluorescence (IFI) or positive with low titer by IFA were tested by Western blot (WB). Serologically confirmed patients (WB) were evaluated in terms of epidemiological, clinical, ECG, and echocardiography characteristics. RESULTS: Fifteen patients had serologically confirmed T. cruzi infection, and 12 of them were autochthonous to the state of Amazonas, for an overall seroprevalence of 1.2% and 0.9% for the state of Amazonas. Five of the 15 cases were males, and the average age was 47 years old; most were farmers with low education. One patient who was not autochthonous, having originated from Alagoas, showed right bundle branch block, bundle branch block, and anterosuperior left ventricular systolic dysfunction with an ejection fraction of 54%. CONCLUSIONS: The results of this study ratify the importance of monitoring CD cases in Amazonia, particularly in the state of Amazonas.

Study on Chagas disease occurrence in the municipality of Monte Negro, State of Rondônia, Brazilian Amazon

INTRODUCTION: Studies on Chagas disease deal with the perspective of its occurrence in the Amazon region, which is directly correlated to the population growth and the spread of the bug biotope. The state of Rondônia has an immense source of vectors (Triatomine) and reservoirs of Trypanosoma cruzi. Environmental changes brought forth by the deforestation in the region may cause vector behavior changes and bring these vectors to a closer contact with humans, increasing the probability of vector infection. METHODS: This study was carried out to check the occurrence of Chagas disease in the municipality of Monte Negro, Rondônia, Brazil, based on a random sampling of the farms and people wherein blood collection from the population and capturing triatomines were done. The blood samples were submitted to serologic tests to detect antibodies of the IgG class against T. cruzi. The triatomines that were collected had their digestive tract checked for the presence of trypanosomatidae with morphology resembling that of the T. cruzi. RESULTS: The population examined was mostly from other states. From the 322 bugs examined on the microscope, 50% showed parasites with morphology compatible with T. cruzi. From the serology of 344 random samples of human blood, 1.2% was found positive, 6% showed inconclusive results, and 92.8% were negative. CONCLUSIONS: Monte Negro shows low prevalence of human infection by T. cruzi and none active vector transmission; however, preventive and surveying measures, which are not performed until now, shall be taken due to the abundance of vectors infected by trypanosomatidae.

Mapping of Chagas disease research: analysis of publications in the period between 1940 and 2009

INTRODUCTION: Publications are often used as a measure of success in research work. Chagas disease occurs in Central and Southern America. However, during the past years, the disease has been occurring outside Latin America due to migration from endemic zones. This article describes a bibliometric review of the literature on Chagas disease research indexed in PubMed during a 70-year period. METHODS: Medline was used via the PubMed online service of the U.S. National Library of Medicine from 1940 to 2009. The search strategy was: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH]. RESULTS: A total of 13,989 references were retrieved. The number of publications increased steadily over time from 1,361 (1940-1969) to 5,430 (2000-2009) (coefficient of determination for linear fit, R²=0.910). Eight journals contained 25% of the Chagas disease literature. Of the publications, 64.2% came from endemic countries. Brazil was the predominant country (37%), followed by the United States (17.6%) and Argentina (14%). The ranking in production changed when the number of publications was normalized by estimated cases of Chagas disease (Panama and Uruguay), population (Argentina and Uruguay), and gross domestic product (Bolivia and Brazil). CONCLUSIONS: Several Latin American countries, where the prevalence of T. cruzi infection was not very high, were the main producers of the Chagas disease literature, after adjusting for economic and population indexes. The countries with more estimated cases of Chagas disease produced less research on Chagas disease than some developed countries.

In-house ELISA method to analyze anti-Trypanosoma cruzi IgG reactivity for differential diagnosis and evaluation of Chagas disease morbidity

INTRODUCTION: The goal was to develop an in-house serological method with high specificity and sensitivity for diagnosis and monitoring of Chagas disease morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and subclasses were tested in successive serum dilutions of patients from Berilo municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the in-house ELISA was also evaluated in samples from other relevant infectious diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected controls (NI). Further analysis was performed to evaluate the applicability of this in-house methodology for monitoring Chagas disease morbidity into three groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG reactivity at serum dilution 1:40 was an excellent approach to Chagas disease diagnosis (100% sensitivity and specificity). The analysis of IgG subclasses showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels and the DIG/Mix group presented higher levels of total IgG as compared with the IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology presents promising applicability in the analysis of anti-T. cruzi IgG reactivity for the differential diagnosis and evaluation of Chagas disease morbidity.

Advanced megaesophagus (Group III) secondary to vector-borne Chagas disease in a 20-month-old infant

The authors report the case of a female infant with Group III (or Grade III) megaesophagus secondary to vector-borne Chagas disease, resulting in severe malnutrition that reversed after surgery (Heller technique). The infant was then treated with the antiparasitic drug benznidazole, and the infection was cured, as demonstrated serologically and parasitologically. After follow-up of several years without evidence of disease, with satisfactory weight and height development, the patient had her first child at age 23, in whom serological tests for Chagas disease yielded negative results. Thirty years after the initial examination, the patient's electrocardiogram, echocardiogram, and chest radiography remained normal.

Chagas disease: What is known and what should be improved: a systemic review

This study consists of a broad review on what is known and what should be improved regarding knowledge of Chagas disease, not only through analysis on the main studies published on the topics discussed, but to a large extent based on experience of this subject, acquired over the past 50 years (1961-2011). Among the subjects covered, we highlight the pathogenesis and evolution of infection by Trypanosoma cruzi, drugs in use and new strategies for treating Chagas disease; the serological tests for the diagnosis and the controls of cure the infection; the regional variations in prevalence, morbidity and response to treatment of the disease; the importance of metacyclogenesis of T. cruzi in different species of triatomines and its capacity to transmit Chagas infection; the risks of adaptation of wild triatomines to human dwellings; the morbidity and need for a surveillance and control program for Chagas disease in the Amazon region and the need to prioritize initiatives for controlling Chagas disease in Latin America and Mexico and in non-endemic countries, which is today a major international dilemma. Finally, we raise the need for to create a new initiative for controlling Chagas disease in the Gran Chaco, which involves parts of Argentina, Bolivia and Paraguay.

Multiple causes of death related to Chagas' disease in Brazil, 1999 to 2007

INTRODUCTION: Chagas' disease is a major public health problem in Brazil and needs extensive and reliable information to support consistent prevention and control actions. This study describes the most common causes of death associated with deaths related to Chagas' disease (underlying or associated cause of death). METHODS: Mortality data were obtained from the Mortality Information System of the Ministry of Health (approximately 9 million deaths). We analyzed all deaths that occurred in Brazil between 1999 and 2007, where Chagas' disease was mentioned on the death certificate as underlying or associated cause (multiple causes of death). RESULTS: There was a total of 53,930 deaths related to Chagas' disease, 44,543 (82.6%) as underlying cause and 9,387 (17.4%) as associated cause. The main diseases and conditions associated with death by Chagas' disease as underlying cause included direct complications of cardiac involvement, such as conduction disorders/arrhythmias (41.4%) and heart failure (37.7%). Cerebrovascular disease (13.2%), ischemic heart disease (13.2%) and hypertensive diseases (9.3%) were the main underlying causes of deaths in which Chagas' disease was identified as an associated cause. CONCLUSIONS: Cardiovascular diseases were often associated with deaths related to Chagas' disease. Information from multiple causes of death recorded on death certificates allows reconstruction of the natural history of Chagas' disease and suggests preventive and therapeutic potential measures more adequate and specifics.

Triatomines in dwellings and outbuildings in an endemic area of Chagas disease in northeastern Brazil

INTRODUCTION: The present study identified the triatomines collected in intra and peri-domestic environments, observed the occurrence of Trypanosoma cruzi infection in triatomines and correlated this information with housing conditions and the fauna associated with the rural areas of the City of Itabaianinha, located in the State of Sergipe, Brazil. METHODS: Quarterly visits were conducted between March 2009 and March 2010, and the homes to be visited for the active search of insects were determined by random selection. In each housing unit, the insects were collected by a manual search with a metal clip and flashlight to inspect openings and cavities, with a collection time of one hour/home/individual. The Pirisa® dislodge chemical was used to force the insects to leave their ecotopes. Analysis of the intestinal contents of triatomines was performed in the laboratory to establish the presence of Trypanosomatidae. RESULTS: Of the 103 dwellings surveyed, 17.5% were infested with Panstrongylus megistus. The village of Mutuca exhibited the highest infestation rate (38.1%). All the villages with relevant infestation rates were situated in the northern area of the city. The highest percentage of vector infection was found in the village of Água Boa (56.5%). The rural dwellings were found to be primarily brick or wooden house with or without roughcast or plastered walls, and the outbuilding most frequently associated with triatomines was the chicken run. CONCLUSIONS: These results emphasise the need for broader vector control and surveillance and for educational campaigns in the context of the Chagas Disease Control Program.