José Borges-Pereira

Chagas disease: 100 years after its discovery. A systemic review☆

Although Chagas disease was only discovered in 1909, it began millions of years ago as an enzootic disease among wild animals. Its transmission to man began accidentally as an anthropozoonosis when mankind invaded wild ecotopes. Endemic Chagas disease became established as a zoonosis over the last 200-300 years through deforestation for agriculture and livestock rearing and adaptation of triatomines to dwellings and to humans and domestic animals as food sources. When T. cruzi is transmitted to man, it invades the bloodstream and lymphatic system and lodges in muscle and heart tissue, the digestive system and phagocytic cells. Through this, it causes inflammatory lesions and an immune response, particularly mediated by CD4(+), CD8(+), IL2 and IL4, with cell and neuron destruction and fibrosis. These processes lead to blockage of the hearts conductive system, arrhythmias, heart failure, aperistalsis and dilatation of hollow viscera, especially the esophagus and colons. Chagas disease is characterized by an acute phase with or without symptoms, with (or more often without) T. cruzi penetration signs (inoculation chagoma or Romañas sign), fever, adenomegaly, hepatosplenomegaly and patent parasitemia; and a chronic phase: indeterminate (asymptomatic, with normal electrocardiogram and heart, esophagus and colon X-rays) or cardiac, digestive or cardiac/digestive forms. There is great regional variation in the morbidity caused by Chagas disease: severe cardiac or digestive forms may occur in 10-50%, and indeterminate forms in the remaining, asymptomatic cases. The epidemiological and control characteristics of Chagas disease vary according to each countrys ecological conditions and health policies.

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.

Chronic phase of Chagas disease: why should it be treated? A comprehensive review

The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

Epidemiology of Chagas disease in Jaguaruana, Ceará, Brazil. I. Presence of triatomines and index of Trypanosoma cruzi infection in four localities of a rural area

In order to assay the triatomine infestation and domiciliation in the rural area of Jaguaruana district, state of Ceará, Brazil, we studied, from November 2000 to April 2002, 4 localities comprising 158 domiciles as a whole, with an average of 4 inhabitants/house, who are dwelling in there for more than 7 years. Most houses have tile-covered roofs and the walls built with plaster-covered bricks (57%), followed by bricks without plaster (33%), and mud walls (7.5%). A total of 3082 triatomines were captured from different locations, according to the following capture plan: (a). intradomiciles: 238 Triatoma brasiliensis, 6 T. pseudomaculata, 9 Rhodnius nasutus, and 2 Panstrongylus lutzi; (b). peridomiciles (annexes): 2069 T. brasiliensis, 223 T. pseudomaculata, 121 R. nasutus, and 1 P. lutzi; (c). wild, in carnauba palms (Copernicia prunifera): 413 R. nasutus. From the captured triatomines, 1773 (57.5%) were examined. The natural index of Trypanosoma cruzi infection ranged from 10.8% to 30.2% (average of 17%), depending on the species and the location from where the triatomines were captured.

Aspects of peridomiciliary ecotopes in rural areas of Northeastern Brazil associated to triatomine (Hemiptera, Reduviidae) infestation, vectors of Chagas disease

Artificial ecotopes of 121 peridomiciliary environments in four rural localities in the state of Ceará, Brazil, were studied and the type of material of the ecotopes was identified as triatomine infestation. Two thousand two hundred and four Triatoma brasiliensis Neiva, 340 Triatoma pseudomaculata Corrêa and Espínola, 121 Rhodnius nasutus Stall, and 5 Panstrongylus lutzi (Neiva and Pinto) were captured. Out of the 323 ecotopes found (X = 2.0 +/- 1.8 per dwelling) - such as pigpens, henhouses, corrals, perches, dovecotes, piles of roofing tiles, bricks, wood, and straw - 30.3% were infested by triatomines in all different developmental stages, including eggs. A substantial number of triatomines were found in perches, however the largest infestation took place in roofing materials used in the construction of goat/sheep corrals, henhouses, and pigpens, where 98% of them were captured: 1372 triatomines were located in the roofing tile covers, 285 in the straw, 187 in the perches, 77 in the coverings of roofing tiles and straw, and 13 in the straw and wood Among all the different pile of materials, roofing tiles were the most infested (50%) followed by bricks (38.9%) and woods (36.1%). T. brasiliensis colonized mainly brick piles (chi-squared = 16.539; p < 0.05) and roofing tiles (chi-squared = 5,090.58; p < 0.05); T. pseudomaculata preferred wood perches (chi-squared = 472.39; p < 0.05) and woodpiles (chi-squared = 126.0 p < 0.05), and R. nasutus was principally found in roofing straw (chi-squared = 384.43; p < 0.05). These findings suggest that triatomines tend to colonize peridomiciliary ecotopes similar to their original habitats.

Epidemiologia da doença de Chagas em quatro localidades rurais de Jaguaruana, Estado do Ceará: soroprevalência da infecção, parasitemia e aspectos clínicos

A cross-sectional study on Chagas disease that examined the populations of four localities (no = 541 inhabitants) in the municipality of Jaguaruana, State of Ceara, showed seroprevalence of Chagas infection of 3.1%, as assessed by indirect immunofluorescence, indirect hemagglutination and ELISA tests. The rate was higher among adults over 50 years old, without any difference in relation to sex. Positive parasitemia was found in 11.8% (2/17) of the seropositive individuals by means of indirect xenodiagnosis and in 75% (9/12) by means of the polymerase chain reaction (p < 0.05). Cardiopathy was found by means of anamnesis, physical examination and resting electrocardiogram in 41% (7/17) of the seropositive individuals and in 11.8% (2/17) of the seronegative controls (p < 0.05). Analysis of these results showed that the prevalences of positive parasitemia and chronic Chagas cardiopathy were similar to those in the Caatinga area of Piaui and greater than in the Sertao area of Paraiba, although all these areas historically presented Triatoma brasiliensis and Triatoma pseudomaculata as the primary vectors responsible for Chagas infection transmission.

Morbidade da doença de Chagas em pacientes autóctones da microrregião do Rio Negro, Estado do Amazonas

INTRODUCTION: A seroepidemiological and clinical study was conducted on 152 autochthonous individuals living in the district of Barcelos, State of Amazonas, to evaluate the seroprevalence of Chagas infection and morbidity of Chagas disease. METHODS: The serological tests used were indirect immunofluorescence, conventional and recombinant ELISA and immunoblot (Tesa-blot). Thirty-eight patients were considered seropositive; 31 were considered serodoubtful; and 83 were considered seronegative. The 38 seropositive cases were paired with 38 seronegative controls of the same age and sex, and underwent epidemiological and clinical evaluations, electrocardiograms and echocardiograms. Twenty-nine pairs underwent radiological examinations of the esophagus. RESULTS: Seropositivity was 19.9 times more frequent among workers gathering plant materials from the forests and 10.4 times more frequent among piassaba gatherers. Eighty six point seven percent of the seropositive individuals recognized the genus Rhodnius as the local vector, while only 34.2% of the seronegative individuals recognized this. The EKG was abnormal in 36.8% of the seropositive individuals and in 21.5% of the seronegative individuals, while the echocardiogram showed abnormalities in 31.6% of the seropositive and 18.4% of the seronegative individuals. Precordialgia and palpitation were more frequent among the seropositive individuals. Clinical evaluation on the digestive system and X-ray on the esophagus did not show significant abnormalities. CONCLUSIONS: Chagas disease in the study region can be considered to be an occupational disease.

Soroprevalência da infecção chagásica no Estado do Piauí, 2002

To evaluate the epidemiological situation of Chagas disease infection in the State of Piauí, Brazil, and its relationships with age, gender, blood transfusion and spontaneous abortion, a serological survey was performed. A random sample of 36,399 inhabitants of rural zones was examined between August and December 2002. Chagas disease infection was defined by the indirect immunofluorescence test, with identification of anti-Trypanosoma cruzi antibodies in blood samples collected on filter paper. The total seroprevalence was 1.9%, ranging from 0.1% in children less than five years old to 6.6% in adults over 79 years old. The seroprevalence was significantly higher in women (2.1%), illiterates (4.1%), individuals receiving blood (3.3%) and women with a history of spontaneous abortion (5.4%). Comparison with the national serological survey (1975-1980) showed that there had been a significant reduction in the seroprevalence of Chagas disease infection in the State of Piauí (4.0% to 1.9%), which was indicative of the efficacy of the vector control measures implemented between 1975 and 2002.

Morbidade da doença de Chagas em áreas do Sertão da Paraíba e da Caatinga do Piauí

A clinical and electrocardiographic case control study was carried out with 186 pairs of persons with positive and negative serology for T. cruzi infection from the Sertão Paraíba and in 200 seropositive cases from the region of Caatinga in the State of Piauí, North-eastern Brazil. The predominant clinical manifestations in seropositive cases in both areas were: palpitations, dyspnea on effort, precordial pain, dysphagia, odynophagia, pyrosis and intestinal constipation. The EKG abnormalities rates suggestive of chronic chagasic cardiopathy were respectively in Paraíba and Piauí: AV block 3.8% and 2%, RBBB III 6.4% and 7%, RBBB III+ LAB 10.7% and 10.5%, and multifocal extrasystoles 2.7% and 3%. Xenodiagnosis in a sample of 54 seropositive individuals in the Sert-ao of Para-iba and in 120 in the Caatinga of Piauí was revealed 13% and 34% positive; PCR tests in a sample of 47 seropositives in Paraíba and 101 in Piauí revealed positives in 44.6% and 59.5% respectively. Blood culture in LIT media of 101 seropositive cases from the Caatinga of Piauí was positive for T. cruzi in 25.7%. A triatomine survey carried out in a sample of 132 domiciles and peridomiciles in the Sertão of Paraíba and in a sample of 159 in the Caatinga of Piauí showed the following results: In Paraíba, 16 specimens of T. brasiliensis, not infected with T. cruzi, were captured. In Piauí, 750 triatomines were captured, of these 625 were examined: 49 were T. pseudomaculata, not infected with T. cruzi (19 in peridomiciles and 30 in the domiciles), and 576 were T. brasiliensis (371 in the domiciles and 205 in the peridomiciles) and of this latter specie 32 (5.5%) were infected with T. cruzi (31 in the domiciles and one in the peridomicile).

On the possibility of autochthonous Chagas disease in Roraima, Amazon region, Brazil, 2000-2001

Chagas disease has been almost entirely eradicated from the arid zones in Central and Northeastern Brazil where rare or no autochthonous cases have been reported. However, in the last 10 years the disease has increasingly been registered in the Amazon Region. Aiming to investigate the possibility of the occurrence of autochthonous cycle of Chagas disease in Roraima, triatomine collections, vectorial susceptibility studies (this one to be shown elsewhere), parasitological and serological analyses were conducted in three agricultural settlement areas (Rorainópolis, Passarão Project and Ilha Community). Blood-donor candidates were also investigated. This is the first epidemiological survey on Chagas disease conducted in agricultural settlements in Roraima. Triatomine species found were Triatoma maculata, Rhodnius pictipes, Rhodnius robustus and Panstrongylus geniculatus. Trypanosoma cruzi detection analyses included xenodiagnosis, indirect immunofluorescence, indirect hemaglutination, ELISA and kinetoplast PCR amplification. Natural triatomine infection was not found in intestinal contents. Twenty-five adult settlers (1.4% out of 1821, all > 15 year-old, 20 migrants) presented anti-T. cruzi antibodies. Two migrant settlers (from Minas Gerais and Maranhão) tested positive for more than two serological tests, besides either being positive for xenodiagnosis or PCR. Results show that Chagas disease is not endemic in the areas studied. However, all elements of the transmission cycle are present, demanding for an adequate and continuous vigilance.