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Epidemiology 17/10/2022

Current status

Current status of Chagas disease epidemiology

Adauto Jose Goncalves de Araújo

Samuel Pessoa Endemic Diseases Department, National School of Public Health/Fiocruz

Paulo Chagastelles Sabroza

Samuel Pessoa Endemic Diseases Department, National School of Public Health/Fiocruz

Email: sabroza@ensp.fiocruz.br

Luiz Fernando Rocha Ferreira da Silva

Samuel Pessoa Endemic Diseases Department, National School of Public Health/Fiocruz

Email: ludovico@ensp.fiocruz.br

Dias in 2007, discusses the Chagas disease epidemiology in the globalization and inequity context, in an occurrences crescendo of anthropic changes, particularly natural environments migrations and invasion. It is a prevalent disease in rural populations, where thousands of insect vectors are found in adobe dwellings. There are an estimated 12 to 14 million people infected in Latin America, as described by Dias. Here was a remarkable effort to eliminate domiciliary transmission by Triatoma infestans, as described by Ramos Jr and Carvalho and Schofield and collaborators, and Brazil was considered free of this infection modality by the Intergovernmental Committee of the Southern Cone (see the files: The Southern Cone Initiative (Incosur) and The Chagas disease transmission interruption certification by Triatoma infestans in Brazil, in 2006). However, this situation does not consider important regional aspects. In Northeastern Brazil, for example, there are wild triatomine species that adapt very well to dwellings, attracted by house lights. The predominant species is Triatoma brasiliensis, but there are other important Trypanosoma cruzi vectors, as shown by Dias et al. in 2000 and Borges-Pereira et al. in 2002.

The parasite transmission is mainly through the vector, triatomine insects, in whose feces the parasite infective forms are found. It is followed in importance by transfusion and congenital transmission, which is becoming increasingly important. Transmission by laboratory accidents and maternal milk also occurs, but with little epidemiological significance, as reported in 2006 Guide from Epidemiological Surveillance of the Ministry of Health 2006.

In Brazil, the rural migration phenomenon toward urban centers gave rise to transmission through blood transfusion, when infected individuals started selling blood to survive. With about 70% of infected individuals living in cities, as reviewed by Dias, the transmission risk through blood transfusion is very high if strict control is not observed in blood banks.

The main form of control for vector transmission is done with chemicals applied directly to the dwellings and annexes, to combat the insects. Another, more socially appropriate, form of control is rural housing improvement programs where vector insects are unable to colonize. These associated measures, insect control and housing improvements, are pointed out as the most effective since the 1980s, as reviewed by Dias in 1986 and in the text “O controle de vetores da doença de Chagas”.

Book: Chagas disease and its main vectors in Brazil

Recently there have been Chagas disease outbreaks with acute form and death by ingestion of dissolved trypomastigotes forms in drinks, such as cane juice and acai in which the vector insects, wild ones probably, were crushed during preparation or their feces contaminated the food, as reported widely in the media and in 2006 in the Guide from Epidemiological Surveillance of the Ministry of Health 2006.

Chagas disease continues as a public health problem throughout all Latin American countries, and its distribution covers South America, including Chile and Argentina, as far south as the United States, wherever there are suitable vectors for the parasite. The Southern Cone Countries Initiative to promote actions to control the vector was successful, with the participation of Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay, as reviewed by Schofield and collaborators. However, as Dias in his 2007 publication points out, both the initiative and its persistence owe a lot to the scientists active participation, who, together with governments, have kept the attention focused on the disease control and prevention.

In Brazil, with the Unified Health System progressive improvement, there have been consistent advances in the care of people with Chagas disease. Both in terms of treatment for heart disease patients, when indicated, and surgical interventions and pacemaker placement for cardiac patients, the results have brought greater comfort to people with disease severe clinical forms. It becomes clear that a set of government prophylactic actions, publicized by the Ministry of Health, associated with the raising of population social standards, can control the disease transmission in the medium and long term, as described by Dias and Coura and Dias. But much remains to be done, especially in relation to populations living far from any health care or treatment possibility and follow-up of their problems and difficulties. There is still a significant contingent of T. cruzi infected people, asymptomatic or oligosymptomatic, whose clinical manifestations may appear in the future in a fraction of this group. It should be emphasized that early diagnosis is important, because there are effective drugs to treat the symptoms.

The most recent data indicate that Chagas disease continues to be a public health problem, especially in large cities, where people infected by the parasite have converged, whether asymptomatic or oligosymptomatic, in search of work, or sick people seeking treatment. Chagas disease is the fourth leading cause of death in Brazil among infectious-parasitic diseases, with the most affected age groups being over 45 years old; it is seen that it is in the large cities that patients are concentrated, especially in the southeast region (more details on the Ministry of Health/Secretariat of Health Surveillance website. Therefore, one cannot neglect to pay attention to the transmission and care of people infected by the parasite, whether they have clinical manifestations or not, even if the home transmission by Triatoma infestans has been successfully interrupted.

Table 1: Epidemiological data of the sero-positives frequency for Chagas disease versus other diseases from: blood bank samples presented at the XI Incosur Meeting, Paraguay in 2002.

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History

The first national serological survey for Chagas disease (Brazil, 1975-1980)

João Carlos Pinto Dias

Titular Researcher at the René Rachou Research Center/Fiocruz

Email: jcpdias@cpqrr.fiocruz.br

Aluízio Rosa Prata

Medical School of the University of “Triângulo Mineiro”

Carlos Chagas very early on realized the great disproportion between American trypanosomiasis acute and chronic cases in endemic areas, the latter being much more numerous and of much greater social and medical impact. He also sensed that the disease must be widespread in the Americas, thanks to the evidence rapid accumulation of infected triatomines in rural homes from Mexico to Patagonia, recorded by his colleague and collaborator, the entomologist Arthur Neiva, as described by Chagas in 1911, Coura in 1997, and Dias and Schofield in 1999. Chagas was aware of the diagnosing chronic infection difficulties at the time, given the circulating parasites scarcity and the lack of sufficiently specific and sensitive serum antibody detection techniques. It was a time when Immunology was just blossoming on the scientific scene, with very little accomplished in parasitic diseases terms, as described by Dias in 2000. The parallel between the trypanosomiasis scenario and the American trypanosomiasi social medical weight had been the motive of many speculations by Chagas, in fact, one of the famous polemic main motives of the National Academy of Medicine, in the 1920s.

The disease would only receive attention, study, and prevention if it were recognized objectively, to an extent that demonstrated its importance. The paths to such recognition would pass through the clinic and the laboratory, as described by Dias in 1948, Laranja et al. in 1956, and Dias and Schofield in 1999. Determined, Chagas embarked on both, calling for research and supporting studies by clinicians and pathologists such as Eurico Villela, Gaspar Vianna, Crowell, Evandro and Margarinos Torres, and clinical pathologists and parasitologists such as A. Machado, C. Guerreiro, Rocha Lima, E. Brumpt and Emmanuel Dias, as reviewed by Coura 1997 and Dias and Schofield. Xenodiagnosis had been the main tool for detecting chronic infection until the 1940s, developed by Brumpt and perfected by Emmanuel Dias, with restrictions due to its low sensitivity and the technical and logistical difficulties of implementing it in mass surveys. Guerreiro and Machado’s complement fixation reaction, described in 1913, was very complex to perform and presented sensitivity problems, in pioneering work by Villela, among others, as described by Camargo and Takeda and Dias and Schofield.

Chronic Chagas disease really started to be recognized in the second half of the 1940s, thanks to work in the endemic zone of Bambuí by Emmanuel Dias and collaborators, as reviewed by Dias and Schofied and Morel 1999. In that focus, chronic chagasic cardiopathy was re-studied and systematized by Laranja, Dias, Nóbrega and Miranda in 1956, and a precise serological diagnosis was fundamental for this. This was accomplished thanks to the excellent work of Júlio Muniz, Gilberto de Freitas, and José Lima Pedreira de Freitas, among others, in perfecting the complement fixation reaction, allowing studies in endemic areas populations that also started in Bambuí, as published by Muniz and Freitas in 1944 and Freitas in 1947.

It was classic the first large-scale survey conducted in that area by Dias and collaborators, followed by similar work in São Paulo, the Northeast, Rio Grande do Sul, Goiás, and Rio de Janeiro, and later in the Northeast and Midwest, as described by Dias and collaborators in 1948 and 1953. In the early sixties, Salgado and Pellegrino, as published in 1968, carried out an extensive school serological survey in Minas Gerais, which showed disease significant transmission rates. Then, systematic surveys in Bambuí and São Paulo were used for the first time to measure the impact of control actions, a strategy also applied in Venezuela and Argentina, as described by Dias in 1967 and 1974, Puigbó and collaborators, Salgado and Pellegrino, Souza and collaborators, and Segura. The surveys multiplied and gained refinements, especially with the modern laboratory techniques advent such as hemagglutination, immunofluorescence, and later ELISA, as described by Camargo and Hoshinu-Shimizu and Camargo and collaborators. Based on the accumulated evidence, in mid-1970, a scientists and sanitarists group, with the support of CNPq, the Ministry of Health, and the University of São Paulo, considered it highly opportune to carry out a broad research on trypanosomiasis in Brazil, planned and executed the First National Prevalence Survey (NPS), which played a key role in prioritizing the control of the endemic disease in our country, as reviewed by Coura, Morel, and Dias in 2002.

From a historical point of view, the establishment of the NPS resulted from a progressive articulation between the Brazilian scientific community and the health authorities during the 1970s. At that decade beginning, an institutional reform had taken place in Brazil that emptied the Ministry of Health of its technical and research staff, generating unease, competition, and scientific references loss, a negative situation that was to be reversed. In counterpoint, an institutional academic process dating back to the early 1950s strengthened the national scientific community, especially marked by the National Research Council (CNPq, acronym in portuguese) creation, the World Health Organization and, more particularly, the Brazilian Society of Tropical Medicine (SBMT), as described by Morel and Dias in 2000. Chagas disease had been put on these institutions agenda, in congresses terms, technical meetings, research encouragement, and publications. As background Emmanuel Dias had called on the Pan American Health Organization (PAHO) at a world congress in Lisbon in 1958 to give priority to the endemic control, genuinely and exclusively Pan-American, receiving from Dr. Fred Soper, then director, the pragmatic response: “you must to sell the idea…”, described by Dias in 1959 and Dias and Schofield. In fact, the disease burden was suspected and even calculated, but in practice, prevalence and morbidity and mortality data that would motivate and justify the necessary investments in its control, in a rational and continuous manner, were still lacking. In 1975, the ministerial program was revised and streamlined. The resources available in Sucam were approximately what was needed to cover 60% of the endemic area (anti-vector control). At the time, when the CNPq’s Integrated Program for Endemic Diseases (PIDE, acronym in portuguese) had just been created, a technical meeting between researchers and the Ministry decided to initiate two epidemiological surveys that would serve to dimension the Chagas disease problem in Brazil, to better direct and guide control actions, and also to motivate and justify the necessary material, human and financial resources that would allow the endemic area total coverage. These would be the National Household Triatomine Survey and the National Prevalence Survey by sero-epidemiology, as described by Camargo and collaborators, Fiúsa Lima and Silveira, Silveira and collaborators, and revised by Dias in 2002. The triatomine survey covered more than 2,400 municipalities, was carried out entirely by the regional teams and Sucam financial resources, and was published by Silveira and et al. in 1984.

As a fundamental basis for the NPS, it was of high importance to systematize the epidemiological and serological methodologies, so as to have an universe significant representation to be studied and that the serological technique was very reproducible, with high sensitivity and high specificity. The serology practice in chronic Chagas disease had evolved greatly, with the advent and improvement of simpler, more reliable techniques than the classic Guerreiro and Machado test. This was complex and showed discrepancies in results between different laboratories, although it provided excellent information in the hands of good serologists in several regional surveys, as described by Dias et al. in 1947, Dias in 1967, Salgado and Pellegrino in 1968, Prata et al. in 1976, and Camargo et al. in 1977. In the 1960s, among others, indirect hemagglutination and indirect immunofluorescence techniques would already be available, improved for the anti-T. cruzi detection antibodies, as described by Camargo and Hoshimu-Shimizu and Camargo and Takeda. In particular, both allowed an important simplification, by enabling collection on filter paper slides, facilitating field collection and transport, as well as being independent of venipuncture.

The survey was carried out starting in 1975, with the most intense collection phase in the years 1976-79, with consolidation activities (including sub-regional repeats) until late 1981. The entire operation was conducted and coordinated in an inter-institutional and trans-disciplinary manner, with the overall coordination being the responsibility of a collegiate group formed by the Ministry of Health (Sucam, PhDs Antônio Carlos Silveira and Pedro Tauil) and by the University of São Paulo, the latter through the Department of Preventive Medicine of the São Paulo School of Medicine (PhD Profs. Guilherme Rodrigues da Silva and Euclydes A. Castilho) and the Immunology Laboratory at the Institute of Tropical Medicine of São Paulo (Prof. Mário E. Camargo). By simple sampling, teams of Sucam agents collected more than 1.5 million blood samples by digital puncture and transport on filter paper in rural localities with less than 2,500 inhabitants in all the Brazilian municipalities of the time, except for those in the State of São Paulo, which was developing its own control and evaluation actions, as described by Silva and collaborators and Souza and collaborators Sampling was calculated in a simple random way in rural areas, with localities stratification by the number of houses, as shown by Camargo and collaborators and Fiúsa Lima and Silveira 1984. The collection was done on the general population of rural areas, covering all residents of the randomly selected dwelling, using disposable lancets for digital pulp puncture. The support was made on a standardized area of filter paper (Whatmann number 1), which greatly facilitated harvesting, storage, and transportation. It was dried in the environment and packed in plastic envelopes, for preservation in common refrigerators and Styrofoam boxes until arrival at the regional laboratories. These laboratories were 17 in number, located in several Brazilian states (state laboratories, or university or research institute laboratories), and were set up, supervised, and equipped by the Central Laboratory of the Institute of Tropical Medicine in São Paulo, as described by Camargo and collaborators. The technique used was indirect immunofluorescence, with antigen and conjugate prepared by the Central Laboratory, using a 1:40 dilution as a cut-off. For quality control, each laboratory received a standardized panel of positive and negative sera, prepared by the Institute of Tropical Medicine of São Paulo. All positive sera and part of the negative ones from the regional laboratories were retested by the Central Laboratory, also noting several episodes of repetition in regions or municipalities with problems in the first collection (conservation, identification, etc.).

The general results of the survey have been widely disseminated, and are appropriate in terms of overall prevalence in the country, states, and municipalities, calculating the positive sera by age group proportion. An overall prevalence of 4.2% of T. cruzi infection was estimated for the general rural Brazilian population, with higher prevalence rates in Minas Gerais and Rio Grande do Sul (8.8%), Goiás (7.4%), DF (6.1%), Sergipe (6.0%), and Bahia (5.4%). This was followed by Piauí and Paraná (4.0%), Paraíba (3.5%), Pernambuco and Mato Grosso (2.8%), Alagoas and Mato Grosso do Sul (2.5%), Acre (2.4%), Amazonas (1.9%), Rio Grande do Norte (1.8%), Rio de Janeiro (1.7%), Santa Catarina (1.4%), Ceará (0.8%), Pará (0.5%), Rondônia (0.4%), Roraima and Espírito Santo (0.3%) and Maranhão (0.1%), with Amapá remaining negative, according to Fiúsa Lima and Silveira. In general, it was observed that the prevalence rates distribution did not follow a continuity pattern, but showed the sub-regional pockets existence of more intense transmission, generally linked to higher trypanosome densities, revealed by the entomological survey, a fact, in fact, already observed in sub-regional surveys previously carried out, as shown by Dias et al. 1947, Dias in 1967, Camargo and collaborators, and Silveira and collaborators. Since the data on autochthony could not be disaggregated, unexpected prevalence rates as in DF, Western Amazonia and Santa Catarina were later reviewed, possibly explainable by internal migrations from areas of higher endemicity, as described by Fiúsa Lima and Silveira. Other situations, such as the Barcelos (Amazonas) municipality have particularized a focal feature of higher triatomine density, in this case Rhodnius brethesi, as described by Coura in 1990.

As expected, this NPS made it possible to better direct the control program and was a very important argument for the governmental actions prioritization, which occurred through supplementary financial resources, starting in 1983, which allowed the endemic area total coverage, as Dias reviewed in 2002. It also yielded important results in the chagasic infection diagnosis dissemination throughout the country, as well as providing a relevant development in making possible a national electrocardiographic survey (1980-86), using an adequate methodology and pairing seropositive and seronegative individuals, which revealed variable morbidity patterns in different regions, as described by Macedo. The methodology developed has allowed numerous focal or regional studies, disseminating the use of filter paper collection and generating the regional serology laboratories use as embryos of the state reference and training systems for the Chagas disease diagnosis in the Brazilian Unified Health System. Another good product was the measurement of the control actions impact by Sucen, in São Paulo (in the 1980s) and the Brazil Program (in the 1990s), showing an enormous reduction in the disease incidence in young age groups in the areas studied. The NPS also served, from a distance, as a model and reference for similar studies in several other countries, such as Mexico, Honduras, Bolivia, etc. And it was, above all, an important milestone in Brazilian Public Health, demonstrating competence, methodological excellence, and political will, emulated by correct and coherent scientific motivation, as described by Morel, Dias and Schofield, Silveira and collaborators, and several WHO reports.About thirty years later, the results of the NPS are being reviewed by a researchers group associated with the Ministry of Health and the University of São Paulo, mainly to determine the prevalence rates by age group, which will allow comparisons and cohort studies in later studies, especially regarding the control actions impact evaluation. It will also make it possible to indirectly estimate the congenital transmission importance of chagasic infection by studying the prevalence in young children. To complement it, in both directions, a new national survey is underway for individuals from 0 to 5 years old, in a sample study of about 150,000 Brazilians, covering all the Federation states, already being finalized. As expected, the prevalence found is extremely low, indicating very transmission low degrees. Preliminary results from almost 100,000 samples revealed only 21 positive cases, or 0.021% prevalence, with positivity in only six states so far (CE, PB, AL, BA, MG, and RS). A significant number of children who were seropositive before six months old were negative when the reaction was repeated after seven months, which is passive maternal antibody evidence transfer, and also indicates a very low level of congenital transmission in Brazil (except, perhaps, for Rio Grande do Sul). The negative results for the Amazon Region reveal, so far, minimal or no incidence of transmission in the age group examined in that area. The new survey should end in 2007, and may indicate, besides the control actions positive impact, operational failures or new epidemiological situations, represented by some residual pockets persistence of Chagas disease natural or congenital transmission.

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Paleoparasitology

Chagas disease paleoepidemiology

Adauto Jose Goncalves de Araújo

Samuel Pessoa Endemic Diseases Department, National School of Public Health/Fiocruz

Paulo Chagastelles Sabroza

Samuel Pessoa Endemic Diseases Department, National School of Public Health/Fiocruz

Email: sabroza@ensp.fiocruz.br

Luiz Fernando Rocha Ferreira da Silva

Samuel Pessoa Endemic Diseases Department, National School of Public Health/Fiocruz

Email: ludovico@ensp.fiocruz.brPaleoparasitology data show that Trypanosoma cruzi infection was found in pre-Columbian populations in the Andean regions as well as in the Brazilian cerrado or the North American desert plains. The oldest evidence comes from Chinchorro mummies (Figure 1) in Peru, dating back 9,000 years, described by Aufderheide et al. in 2004, and from a mummified body in Brazil, dating back 7,000 years, recently described by Lima and collaborators.

Figure 1

It was believed that the chagasic infection would have appeared in human populations after the sedentary habits adoption among the Andean region inhabitants, coinciding with the small rodents of the genus Cavia domestication, for food or funeral rituals, as described in Dias and Coura. The animals presence, raised inside the adobe houses, attracted the insect vectors that adapted to the dwellings and started feeding on human blood and domestic animals. The archaeological remains point out that the coexistence between humans, rodents, and triatomine vectors, particularly the Triatoma infestans species, would have started in the Andean valleys, in the region that now corresponds to Bolivian territory, as shown by Bargues and collaborators. The stable dwellings establishment, whose characteristics offered colonizable niches for the triatomines, together with the animals domestication, would have facilitated the insects domiciliation among the populations in the South America highlands, while in the lowlands, due to nomadic habits and the use of dwellings built with straw and wood, the insects would not have been able to adapt and, therefore, Chagas disease would only have spread from the Pacific coast populations to the South America lowlands after the Europeans and Africans arrival, as described by Coimbra Jr. The Chagas infection spread would thus coincide with the introduction of adobe houses in the lowlands and increased trade and transit among human populations.

The first paleoparasitology studies seemed to confirm the theory about the Chagas disease origin in Andean populations. Pathological lesions identified in Peruvian and Chilean mummies, compatible with Chagas disease, verified the Chagas infection and its consequences. Investigations focused on mummified bodies from the Atacama Desert and nearby archaeological regions, describing lesions suggestive of megas, first described by Rothhammer et al. in 1985, with histopathological detail showing amastigote forms nests was described by Fornaciari and collaborators. Guhl and collaborators and Ferreira and collaborators confirmed these diagnoses by employing molecular biology techniques, and recovering genetic material from T. cruzi in Andean mummies. Aufderheide and collaborators studied mummies dating back about 9,000 years infected by the parasite, dating therefore to a period before the admitted rodents domestication and sedentary habits adoption in the Andean region.

However, since 1984, we had raised another hypothesis about the Chagas disease origin in prehistoric American populations. By examining triatomines of the species T. brasiliensis infected by T. cruzi, which were trying to feed on the archaeologists copying cave paintings from the under-rock shelters walls in the Serra da Capivara National Park, Piauí southeastern, we thought that the ancient artists might also have been bitten by the insects and infected by the parasite. But, at that time, there was no way to test the hypothesis about T. cruzi infection in the meager human remains found at the archeological sites, as described by Araújo and collaborators. Only with the molecular biology techniques advent has it become possible to prove such a hypothesis. We have started a research project on prehistoric South American populations.

The first tests sought to establish standards for applying molecular biology techniques to archaeological material. We performed experimental T. cruzi infections in laboratory animals, and then sacrificed and desiccated them, simulating natural mummification. When molecular biology techniques were applied, the results were suitably positive, as demonstrated by Bastos and collaborators. Thus, it was possible to use this methodology on archaeological material with accurate results on Chilean mummies from the Atacama Desert, as described by Ferreira and collaborators.

We then moved on to test organic remains from archaeological sites outside the Andes region. The first came from a partially mummified body found in the United States and Mexico border region, dated at 1,200 years, in which Reinhard and collaborators described fecal masses suggestive of posterior intestinal dilatation, compatible with a chagasic lesion. Dittmar and collaborators describe that the molecular biology tests results were positive, confirming the chagasic infection in the individual. Reinhard and collaborators in 2007 speculated on the Chagas disease significance in prehistoric North American groups, as well as the parasite transmission mechanisms, according to the eating habits of the time.

Prous and Schlobach and Kipnis found partially mummified bodies at the archaeological site in the Peruaçu valley, north of the Minas Gerais state, Brazil, all dating from times before the European invasion. One of them, dated around 600 years old, contained a huge coprolith in the pelvic cavity, suggesting megacolon, Chagas disease characteristic. In our laboratory the intestinal parasites examination showed infection by hookworms and Echinostoma sp. as described by Sianto and collaborators while molecular biology tests on soft tissues and bones were positive for T. cruzi, as described by Araújo and collaborators and Fernandes and collaborators. In the same archaeological region Lima and collaborators examined a skeletonized body, dated 7,000 years old, with a positive result for chagasic infection. It must be emphasized that, in these regions, Chagas disease still prevails as a public health problem because, although natural transmission activity is not recorded, the chronically ill remain.

It is therefore confirmed that T. cruzi infection affected human groups long before sedentary habits were established through animals and plants domestication, beyond the Andean region, extending to where hunter-gatherer bands cohabited territories shared with parasite mammalian reservoirs, such as rodents and marsupials, and their vectors, triatomine insects adapted to feed on blood. It should be noted, however, that the T. infestans species presence in pre-Columbian settlements in the Andean region marks the beginning of a Chagas disease development process in human populations, due to this vector species domiciliation, while in the Brazilian lowlands and other regions, the infection transmission occurred by coexistence with wild vector species.

Chagas disease seems to be as old as the human presence in the Americas, where humans, mammalian reservoirs, and triatomine vectors existed, Araújo and collaborators. In addition to the region where the Andean civilizations developed, Chagas disease affected people from other regions, different in their cultures, such as those living in the border area between Texas and northern Mexico and the cerrado (savannah) of Minas Gerais. Molecular biology techniques have made it possible to the parasite separate strains between TC I and TC II, characterizing human coexistence aspects with T. cruzi in the remote past, as described by Dittmar et al. and Lima and collaborators.

Such aspects are important for public health approaches, since the parasite-host relationship evolution reveals control and intervention measures in the mechanisms of infection transmission and disease treatment. Pathogenic attributes attenuations and increments the parasite can now be recovered by molecular paleoparasitology techniques. The possibilities for studies of evolution by the genetic material recovery in past epochs, already outlined by Greenblatt and Spigelman with respect to Mycobacterium tuberculosis and other parasites, are envisaged.Studies on the Chagas disease paleoepidemiology seek to understand the origin and evolution of T. cruzi infection in humans and other mammalian hosts. As already shown in other parasites, molecular paleoparasitology studies are able to provide insights into virulence and pathogenicity evolutionary aspects extracted from organic traces accumulated over time. Thus, the T. cruzi genetic material recovery and its hosts in different geographical areas and with different dates, allows the prospect of tracing the Chagas disease origin and dispersion paths, as well as possibilities for studies on its impact on prehistoric populations.

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Social Importance

The social importance of Chagas disease: an American continent problem

João Carlos Pinto Dias

René Rachou Research Center/Fiocruz

Email: jcpdias@cpqrr.fiocruz.br

José Rodrigues Coura

Laboratory for Parasite-caused Diseases, Oswaldo Cruz Institute/Fiocruz

Email: coura@ioc.fiocruz.br

This theme presents two main strands, according to the approach angle, (a) the first referring to the eco-biological and historical American trypanosomiasis origins and, (b) the second, to its social impact aspects and control in the region. From one angle will be (i) the bio-ecological factors that determined the occurrence of the Trypanosoma cruzi primitive cycles and, from the other, (ii) the whole political, social, and economic context that caused the endemic disease dispersion and particularized the affected populations, also determining the control perspectives. A (iii) third angle focuses on and shows the Latin American scientific production importance on the subject, as well as the researchers political and social role in confronting the disease.

Several studies, since Carlos Chagas, have already placed the practically exclusive the disease distribution in New World lands, initially based on surveys of domiciliary vectors and their natural infection by T. cruzi degrees, gradually complemented with data from the human disease (initially description of acute cases) and also by the detection of domestic and wild reservoirs infected by Chagas in 1911 and 1932, Mazza in 1949, Dias in 1953, Freitas in 1960, Dias and Coura in 1997, and reported by WHO in 2002. In the original description, Carlos Chagas already defined an American entity by recognizing that it was a new trypanosomiasis he had discovered in America, different from the African one. Besides T. minasense, also discovered by Chagas, an other trypanosomatids series were described in the continent, especially the group vespertilionis(from bats) and especially T. rangeli, also carried by triatomines, but not pathogenic to human. With the findings of natural T. cruzi infections of humans, triatomines, and wild and domestic reservoirs from the southern United States to Patagonia, the designation “American” for trypanosomiasis cruzi has never been disputed, as reviewed by Dias in 1953, Coura in 1997, and Romero Sá in 2006.

The T. cruzi natural transmission has been occurring in the American continent for several millennia, from a sylvatic cycle that is much older than the domestic one. The earliest human infection evidence dates from much more recent times, detected in Peruvian and Chilean mummies from around two thousand years BC (see archive: Chagas disease paleoepidemiology. The endemic disease spread occurred fundamentally after the Columbus discovery, originating from large population movements, reachingendemicity peaks in the first half of the 20th century, as described by Dias and Coura in 1997 and reported by WHO in 2002. Modern molecular biology and genetic studies indicate the T. cruzi evolution from common ancestors with the Australian trypanosomatids, which existed before the separation from Pangaea, with cruzi being restricted to the Americas and transmitted by hematophagous hemiptera from the triatominae subfamily, whose almost all known species were limited to the New World, as reviewed by Schofield in 1994 and Zingales et al. in 1999. Human infection basically depended on the human approximation with the triatomines, corresponding to the domiciliation process (artificial ecotopes colonization) of the latter, which occurred for a few species throughout Latin America, as reviewed by Martins in 1968, Barretto in 1979, Forattini 1980, and Dias and Coura in 1997. In the last decades, human Chagas disease autochthonous cases have been detected in other continents, due to the infected people migration that enable transfusion, congenital transmission, organ transplantation, and laboratory accidents, as reviewed by Dias and Coura in 1997 and reported by WHO in 2002.

From an epidemiological and political point of view, Chagas disease is basically a problem for Latin America, more specifically for its continental countries. An estimated 12-14 million individuals are infected with T. cruzi in 19 Iberian-settled American countries, with only natural transmission sporadic cases occurring in the United States. It is also estimated that there is a proportion between 10 and 40 %, among those infected, who already have or will have a chronic heart disease due to American trypanosomiasis, of which at least 10 % will present a severe form that will probably cause their death and productive life precious years loss, as shown by Dias and Coura 1997, Akhavan in 1998, and WHO in 2002. Besides heart disease, digestive forms (predominant in South America), absenteeism, social security and medical-hospital costs, perpetuation processes of family poverty in endemic areas, low productivity, and control and surveillance programs costs (including in blood banks, among others, are elements that indicate important financial and social expenses in the countries affected by the endemic. In addition, the increasing migration of people with Chagas’ disease to the United States (much more than to Canada), is creating in this country an important concern with the transfusion natural risks, congenital transmission, and organ transplantation, as well as the chronic patients managing costs, especially those with heart disease, as reviewed by Schmunis in 1997 and reported by WHO in 2002. From the primitive enzootic cycle, human disease has spread in the Americas by circumstances and factors of basically anthropic and social-political nature, portrayed in poor-quality rural ranches, socially excluded populations, poverty and low production pockets, inefficient health systems, and geographically open spaces, mainly by intensive deforestation. In this context, the domiciliated triatomine will be buoyed by geo-ecological factors such as high salinity contents, very dense umbrageous spaces, varied hygrometric indexes, high altitudes and latitudes beyond the 49th parallel. S., as reviewed by Forattini, Schofield, Carcavallo and collaborators, Dias and Coura in 1997 and reported by WHO in 2002. In the north of North America, in addition to latitude and the triatomines with high domiciliary power absence, socioeconomic and political factors will be in play, such as the human colonization type in the United States and Canada, which will not give rise to rough housing such as cafuas, nor the Latin region social exclusion, as pointed out by Briceño-León and Dias and Borges Dias.

Plagued in the New World poorest part, this trypanosomiasis will not have the repercussion or the motivation to study other more universal protozoa diseases, such as malaria and the leishmaniases. It will basically configure itself as a region problem, due to its incidence, distribution and social medical impact, naturally generating more interest and expertise in the Latin American segment, starting with its discovery. Chagas disease will not be an obstacle to the spaces occupation process by foreign powers, given its slow clinical evolution and the epidemic peaks recent timing, occurring mainly in the 20th century, when the affected countries were already politically independent. For this reason, Carlos Chagas, in 1911, called for the affected countries governments to take charge of the relentless fight against Conorhinus, linking this fight to the nations development, the soil occupation and the race improvement. Three decades after this position, Chagas’ disciples will resume the motto, mainly as a consequence of the Mendoza well-known events (IX Meeting of MEPRA and the Romaña description) and the works of Bambuí, which culminated with the epidemiological studies systematization and the chronic chagasic picture definitive characterization of cardiopathy Rassi, as reviewed by Coura in 1997 and Dias and Schofield. And it was Emmanuel Dias, Cecílio Romaña, Salvador Mazza, Pedreira de Freitas, and Francisco Laranja, who pioneered the idea that the disease was a continental problem and that the endemic countries had unequivocal governmental responsibilities, as Dias reviewed in 1988. In this context, two fundamental situations intersected: on one hand, the scientific Latin American “chagologists” evolution (including the tools and strategies development to prospect the disease, such as historical text serology and electrocardiography) and, on the other hand, the Pan American Health Organization (PAHO) involvement, assuming a catalytic and motivating role with the regional governments and the scientific community, as discussed by Dias and Schofield. In general, both situations occurred from the second half of the 1950s on, thanks to the very particular efforts of researchers and sanitarians involved with the disease, with the main clinical pictures and transmission forms already described, as well as the basic tools for prospecting and control (vectorial and transfusion) becoming available. Although prevalence surveys were expanded in a relatively short time in Continent various parts, what took longer were the morbidity and mortality studies, which are still very scarce in several countries, which has slowed down control actions in several of them, as reviewed by Coura in 1997 and Dias and Schofield. In a more incisive way, Emmanuel Dias was the studies and actions important instigator to control the disease in the continent, not only mapping it in an exemplary way already in the 1950s, but also stimulating regional studies, developing work strategies, forming followers and stimulating several countries and PAHO itself. In this journey he was accompanied by formidable partners such as Pedreira de Freitas, Mário Pinotti, Félix Pífano, Amador Neghme, Cecílio Romaña, Arnoldo Gabaldón, Hugo Escomel, Rafael Torrico, Rodrigo Zeledón, and several others, as reported by Dias in 1947 and 1988. The publications growth, control experiences, and surveys on the disease became logarithmic by the end of the 1950s, a time that coincided with a great sanitary effervescence in the fight against malaria in the region. A charge made by Dias to the health authorities and particularly to PAHO, in 1958, when he vehemently denounced the Chagas disease neglect by the health authorities at the International Congress on Tropical Medicine and Malaria, in Lisbon, described by Dias in 1959, will be emblematic. Gradually, this situation began to change, especially with the PAHO greater inclusion in the fight against the disease and with the greater closeness among the scientists involved, as described by Romaña in 1979 and Dias and Schofield. Regional bodies and programs such as the CNPq’s Integrated Program for Endemic Diseases (Brazil), the Human Health Program (Argentina), the Brazilian Society of Tropical Medicine, and Tropical Disease Research (WHO/UNDP, WB) will play a special role. In the 1980s some national vector control programs will be mature and, with the advent of human immunodeficiency syndrome (AIDS), the blood banks definitive control will be established. In the following decade there will be coalition and greater cooperation among several countries in the region, setting up the International Initiatives to fight the disease, a harbinger of new times and substantial advances on the T. cruzi transmission in Latin America, as reported by Coura in 1997 and Dias in 1988 by WHO in 2002.At the more Continent contextual level, the disease recognition and its management will go through complex political issues, starting from the fragmentation of social and international policies, for decades the region has been dependent on foreign aid and lacking in ethical and democratic values, as described by Dias and Borges Dias, Briceño-León and Coura. In fact, the human Chagas disease big problem was its enormous regional expansion, dependent on spurious relations of production and the consequent affected populations political and social exclusion, difficult situations, slow and complex solution, as proposed by Martins in 1968 and Dias et al. in 1994. In contrast, Chagas disease has unequivocally contributed to the Latin American scientific community improvement and maturity, which has the greatest “expertise” on the endemic and is a committed proponent of its control. It has also served, in the region, as a motivator for important medical-social analyses, uncovering and helping to understand problems and political and social nature causal factors involved in the endemic production, expansion and control. On the positive side, since the 1990s disease control in the region has taken on a form of cooperation and integration among countries, in the wake of the so-called and successful “Initiatives, such as the Southern Cone – Incosur, the Andean Pact, Central America, Mexico, and the Amazon, thus contributing to the regional identity consolidation, as reviewed by Dias et al. in 1994, Schmunis in 1997, and reported by the WHO in 2002.

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Chagas Disease Eco-epidemiology

Marli Lima

Chagas Disease Eco-epidemiology Laboratory, Oswaldo Cruz Institute/Fiocruz

Email: mmlima@ioc.fiocruz.br

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