Alejandro M. Hasslocher Moreno
Laboratory of Clinical Research in Chagas Disease/Evandro Chagas National Infectology Institute/Fiocruz
Chagas disease is a zoonosis transmitted in nature within a geographically well-defined ecological context, in which reservoirs/hosts and vectors, infected by Trypanosoma cruzi, even in the absence of humans, perpetuate the cycle. Monkeys, marsupials, rodents and lagomorphs, wild reservoirs, just like cats, dogs, pigs and goats, domestic and peridomestic reservoirs, can all be reservoirs for the disease. Triatomines, popularly known as kissing bugs, are vectors for the disease, and two species out of about a hundred were predominantly responsible for intradomiciliary transmission in humans: Triatoma infestans and Rhodnius prolixus, in South America and in Central America and Mexico, respectively. These transmission conditions are present from latitude 42°N to 40°S, which corroborates the fact that Chagas disease occurs since the southern United States to southern Argentina.
The etiologic agent of Chagas disease is a flagellated protozoa called Trypanosoma cruzi. The traditional mechanism of transmission of the parasite is vectorial, taking place within households that are home to triatomines. This transmission occurs via contact of mucosa or skin with a lesion and contaminated feces resulting from the bloodmeal of infected triatomines as they feed on humans. This was frequent in wattle and daub homes, typical of poor populations in rural areas, in which the kissing bug found shelter in the nooks and crannies of the clay walls. As these homes were improved and/or the former Sucam (Superintendence of Public Health Campaigns) sprayed insecticides in a systematic fashion, the peridomicilary environment has become the main risk area for Chagas disease. Peridomiciliary areas consists of chicken coops, pigsties, piles of firewood, leaky constructions that serve as food stores, and dog houses, and they are currently the natural habitat of wild triatomines.
Outside of the domiciliary environment, other mechanisms are involved in the transmission of the disease: blood transfusion, congenital/vertical transmission, oral contamination (by accidentally ingesting foods contaminated with infected triatomines or their feces), laboratory/occupational accidenets, manipulation and consumption of game meat, and organ transplantation.
Hypothetically feasible alternative mechanisms, in conditions of high parasitemia of the infected individual, include other possibilities such as sexual transmission, breastfeeding, participation of other types of arthropods, contact with the secretion of the anal glands of marsupials, and other practices such as love vows that include the exchange of blood and sharing needles and syringes when using injectable drugs.
In Brazil, up to the early 1960’s the vectorial pathway was responsible for most cases and was concentrated in rural areas, predominantly in the states of Minas Gerais, Bahia and Goiás. As a consequence of the rural exodus that occurred due to the country’s economic development model, the disease became urbanized and the transfusional pathway began to play a significant role in the transmission of Chagas disease in cities, especially in large capitals. Likewise, congenital transmission, albeit never considered a relevant public health issue in Brazil, has also diminished as a consequence of the ageing of the female population in the country and of the drastic reduction in the rates of the disease in children.
In 2006, Brazil was granted an international certification of vectorial and blood transfusion interruption of Chagas disease, which was possible thanks to epidemiological changes that have occurred in the past decades, when transmission mechanisms suffered modifications. Very successful vectorial and transfusional control programs implanted in Brazil after the 1980’s, involving the fight against the vector, improving living conditions, and effective serological control at blood banks, resulted in a very significant reduction in vectorial transmission, in rural areas, and of transfusional transmission in urban centers.
In Brazil, oral transmission currently corresponds to almost the entirety of new cases that have occurred in the last decade, and the disease has shifted its geographical axis, now affecting the Amazon region and, in particular, the state of Pará. Outside of Brazil, more specifically, in the Southern Cone region, especially in Argentina, congenital transmission is still a relevant risk situation for Chagas disease. Due to the globalization of the last decades, with its huge migration flows, for non-endemic countries such as the United States and European countries, blood transfusion and organ transfusions are now a public health challenge.
João Carlos Pinto Dias
René Rachou Research Center/Fiocruz
Christopher John Schofield
London School of Tropical Medicine and Hygiene, London, England
The Southern Cone Initiative (Incosul) is one of the largest international cooperation programs against a metaxenic disease, covering an area that exceeds six million square kilometers and involving seven countries: Argentina, Brazil, Chile, Uruguay, Paraguay, Bolivia and Peru (southern region), where more than two thirds of people in the American continent with Chagas disease are located, as described by Schmunis in 1997, Schofield and Dias in 1999, and reported by the WHO in 2002. Like their main antecedents, one can consider the development of control tools and strategies in the area, the medical, social and economical dimensioning of the issue that is the disease by investigators and by institutions such as the World Bank and the Pan-American Health Organization, the unity and the consent among scientists dedicated to trypanosomiasis and the good results of well-conducted actions on a regional scale. On a more contextual plane, there had been a successful initiative by African countries against oncocercosis, and in Latin America a cooperation spirit between countries was being formed around common interests, as is the case of Mercosur, as reviewed by Dias and Schofield and by Schmunis. Launched in July 1991 by the resolution of Ministries of Health of the Southern Cone, Incosul was the first of a series of other initiatives against Chagas disease in the Americas and can be considered the scientific response to a problem that is not very discussed from the political standpoint. In part, although control tools and strategies had been defined and available since the 1950s, the national programs did not demarcate or assume the necessary coverage and continuity because of factors inherent to the disease itself and its knowledge (slow evolution, lack of data), the population involved (poor, rural, not politically expressive), the lack of human and financial resources, political immaturity, and successive governmental discontinuities, reviewed by Dias in 1994. In fact, since the pioneering claims of scholars such as Emmanuel Dias in 1959 and Cecílio Romaña in 1979, a possible political and institutional agenda was already being outlined, based on the problem importance (high prevalence and morbidity and mortality estimated as severe, alongside proven vulnerability of main transmission forms control) and in the growing governmental responsibility for the poor populations health, developed in Alma Ata through a progressive pressure from the scientific community, particularly conveyed and catalyzed by PAHO, important meetings and workshops on disease control became more frequent in the 1970s. In 1986, in the first Southern Cone Ministers of Health meetings (organized by PAHO), the problem had already been understood as a governmental responsibility, foreseeing opportune multinational cooperation actions.
In the 1980s, there were also antecedents of technical and scientific cooperation, such as the work on the Brazil-Uruguay, Brazil-Paraguay, Argentina-Bolivia border, and the Programa de Salud Humana (from the Universidad El Salvador, Buenos Aires), reviewed by Dias and Schofield in 1999 and Silveira et al. in 2002. Particularly noteworthy are the Brazilian Control Program (reorganized in 1975 and prioritized in 1983) achievements and landmark events such as the International Congress on the disease in Rio de Janeiro, 1979, as shown by Dias and Schofield in 1999. In 1990, at a Pan American Health Conference, American trypanosomiasis was placed among the regional candidates for elimination. Ideas about a Regional Initiative took shape in 1991 at a scientific meeting in Uberaba, Brazil, and were taken to the PAHO Directors Board in May of that year, also discussed at an Italian Research Council special session a month later. At the same time, the Argentine government made the fight against the disease a high priority, and it was up to the Platinum delegation to present the final proposal for the implementation of Incosur to the regional health conference in Brasilia on July 30, 1991, together with the Uruguayan Minister. It was resolution 04-3 CS, determining the Intergovernmental Committee for Chagas disease creation, charged with the program and plan of action development, with two fundamental objectives, as described by Schofield and Dias in 1999, Silveira et al. in 2002, and WHO realto in 2002:
- Interrupt the protozoa vectorial transmission, through the elimination of Triatoma infestans domestic and peridomestic populations in the endemic area, together with the domestic populations control of other vector species occurring in the same regions, and
- Interrupt transfusion transmission, especially by improving blood donors serological screening in the region countries.
The rationale for the proposed actions and strategy was based on field findings and accumulated scientific knowledge about the disease and the most vulnerable points for intervention, reviewed by Coura and Dias and Schofield. The lack of an effective specific treatment, especially for the millions of chronically infected, made transmission prevention a priority. In the vaccine absence, the program focused on the chemical control of vectors and the blood donors selection through pre-transfusion serology, estimating that this would prevent at least 98% of the transmission occurring in the target species dispersion area, as had happened in the São Paulo state, reviewed by Dias in 2002. The target trypanosomiasis showed to be highly vulnerable to the control strategy used in pioneering work in Bambuí and São Paulo (Brazil), which allowed a nod to its elimination and showed immediate and persistent impact on the American trypanosomiasis incidence, reviewed by Dias in 1957 and 2002 and Rocha e Silva. Four factors justified the priority action on T. infestans, the main (and often the only) human Chagas disease transmitter in the Southern Cone, as reviewed by Schofield and Dias and Dias and collaborators:
- Its limited number of habitats, with all stages confined to artificial ecotopes (houses and peridomicile);
- Population growth slow rate and consequent gene rearrangements low level;
- Extreme degree of specialization, with genetic variability very low rates, conditioning a very limited genetic repertoire for further adaptations (for example, in the resistance to pesticides development) and
- Total vulnerability to modern pyrethroid insecticides.
At the time, the epidemiological and control panorama in the six countries that launched the Initiative showed triatomine infestation and transmission important pockets of infection in all countries, basically relying on T. infestans, and, almost exclusively in Brazil, other species were also involved. Vector control was organized in four countries (Argentina, Brazil, Chile, and Uruguay), but uniformity and continuity of actions were lacking. On the other hand, it was very incipient and reducing in Bolivia and Paraguay, and a program was totally lacking in Peru. In fact, it was very clear in the various meetings that preceded the launch that the Initiative should be, above all, a mechanism for international cooperation that would be able to sustain and improve vector control in the four countries already in action, but that it would also, and above all, be able to get a minimally efficient program off the ground in Bolivia and Paraguay, with very serious epidemiological situations. From the institutional point of view, PAHO had matured its political and integrating role in the area, prioritizing the most transcendental targets from the medical-social point of view and willing to reinforce the technical references and its intermediary role in the inputs and strategies provision against the main diseases, even taking on tasks such as international bidding.
The Initiative general scope was based on the countries formal commitment, with the PAHO endorsement, to a continuous and shared work, with the initial goals foreseen to be fulfilled within ten years. The intergovernmental commissions of the respective Ministries of Health were formed and have been functioning with full regularity, holding annual meetings for evaluation, information exchange, and programming, with countries as hosts rotation. Besides this, as cooperation and shared activity mechanisms, during the fifteen years of its operation, concepts, criteria, and action strategies have been systematized and standardized, numerous workshops on the disease and its control have been held, training and capacity building programs have been developed in several countries, regular international supervisions have been carried out in all countries, aiming at field evaluations and exchange, all of this taking into account, basically, the main anti-vector actions and transfusion control, reviewed by Silveira et al. in 2002. Incosur has also served as a parameter and motivation for the similar initiatives establishment in the Andean Pact Region, Central America, Mexico and the Amazon, in that order, as reviewed by Dias et al.in 2002. In particular, the scientific body promotion, which currently works very well in terms of medical care, diagnosis and large-scale entomological studies, stands out as a gain, improving the care and control scope.
At ten years of operation, the Initiative was re-evaluated, as described by Silveira and collaborators: Bolivia and Paraguay had taken off, the former with an important loan from the IDB, and the latter with extraordinary rationalization of its resources and its Malariology Department (Senepa) involvement. In the other countries, surveillance was advanced and national programs were sustained (even under administrative difficulties and due to the transition to decentralization). Southern Peru had been inserted and blood bank control was over 90% in all but Bolivia (then about 40%). Uruguay, Chile, most of Brazil, and 20 percent of the endemic area in Argentina had been certified as having eliminated T. infestans transmission, an intermediate but very significant goal. A key role had been played by PAHO, in the secretariat and Initiative’s activities articulation, also helping substantially in financing the supervisions, workshops, and intergovernmental or technical meetings.
Today, at fifteen years old, Incosur is alive and active, as recently reviewed by Dias article from 2007. There has been a drastic reduction in household infestation levels in all countries, particularly Bolivia and Paraguay, and transmission has been interrupted in most of the regularly worked areas. Blood banks remain under control (above 95%, Bolivia reaching 70 or 80%) and efforts are being made to improve entomological surveillance. New age-specific treatment actions are multiplying, with cure rates of over 60% expected. The evaluation criteria and fight strategies are homogenized, and the diagnostic laboratories and the inputs acquisition activities are also improved. The Benzonidazole provision for textTreatment and Nifurtimox for textTreatment is being addressed with the PAHO and WHO cooperation, including for production in Brazil and El Salvador, respectively. New partners such as Doctors Without Borders, ECLAT, and International Cooperation (Japanese, Belgian, Canadian etc.) are strengthening the Initiative. New fields of action such as congenital transmission, medical care for the infected, and the secondary species control are being worked on. At the epidemiological level, the transmission and, probably, morbidity and mortality rates are very low. At the political-institutional level, PAHO has been greatly strengthened and the self-esteem and identity of the region’s health professionals has been reinforced, in line with the reactive advances in the greater countries in question integration. In practice, the international cooperation character has provided the national programs with many operational advantages, in addition to the annual progress reporting and monitoring obligation of activities. Also noteworthy is the easier and more frequent access of national technicians to their ministers and higher authorities. The intergovernmental commissions have been received by the ministers of health and even by the Republic presidents on several occasions, which has always led to constructive discussions about Chagas disease and its control, naturally facilitating planning and budgetary adjustments. In particular, in successive regional or continental health conferences, the agenda has been opened for reports on the Initiative. From the initial dream, Incosur became a tangible reality and proved to be possible, even in a still immature political context and in a market economy scenario (difficult to apply in chagasic areas).
Dias in 2007 points out the main concerns and future challenges:
- Maintaining interest and priority on Chagas disease and its control
- Maintain the Incosur system cohesion
- Adapt to the health systems decentralization
- Achieving triatomine control in the peridomicile
- Leverage education and participation actions
- Achieve coverage and access for chagasic infected in health systems
- Maintain the operational research necessary for improvement and possible new epidemiological and control situations;
- Keep PAHO within the Initiative.
Looking ahead, new scenarios are presented, starting with the positive impact of the actions taken on other transmission routes, as well as, probably, on human disease the morbidity and mortality. The infected people concentration will be in high age groups, complicating the disease with other chronic degenerative conditions. Progressively, the residual transmission areas will be reduced (if actions are not discontinued), probably remaining in pockets of poverty, isolation, and political and sanitary precariousness. New expansion areas (as is the case in the Amazon) could overlap into agricultural frontiers. Urban outbreaks and alternative transmission modes (by mouth, for example), may occur, randomly and unpredictably. A progressive lack of interest in research on Chagas disease can be expected throughout the region. However, future priorities are research into strategies to maintain surveillance and improve detection and human cases treatment of the disease. In particular, it is necessary to consider the plan for actions technical renewal and sustainability in the face of the natural aging of personnel and the disease decrease in interest and visibility, complicated by other priorities emergence. The technical teams have been renewed with difficulty in all countries, and the articulation and municipal cadres training complexity as a decentralization requirement, as reviewed by Dias in 2007, Dias and collaborators, and Silveira et al. in 2002, has also increased. Finally, it is worth considering that this Initiative has not only been successful epidemiologically and scientifically. Dias and collaborators and Schmunis point out that this initiative is possibilities scenario part for the conformation and rescue of Latin America, as a region that seeks its identity and its best political and social expression.
João Carlos Pinto Dias
René Rachou Research Center/Fiocruz
In an official ceremony, the Brazilian Minister of Health received on June 9, 2006, a certification from the World Health Organization for the virtual elimination, in the country, of the Chagas disease transmission by the main regional vector, Triatoma infestans, reported by Dias in 2006. Carlos Chagas’ greatest dream was realized there, when he said that one day we would not lack the necessary energy to solve, in a profitable way, the disease enormous problem that had just been discovered, as described by Chagas in 1912. A great and renowned achievement, the certification was the tenacious work of dozens of scientists and thousands of anonymous health guards product, a saga started in Minas Gerais by Emmanuel Dias, in the 1940s, as reviewed by Dias in 2002.
In the 1970s, the Brazilian endemic area for American trypanosomiasis included more than 2,450 municipalities, 711 of which had detected T. infestans. At that time there were more than five million people affected by the disease in Brazil, with an incidence of about one hundred thousand new cases annually and a mortality rate of more than ten thousand cases per year. Less than five percent of the blood banks checked their donors and more than 700 municipalities had their houses infested with T. infestans. People died early, mainly young men, estimating that more than 10,000 Brazilians died annually due to the disease, mainly due to advanced heart disease, as reviewed by Dias and Coura in 1997. There was no vaccine or effective treatment. The medico-social problem was enormous, orphans and widows multitudes, of those incapacitated by serious heart disease. The only vulnerable links in the epidemiological chain were the insect vector, housed in poor rural shanties, and the blood banks, where between 5 and 7% of the donors were infected with T. cruzi.
In the 1980s, thanks to pioneering work in Bambuí and “Triângulo Mineiro” (soon followed by the São Paulo state), the good results and a great deal of pressure from Brazilian scientists on the government succeeded in prioritizing a national program against the disease, covering the whole endemic area with the appropriate insecticide and installing, by law, the blood donors mandatory selection throughout Brazil, as reviewed by Dias in 2002.
In 1991, a great step forward was made by associating the six Southern Cone countries in a common fight, achieving exceptional results in Uruguay, Chile, and parts of Argentina and Paraguay, with the Incosur Initiative. To be certified, Brazil had millions of homes purged and inspected over the years, with T. infestans catches dropping from over 80,000 in 1979 to just over forty in 2005 (Figure 1). With the launching of the Southern Cone Initiative in 1991, the Brazilian Program prioritized the areas of T. infestans dispersion, concentrating the research and spraying activities there. The T. infestans species of the Chagas disease vector triatomine was the Program main target due to its (i) great epidemiological impact, (ii) being restricted to the domestic environment, (iii) having been introduced in the country (therefore being an eliminable species), (iv)its high vulnerability to the indicated insecticides, (v) its very slow population recovery capacity and (vi) its low genetic plasticity, as reviewed by Schofield and Dias. Thus, in 1991, in the municipalities with species presence history in the last five years (since 1986), intensive household surveys were carried out, spraying with modern pyrethroid insecticides all the localities where the species was detected and the neighboring localities, in complete disinsectization schemes with re-expurgation between sixty and one hundred and eighty days. In the sequence of actions, the species became focused and the purging was repeated in all the houses in the localities found positive, as reviewed by Dias in 2002.
With the actions improvement, the acute cases have miraculously disappeared, and practically no more infected children and youngsters are found in dozens of serological surveys. Blood banks were gradually brought under control, at a level very close to 100%, in fact, in the wake of the HIV/AIDS epidemic. Far fewer “chagas sufferers” are dying today, and the remaining two million infected are surviving longer, due to advances in medicine and medical and social security care greater coverage, as reviewed by Dias et al. in 2002.
With a view to a well-documented certification granted under scientific and consistent criteria, the successive Intergovernmental Commissions of the Southern Cone Initiative (Incosur) have mandated multiple rigorous entomological and sero-epidemiological surveys throughout the endemic area, which have been presented and discussed at successive annual meetings and submitted to various International and National Evaluation Commissions, which have occurred routinely since 1992. The effort undertaken since the Incosur beginning was planned by specialists based on the strategy of the National Chagas disease Control Program (“PCDoença de Chagas”, in portuguese) itself, prioritizing the areas infested by the target species in the last five years and reinforcing the insecticide actions, with full spraying of municipalities through two initial purges with intervals between ninety and one hundred and eighty days, according to the technique described by Emmanuel Dias in 1958, followed by these municipalities annual inspection and full spraying of positive localities and their borders, as described by Dias in 2002. With this concentrated effort, the household infestation rates, the insects captured densities, and the number of positive municipalities and localities gradually dropped in all the areas worked on. This was observed in several pioneering works, which justified and supported the PCDoença de Chagas/Brasil (in portuguese), including the prediction of the species elimination in Brazil, by Emmanuel Dias in 1957. The continuity of the work produced the expected results: for example, from 711 municipalities infested by the species and 84,334 specimens of T. infestans captured in 1983, in 1991(Incosur base) there were 322 municipalities with 16,937 specimens captured; in 1997, 1,080 specimens were captured in 106 municipalities infested and, in 2000, there were 256 insects in 53 municipalities, according to what Dias described in 2002. The official Incosur website describes the vector control evolution in Brazil from 1993 to 2001 (Figure 1). As expected, the targeting and the trypanosome density reduction was progressively taking place in all the areas worked on, with variable responses according to the actions complexity, continuity, and rigor.
At the turn of the millennium, Incosur admitted certification goals per Federative Unit, certifying the states of São Paulo, Rio de Janeiro, Mato Grosso, Mato Grosso do Sul, Goiás, and Paraíba. The following year Minas Gerais and Pernambuco were certified, followed by Tocantins. Between 2004 and 2006 the last three states (RS, PR, and BA) were certified. Throughout the Initiative, followed serological surveys were demonstrating the progressive negativation of chagasic infection in low-age populations. In 2001 a large survey was started among more than 100,000 children from zero to five years old, which has resulted in very low positivity data (preliminarily below 0.02%, according to Brazil in 2002. The possibilities of T. infestansreturning to pre-1980 levels in Brazil are remote. The species has no natural (wild) foci in Brazil and reinfestation, from other border countries still with home foci such as Bolivia, Uruguay and Argentina, is unlikely. To begin with, because the infestation levels in such countries have also been immensely reduced in recent years, but also because human migrations to our country are generally occurring to urban spaces in Brazil, where T. infestans has shown enormous difficulty in colonizing, according to Dias and Coura and Rocha and Silva.
With good reason, the country and the scientific community celebrated the victory, coincidentally on the eve of the Chagas discovery centennial. On the certification occasion, institutions such as PAHO, the Ministry of Health, and FIOCRUZ decided to publicize the fact, understanding that the achievement should be honored, but also as a way to discuss with society the next perspectives and the consolidation work. Looking to the future, it is a conscience and responsibility duty to warn that the matter is not closed: there is a lot to do. The massive infestation by T. infestans will hardly return to the country, because it is a vector introduced in the past (coming from Bolivia) and not because it has natural wild foci in Brazil. Eventual residual outbreaks, very small and scattered, have appeared sporadically in Bahia, Rio Grande do Sul, Minas Gerais, and even in São Paulo, in past years, having been detected by the entomological surveillance system and fumigated in an intensive and effective way, with modern insecticides. Fortunately, no resistance of the species to these insecticides has been detected in the country, unlike a few foci of resistance observed in northern Argentina and southern Bolivia, according to Dias in 2002.
American trypanosomiasis transmission among us is not restricted by T. infestans alone. Other “barbeiros (in portuguese)” species persist in the Brazilian environment, which may occupy the eliminated species niche, in a progressive colonization process. The elimination of T. infestans itself requires a consolidation process, to detect and promptly destroy any residual foci. In this context, the key word is epidemiological surveillance. It is necessary, above all, to take into account that as of the year 2000, the Health Reform decentralized the control actions then carried out by Funasa, transferring them to the states and municipalities that are autonomous to carry out the necessary surveillance. The surveillance work logic and systematics are the same, but the actions continuity cannot be undone. Municipal and state secretariats have to equip themselves, maintain technical staff, allocate pertinent human resources and materials, under their managers necessary political will. Since most of the municipalities are small, underdeveloped, and lack tradition in vector control, the state and sub-regional levels (state secretariats and regional health directorates) will have a great task in motivating, supervising, and training the municipalities, as described by Dias in 2006. Epidemiological agencies must be trained to deal with rare situations such as the recent disease oral transmission outbreaks in Santa Catarina, Bahia, and Ceará, as well as to monitor possible resistance of the “barbeiros” to current insecticides. Possible congenital cases need to be taken care of and people who have been infected in the past need to be cared for properly. Blood banks need to remain under control. Clinical research needs to continue, in search of a more effective drug against the chronic disease.One wonders until when, and who will do all this. Surely two or three decades of surveillance are necessary, and the Unified Health System will be the great responsible for the actions continuity. The research and services that resulted in the present victory must continue, in order not to allow the interest in the endemic to fade away and the achievements to be reversed, or new or unexpected epidemiological situations to be dealt with, as described by Dias in 2002 and 2006. The final battles against Chagas disease in Brazil will from now on involve other protagonists besides the Sucam brave guards, of nostalgic and heroic memory. The entire health system must be involved, sustaining surveillance and providing adequate medical and social security care to infected people. Mayors, secretaries, and educators, among others, are required for the success of the new phase. In particular, it requires a good structure and a competence high level of the “PCDoença de Chagas” (in portuguese) command teams at the national and state levels, in order to train and supervise the Program in thousands of municipalities, ensuring the surveillance continuity and effectiveness. It also requires, especially, a great society insertion in this surveillance, to be obtained mainly at the expense of organized and continued educational actions.Such actions are unfortunately not yet on the agendas of the Ministry and the State Education Departments, which deserves and urgently requires a special effort on the part of sanitarians, politicians, and government leaders.
Congenital Chagas disease – current status e outlook
Oral Trypanosoma cruzi infection has been responsible for frequent outbreaks of acute Chagas disease reported in Brazil, Colombia, and Venezuela in the last 13 years. Metacyclic trypomastigote, present in the insect vector and also in the scent gland of the marsupial Didelphis, is the T. cruzi orally transmitted form in the mentioned outbreaks. The first published work on the Chagas disease outbreak by oral infection refers to an episode that occurred in 1965 in Rio Grande do Sul. In this case, the infection source would have been food contaminated with D. marsupialis secretion captured on site that was infected with T. cruzi, and no triatomine insect was found. Of the acute Chagas disease recorded outbreaks in Pará in 1969, in Paraíba in 1986, and in Santa Catarina in 2005, the last two were associated with sugarcane juice contaminated ingestion with parasite from the vector insect or Didelphis secretion. In Brazil, the Chagas disease occurrence by oral transmission is more frequent in the Amazon and is associated with açaí fruit or juice consumption, a typical region palm tree.
Experiments of oral T. cruzi infection in mice have shown that metacyclic trypomastigotes invade the gastric epithelium as a gateway to systemic infection. The metacyclic forms are not digested by the gastric juice because they express on their surface mucin-like molecules that are highly glycosylated and extremely resistant to proteolytic degradation. To reach the target cells, the parasites need to cross the thick mucus layer that protects the gastric mucosa and has mucins of different types as its main macromolecular component. Determinant for directing the parasites to their target is the selective binding to gastric mucin of the surface molecule gp82, specific to metacyclic forms. The subsequent migration of metacyclic forms through the mucus layer is driven by ATP.There are T. cruzi strains that are very efficient in infecting by the oral route and others that are not very efficient. This difference is related to the expression levels and resistance/susceptibility to peptic digestion of the stage-specific surface molecules, gp82 and gp90, which function respectively as a cell invasion mediator and negative modulator. The gp82 is expressed at similar levels in different T. cruzi strains, is highly conserved and resistant to peptic digestion at acidic pH, while gp90 with distinct pepsin susceptibility is expressed in a strain-dependent manner. Upon mice oral infection with metacyclic forms expressing gp90 low levels, there is gastric epithelium efficient invasion, where the parasites multiply in the amastigotes form. Parasites expressing gp90 high levels invade gastric cells poorly if gp90 is resistant to peptic digestion, and effectively if gp90 is susceptible to pepsin. Studies with a T. cruzi strain isolated from an orally infected patient with acute Chagas disease have shown that metacyclic forms expressing high levels of gp90 can have their infective capacity increased after contact with gastric juice. Mice oral infection with this strain resulted in high parasitemia levels and high mortality. In parasites recovered from the stomach 1 hour after oral administration, there was no longer any sign of gp90, which had been completely digested.