Keywords

1 Introduction

Chagas disease or American trypanosomiasis is a parasitic disease caused by the protozoan Trypanosoma cruzi (T. cruzi). The parasite lives in the blood and tissues of different mammals, man, and intestines of blood-sucking bugs of the family Reduviidae, subfamily Triatominae, known in Argentina, Chile, Uruguay, and Bolivia as “vinchucas” (Quechua voice: wikchukuy means “throw”) [1].

In 1909 [2] and subsequent years, Carlos Chagas characterized the disease in humans, as well as causing the parasite and the transmitting vector as a unit of transmission in Argentina [3], Venezuela [4], and other American countries. Coexistence among the different actors of the infection process in the American continent has occurred since much earlier, and in the beginning, this was an enzootic infection, and the parasite was restricted to wild animals. It became a zoonosis when contact between humans and domestic and synanthropic animals started human transmission in dwellings (domestic cycle ), with a high number of vector colonies and elevated parasite infection [5, 6].

The following transmission routes of T. cruzi have been reported:

  1. (a)

    Vectorial (when the vector insects feed and deposit their feces simultaneously)

  2. (b)

    Transplacental or congenital (when the parasite crosses the placenta of the seropositive mother and infects the child during pregnancy or childbirth)

  3. (c)

    Oral route of trypomastigotes (by parasite-contaminated food)

  4. (d)

    Blood transfusion through T. cruzi-contaminated blood

  5. (e)

    Organ transplants

The acute stage, connected with the first infection and particularly in children, is often unapparent and not opportunely diagnosed. If there are symptoms, they are generally unspecific, characterized by fever, localized or generalized edema, localized and/or generalized lymphatic adenopathy, myocarditis, and encephalitis, and the diagnosis is made by parasite evidence. The chronic phase may induce nerve diseases with different forms of manifestation, neurological disorders, or massive organ dilatation (megacolon and megaesophagus).

2 The Vectors

Most of the 110 species of triatomine have strictly wild habits, and they live in association with birds, edentates, lizards, and mammals. As wild enzootic, it extends from 42° N (North Carolina and Maryland, USA) to 49° S (south of Argentina and Chile) including the Caribbean islands [7]. The wild reservoirs reported infected by the T. cruzi parasite are armadillos (Dasypus), opossum (Didelphis sp.), bats, raccoons, squirrels, edentates, and primates. These wild foci do not include humans. It has been reported that Andean cultures came into contact with guinea pig species approximately 7000–8000 years ago in the regions of Peru and Bolivia, and between 5000 and 3500 years ago, they began to keep them in the houses and to use them as a food source. The precondition of the use of wild animals in the ancients’ diet suggests that the ample contact between T. cruzi and humans gave rise to the oral contagion of the disease, showed by:

  1. (a)

    Parasite findings in some mummies in the Rio Grande Valley (Rio Bravo) (1150 BP), to the north of the states of Chihuahua and Coahuila (Mexico) and south of the Rio Grande (Texas, USA)

  2. (b)

    The presence of hairs and bones of wild rodents without cooking in human coprolites associated with megacolon and very large fecal pellets that filled the pelvic cavity [8,9,10,11]

This practice was also described for the last Incas and is common in the current populations of Latin America [9, 12].

It has been proposed that the guinea pig, with its wild habits, is still a reservoir of T. cruzi. It once took part in the parasitic cycle, since, at the time of its domestication, it was able to attract wild triatomines, among other insects, thus originating the domestic circle. This presumption is based on the finding of mummies with megacolon in rooms of Chiribaya, dating from 900 AD to 1350 AD. It is possible to establish this relationship today, thanks to the finding of mummies with megacolon [13]. An analogous situation can be described for the Chinchorro culture (6000–2000 BC) that inhabited the valleys of Azapa, Camarones, and Lluta (Chile) [14]. There, populations were exposed to vectors when they spent the night in the mountain slopes, in their small huts made of sticks, skins, and vegetable mats (Fig. 1).

Fig. 1
figure 1

Representation of vector-associated transmission. Source Elaborated by the author

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Different investigations have shown that the T. cruzi complete cycle can develop in marsupials, and infectious forms were found in their anal glands as well as in their peripheral blood [15]. Due to the presence of the complete cycle in these reservoirs, it can be assumed that they have been significantly relevant in parasite contribution regarding the installation of an intradomiciliary cycle [16,17,18].

Today, it is common to use construction materials such as mud, straw, and palm leaves that offer a physical medium equivalent to the nests and dens of wild animals, where the vector can have access to a blood meal. T. infestans (main vector domiciled in southern Peru, Bolivia, Chile, Argentina, Paraguay, Brazil, and Uruguay) and Panstrongylus megistus (main vector domiciled in large areas of Brazil) live in wall cracks near the roofs [19]. R. prolixus, on the other hand, prefers the characteristic palm walls and ceilings of Venezuela, Colombia, and Central America. Triatoma dimidiata, the main vector in Ecuador and the Pacific coast of Colombia and Central America to Mexico, prefers cracks in mud walls, but at a low level from the floor or on the ground floor, hiding by means of a phenomenon known as “camouflage.” It is also possible that while performing their subsistence activities, individuals were exposed to triatomines while shucking, manufacturing hooks, and preparing “totora” and jonquil to make mats [20]. In Chile, Mepraia spinolai is distributed in the regions of Arica and Parinacota, Tarapacá, Antofagasta, Atacama, Coquimbo, and Valparaiso [21].

Each vector species listed has specific conditions and/or attributes that make it biologically or behaviorally different, but as domiciliary species, we can prove that they all have the following characteristics:

  • Lack of mobility and little ability for active distribution, that is, a high degree of stability of domiciled populations.

  • Population replacement is slow, since, on average, the new generations develop in a year approximately.

  • All the evolutionary stages of the vector are present simultaneously in the same ecotope.

3 The Parasite

Different trypanosomes can be identified, and they are infecting vertebrates across the world, including humans, producing the disease known as trypanosomiasis. Chagas disease (T. cruzi) is the most representative in the Americas and the sleeping sickness or African trypanosomiasis (T. brucei) in the African continent [22]. A novel nosological entity (T. evansi) was linked with a human case in India. The American and African trypanosomiasis as a nosological entity affecting human has more than 100 years.

Trypanosomes belong to different subgenera with particular biological aspects; the American are intracellular parasites of the vertebrate host, deposited in situ with the stool of the vector (triatomine), which defecates after the blood inlet, and the African live and replicate in the salivary glands and are inoculated with the slobber through the vector bite (tsetse fly) [23].

This parasitic differentiation could have occurred 475 million years ago, when the breakup of the supercontinent Pangea separated the family Trypanosomatidae, and the ancestor of T. cruzi diverged from the ancestor of the salivary parasites (T. gambiense, T. rangeli, T. rhodesiense, T brucei) to become dregs. T. cruzi would have risen 280–150 million years ago in America, and, between 88 and 37 million years ago, the subpopulations of T. cruzi I and T. cruzi II would have been separated as genotypes [24]. The T. cruzi I would be autochthonous of South America and would have coevolved with primates and rodents. T. cruzi II would have entered from North America 5 million years ago with the great exchange of mammals in the small islands that gave origin to the Isthmus of Panama [25, 26]. At present, both groups would be circulating in different environments [27, 28].

4 Possible Routes of Dissemination of Domestic Vector Species

Paleoparasitological studies found T. cruzi DNA in Chinchorro mummies (+9000 years old), found in the Chilean coastal desert, that is, before the domestication of guinea pigs (8000 years ago [29]). Therefore, Chagas disease is present since ancient times in the Americas, and it is probably older than animal domestication and human presence in any part of America where wild vectors and reservoirs are present [30]. The dispersal of host mammals in South America and, perhaps, that of Triatoma infestans could have occurred in times prior to the uplift of the Andes Mountains [31]. In this way, the native species of the western slope of the Andes (degu or mouse of the pircas—Octodon degus and Triatoma spinolai) remained genetically isolated, living together inside the caves and multiple galleries excavated by the degu [32].

The reciprocal relationship would have favored the wild cycle of T. cruzi between vectors and reservoirs, long before the appearance of man. Men would have been incorporated into that cycle when they displaced mammals from their shelters or when they domesticated some of them. This scenario would have favored the introduction of infected vectors in the peridomiciliary areas and later in the dwellings. Evidences of this contact are found in mummified remains in different parts of the continent (Chihuahua desert in Mexico, Inca area of Peru, Minas Gerais in Brazil, and Atacama Desert in Chile), with an age of 4000–9000 years. Other mummies found in the Tarapacá gorge (Chile) at 1500 m high, corresponding to indigenous Wankarani, with an antiquity extending back to 1500 BC, who emigrated from Bolivia 3500 years ago, have shown a sign compatible with megacolon and cardiomegaly, characteristic conditions of this disease. As primitive populations went from nomad (hunter-gatherers) to sedentary (farmers) and, therefore, brought wild species (vectors and animals) into the interior of dwellings, they gave rise to the domestic cycle of transmission. With the complete cycle installed in the housing − parasite, vector, and human reservoir in the same reduced unit − human relationships and their migratory movements were enough for this biotic unit to install in other regions, far away from those considered initially.

We can conclude that the geographical distribution of the most important vectors of the disease in the Americas before the implementation of vector control programs was as follows [33]:

4.1 Triatoma infestans

  • Argentina (except the provinces of Chubut, Santa Cruz, and Tierra del Fuego)

  • Bolivia (Beni, Chuquisaca, Cochabamba, La Paz, Potosí, Santa Cruz, Tarija)

  • Brazil (Alagoas, Bahia, Goiás, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Paraíba, Paraná, Pernambuco, Piauí, Rio de Janeiro, Rio Grande do Sul, São Paulo, Sergipe, Tocantins)

  • Chile (Regions I–VI and the Metropolitan Santiago area)

  • Paraguay (Alto Paraguay, Boquerón, Caaguazú, Caazapá, Central, Chaco, Concepción, Cordillera, Guairá, Misiones, Nueva Asunción, Paraguarí, Presidente Hayes, San Pedro)

  • Peru (Arequipa, Ica, Moquegua, Tacna)

  • Uruguay

4.2 Panstrongylus megistus

  • Argentina (Corrientes, Jujuy, Misiones, Salta)

  • Brazil (Alagoas, Bahia, Ceará , Espirito Santo, Goiás, Maranhão, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Pará, Paraíba, Paraná, Pernambuco, Piauí, Rio de Janeiro, Rio Grande del Norte, Rio Grande do Sul, Santa Catarina, São Paulo, Sergipe)

  • Paraguay (Amambay, Cordillera)

  • Uruguay

4.3 Rhodnius prolixus

  • Colombia (Antioquia , Arauca, Boyacá, Caquetá, Casanare, César, Cundinamarca, Guajira, Huila, Magdalena, Meta, Norte de Santander, Putumayo, Santander, Tolima, Vichada)

  • El Salvador

  • Guatemala (in five of the 22 departments)

  • Honduras (in 11 of the 18 departments)

  • México (Chiapas, Oaxaca)

  • Nicaragua

  • Venezuela (Aragua, Carabobo, Cojedes, Miranda, Portuguesa, Yaracuy)

4.4 Triatoma brasiliensis

  • Brazil (widespread in all the semiarid northeast of the country Alagoas, Bahia, Ceará, Maranhão, Paraíba, Piauí, Rio Grande del Norte, Sergipe, Tocantins—and the north of Minas Gerais)

4.5 Triatoma dimidiata

  • Belize

  • Colombia

  • Costa Rica

  • Ecuador

  • El Salvador

  • Guatemala

  • Honduras (in 16 of the 18 departments)

  • Mexico (Campeche, Chiapas, Guerrero, Jalisco, Nayarit, Oaxaca, Puebla, Quintana Róo, San Luis Potosi, Tabasco, Veracruz, Yucatan)

  • Nicaragua

  • Panama

  • Peru (Tumbes)

  • Venezuela

At present, the geographical distribution of these species as transmission risk has been modified as an effect of the control actions developed by the countries.

5 Transmission and Infection

Chagas disease is not homogeneous in the Americas, and it has a varying epidemiology associated with distribution, transmission mechanisms, clinical manifestations, and predominant pathologies. There are regional forms in which acute cases can be clinically lethal, frequent and florid, or asymptomatic and benign. The chronic forms show cardiomyopathy, megaesophagus, megacolon, or cardiomegaly according to geographic areas; mother-to-child transmission varies, and it is frequent in some regions and extremely low in others.

If untreated, T. cruzi infection is lifelong; 90% of new infections occur before 10 years of age [34]. During the disease evolution, 25% of infected cases would develop some alteration, where 18% would develop cardiomyopathy without heart failure, 4% cardiomyopathy with heart failure, and 3% megavisceras [35,36,37,38,39,40]. High mortality appears in infected individuals aged between 20 and 59, increasing among those with electrocardiographic alterations [41].

The transmission ways showed in Fig. 2 can be defined differently with the various weights already stated.

Fig. 2
figure 2

Transmission of T. cruzi infection. Source Elaborated by the author

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Historically, the classic model of transmission can be defined as that associated with the presence of the vector in the domiciliary units in an environment conducive to its development. This environment, associated with wild or domestic reservoirs (cats and/or dogs) [42] infected by T. cruzi, established the condition of intradomiciliary or domestic transmission . This cycle was for years responsible for the occurrence of new infections in the Americas. Also, it was considered the classic model of vector transmission, with abundant rural population above urban, precarious housing and coexistence of different transmission routes, associated with bioclimatic factors of the regions of poor areas characterized by subsistence agriculture. This model no longer exists; it has changed from rural areas to marginal urban areas, where the domestic cycle is maintained and the peridomiciliary influence is low or inexistent for transmission maintenance. Population is no longer dispersed, but it is grouped in such a way that it gives rise to a new Chagas transmission model (Fig. 3).

Fig. 3
figure 3

Change of the vectorial transmission model. Source Elaborated by the author

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This model changes depending on vector control interventions developed by the countries and shows an impact on the prevalence of T. cruzi in the populations of the Americas. These figures can be explained by the reduced number of cases that started at more than 20,000,000 positive cases in the middle of the twentieth century (result of estimations made according to the estimated value of exposed population and possibly infected people that arises from mid-century publications of the different countries) [43, 44] and decreased to less than 7,000,000 in 2015 (Fig. 4).

Fig. 4
figure 4

Estimated prevalences for T. cruzi infection. Region of the Americas. 1909–2016. Source Elaborated by the author

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The reduction of new infections associated with vectorial transmission led to a decrease in prevalence in all the countries of the region, as a direct result of the regional initiatives to “Eliminate Intradomiciliary Vector Transmission and Control of Blood Banks” launched in 1991 under the executive secretary of the PAHO/WHO. The first one was the Southern Cone Initiative in 1991 (T. infestans, T. brasiliensis, T. sordida). Afterward, the Andean Initiative was organized in 1997 (for R. prolixus, T. dimidiata, T. maculata, R. ecuadoriensis), in conjunction with the Central American Initiative (for R. prolixus, T. dimidiata, T. barberi, R. pallescens), and finally the Amazon Initiative in 2004 (for R. prolixus, R. robustus, P. geniculatus, R. brethesi) (Fig. 5).

Fig. 5
figure 5

Regional initiatives for the control of vectorial transmission. Source Elaborated by the author based on countries’ report to OPS/OMS

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These initiatives allowed the actions toward the interior of the countries and between them to have common standards regarding the application of the insecticides used (formulations and doses) [45] normalized from local experiences. Also, the methods to detect intradomiciliary triatomine infestation and the minimum resources (human, infrastructure, and economic) necessary to carry out the commitments of the initiatives were agreed upon.

These actions had a substantial impact on vector transmission, as evidenced by the studies and reports, where studies in different population groups and ages show that initial prevalence averages were around 10% down to less than 1% [46,47,48,49] (Fig. 6).

Fig. 6
figure 6

Chagas disease, major vector transmission 2005–2014. Source Elaborated by the author of PAHO information

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As we have presented, Chagas disease is characterized by a large diversity of epidemiological data, resulting from the variety of vectors and reservoirs that serve as sources of infection. In this epidemiological scenario, it is important to distinguish national and/or local conditions.

For the control of the domiciled vector, it is necessary to know the species present or the species that intervene in the transmission of the infection in the home environment, the degree of vulnerability to the control measures that depend on vulnerability (with greater adaptation to human housing) and human behaviors. The removal of a vector from a determined area depends primarily on whether the species is invasive or introduced and, as such, strictly domiciliary.

The maximum degree of vector control achieved in the case of autochthonous species is the extinction of intradomiciliary colonies through chemical treatment with insecticides. Also, the absence of vector colonies in the interior of the house could represent the interruption of the transmission or its transformation into a fortuitous or accidental event.

The WHO Report [50] updated the epidemiological information on Chagas disease in Latin American countries, based on the available 2010 demographic and epidemiologic information, and it is possible to calculate the population infected, new cases due to vector transmission, number of women infected, and positive children due to mother-to-child transmission. For countries included in the Southern Cone Initiative (Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay), the average prevalence is 2.17% (0.03–6.14%); in the Andean Initiative (Colombia, Ecuador, Peru, and Venezuela), it is 1.08% (0.043–1.38%); and in the Central American Initiative with Mexico (Belize, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama), it is 0.72% (0.16–1.30%) (Table 1).

Table 1 Number of cases of positive population, women, and cases due to vectorial and mother-to-child transmission
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6 Mother-to-Child Transmission

Due to population movements (migration) or due to old infections transmitted by mothers, by the vector, or by transfusions, the distribution of congenital Chagas disease is not restricted to rural areas only. Therefore, congenital transmission goes beyond traditional transmission areas and occurs in remote areas where the vector does not exist. In this way, it becomes a world disease where the transmission factor is the person (mother to child or transfusions), in such remote places as Europe or Japan [51].

The most significant number and case studies of congenital Chagas disease have been reported from Argentina, Bolivia, Brazil, Chile, Colombia, Guatemala, Honduras, Paraguay, Uruguay, and Venezuela. The risk of congenital transmission varies according to the confluence of epidemiological factors, and perhaps here the strain of the parasite, the level of parasitemia of the mother, and the existence of placental lesions are critical. It is estimated that, under these conditions, the risk would vary between 1% and 7%, or more, in some regions of Argentina, Bolivia, Chile, and Paraguay. The number of cases to be detected caused by congenital transmission depends on the prevalence of infection in fertile women who become pregnant, so to achieve control and cutting maternal-fetal transmission, it is necessary to develop actions that allow women to reach their delivery with a proper diagnosis to follow and treat newborns properly.

With vectorial transmission controlled, it can be said that congenital transmission is becoming the primary way of occurrence of new cases in many countries. The absence of sensitive and adequate systems for the detection of infection in newborns leads to the assumption that these will be the new chronic cases in the future.

We can make an estimate, through a theoretical and modeling exercise, of the situation in Argentina from official data [52]. Based on these official data, in Argentina, there is an average of 700,000 deliveries per year, and the prevalence of infection by T. cruzi in pregnant women is 2.8% (12–0.5%). According to this information, between 1400 and 2100 cases of T. cruzi-positive newborns would occur in the country. If this estimated value is compared with detected values, and corrections are made for those possibly treated (detected and not notified), a final result is obtained showing that in Argentina, only for this cause, more than 1000 new chronic cases per year would be produced. These numbers, compared with those reported by vector transmission , are widely superior (Fig. 7).

Fig. 7
figure 7

Notified cases of congenital Chagas disease, correction of really detected non-notified and estimated that should be detected. Argentina 2017. Source Elaborated by the author

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7 Transfusions and Blood Banks

As we described, in the last century, there were important population movements from rural areas to urban areas in the region of the Americas. This motivated a change not only in the pattern of vector transmission, since in areas that were not defined as risky, infected persons were blood suppliers generating the risk of transmission by blood transfusions. Although the risk is present in all regions, the prevalence of blood givers is not the same in all countries.

Since 2005, Spain has a clear regulation regarding the disease of Chagas, which indicates that people with positive T. cruzi serology should not donate blood and requires serological testing of all donors who have lived in countries where Chagas disease is endemic or of children from a mother who has lived in those countries [53].

In Latin America, legislation and regulations or regulations related to blood transfusion began to appear between 1939 and the 1950s–1960s in some countries like Argentina, Brazil, and Chile. In others, they started appearing in the 1970s (Bolivia, Colombia, Costa Rica, Ecuador, Paraguay, Venezuela) and 1980s (Honduras, Mexico, Nicaragua, Uruguay) and in the 1990s, in Guatemala, Panama, and Peru.

In Latin America, there are varieties of national blood system modalities, but the most common situation is an excessive number of institutions that obtain and process blood [54]. Although economies of scale could save resources in the collection and processing of blood donations, as well as in guaranteeing quality procedures, this does not seem to have served to reduce the excessive number of blood banks in operation in the countries.

The 37 states of this region have a regulatory framework that would assure the production and utilization of safe blood through proper selection of donors, screening to detect infectious diseases of 100% of the donors and the prescription of blood products as suggested by good clinical practices. Nevertheless, despite improvements, not all blood for donation is analyzed as required by the standards, and it can be estimated that for HIV, syphilis, and T. cruzi infections, the screening coverage is almost 99%, according to 2005 data [55].

Since regional initiatives, the danger of being infected after a blood transfusion was modified. Most of the states of the area have proven schemes and mechanisms to study all blood to be transfused, achieving around 100% of control of the stock to be transfused in blood banks.

Thus, the prevalence of infection by T. cruzi in blood banks cannot be used as an indicator of prevalence in the population.

8 Oral Transmission

As we have stated, perhaps in its origins, oral transmission had a greater importance than the other routes. As progress is being made in the control of vectorial, transfusional, and mother-to-child transmission, oral transmission becomes increasingly important, being currently responsible for localized foci of risk and fundamentally associated with food [56, 57].

In the Amazon, there have been frequent and epidemiologically significant outbreaks between 1968 and 2005. The Evandro Chagas Institute [58] reported 442 cases in 62 different outbreaks associated mainly with the consumption of açai juice. As a hypothesis, it was suggested that the fruit would have been transported with triatomine and squeezed together to prepare the juice and thus contaminated the drinking.

Diaz presents a summary of the contamination routes for the occurrence of oral transmission. It includes the contamination of food by the reservoirs either directly by the vector in the preparation or directly by the consumption of infective animals [59]. Recently, Rueda Karina [60] published, in a review of oral transmission mechanisms and records, outbreaks, case number, and sources of infection showing that by 2013 Argentina, Bolivia, Brazil, Colombia, French Guiana, Ecuador, and Venezuela reported outbreaks with varying numbers of affected people between 2 and 217 cases.

Of all the routes of transmission, the oral route is the most difficult to control because it is associated with the habits and customs of the population, infected vectors of wild origin, and infected reservoirs present in the diet of many populations of the Americas.

9 Economic Impact

The control program is both costly and cost-effective as control intervention. This is shown in the Southern Cone Initiative that has spent more than USD 345 million from its national budget between 1991 and 2000 to finance vector control and blood banks (transmission through blood transfusion) activities in its territories since the launch of the initiative [44].

Research to measure the impact of interventions by different researchers in the region’s countries [61] showed that the actions developed were effective to achieve an interruption of vectorial transmission, shown by the reduction of T. cruzi prevalence in humans.

Effectiveness was defined using various parameters, with the main one being the measurement of the burden of disease prevented, in DALYs (disability-adjusted life years), potential disease transmission, the overall burden of Chagas disease, etc.

With data from different studies of T. cruzi infection (prevalence), mathematical models were developed trying to determine the trend of the disease in the region countries, giving an economic value to each of the stages of infection, disease, or death [62, 63].

If we carried out an exercise using different serological data of the region and summarized it in the present chapter, associated with average economic values emerging from the various models, we could construct a theoretical economic impact scenario of money savings produced by the countries’ interventions. In 1909, it was estimated that the total expenditure on Chagas disease was almost USD 900 million, reduced by half to the present day with a downward trend for the future (Fig. 8).

Fig. 8
figure 8

Total expenditure in USD dollars by American region and year. 1909–2015. Source Elaborated by the author

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In current times , it is necessary to ensure sustainability of the control program in an unsteady epidemiological context with low T. cruzi infection rates and a political-institutional context of health sector reforms, in which the decentralization of operations may result in the risk of control activities losing priority.

The new scenario requires Chagas disease control activities to be integrated into other programs as EMTCT Plus (PAHO) [64] and become part of a broader scheme for meeting the health needs of the population.

We can say that in terms of transmission, after millennial of evolution, we are where we started.