Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 116 | 2021
Review

Chagas disease control-surveillance in the Americas: the multinational initiatives and the practical impossibility of interrupting vector-borne Trypanosoma cruzi transmission

Antonieta Rojas de Arias1,+, Carlota Monroy2, Felipe Guhl3, Sergio Sosa-Estani4,5, Walter Souza Santos6, Fernando Abad-Franch7

1Centro para el Desarrollo de la Investigación Científica, Asunción, Paraguay
2Universidad de San Carlos, Laboratorio de Entomología y Parasitología Aplicadas, Ciudad de Guatemala, Guatemala
3Universidad de los Andes, Facultad de Ciencias, Centro de Investigaciones en Microbiología y Parasitología Tropical, Bogotá, Colombia
4Drugs for Neglected Diseases initiative Latin America, Rio de Janeiro, RJ, Brasil
5Centro de Investigaciones en Epidemiología y Salud Pública, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
6Ministério da Saúde, Secretaria de Vigilância em Saúde, Instituto Evandro Chagas, Laboratório de Epidemiologia das Leishmanioses, Ananindeua, PA, Brasil
7Universidade de Brasília, Faculdade de Medicina, Núcleo de Medicina Tropical, Brasília, DF, Brasil

DOI: 10.1590/0074-02760210130
615 views 377 downloads
ABSTRACT

Chagas disease (CD) still imposes a heavy burden on most Latin American countries. Vector-borne and mother-to-child transmission cause several thousand new infections per year, and at least 5 million people carry Trypanosoma cruzi. Access to diagnosis and medical care, however, is far from universal. Starting in the 1990s, CD-endemic countries and the Pan American Health Organization-World Health Organization (PAHO-WHO) launched a series of multinational initiatives for CD control-surveillance. An overview of the initiatives’ aims, achievements, and challenges reveals some key common themes that we discuss here in the context of the WHO 2030 goals for CD. Transmission of T. cruzi via blood transfusion and organ transplantation is effectively under control. T. cruzi, however, is a zoonotic pathogen with 100+ vector species widely spread across the Americas; interrupting vector-borne transmission seems therefore unfeasible. Stronger surveillance systems are, and will continue to be, needed to monitor and control CD. Prevention of vertical transmission demands boosting current efforts to screen pregnant and childbearing-aged women. Finally, integral patient care is a critical unmet need in most countries. The decades-long experience of the initiatives, in sum, hints at the practical impossibility of interrupting vector-borne T. cruzi transmission in the Americas. The concept of disease control seems to provide a more realistic description of what can in effect be achieved by 2030.

In spite of substantial reductions of prevalence and incidence over the last 3-4 decades, Chagas disease (CD) still imposes a heavy social, economic, and public-health burden on most Latin American countries. Transmission mediated by native triatomine-bug vectors and mother-to-child transmission cause several thousand new infections per year across the continent. Moreover, while an estimate 5-6 million people carry Trypanosoma cruzi, access to diagnosis and integral medical care is far from universal.

Starting in the early 1990s, Latin American countries where T. cruzi infection is endemic and the Pan American Health Organization-World Health Organization (PAHO-WHO) launched a series of multinational initiatives for the control and surveillance of CD. Here, we present an overview of what those initiatives aimed at, what they have so far achieved, the main challenges they continue to face, and what decades of hard-won experience suggest may be the best ways forward. We follow a north-south course, from Central America-Mexico to the Southern Cone of South America, and close with a summary of a few key, common themes - on the control and interruption of T. cruzi transmission, on disease prevention, and on patient care - emerging from this overview. In discussing these common themes, we pay special attention to the CD-specific targets recently set by the WHO in the context of the United Nations 2030 Sustainable Development Goals.(1)

 

The Initiative of the Central American Countries and Mexico (IPCAM)

 

The Initiative of the Central American Countries for the control of CD (IPCA in its Spanish acronym) was launched in 1997 by Guatemala, Belize, El Salvador, Honduras, Nicaragua, Costa Rica, and Panama; its stated goals were (i) to eliminate the introduced vector, Rhodnius prolixus; (ii) to reduce dwelling infestation by native Triatoma dimidiata; and (iii) to interrupt blood transfusion-mediated transmission of T. cruzi.(2) The elimination of R. prolixus, a highly efficient but non-native (hence entirely domestic) vector, was the top-priority aim.(2, 3, 4) The goal of strengthening CD-specific healthcare within national health systems was incorporated in 2005.(2) Mexico formally joined the IPCA in 2013, and the acronym of the initiative changed to IPCAM. In line with IPCAM goals, Mexico’s “specific action program” for the control and prevention of CD aims at controlling transmission mediated by house-infesting vectors and eliminating mother-to-child and transfusion-mediated transmission.(5) Estimates by the WHO (2010) and the Global Burden of Disease Study (GBD; 2019) suggest that ~1.2 to 1.6 million people may be infected with T. cruzi in IPCAM countries, and that ~13,000 to 47,000 new infections may be expected to occur annually (Table I).(6, 7)

 

table01

 

In Guatemala, the Ministry of Health, researchers from San Carlos University, and the Japanese International Cooperation Agency (JICA) outlined the first national control program after several years of baseline research.(8) Between 2000 and 2005, interventions included area-wide insecticide spraying and measures to prevent transfusion-mediated transmission; the surveillance phase started in 2009.(2) Drawing on the fruitful Guatemalan experience, JICA supported the establishment of control programs in Honduras and El Salvador. Large-scale insecticide-spraying campaigns began in 2003 and both countries entered the surveillance phase in 2008. By 2009, control and surveillance procedures were also in place across Nicaragua.(2)

Entomological surveillance systems implemented with JICA support strongly rely on community involvement. Homeowners collect suspected vectors in labelled containers and drop them in dedicated “bug mailboxes” set in health posts, schools, or volunteer homes. Staff of the vector control program then visits vector-reporting houses to actively search for bugs and take action as required, including selective insecticide spraying and educational interventions. Vector-control agents engage in active entomological surveillance in villages where there are no “bug mailboxes”.(9, 10, 11)

In 2014, JICA discontinued its direct support of vector control activities in Central America. By then, the interruption of T. cruzi transmission by R. prolixus and a reduction of domestic infestations by T. dimidiata had significantly lowered Chagas disease incidence, and coverage of blood-donor screening was 100% throughout the region.(2, 12, 13, 14) Because JICA-sponsored projects did not include infection diagnosis and treatment, IPCA countries sought alternative support sources; an example of international cooperation towards that end is the “Alliances project” in Guatemala.(15)

The interruption of CD transmission by non-native R. prolixus in Mexico and Central America is, together with universal, mandatory blood-donor screening, the most important IPCAM achievement.(2) By 2011, the PAHO-WHO had certified the elimination of R. prolixus from Mexico, Guatemala, Honduras, El Salvador, Nicaragua, and Costa Rica.(2, 13, 14) Along with IPCAM-related activities, insecticide-based malaria-vector control and steadily improving rural housing conditions across the region likely contributed to this elimination.(13, 14) Recently, however, R. prolixus was found infesting houses and outbuildings in two rural sites of Oaxaca, Mexico - a state that was certified R. prolixus-free in 2009 (Table II).(16) This is a stark reminder of the crucial role of long-term entomological surveillance in first achieving, and then sustaining, the huge progress made by control programs aimed at eliminating non-native vector species.(17, 18)

The elimination of one non-native species, in any case, leaves a vacant domestic-peridomestic niche that may be taken over by native species.(17) Decades-long experience from across Latin America shows that insecticide spraying alone cannot eliminate domestic-peridomestic populations of such native triatomines in the long run.(17) In the IPCAM region, T. dimidiata became the main domestic vector in areas once infested by R. prolixus (Table II). As a response, integrative control approaches were devised and tested in the region; some of the key components of this research-action program are (i) identifying and reducing dwelling-infestation risk factors; (ii) ascertaining domestic-infestation thresholds below which T. cruzi transmission becomes sporadic; and (iii) stimulating gender-sensitive community involvement in, e.g., housing improvement or animal husbandry.(19, 20, 21, 22, 23, 24)

 

table02

 

As elimination of R. prolixus was certified, funding for CD control-surveillance programs declined. Among other effects, this decline limited the capacity of local health services to respond to infestation records arising from community-based surveillance;(11) insecticide availability and “bug mailbox” maintenance were also affected. Further, vector-control agents working on CD surveillance have historically been redirected to support public-health responses to epidemics and outbreaks of, e.g., dengue and other arboviral diseases; the current Coronavirus disease 2019 (COVID-19) pandemic is obviously having an even larger impact on the operation of local-scale surveillance systems.

Triatoma dimidiata and several further native species, including R. pallescens, T. ryckmani, T. nitida, T. barberi, T. pallidipennis, T. longipennis, or the recently described T. huehuetenanguensis, are routinely collected inside and around houses across IPCAM countries (Table II). Invasion of houses by (often infected) adult bugs is also common, and some vector-surveillance systems now incorporate a “visitation index” to keep track of this phenomenon; research on the drivers and seasonality of flight-mediated bug dispersal and house invasion has also yielded useful insights.(25, 26, 27) In this scenario of persistent house reinvasion and reinfestation by native vectors, selective insecticide spraying is just one component of a multifaceted, long-term vector control-surveillance strategy that also emphasises gender-sensitive environmental management (particularly at the dwelling level, and covering housing improvements, animal-husbandry practices, waste management, or rodent control) and community involvement.(22, 23, 28, 29, 30, 31, 32) Overall, it has now become clear that elimination of vector-borne CD is not a feasible goal in any of the countries of the IPCAM initiative - some level of transmission will always exist, and local healthcare systems must be prepared to meet this inescapable challenge.(4, 22, 23, 33, 34, 35)

Currently, the Drugs for Neglected Diseases initiative (DNDi), Fundación Mundo Sano, and San Carlos University are working together in Guatemala to include CD diagnosis and patient care in the regular functioning of the Ministry of Health; this will require that health staff at all levels of the system acquire new managerial and clinical skills.(11, 35) In sum, although IPCAM-supported action has led to remarkable advances towards reducing the burden of CD in the region, effectively implementing the long-term strategies needed to control CD in Mexico and Central America will require both stronger policies and larger amounts of committed, stable funding.

 

The Initiative of the Andean Countries (IPA)

 

The Initiative of the Andean Countries for CD control-surveillance (IPA hereafter) was officially launched in 1997 in Bogotá, Colombia within the framework of the Hipólito Unanue Agreement signed by the Ministries of Health of Colombia, Ecuador, Peru, and Venezuela. Its objective was to interrupt vector- and blood transfusion-mediated transmission of T. cruzi in the region.(36, 37) The IPA was ratified by the Ministers of Health of member countries in November 2002. In the last decade, and to the extent that vector control activities and blood-donor screening were implemented, IPA incorporated new goals focused on (i) providing specific treatment to infected patients; (ii) identifying and treating children infected via mother-to-child transmission; and (iii) the study of acute-disease outbreaks linked to oral T. cruzi transmission. Screening of blood donations for T. cruzi infection is mandatory in all IPA countries - where, in spite of operational and financial constraints, control interventions against house-infesting vectors have taken place since the launching of the initiative.(38, 39, 40, 41, 42) WHO (2010) and GBD (2019) estimates suggest that about 1 million people carry T. cruzi in IPA countries, with ~13,000 to 27,000 new infections occurring each year (Table I).(6, 7)

Three heavily synanthropic triatomine-bug vector species are non-native to IPA countries and have been targeted by area-wide control-surveillance campaigns similar to those successfully deployed against T. infestans in Uruguay, Brazil, and parts of Paraguay and Argentina (Table II).(43) R. prolixus is most likely non-native to trans-Andean north-western Colombia (i.e., out of the Orinoco basin) and could hence be locally eliminated. After extensive control efforts across the region, about half of the municipalities considered at high risk of vector-borne CD were certified by the PAHO-WHO as free of transmission mediated by domestic R. prolixus.(44) Similarly, there is compelling evidence that T. dimidiata was introduced into western Ecuador-north-western Peru, and insecticide-based vector-control interventions (likely including those against mosquitoes) seem to have had a substantial impact on domestic populations of the species across that sub-region.(43, 45, 46, 47, 48, 49) Finally, introduced T. infestans occur in several areas of southern Peru; hence, the country also participates in the Southern Cone Initiative (INCOSUR) and adopts the strategies agreed at INCOSUR meetings for the control of non-native populations of this species (see below and Table II).

Key IPA unmet challenges include timely diagnosis of T. cruzi infection and integral patient care. In particular, IPA countries lack dedicated programs for aetiological treatment and clinical follow-up or for the early detection and management of congenital CD. In some disease-endemic regions of Colombia, non-governmental organisations offer CD diagnosis and treatment; to be effective in the long run, however, such worthy efforts must be placed within the context of stronger public healthcare systems.

The progress of vector-control activities has been slow, and interventions are yet to be implemented in some geographical areas where domestic triatomine populations are known to occur. This has been partly due to the lack of adequate knowledge about the ecological and behavioural characteristics of locally native vectors, which generates uncertainty about what control measures and strategies are most appropriate. Native triatomine-bug species are highly diverse (taxonomically, ecologically, and behaviourally) across IPA countries, and vector control-surveillance strategies need to be fine-tuned for species that occur in both domestic-peridomestic and wild habitats (Table II).(39, 43, 50) Findings from Colombia and Venezuela, for example, clearly substantiate the need for surveillance programs capable of gauging the epidemiological risk posed by wild R. prolixus populations inhabiting palms of the Orinoco basin.(51, 52, 53, 54) Recent records of R. prolixus in agribusiness plantations of African oil-palms (Elaeis guineensis) outline a potentially emerging challenge that is yet to be characterised in terms of human infection risk.(55, 56)

Wild R. ecuadoriensis populations are similarly common in Phytelephas palm-crowns across central-western Ecuador.(57) However, R. ecuadoriensis is also a well-known domestic pest in dry inter-Andean valleys of southern Ecuador and northern Peru that lack native palms; since most Rhodnius are tightly associated with palms, this suggested the possibility that wild R. ecuadoriensis could be absent from the region - and, therefore, that insecticide-based control could eliminate local domestic populations.(58) However, the discovery that R. ecuadoriensis often infest tree-squirrel nests in southern Ecuador,(59) together with isolated records from Peru,(60) suggests that wild populations are also present in those dry inter-Andean valleys.

Triatoma dimidiata is widely distributed in IPA countries and often colonises in human dwellings, where it can transmit T. cruzi; the species has thus become the target of extensive control-surveillance interventions. Wild T. dimidiata populations, however, are common in north and central-western Colombia and probably occur also in northern Venezuela.(61, 62, 63, 64) The species, consequently, is not a candidate for local elimination, and research aimed at developing and testing new, long-term, sustainable control options is - as discussed above for IPCAM countries - critical.

Panstrongylus lignarius/herreri is an important domestic vector of T. cruzi in the dry middle-upper Marañón valley of north-western Peru.(65) Other native triatomine-bug species that regularly infest houses and outbuildings in different parts of IPA countries are T. maculata, T. carrioni, T. venosa, P. howardi, and P. chinai; occasionally, P. rufotuberculatus, T. dispar or T. nigromaculata may also be involved in domestic-peridomestic T. cruzi transmission (Table II).(39, 50) Although it rarely breeds in human-made structures, P. geniculatus has been associated with outbreaks of orally-transmitted, acute CD in Venezuela.(66, 67)

The scenario outlined above leads to concluding that, in spite of some advances towards preventing and controlling CD in the IPA region, there is still a long way to go. The Andean countries must develop integral and integrated, long-term programs covering all aspects of the disease - from primary prevention to highly-specialised tertiary care. This must include implementing universal antenatal screening of all pregnant women in T. cruzi-endemic areas and strengthening national healthcare systems so that they can provide diagnosis, aetiological treatment, and broader care and support to all patients with CD, whether acute or chronic.

 

The Initiative of the Amazon Countries (AMCHA)

 

Carlos Chagas was the first to report T. cruzi from Amazonia.(68) The parasite was eventually shown to circulate widely among wild mammals and triatomines, but early surveys suggested that human infections were rare and that local triatomine-bug species did not infest houses.(69, 70, 71, 72, 73, 74, 75) Because endemic transmission of T. cruzi was thought to require stable house infestation, human infections were interpreted as the result of occasional spillover from sylvatic cycles.(73, 74, 75, 76) This led to the conclusion that CD was enzootic, but not endemic, in Amazonia, where only sporadic cases occurred in more-or-less discrete geographic clusters.(76, 77)

This view of Amazonia as “free” from endemic CD was to prevail for decades.(77) When the 1975-1980 Brazilian national serosurvey reported an average prevalence close to 1% for six Amazonian states,(78) the results were thought to signal widespread presence of cross-reactive antibodies, immigration of infected people, or labelling or data-processing errors; as Silveira(79) later put it, “none of those hypotheses […] could be confirmed”. The 2001-2008 Brazilian national survey(80) did not help clarify the status of the disease in the region. Since the primary goal was to measure the impact of domestic-vector control, sampling was limited to children < 5 years-old; exposure time thus averaged just ~2.5 years, and only six of 14,877 children sampled in Amazonia tested positive.(80) The survey was hence, in a way, a lost opportunity: wider age-class sampling would have provided a much more faithful picture of regional transmission dynamics, which primarily involve non-domiciliated vectors.(81, 82)

In the meantime, slowly-accruing evidence started to suggest that CD was more frequent than suspected in Amazonia. New cases were described, several “transmission foci” were identified, infection frequencies > 5% were reported from some sub-regions, and outbreaks of acute CD likely related to food contamination began to crop up at a seemingly increasing rate, mainly in eastern Amazonia.(82-96) In 2002, the European Community-Latin American (ECLAT) network for research on the Triatominae convened a workshop on CD surveillance in Amazonia.(97) Two years later, the PAHO-WHO launched the Initiative for the Surveillance and Prevention of Chagas disease in Amazonia (AMCHA). Bolivia, Brazil, Colombia, Ecuador, France, Guyana, Peru, Suriname, and Venezuela are members of AMCHA, whose stated goal is to prevent the large-scale establishment of endemic vector-borne CD in the region.(98)

PAHO-WHO-supported AMCHA activities and advocacy, together with popular-media reports on acute-disease outbreaks, started to spread awareness of CD among healthcare workers, the general public, and decision-makers - including those in charge of defining research-funding priorities and disease-notification policies. This set the stage for the generation of new epidemiological, entomological, parasitological, and clinical evidence.(82, 83) Below we outline what that evidence, taken as a whole, suggests.

(i) CD is probably (hypo)endemic in Amazonia. Overall prevalence may be about 1-2%, with higher values (~4-5 to > 10%) in some sub-regions (such as the Ecuadorian Amazon or the high-jungle of Peru)(65, 82, 84, 85) and human groups (such as Leopoldinia piassaba palm-fibre gatherers).(77, 82, 83, 87) For a population of ~34 million, a 1.5% global prevalence would imply that some 500,000 people are infected with T. cruzi in Amazonia.

(ii) CD is primarily vector-borne in Amazonia.(82, 99) Non-domiciliated native triatomines mediate “classical” transmission through direct human-vector contact and are probably also involved in most food-borne outbreaks; thus, “oral transmission” of CD is essentially vector-borne too.(82, 83, 95)

(iii) Classical vector-borne transmission is probably overall more frequent than food-borne transmission. Food-borne cases are just more visible because they tend to be more severe and because active contact-tracing enhances case detection.(82, 83, 95) Underdetection and underreporting, therefore, are in all likelihood much more extensive for the often oligosymptomatic/asymptomatic classical vector-borne infections than for food-borne infections.(81, 82)

(iv) Outbreaks of food-borne CD cluster heavily in the Brazilian eastern Amazon.(96, 100) This is most likely because raw açaí (Euterpe spp.) juice, often prepared using substandard food-safety practices, is massively consumed in that sub-region. The apparent recent rise of outbreak frequency(100) parallels local açaí production trends: the State of Pará (where > 95% of Brazilian açaí is grown) reported a nearly 10-fold rise of açaí fruit production between 2000 (150,500 tonnes) and 2018 (1,440,000 tonnes).(101)

(v) Infection with Amazonian T. cruzi strains (mainly in TcI, TcIII, and TcIV) can cause severe, even fatal, acute and chronic CD.(77, 82, 83, 91, 92, 93, 102, 103)

(vi) Wild (and some domestic) mammals make up a huge T. cruzi reservoir in Amazonia.(77, 82, 103)

(vii) Triatomines are widespread across Amazonia (Table II).(77, 99, 104, 105) Palms and hollow trees/logs are key ecotopes, but populations of a few species do infest houses.(77, 99, 105, 106) Wild bugs often invade houses and other premises;(95, 107) this behaviour underpins the main mechanism of CD transmission in Amazonia.

Our understanding of the epidemiology of CD in Amazonia has grown substantially, yet much remains to be done. Crucially, most people infected with T. cruzi simply remain undiagnosed and therefore do not get the care they need. They deserve better. We now outline some of the most pressing challenges and suggest ways to address them.

(i) We lack reliable estimates of key epidemiological parameters. Prevalence could be estimated through coordinated serosurveys; a complementary/alternative strategy might draw on malaria diagnosis/management networks to collect blood-spot samples and ship them for serological testing. Estimating incidence would ideally require enhanced surveillance/reporting (see below), but data on prevalence by age class can also be used to estimate incidence.(108) Statistically accounting for imperfect diagnostic-test performance and for underreporting can help improve epidemiological-parameter estimates.(108, 109, 110)

(ii) Surveillance is weak and must be strengthened. Notification of acute and chronic CD should be compulsory in all countries. Trained malaria microscopists can help detect T. cruzi infections; more generally, primary healthcare workers should be better trained to identify the disease.(111) Serological screening is done in all blood banks and should be extended to pregnant women.(112) Death records can also be informative, again with the caveat of underreporting.(113)

(iii) Preventing CD in Amazonia would require a combination of food-safety measures, serological screening of pregnant women, and insecticide-based control of domestic-vector foci. Personal-protection measures for piaçava-fibre gatherers, insect-screening of houses and food-processing equipment/premises, and insecticide-impregnated bednets/curtains might help reduce transmission by wild vectors.(114)

(iv) As stressed above, the vast majority of those infected with T. cruzi (i.e., tens of thousands) do not receive any specific care in Amazonia. Primary-health workers are overall ill-equipped to identify and manage these patients; key needs include stronger, specific training and a wider availability of diagnostic tests and drugs.(82)

(v) Although food-borne outbreaks have received much attention, awareness of CD is still low in Amazonia. We need to develop better communication/advocacy strategies aimed at health workers, health authorities, researchers, people living at higher risk, and the general public.(115)

This overview suggests that CD is today in Amazonia what CD will likely become across most of Latin America as house infestations are controlled - a hypoendemic disease with some “hotspots” due to more intense exposure to native vectors.(18) Exposure can be direct (in the wild or when bugs invade or colonise houses) or food-mediated. House-infesting triatomines can be controlled with traditional insecticide-based interventions in the context of long-term surveillance; exposure to wild bugs is less well understood and more research is needed.(18, 107) Food-mediated exposure is primarily a matter of food-safety standards; both regulation and communication have important roles to play.(83) Whatever the origin of the infection (vector-borne, food-borne, or mother-to-child), stronger healthcare and surveillance systems hold the key to reducing the burden of CD in Amazonia.

 

The Initiative of the Southern Cone Countries (INCOSUR)

 

Created in 1991 by the governments of Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay, the Initiative of the Southern Cone Countries (INCOSUR) has played a key role in CD control in the region. Since its inception, INCOSUR has aimed primarily at (i) eliminating house-infesting populations of the main regional vector, Triatoma infestans; (ii) reducing/controlling domestic infestations by other (“secondary”) vector species; and (iii) interrupting T. cruzi transmission mediated by blood transfusion. INCOSUR provided crucial guidance and drive, both technical and political, to the rest of initiatives.(50, 116) Because domestic T. infestans populations were widespread over the south-west of the Peru, representatives of this country regularly joined INCOSUR meetings from 1993 on.(50) Recent estimates suggest that between ~3.5 and ~4.5 million people may carry T. cruzi in INCOSUR countries, with perhaps about 100,000 new cases per year (Table I).

Even before INCOSUR was launched, Southern Cone scientists and public-health workers had made fundamental contributions to our understanding of CD aetiology, pathogenesis, management, transmission dynamics, and control.(117, 118) Prevention programs focusing on vector control were implemented in Brazil, Argentina, Chile, and Uruguay in the 1960s. By the late 1970s, blood-donor screening was mandatory in all INCOSUR countries.(50, 119) Strategies to control mother-to-child transmission began to be developed, tested, and put into practice in the 1980s, mainly in Argentina; because of the perception that vertical transmission of the parasite could not be actually prevented, efforts concentrated on the early diagnosis and treatment of children with congenital infection.(120)

Extensive insecticide-spraying campaigns led to the effective elimination of non-native T. infestans populations from Uruguay, Brazil, and parts of Paraguay, Argentina and Peru; the PAHO-WHO eventually certified those areas, as well as two Bolivian departments, as free from T. cruzi transmission by that particular vector species.(50, 121) As with R. prolixus in Mexico,(16) however, a few T. infestans residual foci have since been detected in Brazil, again underscoring the need for long-term surveillance.(122, 123, 124, 125) Non-native T. infestans have also proven difficult to control in urban Arequipa, Peru.(126, 127) Importantly, moreover, T. infestans is native, and hence widespread in wild environments, across the dry Chaco (Argentina, Paraguay and Bolivia) and the inter-Andean temperate-dry valleys of south-eastern Bolivia.(64) House reinfestation by native T. infestans is common, and transmission of T. cruzi can persist or resume (even if at relatively low intensities) in areas under control-surveillance.(128, 129, 130, 131, 132) Many other native triatomines, some of which readily infest human dwellings (e.g., T. brasiliensis, T. pseudomaculata, T. sordida, or P. megistus), are common in different INCOSUR countries and territories (Table II).(18, 64) Hence, vector-mediated transmission of CD should be expected to continue (at relatively low, yet non-zero, rates) in the region - and to disproportionately affect those living in rural substandard houses.(18, 81) As noted above, blood-donor screening was also central to INCOSUR goals, and universal coverage was in place by the end of the 1970s.(50, 116, 117, 119)

Control of mother-to-child transmission was incorporated as a third strategic component of national control programs; the strategy is largely based on the serological screening of pregnant women during prenatal care, and on the follow-up of babies born to infected mothers.(133, 134) Bolivia, Argentina, Uruguay, and the Brazilian states of Goiás and Mato Grosso do Sul have regulations for universal screening of pregnant women; in Chile, screening covers women living in regions where vector-mediated transmission is considered endemic. Recently, the PAHO-WHO promoted a supranational initiative for the elimination of mother-to-child transmission of CD, HIV, syphilis, and hepatitis B; this “EMTCT Plus” initiative recommends the screening of pregnant women and, when infection is detected, the timely diagnosis, treatment, and follow-up of their children.(135)

Serological surveys, and in particular those involving children living in areas where vector-mediated transmission may still be active, have been used to gauge the impact of control interventions.(80, 117, 121, 136) Apart from intrinsic methodological difficulties, these surveys have often raised the issue of whether specific anti-T. cruzi treatment and adequate follow-up is in effect available to all those testing positive.(18, 81, 136) More generally, offering diagnosis and aetiological treatment to as many people as possible is increasingly seen, together with case notification, as a key component of integrated control programs aimed at reducing the burden of CD and at eliminating it as a public health issue.(1, 108, 137, 138) While primary-healthcare systems can and should manage most T. cruzi infections, in many local settings such systems need to be strengthened with suitably trained staff, appropriate technology, and effective patient referral/counter-referral networks. With adequate training and support, primary-healthcare workers can and should, in addition, actively seek further cases in the families of newly diagnosed patients.(139) In sum, the current strategy in most INCOSUR countries to reduce the number of people infected with T. cruzi combines primary prevention (through vector control-surveillance and blood/organ-donor screening) and secondary prevention (through adequate patient care, including aetiological treatment, and the screening of pregnant women and their offspring).(108, 138, 140)

The main challenges faced by INCOSUR countries in their efforts to bring CD under control can be summarised as follows.

(i) Widespread presence of efficient native vectors. This includes native T. infestans and several other species that often breed in or around houses and can thus maintain domestic-peridomestic transmission of T. cruzi (Table II).

(ii) Insecticide-resistant vector populations. Pyrethroid-resistant T. infestans were discovered in Yacuiba, Bolivia, and Salvador Mazza, Argentina, in the 2000s, and later shown to be widespread across the Chaco and in parts of the south-eastern Bolivian Andes.(141, 142, 143) Continuous monitoring of resistance is thus necessary, and further research required to find new alternatives for sustainable vector control.

(iii) Structure of control programs. Decentralisation of the health sector in Latin America since the mid-1980s led to the transfer of most CD control activities to states, provinces, or municipalities.(144) This brought decision power closer to the communities where interventions are in fact delivered, thus enhancing, to a certain extent, the management of control programs. Decentralisation, however, also had negative effects - on the one hand, it swiftly distributed duties, but, on the other, it overall failed to fairly distribute the resources and expertise needed to tackle those duties, and this generated inequities in the levels of protection enjoyed by different local populations.(144)

(iv) Control of congenital transmission. Mother-to-child transmission is the main mode of T. cruzi transmission in vector-free areas within and outside Latin America. The PAHO-WHO estimates that ~15,000 new cases occur each year in Latin America.(134, 135) Diagnostic algorithms for congenital CD have well-known limitations, including the low sensitivity of microscopy-based tests, the fact that serological tests cannot be used in newborns because maternal antibodies can result in false-positive results, and the frequent loss to follow-up of initially negative babies.(134) Molecular tests show much promise, but they need further standardisation and are overall too expensive to be universally accessible.(134, 145) There is increasing evidence that congenital transmission can be prevented by treating infected, non-pregnant women of childbearing age with anti-T. cruzi drugs.(134, 146, 147, 148, 149, 150)

(v) Patient coverage. The large gap between the national demand for specific aetiological treatment and the estimates of CD prevalence and incidence suggests that many patients simply remain undiagnosed, and hence untreated, across INCOSUR countries. Better strategies are critically needed to remove the barriers that keep patients from getting adequate diagnosis and integral care.(151)

(vi) Demonstration of disease burden. Strategic public-health decisions often hinge on the capacity of researchers and program officials to demonstrate disease burden. The visibility of CD, however, is paradigmatically low.(18, 81) Compulsory notification of both chronic and acute cases to national surveillance systems could fundamentally help highlight the real burden of the disease.(152) Notification is now mandatory for all chronic cases in Brazil and for pregnant women and children/adolescents under 18 years of age in Argentina.(153, 154)

In sum, the long-term INCOSUR experience shows that although T. cruzi transmission by non-native vectors, blood transfusion, and organ transplantation can effectively be curbed, preclinical, clinical, social, and implementation research is still needed to achieve the WHO 2030 goals for CD control and prevention.(1, 108, 155, 156)

 

In conclusion

 

A few common themes emerge from this quick overview of the history, achievements, and challenges of the inter-governmental initiatives for CD control and surveillance. Below we briefly summarise these main topics (see also Table III) and discuss them in the context of the United Nations Sustainable Development Goals and the specific targets set by the WHO to “eliminate Chagas disease as a public health problem” by 2030.(1, 108)

First, T. cruzi transmission mediated by blood transfusion and organ transplantation is effectively under control; because no screening test performs perfectly, however, clinicians should be aware of the possibility that rare, isolated cases arise on occasion. In practice, the WHO 2030 targets of interrupting transmission mediated by blood transfusion and organ transplantation seem both feasible (Table III). Similarly, laboratory or field accidents involving T. cruzi (in culture or in its vectors or hosts) can result in sporadic events of transmission (Table III).

 

table03

 

Second, the zoonotic nature of T. cruzi and the widespread presence of native vectors across the Americas mean that, in practice, interrupting vector-mediated transmission of the parasite is unfeasible (Tables II-III). Stronger, more sensitive surveillance systems with adequate spatial and population coverage are, and will continue to be, critically needed to detect incident cases. Control of non-native vectors was possible because the exclusively domestic-peridomestic habits of introduced bugs rendered them highly vulnerable to insecticide spraying; native vectors, in contrast, persistently reinvade and reinfest insecticide-treated houses and can maintain transmission, even if at slower rates, from the southern United States to Argentina (Tables II-III). Outbreaks of acute CD linked to contamination of food by infected vectors are the most visible, but by no means the only, manifestation of this problem. In general, then, the WHO 2030 target of interrupting transmission mediated by house-infesting vectors, which involves bringing incidence down to zero, seems unfeasible (Table III).

Finally, adequate patient care across all levels of complexity - from primary to tertiary - is a crucial unmet need in most countries. Over the last years, renewed focus on the patient has inspired a good deal of useful discussion about integral care; it seems hardly controversial, however, that most T. cruzi infections still remain undiagnosed in Latin America - and that only a fraction of patients with a diagnosis get the care they need. On a more positive note, discussion over patient care has also promoted the view that diagnosing and treating T. cruzi infection in women of childbearing age can help prevent mother-to-child transmission. Of course, diagnosing mothers also increases the odds of that, if infected, their babies will be diagnosed and treated. Achieving the WHO 2030 target of interrupting congenital transmission, however, is thought to require ~90% screening coverage of childbearing-aged women, plus treatment of those testing positive and screening of their offspring; there seems to be a long way before these targets are attained in disease-endemic settings (Table III). More generally, providing aetiological treatment to 75% of all people infected with T. cruzi - as the WHO targets suggest should be done (together with interruption of transmission by house-infesting vectors, blood transfusion and organ transplantation) to eliminate CD as a public health problem - will require substantial efforts.

By providing sharply defined common goals and encouraging the exchange of expertise and experience between countries, the multinational initiatives coordinated by the PAHO-WHO have played a crucial role in advancing CD control in Latin America. Transmission of T. cruzi mediated by blood transfusion and organ transplantation has been interrupted throughout the region, and non-native vectors have been eliminated from most of their past distribution range. Introduced vector populations persist, however, in Peru, Ecuador, Colombia, and parts of Brazil, Chile, or Argentina, and over 100 native species (including all the major domestic vectors) maintain endemic transmission of this zoonotic parasite across the region. Such a scenario suggests that, as continuing control efforts and slowly-improving housing conditions further reduce the incidence of vector-borne infections, prevalence might eventually stabilise at ~1-2% of the population at risk. With ~100 million rural residents in Latin America, it follows that public-health and healthcare systems should be prepared to provide support to a relatively steady pool of at least ~1-2 million T. cruzi-infected people. This must include (i) truly universal patient care and antenatal screening and (ii) stronger, continuous, high-coverage control-surveillance systems, both entomological and epidemiological.

The now vast experience of the multinational initiatives and their member countries, in sum, seems to hint at the practical impossibility of interrupting vector-borne T. cruzi transmission in the Americas - with “interruption of transmission” defined by the WHO as the “[r]eduction to zero of the incidence of infection caused by a specific pathogen in a defined geographical area, with minimal risk of reintroduction, as a result of deliberate efforts”.(1) Instead, it would seem that “disease control”, which the WHO defines as the “[r]eduction of disease incidence, prevalence, morbidity and/or mortality to a locally acceptable level as a result of deliberate efforts”,(1) provides a more realistic description of what can be achieved in practice by 2030 and beyond.

 

ACKNOWLEDGEMENTS

 

To the donors, public and private, who have provided funding for all DNDi activities since its inception in 2003. A full list of DNDi’s donors can be found at http://www.dndi.org/donors/donors/.

 

AUTHORS’ CONTRIBUTION

 

ARA and FA-F coordinated the writing of the review; ARA, CM, FG, SS-E, WSS and FA-F wrote the review.

REFERENCES
01. WHO - World Health Organization. Ending the neglect to attain the sustainable development goals: a road map for neglected tropical diseases 2021-2030. Geneva: World Health Organization; 2020.
02. Mancero BT, Ponce CG, editors. Iniciativa de los Países de América Central, para la interrupción de la transmisión vectorial y transfusional de la enfermedad de Chagas (IPCA). Historia de 12 años de una Iniciativa Subregional 1998-2010. Representación de la OPS/OMS en Honduras; 2011. Document OPS/HSD/CD/005-11. Available from: https://www.paho.org/hq/dmdocuments/2012/chagas-Historia-IPCA.pdf.
03. Paz-Bailey G, Monroy C, Rodas A, Rosales R, Tabaru Y, Davies C, et al. Incidence of Trypanosoma cruzi infection in two Guatemalan communities. Trans R Soc Trop Med Hyg. 2002; 96(1): 48-52.
04. Monroy C, Rodas A, Mejía M, Rosales R, Tabaru Y. Epidemiology of Chagas disease in Guatemala: infection rate of Triatoma dimidiata, Triatoma nitida and Rhodnius prolixus (Hemiptera, Reduviidae) with Trypanosoma cruzi and Trypanosoma rangeli (Kinetoplastida: Trypanosomatidae). Mem Inst Oswaldo Cruz. 2003; 98(3): 305-10.
05. Rojo-Medina J, Ruiz-Matus C, Salazar-Schettino PM, González-Roldán JF. Enfermedad de Chagas en México. Gac Med Mex. 2018; 154(5): 605-12.
06. WHO - World Health Organization. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec. 2015; 90(6): 33-43.
07. GBD - Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019) results. Seattle: Institute for Health Metrics and Evaluation; 2020. Available from: http://ghdx.healthdata.org/gbd-results-tool.
08. Tabaru Y, Monroy C, Rodas A, Mejía M, Rosales R. The geographical distribution of vectors of Chagas disease and populations at risk of infection in Guatemala. Med Entomol Zool. 1999; 50(1): 9-17.
09. Hashimoto K, Yoshioka K. Review: surveillance of Chagas disease. Adv Parasitol. 2012; 79: 375-428.
10. Yoshioka K. Impact of a community-based bug-hunting campaign on Chagas disease control: a case study in the department of Jalapa, Guatemala. Mem Inst Oswaldo Cruz. 2013; 108(2): 205-11.
11. Hashimoto K, Zúniga C, Romero E, Morales Z, Maguire JH. Determinants of health service responsiveness in community-based vector surveillance for Chagas disease in Guatemala, El Salvador, and Honduras. PLoS Negl Trop Dis. 2015; 9(8): e0003974.
12. Nakagawa J, Hashimoto K, Cordon-Rosales C, Juarez J, Trampe R, Marroquin L. The impact of vector control on Triatoma dimidiata in the Guatemalan department of Jutiapa. Ann Trop Med Parasitol. 2003; 97(3): 289-98.
13. Cedillos RA, Romero JE, Sasagawa E. Elimination of Rhodnius prolixus in El Salvador, Central America. Mem Inst Oswaldo Cruz. 2012; 107(8): 1068-9.
14. Hashimoto K, Schofield CJ. Elimination of Rhodnius prolixus in Central America. Parasit Vectors. 2012; 5: 45.
15. Peterson J, Yoshioka K, Hashimoto K, Caranci A, Gottdenker N, Monroy C, et al. Chagas disease epidemiology in Central America: an update. Curr Trop Med Rep. 2019; 6(2): 76-91.
16. Antonio-Campos A, Nicolás-Cruz A, Girón-Arias JI, Rivas N, Alejandre-Aguilar R. Presence of Rhodnius prolixus Stål, 1859 (Hemiptera: Reduviidae) in Oaxaca, Mexico, ten years after the certification of its elimination. J Vector Ecol. 2019; 44(2): 293-5.
17. Abad-Franch F, Vega MC, Rolon MS, Santos WS, Rojas de Arias A. Community participation in Chagas disease vector surveillance: systematic review. PLoS Negl Trop Dis. 2011; 5(6): e1207.
18. Abad-Franch F, Diotaiuti L, Gurgel-Gonçalves R, Gürtler RE. Certifying the interruption of Chagas disease transmission by native vectors: cui bono? Mem Inst Oswaldo Cruz. 2013; 108(2): 251-4.
19. Yoshioka K, Nakamura J, Pérez B, Tercero D, Pérez L, Tabaru Y. Effectiveness of large-scale Chagas disease vector control program in Nicaragua by residual insecticide spraying against Triatoma dimidiata. Am J Trop Med Hyg. 2015; 93(6): 1231-9.
20. Bustamante D, Monroy C, Pineda S, Rodas A, Castro X, Ayala V, et al. Risk factors for intra-domiciliary infestation by the Chagas disease vector Triatoma dimidiata in Jutiapa, Guatemala. Cad Saude Publica. 2009; 25(Suppl. I): S83-92.
21. Rodríguez D, Mertenes F, Zuniga C, Mendoza Y, Nakano E, Monroy M. The role of gender in Chagas disease preventions and control in Honduras: an analysis of communication and collaborations networks. EcoHealth. 2016; 13(3): 535-48.
22. Monroy C, Bustamante D, Pineda S, Rodas A, Castro X, Ayala V, et al. House improvements and community participation in the control of Triatoma dimidiata re-infestation in Jutiapa, Guatemala. Cad Saude Publica. 2009; 25(Suppl. I): S168-78.
23. Pellecer M, Dorn P, Bustamante D, Rodas A, Monroy C. Vector blood meals are an early indicator of the effectiveness of the Ecohealth approach in halting Chagas transmission in Guatemala. Am J Trop Med Hyg. 2013; 88(4): 638-44.
24. Aiga H, Sasagawa E, Hashimoto K, Nakamura J, Zuñiga C, Romero J, et al. Chagas disease: assessing the existence of a threshold for bug infestation rate. Am J Trop Med Hyg. 2012; 86(6): 972-9.
25. Barbu C, Dumonteil E, Gourbière S. Optimization of control strategies for non-domiciliated Triatoma dimidiata, Chagas disease vector in the Yucatan Peninsula, Mexico. PLoS Negl Trop Dis. 2009; 3(4): e416.
26. Pacheco-Tucuch FS, Ramirez-Sierra MJ, Gourbière S, Dumonteil E. Public street lights increase house infestation by the Chagas disease vector Triatoma dimidiata. PLoS One. 2012; 7(4): e36207.
27. Dumonteil E, Nouvellet P, Rosecrans K, Ramirez-Sierra MJ, Gamboa-León R, Cruz-Chan V, et al. Eco-bio-social determinants for house infestation by non-domiciliated Triatoma dimidiata in the Yucatan Peninsula, Mexico. PLoS Negl Trop Dis. 2013; 7(9): e2466.
28. Gürtler RE, Yadon ZE. Eco-bio-social research on community-based approaches for Chagas disease vector control in Latin America. Trans R Soc Trop Med Hyg. 2015; 109(2): 91-8.
29. Waleckx E, Camara-Mejia J, Ramirez-Sierra MJ, Cruz-Chan V, Rosado-Vallado M, Vazquez-Narvaez S, et al. An innovative Ecohealth intervention for Chagas disease vector control in Yucatan, Mexico. Trans R Soc Trop Med Hyg. 2015; 109(2): 143-9.
30. Waleckx E, Pérez-Carrillo S, Chávez-Lazo S, Pasos-Alquicira R, Cámara-Heredia M, Acuña-Lizama J, et al. Non-randomized controlled trial of the long-term efficacy of an Ecohealth intervention against Chagas disease in Yucatan, Mexico. PLoS Negl Trop Dis. 2018; 12(7): e0006605.
31. Lucero DE, Morrissey LA, Rizzo DM, Rodas A, Garnica R, Stevens L, et al. Ecohealth interventions limit triatomine reinfestation following insecticide spraying in La Brea, Guatemala. Am J Trop Med Hyg. 2013; 88(4): 630-7.
32. Monroy C, Castro X, Bustamante DM, Pineda SS, Rodas A, Moguel B, et al. An ecosystem approach for the prevention of Chagas disease in rural Guatemala. In Charron DF, editor. Ecohealth research in practice. New York: Springer; 2012. p. 153-62.
33. Stevens L, Monroy C, Rodas A, Hicks R, Lucero D, Lyons L, et al. Migration and gene flow among domestic populations of the Chagas insect vector Triatoma dimidiata detected by microsatellite loci. J Med Entomol. 2015; 52(3); 419-28.
34. Lima-Cordón R, Monroy M, Stevens L, Rodas A, Rodas G, Dorn P, et al. Description of Triatoma huehuetenanguensis sp. n., a potential Chagas disease vector (Hemiptera, Reduviidae, Triatominae). ZooKeys. 2019; 820: 51-70.
35. Castro-Arroyave D, Monroy C, Irurita M. Integrated vector control of Chagas disease in Guatemala: a case of social innovation in health. Infect Dis Poverty. 2020; 9(1): 25.
36. Guhl F, Vallejo GA. Interruption of Chagas disease transmission in the Andean countries: Colombia. Mem Inst Oswaldo Cruz. 1999; 94(Suppl. I): 413-5.
37. Salvatella R. Andean subregional Chagas disease area and the Andean Initiative of Chagas Disease. Mem Inst Oswaldo Cruz. 2007; 102(Suppl. I): 39-40.
38. Guhl F, Restrepo M, Angulo VM, Antunes CM, Campbell-Lendrum D, Davies C. Lessons from a national survey of Chagas disease transmission risk in Colombia. Trends Parasitol. 2005; 21(6): 259-62.
39. Guhl F. Chagas disease in Andean countries. Mem Inst Oswaldo Cruz. 2007; 102(Suppl. I): 29-37.
40. Quinde-Calderón L, Rios-Quituizaca P, Solorzano L, Dumonteil E. Ten years (2004-2014) of Chagas disease surveillance and vector control in Ecuador: successes and challenges. Trop Med Int Health. 2016; 21(1): 84-92.
41. Aché A, Matos AJ. Interrupting Chagas disease transmission in Venezuela. Rev Inst Med Trop São Paulo. 2001; 43(1): 37-43.
42. Feliciangeli MD, Campbell-Lendrum D, Martinez C, Gonzalez D, Coleman P, Davies C. Chagas’ disease control in Venezuela: lessons for the Andean region and beyond. Trends Parasitol. 2003; 19(1): 44-9.
43. Abad-Franch F. A simple, biologically sound, and potentially useful working classification of Chagas disease vectors. Mem Inst Oswaldo Cruz. 2016; 111(10): 649-51.
44. PAHO - Pan American Health Organization. Evaluación internacional de la situación epidemiológica y de control de Chagas en 34 municipios de los departamentos de Arauca, Boyacá, Casanare, Norte Santander, Santander y Vichada, Colombia. 2019. Available from: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ET/informe-verificacion-interrupcion-transmision-vectorial-chagas-2019.pdf.
45. Bargues MD, Klisiowicz DR, Gonzalez-Candelas F, Ramsey JM, Monroy C, Ponce C, et al. Phylogeography and genetic variation of Triatoma dimidiata, the main Chagas disease vector in Central America, and its position within the genus Triatoma. PLoS Negl Trop Dis. 2008; 2(5): e233.
46. Monteiro FA, Peretolchina T, Lazoski C, Harris K, Dotson EM, Abad-Franch F, et al. Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata. PLoS One. 2013; 8(8): e70974.
47. Wong YY, Macias KJS, Martínez DG, Solórzano LF, Ramírez-Sierra, MJ, Herrera C, et al. Molecular epidemiology of Trypanosoma cruzi and Triatoma dimidiata in costal Ecuador. Infect Genet Evol. 2016; 41: 207-12.
48. Cuba CAC, Vallejo GA, Gurgel-Gonçalves R. Triatomines (Hemiptera, Reduviidae) prevalent in the northwest of Peru: species with epidemiological vectorial capacity. Parasitol Latinoam. 2007; 62(3-4): 154-64.
49. Grijalva MJ, Palomeque FS, Villacís AG, Black CL, Arcos-Terán L. Absence of domestic triatomine colonies in an area of the coastal region of Ecuador where Chagas disease is endemic. Mem Inst Oswaldo Cruz. 2010; 105(5): 677-81.
50. Coura JR, Abad-Franch F, Aguilera X, Dias JCP, Gil E, Junqueira ACV, et al. The initiatives for the control of Chagas disease in the Americas and in non-endemic countries: overview and perspectives. Rev Soc Bras Med Trop. 2009; 42(Suppl. II): 106-10.
51. Fitzpatrick S, Feliciangeli MD, Sanchez-Martin MJ, Monteiro FA, Miles MA. Molecular genetics reveal that silvatic Rhodnius prolixus do colonise rural houses. PLoS Negl Trop Dis. 2008; 2(4): e210.
52. Cordovez JM, Guhl F. The impact of landscape transformation on the reinfestation rates of Rhodnius prolixus in the Orinoco Region, Colombia. Acta Trop. 2015; 151: 73-9.
53. Rendón LM, Guhl F, Cordovez JM, Erazo D. New scenarios of Trypanosoma cruzi transmission in the Orinoco region of Colombia. Mem Inst Oswaldo Cruz. 2015; 110(3): 283-8.
54. Rincón-Galvis HJ, Urbano P, Hernández C, Ramírez JD. Temporal variation of the presence of Rhodnius prolixus (Hemiptera: Reduviidae) into rural dwellings in the department of Casanare, eastern Colombia. J Med Entomol. 2020; 57(1): 173-80.
55. Guhl F, Pinto N, Marín D, Herrera C, Aguilera G, Naranjo JM, et al. Primer reporte de Rhodnius prolixus Stål, en Elaeis guineensis variedad Papúa, en plantaciones agroindustriales de Villanueva, Casanare. Biomedica. 2005; 25(Suppl. I): 158-9.
56. Erazo D, González C, Guhl F, Umaña JD, Morales-Betancourt JA, Cordovez J. Rhodnius prolixus colonization and Trypanosoma cruzi transmission in oil palm (Elaeis guineensis) plantations in the Orinoco Basin, Colombia. Am J Trop Med Hyg. 2020; 103(1): 428-36.
57. Abad-Franch F, Palomeque FS, Aguilar VHM, Miles MA. Field ecology of sylvatic Rhodnius populations (Heteroptera, Triatominae): risk factors for palm tree infestation in western Ecuador. Trop Med Int Health. 2005; 10(12): 1258-66.
58. Abad-Franch F, Paucar A, Carpio C, Cuba CA, Aguilar M, Miles MA. Biogeography of Triatominae (Hemiptera: Reduviidae) in Ecuador: implications for the design of control strategies. Mem Inst Oswaldo Cruz. 2001; 96(5): 611-20.
59. Grijalva MJ, Villacis AG. Presence of Rhodnius ecuadoriensis in sylvatic habitats in the southern highlands (Loja Province) of Ecuador. J Med Entomol. 2009; 46(3): 708-11.
60. Herrer A, Wygodzinsky P, Napan M. Presencia de Trypanosoma rangeli Tejera, 1920, en el Perú. I. El insecto vector, Rhodnius ecuadoriensis Lent & León, 1958. Rev Biol Trop. 1972; 20(1): 141-9.
61. Ramirez CJ, Jaramillo C, Delgado MP, Pinto N, Aguilera G, Guhl F. Genetic structure of sylvatic, peridomestic and domestic populations of Triatoma dimidiata (Hemiptera: Reduviidae) from an endemic zone of Boyacá, Colombia. Acta Trop. 2005; 93(1): 24-9.
62. Gomez-Palacio A, Arboleda S, Dumonteil E, Peterson AT. Ecological niche and geographic distribution of the Chagas disease vector, Triatoma dimidiata (Reduviidae: Triatominae): evidence for niche differentiation among cryptic species. Infect Genet Evol. 2015; 36: 15-22.
63. Parra-Henao G, Angulo VM, Osorio L, Jaramillo-O N. Geographic distribution and ecology of Triatoma dimidiata (Hemiptera: Reduviidae) in Colombia. J Med Entomol. 2016; 53(1): 122-9.
64. Monteiro FA, Weirauch C, Felix M, Lazoski C, Abad-Franch F. Evolution, systematics, and biogeography of the Triatominae, vectors of Chagas disease. Adv Parasitol. 2018; 99: 265-344.
65. Alroy KA, Huang C, Gilman RH, Quispe-Machaca VR, Marks MA, Ancca-Juarez J, et al.; Working Group on Chagas Disease in Peru. Prevalence and transmission of Trypanosoma cruzi in people of rural communities of the high jungle of northern Peru. PLoS Negl Trop Dis. 2015; 9(5): e0003779.
66. Alarcón de Noya B, Díaz-Bello Z, Colmenares C, Ruiz-Guevara R, Mauriello L, Zavala-Jaspe R, et al. Large urban outbreak of orally acquired acute Chagas disease at a school in Caracas, Venezuela. J Infect Dis. 2010; 201(9): 1308-15.
67. Alarcón de Noya BA, González ON. An ecological overview on the factors that drives to Trypanosoma cruzi oral transmission. Acta Trop. 2015; 151: 94-102.
68. Chagas C. Sôbre a verificação do Trypanosoma cruzi em macacos do Pará (Chrysothrix sciureus). Nota prévia. Sciencia Med. 1924; 2(2): 75-6.
69. Rodrigues BA, Melo GB. Contribuição ao estudo da Tripanosomiase Americana. Mem Inst Oswaldo Cruz. 1942; 37(1): 77-90.
70. Deane LM. Tripanosomatídeos de mamíferos da Região Amazônica. I: Alguns hemoflagelados encontrados em mamíferos do Estado do Pará. Rev Inst Med Trop São Paulo. 1961; 3(1): 15-28.
71. Deane LM. Inquérito de toxoplasmose e de tripanossomíases realizado no Territorio do Amapá, pela V Bandeira Científica do Centro Acadêmico “Oswaldo Cruz” da Faculdade de Medicina da Universidade de São Paulo. Rev Med (São Paulo). 1963; 47(1): 1-12.
72. Deane LM. Inquérito de toxoplasmose e de tripanossomíase realizado em Cachoeira do Arari, Ilha do Marajó, Pará, pela V Bandeira Científica do Centro Acadêmico “Oswaldo Cruz” da Faculdade de Medicina da Universidade de São Paulo. Rev Med (São Paulo). 1964; 48(3): 107-16.
73. Shaw J, Lainson R, Fraiha H. Considerações sôbre a epidemiología dos primeiros casos autóctones de doença de Chagas registrados em Belém, Pará, Brasil. Rev Saude Publica. 1969; 3(2): 153-7.
74. Lainson R, Shaw JJ, Fraiha H, Miles MA, Draper CC. Chagas’s disease in the Amazon Basin: I. Trypanosoma cruzi infections in silvatic mammals, triatomine bugs and man in the State of Pará, north Brazil. Trans R Soc Trop Med Hyg. 1979; 73(2): 193-204.
75. Lainson R, Shaw JJ, Naiff RD. Chagas’ disease in Amazon Basin: speculations on transmission per os. Rev Inst Med Trop São Paulo. 1980; 22(6): 294-7.
76. Coura JR. Chagas’ disease as endemic to the Brazilian Amazon: risk or hypothesis? Rev Soc Bras Med Trop. 1990; 23(2): 67-70.
77. Coura CR, Junqueira ACV, Fernandes O, Valente SAS, Miles MA. Emerging Chagas disease in Amazonian Brazil. Trends Parasitol. 2002; 18(4): 171-6.
78. Camargo ME, Silva GR, Castilho EA, Silveira AC. Inquérito sorológico da prevalência de infecção chagásica no Brasil 1975/1980. Rev Inst Med Trop São Paulo. 1984; 26(4): 192-204.
79. Silveira AC. A doença de Chagas na região amazônica do Brasil. In Guhl F, Schofield CJ, editors. Proceedings of the ECLAT-AMCHA International Workshop on Chagas Disease Surveillance in the Amazon Region, Palmari, Brazil. Bogotá: Universidad de los Andes; 2004. p. 16-21.
80. Ostermayer AL, Passos ADC, Silveira AC, Ferreira AW, Macedo V, Prata AR. O inquérito nacional de soroprevalência de avaliação do controle da doença de Chagas no Brasil (2001-2008). Rev Soc Bras Med Trop. 2011; 44(Suppl. II): 108-21.
81. Abad-Franch F, Diotaiuti L, Gurgel-Gonçalves R, Gürtler RE. On bugs and bias: improving Chagas disease control assessment. Mem Inst Oswaldo Cruz. 2014; 109(1): 125-30.
82. Aguilar HM, Abad-Franch F, Dias JCP, Junqueira ACV, Coura JR. Chagas disease in the Amazon Region. Mem Inst Oswaldo Cruz. 2007; 102(Suppl. I): 47-55.
83. Dias JCP, Ramos-Jr NA, Gontijo ED, Luquetti A, Shikanai-Yasuda MA, Coura JR, et al. 2nd Brazilian Consensus on Chagas Disease, 2015. Rev Soc Bras Med Trop. 2016; 49(Suppl. I): 3-60.
84. Grijalva MJ, Escalante L, Paredes RA, Costales JA, Padilla A, Rowland EC, et al. Seroprevalence and risk factors for Trypanosoma cruzi infection in the Amazon region of Ecuador. Am J Trop Med Hyg. 2003; 69(4): 380-5.
85. Amunárriz M, Quito S, Tandazo V, López M. Seroprevalencia de la enfermedad de Chagas en el cantón Aguarico, Amazonía ecuatoriana. Rev Panam Salud Publica. 2010; 28(1): 25-9.
86. Magalhães BML, Coelho LIARC, Ferreira JMBB, Umezawa ES, Coura JR, Guerra JAO, et al. Serological survey for Chagas disease in the rural areas of Manaus, Coari, and Tefé in the western Brazilian Amazon. Rev Soc Bras Med Trop. 2011; 44(6): 697-702.
87. Coura JR, Marquez MHP, Guerra JAO, Zauza PL, Miguel JC, Pereira JB. A new survey of the serology of human Trypanosoma cruzi infection in the Rio Negro microregion, Brazilian Amazon: a critical analysis. Mem Inst Oswaldo Cruz. 2013; 108(7): 909-13.
88. Guevara AG, Atherton RD, Wauters MA, Vicuña Y, Nelson M, Prado J, et al. Seroepidemiological study of Chagas disease in the Southern Amazon region of Ecuador. Trop Med Health. 2013; 41(1): 21-5.
89. Vargas CC, Narváez AO, Aroca JM, Shiguango G, Robles LM, Herrera C, et al. Seroprevalence of Trypanosoma cruzi infection in schoolchildren and in pregnant women from an Amazonian region in Orellana province, Ecuador. Am J Trop Med Hyg. 2015; 93(4): 774-8.
90. Flórez C, Guasmayan L, Cortés L, Caicedo A, Beltrán M, Muñoz L. Enfermedad de Chagas y su seroprevalencia en tres departamentos de la Amazonia colombiana. Nova. 2016; 13(26): 35-43.
91. Pinto AYN, Valente SA, Valente VC, Ferreira Jr AG, Coura JR. Fase aguda da doença de Chagas na Amazônia brasileira. Estudo de 233 casos do Pará, Amapá e Maranhão observados entre 1988 e 2005. Rev Soc Bras Med Trop. 2008; 41(6): 602-14.
92. Monteiro WM, Barbosa MGV, Toledo MJO, Fé FA, Fé NF. Série de casos agudos de doença de Chagas atendidos num serviço terciário de Manaus, Estado do Amazonas, de 1980 a 2006. Rev Soc Bras Med Trop. 2010; 43(2): 207-10.
93. Barbosa MGV, Ferreira JMBB, Arcanjo ARL, Santana RAG, Magalhães LKC, Magalhães LKC, et al. Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives. Rev Soc Bras Med Trop. 2015; 48(Suppl. I): 27-33.
94. Nóbrega AA, Garcia MH, Tatto E, Obara MT, Costa E, Sobel J, et al. Oral transmission of Chagas disease by consumption of açaí palm fruit, Brazil. Emerg Infect Dis. 2009; 15(4): 653-5.
95. Valente SAS, Valente VC, Pinto AYN, César MJR, dos Santos MP, Miranda COS, et al. Analysis of an acute Chagas disease outbreak in the Brazilian Amazon: human cases, triatomines, reservoir mammals and parasites. Trans R Soc Trop Med Hyg. 2009; 103(3): 291-7.
96. Shikanai-Yasuda MA, Carvalho NB. Oral transmission of Chagas disease. Clin Infect Dis. 2012; 54(6): 845-52.
97. Guhl F, Schofield CJ. Proceedings of the ECLAT-AMCHA International Workshop on Chagas Disease Surveillance in the Amazon Region, Palmari, Brazil. Bogotá: Universidad de los Andes; 2004.
98. Rojas A, Vinhães M, Rodríguez M, Monroy J, Persaud N, Aznar C, et al. Reunião internacional sobre vigilância e prevenção da doença de Chagas na Amazônia. Implementação da iniciativa intergovernamental de vigilância e prevenção da doença de Chagas na Amazônia. Rev Soc Bras Med Trop. 2005; 38(1): 82-9.
99. Abad-Franch F, Monteiro FA. Biogeography and evolution of Amazonian triatomines (Heteroptera: Reduviidae): implications for Chagas disease surveillance in humid forest ecoregions. Mem Inst Oswaldo Cruz. 2007; 102(Suppl. I): 57-69.
100. Santos VRC, Meis J, Savino W, Andrade JAA, Vieira JRS, Coura JR, et al. Acute Chagas disease in the state of Pará, Amazon Region: is it increasing? Mem Inst Oswaldo Cruz. 2018; 113(5): e170298.
101. SEDAP - Secretaria de Estado de Desenvolvimento Agropecuário e Pesca do Pará [homepage on the Internet]. Açaí [cited 2021 Mar 19]. Available from: http://www.sedap.pa.gov.br/content/açai.
102. Coura JR, Viñas PA, Brum-Soares LM, Sousa AS, Xavier SS. Morbidity of Chagas heart disease in the microregion of Rio Negro, Amazonian Brazil: a case-control study. Mem Inst Oswaldo Cruz. 2013; 108(8): 1009-13.
103. Jansen AM, Xavier SCC, Roque ALR. Trypanosoma cruzi transmission in the wild and its most important reservoir hosts in Brazil. Parasite Vectors. 2018; 11(1): 502.
104. Abad-Franch F, Ferraz G, Campos C, Palomeque FS, Grijalva MJ, Aguilar HM, et al. Modeling disease vector occurrence when detection is imperfect: infestation of Amazonian palm trees by triatomine bugs at three spatial scales. PLoS Negl Trop Dis. 2010; 4(3): e620.
105. Abad-Franch F, Lima MM, Sarquis O, Gurgel-Gonçalves R, Sánchez-Martín M, Calzada J, et al. On palms, bugs, and Chagas disease in the Americas. Acta Trop. 2015; 15: 126-41.
106. Abad-Franch F, Gurgel-Gonçalves R. The ecology and natural history of wild Triatominae in the Americas. In Guarneri AA, Lorenzo MG, editors. Triatominae: the biology of Chagas disease vectors. Entomology in focus. Vol. 5. Cham: Springer; 2021. in press.
107. Brito RN, Gorla DE, Diotaiuti L, Gomes ACF, Souza RCM, Abad-Franch F. Drivers of house invasion by sylvatic Chagas disease vectors in the Amazon-Cerrado transition: a multi-year, state-wide assessment of municipality-aggregated surveillance data. PLoS Negl Trop Dis. 2017; 11(11): e0006035.
108. Cucunubá ZM, Nouvellet P, Gourbière S, Villar JC, Rabinovich JE, Levy MZ, et al. Insights from quantitative and mathematical modelling on the proposed WHO 2030 goals for Chagas disease. Gates Open Res. 2019; 3: 1539.
109. Walter SD, Irwig LM. Estimation of test error rates, disease prevalence and relative risk from misclassified data: a review. J Clin Epidemiol. 1988; 41(9): 923-37.
110. Van Hest NAH, Story A, Grant AD, Antoine D, Crofts JP, Watson JM. Record-linkage and capture-recapture analysis to estimate the incidence and completeness of reporting of tuberculosis in England 1999-2002. Epidemiol Infect. 2008; 136(12): 1606-16.
111. Monteiro WM, Barbosa MGV, Guerra JAO, Melo GC, Barbosa LRA, Machado KVA, et al. Driving forces for strengthening the surveillance of Chagas disease in the Brazilian Amazon by “training the eyes” of malaria microscopists. Rev Soc Bras Med Trop. 2020; 53: e20190423.
112. PAHO - Pan American Health Organization [homepage on the Internet]. Enfermedad de Chagas en las Américas: una revisión de la situación actual de salud pública y su visión para el futuro [cited 2021 Mar 19]. Available from: https://www.paho.org/hq/index.php?option=com_docman&view=download&category_slug=informes-tecnicos-6200&alias=45142-enfermedad-chagas-americas-una-revision-situacion-actual-salud-publica-su-vision-futuro-informe-conclusiones-recomendaciones-2018-142&Itemid=270&lang=es.
113. Martins-Melo FR, Alencar CH, Ramos Jr AN, Heukelbach J. Epidemiology of mortality related to Chagas’ disease in Brazil, 1999-2007. PLoS Negl Trop Dis. 2012; 6(2): e1508.
114. Kroeger A, Villegas E, Ordoñez-González J, Pabon E, Scorza JV. Prevention of the transmission of Chagas’ disease with pyrethroid-impregnated materials. Am J Trop Med Hyg. 2003; 68(3): 307-11.
115. Coura JR, Junqueira ACV. Surveillance, health promotion and control of Chagas disease in the Amazon Region - Medical attention in the Brazilian Amazon Region: a proposal. Mem Inst Oswaldo Cruz. 2015; 110(7): 825-30.
116. Dias JCP. Southern Cone Initiative for the elimination of domestic populations of Triatoma infestans and the interruption of transfusion Chagas disease. Historical aspects, present situation, and perspectives. Mem Inst Oswaldo Cruz. 2007; 102(Suppl. I): 11-8.
117. WHO - World Health Organization. Control of Chagas disease: second report of the WHO Expert Committee. WHO Tech Rep Ser. 2002; 905: 1-109.
118. Abad-Franch F, Santos WS, Schofield CJ. Research needs for Chagas disease prevention. Acta Trop. 2010; 115(1-2): 44-54.
119. Schmunis GA, Cruz JR. Safety of the blood supply in Latin America. Clin Microbiol Rev. 2005; 18(1): 12-29.
120. Blanco SB, Segura EL, Cura EN, Chuit R, Tulián L, Flores I, et al. Congenital transmission of Trypanosoma cruzi: an operational outline for detecting and treating infected infants in north-western Argentina. Trop Med Int Health. 2000; 5(4): 293-301.
121. Salvatella R, Irabedra P, Castellanos LG. Interruption of vector transmission by native vectors and “the art of the possible”. Mem Inst Oswaldo Cruz. 2014; 109(1): 122-30.
122. Araújo RF, Mendonça VJ, Rosa JA, Matos JFM, Lima SCR, de Araújo Figueiredo MA. Description of a newly discovered Triatoma infestans (Hemiptera: Reduviidae) foci in Ibipeba, State of Bahia Brazil. Rev Soc Bras Med Trop. 2014; 47(4): 513-6.
123. Brandão H, Fonseca E, Santos R, Ribeiro Jr G, Santos CG, Cova B, et al. Descrição de focos residuais de Triatoma infestans (Klug, 1834) no município de Novo Horizonte, Bahia. Rev Baiana Saude Publica. 2015; 39(Suppl. 1): 91-104.
124. Ribeiro Jr G, dos Santos CGS, Lanza F, Reis J, Vaccarezza F, Diniz C, et al. Wide distribution of Trypanosoma cruzi-infected triatomines in the State of Bahia, Brazil. Parasit Vectors. 2019; 12(1): 604.
125. Bedin C, Wilhelms T, Villela MM, Silva GCCD, Riffel APK, Sackis P, et al. Residual foci of Triatoma infestans infestation: surveillance and control in Rio Grande do Sul, Brazil, 2001-2018. Rev Soc Bras Med Trop. 2021; 54: e0530-2020.
126. Delgado S, Ernst KC, Pumahuanca ML, Yool SR, Comrie AC, Sterling CR, et al.; Chagas Disease Working Group in Arequipa, Peru. A country bug in the city: urban infestation by the Chagas disease vector Triatoma infestans in Arequipa, Peru. Int J Health Geogr. 2013; 12: 48.
127. Barbu CM, Buttenheim AM, Pumahuanca ML, Calderón JE, Salazar R, Carrión M, et al. Residual infestation and recolonization during urban Triatoma infestans bug control campaign, Peru. Emerg Infect Dis. 2014; 20(12): 2055-63.
128. Gürtler RE, Kitron U, Cecere MC, Segura EL, Cohen JE. Sustainable vector control and management of Chagas disease in the Gran Chaco, Argentina. Proc Natl Acad Sci USA. 2007; 104(41): 16194-9.
129. Samuels AM, Clark EH, Galdos-Cardenas G, Wiegand RE, Ferrufino L, Menacho S, et al., the Working Group on Chagas Disease in Bolivia and Peru. Epidemiology of and impact of insecticide spraying on Chagas disease in communities in the Bolivian Chaco. PLoS Negl Trop Dis. 2013; 7(8): e2358.
130. Espinoza N, Borrás R, Abad-Franch F. Chagas disease vector control in a hyperendemic setting: the first 11 years of intervention in Cochabamba, Bolivia. PLoS Negl Trop Dis. 2014; 8(4): e2782.
131. Espinoza Echeverria J, Rodriguez AN, Cortez MR, Diotaiuti LG, Gorla DE. Spatial and temporal distribution of house infestation by Triatoma infestans in the Toro Toro municipality, Potosi, Bolivia. Parasit Vectors. 2017; 10(1): 58.
132. Hopkins T, Gonçalves R, Mamani J, Courtenay O, Bern C. Chagas disease in the Bolivian Chaco: persistent transmission indicated by childhood seroscreening study. Int J Infect Dis. 2019; 86: 175-7.
133. Carlier Y, Sosa-Estani S, Luquetti AO, Buekens P. Congenital Chagas disease: an update. Mem Inst Oswaldo Cruz. 2015; 110(3): 363-8.
134. Carlier Y, Altcheh J, Angheben A, Freilij H, Luquetti AO, Schijman AG, et al. Congenital Chagas disease: updated recommendations for prevention, diagnosis, treatment, and follow-up of newborns and siblings, girls, women of childbearing age, and pregnant women. PLoS Negl Trop Dis. 2019; 13(10): e0007694.
135. PAHO - Pan American Health Organization. EMTCT Plus. Framework for elimination of mother-to-child transmission of HIV, Syphilis, Hepatitis B, and Chagas. Washington, DC: PAHO; 2017.
136. Sosa-Estani S. La seroepidemiología en la investigación de la infección con Trypanosoma cruzi. Grupo de trabajo OPS en enfermedad de Chagas, Montevideo, Uruguay. 2001. Available from: https://www.paho.org/spanish/ad/dpc/cd/consulta-4.pdf.
137. Sosa-Estani S, Colantonio L, Segura EL. Therapy of Chagas disease: implications for levels of prevention. J Trop Med. 2012; 2012: 292138.
138. Sosa-Estani S, Segura EL. Integrated control of Chagas disease for its elimination as public health problem - A Review. Mem Inst Oswaldo Cruz. 2015; 110(3): 289-98.
139. Echeverría LE, Marcus R, Novick G, Sosa-Estani S, Ralston K, Zaidel EJ, et al. WHF IASC Roadmap on Chagas disease. Glob Heart. 2020; 15(1): 26.
140. Sosa-Estani S, Altcheh J, Riarte A, Freilij H, Fernández M, Lloveras S, et al.; Grupo de Trabajo. Lineamientos básicos del tratamiento etiológico de enfermedad de Chagas. Medicina (B Aires). 2015; 75(4): 270-2.
141. Picollo MI, Vassena C, Santo Orihuela P, Barrios S, Zaidemberg M, Zerba E. High resistance to pyrethroid insecticides associated with ineffective field treatments in Triatoma infestans (Hemiptera: Reduviidae) from Northern Argentina. J Med Entomol. 2005; 42(4): 637-42.
142. Germano MD, Roca Acevedo G, Mougabure Cueto GA, Toloza AC, Vassena CV, Picollo MI. New findings of insecticide resistance in Triatoma infestans (Heteroptera: Reduviidae) from the Gran Chaco. J Med Entomol. 2010; 47(6): 1077-81.
143. Gómez MB, Diotaiuti LG, Gorla DE. Distribution of pyrethroid resistant populations of Triatoma infestans in the Southern Cone of South America. PLoS Negl Trop Dis. 2016; 10(3): e0004561.
144. Yadón Z, Gürtler R, Tobar F, Médici AC, editors. Descentralización y gestión del control de enfermedades transmisibles en América Latina. Buenos Aires: PAHO/WHO; 2006.
145. Picado A, Cruz I, Redard-Jacot M, Schijman AG, Torrico F, Sosa-Estani S, et al. The burden of congenital Chagas disease and implementation of molecular diagnostic tools in Latin America. BMJ Glob Health. 2018; 3(5): e001069.
146. Sosa-Estani S, Cura E, Velázquez E, Yampotis C, Segura EL. Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission. Rev Soc Bras Med Trop. 2009; 42(5): 484-7.
147. Fabbro DL, Danesi E, Olivera V, Codebo MO, Denner S, Heredia C, et al. Trypanocide treatment of women infected with Trypanosoma cruzi and its effect on preventing congenital Chagas. PLoS Negl Trop Dis. 2014; 8(11): e3312.
148. Moscatelli G, Moroni S, García-Bournissen F, Ballering G, Bisio M, Freilij H, et al. Prevention of congenital Chagas through treatment of girls and women of childbearing age. Mem Inst Oswaldo Cruz. 2015; 110(4): 507-9.
149. Alvarez MG, Vigliano C, Lococo B, Bertocchi G, Viotti R. Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study. Acta Trop. 2017; 174: 149-52.
150. Murcia L, Simon M, Carrilero B, Roig M, Segovia M. Treatment of infected women of childbearing age prevents congenital Trypanosoma cruzi infection by eliminating the parasitemia detected by PCR. J Infect Dis. 2017; 215(9): 1452-8.
151. Pinazo MJ, Pereiro A, Herazo R, Chopita M, Forsyth C, Lenardón M, et al. Interventions to bring comprehensive care to people with Chagas disease: Experiences in Bolivia, Argentina and Colombia. Acta Trop. 2020; 203: 105290.
152. Hotez P, Bottazzi ME, Strub-Wourgaft N, Sosa-Estani S, Torrico F, Pajín L, et al. A new patient registry for Chagas disease. PLoS Negl Trop Dis. 2020; 14(10): e0008418.
153. CONITEC - Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde, Ministério da Saúde do Brasil. Protocolo clínico e diretrizes terapêuticas doença de Chagas. Relatório de Recomendação. 2018. Available from: http://conitec.gov.br/images/Relatorios/2018/Recomendacao/Relatorio_PCDT_Doenca_de_Chagas.pdf.
154. DNDi - Drugs for Neglected Diseases initiative. Santa Cruz Letter. 2018. Available from: https://dndi.org/news/2018/santacruzletter/.
155. WHO - World Health Organization. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis. World Health Organ Tech Rep Ser. 2012; 975: v-xii, 1-100.
156. Chagas Platform. Newsletter. 2019. Available from: https://dndi.org/wp-content/uploads/2019/08/2019NewsletterChagasPlatform_ENG.pdf.

+ Corresponding author: rojasdearias@gmail.com
ORCID https://orcid.org/0000-0002-6207-1870
Received 12 April 2021
Accepted 13 April 2021

Our Location

Memórias do Instituto Oswaldo Cruz

Av. Brasil 4365, Castelo Mourisco 
sala 201, Manguinhos, 21040-900 
Rio de Janeiro, RJ, Brazil

Tel.: +55-21-2562-1222

This email address is being protected from spambots. You need JavaScript enabled to view it.

Support Program

ioc

fiocruz governo
faperj cnpq capes