Etienne Waleckx

Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

An innovative ecohealth intervention for Chagas disease vector control in Yucatan, Mexico

Background Non-domiciliated (intrusive) triatomine vectors remain a challenge for the sustainability of Chagas disease vector control as these triatomines are able to transiently (re-)infest houses. One of the best-characterized examples is Triatoma dimidiata from the Yucatan peninsula, Mexico, where adult insects seasonally infest houses between March and July. Methods We focused our study on three rural villages in the state of Yucatan, Mexico, in which we performed a situation analysis as a first step before the implementation of an ecohealth (ecosystem approach to health) vector control intervention. Results The identification of the key determinants affecting the transient invasion of human dwellings by T. dimidiata was performed by exploring associations between bug presence and qualitative and quantitative variables describing the ecological, biological and social context of the communities. We then used a participatory action research approach for implementation and evaluation of a control strategy based on window insect screens to reduce house infestation by T. dimidiata. Conclusions This ecohealth approach may represent a valuable alternative to vertically-organized insecticide spraying. Further evaluation may confirm that it is sustainable and provides effective control (in the sense of limiting infestation of human dwellings and vector/human contacts) of intrusive triatomines in the region.

Over Six Thousand Trypanosoma cruzi Strains Classified into Discrete Typing Units (DTUs): Attempt at an Inventory.

Trypanosoma cruzi, the causative agent of Chagas disease, presents wide genetic diversity. Currently, six discrete typing units (DTUs), named TcI to TcVI, and a seventh one called TcBat are used for strain typing. Beyond the debate concerning this classification, this systematic review has attempted to provide an inventory by compiling the results of 137 articles that have used it. A total of 6,343 DTU identifications were analyzed according to the geographical and host origins. Ninety-one percent of the data available is linked to South America. This sample, although not free of potential bias, nevertheless provides today’s picture of T. cruzi genetic diversity that is closest to reality. DTUs were genotyped from 158 species, including 42 vector species. Remarkably, TcI predominated in the overall sample (around 60%), in both sylvatic and domestic cycles. This DTU known to present a high genetic diversity, is very widely distributed geographically, compatible with a long-term evolution. The marsupial is thought to be its most ancestral host and the Gran Chaco region the place of its putative origin. TcII was rarely sampled (9.6%), absent, or extremely rare in North and Central America, and more frequently identified in domestic cycles than in sylvatic cycles. It has a low genetic diversity and has probably found refuge in some mammal species. It is thought to originate in the south-Amazon area. TcIII and TcIV were also rarely sampled. They showed substantial genetic diversity and are thought to be composed of possible polyphyletic subgroups. Even if they are mostly associated with sylvatic transmission cycles, a total of 150 human infections with these DTUs have been reported. TcV and TcVI are clearly associated with domestic transmission cycles. Less than 10% of these DTUs were identified together in sylvatic hosts. They are thought to originate in the Gran Chaco region, where they are predominant and where putative parents exist (TcII and TcIII). Trends in host-DTU specificities exist, but generally it seems that the complexity of the cycles and the participation of numerous vectors and mammal hosts in a shared area, maintains DTU diversity.

Triatoma sanguisuga blood meals and potential for Chagas disease, Louisiana, USA.

To evaluate human risk for Chagas disease, we molecularly identified blood meal sources and prevalence of Trypanosoma cruzi infection among 49 Triatoma sanguisuga kissing bugs in Louisiana, USA. Humans accounted for the second most frequent blood source. Of the bugs that fed on humans, ≈40% were infected with T. cruzi, revealing transmission potential.

Chagas Disease Has Not Been Controlled in Ecuador.

A recent study by Cartelle Gestal et al. reported an analysis of data from the Ministry of Public Health on the epidemiological situation of neglected tropical diseases in Ecuador [1]. Based on a misleading definition of Chagas disease cases not corresponding to that of the Ministry of Public Health [2], the authors concluded that the government had mounted successful control campaigns, and as a result Chagas disease (among others) had been effectively controlled as no cases in children under age five had been reported since 2009. Ecuador is thus identified as one of the first countries to control Chagas disease. While we certainly agree that efforts have been made in terms of Chagas disease surveillance and control campaigns in Ecuador, a more comprehensive analysis of available data, from both the Ministry of Public Health and the literature, provides a very different picture, and the claim that Chagas disease is controlled made by Cartelle Gestal et al. seems largely inadequate and sends an equivocal message which can undermine current control efforts. As mentioned in this study, the Chagas disease control program in the country was formally established in 2003–2004, in response to recommendations from a technical consultation through PAHO/WHO [3] and field studies [4,5]. This consultation and data provided a baseline to prioritize activities. It reported a national seroprevalence of Trypanosoma cruzi infection of 1.38%, corresponding to 165–170,000 seropositive patients in the country. Three regions were prioritized: the coastal region (seroprevalence of 1.99%), the Amazon region (1.75%) and the southern highlands (0.65%). The incidence was estimated at 36 cases/100,000 inhabitants/year, resulting in 4,400 new cases each year [3]. Today, the most recent estimates from the WHO suggest the presence of nearly 200,000 seropositive patients and a current incidence of 14 cases/100,000 inhabitants/year [6]. An in depth analysis of the complete records from the Ministry of Public Health from 2004–2014, indicates a total of 915 reported human cases in the country, with a major increase over the years followed by a decrease in the past two years [7]. This increase reflects the efforts at improving the epidemiologic surveillance program, but it is clear that there is still significant underreporting of cases in the country. Indeed, several independent and recent seroprevalence studies in different regions and communities point out relatively high levels of seroprevalence of T. cruzi infection (ranging from 0.6 to 13.3%), and persistent active parasite transmission, as evidenced by the detection of seropositive children [8–12]. Additionally, there are reports of Chagas disease cases in regions where the Ministry of Public Health has no records of patients, further highlighting current underreporting [5,11,12]. Furthermore, while during the last decade Ecuador has achieved near 100% blood screening coverage for T. cruzi infection, the 15 participating blood banks regularly report seropositive blood donors to the External Performance Evaluation of Serological Screening Program administered by the Pontifical Catholic University of Ecuador. The vector control program was effectively started in 2004. However, due to limited human and financial resources, there have been important variations in the geographic coverage of the surveillance and control activities from year to year [7]. Importantly, a total of 12 provinces have not been included in these activities, representing an area larger than the covered provinces. Therefore, the available data do not correspond to a systematic national coverage, and thus still present an incomplete picture of the current transmission of Chagas disease in Ecuador. In the 11 provinces in which surveillance and control activities have been performed, house infestation by triatomines is still observed in many regions [7,13]. While vector control activities have had a significant effect and allowed reducing the infestation level, particularly in coastal Ecuador, these need to be sustained to avoid reinfestation and provide long-term effects. Also, while insecticide spraying may be effective against Triatoma dimidiata, a possibly domiciliated species which is poised for elimination in Ecuador, alternative control strategies may be needed against intrusive triatomine species such as Rhodnius ecuadoriensis or Panstrongylus howardi or for occasional exposure outside of homes [14–19]. Moreover, no formal vector control intervention has been implemented in the Amazon region, where nearly half of the cases of the country seem to originate [7], and active transmission still occurs through triatomine species including Rhodnius robustus and R. pictipes [8,9]. Especially in the Amazon, human activities (deforestation, urbanization) disturb the natural balance between the vectors, their wild hosts and the parasite, favoring the emergence of new transmission cycles in which humans may be included [8,9,11,20]. An accurate description of the situation of Chagas disease in Ecuador should mention that access to diagnosis throughout the country is limited and case detection during the last two decades has been sporadic and geographically restricted. Indeed, only one laboratory in the whole country, at the Instituto Nacional de Investigacion en Salud Publica (INSPI), performs official confirmation of anti-T. cruzi seropositivity and releases Nifurtimox for the treament of patients. In fact, we believe that lack of awareness by health care personnel in areas with active vectorial transmission, combined with lack of diagnostic capacity elsewhere in the country, have resulted in a gross under reporting of cases in Ecuador. Taken together, these data and studies highlight that Chagas disease is all but controlled in Ecuador, contrary to what is stated by Cartelle Gestal et al. While it is clear that disease surveillance and vector control activities from the Ministry of Public Health have improved over the years, these need to (i) reach national coverage to ensure the inclusion of all endemic provinces, and (ii) be sustained to ensure that what has been achieved can result in long-term control of the disease. These represent a clear challenge at a time when the Ministry of Public Health is undergoing major structural reorganization and many of its activities are being decentralized or interrupted. Indeed, there is a decrease in reported human cases and in vector controls activities observed in the past two years in Ecuador [7], which may reflect the interruption of the National Chagas Program and the Servicio Nacional de Control y Vigilancia de Enfermedades Transmitidas por Vectores Artropodos (SNEM) in late 2015. Their actions have not been replaced yet, so that there is currently no Chagas vector control program in the country. This can strongly jeopardize the results achieved so far and may be a lost opportunity to eliminate vectorial transmission with domiciliated vectors in some regions of Ecuador. Finally, as in many other countries in Latin America, current activities for Chagas disease control in Ecuador still need to improve treatment access and care for Chagas disease patients [21–23] as well as to better understand the importance of congenital transmission in the epidemiology of the disease [9,24]. Thus, control of Chagas disease in the country will only be reached if the programs from the Ministry of Public Health are strengthened and expanded. The National Chagas disease control programs in other Latin America countries such as Brazil, Argentina, or Colombia (among others) can provide key examples of successful strategies for Chagas disease surveillance and control, as well as of the challenges encountered for their implementation. Additionally, research needs to be performed to further expand our understanding of triatomine infestation and T. cruzi transmission cycles in the different specific endemic areas, to help further tailor surveillance and interventions. More than claiming that Chagas disease is controlled, we need to promote further political commitment to sustain current achievements in Chagas disease surveillance and control in Ecuador and to ensure that the goals of the London declaration on neglected tropical diseases [25] are met in the near future.

Evolutionary ecology of Chagas disease; what do we know and what do we need?

The aetiological agent of Chagas disease, Trypanosoma cruzi, is a key human pathogen afflicting most populations of Latin America. This vectorborne parasite is transmitted by haematophageous triatomines, whose control by large‐scale insecticide spraying has been the main strategy to limit the impact of the disease for over 25 years. While those international initiatives have been successful in highly endemic areas, this systematic approach is now challenged by the emergence of insecticide resistance and by its low efficacy in controlling species that are only partially adapted to human habitat. In this contribution, we review evidences that Chagas disease control shall now be entering a second stage that will rely on a better understanding of triatomines adaptive potential, which requires promoting microevolutionary studies and –omic approaches. Concomitantly, we show that our knowledge of the determinants of the evolution of T. cruzi high diversity and low virulence remains too limiting to design evolution‐proof strategies, while such attributes may be part of the future of Chagas disease control after the 2020 WHOs target of regional elimination of intradomiciliary transmission has been reached. We should then aim at developing a theory of T. cruzi virulence evolution that we anticipate to provide an interesting enrichment of the general theory according to the specificities of transmission of this very generalist stercorarian trypanosome. We stress that many ecological data required to better understand selective pressures acting on vector and parasite populations are already available as they have been meticulously accumulated in the last century of field research. Although more specific information will surely be needed, an effective research strategy would be to integrate data into the conceptual and theoretical framework of evolutionary ecology and life‐history evolution that provide the quantitative backgrounds necessary to understand and possibly anticipate adaptive responses to public health interventions.

Detailed ecological associations of triatomines revealed by metabarcoding and next-generation sequencing: implications for triatomine behavior and Trypanosoma cruzi transmission cycles

Trypanosoma cruzi is the agent of Chagas disease, transmitted by hematophagous triatomine vectors. Establishing transmission cycles is key to understand the epidemiology of the disease, but integrative assessments of ecological interactions shaping parasite transmission are still limited. Current approaches also lack sensitivity to assess the full extent of this ecological diversity. Here we developed a metabarcoding approach based on next-generation sequencing to identify triatomine gut microbiome, vertebrate feeding hosts, and parasite diversity and their potential interactions. We detected a dynamic microbiome in Triatoma dimidiata, including 23 bacterial orders, which differed according to blood sources. Fourteen vertebrate species served as blood sources, corresponding to domestic, synantropic and sylvatic species, although four (human, dog, cow and mice) accounted for over 50% of blood sources. Importantly, bugs fed on multiple hosts, with up to 11 hosts identified per bug, indicating very frequent host-switching. A high clonal diversity of T. cruzi was detected, with up to 20 haplotypes per bug. This analysis provided much greater sensitivity to detect multiple blood meals and multiclonal infections with T. cruzi, which should be taken into account to develop transmission networks, and characterize the risk for human infection, eventually leading to a better control of disease transmission.

Estimating the current burden of Chagas disease in Mexico: a systematic review of epidemiological surveys from 2006 to 2017

Background In Mexico, estimates of Chagas disease prevalence and burden vary widely. Updating surveillance data is therefore an important priority to ensure that Chagas disease does not remain a barrier to the development of Mexico’s most vulnerable populations. Methodology/Principal Findings The aim of this systematic review was to analyze the literature on epidemiological surveys to estimate Chagas disease prevalence and burden in Mexico, during the period 2006 to 2017. A total of 2,764 articles were screened and 38 were retained for the final analysis. Epidemiological surveys have been performed in most of Mexico, but with variable geographic coverage. Based on studies reporting confirmed cases, i.e. using at least 2 serological tests, the national seroprevalence of Trypanosoma cruzi infection was 2.26% [95% Confidence Interval (CI) 2.12-2.41], suggesting that there are 2.71 million cases in Mexico. Studies focused on pregnant women, which may transmit the parasite to their newborn during pregnancy, reported a seroprevalence of 1.00% [95% CI 0.87-1.14], suggesting that there are 22,930 births from T. cruzi infected pregnant women per year, and 1,445 cases of congenitally infected newborns per year. Children under 18 years had a seropositivity rate of 1.49% [95% CI 1.20-1.85], which indicate ongoing transmission. Finally, cases of T. cruzi infection in blood donors have also been reported in most states, with a national seroprevalence of 0.51% [95% CI 0.49-0.53]. Conclusions/Significance Our analysis suggests a disease burden for T. cruzi infection higher than previously recognized, highlighting the urgency of establishing Chagas disease surveillance and control as a key national public health priority in Mexico, to ensure that it does not remain a major barrier to the economic and social development of the country’s most vulnerable populations. Author summary In Mexico, estimates of Chagas disease prevalence and burden vary widely due to the ecology and epidemiology of this disease resulting of many geographical, ecological, biological, and social interactions. Better data are thus urgently needed to help develop appropriate public health programs for disease control and patient care. In this study we analyzed published data on T. cruzi seroprevalence infection in Mexico between 2006 and 2017. This systematic review shows a national seroprevalence of T. cruzi infection of 2.26% [95%CI 2.12-2.41], with over 2.71 million cases in Mexico, which is higher than previously recognized. The presence of T. cruzi infection in specific subpopulations such as pregnant women, children and blood donors also informs on specific risks of infection and call for the implementation of well-established control interventions. This work confirms the place of Mexico as the country with the largest number of cases, highlighting the urgency of establishing Chagas disease control as a key national public health priority.

Non-randomized controlled trial of the long-term efficacy of an Ecohealth intervention against Chagas disease in Yucatan, Mexico

Non-domiciliated intrusive triatomine vectors are responsible for a low but significant transmission of Trypanosoma cruzi to humans. Their control is a challenge as insecticide spraying is of limited usefulness, and alternative strategies need to be developed for a sustainable control. We performed a non-randomized controlled trial of an Ecohealth intervention based on window insect screens and community participation to reduce house infestation by Triatoma dimidiata in two rural villages in Yucatan, Mexico. Efficacy of the intervention was measured over a three years follow-up period and entomological indicators showed that the proportion of triatomines found inside houses was significantly reduced in houses with insect screens, which effectively kept more bugs on the outside of houses. Using a previously developed model linking entomological data to the prevalence of infection in human, we predicted that the intervention would lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi infection. The cost for the coverage of all the windows of a house was of comparable magnitude to what families currently spend on various domestic insecticide, and most screens were still in good conditions after three years. In conclusion, the Ecohealth approach proposed here is effective for the long-term and sustainable control of intrusive T. dimidiata vectors in the Yucatan peninsula, Mexico. This strategy may also be easily adapted to other intrusive triatomine species as well as other regions/countries with comparable eco-epidemiological settings, and would be an excellent component of a larger integrated program for the control of a variety of other vector-borne diseases, bringing additional benefits to the communities. Our results should encourage a further scaling-up of our implementation strategy in additional villages in the region.

First report of phoresy by an oribatid mite (Acari: Oribatida) on a triatomine bug (Hemiptera: Reduviidae)

ABSTRACT A dozen specimens of the oribatid mite Archegozetes magnus (Trhypochthoniidae) were collected from the Chagas disease vector Triatoma dimidiata (Hemiptera: Reduviidae), in Teya, Yucatán, Mexico. This is the first report of phoresy by an oribatid mite on a hemipteran.