From serological surveys to disease burden: a modelling pipeline for Chagas disease.

In 2012, the World Health Organization (WHO) set the elimination of Chagas disease intradomiciliary vectorial transmission as a goal by 2020. After a decade, some progress has been made, but the new 2021-2030 WHO roadmap has set even more ambitious targets. Innovative and robust modelling methods are required to monitor progress towards these goals. We present a modelling pipeline using local seroprevalence data to obtain national disease burden estimates by disease stage. Firstly, local seroprevalence information is used to estimate spatio-temporal trends in the Force-of-Infection (FoI). FoI estimates are then used to predict such trends across larger and fine-scale geographical areas. Finally, predicted FoI values are used to estimate disease burden based on a disease progression model. Using Colombia as a case study, we estimated that the number of infected people would reach 506 000 (95% credible interval (CrI) = 395 000-648 000) in 2020 with a 1.0% (95%CrI = 0.8-1.3%) prevalence in the general population and 2400 (95%CrI = 1900-3400) deaths (approx. 0.5% of those infected). The interplay between a decrease in infection exposure (FoI and relative proportion of acute cases) was overcompensated by a large increase in population size and gradual population ageing, leading to an increase in the absolute number of Chagas disease cases over time. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Novel Putative Tymoviridae-like Virus Isolated from Culex Mosquitoes in Colombia.

The family Tymoviridae comprises positive-sense RNA viruses, which mainly infect plants. Recently, a few Tymoviridae-like viruses have been found in mosquitoes, which feed on vertebrate sources. We describe a novel Tymoviridae-like virus, putatively named, Guachaca virus (GUAV), isolated from Culex pipiens and Culex quinquefasciatus species of mosquitoes and collected in the rural area of Santa Marta, Colombia. After a cytopathic effect was observed in C6/36 cells, RNA was extracted and processed through the NetoVIR next-generation sequencing protocol, and data were analyzed through the VirMAP pipeline. Molecular and phenotypic characterization of the GUAV was achieved using a 5'/3' RACE, transmission electron microscopy, amplification in vertebrate cells, and phylogenetic analysis. A cytopathic effect was observed in C6/36 cells three days post-infection. The GUAV genome was successfully assembled, and its polyadenylated 3' end was corroborated. GUAV shared only 54.9% amino acid identity with its closest relative, Ek Balam virus, and was grouped with the latter and other unclassified insect-associated tymoviruses in a phylogenetic analysis. GUAV is a new member of a family previously described as comprising plant-infecting viruses, which seem to infect and replicate in mosquitoes. The sugar- and blood-feeding behavior of the Culex spp., implies a sustained contact with plants and vertebrates and justifies further studies to unravel the ecological scenario for transmission.

Usefulness of an in vitro-transcribed RNA control for the detection and quantification of Yellow fever virus through real-time reverse transcription-polymerase chain reaction.

INTRODUCTION: Unvaccinated individuals in endemic areas with proven enzootic transmission of Yellow fever virus are at risk of infection due to a dramatic shift in the epidemiology of the disease over recent years. For this reason, epidemiological surveillance and laboratory confirmation of cases have become mandatory. OBJECTIVE: To develop and test a control RNA for YFV detection through real-time RT-PCR. METHODS: A 437-bp insert containing the T7 promoter and the target sequences for two different in-house protocols was designed in the context of the pUC57 vector and obtained through gene synthesis. After T7-driven in vitro transcription, standard curves were developed for Log10 serial dilutions of the YFV control RNA with 8 replicates. RESULTS: A dynamic range of quantification of 10 orders of magnitude was observed with a limit of detection of 6.3 GCE/µL (95% CI, 2.6 to 139.4 GCE/µL). CONCLUSION: The plasmid construct is available for YFV molecular test validation on clinical, entomological, and epizootic samples.

Characterization of Feeding Behavior and its Relationship With the Longevity of Wild and Peridomestic Triatoma dimidiata, Latreille 1811 (Hemiptera, Reduviidae) Under Laboratory Conditions.

Triatoma dimidiata (Latreille 1811) is considered the second most important vector of the Trypanosa cruzi etiological agent of Chagas disease in Colombia. It has a life cycle that involves a domiciled, peridomiciled, and wild distribution. The study of feeding behavior and its influence on the survival of sylvatic and peridomestic populations can help identify a possible differential risk in the transmission of Chagas disease to humans, mainly in northwestern and east-central Colombia. We characterize the main parameters of feeding behavior and their influence on the longevity and survival of two rat-fed populations of T. dimidiata from Colombia, one in the north-west (from palms in a tropical dry forest area) and the other in the center-east (peridomiciliated), under controlled environmental conditions. The palm population took considerably longer than the peridomestic population to complete its life cycle under experimental laboratory conditions, being both populations univoltine since they have only one life cycle per year. Statistically significant differences were evidenced using Box-Cox model between the survival rates of T. dimidiata populations when the parameters related to blood intake and behavior were incorporated, in contrast to the survival models in which the origin only was considered as a factor. Our results could be used to generate recommendations to guide prevention strategies in communities near sylvatic and peridomiciliated populations of T. dimidiata.

Linear and Machine Learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease.

BACKGROUND: Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues. METHODOLOGY/PRINCIPAL FINDINGS: We compare three methods in their ability to propagate uncertainty and provide reliable estimates of FoI for Chagas disease in Colombia as a case study: two Machine Learning (ML) methods (Boosted Regression Trees (BRT) and Random Forest (RF)), and a Linear Model (LM) framework that we had developed previously. Our analyses show consistent results between the three modelling methods under scrutiny. The predictors (explanatory variables) selected, as well as the location of the most uncertain FoI values, were coherent across frameworks. RF was faster than BRT and LM, and provided estimates with fewer extreme values when extrapolating to areas where no ground-truth data were available. However, BRT and RF were less efficient at propagating uncertainty. CONCLUSIONS/SIGNIFICANCE: The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries and to other infectious diseases for which serosurveys are regularly conducted for surveillance.

Comparison of 1-year healthcare resource utilization and related costs for patients with heart failure in the Chagas and non-Chagas matched cohorts.

Background: Chagas disease is one of the leading causes of heart failure (HF) in Latin Americans, and there are limited data available that examine related costs of care for patients with HF. This study aimed to compare healthcare resource utilization and related costs for patients with HF, with and without Chagas disease. Methods: A prospective matched-cohort study comparing the healthcare costs for patients with HF with Chagas disease and care costs for patients with HF without Chagas disease was conducted between January 2019 and December 2019. Only direct costs have been estimated, including hospitalization costs, medications and other cardiovascular interventions, and clinical and laboratory follow-up for up to 1 year. Results: A total of 80 patients with chronic HF were included in the study. Of the 80 patients, 40 patients in the Chagas cohort and 40 patients in the non-Chagas cohort were matched for age, insurer and sex. From a social security system perspective, the total costs for the two cohorts during the study period were U$970,136. Specifically, the healthcare costs for the Chagas cohort were greater than the total healthcare costs for the non-Chagas group (U$511,931 versus U$458,205; p = 0.6183) Most costs were associated with hospitalizations (65.5% versus 59.6%), with averages of U$12,798.5 and U$11,455.1 per person in the Chagas and non-Chagas groups, respectively. In both the Chagas (51.6%) and non-Chagas cohorts (54.5%), causes of readmission unrelated to HF outweighed causes of readmission related to HF. High incidences of hospital admissions were observed during the rainy (cold) season for both cohorts. Conclusions: Over a 12-month follow-up period, patients with chronic HF and Chagas consume as many healthcare resources as those with chronic HF and without Chagas. These data highlight the considerable and growing economic burden of HF on the Colombian health system.

The CUIDA Chagas Project: towards the elimination of congenital transmission of Chagas disease in Bolivia, Brazil, Colombia, and Paraguay.

BACKGROUND: Mother-to-child transmission of Chagas disease (CD) has become a relevant problem in both endemic and non-endemic areas. METHODS: Description of the CUIDA Chagas Project - Communities United for Innovation, Development and Attention for Chagas disease'. RESULTS: Through innovative and strategic research, this project will provide improved diagnostic and treatment options as well as replicable implementation models that are adaptable to different contexts. CONCLUSIONS: By integrating test, treat and care actions for CD into primary health care practices, the burden of CD on people and health systems may be significantly reduced.

Risk factors and spatial analysis for domiciliary infestation with the Chagas disease vector Triatoma venosa in Colombia.

Background: In Colombia, communities living in the Andean region are the most affected by Chagas disease due to the presence of the main vectors, the environmental and risk factors associated with house infestation. Triatoma venosa is classified as a secondary vector that is frequently found in the departments of Boyaca and Cundinamarca, but epidemiological information and its association with risk factors in domestic and peridomestic areas is unknown. The study aimed to evaluate housing and environmental characteristics associated with domestic and peridomestic infestation by T. venosa and a risk map was estimated. Methods: A cross-sectional study was conducted in municipalities of Boyaca and Cundinamarca, Colombia. From March to July 2015, triatomine infestation screening surveys were conducted in 155 households. Multivariate analysis was performed to evaluate associations with the infestation and ecological niche modeling was estimated using environmental variables. Results: No statistical association was found with any of the housing variables in the adjusted multivariate analysis. However, in raw relationship infestation was associated with bushes < 10 m (OR = 3; 95% CI: 1.3-7.3) and higher temperature p value < 0.05. The developed final risk map pointed to 12 municipalities with no previous report of the disease, which should be sampled for the presence of T. venosa. Conclusion: This study highlights the relationship between environmental factors and T. venosa in Colombia and the importance of modeling tools to improve mapping efforts. Additional studies are needed to verify the association with bushes and higher temperatures and to verify infestation in predicted risk area with no previous report of the species.

Spatiotemporal variations in exposure: Chagas disease in Colombia as a case study.

Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980-2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease.

The CUIDA Chagas Project: towards the elimination of congenital transmission of Chagas disease in Bolivia, Brazil, Colombia, and Paraguay

ABSTRACT Background: Mother-to-child transmission of Chagas disease (CD) has become a relevant problem in both endemic and non-endemic areas. Methods: Description of the CUIDA Chagas Project - Communities United for Innovation, Development and Attention for Chagas disease'. Results: Through innovative and strategic research, this project will provide improved diagnostic and treatment options as well as replicable implementation models that are adaptable to different contexts. Conclusions: By integrating test, treat and care actions for CD into primary health care practices, the burden of CD on people and health systems may be significantly reduced.

House-Level Risk Factors for Aedes aegypti Infestation in the Urban Center of Castilla la Nueva, Meta State, Colombia.

Aedes aegypti is the main vector of the dengue virus in Colombia. Some factors have been associated with its presence; however, in the local context, it has not been sufficiently evaluated. The present study seeks to identify the socioeconomic, environmental, and behavioral factors associated with the presence and abundance of A. aegypti in urban dwellings in the municipality of Castilla la Nueva. A cross-sectional cohort study was conducted in houses in the urban area of the municipality of Castilla la Nueva, where 307 houses were sampled by systematic random sampling during May 2018. A multifactorial survey was used to measure the socioeconomic, environmental, and behavioral factors as explanatory variables. The infestation and relative abundance were established by the presence of larval stages and ovitraps. The associated factors for the presence and abundance of A. aegypti were identified using negative binomial and logistic regression models. A positive housing infestation of 33.2% was identified by direct inspection and 78.5% with ovitraps. The main factors positively associated with the presence and abundance of A. aegypti were one-story homes (PR = 2.26; 95% CI: 1.31-3.87), the storage of water for domestic use (PR = 1.91; 95% CI: 1.18-3.09), and local conditions such as disorganized backyard (PR = 79.95; 95% CI: 10.96-583.24) and the proportion of shade greater than 50% of the backyard (PR = 62.32; 95% CI: 6.47-600.32). And, it is negatively associated with residential gas service (PR = 0.3; 95% CI: 0.16-0.58) and self-administered internal fumigation (PR = 0.37; 95% CI: 0.2-0.69). The presence and abundance of A. aegypti were explained by interrelated socioeconomic, environmental, and behavioral factors where local conditions and habits such as the organization of the patio, knowledge about vector biology, and cleaning containers are identified as main topics for future prevention strategies for the transmission of dengue in the local and national context.

Risk factors for triatominae infestation in a municipality of Colombia.

BACKGROUND: Identifying risk factors for Triatominae infestation is essential for the development of vector control interventions. METHODS: To determine the intra- and peridomiciliary risk factors associated with triatomine infestation, a cross-sectional analytical study was carried out with random cluster sampling in two stages, which included the identification of risk factors by survey and direct observation, as well as the search and capture of triatomines. The detection of trypanosomes in triatomines was carried out by observing the rectal content and then by conventional polymerase chain reaction (PCR). RESULTS: In 21 of the 207 houses inspected, 13 specimens of R. colombiensis and 19 specimens of P. geniculatus were found. Entomological indices included: dispersion 36%, infestation 10%, infection 65%, colonization 4.7%, density 15%, and concentration 152%. An association was found between the presence of Triatominae and the existence of branches and fissures in the floors, as well as with the presence of accumulated objects and with knowledge about Chagas disease. The risk of having triatomines in urban homes is 5.7 times higher than the risk in rural areas [confidence interval (CI) 0.508-67.567]; 6.6 times in houses with cracked soil (CI 0.555-81.994), 6 times in houses located near caneys (CI 0.820-44.781), and 6.16 times with accumulated objects (CI 1.542-39.238). CONCLUSION: Chagas disease is a complex problem that requires control based on the vector's elimination or surveillance, which implies identifying species and their distribution, generating alerts, knowledge, and awareness in the population. It is necessary to intensify surveillance activities for the event, especially in changing aspects of Chagas diseases' transmission dynamics, such as urbanization and the type of housing associated with the vector's presence.

Diversity and interactions among triatomine bugs, their blood feeding sources, gut microbiota and Trypanosoma cruzi in the Sierra Nevada de Santa Marta in Colombia.

Chagas disease remains a major neglected disease in Colombia. We aimed to characterize Trypanosoma cruzi transmission networks in the Sierra Nevada de Santa Marta (SNSM) region, to shed light on disease ecology and help optimize control strategies. Triatomines were collected in rural communities and analyzed for blood feeding sources, parasite diversity and gut microbiota composition through a metagenomic and deep sequencing approach. Triatoma dimidiata predominated, followed by Rhodnius prolixus, Triatoma maculata, Rhodnius pallescens, Panstrongylus geniculatus and Eratyrus cuspidatus. Twenty-two species were identified as blood sources, resulting in an integrated transmission network with extensive connectivity among sylvatic and domestic host species. Only TcI parasites were detected, predominantly from TcIb but TcIa was also reported. The close relatedness of T. cruzi strains further supported the lack of separate transmission cycles according to habitats or triatomine species. Triatomine microbiota varied according to species, developmental stage and T. cruzi infection. Bacterial families correlated with the presence/absence of T. cruzi were identified. In conclusion, we identified a domestic transmission cycle encompassing multiple vector species and tightly connected with sylvatic hosts in the SNSM region, rather than an isolated domestic transmission cycle. Therefore, integrated interventions targeting all vector species and their contact with humans should be considered.

Molecular characterization of mosquitoes (Diptera: Culicidae) from the Colombian rainforest.

A few studies have carried out the taxonomic and molecular characterization of sylvatic mosquito species in Latin America, where some species have been incriminated as vectors for arboviruses and parasites transmission. The present study reports the molecular characterization of mosquito species in the Sierra Nevada de Santa Marta, a natural ecosystem in the Northern coast of Colombia. Manual capture methods were used to collect mosquitoes, and the specimens were identified via classical taxonomy. The COI marker was used for species confirmation, and phylogenetic analysis was performed using the neighbor-joining method, with the Kimura-2-Parameters model. Aedes serratus , Psorophora ferox , Johnbelkinia ulopus , Sabethes chloropterus , Sabethes cyaneus , Wyeomyia aporonoma , Wyeomyia pseudopecten , Wyeomyia ulocoma and Wyeomyia luteoventralis were identified. We assessed the genetic variability of mosquitoes in this area and phylogenetic reconstructions allowed the identification at the species level. Classical and molecular taxonomy demonstrated to be useful and complementary when morphological characteristics are not well preserved, or the taxonomic group is not represented in public molecular databases.