Toward global estimates of spatial and temporal transmission of Chagas disease

Estimating spatiotemporal variation in disease exposure is critical to developing cost-effective and targeted strategies to reduce the burden of the disease. As The WHO is expecting to eliminate Chagas disease as a public health problem by 2030, being able to measure the local burden of the disease and the progress made thus far is critical. However, obtaining such information when there is no dedicated surveillance system set up to monitor incidence can be challenging. Cross-sectional prevalence studies provide information on past exposure but cannot be used directly to evaluate the epidemiological situation, especially for long-lasting diseases such as Chagas disease. However, the Force-of-Infection (FoI), i.e., the yearly per-susceptible rate of disease acquisition, can be estimated using age prevalence data and provide insight into the local temporal pattern of the disease. Such methodology, relying on localised surveys, can inform the dynamic of transmission locally, but extrapolating FoI estimates from them to assess the burden across the country requires robust statistical methods. In this thesis, we develop and implement a modelling process to, first, predict FoI in space and time from cross-sectional studies and, estimate the burden of the disease, while appropriately propagating uncertainties. Where such an approach has been used, typically mean or median FoI estimates are used as a dependent variable, ignoring the uncertain nature of such FoI being estimates rather than observations. Therefore, the first objective of this thesis was to account for such uncertainty both when fitting models and evaluating their predictive ability. We implemented a set of comprehensive analyses to assess the impact of this uncertainty on performance, by characterising the ability to estimate accurately the central trends while correctly characterising the level of uncertainty. We, then, compare the implementation and performance of this framework to Machine Learning methods to optimise the methodology. Finally, we, propose a modelling process where the predicted FoIs at a fine spatial resolution are used to estimate the burden of Chagas disease. The process, applied to the 76 serosurveys conducted in Colombia, showed a substantial risk of overconfidence when using median estimates to fit and evaluate models, instead of accounting for the uncertain nature of estimated FoI. Machine Learning methods provided a more flexible and reproducible framework while recentring the uncertainty and are thus better suited to provide good burden estimates. Implementing the modelling pipeline, we estimated that the FoI varied considerably across Colombia, but temporal changes were less marked. Relying on predicted current and past exposure, 506,000 (95%CrI: 395,000-648,000) people were estimated to be infected by T. cruzi in Colombia in 2020, representing a 1.0% (95%CrI: 0.8%-1.3%) prevalence in the general population and leading to an estimated 2,400 (95%CrI: 1,900-3,400) deaths. We estimated a substantial increase in the burden of Chagas disease over time, resulting from the interplay between exposure and demography: a slight decrease in exposure was overcompensated by the large increase in population size and the gradual ageing of the population

Assessing the performance of remotely-sensed flooding indicators and their potential contribution to early warning for leptospirosis in Cambodia

Remote sensing can contribute to early warning for diseases with environmental drivers, such as flooding for leptospirosis. In this study we assessed whether and which remotely-sensed flooding indicator could be used in Cambodia to study any disease for which flooding has already been identified as an important driver, using leptospirosis as a case study. The performance of six potential flooding indicators was assessed by ground truthing. The Modified Normalized Difference Water Index (MNDWI) was used to estimate the Risk Ratio (RR) of being infected by leptospirosis when exposed to floods it detected, in particular during the rainy season. Chi-square tests were also calculated. Another variable—the time elapsed since the first flooding of the year—was created using MNDWI values and was also included as explanatory variable in a generalized linear model (GLM) and in a boosted regression tree model (BRT) of leptospirosis infections, along with other explanatory variables. Interestingly, MNDWI thresholds for both detecting water and predicting the risk of leptospirosis seroconversion were independently evaluated at -0.3. Value of MNDWI greater than -0.3 was significantly related to leptospirosis infection (RR = 1.61 [1.10–1.52]; χ2 = 5.64, p-value = 0.02, especially during the rainy season (RR = 2.03 [1.25–3.28]; χ2 = 8.15, p-value = 0.004). Time since the first flooding of the year was a significant risk factor in our GLM model (p-value = 0.042). These results suggest that MNDWI may be useful as a risk indicator in an early warning remote sensing tool for flood-driven diseases like leptospirosis in South East Asia

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

El aprendizaje profundo desde el uso de múltiples representaciones del concepto razones y proporciones: una aproximación desde una unidad didáctica basada en la economía tradicional Wayúu

El presente proyecto de investigación es un estudio cualitativo de tipo estudio de caso, cuyo objetivo principal es interpretar cómo una unidad didáctica basada en la economía tradicional Wayúu promueve la transformación del aprendizaje profundo (uso de múltiples representaciones) sobre razones y proporciones en los estudiantes del grado noveno de las Instituciones Etnoeducativas Rural Akua´ipa y San Rafael del Pájaro en el departamento de La Guajira. Se emplearon como instrumentos: cuestionario de preguntas abiertas (inicial y final), una entrevista semiestructurada, seguimiento a un contrato didáctico y una serie de actividades aplicadas durante el desarrollo de una unidad didáctica centrada en el uso de múltiples representaciones relacionados con las razones y proporciones y que siguió el modelo del ciclo de aprendizaje dividido en cuatro fases: fase de exploración de ideas previas, de introducción de nuevos conocimientos, de síntesis y de aplicación. De acuerdo con los resultados obtenidos, se evidenció que la unidad didáctica generó transformaciones evidentes en el uso de múltiples representaciones del concepto razones y proporciones en los estudiantes, lo cual posibilitó que mantuvieran un lenguaje matemático más estructurado que los condujo hacia la profundidad en su aprendizaje para la construcción de su propio conocimiento.The present research project is a qualitative case study, whose main objective is to interpret how a didactic unit based on the Wayúu traditional economy promotes the transformation of deep learning (use of multiple representations) about ratios and proportions in ninth grade students of the Akua'ipa and San Rafael del Pájaro Rural Ethnoeducational Institutions in the department of La Guajira. The following instruments were used: a questionnaire with open questions (initial and final), a semi-structured interview, a didactic contract and a series of activities applied during the development of a didactic unit focused on the use of multiple representations related to ratios and proportions and which followed the model of the learning cycle divided into four phases: phase of exploration of previous ideas, introduction of new knowledge, synthesis and application. According to the results obtained, it was evidenced that the didactic unit generated evident transformations in the use of multiple representations of the concept of ratios and proportions in the students, which made it possible for them to maintain a more structured mathematical language that led them towards depth in their learning for the construction of their own knowledge.PregradoMagíster en Educación, Metodología VirtualTabla de contenido Resumen............................................................................................................................... 12 Abstract ................................................................................................................................ 13 Introducción ......................................................................................................................... 14 1. Ámbito problémico ....................................................................................................... 16 1.1 Formulación del problema..................................................................................... 16 1.2 Justificación......................................................................................................... 210 1.3 Antecedentes........................................................................................................ 266 2. Objetivos....................................................................................................................... 30 2.1. Objetivo general ........................................................................................................ 30 2.2. Objetivos específicos................................................................................................. 30 3. Referente teórico........................................................................................................... 31 3.1. Didáctica de las matemáticas desde la perspectiva socioconstructivista del aprendizaje. ........................................................................................................................................ 310 3.2. Las etnomatemáticas como medio de aprendizaje. ................................................. 332 3.3. Aprendizaje profundo.............................................................................................. 387 3.4. Múltiples representaciones para el aprendizaje profundo ......................................... 40 3.5. Unidad didáctica ...................................................................................................... 422 3.5.1. Criterios para el diseño de una Unidad Didáctica............................................. 453 3.5.1.1. Definición de finalidades y objetivos. ............................................................. 45 3.5.1.2. Criterios para la selección de contenidos......................................................... 46 3.5.1.3. Criterios para organizar y secuenciar los contenidos..................................... 466 3.5.1.4. Criterios para la selección y secuenciación de actividades............................ 478 7 3.5.1.5. Criterios para la organización y gestión del aula. .......................................... 498 3.6. El concepto de razones y proporciones ................................................................... 499 3.7. Economía tradicional Wayúu. ................................................................................... 51 3.7.1. Ganado ovino y caprino...................................................................................... 52 4. Metodología ................................................................................................................... 533 4.1. Enfoque de investigación......................................................................................... 543 4.2. Tipo de investigación............................................................................................... 554 4.3. Categorías de análisis de la investigación. .............................................................. 565 4.4. Unidad de trabajo..................................................................................................... 577 4.5. Unidad de análisis...................................................................................................... 58 4.6. Técnicas e instrumentos de la investigación........................................................... 598 4.6.1. Cuestionarios..................................................................................................... 610 4.6.2. Contrato didáctico............................................................................................. 621 4.6.3. Entrevistas semiestructuradas........................................................................... 621 4.7. Organización de la información, análisis e interpretación de resultados ................ 632 4.7.1. Organización de la información........................................................................ 632 4.7.2. Análisis e interpretación ................................................................................... 653 4.8. Descripción metodológica ....................................................................................... 665 5. Análisis e interpretación de resultados........................................................................... 668 5.1. Cuestionario sociodemográfico ................................................................................. 69 5.2. Análisis general del momento de exploración......................................................... 721 5.2.1. Análisis del cuestionario inicial........................................................................ 732 5.2.2. Análisis del contrato didáctico.......................................................................... 786 8 5.3. Interpretación de la transformación de las representaciones de los estudiantes de la unidad de trabajo .......................................................................................................................... 78 6. Conclusiones ................................................................................................................ 1130 7. Recomendaciones ..................................................................................................... 1163 8. Referencias.............................................................................................................. 11816 9. Anexos .................................................................................................................... 1282

Linear and machine learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease

Q1Q1Background: 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.https://orcid.org/0000-0002-8165-3198Revista Internacional - IndexadaA1N

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’

An algorithm applied to national surveillance data for the early detection of major dengue outbreaks in Cambodia

Dengue is a national priority disease in Cambodia. The Cambodian National Dengue Surveillance System is based on passive surveillance of dengue-like inpatients reported by public hospitals and on a sentinel, pediatric hospital-based active surveillance system. This system works well to assess trends but the sensitivity of the early warning and time-lag to usefully inform hospitals can be improved. During The ECOnomic development, ECOsystem MOdifications, and emerging infectious diseases Risk Evaluation (ECOMORE) project’s knowledge translation platforms, Cambodian hospital staff requested an early warning tool to prepare for major outbreaks. Our objective was therefore to find adapted tools to improve the early warning system and preparedness. Dengue data was provided by the National Dengue Control Program (NDCP) and are routinely obtained through passive surveillance. The data were analyzed at the provincial level for eight Cambodian provinces during 2008–2015. The R surveillance package was used for the analysis. We evaluated the effectiveness of Bayesian algorithms to detect outbreaks using count data series, comparing the current count to an expected distribution obtained from observations of past years. The analyses bore on 78,759 patients with dengue-like syndromes. The algorithm maximizing sensitivity and specificity for the detection of major dengue outbreaks was selected in each province. The overall sensitivity and specificity were 73% and 97%, respectively, for the detection of significant outbreaks during 2008–2015. Depending on the province, sensitivity and specificity ranged from 50% to 100% and 75% to 100%, respectively. The final algorithm meets clinicians’ and decisionmakers’ needs, is cost-free and is easy to implement at the provincial level

Les soumissionnaires (roman) suivi de "Ironihilisme" : radicalités du roman noir français du XXIe siècle (essai)

Les deux volets de cette thèse en recherche-création explorent les crises sociales que remet en scène le roman noir français de l'extrême contemporain. Ils examinent aussi les tensions éthiques et esthétiques qui habitent le genre tel que pratiqué dans l'Hexagone. Le volet création, un roman noir choral intitulé Les soumissionnaires, s'inspire de faits réels en rapport avec la Commission d'enquête sur l'octroi et la gestion des contrats publics dans l'industrie de la construction - appelée plus familièrement « commission Charbonneau » décrétée par le gouvernement du Québec en 2011. Le récit aborde également des thèmes forts du genre tels que la corruption et la violence policières, les traumatismes de guerre et le narcoterrorisme. Mythe majeur de l'imaginaire québécois, l'hiver constitue l'autre grand motif du texte, ce qui donne aussi à cette histoire américaine racontée en langue française de France des airs de « polar nordique ». Les soumissionnaires relate la sanglante épopée de Martin Thériaux, ancien chasseur alpin et tireur d'élite français devenu déneigeur de toits à Québec. Secret quant à son passé, Thériaux voit ses instincts guerriers se réveiller à la suite d'une altercation avec des membres du crime organisé. En parallèle, la narration suit le destin d'une foule de personnages, parmi lesquels un lieutenant-détective du SPVM et une journaliste new-yorkaise venue couvrir à Montréal les audiences de la CEIC. L'essai critique quant à lui se propose d'analyser les formes paradoxales qui caractérisent le roman noir français actuel. L'étude se concentre sur la manière dont des auteurs comme Antoine Chainas, DOA, Jérôme Leroy, Dominique Manotti et Elsa Marpeau subvertissent les positions énonciatives qui avaient court par exemple dans le « néo-polar ». À travers le maniement d'une ironie qui implique des rapprochements d'éléments contradictoires, des écarts de langage ainsi qu'une certaine incongruité des mots et des idées, se dessine un mouvement de balancier, oscillation entre fascination et répulsion, raillerie et tentation du vide. Confrontations et distanciations ne cessent ainsi de rivaliser, générant dans les textes de constants rapports de méfiance. On savait le roman noir fertile à ce sujet en matière de relations entre protagonistes de pouvoir ; on le découvre également labile sur le plan des stratégies discursives des narrateurs. Que ces derniers soient absents de la diégèse ou présents comme personnages, ils font invariablement preuve de duplicité, aussi bien dans leur effet d'engagement que dans leur désengagement subjectif.The two parts of this research-creation thesis explore the social crises that the French noir fictions of the extreme contemporary bring to life. They also examine the ethical and aesthetic tensions that inhabit the genre as it is practiced by writers, mainly in France. The creative writing part, a choral novel entitled Les soumissionnaires, is inspired by real facts relating to the Commission of Inquiry into the Granting and Management of Public Contracts in the Construction Industry (more colloquially known as the "Charbonneau Commission") decreed by the government of Quebec in 2011. The story also addresses strong themes of the genre such as police corruption and violence, war trauma and narcoterrorism. A major myth in the Quebec imagination, winter is the other main motif of the text, which also gives this American story told in French from France an air of "Nordic thriller". The bidders recount the bloody epic of Martin Thériaux, a former French alpine hunter and sniper who became a snow clearer in Quebec City. Secret as to his past, Thériaux sees his warrior instincts awakened following an altercation with members of organized crime. At the same time, the narration follows the fate of other characters, including a lieutenant-detective from the SPVM and a New York journalist who came to cover the CEIC hearings in Montreal. The critical essay sets out to analyze the paradoxical forms that characterize the current French noir fiction. The study focuses on the way in which authors like Antoine Chainas, DOA, Jérôme Leroy, Dominique Manotti and Elsa Marpeau subvert the enunciative positions that had prevailed for example in the French "neo-polar". Through the handling of an irony involving bringing together contradictory elements, language differences, and a certain incongruity of words and ideas, a pendulum movement emerges, an oscillation between fascination and repulsion, mockery and the temptation of existential void. Confrontations and distancing thus never cease to compete, generating constant reports of mistrust in the texts. We knew that the noir fiction was fertile on this subject in terms of relations between protagonists of power; we also find it labile in terms of the narrators' discursive strategies. Whether these are absent from the diegesis or present as characters, they invariably demonstrate duplicity, both in their effect of engagement and in their subjective disengagement

Associations of water contact frequency, duration, and activities with schistosome infection risk: A systematic review and meta-analysis.

BackgroundSchistosomiasis is a water-borne parasitic disease which affects over 230 million people globally. The relationship between contact with open freshwater bodies and the likelihood of schistosome infection remains poorly quantified despite its importance for understanding transmission and parametrising transmission models.MethodsWe conducted a systematic review to estimate the average effect of water contact duration, frequency, and activities on schistosome infection likelihood. We searched Embase, MEDLINE (including PubMed), Global Health, Global Index Medicus, Web of Science, and the Cochrane Central Register of Controlled Trials from inception until May 13, 2022. Observational and interventional studies reporting odds ratios (OR), hazard ratios (HR), or sufficient information to reconstruct effect sizes on individual-level associations between water contact and infection with any Schistosoma species were eligible for inclusion. Random-effects meta-analysis with inverse variance weighting was used to calculate pooled ORs and 95% confidence intervals (CIs).ResultsWe screened 1,411 studies and included 101 studies which represented 192,691 participants across Africa, Asia, and South America. Included studies mostly reported on water contact activities (69%; 70/101) and having any water contact (33%; 33/101). Ninety-six percent of studies (97/101) used surveys to measure exposure. A meta-analysis of 33 studies showed that individuals with water contact were 3.14 times more likely to be infected (OR 3.14; 95% CI: 2.08-4.75) when compared to individuals with no water contact. Subgroup analyses showed that the positive association of water contact with infection was significantly weaker in children compared to studies which included adults and children (OR 1.67; 95% CI: 1.04-2.69 vs. OR 4.24; 95% CI: 2.59-6.97). An association of water contact with infection was only found in communities with ≥10% schistosome prevalence. Overall heterogeneity was substantial (I2 = 93%) and remained high across all subgroups, except in direct observation studies (I2 range = 44%-98%). We did not find that occupational water contact such as fishing and agriculture (OR 2.57; 95% CI: 1.89-3.51) conferred a significantly higher risk of schistosome infection compared to recreational water contact (OR 2.13; 95% CI: 1.75-2.60) or domestic water contact (OR 1.91; 95% CI: 1.47-2.48). Higher duration or frequency of water contact did not significantly modify infection likelihood. Study quality across analyses was largely moderate or poor.ConclusionsAny current water contact was robustly associated with schistosome infection status, and this relationship held across adults and children, and schistosomiasis-endemic areas with prevalence greater than 10%. Substantial gaps remain in published studies for understanding interactions of water contact with age and gender, and the influence of these interactions for infection likelihood. As such, more empirical studies are needed to accurately parametrise exposure in transmission models. Our results imply the need for population-wide treatment and prevention strategies in endemic settings as exposure within these communities was not confined to currently prioritised high-risk groups such as fishing populations