RESUMEN
Retrospective cohort studies in Cameroon found an association between Onchocerca volvulus microfilarial load in childhood (measured in 1991-1993) and risk of developing epilepsy later in life (measured in 2017). We parameterised and integrated this relationship (across children aged 3-15 years) into the previously published, stochastic transmission model, EPIONCHO-IBM, for Simulium damnosum sensu lato-transmitted onchocerciasis. We simulated 19 years (1998-2017) of annual ivermectin mass drug administration (MDA) reflecting coverage in the study area, and modelled epilepsy prevalence and incidence. Scenario-based simulations of 25 years of (annual and biannual) MDA in hyper- and holoendemic settings, with 65% and 80% therapeutic coverage, were also conducted. EPIONCHO-IBM predicted 7.6% epilepsy prevalence (compared to 8.2% in the Cameroon study) and incidence of 317 cases/100,000 person-years (compared to 350). In hyperendemic areas, 25 years of biannual MDA (80% coverage) eliminated onchocerciasis-associated epilepsy (OAE) and protected untreated under-fives from its development. Strengthening onchocerciasis programmes, implementing alternative strategies, and evaluating treatment for under-fives and school-age children are crucial to prevent OAE in highly-endemic settings.
Asunto(s)
Epilepsia , Ivermectina , Onchocerca volvulus , Oncocercosis , Ivermectina/uso terapéutico , Oncocercosis/epidemiología , Oncocercosis/tratamiento farmacológico , Oncocercosis/complicaciones , Humanos , Niño , Epilepsia/epidemiología , Epilepsia/tratamiento farmacológico , Epilepsia/parasitología , Adolescente , Preescolar , Prevalencia , Incidencia , Camerún/epidemiología , Animales , Femenino , Masculino , Onchocerca volvulus/efectos de los fármacos , Administración Masiva de Medicamentos , Estudios Retrospectivos , Simuliidae/parasitologíaRESUMEN
Understanding disease transmission in the workplace is essential for protecting workers. To model disease outbreaks, the small populations in many workplaces require that stochastic effects are considered, which results in higher uncertainty. The aim of this study was to quantify and interpret the uncertainty inherent in such circumstances. We assessed how uncertainty of an outbreak in workplaces depends on i) the infection dynamics in the community, ii) the workforce size, iii) spatial structure in the workplace, iv) heterogeneity in susceptibility of workers, and v) heterogeneity in infectiousness of workers. To address these questions, we developed a multiscale model: A deterministic model to predict community transmission, and a stochastic model to predict workplace transmission. We extended this basic workplace model to allow for spatial structure, and heterogeneity in susceptibility and infectiousness in workers. We found a non-monotonic relationship between the workplace transmission rate and the coefficient of variation (CV), which we use as a measure of uncertainty. Increasing community transmission, workforce size and heterogeneity in susceptibility decreased the CV. Conversely, increasing the level of spatial structure and heterogeneity in infectiousness increased the CV. However, when the model predicts bimodal distributions, for example when community transmission is low and workplace transmission is high, the CV fails to capture this uncertainty. Overall, our work informs modellers and policy makers on how model complexity impacts outbreak uncertainty. In particular: workforce size, community and workplace transmission, spatial structure and individual heterogeneity contribute in a specific and individual manner to the predicted workplace outbreak size distribution.
Asunto(s)
Enfermedades Transmisibles , Modelos Biológicos , Humanos , Incertidumbre , Conceptos Matemáticos , Brotes de Enfermedades , Enfermedades Transmisibles/epidemiologíaRESUMEN
Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
Asunto(s)
Oncocercosis , Humanos , Oncocercosis/tratamiento farmacológico , Oncocercosis/epidemiología , Oncocercosis/prevención & control , Ivermectina , Administración Masiva de Medicamentos , África/epidemiología , Enfermedades DesatendidasRESUMEN
BACKGROUND: In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. CONCLUSIONS/SIGNIFICANCE: The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance.
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Anticuerpos/sangre , Mordeduras y Picaduras de Insectos/epidemiología , Saliva/inmunología , Simuliidae/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Insectos Vectores/inmunología , Insectos Vectores/parasitología , Masculino , Persona de Mediana Edad , Onchocerca volvulus/crecimiento & desarrollo , Oncocercosis/epidemiología , Oncocercosis/transmisión , Simuliidae/parasitología , Adulto JovenRESUMEN
Protecting healthcare professionals is crucial in maintaining a functioning healthcare system. The risk of infection and optimal preventive strategies for healthcare workers during the COVID-19 pandemic remain poorly understood. Here we report the results of a cohort study that included pre- and asymptomatic healthcare workers. A weekly testing regime has been performed in this cohort since the beginning of the COVID-19 pandemic to identify infected healthcare workers. Based on these observations we have developed a mathematical model of SARS-CoV-2 transmission that integrates the sources of infection from inside and outside the hospital. The data were used to study how regular testing and a desynchronisation protocol are effective in preventing transmission of COVID-19 infection at work, and compared both strategies in terms of workforce availability and cost-effectiveness. We showed that case incidence among healthcare workers is higher than would be explained solely by community infection. Furthermore, while testing and desynchronisation protocols are both effective in preventing nosocomial transmission, regular testing maintains work productivity with implementation costs.
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Infecciones Asintomáticas , Prueba de COVID-19/métodos , COVID-19/diagnóstico , COVID-19/economía , Personal de Salud , SARS-CoV-2 , Algoritmos , Análisis Costo-Beneficio , Infección Hospitalaria , Recolección de Datos , Atención a la Salud , Hospitales , Humanos , Tamizaje Masivo/métodos , Modelos Teóricos , Exposición Profesional , Pandemias , Riesgo , Procesos Estocásticos , Suiza/epidemiologíaRESUMEN
Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.
Asunto(s)
Control de Enfermedades Transmisibles/métodos , Recolección de Datos/métodos , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/prevención & control , Filariasis Linfática/epidemiología , Filariasis Linfática/transmisión , Humanos , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/transmisión , Modelos Teóricos , Oncocercosis/epidemiología , Oncocercosis/transmisión , Esquistosomiasis/epidemiología , Esquistosomiasis/transmisión , Suelo/parasitología , Tracoma/epidemiología , Tracoma/transmisión , Medicina Tropical/métodos , Tripanosomiasis Africana/epidemiología , Tripanosomiasis Africana/transmisiónRESUMEN
Although mortality increases with age in most organisms, senescence is missing from models of parasite evolution. Since virulence evolves according to the host's mortality, and since virulence influences the intensity of transmission, which determines the average age at infection and thus the mortality rate of a senescing host, we expected that epi-evolutionary feedbacks would underlie the evolution of virulence in a population of senescing hosts. We tested this idea by extending an age-structured model of epidemiological dynamics with the parasite's evolution. A straightforward prediction of our model is that stronger senescence forces the evolution of higher virulence. However, the model also reveals that the evolved virulence depends on the average age at infection, giving an evolutionary feedback with the epidemiological situation, a prediction not found when assuming a constant mortality rate with age. Additionally, and in contrast to most models of parasite evolution, we found that the virulence at the evolutionary equilibrium is influenced by whether the force of infection depends on the density or on the frequency of infected hosts, due to changes in the average age at infection. Our findings suggest that ignoring age-specific effects, and in particular senescence, can give misleading predictions about parasite evolution.
Asunto(s)
Parásitos , Animales , Evolución Biológica , Interacciones Huésped-Parásitos , Modelos Biológicos , Parásitos/genética , VirulenciaRESUMEN
BACKGROUND: Due to spatial heterogeneity in onchocerciasis transmission, the duration of ivermectin mass drug administration (MDA) required for eliminating onchocerciasis will vary within endemic areas and the occurrence of transmission "hotspots" is inevitable. The geographical scale at which stop-MDA decisions are made will be a key driver in how rapidly national programs can scale down active intervention upon achieving the epidemiological targets for elimination. METHODS: We used 2 onchocerciasis models (EPIONCHO-IBM and ONCHOSIM) to predict the likelihood of achieving elimination by 2030 in Africa, accounting for variation in preintervention endemicity levels and histories of ivermectin treatment. We explore how decision making at contrasting geographical scales (community vs larger scale "project") changes projections on populations still requiring MDA or transitioning to post-treatment surveillance. RESULTS: The total population considered grows from 118 million people in 2020 to 136 million in 2030. If stop-MDA decisions are made at project level, the number of people requiring treatment declines from 69-118 million in 2020 to 59-118 million in 2030. If stop-MDA decisions are made at community level, the numbers decline from 23-81 million in 2020 to 15-63 million in 2030. The lower estimates in these prediction intervals are based on ONCHOSIM, the upper limits on EPIONCHO-IBM. CONCLUSIONS: The geographical scale at which stop-MDA decisions are made strongly determines how rapidly national onchocerciasis programs can scale down MDA programs. Stopping in portions of project areas or transmission zones would free up human and economic resources.
Asunto(s)
Oncocercosis , África , Toma de Decisiones , Humanos , Ivermectina/uso terapéutico , Administración Masiva de Medicamentos , Oncocercosis/tratamiento farmacológicoRESUMEN
Drug-based interventions are at the heart of global efforts to reach elimination as a public health problem (trachoma, soil-transmitted helminthiases, schistosomiasis, lymphatic filariasis) or elimination of transmission (onchocerciasis) for 5 of the most prevalent neglected tropical diseases tackled via the World Health Organization preventive chemotherapy strategy. While for some of these diseases there is optimism that currently available drugs will be sufficient to achieve the proposed elimination goals, for others-particularly onchocerciasis-there is a growing consensus that novel therapeutic options will be needed. Since in this area no high return of investment is possible, minimizing wasted money and resources is essential. Here, we use illustrative results to show how mathematical modeling can guide the drug development pathway, yielding resource-saving and efficiency payoffs, from the refinement of target product profiles and intended context of use to the design of clinical trials.
Asunto(s)
Oncocercosis , Esquistosomiasis , Medicina Tropical , Desarrollo de Medicamentos , Humanos , Enfermedades Desatendidas/tratamiento farmacológico , Enfermedades Desatendidas/prevención & control , Oncocercosis/tratamiento farmacológico , Oncocercosis/prevención & control , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/prevención & controlRESUMEN
BACKGROUND: Mass drug administration (MDA) of ivermectin for onchocerciasis has been disrupted by the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modelling can help predict how missed/delayed MDA will affect short-term epidemiological trends and elimination prospects by 2030. METHODS: Two onchocerciasis transmission models (EPIONCHO-IBM and ONCHOSIM) are used to simulate microfilarial prevalence trends, elimination probabilities and age profiles of Onchocerca volvulus microfilarial prevalence and intensity for different treatment histories and transmission settings, assuming no interruption, a 1-y (2020) interruption or a 2-y (2020-2021) interruption. Biannual MDA or increased coverage upon MDA resumption are investigated as remedial strategies. RESULTS: Programmes with shorter MDA histories and settings with high pre-intervention endemicity will be the most affected. Biannual MDA is more effective than increasing coverage for mitigating COVID-19's impact on MDA. Programmes that had already switched to biannual MDA should be minimally affected. In high-transmission settings with short treatment history, a 2-y interruption could lead to increased microfilarial load in children (EPIONCHO-IBM) and adults (ONCHOSIM). CONCLUSIONS: Programmes with shorter (annual MDA) treatment histories should be prioritised for remedial biannual MDA. Increases in microfilarial load could have short- and long-term morbidity and mortality repercussions. These results can guide decision-making to mitigate the impact of COVID-19 on onchocerciasis elimination.
Asunto(s)
COVID-19/epidemiología , Control de Enfermedades Transmisibles/organización & administración , Filaricidas/uso terapéutico , Ivermectina/uso terapéutico , Oncocercosis/epidemiología , Oncocercosis/prevención & control , Erradicación de la Enfermedad , Humanos , Administración Masiva de Medicamentos , Modelos Teóricos , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/prevención & control , Pandemias , Prevalencia , SARS-CoV-2RESUMEN
Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.
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COVID-19 , Medicina Tropical , Humanos , Enfermedades Desatendidas/epidemiología , Pandemias , SARS-CoV-2RESUMEN
INTRODUCTION: Moxidectin is a milbemycin endectocide recently approved for the treatment of human onchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemic in Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether the predominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient to achieve elimination in all endemic foci have refocussed attention upon alternative treatments. Moxidectin's stronger and longer microfilarial suppression compared to ivermectin in both phase II and III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination. AREAS COVERED: This work summarizes the chemistry and pharmacology of moxidectin, reviews the phase II and III clinical trials evidence on tolerability, safety, and efficacy of moxidectin versus ivermectin, and discusses the implications of moxidectin's current regulatory status. EXPERT OPINION: Moxidectin's superior clinical performance has the potential to substantially reduce times to elimination compared to ivermectin. If donated, moxidectin could mitigate the additional programmatic costs of biannual ivermectin distribution because, unlike other alternatives, it can use the existing community-directed treatment infrastructure. A pediatric indication (for children <12 years) and determination of its usefulness in onchocerciasis-loiasis co-endemic areas will greatly help fulfill the potential of moxidectin for the treatment and elimination of onchocerciasis.
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Antihelmínticos/administración & dosificación , Macrólidos/administración & dosificación , Oncocercosis/tratamiento farmacológico , Administración Oral , Animales , Antihelmínticos/efectos adversos , Erradicación de la Enfermedad , Humanos , Ivermectina/administración & dosificación , Ivermectina/efectos adversos , Macrólidos/efectos adversos , Administración Masiva de Medicamentos/métodos , Oncocercosis/epidemiologíaRESUMEN
As neglected tropical disease programs look to consolidate the successes of moving towards elimination, we need to understand the dynamics of transmission at low prevalence to inform surveillance strategies for detecting elimination and resurgence. In this special collection, modelling insights are used to highlight drivers of local elimination, evaluate strategies for detecting resurgence, and show the importance of rational spatial sampling schemes for several neglected tropical diseases (specifically schistosomiasis, soil-transmitted helminths, lymphatic filariasis, trachoma, onchocerciasis, visceral leishmaniasis, and gambiense sleeping sickness).
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Erradicación de la Enfermedad/estadística & datos numéricos , Enfermedades Desatendidas/diagnóstico , Vigilancia de la Población/métodos , Medicina Tropical , HumanosRESUMEN
Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.
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Ensayos Clínicos como Asunto/métodos , Filariasis Linfática/tratamiento farmacológico , Filaricidas/uso terapéutico , Oncocercosis/tratamiento farmacológico , Protocolos de Ensayos Clínicos como Asunto , Ensayos Clínicos como Asunto/estadística & datos numéricos , Simulación por Computador , Evaluación de Medicamentos/métodos , Evaluación de Medicamentos/estadística & datos numéricos , Humanos , Ivermectina/uso terapéutico , Modelos Biológicos , Oncocercosis/parasitología , Oncocercosis/transmisiónRESUMEN
The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.
Taenia solium est un cestode qui entraîne une charge intersectorielle économique et sanitaire considérable en provoquant une neurocysticercose humaine et une cysticercose porcine. La feuille de route sur les maladies tropicales négligées, publiée en 2012 par l'Organisation mondiale de la Santé (OMS), appelait à développer une stratégie de contrôle validée pour T. solium ; cependant, cette stratégie n'est pas encore disponible à l'heure actuelle. En 2019, l'OMS a lancé une procédure de consultation mondiale visant à préciser les objectifs de contrôle de T. solium après 2020, afin de rédiger une nouvelle feuille de route sur les maladies tropicales négligées. Deux groupes qui travaillent sur des modèles mathématiques de taeniasis et cysticercose (modèles cystiSim et EPICYST) ainsi qu'une série d'autres intervenants ont donc organisé un atelier pour fournir une contribution technique à cette consultation et développer un programme de recherche destiné à soutenir les efforts de réalisation des objectifs ultérieurs à 2020. L'atelier a donné naissance à une collaboration, CystiTeam, qui s'intéresse à la biologie des populations, à la dynamique de transmission, à l'épidémiologie et au contrôle de T. solium en employant des méthodes de modélisation mathématique. Le présent document retrace l'évolution du contrôle de T. solium, en particulier l'usage de la modélisation pour contribuer à atteindre les objectifs d'après 2020 en la matière. Nous abordons les diverses étapes de renforcement de la confiance accordée aux capacités prédictives des modèles mathématiques et informatiques existants sur la transmission de T. solium, notamment la comparaison, l'optimisation, le calibrage et la validation des modèles. Élargir le partenariat CystiTeam en intégrant d'autres groupes de recherche et intervenants, surtout ceux opérant dans différentes zones géographiques et endémiques, accroîtra les chances d'amélioration de l'applicabilité pour les modèles de transmission de T. solium, et permettra ainsi d'établir des stratégies de lutte contre la taeniasis et la cysticercose.
El cestodo Taenia solium es responsable de una importante carga sanitaria y económica transversal debido a la neurocisticercosis humana y la cisticercosis porcina. En la hoja de ruta de la Organización Mundial de la Salud (OMS) de 2012 sobre las enfermedades tropicales desatendidas se solicitaba la elaboración de una estrategia validada para el control de T. solium; sin embargo, dicha estrategia aún no está disponible. En 2019, la OMS inició una consulta mundial destinada a perfeccionar los objetivos de control de T. solium aplicables a partir de 2020 con miras a elaborar una hoja de ruta nueva sobre las enfermedades tropicales desatendidas. Consecuentemente, dos grupos que trabajan en modelos matemáticos de teniasis y cisticercosis (modelos cystiSim y EPICYST), junto con un grupo de otros interesados, organizaron un seminario para contribuir técnicamente a la consulta de la OMS y elaborar un plan de investigación a fin de apoyar los esfuerzos para lograr los objetivos a partir de 2020. El seminario impulsó la formación de un equipo de colaboración, CystiTeam, para abordar la biología de la población, la dinámica de la transmisión, la epidemiología y el control de T. solium mediante enfoques de modelos matemáticos. En el presente documento se describen las novedades en el control de T. solium y, en particular, la aplicación de modelos para ayudar a lograr los objetivos a partir de 2020 sobre el control de T. solium. Se analizan las etapas necesarias para mejorar la confianza en las capacidades de predicción de los modelos matemáticos y computacionales existentes sobre la transmisión de T. solium, incluyendo la comparación, el perfeccionamiento, el ajuste y la validación de los modelos. La ampliación de la asociación CystiTeam a otros grupos de investigación e interesados, en particular los que operan en diferentes zonas geográficas y endémicas, reforzará las perspectivas de mejorar la aplicabilidad de los modelos sobre las transmisión de T. solium para fundamentar las estrategias de control de la teniasis y la cisticercosis.
Asunto(s)
Cisticercosis/veterinaria , Neurocisticercosis/prevención & control , Taenia solium , Teniasis/prevención & control , Animales , Cisticercosis/prevención & control , Cisticercosis/transmisión , Humanos , Modelos Teóricos , Neurocisticercosis/transmisión , Porcinos , Organización Mundial de la Salud , Zoonosis/prevención & controlRESUMEN
BACKGROUND: The World Health Organization recommends monitoring Onchocerca volvulus Ov16 serology in children aged <10 years for stopping mass ivermectin administration. Transmission models can help to identify the most informative age groups for serological monitoring and investigate the discriminatory power of serology-based elimination thresholds. Model predictions depend on assumed age-exposure patterns and transmission efficiency at low infection levels. METHODS: The individual-based transmission model, EPIONCHO-IBM, was used to assess (1) the most informative age groups for serological monitoring using receiver operating characteristic curves for different elimination thresholds under various age-dependent exposure assumptions, including those of ONCHOSIM (another widely used model), and (2) the influence of within-human density-dependent parasite establishment (included in EPIONCHO-IBM but not ONCHOSIM) on positive predictive values for different serological thresholds. RESULTS: When assuming EPIONCHO-IBM exposure patterns, children aged <10 years are the most informative for seromonitoring; when assuming ONCHOSIM exposure patterns, 5-14 year olds are the most informative (as published elsewhere). Omitting density-dependent parasite establishment results in more lenient seroprevalence thresholds, even for higher baseline infection prevalence and shorter treatment durations. CONCLUSIONS: Selecting appropriate seromonitoring age groups depends critically on age-dependent exposure patterns. The role of density dependence on elimination thresholds largely explains differing EPIONCHO-IBM and ONCHOSIM elimination predictions.
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Envejecimiento , Modelos Biológicos , Oncocercosis/transmisión , Vigilancia de la Población/métodos , Pruebas Serológicas , Incertidumbre , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Factores SexualesRESUMEN
BACKGROUND: Density dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin. METHODOLOGY/PRINCIPAL FINDINGS: Density dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d'Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model. CONCLUSIONS/SIGNIFICANCE: This is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improving model predictions during MDA. We discuss possible ways in which such data may be collected as well as the importance of better understanding the effects of immunological responses on establishing parasites prior to and during ivermectin treatment.