RESUMEN
BACKGROUND: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. METHODS: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. RESULTS: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. CONCLUSIONS: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.
Asunto(s)
Ivermectina , Macrólidos , Oncocercosis , Macrólidos/uso terapéutico , Macrólidos/economía , Macrólidos/administración & dosificación , Oncocercosis/tratamiento farmacológico , Oncocercosis/prevención & control , Oncocercosis/economía , Oncocercosis/epidemiología , Humanos , Ivermectina/economía , Ivermectina/uso terapéutico , Ivermectina/administración & dosificación , Administración Masiva de Medicamentos/economía , Erradicación de la Enfermedad/economía , Análisis Costo-BeneficioRESUMEN
BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.
Asunto(s)
Erradicación de la Enfermedad , Schistosoma mansoni , Esquistosomiasis mansoni , Humanos , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/prevención & control , Niño , Animales , Adolescente , Schistosoma mansoni/efectos de los fármacos , Adulto , Prevalencia , Administración Masiva de Medicamentos , Salud Pública , Adulto Joven , Preescolar , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificación , Masculino , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.
Asunto(s)
Análisis Costo-Beneficio , Recuento de Huevos de Parásitos , Schistosoma mansoni , Esquistosomiasis mansoni , Humanos , Animales , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/prevención & control , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/epidemiología , Antihelmínticos/uso terapéutico , Antihelmínticos/economía , Femenino , Masculino , Esquistosomiasis/diagnóstico , Esquistosomiasis/prevención & control , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Adulto , Adolescente , Niño , Quimioprevención/economía , Quimioprevención/métodos , Adulto Joven , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.
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Albendazol , Filariasis Linfática , Filaricidas , Ivermectina , Administración Masiva de Medicamentos , Filariasis Linfática/tratamiento farmacológico , Filariasis Linfática/prevención & control , Filariasis Linfática/epidemiología , Filariasis Linfática/transmisión , Humanos , Animales , Filaricidas/uso terapéutico , Filaricidas/administración & dosificación , Albendazol/administración & dosificación , Albendazol/uso terapéutico , Ivermectina/administración & dosificación , Ivermectina/uso terapéutico , Prevalencia , Anopheles/parasitología , Erradicación de la Enfermedad/métodos , Wuchereria bancrofti/efectos de los fármacos , Dietilcarbamazina/administración & dosificación , Dietilcarbamazina/uso terapéutico , Quimioterapia CombinadaRESUMEN
Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.
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COVID-19 , Enfermedades Desatendidas , Medicina Tropical , Enfermedades Desatendidas/prevención & control , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Modelos Teóricos , Organización Mundial de la Salud , SARS-CoV-2 , Toma de Decisiones , Salud GlobalRESUMEN
BACKGROUND: The World Health Organization previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals. METHODS: We used 2 independently developed, individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multiyear program to maintain the morbidity control and the EPHP goals. RESULTS: We found that, in moderate-prevalence settings, once the morbidity control and EPHP goals are reached it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high-transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence. CONCLUSIONS: To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.
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Antihelmínticos , Esquistosomiasis mansoni , Esquistosomiasis , Animales , Antihelmínticos/uso terapéutico , Humanos , Administración Masiva de Medicamentos , Prevalencia , Schistosoma mansoni , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis mansoni/tratamiento farmacológicoRESUMEN
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
Vector-borne diseases are a major public health concern inflicting high levels of disease morbidity and mortality. Vector control is one of the principal methods available to manage infectious disease burden. One approach, releasing modified vectors (such as sterile or GM mosquitoes) Into the wild population has been suggested as an effective method of vector control. However, the effects of dispersal and the spatial distribution of disease vectors (such as mosquitoes) remain poorly studied. Here, we develop a novel mathematical framework using an integrodifference equation (discrete in time and continuous in space) approach to understand the impact of releasing sterile insects into the wild population in a spatially explicit environment. We prove that an optimal release strategy exists and show how it may be characterized by defining a sensitivity variable and an adjoint system. Using simulations, we show that the optimal strategy depends on the spatially varying carrying capacity of the environment.
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Modelos Biológicos , Control de Mosquitos/métodos , Mosquitos Vectores/genética , Control Biológico de Vectores/métodos , Enfermedades Transmitidas por Vectores/prevención & control , Aedes/genética , Animales , Animales Modificados Genéticamente , Simulación por Computador , Humanos , Enfermedades Transmitidas por Vectores/epidemiologíaRESUMEN
Underdominance gene drives are frequency-dependent drives that aim to spread a desired homozygote genotype within a population. When the desired homozygote is released above a threshold frequency, heterozygote fitness disadvantage acts to drive the desired trait to fixation. Underdominance drives have been proposed as a way to control vector-borne disease through population suppression and replacement in a spatially contained and reversible way-benefits that directly address potential safety concerns with gene drives. Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair of chromosomes at the same locus or homozygously on different pairs at different loci, genetic lethality that affects both sexes or only females, and bi-sex or male-only releases. Further, the different genetic and ecological fitness costs that can arise from genetic modification and artificial rearing are investigated through their effect on the population threshold frequency that is required to trigger the drive mechanism. We show that male-only releases must be significantly larger than bi-sex releases to trigger the underdominance drive. In addition, we find that female-specific lethality averts a higher percentage of disease cases over a control period than does bi-sex lethality. Decreases in the genetic fitness of the engineered homozygotes can increase the underdominance threshold substantially, but we find that the mating success of transgenic mosquitoes with wild-type females (influenced by a lack of competitiveness or the evolution of behavioural resistance in the form of active female mate preference) and the longevity of artificially-reared mosquitoes are vitally important to the success chances of underdominance based gene drive control efforts.
Asunto(s)
Aedes/genética , Tecnología de Genética Dirigida/métodos , Control de Mosquitos/métodos , Mosquitos Vectores/genética , Animales , Animales Modificados Genéticamente , Femenino , Masculino , Modelos Genéticos , Dinámica Poblacional , Factores SexualesRESUMEN
BACKGROUND: The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes. RESULTS: An optimal control framework based on coupled models of mosquito population dynamics and malaria epidemiology is used to investigate the cost-effectiveness of combining vector control with drug therapies in homogeneous environments with and without vector migration. The costs of endemic malaria are weighed against the costs of administering artemisinin therapies and releasing modified mosquitoes using various cost structures. Larval density dependence is shown to reduce the cost-effectiveness of conventional sterile insect releases compared with transgenic mosquitoes with a late-acting lethal gene. Using drug treatments can reduce the critical vector control release ratio necessary to cause disease fadeout. CONCLUSIONS: Combining vector control and drug therapies is the most effective and efficient use of resources, and using optimized implementation strategies can substantially reduce costs.
Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Control de Enfermedades Transmisibles/métodos , Malaria Falciparum/prevención & control , Control de Mosquitos , Mosquitos Vectores , Combinación de Medicamentos , Humanos , Modelos Teóricos , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/fisiologíaRESUMEN
Many animals spend large parts of their lives in groups. Within such groups, they need to find efficient ways of dividing available resources between them. This is often achieved by means of a dominance hierarchy, which in its most extreme linear form allocates a strict priority order to the individuals. Once a hierarchy is formed, it is often stable over long periods, but the formation of hierarchies among individuals with little or no knowledge of each other can involve aggressive contests. The outcome of such contests can have significant effects on later contests, with previous winners more likely to win (winner effects) and previous losers more likely to lose (loser effects). This scenario has been modelled by a number of authors, in particular by Dugatkin. In his model, individuals engage in aggressive contests if the assessment of their fighting ability relative to their opponent is above a threshold [Formula: see text]. Here we present a model where each individual can choose its own value [Formula: see text]. This enables us to address questions such as how aggressive should individuals be in order to take up one of the first places in the hierarchy? We find that a unique strategy evolves, as opposed to a mixture of strategies. Thus, in any scenario there exists a unique best level of aggression, and individuals should not switch between strategies. We find that for optimal strategy choice, the hierarchy forms quickly, after which there are no mutually aggressive contests.
Asunto(s)
Teoría del Juego , Predominio Social , Agresión , Animales , Conducta Animal , Evolución Biológica , Conceptos Matemáticos , Modelos Biológicos , Densidad de PoblaciónRESUMEN
Animals that live in groups commonly form themselves into dominance hierarchies which are used to allocate important resources such as access to mating opportunities and food. In this paper, we develop a model of dominance hierarchy formation based upon the concept of winner and loser effects using a simulation-based model and consider the linearity of our hierarchy using existing and new statistical measures. Two models are analysed: when each individual in a group does not know the real ability of their opponents to win a fight and when they can estimate their opponents' ability every time they fight. This estimation may be accurate or fall within an error bound. For both models, we investigate if we can achieve hierarchy linearity, and if so, when it is established. We are particularly interested in the question of how many fights are necessary to establish a dominance hierarchy.
Asunto(s)
Modelos Biológicos , Predominio Social , Agresión , Animales , Conducta Animal , Simulación por Computador , Modelos Lineales , Conceptos Matemáticos , Dinámicas no LinealesRESUMEN
BACKGROUND: A recent study comparing results of multiple cost-effectiveness analyses (CEAs) in a hypothetical population found that monoclonal antibody (mAb) immunoprophylaxis for respiratory syncytial virus (RSV) in infants averted fewer medically attended cases when estimated using dynamic transmission models (DTMs) versus static cohort models (SCMs). We aimed to investigate whether model calibration or parameterization could be the primary driver of inconsistencies between SCM and DTM predictions. METHODS: A recently published DTM evaluating the CEA of infant mAb immunoprophylaxis in England and Wales (EW) was selected as the reference model. We adapted our previously published SCM for US infants to EW by utilizing the same data sources used by the DTM. Both models parameterized mAb efficacy from a randomized clinical trial (RCT) that estimated an average efficacy of 74.5% against all medically attended RSV episodes and 62.1% against RSV hospitalizations. To align model assumptions, we modified the SCM to incorporate waning efficacy. Since the estimated indirect effects from the DTM were small (i.e., approximately 100-fold smaller in magnitude than direct effects), we hypothesized that alignment of model parameters should result in alignment of model predictions. Outputs for model comparison comprised averted hospitalizations and averted GP visits, estimated for seasonal (S) and seasonal-with-catchup (SC) immunization strategies. RESULTS: When we aligned the SCM intervention parameters to DTM intervention parameters, significantly more averted hospitalizations were predicted by the SCM (S: 32.3%; SC: 51.3%) than the DTM (S: 17.8%; SC: 28.6%). The SCM most closely replicated the DTM results when the initial efficacy of the mAb intervention was 62.1%, leading to an average efficacy of 39.3%. Under this parameterization the SCM predicted 17.4% (S) and 27.7% (SC) averted hospitalizations. Results were similar for averted GP visits. CONCLUSIONS: Parameterization of the RSV mAb intervention efficacy is a plausible primary driver of differences between SCM versus DTM model predictions.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Lactante , Humanos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/epidemiología , Gales , Anticuerpos Monoclonales/uso terapéutico , InmunizaciónRESUMEN
Repeated distribution of preventative chemotherapy (PC) by mass drug administration forms the mainstay of transmission control for five of the 20 recognised neglected tropical diseases (NTDs); soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. The efficiency of such programmes is reliant upon participants swallowing the offered treatment consistently at each round. This is measured by compliance, defined as the proportion of eligible participants swallowing treatment. Individually linked longitudinal compliance data is important for assessing the potential impact of MDA-based control programmes, yet this accurate monitoring is rarely implemented in those for NTDs. Longitudinal compliance data reported by control programmes globally for the five (PC)-NTDs since 2016 is examined, focusing on key associations of compliance with age and gender. PubMed and Web of Science was searched in January 2022 for articles written in English and Spanish, and the subsequent extraction adhered to PRISMA guidelines. Study title screening was aided by Rayyan, a machine learning software package. Studies were considered for inclusion if primary compliance data was recorded for more than one time point, in a population larger than 100 participants. All data analysis was conducted in R. A total of 89 studies were identified containing compliance data, 57 were longitudinal studies, of which 25 reported individually linked data reported by varying methods. The association of increasing age with the degree of systematic treatment was commonly reported. The review is limited by the paucity of data published on this topic. The varying and overlapping terminologies used to describe coverage (receiving treatment) and compliance (swallowing treatment) is reviewed. Consequently, it is recommended that WHO considers clearly defining the terms for coverage, compliance, and longitudinal compliance which are currently contradictory across their NTD treatment guidelines. This review is registered with PROSPERO (number: CRD42022301991).
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Helmintos , Oncocercosis , Esquistosomiasis , Medicina Tropical , Animales , Humanos , Administración Masiva de Medicamentos , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Esquistosomiasis/prevención & control , Oncocercosis/tratamiento farmacológico , Enfermedades Desatendidas/tratamiento farmacológico , Enfermedades Desatendidas/prevención & control , Enfermedades Desatendidas/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'.
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Oncocercosis , Humanos , Oncocercosis/tratamiento farmacológico , Oncocercosis/epidemiología , Oncocercosis/prevención & control , Ivermectina , Administración Masiva de Medicamentos , África/epidemiología , Enfermedades DesatendidasRESUMEN
BACKGROUND: In January 2021, the World Health Organization published the 2021-2030 roadmap for the control of neglected tropical diseases (NTDs). The goal for schistosomiasis is to achieve elimination as a public health problem (EPHP) and elimination of transmission (EOT) in 78 and 25 countries (by 2030), respectively. Mass drug administration (MDA) of praziquantel continues to be the main strategy for control and elimination. However, as there is limited availability of praziquantel, it is important to determine what volume of treatments are required, who should be targeted and how frequently treatment must be administered to eliminate either transmission or morbidity caused by infection in different endemic settings with varied transmission intensities. METHODS AND RESULTS: In this paper, we employ two individual-based stochastic models of schistosomiasis transmission developed independently by the Imperial College London (ICL) and University of Oxford (SCHISTOX) to determine the optimal treatment strategies to achieve EOT. We find that treating school-age children (SAC) only is not sufficient to achieve EOT within a feasible time frame, regardless of the transmission setting and observed age-intensity of infection profile. Both models show that community-wide treatment is necessary to interrupt transmission in all endemic settings with low, medium and high pristine transmission intensities. CONCLUSIONS: The required MDA coverage level to achieve either transmission or morbidity elimination depends on the prevalence prior to the start of treatment and the burden of infection in adults. The higher the worm burden in adults, the higher the coverage levels required for this age category through community-wide treatment programmes. Therefore, it is important that intensity and prevalence data are collected in each age category, particularly from SAC and adults, so that the correct coverage level can be calculated and administered.
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Antihelmínticos , Esquistosomiasis mansoni , Esquistosomiasis , Animales , Antihelmínticos/uso terapéutico , Humanos , Administración Masiva de Medicamentos , Praziquantel/uso terapéutico , Prevalencia , Schistosoma mansoni , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/prevención & controlRESUMEN
BACKGROUND: Soil-transmitted helminths (STH) and schistosome parasites are highly aggregated within the human population. The probability distribution of worms per person is described well by the negative binomial probability distribution with aggregation parameter, k, which varies inversely with parasite clustering. The relationship between k and prevalence in defined populations subject to mass drug administration is not well understood. METHODS AND RESULTS: We use statistical methods to estimate k using two large independent datasets for STH and schistosome infections from India and Niger, respectively, both of which demonstrate increased aggregation of parasites in a few hosts, as the prevalence of infections declines across the dataset. CONCLUSIONS: A greater attention needs to be given in monitoring and evaluation programmes to find and treat the remaining aggregates of parasites.
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Helmintiasis , Helmintos , Parásitos , Animales , Humanos , Helmintiasis/tratamiento farmacológico , Prevalencia , Suelo/parasitología , SchistosomaRESUMEN
Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5-14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R0) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA programmes.
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Inmunidad Adaptativa , Antihelmínticos/uso terapéutico , Administración Masiva de Medicamentos/normas , Esquistosomiasis/inmunología , Esquistosomiasis/transmisión , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Masculino , Administración Masiva de Medicamentos/estadística & datos numéricos , Modelos Teóricos , Morbilidad , Prevalencia , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The 2030 goal for schistosomiasis is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-age children (SAC) as a central pillar of the strategy. However, due to coronavirus disease 2019, many mass treatment campaigns for schistosomiasis have been halted, with uncertain implications for the programmes. METHODS: We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni and S. haematobium. RESULTS: For both S. mansoni and S. haematobium in moderate- and some high-prevalence settings, the disruption may delay the goal by up to 2 y. In some high-prevalence settings, EPHP is not achievable with current strategies and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and the stage of the programme. CONCLUSIONS: Schistosomiasis MDA programmes in medium- and high-prevalence areas should restart as soon as is feasible and mitigation strategies may be required in some settings.
Asunto(s)
COVID-19/epidemiología , Control de Enfermedades Transmisibles/organización & administración , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/prevención & control , Esquistosomiasis/epidemiología , Esquistosomiasis/prevención & control , Animales , Humanos , Administración Masiva de Medicamentos , Modelos Teóricos , Pandemias , Salud Pública , SARS-CoV-2 , Schistosoma haematobium , Esquistosomiasis mansoniRESUMEN
BACKGROUND: Schistosomiasis remains an endemic parasitic disease causing much morbidity and, in some cases, mortality. The World Health Organization (WHO) has outlined strategies and goals to combat the burden of disease caused by schistosomiasis. The first goal is morbidity control, which is defined by achieving less than 5% prevalence of heavy intensity infection in school-aged children (SAC). The second goal is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection in SAC is reduced to less than 1%. Mass drug administration (MDA) of praziquantel is the main strategy for control. However, there is limited availability of praziquantel, particularly in Africa where there is high prevalence of infection. It is therefore important to explore whether the WHO goals can be achieved using the current guidelines for treatment based on targeting SAC and, in some cases, adults. Previous modelling work has largely focused on Schistosoma mansoni, which in advance cases can cause liver and spleen enlargement. There has been much less modelling of the transmission of Schistosoma haematobium, which in severe cases can cause kidney damage and bladder cancer. This lack of modelling has largely been driven by limited data availability and challenges in interpreting these data. RESULTS: In this paper, using an individual-based stochastic model and age-intensity profiles of S. haematobium from two different communities, we calculate the probability of achieving the morbidity and EPHP goals within 15 years of treatment under the current WHO treatment guidelines. We find that targeting SAC only can achieve the morbidity goal for all transmission settings, regardless of the burden of infection in adults. The EPHP goal can be achieved in low transmission settings, but in some moderate to high settings community-wide treatment is needed. CONCLUSIONS: We show that the key determinants of achieving the WHO goals are the precise form of the age-intensity of infection profile and the baseline SAC prevalence. Additionally, we find that the higher the burden of infection in adults, the higher the chances that adults need to be included in the treatment programme to achieve EPHP.