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Structural Uncertainty in Onchocerciasis Transmission Models Influences the Estimation of Elimination Thresholds and Selection of Age Groups for Seromonitoring.

ABSTRACT: 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.

SUBMITTER: Hamley JID

PROVIDER: S-EPMC7289547 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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Project description:The onchocerciasis transmission models EPIONCHO and ONCHOSIM have been independently developed and used to explore the feasibility of eliminating onchocerciasis from Africa with mass (annual or biannual) distribution of ivermectin within the timeframes proposed by the World Health Organization (WHO) and endorsed by the 2012 London Declaration on Neglected Tropical Diseases (i.e. by 2020/2025). Based on the findings of our previous model comparison, we implemented technical refinements and tested the projections of EPIONCHO and ONCHOSIM against long-term epidemiological data from two West African transmission foci in Mali and Senegal where the observed prevalence of infection was brought to zero circa 2007-2009 after 15-17 years of mass ivermectin treatment. We simulated these interventions using programmatic information on the frequency and coverage of mass treatments and trained the model projections using longitudinal parasitological data from 27 communities, evaluating the projected outcome of elimination (local parasite extinction) or resurgence. We found that EPIONCHO and ONCHOSIM captured adequately the epidemiological trends during mass treatment but that resurgence, while never predicted by ONCHOSIM, was predicted by EPIONCHO in some communities with the highest (inferred) vector biting rates and associated pre-intervention endemicities. Resurgence can be extremely protracted such that low (microfilarial) prevalence between 1% and 5% can be maintained for 3-5 years before manifesting more prominently. We highlight that post-treatment and post-elimination surveillance protocols must be implemented for long enough and with high enough sensitivity to detect possible residual latent infections potentially indicative of resurgence. We also discuss uncertainty and differences between EPIONCHO and ONCHOSIM projections, the potential importance of vector control in high-transmission settings as a complementary intervention strategy, and the short remaining timeline for African countries to be ready to stop treatment safely and begin surveillance in order to meet the impending 2020/2025 elimination targets.

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Structural Uncertainty in Onchocerciasis Transmission Models Influences the Estimation of Elimination Thresholds and Selection of Age Groups for Seromonitoring.

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