4.7 Article

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 221, Issue -, Pages S510-S518

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz674

Keywords

onchocerciasis; Ov16 serology; receiver operating characteristic curve; age-dependent exposure; density dependence; elimination; threshold; positive predictive value; ivermectin; microfilarial prevalence

Funding

  1. Bill and Melinda Gates Foundation via the NTD Modelling Consortium [OPP1184344]
  2. UK Medical Research Council (MRC Doctoral Training Programme)
  3. MRC
  4. UK Department for International Development (DFID) Joint Centre Funding under the MRC/DFID Concordat of the European Union European and Developing Countries Clinical Trials Partnership 2 [MR/R015600/1]
  5. Dutch Research Council [016.Veni.178.023]
  6. MRC [MR/R015600/1] Funding Source: UKRI

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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, EP IONCHO-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 agedependent 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 ONCHOSI M) on positive predictive values for different serological thresholds. Results. When assuming EPIONCHO-1BM 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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