
medrxiv.orgCharacterizing the relative strength of metapopulation dynamics in measles persistenceBackground/Aims Measles is a highly infectious, vaccine-preventable disease that remains persistent across much of the world despite continued large-scale control efforts. Local dynamics of measles are shaped by births of susceptible individuals and seasonal drivers of transmission, while broader regional dynamics are shaped by population mobility and metapopulation connectivity. Incidence data, useful for tracking the progress of measles control, are frequently reported only at the aggregate level (e.g., states/provinces), and persistence at this scale may arise because of the independent persistence in all local sub-units or because of regional metapopulation dynamics. Disentangling the contribution of local versus regional persistence is critical in identifying effective strategies for control. Methods/Results We show, as vaccination reduces local measles prevalence, metapopulation colonization and extinction events dominate regional persistence. This manifests as a change in the seasonal distribution of cases throughout the year; incidence becomes more uniformly distributed through the year even with no change in underlying seasonal drivers. We demonstrate this using: 1) a seasonally forced, stochastic metapopulation compartmental model; 2) historical measles incidence in the USA; and 3) recent subnational-level measles incidence in Nigeria. We create a novel, scale-free measure to quantify the contribution of metapopulation dynamics to persistence, roundness, defined as the geometric mean of the scaled maximum and minimum monthly incidence. A low value of roundness indicates strong local persistence dominated by the seasonal attractor, while a high value indicates strong metapopulation persistence. We illustrate the properties of this measure using simulations and observed data. In the USA, roundness nearly doubled after the introduction of the measles-containing vaccine. In Nigeria, roundness is well correlated with observed vaccine coverage, with a Pearson's r of 0.70 (95% CI: 0.57, 0.80), discriminating between northern states dominated by local persistence of measles and southern states where persistence is maintained by regional dynamics. Conclusion Identifying how measles persists is important in its control; vaccination strategies may differ if persistence is largely local, or if persistence is driven by connectivity from surrounding areas, even where yearly incidence is comparable. Our approach can be valuable areas where other measures (connectivity, mobility, laboratory confirmed illness) are not widely available. ### Competing Interest Statement The authors have declared no competing interest. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study does not use any individually-identifiable data. Rather, all data used are either aggregated at the spatial and temporal level (e.g., months, first-level administrative units, i.e., ADM1). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Measles model parametrization data are available from Dalziel et. al through the epimdr2 package on GitHub. Historic measles time series data in the United States is available through Project Tycho. Proposals for aggregated case-based in Nigeria should be directed to the WHO. To gain access, data requestors will need to sign a data access agreement. These data are also publicly available in a similar format from the Nigeria Centre for Disease Control and Prevention. <https://github.com/objornstad/epimdr2> <https://www.tycho.pitt.edu/dataset/api/> <https://ncdc.gov.ng/data> NSF-NIH-NIFA (National Science Foundation - National Institutes of Health - National Institute of Food and Agriculture) Gates Foundation, https://ror.org/0456r8d26