A framework for guiding integrated disease control measures through multipathogen surveillance

Abstract Global health programs have traditionally focused on single diseases. There is potential for synergy through integrated intervention delivery, particularly in areas with overlapping geographic disease burden, but there is limited methodology developed for assessing potential efficiency gains through integration. Here, we applied a measure of diversity, Rao’s quadratic index, to quantify multipathogen burden across two large-scale surveys: Bangladesh (90 clusters, 2,396 children) and Cambodia (100 clusters, 2,150 women). In both settings, we observed geographic clustering of multiple pathogens, indicating potential for more efficient, integrated disease control strategies. We assessed the efficiency of a multipathogen-targeted strategy compared to traditional single-pathogen approaches by calculating the percent reduction in the number of spatial clusters needed to reach 75% of the disease burden (infections or unvaccinated individuals) in a hypothetical intervention. In Bangladesh, integrating deworming with measles vaccination guided by Rao’s quadratic index improved efficiency by 15% for Ascaris lumbricoides, 31% for hookworm, and 38% for Trichuris trichiura, compared to a measles-focused approach. In Cambodia, a Rao-guided strategy performed similarly to the best single-pathogen strategy for Strongyloides stercoralis, and reduced the number of spatial clusters that would need to be targeted by 57% (lymphatic filariasis), 83% (Plasmodium falciparum), and 59% (Plasmodium vivax). We also found that higher multipathogen burden was significantly associated with lower household wealth, suggesting that Rao-guided strategies may be more effective in reaching under-resourced populations. These findings support the use of multipathogen burden metrics to guide integrated program delivery, offering potential for greater efficiency in disease control. Significance Statement Global health programs often focus on single diseases, despite many communities facing multiple, geographical overlapping infections. In this study, we applied a diversity metric, Rao’s quadratic index, to identify multipathogen burden in large-scale studies in Bangladesh and Cambodia. We found that interventions guided by multipathogen burden substantially improved efficiency compared to single-pathogen strategies, reducing the number of areas needed to reach 75% of disease burden by 15-83% across infectious diseases in both settings. Multipathogen-motivated strategies also targeted populations with lower household wealth, where disease burden was highest. The approach offers a practical way to synthesize high-dimensional information across diverse diseases to inform more efficient integrated delivery platforms. Competing Interest Statement NCL reports consulting fees from the World Health Organization related to guidelines on neglected tropical diseases, which are outside the scope of the present work. Funding Statement This work was supported by the National Institutes of Health (R01AI166671 to BFA and R01AI179771 to NCL). JBC is a Chan Zuckerberg Biohub Investigator. 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: The study used only openly available human data that were originally located at: https://doi.org/10.1371/journal.pntd.0004699.s003 https://osf.io/cxb5e/overview 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 Code and Data Availability All data used in the study is publicly available and code used for all analyses is publicly available at: https://github.com/sbents/multipathogen.