Synthesising environmental, epidemiological, and genetic data to assist decision making for onchocerciasis elimination

Background Population genetics is crucial for understanding the transmission dynamics of diseases like onchocerciasis. Landscape genetics identifies the ecological features that impact genetic variation between sampling sites. Here, we have used a landscape genetics framework to understand the relationship between environmental features and gene flow of the filarial parasite Onchocerca volvulus and of its intermediate host and vector, blackflies in the genus Simulium . We analysed samples from the ecological transition region separating the savannah and forest ecological regions of Ghana, where the transmission of O. volvulus has persisted despite almost half a century of onchocerciasis control efforts. Methods We generated a baseline microfilarial prevalence map from the point estimates of pre-ivermectin microfilarial prevalence from 47 locations in the study area. We analysed mitochondrial data from 164 parasites and 93 blackflies collected from 15 communities and four breeding sites, respectively. We estimated population genetic diversity and identified correlations with environmental variables. Finally, we compared baseline prevalence maps to movement suitability maps that were based on significant environmental variables. Results We found that the resistance surfaces derived from elevation (r = 0.793, p = 0.005) and soil moisture (r = 0.507, p = 0.002) were significantly associated with genetic distance between parasite sampling locations. Similarly, for the vector populations, the resistance surfaces derived from soil moisture (r = 0.788, p = 0.0417) and precipitation (r = 0.835, p = 0.0417) were significant. The correlation between the baseline parasite prevalence map and the parasite resistance surface map was stronger than the correlation between baseline prevalence and the vector resistance surface map. The central parts of the transition region which were conducive for both the parasite and the vector gene flow were most strongly associated with high baseline onchocerciasis prevalence. Conclusions We present a framework for incorporating environmental, genetic, and prevalence data for identifying when ecological conditions are favourable for onchocerciasis transmission between communities. We identified areas with higher suitability for parasite and vector gene flow, which ultimately might help us gain deeper insights into defining transmission zones for onchocerciasis. Furthermore, this framework is translatable to other onchocerciasis endemic areas and to other vector-borne diseases. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funding from UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) to SMH (P21-00481). HS was supported by Australian Government Research Training Program Scholarship, a La Trobe Graduate Research Scholarship and a La Trobe University Full-Fee Research Scholarship. ### 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 source data for onchocerciasis prevalence that are openly available at the ESPEN data portal (https://espen.afro.who.int/tools-resources/download-data). 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The parasite sequence data are available at NCBI (Accession #: PRJNA560089), and the blackfly sequence data have been uploaded to EMBL-EBI (Accession #: PRJEB57094). The onchocerciasis prevalence data were obtained from the ESPEN data portal, and the sources for the environmental data are provided in the supplementary information. The scripts for the analysis pipeline are uploaded to the GitHub repository. [https://github.com/himal2007/landscape\_genetics\_ghana][1] * BCI : Bayesian credible interval BIC : Bayesian information criteria DAPC : Discriminant analysis of principal components DNA : Deoxyribonucleic Acid EBI : European Bioinformatics Institute EMBL : European Molecular Biology Laboratory ENA : European Nucleotide Archive ESPEN : Expanded Special Project for Elimination of Neglected Tropical Disease INLA : Integrated nested Laplace approximations MDAi : Mass drug administration with ivermectin MLPE : Maximum likelihood population effects MMRR : Mixed matrix regression with randomisation NCBI : National centre for biotechnology information OCP : Onchocerciasis Control Programme PCA : Principal component analysis SD : Standard deviation SE : Standard error SNP : Single nucleotide polymorphism SOR : Sub-optimal response [1]: https://github.com/himal2007/landscape_genetics_ghana