부산대학교 도서관

Background: Guinea worm (Dracunculus medinensis) was detected in Chad in 2010 after a supposed ten-year absence, posing a challenge to the global eradication effort. Initiation of a village-based surveillance system in 2012 revealed a substantial number of dogs infected with Guinea worm, raising questions about paratenic hosts and cross-species transmission. Methodology/principal findings: We coupled genomic and surveillance case data from 2012-2018 to investigate the modes of transmission between dog and human hosts and the geographic connectivity of worms. Eighty-six variants across four genes in the mitochondrial genome identified 41 genetically distinct worm genotypes. Spatiotemporal modeling revealed worms with the same genotype ('genetically identical') were within a median range of 18.6 kilometers of each other, but largely within approximately 50 kilometers. Genetically identical worms varied in their degree of spatial clustering, suggesting there may be different factors that favor or constrain transmission. Each worm was surrounded by five to ten genetically distinct worms within a 50 kilometer radius. As expected, we observed a change in the genetic similarity distribution between pairs of worms using variants across the complete mitochondrial genome in an independent population. Conclusions/significance: In the largest study linking genetic and surveillance data to date of Guinea worm cases in Chad, we show genetic identity and modeling can facilitate the understanding of local transmission. The co-occurrence of genetically non-identical worms in quantitatively identified transmission ranges highlights the necessity for genomic tools to link cases. The improved discrimination between pairs of worms from variants identified across the complete mitochondrial genome suggests that expanding the number of genomic markers could link cases at a finer scale. These results suggest that scaling up genomic surveillance for Guinea worm may provide additional value for programmatic decision-making critical for monitoring cases and intervention efficacy to achieve elimination. Author summary: The global eradication effort for Guinea worm disease has dramatically decreased the global burden of the disease and enabled 187 countries to be certified by the World Health Organization to be free of endemic transmission. Despite this progress, several countries continue to have endemic transmission. In Chad, a long absence of reported cases was interrupted with the identification of new Guinea worm cases, prompting a substantial scale up of surveillance and intervention efforts. Here, we study the value of increasing genomic surveillance as a tool for programmatic evaluation of surveillance and intervention efforts in Chad. Linking surveillance and genomic samples, parsimonious spatial models help reveal a consistent geographic clustering of similar genetic sequences across Chad. We also demonstrate that expanding the sequencing can offer better resolution for distinguishing Guinea worm samples. In this retrospective study, we found evidence that scaling up genomic surveillance can be an important monitoring and evaluation tool for the eradication program in Chad. [ABSTRACT FROM AUTHOR]