Population genomic evidence that human and animal infections in Africa come from the same populations ofDracunculus medinensis

Abstract

24Background: Guinea worm -Dracunculus medinensis -was historically one of the major parasites of 25 humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as 26 efforts to interrupt transmission have reduced the annual burden of disease from millions of 27 infections per year in the 1980s to only 30 human cases reported globally last year. Despite the 28 enormous success of eradication efforts to date, one complication has arisen. Over the last few 29 years, hundreds of dogs have been found infected with this previously apparently anthroponotic 30 parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs 31 suggests that dogs may be key in maintaining transmission in that country.32 Results: In an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have 33 sequenced and compared the genomes of worms from dog, human and other animal infections. 34Confirming previous work with other molecular markers, we show that all of these worms are D. 35 medinensis, and that the same population of worms are causing both infections, can confirm the 36 suspected transmission between host species and detect signs of a population bottleneck due to the 37 eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were 38 no, or very few, worms present in the country during a 10-year absence of reported cases.39 Conclusions: This work reinforces the importance of adequate surveillance of both human and dog 40 populations in the Guinea worm eradication campaign and suggests that control programs should 41 stay aware of the possible emergence of unusual epidemiology as they approach elimination. 42 43 44 Background

Linked surveillance and genetic data uncovers programmatically relevant geographic scale of Guinea worm transmission in Chad

“…Nonetheless, genetic data collected from Guinea worms in Chad has already revealed research and programmatically relevant insights: human and dog hosts share a common genetic population suggesting transmission between species [47]. Genome wide data from a much smaller sample of worms confirms this finding [18]. We build upon those research insights using linked genetic and surveillance data from Chad to investigate the geographic connectivity of genetically defined worm populations.…”

“…Nineteen publicly available, untargeted mitochondria DNA sequences were downloaded from the European Nucleotide Archive [18]. Low quality bases with a minimum mapping quality of 20 were trimmed from the ends of reads.…”

“…Instead, bootstrap base recalibration was done using higher confidence calls (QD >2.0, FS >60.0, MQ <40.0, MQRankSum < −12.5, ReadPos-RankSum < −8.0) until the final calls converged (2-3 steps) [49]. Final variants were filtered using the following input parameters for GATK: FS <= 13.0 or missing, SOR <3.0 or missing, and −3.1 <= ReadRankPos, BaseQRankSum, MQRankSum, ClippingRankSum <= 3.1 [18]. Given the low sample size for recalibration, orthogonal variant calling was performed using the bcftools program [34].…”

“…In Chad, a decade long absence of reported cases was interrupted with a detected resurgence of Guinea worm cases in 2010 [45]; moreover, human cases continue to be reported [2] with a growing understanding of the role of animal reservoirs in transmission [10, 19, 38, 12, 47]. The stalled progress in Chad has led to a substantial increase in surveillance and programmatic efforts [1] as well as investments in research and novel interventions [18, 24].…”

Dogs and the classic route of Guinea Worm transmission: an evaluation of copepod ingestion

“…Recent data indicates that amphibians can be paratenic hosts and fish can be transport hosts, possibly contributing to this unusual epidemiology [4][5][6] . Two recent genomic studies showed that the D. medinensis derived from humans and animals are the same species and part of the same population of worms 7,8 . Thus, animal infections are a major concern for the eradication campaign as they can contaminate water sources, which thereby could increase the risk of human or additional animal infections 2 .…”