Epidemiological and molecular investigations of a point-source outbreak of Dracunculus medinensis infecting humans and dogs in Chad: a cross-sectional study.

BACKGROUND: Dracunculiasis (also known as Guinea worm disease), caused by the Dracunculus medinensis nematode, is progressing towards eradication, with a reduction in cases from 3·5 million cases in the mid-1980s to only 54 human cases at the end of 2019. Most cases now occur in Chad. On April 19, 2019, a 19-year-old woman presented with D medinensis in an area within the Salamat region of Chad, where the disease had not been previously reported. We aimed to investigate the connection between this case and others detected locally and elsewhere in Chad using a combination of epidemiological and genetic approaches. METHODS: In this cross-sectional field study, we conducted household case searches and informal group interviews in the Bogam, Liwi, and Tarh villages in Chad. All community members including children were eligible for participation in the outbreak investigation. Adult female D medinensis associated with this outbreak were collected for genetic analysis (18 from humans and two from dogs). Four mitochondrial genes and 22 nuclear microsatellite markers were used to assess relatedness of worms associated with the outbreak in comparison with other worms from elsewhere in Chad. FINDINGS: Between April 12 and Sept 6, 2019, we identified 22 human cases and two canine cases of dracunculiasis associated with 15 households. Six (40%) of the 15 affected households had multiple human or canine cases within the household. Most cases of dracunculiasis in people were from three villages in Salamat (21 [95%] of 22 cases), but one case was detected nearly 400 km away in Sarh city (outside the Salamat region). All people with dracunculiasis reported a history of consuming fish and unfiltered water. Worms associated with this outbreak were genetically similar and shared the same maternal lineage. INTERPRETATION: Molecular epidemiological results suggest a point-source outbreak that originated from a single female D medinensis, rather than newly identified sustained local transmission. The failure of the surveillance system to detect the suspected canine infection in 2018 highlights the challenge of canine D medinensis detection, particularly in areas under passive surveillance. Human movement can also contribute to dracunculiasis spread over long distances. FUNDING: The Carter Center.

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

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.

Correlates of Variation in Guinea Worm Burden among Infected Domestic Dogs.

The Guinea Worm Eradication Program has been extraordinarily successful-in 2019, there were 53 human cases reported, down from the estimated 3.5 million in 1986. Yet the occurrence of Guinea worm in dogs is a challenge to eradication efforts, and underlying questions about transmission dynamics remain. We used routine surveillance data to run negative binomial regressions predicting worm burden among infected dogs in Chad. Of 3,371 infected dogs reported during 2015-2018, 38.5% had multiple worms. A multivariable model showed that the number of dogs in the household was negatively associated with worm burden (adjusted incidence rate ratio [AIRR] = 0.95, 95% CI: 0.93-0.97, P < 0.0001) after adjusting for dog age (AIRR = 0.99, 95% CI: 0.96-1.01, P > 0.1). This could relate to the amount of infective inocula (e.g., contaminated food or water) shared by multiple dogs in a household. Other significant univariable associations with worm burden included dog history of Guinea worm infection (IRR = 1.30, 95% CI: 1.18-1.45) and dog owners who were hunters (IRR = 0.78, 95% CI: 0.62-0.99, P < 0.05) or farmers (IRR = 0.83, 95% CI: 0.77-0.90, P < 0.0001). Further analysis showed that the number of dogs in the household was significantly and positively correlated with nearly all other independent variables (e.g., owner occupation: farmer, fisherman, or hunter; dog age, sex, and history of Guinea worm). The associations we identified between worm burden and dogs per household, and dogs per household and owner characteristics should be further investigated with more targeted studies.

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

BACKGROUND: Guinea worm-Dracunculus medinensis-was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 54 human cases reported globally in 2019. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs are currently the principal reservoir on infection and key to maintaining transmission in that country. PRINCIPAL FINDINGS: In an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms are D. medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases. CONCLUSIONS: This work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs aiming to interrupt disease transmission should stay aware of the possible emergence of unusual epidemiology as pathogens approach elimination.

Identifying correlates of Guinea worm (Dracunculus medinensis) infection in domestic dog populations.

Few human infectious diseases have been driven as close to eradication as dracunculiasis, caused by the Guinea worm parasite (Dracunculus medinensis). The number of human cases of Guinea worm decreased from an estimated 3.5 million in 1986 to mere hundreds by the 2010s. In Chad, domestic dogs were diagnosed with Guinea worm for the first time in 2012, and the numbers of infected dogs have increased annually. The presence of the parasite in a non-human host now challenges efforts to eradicate D. medinensis, making it critical to understand the factors that correlate with infection in dogs. In this study, we evaluated anthropogenic and environmental factors most predictive of detection of D. medinensis infection in domestic dog populations in Chad. Using boosted regression tree models to identify covariates of importance for predicting D. medinensis infection at the village and spatial hotspot levels, while controlling for surveillance intensity, we found that the presence of infection in a village was predicted by a combination of demographic (e.g. fishing village identity, dog population size), geographic (e.g. local variation in elevation), and climatic (e.g. precipitation and temperature) factors, which differed between northern and southern villages. In contrast, the presence of a village in a spatial infection hotspot, was primarily predicted by geography and climate. Our findings suggest that factors intrinsic to individual villages are highly predictive of the detection of Guinea worm parasite presence, whereas village membership in a spatial infection hotspot is largely determined by location and climate. This study provides new insight into the landscape-scale epidemiology of a debilitating parasite and can be used to more effectively target ongoing research and possibly eradication and control efforts.