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.

Investigating Flubendazole as an Anthelmintic Treatment for Guinea Worm (Dracunculus medinensis): Clinical Trials in Laboratory-Reared Ferrets and Domestic Dogs in Chad.

Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in domestic dog GW infections highlight the need for novel approaches. We conducted two clinical trials evaluating the efficacy of subcutaneously injected flubendazole (FBZ) as a treatment of GW infection. The first trial was conducted administering FBZ to experimentally infected ferrets; the second trial involved administering FBZ or a placebo to domestic dogs in the Republic of Tchad (Chad). We found contrasting results between the two trials. When adult gravid female GW were recovered from ferrets treated with FBZ, larvae presented in poor condition, with low to no motility, and an inability to infect copepods. Histopathology results indicated a disruption to morulae development within uteri of worms from treated animals. Results from the trial in Chadian dogs failed to indicate significant treatment of or prevention against GW infection. However, the difference in treatment intervals (1 month for ferrets and 6 months for dogs) or the timing of treatment (ferrets were treated later in the GW life-cycle than dogs) could explain different responses to the subcutaneous FBZ injections. Both trials provided valuable data guiding the use of FBZ in future trials (such as decreasing treatment intervals or increasing the dose of FBZ in dogs to increase exposure), and highlighted important lessons learned during the implementation of a field-based, double-blinded randomized control trial in Chadian dogs.

Assessment of the Chad guinea worm surveillance information system: A pivotal foundation for eradication.

BACKGROUND: In the absence of a vaccine or pharmacological treatment, prevention and control of Guinea worm disease is dependent on timely identification and containment of cases to interrupt transmission. The Chad Guinea Worm Eradication Program (CGWEP) surveillance system detects and monitors Guinea worm disease in both humans and animals. Although Guinea worm cases in humans has declined, the discovery of canine infections in dogs in Chad has posed a significant challenge to eradication efforts. A foundational information system that supports the surveillance activities with modern data management practices is needed to support continued program efficacy. METHODS: We sought to assess the current CGWEP surveillance and information system to identify gaps and redundancies and propose system improvements. We reviewed documentation, consulted with subject matter experts and stakeholders, inventoried datasets to map data elements and information flow, and mapped data management processes. We used the Information Value Cycle (IVC) and Data-Information System-Context (DISC) frameworks to help understand the information generated and identify gaps. RESULTS: Findings from this study identified areas for improvement, including the need for consolidation of forms that capture the same demographic variables, which could be accomplished with an electronic data capture system. Further, the mental models (conceptual frameworks) IVC and DISC highlighted the need for more detailed, standardized workflows specifically related to information management. CONCLUSIONS: Based on these findings, we proposed a four-phased roadmap for centralizing data systems and transitioning to an electronic data capture system. These included: development of a data governance plan, transition to electronic data entry and centralized data storage, transition to a relational database, and cloud-based integration. The method and outcome of this assessment could be used by other neglected tropical disease programs looking to transition to modern electronic data capture systems.

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.

Surveillance of Human Guinea Worm in Chad, 2010-2018.

The total number of Guinea worm cases has been reduced by 99.9% since the mid-1980s when the eradication campaign began. Today, the greatest number of cases is reported from Chad. In this report, we use surveillance data collected by the Chad Guinea Worm Eradication Program to describe trends in human epidemiology. In total, 114 human cases were reported during the years 2010-2018, with highest rates of containment (i.e., water contamination prevented) in the years 2013, 2014, 2016, and 2017 (P < 0.0001). Approximately half of case-patients were female, and 65.8% of case-patients were aged 30 years or younger (mean: 26.4 years). About 34.2% of case-patients were farmers. Cases were distributed across many ethnicities, with a plurality of individuals being of the Sara Kaba ethnicity (21.3%). Most cases occurred between the end of June and the end of August and were clustered in the Chari Baguirmi (35.9%) and Moyen Chari regions (30.1%). Cases in the northern Chari River area peaked in April and in August, with no clear temporal pattern in the southern Chari River area. History of travel within Chad was reported in 7.0% of cases, and male case-patients (12.5%) were more likely than female case-patients (1.7%) to have reported a history of travel (P = 0.03). Our findings confirm that human Guinea worm is geographically disperse and rare. Although the proportion of case-patients with travel history is relatively small, this finding highlights the challenge of surveillance in mobile populations in the final stages of the global eradication campaign.

Community-based Guinea worm surveillance in Chad: Evaluating a system at the intersection of human and animal disease.

BACKGROUND: Guinea worm is a debilitating parasitic infection targeted for eradication. Annual human cases have dropped from approximately 3,500,000 in 1986 to 54 in 2019. Recent identification of canine cases in Chad threatens progress, and therefore detection, prevention, and containment of canine cases is a priority. We investigated associations between disease knowledge, community engagement, and canine cases in Chad to identify opportunities to improve active surveillance. METHODS: We surveyed 627 respondents (villagers, local leaders, community volunteers, and supervisors) across 45 villages under active surveillance. Descriptive statistics were analyzed by respondent category. Logistic regression models were fitted to assess the effects of volunteer visit frequency on villager knowledge. RESULTS: Knowledge increased with respondents' associations with the Guinea worm program. Household visit frequency by community volunteers was uneven: 53.0% of villagers reported visits at least twice weekly and 21.4% of villagers reported never being visited. Villagers visited by a volunteer at least twice weekly had better knowledge of Guinea worm symptoms (OR: 1.71; 95% CI: 1.04-2.79) and could name more prevention strategies (OR: 2.04; 95% CI: 1.32-3.15) than villagers visited less frequently. The primary motivation to report was to facilitate care-seeking for people with Guinea worm. Knowledge of animal "containment" to prevent contamination of water, knowledge of rewards for reporting animal cases, and ability to name any reasons to report Guinea worm were each positively correlated with village canine case counts. CONCLUSIONS: Community volunteers play crucial roles in educating their neighbors about Guinea worm and facilitating surveillance. Additional training and more attentive management of volunteers and supervisors could increase visit frequency and further amplify their impact. Emphasizing links between animal and human cases, the importance of animal containment, and animal rewards might improve surveillance and canine case detection. The surveillance system should be evaluated routinely to expand generalizability of data and monitor changes over time.

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.

Investigation of Dracunculiasis Transmission among Humans, Chad, 2013-2017.

Dracunculiasis, slated for global eradication, typically is acquired by drinking stagnant water containing microscopic crustaceans (copepods) infected with Dracunculus medinensis larvae, causing clusters of case persons with worms emerging from the skin. Following a 10-year absence of reported cases, 9-26 sporadic human cases with few epidemiologic links have been reported annually in Chad since 2010; dog infections have also been reported since 2012. We conducted an investigation of human cases in Chad to identify risk factors. We conducted a case-control study using a standardized questionnaire to assess water and aquatic animal consumption, and links to dog infections. Case persons had laboratory-confirmed D. medinensis during 2013-2017. Each case person was matched to one to three controls without history of disease by age, gender, and residency in the village where the case person was likely infected. We estimated odds ratios (ORs) using simple conditional logistic regression. We enrolled 25 case persons with 63 matched controls. Dracunculiasis was associated with consumption of untreated water from hand-dug wells (OR: 13.4; 95% CI: 1.7-108.6), but neither with consumption of aquatic animals nor presence of infected dogs in villages. Unsafe water consumption remains associated with dracunculiasis. Education of populations about consuming safe water and using copepod filters to strain unsafe water should continue and expand, as should efforts to develop and maintain safe drinking water sources. Nevertheless, the peculiar epidemiology in Chad remains incompletely explained. Future studies of dogs might identify other risk factors.

Guinea worm in domestic dogs in Chad: A description and analysis of surveillance data.

After a ten-year absence of reported Guinea worm disease in Chad, human cases were rediscovered in 2010, and canine cases were first recorded in 2012. In response, active surveillance for Guinea worm in both humans and animals was re-initiated in 2012. As of 2018, the Chad Guinea Worm Eradication Program (CGWEP) maintains an extensive surveillance system that operates in 1,895 villages, and collects information about worms, hosts (animals and humans), and animal owners. This report describes in detail the CGWEP surveillance system and explores epidemiological trends in canine Guinea worm cases during 2015-2018. Our results showed an increased in the number of canine cases detected by the system during the period of interest. The proportion of worms that were contained (i.e., water contamination was prevented) improved significantly over time, from 72.8% in 2015 to 85.7% in 2018 (Mantel-Haenszel chi-square = 253.3, P < 0.0001). Additionally, approximately 5% of owners of infected dogs reported that the dog had a Guinea worm-like infection earlier that year; 12.6% had a similar worm in a previous year. The proportion of dogs with a history of infection in a previous year increased over time (Mantel-Haenszel chi-square = 18.8, P < 0.0001). Canine cases were clustered in space and time: most infected dogs (80%) were from the Chari Baguirmi (38.1%) and Moyen Chari Regions (41.9%), and for each year the peak month of identified canine cases was June, with 78.5% occurring during March through August. Findings from this report evoke additional questions about why some dogs are repeatedly infected. Our results may help to target interventions and surveillance efforts in terms of space, time, and dogs susceptible to recurrent infection, with the ultimate goal of Guinea worm eradication.

A search for tiny dragons (Dracunculus medinensis third-stage larvae) in aquatic animals in Chad, Africa.

Dracunculus medinensis, or human Guinea worm (GW), causes a painful and debilitating infection. The global Guinea Worm Eradication Program (GWEP) has successfully reduced human GW cases from 3.5 million in 21 countries in 1986 to only 30 cases in three remaining countries in 2017. Since 2012, an increase in GW infections in domestic dogs, cats and baboons has been reported. Because these infections have not followed classical GW epidemiological patterns resulting from water-borne transmission, it has been hypothesized that transmission occurs via a paratenic host. Thus, we investigated the potential of aquatic animals to serve as paratenic hosts for D. medinensis in Chad, Africa. During three rainy and two dry season trips we detected no GW larvae in 234 fish, two reptiles and two turtles; however, seven GW larvae were recovered from 4 (1.4%) of 276 adult frogs. These data suggest GW infections may occur from ingestion of frogs but the importance of this route is unknown. Additional studies are needed, especially for other possible routes (e.g., ingestion of fish intestines that were recently shown to be a risk). Significantly, 150 years after the life cycle of D. medinensis was described, our data highlights important gaps in the knowledge of GW ecology.

Possible Role of Fish as Transport Hosts for Dracunculus spp. Larvae.

To inform Dracunculus medinensis (Guinea worm) eradication efforts, we evaluated the role of fish as transport hosts for Dracunculus worms. Ferrets fed fish that had ingested infected copepods became infected, highlighting the importance of recommendations to cook fish, bury entrails, and prevent dogs from consuming raw fish and entrails.

Guinea Worm (Dracunculus medinensis) Infection in a Wild-Caught Frog, Chad.

A third-stage (infective) larva of Dracunculus medinensis, the causative agent of Guinea worm disease, was recovered from a wild-caught Phrynobatrachus francisci frog in Chad. Although green frogs (Lithobates clamitans) have been experimentally infected with D. medinensis worms, our findings prove that frogs can serve as natural paratenic hosts.

Possible Role of Fish and Frogs as Paratenic Hosts of Dracunculus medinensis, Chad.

Copepods infected with Dracunculus medinensis larvae collected from infected dogs in Chad were fed to 2 species of fish and tadpoles. Although they readily ingested copepods, neither species of fish, Nile tilapia (Oreochromis niloticus) nor fathead minnow (Pimephalis promelas), were found to harbor Dracunculus larvae when examined 2-3 weeks later. Tadpoles ingested copepods much more slowly; however, upon examination at the same time interval, tadpoles of green frogs (Lithobates [Rana] clamitans) were found to harbor small numbers of Dracunculus larvae. Two ferrets (Mustela putorius furo) were fed fish or tadpoles that had been exposed to infected copepods. Only the ferret fed tadpoles harbored developing Dracunculus larvae at necropsy 70-80 days postexposure. These observations confirm that D. medinensis, like other species in the genus Dracunculus, can readily survive and remain infective in potential paratenic hosts, especially tadpoles.