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PLoS Pathogens Nov 2022Neurotransmission is an important target for anthelmintic drugs, where receptor characteristics and response can be examined through reconstitution ex vivo in Xenopus...
Neurotransmission is an important target for anthelmintic drugs, where receptor characteristics and response can be examined through reconstitution ex vivo in Xenopus laevis oocytes. The homomeric ACR-16 nicotine sensitive acetylcholine receptors (N-AChRs) of several helminth species have been characterized in this way. Our efforts to reconstitute the N-AChR from the clade III filarial parasite, Brugia malayi using similar conditions, initially produced no detectable response. A robust response to acetylcholine is obtained from the closely related clade III parasite Ascaris suum, suggesting that specific changes have occurred between Ascaris and Brugia. N-AChRs from three species intermediate between A. suum and B. malayi were characterized to provide information on the cause. Maximal response to acetylcholine did not change abruptly, consistent with a discrete event, but rather decreased progressively from A. suum through Dracunculus medinensis, Gonglylonema pulchrum and Thelazia callipaeda. Receptor responses to the characteristic nicotine, and other agonists were generally similar. The decrease in maximal current did correlate with a delayed time to reach larger response. Together, this suggested that the failure to reconstitute the B. malayi N-AChR was one extreme of a progressive decrease and that an issue with synthesis of the receptor in oocytes was responsible. Addition of accessory proteins EMC-6, NRA-2 and NRA-4, in addition to RIC-3, produced a small, but measurable B. malayi N-AChR response. Pharmacological properties of a chimeric B. malayi N-AChR were equivalent to the other species, confirming the receptor response remains unchanged while its production is increasingly dependent on accessory proteins. One possibility is that loss of many subunits for acetylcholine receptors from the filarial nematode genome is linked to new subunit combinations that lead to such a dependence. This novel phylogenetic approach allowed the first characterization of a B. malayi AChR ex vivo and in doing so, provides a framework for the successful characterization of other receptors that have yet to be reconstituted.
Topics: Animals; Brugia malayi; Parasites; Acetylcholine; Nicotine; Phylogeny; Receptors, Cholinergic; Receptors, Nicotinic
PubMed: 36374934
DOI: 10.1371/journal.ppat.1010962 -
The American Journal of Tropical... Feb 2021The 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...
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.
Topics: Animals; Animals, Domestic; Chad; Dog Diseases; Dogs; Dracunculiasis; Dracunculus Nematode; Family Characteristics; Female; Male; Parasite Load; Regression Analysis; Risk Factors
PubMed: 33617473
DOI: 10.4269/ajtmh.19-0924 -
Lancet (London, England) Feb 2021
Topics: Animals; Disease Eradication; Dracunculiasis; Dracunculus Nematode; Humans
PubMed: 33640060
DOI: 10.1016/S0140-6736(21)00262-2 -
Indian Journal of Dermatology,... 2023A nematode parasite, Dracunculus medinensis, causes dracunculiasis. Despite being non-fatal, this condition causes significant morbidity. Dracunculiasis is considered an...
A nematode parasite, Dracunculus medinensis, causes dracunculiasis. Despite being non-fatal, this condition causes significant morbidity. Dracunculiasis is considered an eradicated disease in India since 1999. We report two cases that document the unusual linear morphea-like morphology of the calcified D. medinensis and the rare periorbital location of the worm. The cases presented here are rare and a diagnostic challenge, considering the eradicated status of dracunculiasis.
Topics: Animals; Humans; Dracunculiasis; Dracunculus Nematode; India; Skin Diseases
PubMed: 33969654
DOI: 10.25259/IJDVL_909_20 -
PLoS Neglected Tropical Diseases Mar 2021Guinea 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...
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.
Topics: Adult; Animals; Chad; Dog Diseases; Dogs; Dracunculiasis; Dracunculus Nematode; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Patient Education as Topic; Primary Prevention; Surveys and Questionnaires
PubMed: 33735242
DOI: 10.1371/journal.pntd.0009285 -
International Journal For Parasitology.... Apr 2024The genus contains numerous species of subcutaneous parasites of mammals and reptiles. In North America, there are at least three mammal-infecting species of . Reports...
The genus contains numerous species of subcutaneous parasites of mammals and reptiles. In North America, there are at least three mammal-infecting species of . Reports of infections have been reported from river otters () since the early 1900s; however, little is known about the species infecting otters or their ecology. Most reports of do not have a definitive species identified because females, the most common sex found due to their larger size and location in the extremities of the host, lack distinguishing morphological characteristics, and few studies have used molecular methods to confirm identifications. Thus, outside of Ontario, Canada, where both and have been confirmed in otters, the species of in river otters is unknown. In the current study, molecular characterization of nematodes from river otters revealed a high diversity of species. In addition to confirming infections, two new clades were detected. One clade was a novel species in any host and the other was a clade previously detected in Virginia opossums () from the USA and a domestic dog from Spain. No infections with were detected and neither new lineage was genetically similar to , which was recently described from a neotropical otter () from Argentina. These data also indicate that spp. infections in otters are widespread throughout Eastern North America. Currently the life cycles for most of the spp. infecting otters are unknown. Studies on the diversity, life cycle, and natural history of Dracunculidae parasites in wildlife are important because the related parasite, (human Guinea worm) is the subject of an international eradication campaign and there are increasing reports of these parasites in new geographic locations and new hosts, including new species in humans and domestic dogs.
PubMed: 38516639
DOI: 10.1016/j.ijppaw.2024.100922 -
PLoS Neglected Tropical Diseases May 2020After 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,...
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.
Topics: Animals; Chad; Dog Diseases; Dogs; Dracunculiasis; Dracunculus Nematode; Epidemiological Monitoring; Female; Humans; Male
PubMed: 32463811
DOI: 10.1371/journal.pntd.0008207 -
Medical History Apr 2023Guinea worm disease (dracunculiasis) is a debilitating waterborne disease. Once widespread, it is now on the brink of eradication. However, the Guinea Worm Eradication...
Guinea worm disease (dracunculiasis) is a debilitating waterborne disease. Once widespread, it is now on the brink of eradication. However, the Guinea Worm Eradication Programme (GWEP), like guinea worm itself, has been under-studied by historians. The GWEP demonstrates an unusual model of eradication, one focused on primary healthcare (PHC), community participation, health education and behavioural change (safe drinking). The PHC movement collided with a waterborne disease, which required rapid but straightforward treatment to prevent transmission, creating a historical space for the emergence of village-based volunteer health workers, as local actors realigned global health policy on a local level. These Village Volunteers placed eradication in the hands of residents of endemic areas, epitomising the participation-focused nature of the GWEP. This participatory mode of eradication highlights the agency of those in endemic areas, who, through volunteering, safe drinking and community self-help, have been the driving force behind dracunculiasis eradication. In the twenty-first century, guinea worm has become firstly a problem of human mobility, as global health has struggled to contain cases in refugees and nomads, and latterly a zoonotic disease, as guinea worm has shifted hosts to become primarily a parasite of dogs. This demonstrates both the potential of One Health approaches and the need for One Health to adopt from PHC and the GWEP a focus on the health of humans and animals in isolated and impoverished areas. Guinea worm demonstrates how the biological and the historical interact, with the GWEP and guinea worm shaping each other over the course of the eradication programme.
Topics: Humans; Animals; Dogs; Dracunculus Nematode; Dracunculiasis; Waterborne Diseases; Health Education; Health Policy; Disease Eradication
PubMed: 37525460
DOI: 10.1017/mdh.2023.18 -
The American Journal of Tropical... Dec 2020The success of the Guinea Worm (GW) Eradication Program over the past three decades has been tempered by the persistence of GW disease in a few African nations and the...
The success of the Guinea Worm (GW) Eradication Program over the past three decades has been tempered by the persistence of GW disease in a few African nations and the potential for a future resurgence in cases. Domestic dogs are now a major concern as a disease reservoir as large numbers of cases of canine GW disease are now reported each year, mainly along the Chari River in Chad. As a first step toward the development of a serologic assay for dogs, archived human plasma samples from dracunculiasis-positive donors from Togo were used to select adult female GW antigens for peptide sequencing and cloning. Eight protein sequences of interest were expressed as recombinant glutathione--transferase (GST) fusion proteins, and the most promising proteins were coupled to carboxylated microspheres for use in multiplex assays. A thioredoxin-like protein (TRXL1) and a domain of unknown function (DUF148) were assessed for total IgG and IgG reactivities using a panel of specimens from GW cases, uninfected donors, and individuals infected with various nematode worms, including . Both the DUF148-GST and the TRXL1-GST assays cross-reacted with sera, but the latter assay was always the more specific. The IgG and total IgG TRXL1-GST assays both had sensitivities > 87% and specificities > 90%. Maximum specificity (> 96%) was obtained with the total IgG assay when reactivity to both antigens was used to define a positive case. Given the good performance of the human assay, we are now working to modify the assay for dog assessments.
Topics: Animals; Antibodies, Helminth; Antigens, Helminth; Blotting, Western; Cross Reactions; Disease Eradication; Disease Reservoirs; Dog Diseases; Dogs; Dracunculiasis; Dracunculus Nematode; Electrophoresis, Polyacrylamide Gel; Glutathione Transferase; Humans; Immunoglobulin G; Onchocerca volvulus; Onchocerciasis; Recombinant Fusion Proteins; Sensitivity and Specificity; Serologic Tests; Thioredoxins
PubMed: 32901602
DOI: 10.4269/ajtmh.20-0511 -
Current Biology : CB Feb 2022Domestic dogs have an important role in the ecology of transmission of the Guinea worm, a debilitating human parasite. A new study documents how fish content in dogs'...
Domestic dogs have an important role in the ecology of transmission of the Guinea worm, a debilitating human parasite. A new study documents how fish content in dogs' diets can predict Guinea worm infection status, suggesting additional avenues for control.
Topics: Animals; Communicable Diseases; Diet; Dog Diseases; Dogs; Dracunculiasis; Dracunculus Nematode; Humans
PubMed: 35231412
DOI: 10.1016/j.cub.2022.01.005