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The American Journal of Tropical... Feb 2022Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in...
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.
PubMed: 35226875
DOI: 10.4269/ajtmh.21-1222 -
British Medical Journal Jan 1899
PubMed: 20758275
DOI: 10.1136/bmj.1.1986.146 -
Le Infezioni in Medicina 2023Dracunculiasis (Guinea Worm Disease) is a chronic disease that is primarily found in the arid and poor areas of our planet where water supply systems consist of open... (Review)
Review
Dracunculiasis (Guinea Worm Disease) is a chronic disease that is primarily found in the arid and poor areas of our planet where water supply systems consist of open wells. This parasitic disease is transmitted to humans not only through the consumption of water contaminated with crustaceans harbouring larvae of , but also through the ingestion of paratenic (frogs) or transport hosts (fish). The natural progression of the disease is caused by adult worms invading connective tissues, leading to blistering and ulceration of the extremities, approximately one year after infection. In 1986, the Guinea Worm Eradication Program (GWEP) was launched and since then, the incidence of the disease has been reduced by over 99%. Indeed, the most recent global report from 2022 shows only 13 cases of human dracunculiasis worldwide, the lowest annual incidence ever reported. The new found knowledge of potential animal reservoirs and the recent discovery of possible edible paratenic hosts could pose challenges to the future eradication of this debilitating disease. Therefore, attempts to eradicate this parasitosis should not be postponed. Intensive research is needed in this neglected area of medicine, now that the goal is within reach.
PubMed: 38075414
DOI: 10.53854/liim-3104-9 -
The American Journal of Tropical... May 2018
Topics: Adult; Animals; Calcinosis; Dracunculiasis; Dracunculus Nematode; Female; Humans; Radiography
PubMed: 29745364
DOI: 10.4269/ajtmh.17-0944 -
Veterinary Parasitology, Regional... Oct 2022Neglected tropical diseases pose a threat to domestic animal health, as domestic animals can serve as reservoirs for certain zoonotic parasitic infections, including...
Neglected tropical diseases pose a threat to domestic animal health, as domestic animals can serve as reservoirs for certain zoonotic parasitic infections, including Guinea worm (Dracunculus medinensis) and lymphatic filariasis. Surveillance for these parasites in domestic animals is needed to understand infection prevalence and transmission cycles, with the goal of instituting appropriate interventions. The goal of this research was to report our finding of Brugia sp. infection in dogs from Chad, Africa, and to characterize the genetics and epidemiology of the parasite. During a recent Chadian canine pathogen surveillance project, we identified Brugia sp. infections in a total of 46 out of 428 dogs (10.7%) sampled at three time points in 2019-2020. We found high levels of sequence similarity to B. malayi and B. pahangi based on amplification of 18S rRNA, 5.8S rRNA, and ITS-2 regions. Phylogenetic analysis of 18S rRNA gene sequences placed the Chadian Brugia sp. in a clade with other Brugia spp. but grouped it separately from both B. malayi and B. pahangi. Analysis of Hha I sequences showed the greatest similarity with B. patei, a parasite previously reported from dogs, cats, and wildlife hosts in Kenya. Epidemiologic analysis using generalized linear regression modeling found significantly higher odds of Brugia sp. detection among dogs in villages in southern Chad compared to those in the northern region. Further, within the northern region, there were higher odds of detection in the dry season, compared to the wet season, which is consistent with the ecology of a presumably mosquito-borne parasite. The same 428 dogs were tested for Dirofilaria immitis antigen using a commercial assay (IDEXX SNAP 4Dx) at the earliest time point of the study, with 119 dogs testing positive. However, no association was noted between Brugia infection and a dog being positive for Di. immitis antigen, with only seven of the 119 Di. immitis antigen-positive dogs being Brugia-positive. This is the first report of Brugia sp. in domestic dogs in Chad and additional research is needed to definitively identify the species present, elucidate transmission, and understand potential risks to canine and human health.
Topics: Animals; Brugia; Cat Diseases; Cats; Chad; Dog Diseases; Dogs; Dracunculus Nematode; Filariasis; Humans; Phylogeny; RNA, Ribosomal, 18S; RNA, Ribosomal, 5.8S; Zoonoses
PubMed: 36184112
DOI: 10.1016/j.vprsr.2022.100784 -
Tropical Medicine and Infectious Disease Oct 2020Guinea worm disease (GWD) is a neglected tropical disease that was targeted for eradication several decades ago because of its limited geographical distribution,... (Review)
Review
Guinea worm disease (GWD) is a neglected tropical disease that was targeted for eradication several decades ago because of its limited geographical distribution, predictable seasonality, straightforward diagnosis, and exclusive infection of humans. However, a growing body of evidence challenges this last attribute and suggests that GWD can affect both humans and animal populations. The One Health approach emphasizes the relatedness of human, animal, and environmental health. We reviewed epidemiological evidence that could support the utility of a One Health approach for GWD control in the six countries that have reported human GWD cases since 2015-Angola, Cameroon, Chad, Ethiopia, Mali, and South Sudan. Human GWD cases have dramatically declined, but recent years have seen a gradual increase in human case counts, cases in new geographies, and a rapidly growing number of animal infections. Taken together, these suggest a need for an adjusted approach for eradicating GWD using a framework rooted in One Health, dedicated to improving disease surveillance and in animals; pinpointing the dominant routes of infection in animals; elucidating the disease burden in animals; determining transmission risk factors among animals and from animals to humans; and identifying practical ways to foster horizontal and multidisciplinary approaches.
PubMed: 33066254
DOI: 10.3390/tropicalmed5040159 -
Protein Science : a Publication of the... Sep 2023Nicotinic acetylcholine receptors (N-AChRs) mediate fast synaptic signaling and are members of the pentameric ligand-gated ion channel (pLGIC) family. They rely on a...
Nicotinic acetylcholine receptors (N-AChRs) mediate fast synaptic signaling and are members of the pentameric ligand-gated ion channel (pLGIC) family. They rely on a network of accessory proteins in vivo for correct formation and transport to the cell surface. Resistance to cholinesterase 3 (RIC-3) is an endoplasmic reticulum protein that physically interacts with nascent pLGIC subunits and promotes their oligomerization. It is not known why some N-AChRs require RIC-3 in heterologous expression systems, whereas others do not. Previously we reported that the ACR-16 N-AChR from the parasitic nematode Dracunculus medinensis does not require RIC-3 in Xenopus laevis oocytes. This is unusual because all other nematode ACR-16, like the closely related Ascaris suum ACR-16, require RIC-3. Their high sequence similarity limits the number of amino acids that may be responsible, and the goal of this study was to identify them. A series of chimeras and point mutations between A. suum and D. medinensis ACR-16, followed by functional characterization with electrophysiology, identified two residues that account for a majority of the receptor requirement for RIC-3. ACR-16 with R/K159 in the cys-loop and I504 in the C-terminal tail did not require RIC-3 for functional expression. Mutating either of these to R/K159E or I504T, residues found in other nematode ACR-16, conferred a RIC-3 requirement. Our results agree with previous studies showing that these regions interact and are involved in receptor synthesis. Although it is currently unclear what precise mechanism they regulate, these residues may be critical during specific subunit folding and/or assembly cascades that RIC-3 may promote.
Topics: Receptors, Nicotinic; Cholinesterases; Cell Membrane; Endoplasmic Reticulum
PubMed: 37417463
DOI: 10.1002/pro.4718 -
Current Biology : CB Feb 2022Exploitation of natural resources is a driver of human infectious disease emergence. The emergence of animal reservoirs of Guinea worm Dracunculus medinensis,...
Exploitation of natural resources is a driver of human infectious disease emergence. The emergence of animal reservoirs of Guinea worm Dracunculus medinensis, particularly in domestic dogs Canis familiaris, has become the major impediment to global eradication of this human disease. 93% of all Guinea worms detected worldwide in 2020 were in dogs in Chad. Novel, non-classical pathways for transmission of Guinea worm in dogs, involving consumption of fish, have been hypothesized to support the maintenance of this animal reservoir. We quantified and analyzed variation in Guinea worm emergence in dogs in Chad, across three climatic seasons, in multiple villages and districts. We applied forensic stable isotope analyses to quantify dietary variation within and among dogs and GPS tracking to characterize their spatial ecology. At the end of the hot-dry season and beginning of the wet season, when fishing by people is most intensive, Guinea worm emergence rates in dogs were highest, dogs ate most fish, and fish consumption was most closely associated with disease. Consumption of fish by dogs enables a non-classical transmission pathway for Guinea worm in Chad. Seasonal fisheries and the facilitation of dogs eating fish are likely contributing to disease persistence and to this key impediment to human disease eradication. Interrelated natural resource use, climatic variation, companion animal ecology, and human health highlight the indispensability of One Health approaches to the challenges of eradicating Guinea worm and other zoonotic diseases.
Topics: Animals; Dogs; Dracunculiasis; Dracunculus Nematode; Fisheries; Humans; Seasons; Zoonoses
PubMed: 34910949
DOI: 10.1016/j.cub.2021.11.050 -
Scientific Reports Jan 2019Dracunculus medinensis, or human Guinea worm (GW), causes a painful and debilitating infection. The global Guinea Worm Eradication Program (GWEP) has successfully...
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.
Topics: Animal Diseases; Animals; Anura; Aquatic Organisms; Chad; Dracunculus Nematode; Humans; Larva; Public Health Surveillance
PubMed: 30675007
DOI: 10.1038/s41598-018-37567-7 -
The London Medical and Physical Journal Oct 1830
PubMed: 30495642
DOI: No ID Found