-
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 -
Tropical Medicine and Infectious Disease Nov 2022Dracunculiasis, also known as Guinea worm disease (GWD), is a neglected tropical disease (NTD) caused by a parasite (). In the past, dracunculiasis was known as "the... (Review)
Review
BACKGROUND
Dracunculiasis, also known as Guinea worm disease (GWD), is a neglected tropical disease (NTD) caused by a parasite (). In the past, dracunculiasis was known as "the disease of the empty granary" because of the difficulties patients had in going to work in fields or to school when affected by this disease. In tropical areas, the condition has been widespread in economically disadvantaged communities, and has been associated with reduced economic status and low levels of education.
METHODS
we searched PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library, and WHO websites for literature addressing dracunculiasis published in the last 50 years.
RESULTS
by development and optimization of multi-layered control measures, transmission by the vector has been interrupted, but there are foci in several African countries with a high risk of compromising the results obtained in the control of this neglected disease.
CONCLUSION
this review features state-of-the-art data on the infection prevalence, geographical distribution, diagnostics, parasite-host interactions, and the pathology of dracunculiasis. Also described are the current state and future perspectives for vector control and elimination strategies.
PubMed: 36355908
DOI: 10.3390/tropicalmed7110366 -
PLoS Neglected Tropical Diseases Oct 2022Dracunculus medinensis (Guinea worm) is a parasitic nematode that can cause the debilitating disease dracunculiasis (Guinea worm disease) in humans. The global Guinea...
Dracunculus medinensis (Guinea worm) is a parasitic nematode that can cause the debilitating disease dracunculiasis (Guinea worm disease) in humans. The global Guinea Worm Eradication Program has led intervention and eradication efforts since the 1980s, and Guinea worm infections in people have decreased >99.99%. With the final goal of eradication drawing nearer, reports of animal infections from some remaining endemic countries pose unique challenges. Currently, confirmation of suspected Guinea worm infection relies on conventional molecular techniques such as polymerase chain reaction (PCR), which is not specific to Guinea worm and, therefore, requires sequencing of the PCR products to confirm the identity of suspect samples, a process that often takes a few weeks. To decrease the time required for species confirmation, we developed a quantitative PCR assay targeting the mitochondrial cytochrome b (cytb) gene of Guinea worm. Our assay has a limit of detection of 10 copies per reaction. The mean analytical parameters (± SE) were as follows: efficiency = 93.4 ± 7.7%, y-intercept = 40.93 ± 1.11, slope = -3.4896 ± 0.12, and the R2 = 0.999 ± 0.004. The assay did not amplify other nematodes found in Guinea worm-endemic regions and demonstrated 100% diagnostic sensitivity and specificity. Implementation of this quantitative PCR assay for Guinea worm identification could eliminate the need for DNA sequencing to confirm species. Thus, this approach can be implemented to provide more rapid confirmation of Guinea worm infections, leading to faster execution of Guinea worm interventions while increasing our understanding of infection patterns.
Topics: Humans; Animals; Dracunculus Nematode; Cytochromes b; Dracunculiasis; Polymerase Chain Reaction
PubMed: 36206300
DOI: 10.1371/journal.pntd.0010830 -
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 -
Journal of Infection in Developing... Aug 2022Guinea worm disease is caused by Dracunculus medinensis. Transmission of the disease depends on vectors (copepods). Abate applications in targeted water sources to...
INTRODUCTION
Guinea worm disease is caused by Dracunculus medinensis. Transmission of the disease depends on vectors (copepods). Abate applications in targeted water sources to control copepod is the main intervention. The aim of this study was to assess vector control practice in the guinea worm endemic region of Gambela, Ethiopia and to identify elimination gaps.
METHODOLOGY
Retrospective analysis of routine program data recorded from 2016 to 2020 was performed. Pre-and post-copepod test is conducted on water ponds to determine the density of copepods. Based on the copepod density, the chemical is applied accordingly. The five years data was obtained from Ethiopian public health institute electronic database with permission.
RESULTS
A total of 22,131 water ponds were treated during the past five years. Out of the total treated in 2020, 4,669/7,266 (64%) were found with > 9 Copepods during pre-copepod test. 130/7,266 (1.79%) of water ponds which were post-tested after Abate application failed the requirement of scoring ≤ 9 copepods. Of the 130 water ponds, 115 (88.5%) were observed during the transmission season (April to November). Abate application trend had increased by 28.9% during the 5 years period. According to the database, some of the largest water sources found in infection reporting villages missed their 28 days regular treatment schedule.
CONCLUSIONS
A single water source that has not been treated effectively could be a source of infection for both humans and animals. The practice of Abate application should be enhanced and monitored regularly. The documenting system should be improved for quality, timely information and action.
Topics: Animals; Dracunculus Nematode; Ethiopia; Humans; Retrospective Studies; Temefos; Water
PubMed: 36156498
DOI: 10.3855/jidc.15972 -
The American Journal of Tropical... Aug 2022This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2021. Dracunculiasis (Guinea worm disease) has been eliminated from...
This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2021. Dracunculiasis (Guinea worm disease) has been eliminated from 17 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only Chad, Ethiopia, Mali, and South Sudan reported cases in humans in 2021. Chad, Ethiopia, and Mali also reported indigenous infections of animals, mostly domestic dogs, with Dracunculus medinensis. Insecurity and infections in animals are the main obstacles remaining to interrupting dracunculiasis transmission completely.
Topics: Humans; Animals; Dogs; Dracunculiasis; Disease Eradication; Water Supply; Ethiopia; Chad
PubMed: 35895421
DOI: 10.4269/ajtmh.22-0197 -
The Lancet. Microbe Feb 2022Dracunculiasis (also known as Guinea worm disease), caused by the Dracunculus medinensis nematode, is progressing towards eradication, with a reduction in cases from...
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.
Topics: Animals; Chad; Cross-Sectional Studies; Disease Outbreaks; Dogs; Dracunculiasis; Dracunculus Nematode; Female; Humans
PubMed: 35544041
DOI: 10.1016/S2666-5247(21)00209-3 -
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 -
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 -
The American Journal of Tropical... Jan 2022Dracunculus medinensis, also known as the African Guinea worm, is the causative agent of dracunculiasis and the focus of the global Guinea Worm Eradication Program...
Dracunculus medinensis, also known as the African Guinea worm, is the causative agent of dracunculiasis and the focus of the global Guinea Worm Eradication Program (GWEP). Transmission of D. medinensis to humans occurs primarily by drinking water containing cyclopoid copepods infected with third-stage D. medinensis larvae. A common intervention to interrupt transmission and decrease the number of copepods in infected water bodies is the application of the organophosphate larvicide Abate® (temephos). However, the use of alternative compounds to help decrease copepod populations would be beneficial to the GWEP. We compared the immobilization of copepods by three compounds: Abate, Natular® (spinosad), and diflubenzuron. Our results confirm that neither diflubenzuron nor Natular immobilized copepods as quickly or as effectively as Abate. However, doubling or tripling the suggested concentration of Natular resulted in immobilization rates similar to Abate over 72 hours of continuous exposure. Further research on the possible effects of higher concentrations of Natular on the environment and nontarget organisms is necessary to determine whether this compound can be used safely to control the copepod population.
Topics: Animals; Copepoda; Diflubenzuron; Dracunculiasis; Dracunculus Nematode; Drug Combinations; Humans; Macrolides; Temefos
PubMed: 35073509
DOI: 10.4269/ajtmh.21-0818