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International Journal For Parasitology.... Apr 2023Anthelmintic resistance to benzimidazole has been detected in the canine hookworm, Ancylostoma caninum. Benzimidazole resistance is believed to have developed originally...
BACKGROUND
Anthelmintic resistance to benzimidazole has been detected in the canine hookworm, Ancylostoma caninum. Benzimidazole resistance is believed to have developed originally in greyhounds, but has also been detected in non-greyhound pet dogs. The aim of this study was to validate a probe-based allele-specific real-time PCR tests for the F167Y polymorphism on the β-tubulin isotype-1 gene and to determine the geographic distribution.
METHODS
Allele-specific real-time PCR tests were established and validated to detect the codon 167 polymorphism in the Ancylostoma caninum β-tubulin isotype-1gene. Additionally, real-time PCR tests were validated for Ancylostoma spp. and Uncinaria stenocephala. Two nucleic acid extraction protocols were validated including mechanical disruption of parasite structures in stool. The frequency of the F167Y single nucleotide polymorphism (SNP) was determined in hookworm confirmed stool samples. Samples with the resistant 167Y genotype were confirmed by β-tubulin gene sequencing and allele frequencies were determined.
RESULTS
The Ancylostoma spp. and A. caninum F167Y allele-specific real-time PCR tests were highly sensitive and specific when tested against synthetic DNA, spiked samples, and characterized parasites. Using an optimized total nucleic acid extraction protocol, 54 of 511 (10.6%) were found to contain the benzimidazole resistance allele. All 55 samples containing hookworms with the resistance mutation were confirmed by β-tubulin gene sequencing. The majority of resistant hookworms (44 resistant, 183 tested; 24.4%) originated from Florida, five from California (103 tested, 4.9%), three from Idaho (40 tested, 7.5%), two from Nevada (22 tested, 9.1%), and one sample from Hawaii (13 tested, 7.7%). Resistant genotypes were found in 14 different dog breeds including eight in Greyhounds. Allele-frequency determination revealed resistance allele frequencies between 1 and 100% with 58% above 50%.
CONCLUSIONS
This data strongly supports recent findings of benzimidazole resistant canine hookworms present throughout the general US pet dog population.
Topics: Dogs; Animals; Ancylostoma; Parasites; Tubulin; Drug Resistance; Anthelmintics; Benzimidazoles; Hookworm Infections; Ancylostomatoidea; Polymorphism, Single Nucleotide; Real-Time Polymerase Chain Reaction
PubMed: 36958067
DOI: 10.1016/j.ijpddr.2023.01.001 -
Emerging Infectious Diseases Aug 2018During 2012-2015, US-bound refugees living in Myanmar-Thailand border camps (n = 1,839) were surveyed for hookworm infection and treatment response by using quantitative...
During 2012-2015, US-bound refugees living in Myanmar-Thailand border camps (n = 1,839) were surveyed for hookworm infection and treatment response by using quantitative PCR. Samples were collected at 3 time points: after each of 2 treatments with albendazole and after resettlement in the United States. Baseline prevalence of Necator americanus hookworm was 25.4%, Ancylostoma duodenale 0%, and Ancylostoma ceylanicum (a zoonosis) 5.4%. Compared with N. americanus prevalence, A. ceylanicum hookworm prevalence peaked in younger age groups, and blood eosinophil concentrations during A. ceylanicum infection were higher than those for N. americanus infection. Female sex was associated with a lower risk for either hookworm infection. Cure rates after 1 dose of albendazole were greater for A. ceylanicum (93.3%) than N. americanus (65.9%) hookworm (p<0.001). Lower N. americanus hookworm cure rates were unrelated to β-tubulin single-nucleotide polymorphisms at codons 200 or 167. A. ceylanicum hookworm infection might be more common in humans than previously recognized.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albendazole; Ancylostoma; Ancylostomiasis; Animals; Anthelmintics; Child; Child, Preschool; Feces; Female; Humans; Infant; Male; Middle Aged; Myanmar; Refugees; Thailand; Young Adult
PubMed: 30014834
DOI: 10.3201/eid2408.180280 -
Pathogens (Basel, Switzerland) Jan 2023The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated...
The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm's excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm , which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in female and male ESPs, respectively, using this improved version, identifying a total of 795 ESPs (70% in both sexes, with the remaining sex-specific). Using functional databases (KEGG, GO and Interpro), common and sex-specific enriched functions were identified. Comparisons with the exclusively human-infective hookworm identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male . The findings provide a deeper understanding of hookworm protein functions that assure long-term host survival and facilitate future engineering of transgenic hookworms and analysis of regulatory elements mediating the high-level expression of ESPs. Furthermore, the findings expand the list of potential vaccine and diagnostic targets and identify biologics that can be explored for anti-inflammatory potential.
PubMed: 36678443
DOI: 10.3390/pathogens12010095 -
Scientific Reports Nov 2019Protein-based drug discovery strategies have the distinct advantage of providing insights into the molecular mechanisms of chemical effectors. Currently, there are no...
Protein-based drug discovery strategies have the distinct advantage of providing insights into the molecular mechanisms of chemical effectors. Currently, there are no known trehalose-6-phosphate phosphatase (TPP) inhibitors that possess reasonable inhibition constants and chemical scaffolds amenable to convenient modification. In the present study, we subjected recombinant TPPs to a two-tiered screening approach to evaluate several diverse compound groups with respect to their potential as TPP inhibitors. From a total of 5452 compounds tested, N-(phenylthio)phthalimide was identified as an inhibitor of nematode TPPs with apparent K values of 1.0 μM and 0.56 μM against the enzymes from the zoonotic roundworms Ancylostoma ceylanicum and Toxocara canis, respectively. Using site-directed mutagenesis, we demonstrate that this compound acts as a suicide inhibitor that conjugates a strictly conserved cysteine residue in the vicinity of the active site of nematode TPPs. The anthelmintic properties of N-(phenylthio)phthalimide were assessed in whole nematode assays using larvae of the ascaroids T. canis and T. cati, as well as the barber's pole worm Haemonchus contortus. The compound was particularly effective against each of the ascaroids with an IC value of 9.3 μM in the survival assay of T. cati larvae, whereas no bioactivity was observed against H. contortus.
Topics: Animals; Anthelmintics; Enzyme Inhibitors; Helminth Proteins; Nematoda; Phosphoric Monoester Hydrolases; Phthalimides
PubMed: 31700060
DOI: 10.1038/s41598-019-52593-9 -
The Korean Journal of Parasitology Dec 2020Human hookworm infections caused by adult Ancylostoma spp. and Necator americanus are one of the most important tropical diseases. We performed a survey of intestinal...
Human hookworm infections caused by adult Ancylostoma spp. and Necator americanus are one of the most important tropical diseases. We performed a survey of intestinal helminths using the Kato-Katz fecal examination technique targeting 1,156 villagers residing in 2 northern provinces (Preah Vihear and Stung Treng) of Cambodia in 2018. The results revealed a high overall egg positive rate of intestinal helminths (61.9%), and the egg positive rate of hookworms was 11.6%. Nine of the hookworm egg positive cases in Preah Vihear Province were treated with 5-10 mg/kg pyrantel pamoate followed by purging with magnesium salts, and a total of 65 adult hookworms were expelled in diarrheic stools. The adult hookworms were analyzed morphologically and molecularly to confirm the species. The morphologies of the buccal cavity and dorsal rays on the costa were observed with a light microscope, and the nucleotide sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were analyzed. The majority of the hookworm adults (90.7%) were N. americanus, whereas the remaining 9.3% were Ancylostoma ceylanicum, a rare hookworm species infecting humans. The results revealed a high prevalence of hookworm infections among people in a northern part of Cambodia, suggesting the necessity of a sustained survey combined with control measures against hookworm infections.
Topics: Adult; Ancylostoma; Animals; Cambodia; Electron Transport Complex IV; Feces; Female; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Male; Microscopy; Necator americanus; Pathology, Molecular; Prevalence; Rural Population; Young Adult
PubMed: 33412765
DOI: 10.3347/kjp.2020.58.6.619 -
The Brazilian Journal of Infectious... 2021Describe the diagnostic characteristics of a conventional multiplex PCR for the diagnosis of S. stercoralis, N. americanus and Ancylostomas spp.
OBJECTIVES
Describe the diagnostic characteristics of a conventional multiplex PCR for the diagnosis of S. stercoralis, N. americanus and Ancylostomas spp.
METHODS
Fecal samples were collected from a cross-sectional study in Orán department, Salta province, Argentina. The stool samples were analyzed using concentration-sedimentation, Harada Mori, McMaster, and Baermann techniques. DNA was extracted from 50 mg fecal sample using the FastPrep® Spin Kit for Soil. Three pairs of primers were used for the amplification of three products of 101, 330, and 577 base pairs (bp) for S. stercoralis, N. americanus and Ancylostoma spp, respectively. The sensitivity and analytical specificity of multiplex PCR were evaluated, as well as the sensitivity and diagnostic specificity, using a composite standard and Bayesian approach.
RESULTS AND CONCLUSIONS
Multiplex PCR did not present cross-reaction with other intestinal parasites, and the detection limit for multiplex PCR was between 2 and 20 pg of genomic DNA. In addition it presented a diagnostic sensitivity of 97.4% for S. stercoralis and 90.3% for hookworms with a specificity of 100% and 87.6%, respectively. PCR identified a higher proportion (p <0.01) of coinfections (15.3%) than microscopic techniques (3.5%). Also, multiplex PCR showed that there was a positive association between S. stercoralis and hookworms (odds ratio = 2.12). However, this association was due to N. americanus (odds ratio= 3.22), since no association was observed between S. stercoralis and Ancylostoma spp. Neither was an association observed between the two species of hookworms.
Topics: Ancylostomatoidea; Animals; Bayes Theorem; Cross-Sectional Studies; Feces; Humans; Intestinal Diseases, Parasitic; Multiplex Polymerase Chain Reaction; Sensitivity and Specificity; Strongyloides stercoralis; Strongyloidiasis
PubMed: 34774469
DOI: 10.1016/j.bjid.2021.101649 -
Veterinary Parasitology, Regional... Dec 2018Cats can be infected by various intestinal parasites, some that are zoonotic. Although surveys of parasite prevalence in owned and shelter cats have been published, none...
Cats can be infected by various intestinal parasites, some that are zoonotic. Although surveys of parasite prevalence in owned and shelter cats have been published, none addressed free-roaming, wild-trapped, domestic cat (Felis catus) populations. An opportunity to determine the prevalence of intestinal parasites in wild-trapped, free-roaming cats in northcentral Oklahoma, United States occurred through a trap-neuter-return (TNR) program conducted at Oklahoma State University, Boren Veterinary Medical Hospital, between February 2015 and April 2016. Approximately 1 g to 5 g of feces was collected from 846 free-roaming cats either from cage traps, when available, or rectally using disposable fecal loops and examined by centrifugal fecal flotation tests with 33% zinc sulfate solution. Parasite infections were confirmed by microscopic detection of eggs, cysts, or oocysts and visual detection of proglottids. Approximately 63.9% (541/846) of free-roaming cats were infected by at least one parasite, and 24.9% (211/846) of cats were infected by multiple parasites. The most common intestinal parasite infections detected were: Toxocara cati (44.6%; 377/846), followed by Alaria (13.4%; 113/846), Ancylostoma (11.2%; 95/846), Cystoisospora (9.7%; 82/846), taeniids (7.7%; 65/846), Dipylidium caninum (4.5%; 38/846), Physaloptera (2.2%; 19/846), Eucoleus aerophilus (1.4%; 12/846), Giardia (1.2%; 10/846), and a small (10-12 μm in diameter) Toxoplasma-like oocyst (0.1%; 1/846). A few ectoparasites, Demodex gatoi (0.5%; 4/846) and Cheyletiella (0.1%; 1/846), were also detected by fecal flotation. Our findings indicate that a higher prevalence of parasite infections occurs in free-roaming cats in Oklahoma than in owned cats, and these free-roaming cats contribute to contamination of the environment with several zoonotic parasites. Regional data on the prevalence of parasites in free-roaming cats can aid in the justification for parasite control programs in owned cats since both can share the same environment and supports the current practice of routine broad-spectrum anthelmintic and ectoparasite treatments for owned cats.
Topics: Animals; Animals, Wild; Cats; Feces; Female; Intestinal Diseases, Parasitic; Male; Oklahoma; Parasites; Prevalence; Surveys and Questionnaires; Toxocara; Toxocariasis; Zoonoses
PubMed: 31014736
DOI: 10.1016/j.vprsr.2018.08.008 -
The Canadian Veterinary Journal = La... Apr 2023The canine hookworm is one of the most prevalent parasitic nematodes in dogs worldwide and has the potential for zoonotic transmission to humans, including the... (Review)
Review
The canine hookworm is one of the most prevalent parasitic nematodes in dogs worldwide and has the potential for zoonotic transmission to humans, including the development of cutaneous larva migrans. Recent confirmation of anthelmintic resistance (AR) in to several anthelmintic classes, mainly in the USA, indicates the potential for this scenario in Canada. We consider various factors that may lead to resistant isolates in Canada, such as the widespread use of antiparasitic drugs without the assessment of efficacy; increased prevalence in various Canadian provinces; and the importation of dogs, mostly from the USA, with a history of persistent infection by . Our objective was to review factors that influence to develop AR and raise awareness regarding the need for a strategic plan to control this parasitic nematode through the appropriate use of anthelmintics.
Topics: Dogs; Animals; Humans; Ancylostoma; Ancylostomatoidea; Ancylostomiasis; Canada; Anthelmintics; Hookworm Infections; Dog Diseases
PubMed: 37008647
DOI: No ID Found -
BMJ (Clinical Research Ed.) Sep 2017To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. Systematic review and network... (Meta-Analysis)
Meta-Analysis Review
To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. Systematic review and network meta-analysis. PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016. Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against , hookworm ( and ) and The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models. 55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against , with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against : by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027). All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against The decrease in efficacy of albendazole against over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against .
Topics: Animals; Anthelmintics; Female; Helminthiasis; Helminths; Humans; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Soil; Treatment Outcome
PubMed: 28947636
DOI: 10.1136/bmj.j4307 -
Medical Science Monitor : International... Mar 2024BACKGROUND Ancylostoma spp., including A. duodenale, A. braziliense, A. caninum, and A. ceylanicum, are hookworms that are transmitted from infected soil and by contact...
BACKGROUND Ancylostoma spp., including A. duodenale, A. braziliense, A. caninum, and A. ceylanicum, are hookworms that are transmitted from infected soil and by contact with domestic animals and rodent hosts, and can cause systemic disease and cutaneous larva migrans. The objective of this study was to describe the ecoepidemiology of Ancylostoma caninum and Ancylostoma spp. in urban-marginal sectors and in rural sectors located in Ecuador. MATERIAL AND METHODS Through addressed sampling, a total of 498 domestic dogs and 40 synanthropic rodents were analyzed via the following coproparasitic methods: direct, flotation, sedimentation with centrifugation using saline (egg identification), modified Baermann (larval identification), and morphometric methods (confirmation). A total of 236 people were surveyed, and a clinical analysis was performed via physical examination. The environmental variables were obtained through reports from the INAMHI of Ecuador and the use of online environmental programs. Through surveys, data related to social determinants were obtained. Epidemiological indicators (prevalence, morbidity, and mortality) were obtained through microbial analysis and surveys. RESULTS A total of 250 domestic dogs were diagnosed with Ancylostoma caninum (50, 20%), and 41 were diagnosed with Ancylostoma spp. (8.23%). One synanthropic rodent (2.5%) was positive for A. caninum. In the clinical analysis, 3 patients were identified as positive (1.27%) for cutaneous larva migrans (CLM). Likewise, environmental variables and social determinants influence the transmission, prevalence, and nature of parasitism by hookworm. CONCLUSIONS People, domestic dogs, and rodents were infected with these parasites. Consequently, there is a risk of ancylostomiasis and cutaneous larvae migrans spreading.
Topics: Humans; Animals; Dogs; Ancylostoma; Larva Migrans; Ecuador; Prevalence; Larva; Feces
PubMed: 38500436
DOI: 10.12659/MSM.943931