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Frontiers in Medicine 2023Hookworm disease is a major global public health concern, annually affecting 500-700 million of the world's poorest people. The World Health Organization is targeting...
Hookworm disease is a major global public health concern, annually affecting 500-700 million of the world's poorest people. The World Health Organization is targeting the elimination of hookworm as a public health problem by 2030 using a strategy of mass drug administration (MDA) to at-risk human populations. However, in Southeast Asia and the Pacific the zoonotic hookworm species, , is endemic in dogs and commonly infects people. This presents a potential impediment to the effectiveness of MDA that targets only humans. Here, we develop a novel multi-host (dog and human) transmission model of and compare the effectiveness of human-only and "One Health" (human plus dog) MDA strategies under a range of eco-epidemiological assumptions. We show that One Health interventions-targeting both dogs and humans-could suppress prevalence in humans to ≤ 1% by the end of 2030, even with only modest coverage (25-50%) of the animal reservoir. With increasing coverage, One Health interventions may even interrupt transmission. We discuss key unresolved questions on the eco-epidemiology of , the challenges of delivering MDA to animal reservoirs, and the growing importance of One Health interventions to human public health.
PubMed: 36960338
DOI: 10.3389/fmed.2023.1092030 -
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 -
Journal of Parasitic Diseases :... Mar 2023The present experiment was carried out to assess the comparative efficacy of ivermectin and fenbendazole individually for anthelmintic therapy for the hookworm infested...
The present experiment was carried out to assess the comparative efficacy of ivermectin and fenbendazole individually for anthelmintic therapy for the hookworm infested dogs. Dogs presented to the Department of Veterinary Clinical Medicine or Veterinary Clinical Complex, Bhubaneswar were randomly screened for infection and the positive dogs were selected for the therapeutic trial Faecal samples were collected randomly from presented dogs immediately after defaecation or from the rectum directly using a faecal scoop. The collected sample was examined by floatation technique to detect the positive cases of infection. The dogs with normal clinical parameters and no eggs or ova in the faeces were included in in group 1 ( = 12). Dogs with faecal sample positive for ova were recruited for the comparative study ( = 24) which were grouped into two groups consisting of 12 dogs in each (group 2 and 3). Group 2 dogs ( = 12) were treated with ivermectin at 200 µg/kg body weight once orally repeated after 15 days with proper supportive therapy each time. Group 3 ( = 12) were treated with fenbendazole at 50 mg/kg body weight once orally repeated after 15 days with proper supportive therapy each time. Haematological examinations and serum biochemical tests were carried out in all groups each time on day 0, 15 and 30 of the experiment. The therapeutic efficacy of both the drugs was calculated on the basis of number of animals found free of infection as determined by reduction in EPG count of the faeces of the group following the treatment. The reduction in eggs per gram (EPG) count on day 15 and day 30 was more significant in group 2 than group 3. The mean EPG count reduced significantly to 24.17 ± 11.44 on day 15 from day 0 level of 1650.00 ± 247.25 in fenbendazole-treated dogs. On day 30, the mean value further reduced to become nil.The 15th day after treatment, mean (± SE) value of protein, albumin and globulin was changed to 5.63 ± 0.12, 2.64 ± 0.12 and 2.99 ± 0.15 g/dl, respectively. The 30th day after treatment, the values were 6.23 ± 0.14, 3.20 ± 0.18 and 3.03 ± 0.21 g/dl, respectively. The total protein and albumin values were significantly changed from day 0 level in group 2 and 3 by 15th day and 30th day, respectively, at 1% level of significance. Following treatment with ivermectin, the 15th day haematological values increased significantly at 1% level ( < 0.01) of significance. There was significant increase in the values at 1% level on the 30th day compared to day 0 and the mean values were non-significantly comparable to the healthy control group except PCV and TEC.
PubMed: 36910310
DOI: 10.1007/s12639-022-01536-9 -
Parasitology May 2023Soil-transmitted nematodes (STNs) place a tremendous burden on health and economics worldwide with an estimate of at least 1.5 billion people, or 24% of the population,...
Soil-transmitted nematodes (STNs) place a tremendous burden on health and economics worldwide with an estimate of at least 1.5 billion people, or 24% of the population, being infected with at least 1 STN globally. Children and pregnant women carry the heavier pathological burden, and disease caused by the blood-feeding worm in the intestine can result in anaemia and delays in physical and intellectual development. These parasites are capable of infecting and reproducing in various host species, but what determines host specificity remains unanswered. Identifying the molecular determinants of host specificity would provide a crucial breakthrough towards understanding the biology of parasitism and could provide attractive targets for intervention. To investigate specificity mechanisms, members of the hookworm genus provide a powerful system as they range from strict specialists to generalists. Using transcriptomics, differentially expressed genes (DEGs) in permissive (hamster) and non-permissive (mouse) hosts at different early time points during infection with were examined. Analysis of the data has identified unique immune responses in mice, as well as potential permissive signals in hamsters. Specifically, immune pathways associated with resistance to infection are upregulated in the non-permissive host, providing a possible protection mechanism that is absent in the permissive host. Furthermore, unique signatures of host specificity that may inform the parasite that it has invaded a permissive host were identified. These data provide novel insight into the tissue-specific gene expression differences between permissive and non-permissive hosts in response to hookworm infection.
Topics: Pregnancy; Cricetinae; Female; Animals; Humans; Mice; Ancylostoma; Ancylostomiasis; Host Specificity; Transcriptome; Hookworm Infections; Intestines
PubMed: 36883013
DOI: 10.1017/S0031182023000227 -
PLoS Pathogens Mar 2023Ancylostoma caninum is an important zoonotic gastrointestinal nematode of dogs worldwide and a close relative of human hookworms. We recently reported that racing...
Molecular evidence of widespread benzimidazole drug resistance in Ancylostoma caninum from domestic dogs throughout the USA and discovery of a novel β-tubulin benzimidazole resistance mutation.
Ancylostoma caninum is an important zoonotic gastrointestinal nematode of dogs worldwide and a close relative of human hookworms. We recently reported that racing greyhound dogs in the USA are infected with A. caninum that are commonly resistant to multiple anthelmintics. Benzimidazole resistance in A. caninum in greyhounds was associated with a high frequency of the canonical F167Y(TTC>TAC) isotype-1 β-tubulin mutation. In this work, we show that benzimidazole resistance is remarkably widespread in A. caninum from domestic dogs across the USA. First, we identified and showed the functional significance of a novel benzimidazole isotype-1 β-tubulin resistance mutation, Q134H(CAA>CAT). Several benzimidazole resistant A. caninum isolates from greyhounds with a low frequency of the F167Y(TTC>TAC) mutation had a high frequency of a Q134H(CAA>CAT) mutation not previously reported from any eukaryotic pathogen in the field. Structural modeling predicted that the Q134 residue is directly involved in benzimidazole drug binding and that the 134H substitution would significantly reduce binding affinity. Introduction of the Q134H substitution into the C. elegans β-tubulin gene ben-1, by CRISPR-Cas9 editing, conferred similar levels of resistance as a ben-1 null allele. Deep amplicon sequencing on A. caninum eggs from 685 hookworm positive pet dog fecal samples revealed that both mutations were widespread across the USA, with prevalences of 49.7% (overall mean frequency 54.0%) and 31.1% (overall mean frequency 16.4%) for F167Y(TTC>TAC) and Q134H(CAA>CAT), respectively. Canonical codon 198 and 200 benzimidazole resistance mutations were absent. The F167Y(TTC>TAC) mutation had a significantly higher prevalence and frequency in Western USA than in other regions, which we hypothesize is due to differences in refugia. This work has important implications for companion animal parasite control and the potential emergence of drug resistance in human hookworms.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Benzimidazoles; Caenorhabditis elegans; Drug Resistance; Mutation; Tubulin
PubMed: 36862759
DOI: 10.1371/journal.ppat.1011146 -
Tropical Medicine and Infectious Disease Feb 2023Hookworms are the most common parasitic nematodes in the genus of that infect both humans and animals in subtropical and tropical South East Asia. The common hookworm...
Hookworms are the most common parasitic nematodes in the genus of that infect both humans and animals in subtropical and tropical South East Asia. The common hookworm species in cats is which is emerging in Thailand. However, the genetic characterization of hookworms in cats is outdated and insufficiently studied in Thailand. We aimed to investigate the prevalence, risk factors and genetic characterization of hookworm infection in semi-domesticated temple cats in Bangkok, Thailand. A total of 500 temple cat fecal samples were collected from 43 monasteries in 24 districts of Bangkok, Thailand. Polymerase Chain Reaction (PCR) was performed by amplifying the internal transcribed spacer (ITS) gene and mitochondrial cytochrome oxidase c subunit I () gene. The infection prevalence of hookworm in temple cats was 13.2% (66/500). The highest prevalence was 34.6% in the Bang Khun Thian district, which is located in a suburban area. The risk factor analysis revealed that cats older than one year (OR 2.4, 95% CI 1.1-5.5, < 0.05), lack of veterinary attention (OR 2.9, 95% CI 1.7-4.9, < 0.001) and Bangkok zone (suburban vs. inner city; OR 2.9, 95% CI 1.6-5.4, < 0.001) were significantly increasing hookworm infection risk. All hookworm positive samples were identified as by ITS gene. Moreover, genetic characterization of gene in isolates indicated a mix of isolates from humans, cats and dogs. The findings show that temple cats can act as a potential source of zoonotic hookworm parasites for the human and animal population in Bangkok, Thailand. Therefore, appropriate control measures for hookworms in semi-domesticated temple cats as well as prevention measures for hookworms in pet cats and humans should be promoted.
PubMed: 36828538
DOI: 10.3390/tropicalmed8020122 -
Journal of Parasitology Research 2023A cross-sectional study was carried out in the Sidama region's Hawassa town from March 2021 to July 2021 with the aim of estimating the prevalence and associated factors...
A cross-sectional study was carried out in the Sidama region's Hawassa town from March 2021 to July 2021 with the aim of estimating the prevalence and associated factors of dog gastrointestinal helminths. A total of 384 dogs were randomly selected, and their feces were examined using a flotation technique. For data analysis, descriptive statistics and chi-square analyses were employed, and a -value of less than 0.05 was considered as significant. Accordingly, 56% ( = 215; 95% CI, 49.26-62.66) of dogs had gastrointestinal helminth parasite infection, of which 42.2% ( = 162) had a single infection and 13.8% ( = 53) had a mixed infection. In this study, sp. was the most detected helminth (24.2%), followed by sp. (15.37%), (14.6%), (5.73%), sp. (5.47%), and (4.43%). Out of the total sampled dogs tested positive for one or more gastrointestinal helminths, 37.5% ( = 144) were males and 18.5% ( = 71) were females. The total prevalence of helminth infections did not change significantly ( > 0.05) by the gender, age, and breed of dogs. The present study's high prevalence of dog helminthiasis reflects a high occurrence of infection and a concern to the public's health. In light of this conclusion, it is advised that dog owners improve their standards of hygiene. In addition, they should regularly take their animals to veterinary care and frequently administer the appropriate anthelmintics available to their dogs.
PubMed: 36793767
DOI: 10.1155/2023/6155741 -
BioRxiv : the Preprint Server For... Feb 2023Hookworms (genera and ) are amongst of the most prevalent and important parasites of humans globally. These intestinal parasites ingest blood, resulting in anemia,...
Hookworms (genera and ) are amongst of the most prevalent and important parasites of humans globally. These intestinal parasites ingest blood, resulting in anemia, growth stunting, malnutrition, and adverse pregnancy outcomes. They are also critical parasites of dogs and other animals. In addition, hookworms and hookworm products are being explored for their use in treatment of autoimmune and inflammatory diseases. There is thus a significant and growing interest in these mammalian host-obligate parasites. Laboratory research is hampered by the lack of good means of cryopreservation. Here, we describe a robust method for long-term (≥3 year) cryoprotection and recovery of both and hookworms that is also applicable to two other intestinal parasites that passages through the infective third larval stage, and H . The key is the use cryo-preserved first-staged larvae raised to the infective third larval stage using activated charcoal mixed with uninfected feces from a permissive host. This technique will greatly facilitate research on and availability of gastrointestinal parasitic nematodes with great importance to global health, companion animal health, and autoimmune/inflammatory disease therapies.
PubMed: 36778351
DOI: 10.1101/2023.02.01.526637 -
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 -
Revista Brasileira de Parasitologia... 2023Gastrointestinal parasitism by helminths and protozoa poses risks to animal and human health owing to clinical changes and transmission of potentially zoonotic agents....
Gastrointestinal parasitism by helminths and protozoa poses risks to animal and human health owing to clinical changes and transmission of potentially zoonotic agents. Thus, the present study aimed to verify the occurrence of gastrointestinal parasites in dogs from the municipality of Cuiabá, Mato Grosso, Brazil, using coproparasitological tests. From June 2021 to April 2022, faecal samples were collected from domestic dogs at the Veterinary Hospital and Animal Protection Shelters in the Cuiabá municipality. A semi-structured questionnaire was applied to the owners and those responsible for the shelters to analyse the factors associated with gastrointestinal parasitism. A total of 353 faecal samples were collected and subjected to parasitological flotation and sedimentation techniques. Data were analysed using the chi-squared test and exploratory factorial analysis. The occurrence of gastrointestinal parasitism was 22.66% and the parasites found alone or in mixed infections were Ancylostoma spp., Trichuris vulpis, Toxocara spp., Dipylidium caninum, Cystoisospora spp., Giardia duodenalis, and coccidia. It was concluded that the occurrence of gastrointestinal parasites in dogs is frequent, and the variables associated with these infections were source origin, breed, age, coexistence with other animals, and dull fur.
Topics: Humans; Animals; Dogs; Parasites; Brazil; Dog Diseases; Prevalence; Intestinal Diseases, Parasitic; Feces
PubMed: 36651423
DOI: 10.1590/S1984-29612023004