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International Journal For Parasitology.... Aug 2023Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to...
Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Dog Diseases; Feces; Hookworm Infections; Nematoda; Parasite Egg Count; Praziquantel
PubMed: 37481894
DOI: 10.1016/j.ijpddr.2023.07.001 -
Scientific Reports Jul 2023Microbes play a key role in human gut homeostasis, metabolic, immunologic and physiopathology of the body. A longitudinal study conducted during 2018-2021 in the...
Microbes play a key role in human gut homeostasis, metabolic, immunologic and physiopathology of the body. A longitudinal study conducted during 2018-2021 in the Kintampo North Municipality in Ghana demonstrated low hookworm infection cure rates following treatment with a single dose of 400 mg albendazole in some communities. To investigate associations between hookworm infection and the gut microbiome, we examined stool samples from consented participants who were either cured or remained infected after treatment. At each time point, stool was collected prior to and 10-14 days after albendazole treatment. We used 16S rRNA amplicon sequencing of DNA extracted from stool samples to investigate the composition and diversity of the gut microbiota and to identify potential microbial biomarkers associated with treatment outcomes. Hookworm infection was associated with increased species richness (p = 0.0093). Among treated individuals, there was also a significant variation in microbiota composition at 10-14 days following single-dose albendazole treatment. Individuals cured of hookworm infection after treatment showed a significant reduction in microbiota composition when compared to their pre-treatment state (ANOSIM; p = 0.02), whilst individuals who failed to clear the infection showed no change in microbiota composition (ANOSIM; p = 0.35). Uninfected individuals and those who were successfully treated were similar in their microbial composition and structure. We also found that the abundance of Clostridia spp. was increased in infected individuals pre- or post-treatment. Predictive functional profiling revealed the enrichment of two pyruvate ferredoxin oxidoreductase subunit pathways in individuals who remained infected after treatment (p < 0.05), alluding to an upturn of strictly anaerobic commensal bacteria such as Clostridia spp. This study suggests a relationship between human gut microbiome dysbiosis and albendazole therapy outcomes of hookworm infection. Future studies will further characterize specific biomarkers identified within this study to establish their potential for assessment of pharmacological responses to anthelminthic therapies, as well as explore the possibility of using probiotic supplementation as an adjunct treatment to increase albendazole effectiveness against hookworm.
Topics: Humans; Animals; Gastrointestinal Microbiome; Ancylostomatoidea; Ghana; Albendazole; Longitudinal Studies; RNA, Ribosomal, 16S; Microbiota; Hookworm Infections
PubMed: 37438457
DOI: 10.1038/s41598-023-38376-3 -
PLoS Neglected Tropical Diseases Jul 2023Mass Drug Administration (MDA) is the main strategy for control of soil-transmitted helminth (STH) infections, with single-dose benzimidazole (albendazole or... (Randomized Controlled Trial)
Randomized Controlled Trial
The impact of dual- versus single-dosing and fatty food co-administration on albendazole efficacy against hookworm among children in Mayuge district, Uganda: Results from a 2x2 factorial randomised controlled trial.
BACKGROUND
Mass Drug Administration (MDA) is the main strategy for control of soil-transmitted helminth (STH) infections, with single-dose benzimidazole (albendazole or mebendazole) the principal MDA option. In Mayuge district, Uganda, an MDA programme has been in place for over fifteen years but hookworm infection remains common and there is concern that the effectiveness of single-dose albendazole as currently used for MDA may be sub-optimal. This study aims to assess the efficacy of dual- versus single-dose albendazole, with and without fatty food co-administration against hookworm, the dominant form of STHs in Mayuge district, Uganda.
METHODOLOGY
This was a 2x2 factorial randomised controlled trial to investigate two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty food (200 grams of avocado eaten directly after medication). School children with hookworm infection were randomised in a 1:1:1:1 ratio to the four possible treatment groups. Three weeks after the treatment, stool samples were collected from trial participants to evaluate trial outcomes: cure rate and egg reduction rate (ERR).
PRINCIPAL FINDINGS
A total of 225 participants were enrolled, and 222 (98.7%) seen at 3 weeks. The cure rate in the dual-dose group was 96.4% (95% CI: 90.9-99%), higher than 83.9% (95% CI: 75.7-90.2%) in the single-dose group (OR: 5.07, 95% CI:1.61-15.96, p = 0.002). The ERR was 97.6% and 94.5% in the dual-dose group and single-dose drug group, respectively (ERR difference 3.1%, 95% CI: -3.89-16.39%, p = 0.553). The cure rates among participants taking albendazole with and without avocado were 90.1% and 89.1%, respectively, with no statistical difference between the two groups (OR: 1.24, 95% CI: 0.51-3.03, p = 0.622). The ERR was 97.0% and 94.2% in the group receiving albendazole with and without avocado, respectively, and the difference in ERR between the two groups was 2.8% (95% CI -8.63-14.3%, p = 0.629).
CONCLUSIONS/SIGNIFICANCE
In Ugandan school children, dual-dose albendazole improves the cure rate of hookworm compared to single-dose albendazole. However, there was no significant improvement in cure rate or egg reduction rate of hookworm with fatty-food co-administration. Dual-dose albendazole is a feasible alternative for improving drug effectiveness against hookworm infection and minimising drug resistance.
TRIAL REGISTRATION
PACTR202202738940158.
Topics: Animals; Humans; Child; Albendazole; Anthelmintics; Ancylostomatoidea; Uganda; Hookworm Infections; Helminthiasis; Biological Products
PubMed: 37399169
DOI: 10.1371/journal.pntd.0011439 -
Archives of Razi Institute Apr 2023ancylostomatid spp. is the common parasitic intestinal nematode of reptiles. West-Asian blunt-nosed viper is a venomous snake found in extensive areas of Iran. From...
ancylostomatid spp. is the common parasitic intestinal nematode of reptiles. West-Asian blunt-nosed viper is a venomous snake found in extensive areas of Iran. From June to September 2017, two dead viper snakes were referred to a parasitology laboratory and examined for intestinal parasites. Several white elongated roundworms were collected and fixed to identify under light and scanning electron microscopes (SEM) based on morphological and molecular characteristics. For the molecular survey, some parts of the identified worms were extracted and the ITS of nuclear ribosomal DNA (rDNA) was amplified by polymerase chain reaction (PCR). Five roundworms were found in one snake and three worms with similar morphological characteristics in another one. All the collected female hookworms were taxonomically identified as . The SEM findings showed the head was small and had three dorsal, ventral, and middle circumoral papillae with a spike-like process on the median papilla of . Moreover, the buccal capsule was bivalvular and included two lateral valves consisting of several chitonid pieces. The tail of the female worm was slim and long with a blunt end and had a terminal spike at its end. In the molecular survey, the ITS of rDNA amplified at about 850 bp was identified as . The ITS gene rDNA phylogeny analysis of the sequence showed that the isolated species had high similarity to species from around the world and is close to with 88% discrepancies in the phylogenetic tree. The morphological characteristics and a large part of rDNA nucleotide sequence were reported in viper snakes for the first time in the world and in Iran.
Topics: Animals; Viperidae; Phylogeny; Iran; Ancylostomatoidea; Intestinal Diseases, Parasitic
PubMed: 37396723
DOI: 10.22092/ARI.2022.359446.2418 -
Parasites & Vectors Jun 2023Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water,...
Epidemiology of soil-transmitted helminths using quantitative PCR and risk factors for hookworm and Necator americanus infection in school children in Dak Lak province, Vietnam.
BACKGROUND
Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes.
METHODS
During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections.
RESULTS
The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P < 0.01), as did those whose primary female carer attended secondary (aOR 0.65, 95% CI 0.51, 0.84, P < 0.01) or tertiary education (aOR 0.39, 95% CI 0.24, 0.63, P < 0.01).
CONCLUSIONS
This study is the largest reported prevalence survey of STH infections conducted using qPCR as a diagnostic technique. The findings of higher adjusted odds of infection amongst ethnic minority children highlight that STH control programmes may not be reaching certain population groups and that additional culturally appropriate approaches may be required. Additionally, the associations between specific WASH factors and infection indicate potential programmatic targets to complement preventive chemotherapy programmes.
Topics: Animals; Humans; Child; Female; Necator americanus; Ancylostomatoidea; Soil; Cross-Sectional Studies; Vietnam; Ethnicity; Minority Groups; Helminths; Helminthiasis; Hookworm Infections; Polymerase Chain Reaction; Schools; Risk Factors; Prevalence; Water; Feces
PubMed: 37370075
DOI: 10.1186/s13071-023-05809-x -
PLoS Neglected Tropical Diseases Jun 2023Schistosomiasis and soil-transmitted helminth infections are among the neglected tropical diseases (NTDs) affecting primarily marginalized communities in low- and...
How do disease control measures impact spatial predictions of schistosomiasis and hookworm? The example of predicting school-based prevalence before and after preventive chemotherapy in Ghana.
BACKGROUND
Schistosomiasis and soil-transmitted helminth infections are among the neglected tropical diseases (NTDs) affecting primarily marginalized communities in low- and middle-income countries. Surveillance data for NTDs are typically sparse, and hence, geospatial predictive modeling based on remotely sensed (RS) environmental data is widely used to characterize disease transmission and treatment needs. However, as large-scale preventive chemotherapy has become a widespread practice, resulting in reduced prevalence and intensity of infection, the validity and relevance of these models should be re-assessed.
METHODOLOGY
We employed two nationally representative school-based prevalence surveys of Schistosoma haematobium and hookworm infections from Ghana conducted before (2008) and after (2015) the introduction of large-scale preventive chemotherapy. We derived environmental variables from fine-resolution RS data (Landsat 8) and examined a variable distance radius (1-5 km) for aggregating these variables around point-prevalence locations in a non-parametric random forest modeling approach. We used partial dependence and individual conditional expectation plots to improve interpretability of results.
PRINCIPAL FINDINGS
The average school-level S. haematobium prevalence decreased from 23.8% to 3.6% and that of hookworm from 8.6% to 3.1% between 2008 and 2015. However, hotspots of high-prevalence locations persisted for both infections. The models with environmental data extracted from a buffer radius of 2-3 km around the school location where prevalence was measured had the best performance. Model performance (according to the R2 value) was already low and declined further from approximately 0.4 in 2008 to 0.1 in 2015 for S. haematobium and from approximately 0.3 to 0.2 for hookworm. According to the 2008 models, land surface temperature (LST), modified normalized difference water index, elevation, slope, and streams variables were associated with S. haematobium prevalence. LST, slope, and improved water coverage were associated with hookworm prevalence. Associations with the environment in 2015 could not be evaluated due to low model performance.
CONCLUSIONS/SIGNIFICANCE
Our study showed that in the era of preventive chemotherapy, associations between S. haematobium and hookworm infections and the environment weakened, and thus predictive power of environmental models declined. In light of these observations, it is timely to develop new cost-effective passive surveillance methods for NTDs as an alternative to costly surveys, and to focus on persisting hotspots of infection with additional interventions to reduce reinfection. We further question the broad application of RS-based modeling for environmental diseases for which large-scale pharmaceutical interventions are in place.
Topics: Animals; Ancylostomatoidea; Prevalence; Ghana; Schistosomiasis; Hookworm Infections; Feces; Water
PubMed: 37327211
DOI: 10.1371/journal.pntd.0011424 -
Frontiers in Immunology 2023Helminth-induced eosinophils accumulate around the parasite at the site of infection, or in parasite-damaged tissues well after the helminth has left the site. The role...
Helminth-induced eosinophils accumulate around the parasite at the site of infection, or in parasite-damaged tissues well after the helminth has left the site. The role of helminth-elicited eosinophils in mediating parasite control is complex. While they may contribute to direct parasite-killing and tissue repair, their involvement in long-term immunopathogenesis is a concern. In allergic Siglec-FCD101, eosinophils are associated with pathology. Research has not shown if equivalent subpopulations of eosinophils are a feature of helminth infection. In this study, we demonstrate that lung migration of rodent hookworm () results in a long-term expansion of distinct Siglec-FCD101 eosinophil subpopulations. -elevated eosinophil populations in the bone marrow and circulation did not present this phenotype. Siglec-FCD101 lung eosinophils exhibited an activated morphology including nuclei hyper-segmentation and cytoplasm degranulation. Recruitment of ST2 ILC2s and not CD4 T cells to the lungs was associated with the expansion of Siglec-FCD101 eosinophils. This data identifies a morphologically distinct and persistent subset of Siglec-FCD101 lung eosinophils induced following infection. These eosinophils may contribute to long-term pathology following helminth infection.
Topics: Animals; Mice; Ancylostomatoidea; Eosinophils; Hookworm Infections; Immunity, Innate; Lung; Lymphocytes; Nippostrongylus; Sialic Acid Binding Immunoglobulin-like Lectins
PubMed: 37251384
DOI: 10.3389/fimmu.2023.1170807 -
International Journal For Parasitology.... Aug 2023Reports of anthelmintic resistance in Ancylostoma caninum are increasing in frequency in the United States of America (USA). In the last few years in vitro and in vivo... (Review)
Review
Reports of anthelmintic resistance in Ancylostoma caninum are increasing in frequency in the United States of America (USA). In the last few years in vitro and in vivo studies characterized individual isolates, demonstrating multiple anthelmintic drug resistance (MADR). In 2021, the American Association of Veterinary Parasitologists initiated a hookworm task force to address this issue. The first report of drug resistant A. caninum occurred in 1987 in Australian racing Greyhounds. In the last five years multiple case reports and investigations show drug resistant A. caninum is becoming a much greater problem in the USA and now extends beyond racing Greyhounds into the general companion animal dog population. The literature, regarding drug resistance in livestock and equine nematodes, provides helpful guidance along with diagnostic methods to better understand the evolution and selection of canine MADR hookworms; however, there are limitations and caveats due to A. caninum's unique biology and zoonotic potential. Mass drug administration (MDA) of anthelminthic drugs to humans to reduce morbidity associated with human hookworms (Necator americanus) should consider the factors that contributed to the development of MADR A. caninum. Finally, as Greyhound racing undergoes termination in some regions and the retired dogs undergo subsequent rehoming, drug resistant parasites, if present, are carried with them. Drug resistant A. caninum requires greater recognition by the veterinary community, and small animal practitioners need to be aware of the spread into current pet dog populations. The current understanding of anthelmintic resistance, available treatments, and environmental mitigation for these drug resistant A. caninum isolates must be monitored for horizontal spread. A major goal in this emerging problem is to prevent continued dissemination.
Topics: Animals; Dogs; Horses; Humans; Ancylostoma; Ancylostomiasis; Dog Diseases; Australia; Anthelmintics; Ancylostomatoidea
PubMed: 37229949
DOI: 10.1016/j.ijpddr.2023.04.003 -
Antimicrobial Agents and Chemotherapy Jun 2023In humans, nematode infections are prevalent in developing countries, causing long-term ill health, particularly in children. Worldwide, nematode infections are...
In humans, nematode infections are prevalent in developing countries, causing long-term ill health, particularly in children. Worldwide, nematode infections are prevalent in livestock and pets, affecting productivity and health. Anthelmintic drugs are the primary means of controlling nematodes, but there is now high prevalence of anthelmintic resistance, requiring urgent identification of new molecular targets for anthelmintics with novel mechanisms of action. Here, we identified orthologous genes for phosphoethanolamine methyltransferases (PMTs) in nematodes within the families , , , , and . We characterized these putative PMTs and found that they possess PMT catalytic activities. By complementing a mutant yeast strain lacking the ability to synthesize phosphatidylcholine, the PMTs were validated to catalyze the biosynthesis of phosphatidylcholine. Using an phosphoethanolamine methyltransferase assay with PMTs as enzymes, we identified compounds with cross-inhibitory effects against the PMTs. Corroboratively, treatment of PMT-complemented yeast with the PMT inhibitors blocked growth of the yeast, underscoring the essential role of the PMTs in phosphatidylcholine synthesis. Fifteen of the inhibitors with the highest activity against complemented yeast were tested against Haemonchus contortus using larval development and motility assays. Among them, four were found to possess potent anthelmintic activity against both multiple drug-resistant and susceptible isolates of , with IC values (95% confidence interval) of 4.30 μM (2.15-8.28), 4.46 μM (3.22-6.16), 28.7 μM (17.3-49.5), and 0.65 μM (0.21-1.88). Taken together, we have validated a molecular target conserved in a broad range of nematodes and identified its inhibitors that possess potent anthelmintic activity.
Topics: Animals; Child; Humans; Saccharomyces cerevisiae; Anthelmintics; Nematoda; Methyltransferases; Haemonchus; Nematode Infections; Phosphatidylcholines
PubMed: 37212658
DOI: 10.1128/aac.00008-23 -
International Journal For Parasitology Jul 2023Hookworms (genera Ancylostoma and Necator) are amongst the most prevalent and important parasites of humans globally. These intestinal parasites ingest blood, resulting...
Hookworms (genera Ancylostoma and Necator) are amongst 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 and recovery of parasites. Here, we describe a robust method for long-term (≥3 year) cryopreservation and recovery of both Ancylostoma and Necator hookworms that is also applicable to two other intestinal parasites that passage through the infective L3 stage, Strongyloides ratti and Heligmosomoides polygyrus bakeri. The key is a revised recovery method, in which cryopreserved L1s are thawed and raised to the infective L3 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.
Topics: Animals; Humans; Dogs; Ancylostomatoidea; Nematoda; Hookworm Infections; Ancylostoma; Intestinal Diseases, Parasitic; Cryopreservation; Mammals
PubMed: 37201563
DOI: 10.1016/j.ijpara.2023.05.001