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Parasites & Vectors May 2023Few anthelminthics are currently available, manifesting the urgent need for new treatment options. In vitro profiling of current anthelminthics against larval and adult...
BACKGROUND
Few anthelminthics are currently available, manifesting the urgent need for new treatment options. In vitro profiling of current anthelminthics against larval and adult stage helminths displayed varying effects on closely related worm species and between life stages of the same species. Conversely, limited research has been performed on the egg stage of human hookworms, and the effects of investigational compounds on the egg stage are not routinely assessed.
METHODS
We profiled the development and hatching of Heligmosomoides polygyrus, Ancylostoma duodenale and Necator americanus eggs isolated from rodent faeces in liquid media with various nutrient levels, osmolar concentrations, and acidities in dependence on incubation temperature and light exposure. Incubation conditions were optimised to allow the study of drug effect on immature and embryonated eggs. We analysed concentration-effect relationships of commercially available anthelminthics over 72 h.
RESULTS
Rapid embryonation and hatching were observed at room temperature with and without light exposure without nutrient supplementation in a wide range of acidities. Hookworms hatched optimally at room temperature in PBS achieving > 75% hatching over 34 h. Developmental delays were seen when eggs were stored at 4 °C with no effect on viability. Similar delays were also seen with increased osmolar concentrations resulting in decreased viability. Benzimidazole anthelminthics effectively reduced the viability and prevented hatching of hookworm eggs, with albendazole and thiabendazole eliciting particularly potent effects at EC values below 1 µM. Macrolide anthelminthics as well as emodepside, oxantel pamoate, and pyrantel pamoate were inactive while monepantel, levamisole, and tribendimidine displayed varied potencies among the hookworm species.
CONCLUSION
The presented egg-hatching assay will complement ongoing anthelminthic drug discovery and allow a full characterisation of drug activity against all life stages. In the development and application of the egg-hatching assay, good accordance was observed between the three hookworm species evaluated. Marketed anthelminthics show differences of drug action compared to larval and adult stages highlighting the importance of profiling drug activity against all life stages.
Topics: Animals; Adult; Humans; Anthelmintics; Hookworm Infections; Ancylostomatoidea; Albendazole; Necator americanus; Ancylostoma; Larva
PubMed: 37143169
DOI: 10.1186/s13071-023-05771-8 -
Pathogens (Basel, Switzerland) Apr 2023Hookworm infection is one of the most common neglected tropical diseases and is mainly found in tropical and subtropical areas. Two species of human hookworm are...
UNLABELLED
Hookworm infection is one of the most common neglected tropical diseases and is mainly found in tropical and subtropical areas. Two species of human hookworm are distributed in China, i.e., (AD) and (NA).
BACKGROUND
Traditional microscopic technology such as the Kato-Katz method is not suitable for hookworm diagnosis due to the rapid degeneration of fragile hookworm eggs or for species identification of hookworm infection. The aim of the present study was to establish and evaluate a novel nucleic acid detection method based on recombinase-aided isothermal amplification (RAA) for the detection of hookworm infections and species identification.
METHODS
Based on the specific target gene sequences of hookworms ( for AD and for NA, respectively), we designed and synthesized amplification primers and fluorescence probes referring to the principle of the fluorescence recombinase-aided amplification (RAA) technique.
RESULTS
Each assay provided specific amplification of larval DNA from AD and NA by fluorescence RAA, and the detection limits in plasmids reached 10 copies and 10 copies, respectively. Genomic DNA of two hookworm species was successfully detected at a concentration of 0.1 pg/μL, revealing a high detection sensitivity. No positive amplification occurred for genomic DNA from crossed hookworm species and genomic DNA from , , , , , and , revealing a satisfactory specificity. Fecal sample detection results demonstrated a similar efficacy to the Kato-Katz method; however, it had a greater sensitivity than the larvae culture method.
CONCLUSION
A simple and rapid nucleic acid method was successfully established based on RAA, which improved the detection efficacy and species identification for human hookworm infections.
PubMed: 37111516
DOI: 10.3390/pathogens12040630 -
International Maritime Health 2023Dermatological disorders are among the most common complaints of patients seeking medical assistance after returning from trips to tropical countries. Among exotic...
Dermatological disorders are among the most common complaints of patients seeking medical assistance after returning from trips to tropical countries. Among exotic dermatoses, one of the frequently encountered diagnoses is Cutaneous Larva Migrans (CLM), primarily caused by the nematodes Ancylostoma braziliense and A. caninum. Cats and dogs, which serve as the definitive hosts for these nematodes, excrete with their stool parasite eggs into the environment, where they transform into larvae. Human infection occurs through the invasive form of the larvae, which penetrate the skin, causing itching and the characteristic serpiginous, slightly raised, and enlarging lesion at the site of invasion. Diagnosis is made based on the highly characteristic clinical presentation, although in non-endemic countries, diagnostic errors and delays in initiating effective causal treatment are relatively common. Effective therapy includes oral albendazole and ivermectin. Prevention of CLM involves avoiding skin contact with potentially contaminated soil by wearing shoes and using towels and mats on the beach. Due to the high interest in travel and the risk of importing exotic diseases, it is important to promote knowledge of tropical medicine among healthcare professionals as well as the travellers.
Topics: Humans; Animals; Cats; Dogs; Larva Migrans; Ivermectin; Albendazole; Travel; Feces
PubMed: 38111246
DOI: 10.5603/imh.98098 -
Tropical Parasitology 2023The complex life cycle of geohelminth parasites make it difficult to manage repeated infections that occur in endemic areas, that requires the development of new...
BACKGROUND
The complex life cycle of geohelminth parasites make it difficult to manage repeated infections that occur in endemic areas, that requires the development of new therapeutic strategies. Human hookworm . and . are a serious problem in many areas of the world where the old age anti-helminthics are ineffective. To address this, we have tried a non-traditional therapeutic approach for a sustainable solution to manage parasite infections.
AIMS AND OBJECTIVES
In this study, we attempted to develop a new type of therapy using value-added probiotics-producing antiparasitic RNA interference (RNAi) molecules against a vital hookworm ( sp.) enzyme, astacin-like metalloprotease -MTP-1. A new gut delivery RNAi vector was designed to produce double-stranded RNA (dsRNA) against the target to be delivered by feeding with a probiotic lactis that when administered in endemic areas can potentially be used to control the spread of infection by interrupting the life cycle of hookworm.
RESULTS
The engineered probiotics colonizing the gut, when consumed by the parasite released the dsRNA that which knocked down the target by RNAi interfering with their moulting and tissue migration. The initial penetration of the larvae into the gut lining was reduced by 70%, followed by a reduction of up to 50% in migration to the critical organs. The damage caused to the liver (30%-40%) and the kidneys (50%-60%) by the hookworm in mouse models as quantitated by enzymes released in the blood was totally reversed when the worms were pre fed with the engineered L. lactis before the parasite challenge.
CONCLUSIONS
We believe that this is the first demonstrated knockdown of a target gene in hookworms using probiotics genetically engineered to stimulate RNAi (RNAi food), administered through the oral route. This novel method of parasite control when extended to other hookworms, and can augment the efficacy of the existing anthelminthics if combined with them.
PubMed: 37860612
DOI: 10.4103/tp.tp_74_22 -
PLoS Neglected Tropical Diseases Oct 2022Soil-transmitted helminths (STH) infect 1.5 billion people and countless animals worldwide. In Australian Indigenous communities, STH infections have largely remained... (Meta-Analysis)
Meta-Analysis
Soil-transmitted helminths (STH) infect 1.5 billion people and countless animals worldwide. In Australian Indigenous communities, STH infections have largely remained endemic despite control efforts, suggesting reservoirs of infection may exist. Dogs fulfil various important cultural, social and occupational roles in Australian Indigenous communities and are populous in these settings. Dogs may also harbour zoonotic STHs capable of producing morbidity and mortality in dogs and humans. This review provides an overview of human and zoonotic STH infections, identifies the Australian Indigenous locations affected and the parasite species and hosts involved. The meta-analysis provides estimates of individual study and pooled true prevalence of STH infections in Australian Indigenous communities and identifies knowledge gaps for further research on zoonotic or anthroponotic potential. A systematic literature search identified 45 eligible studies documenting the presence of Strongyloides stercoralis, Trichuris trichiura, Ancylostoma caninum, Ancylostoma duodenale, Ancylostoma ceylanicum, undifferentiated hookworm, and Ascaris lumbricoides. Of these studies, 26 were also eligible for inclusion in meta-analysis to establish true prevalence in the light of imperfect diagnostic test sensitivity and specificity by Rogan-Gladen and Bayesian methods. These studies revealed pooled true prevalence estimates of 18.9% (95% CI 15.8-22.1) for human and canine S. stercoralis infections and 77.3% (95% CI 63.7-91.0) for canine A. caninum infections indicating continued endemicity, but considerably more heterogenous pooled estimates for canine A. ceylanicum infections, and A. duodenale, undifferentiated hookworm and T. trichiura in humans. This review suggests that the prevalence of STHs in Australian Indigenous communities has likely been underestimated, principally based on imperfect diagnostic tests. Potential misclassification of hookworm species in humans and dogs due to outdated methodology, also obscures this picture. High-quality contemporary studies are required to establish current true prevalence of parasite species in all relevant hosts to guide future policy development and control decisions under a culturally sound One Health framework.
Topics: Humans; Dogs; Animals; Soil; Bayes Theorem; Australia; Helminths; Ascaris lumbricoides; Trichuris; Helminthiasis; Hookworm Infections; Ancylostomatoidea; Ancylostoma; Zoonoses; Prevalence; Feces
PubMed: 36279298
DOI: 10.1371/journal.pntd.0010895 -
Revista Brasileira de Parasitologia... 2020Endoparasitic infections are associated with morbidity in cats. This study aimed to investigate the occurrence of endoparasites among cats of different life stages in...
Endoparasitic infections are associated with morbidity in cats. This study aimed to investigate the occurrence of endoparasites among cats of different life stages in the city of Rio de Janeiro, Brazil. The samples were analyzed individually by macroscopic exploration for proglottids and centrifugal-flotation. Stool samples were obtained from household cats (n = 57) and shelter cats (n = 336). Endoparasites were detected in 50.64% of the samples. Among household and shelter cats, 21.05% and 55.66% were infected with endoparasites, respectively. In household cats, the most prevalent endoparasites were Ancylostoma spp. (in 25.0%) and Strongyloides spp. (in 25.0%), followed by Toxocara spp. (in 16.67%), Dipylidium caninum (in 16.67%), Cystoisospora spp. (in 8.33%), and Uncinaria spp. + Ancylostoma spp. (in 8.33%). In shelter cats, the most prevalent endoparasite was Ancylostoma spp. (in 29.41%), followed by Cystoisospora spp. (in 26.20%) and Toxocara spp. (in 16.58%), as well as Cystoisospora spp. + Toxocara spp. (in 8.02%); Ancylostoma spp. + Toxocara spp. (in 11.76%); Cystoisospora spp. + Ancylostoma spp. (in 3.74%); Cystoisospora spp. + Toxocara spp. + Ancylostoma spp. (in 3.21%); and Dipylidium caninum + Ancylostoma spp. (in 0.53%). Endoparasitic infections in cats underscore the need for preventive veterinary care and routine coproparasitologic tests.
Topics: Animals; Brazil; Cat Diseases; Cats; Feces; Helminthiasis, Animal; Prevalence; Protozoan Infections, Animal
PubMed: 32294719
DOI: 10.1590/S1984-29612019110 -
Parasite Epidemiology and Control Feb 2022is a helminth zoonosis that is estimated to infect more than 100 million dogs and 1 billion people, mostly in the tropics. Humans can be infected by accidentally...
is a helminth zoonosis that is estimated to infect more than 100 million dogs and 1 billion people, mostly in the tropics. Humans can be infected by accidentally ingesting embryonated eggs from the environment or occasionally after ingesting L larvae from paratenic hosts. This study investigated the importance of vertical transmission and the role of puppies in the epidemiology of through the examination of fecal samples from dogs less than one year of age in Grenada, West Indies, a small island tropical developing country. Samples were stored at 4 °C or in 10% formalin until microscopic examination for helminth eggs or using a rapid antigen test for the presence of protozoan species. A knowledge, attitudes and practices study was completed among dog owners, physicians and veterinary students. Of 306 dogs less than one year of age, 147 (48%) were found to have eggs. Vertical transmission was indicated by the proportion of infected dogs increasing from 50% at two weeks of age (from in utero transmission) to 70% by 12 weeks (in utero and lactogenic transmission). After 12 weeks the positivity rate dropped rapidly with no dogs over 40 weeks of age being infected. As eggs were found in puppy feces at two weeks of age, initial treatment of puppies should begin earlier, at twelve days post-partum, than currently recommended to prevent shedding of eggs. Perhaps even more importantly, treatment of pregnant dogs, preventing vertical transmission, would have a major impact on the control of infection. Knowledge of . and other zoonotic helminths such as was found to be low among dog owners, physicians and veterinary students. None of the dog owners treated their dogs for helminths, all were unaware of the risk of zoonoses, and only 9% picked up dog feces. Efforts to prevent vertical transmission and to increase awareness and knowledge of these zoonoses could result in reducing their public health impact.
PubMed: 34917784
DOI: 10.1016/j.parepi.2021.e00232 -
The Cochrane Database of Systematic... Jun 2022It is estimated that 1.5 billion people are infected with soil-transmitted helminths (STHs) worldwide. Re-infection occurs rapidly following deworming, and interruption... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is estimated that 1.5 billion people are infected with soil-transmitted helminths (STHs) worldwide. Re-infection occurs rapidly following deworming, and interruption of transmission is unlikely without complementary control efforts such as improvements in water, sanitation, and hygiene (WASH) access and behaviours.
OBJECTIVES
To assess the effectiveness of WASH interventions to prevent STH infection.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 19 October 2021.
SELECTION CRITERIA
We included interventions to improve WASH access or practices in communities where STHs are endemic. We included randomized controlled trials (RCTs), as well as trials with an external control group where participants (or clusters) were allocated to different interventions using a non-random method (non-RCTs). We did not include observational study designs. Our primary outcome was prevalence of any STH infection. Prevalence of individual worms was a secondary outcome, including for Ascaris lumbricoides, Trichuris trichiura, hookworm (Ancylostoma duodenale or Necator americanus), or Strongyloides stercoralis. Intensity of infection, measured as a count of eggs per gram of faeces for each species, was another secondary outcome.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed titles and abstracts and full-text records for eligibility, performed data extraction, and assessed risk of bias using the Cochrane risk of bias assessment tool for RCTs and the EPOC tool for non-RCTs. We used a random-effects meta-analysis to pool study estimates. We used Moran's I² statistic to assess heterogeneity and conducted subgroup analyses to explore sources of heterogeneity. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 32 studies (16 RCTs and 16 non-RCTs) involving a total of 52,944 participants in the review. Twenty-two studies (14 RCTs (16 estimates) and eight non-RCTs (11 estimates)) reported on our primary outcome, prevalence of infection with at least one STH species. Twenty-one studies reported on the prevalence of A lumbricoides (12 RCTs and 9 non-RCTs); 17 on the prevalence of T trichiura (9 RCTs and 8 non-RCTs); 18 on the prevalence of hookworm (10 RCTs and 8 non-RCTs); and one on the prevalence of S stercoralis (1 non-RCT). Sixteen studies measured the intensity of infection for an individual STH type. Ten RCTs and five non-RCTs reported on the intensity of infection of A lumbricoides; eight RCTs and five non-RCTs measured the intensity of infection of T trichiura; and eight RCTs and five non-RCTs measured the intensity of hookworm infection. No studies reported on the intensity of infection of S stercoralis. The overall pooled effect estimates showed that the WASH interventions under study may result in a slight reduction of any STH infection, with an odds ratio (OR) of 0.86 amongst RCTs (95% confidence interval (CI) 0.74 to 1.01; moderate-certainty evidence) and an OR of 0.71 amongst non-RCTs (95% CI 0.54 to 0.94; low-certainty evidence). All six of the meta-analyses assessing individual worm infection amongst both RCTs and non-RCTs had pooled estimates in the preventive direction, although all CIs encapsulated the null, leaving the possibility of the null or even harmful effects; the certainty of the evidence ranged from very low to moderate. Individual studies assessing intensity of infection showed mixed evidence supporting WASH. Subgroup analyses focusing on narrow specific subsets of water, sanitation, and hygiene interventions did very little to elucidate which interventions might be better than others. Data on intensity of infection (e.g. faecal egg count) were reported in a variety of ways across studies, precluding the pooling of results for this outcome. We did not find any studies reporting adverse events resulting from the WASH interventions under study or from mass drug administration (MDA).
AUTHORS' CONCLUSIONS
Whilst the available evidence suggests that the WASH interventions under study may slightly protect against STH infection, WASH also serves as a broad preventive measure for many other diseases that have a faecal oral transmission route of transmission. As many of the studies were done in addition to MDA/deworming (i.e. MDA was ongoing in both the intervention and control arm), our data support WHO recommendations for implementation of improvements to basic sanitation and adequate access to safe water alongside MDA. The biological plausibility for improved access to WASH to interrupt transmission of STHs is clear, but WASH interventions as currently delivered have shown impacts that were lower than expected. There is a need for more rigorous and targeted implementation research and process evaluations in order that future WASH interventions can better provide benefit to users. Inconsistent reporting of the intensity of infection underscores the need to define the minimal, standard data that should be collected globally on STHs to enable pooled analyses and comparisons.
Topics: Animals; Ascaris lumbricoides; Humans; Hygiene; Observational Studies as Topic; Sanitation; Soil; Water
PubMed: 35726112
DOI: 10.1002/14651858.CD012199.pub2 -
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 -
Veterinary Parasitology Jun 2019A new topical formulation of selamectin plus sarolaner (Revolution Plus/Stronghold Plus, Zoetis) was evaluated in the treatment and control of naturally occurring...
Efficacy and safety of a new topical formulation of selamectin plus sarolaner in the treatment and control of natural infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States.
A new topical formulation of selamectin plus sarolaner (Revolution Plus/Stronghold Plus, Zoetis) was evaluated in the treatment and control of naturally occurring infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States. Three thousand three hundred three (3303) cats were screened in 25 veterinary practices in 15 states and 153 hookworm-positive cats (A. tubaeforme and/or A. braziliense), mainly from Alabama, Mississippi, Texas, and Hawaii, were identified; 135 cats met all the criteria for enrollment and were included on study. The cats were randomly assigned to treatment with Revolution (at the label dosage, to provide a minimum dosage of 6 mg/kg selamectin) or selamectin plus sarolaner (at a dosage of 6-12 mg/kg plus 1-2 mg/kg, respectively). Treatments were administered at the time of enrollment and repeated 30 days later. Fecal samples were collected for differential fecal egg count prior to the first treatment (Day 0), prior to the second treatment (Day 30), and approximately 30 days later (Day 60). Efficacy was based on the percentage reductions in geometric mean fecal egg count for A. tubaeforme on Day 30 and Day 60 compared with Day 0. Where cats were co-infected with T. cati, efficacy against this species was also evaluated. Efficacy data were evaluated for A. tubaeforme for 40 cats on both Day 30 and Day 60 for the group treated with the selamectin/sarolaner combination and reductions in geometric mean fecal egg counts of 99.4% and 99.7% were demonstrated for Day 30 and Day 60, respectively. For the group treated with selamectin alone, 44 and 40 cats were evaluated and percent reductions for Day 30 and Day 60 were 99.5% and 99.9%, respectively. For T. cati, 14 cats were evaluated in the selamectin/sarolaner-treated group for Day 30 and for Day 60, and the reduction in geometric mean fecal egg count was 100% for both days. There were 11 and 9 cats evaluated for Day 30 and Day 60, respectively, for the selamectin-treated group and the reduction was again 100% for both days. The geometric mean fecal egg counts post-treatment were significantly lower than pre-treatment for both A. tubaeforme and T. cati, for both treatments, and for both periods of interest (P < 0.0001). No serious adverse events related to treatment with either product occurred during the study. Thus, both selamectin alone and the combination product of selamectin/sarolaner were safe and effective when administered on a monthly basis for the treatment and control of natural infections of A. tubaeforme and T. cati. The addition of sarolaner to the formulation did not interfere with the efficacy of selamectin against these nematodes.
Topics: Ancylostoma; Ancylostomiasis; Animals; Antiparasitic Agents; Azetidines; Cat Diseases; Cats; Female; Ivermectin; Male; Random Allocation; Spiro Compounds; Toxocara; Toxocariasis; Treatment Outcome; United States
PubMed: 30470638
DOI: 10.1016/j.vetpar.2018.10.012