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Parasites & Vectors May 2021The hookworm, Ancylostoma caninum, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. Both the immature and adult stages of A....
Effectiveness of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio Plus) for the treatment of larval and immature adult stages of Ancylostoma caninum in experimentally infected dogs.
BACKGROUND
The hookworm, Ancylostoma caninum, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. Both the immature and adult stages of A. caninum ingest large volumes of blood during the feeding process and can cause severe anemia and death in young dogs, even before patent infections can be diagnosed using routine faecal examination methods. Thus, effective treatment of any pre-patent stages of immature hookworms can reduce or eliminate the risk of clinical disease in infected dogs and additionally reduce environmental contamination of eggs and infective larvae. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to evaluate the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus) administered orally to dogs experimentally infected with immature (L4 and immature adult [L5]) stages of A. caninum.
METHODS
Treatments using the intended global commercial tablet formulation of Credelio Plus were administered in a time frame relative to inoculation with infective larvae so that effectiveness could be assessed against each specific immature stage of A. caninum. In each study, dogs were randomized to one of six (study 1) or four (study 2) treatment groups. Each treatment group contained 8 (study 1) or 10 (study 2) dogs that had been experimentally inoculated with infective A. caninum larvae on day 0 and were dosed once on day 7 or day 11. Enrolled subjects were administered placebo tablets, Credelio Plus tablets, or lotilaner mono tablets to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 days after their respective treatment. All nematodes recovered from the gastrointestinal tract at necropsy were counted by species and stage.
RESULTS
For both dose confirmation studies and based on geometric mean worm counts, efficacy of Credelio Plus was ≥ 97.3% against L4 larval stage of A. caninum and ≥ 98.7% against immature adult (L5) A. caninum.
CONCLUSIONS
These studies demonstrated that the orally administered Credelio Plus combination tablet was highly efficacious in treating immature (L4 and immature adult [L5]) stages of A. caninum in experimentally infected dogs.
Topics: Administration, Oral; Ancylostoma; Ancylostomiasis; Animals; Anthelmintics; Dog Diseases; Dogs; Drug Combinations; Female; Intestinal Diseases, Parasitic; Larva; Macrolides; Male; Oxazoles; Parasite Egg Count; Random Allocation; Thiophenes; Treatment Outcome
PubMed: 34001200
DOI: 10.1186/s13071-021-04761-y -
BMJ Case Reports Jan 2021Cutaneous larva migrans is an acquired, self-limited infestation caused by cat hookworm, , and dog hookworm, The disease is acquired by direct contact with contaminated...
Cutaneous larva migrans is an acquired, self-limited infestation caused by cat hookworm, , and dog hookworm, The disease is acquired by direct contact with contaminated soil. Circumrotation is a religious ritual practised by devotees of Hinduism as a fulfilment of vows taken at the shrine and involves rolling over with uncovered upper body on the sand over a distance of up to 600 m. It is a reported mode of acquisition of cutaneous larva migrans infestation. The authors report a 10-year-old boy who acquired cutaneous larva migrans on his right forearm after circumrotation. The forearm is an unusual site for this infestation, and most reported cases had lesions on the feet, thighs and buttocks following either sitting or playing on contaminated soil. The child made complete recovery following treatment with albendazole for 1 week.
Topics: Albendazole; Ancylostomiasis; Anthelmintics; Ceremonial Behavior; Child; Forearm; Hinduism; Humans; Larva Migrans; Male
PubMed: 33495176
DOI: 10.1136/bcr-2020-237204 -
Parasitology Dec 2020Hookworms are some of the most widespread of the soil-transmitted helminths (STH) with an estimated 438.9 million people infected. Until relatively recently Ancylostoma...
Hookworms are some of the most widespread of the soil-transmitted helminths (STH) with an estimated 438.9 million people infected. Until relatively recently Ancylostoma ceylanicum was regarded as a rare cause of hookworm infection in humans, with little public health relevance. However, recent advances in molecular diagnostics have revealed a much higher prevalence of this zoonotic hookworm than previously thought, particularly in Asia. This study examined the prevalence of STH and A. ceylanicum in the municipalities of Palapag and Laoang in the Philippines utilizing real-time polymerase chain reaction (PCR) on stool samples previously collected as part of a cross-sectional survey of schistosomiasis japonica. Prevalence of hookworm in humans was high with 52.8% (n = 228/432) individuals positive for any hookworm, 34.5% (n = 149/432) infected with Necator americanus, and 29.6% (n = 128/432) with Ancylostoma spp; of these, 34 were PCR-positive for A. ceylanicum. Considering dogs, 12 (n = 33) were PCR-positive for A. ceylanicum. This is the first study to utilize molecular diagnostics to identify A. ceylanicum in the Philippines with both humans and dogs infected. Control and elimination of this zoonotic hookworm will require a multifaceted approach including chemotherapy of humans, identification of animal reservoirs, improvements in health infrastructure, and health education to help prevent infection.
Topics: Adolescent; Adult; Aged; Ancylostoma; Ancylostomiasis; Animals; Child; Child, Preschool; Dog Diseases; Dogs; Feces; Female; Humans; Male; Middle Aged; Philippines; Prevalence; Real-Time Polymerase Chain Reaction; Soil; Young Adult
PubMed: 32829714
DOI: 10.1017/S0031182020001547 -
Safety and Health At Work Jun 2020The aim of this study is to illustrate the historical role of the International Commission on Occupational Health (ICOH) congresses as an arena where national and...
BACKGROUND
The aim of this study is to illustrate the historical role of the International Commission on Occupational Health (ICOH) congresses as an arena where national and international occupational medicine can dialogue and as the first example of scientific transferability of the research and prevention results that have had such an impact on global public health.
METHODS
We used the ICOH Heritage Repository, in which ICOH congress proceedings (from the first congress in Milan in 1906 to the last congress, held in Dublin in 2018), are organised in an orderly way, updated and easily accessible according to open access logic.
RESULTS
We describe studies by three physicians who submitted significant scientific work to ICOH congresses, one on the battle against ancylostomiasis (Volante, 1906), the second (Quarelli, 1928) on carbon disulphide poisoning, and the third (Viola, 1969) on the carcinogenicity of vinyl chloride monomer. Priority is given to Italian cases, on account of the authors' obvious familiarity with the issues.
CONCLUSION
The visibility offered in ICOH conferences and their published proceedings has boosted the international spread of their findings, contributing to the scientific transferability of the research results and influencing the development of policies and prevention interventions that have had a great impact on global public health.
PubMed: 32596018
DOI: 10.1016/j.shaw.2020.03.004 -
The American Journal of Tropical... Aug 2020We reported 865 cases of soil-transmitted nematodiasis occurring in Japan during 2000-2017. The predominant nematode was ( = 279, 32.3% of all cases), and other species...
We reported 865 cases of soil-transmitted nematodiasis occurring in Japan during 2000-2017. The predominant nematode was ( = 279, 32.3% of all cases), and other species included (30.7%), (23.1%), and spp. (13.9%). was detected primarily in patients in Okinawa and Kagoshima prefectures, which are in the south of Japan and are endemic areas for this parasitic infection, and also in about half of the prefectures of all Japan. At least 15.5 cases of strongyloidiasis occurred on average each year. The period incidence rate of strongyloidiasis cases relative to the total population of Japan was 0.012 cases per 10 person-years. The male-to-female ratio was 2.1. The average age was 75.1 ± 16.9 years, and 96.1% of patients were older than 50 years. Several reasons may explain why this previously non-endemic outside of Okinawa region, serious nematode disease is now found in much of Japan, including the increased number of transmigration and sightseeing trips in Japan, use of immunosuppressive drugs, and lack of awareness of the risks. Thus, information of strongyloidiasis and its risks must be disseminated to travelers, residents, and physicians to prevent this life-threatening parasite infection.
Topics: Adult; Aged; Aged, 80 and over; Ancylostomiasis; Animals; Ascariasis; Ascaris lumbricoides; Female; Humans; Japan; Male; Middle Aged; Strongyloides stercoralis; Strongyloidiasis; Trichuriasis; Trichuris; Young Adult
PubMed: 32588800
DOI: 10.4269/ajtmh.19-0969 -
PLoS Neglected Tropical Diseases Jun 2020The canine hookworms Ancylostoma braziliense, Ancylostoma ceylanicum, Ancylostoma caninum and Uncinaria stenocephala are not only capable of producing morbidity and...
The canine hookworms Ancylostoma braziliense, Ancylostoma ceylanicum, Ancylostoma caninum and Uncinaria stenocephala are not only capable of producing morbidity and mortality in dogs but are also neglected tropical zoonoses. Each hookworm species differs considerably in its geographical distribution, life cycle, biology, pathogenic impacts on both canine and human hosts, zoonotic potential, and response to treatment with anthelminthics. Here we describe the development and validation of two Taq-Man based multiplex PCR assays capable of detecting and differentiating all four canine hookworm species in faeces of naturally infected dogs. The analytical sensitivity of both assays was assessed using 10-fold serial dilutions of synthetic gene block fragments containing individual sequence targets of each hookworm species. The sensitivity of the assays and ability to detect mixed species infections were compared to a conventional PCR-Restriction Fragment Length Polymorphism based-approach when applied to laboratory and field samples from endemic areas. The qPCRs detected at least one species of hookworms in 82.4% of PCR-RFLP-negative but microscopy-positive samples. The qPCRs detected an additional 68% mixed infections with different species of canine hookworms, and additional single species infection with A. caninum (47%), U. stenocephala (33%) and A. ceylanicum (0.02%) that were missed by PCR-RFLP. These multiplex qPCR assays will assist field based epidemiological surveillance studies towards an accurate and sensitive monitoring of canine hookworm infections in dogs, to inform their species-specific zoonotic risks to populations living in endemic areas, globally.
Topics: Ancylostoma; Ancylostomatoidea; Ancylostomiasis; Animals; DNA, Helminth; Dog Diseases; Dogs; Feces; Hookworm Infections; Humans; Multiplex Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sensitivity and Specificity; Zoonoses
PubMed: 32542036
DOI: 10.1371/journal.pntd.0008392 -
International Journal For Parasitology.... Aug 2020Ancylostoma caninum is the most prevalent intestinal nematode of dogs, and has a zoonotic potential. Multiple-drug resistance (MDR) has been confirmed in a number of A....
Ancylostoma caninum is the most prevalent intestinal nematode of dogs, and has a zoonotic potential. Multiple-drug resistance (MDR) has been confirmed in a number of A. caninum isolates, including isolate Worthy 4.1F3P, against all anthelmintic drug classes approved for hookworm treatment in dogs in the United States (US). The cyclooctadepsipeptide emodepside is not registered to use in dogs in the US, but in a number of other countries/regions. The objective of this study was to evaluate the efficacy of emodepside + praziquantel, as well as three commercial products that are commonly used in the US for treatment of hookworms, against a suspected (subsequently confirmed) MDR A. caninum isolate Worthy 4.1F3P. 40 dogs infected on study day (SD) 0 with 300 third-stage larvae, were randomly allocated to one of five treatment groups with eight dogs each: pyrantel pamoate (Nemex®-2), fenbendazole (Panacur® C), milbemycin oxime (Interceptor®), emodepside + praziquantel tablets and non-treated control. Fecal egg counts (FEC) were performed on SDs 19, 20, 22, 27, 31 and 34. All treatments were administered as per label requirements on SD 24 to dogs in Groups 1 through 4. Two additional treatments were administered on SDs 25 and 26 to dogs in Group 2 as per label requirements. Dogs were necropsied on SD 34 and the digestive tract was removed/processed for worm recovery and enumeration. The geometric mean (GM) worm counts for the control group was 97.4, and for the pyrantel pamoate, fenbendazole, milbemycin oxime, and emodepside + praziquantel groups were 74.8, 72.0, 88.9, and 0.4, respectively. These yielded efficacies of 23.2%, 26.1%, and 8.8%, and 99.6%, respectively. These data support previous findings of the MDR status of Worthy 4.1F3P as treatments with pyrantel pamoate, fenbendazole and milbemycin oxime lacked efficacy. In sharp contrast, Worthy 4.1F3P was highly susceptible to treatment with emodepside + praziquantel.
Topics: Ancylostomatoidea; Ancylostomiasis; Animals; Anthelmintics; Depsipeptides; Dog Diseases; Dogs; Drug Combinations; Drug Resistance, Multiple; Hookworm Infections; Intestines; Macrolides; Praziquantel; Pyrantel; Treatment Outcome
PubMed: 32403053
DOI: 10.1016/j.ijpddr.2020.04.003 -
The American Journal of Tropical... Jul 2020Hookworm infections are classified as the most impactful of the human soil-transmitted helminth (STH) infections, causing a disease burden of ∼4 million...
Hookworm infections are classified as the most impactful of the human soil-transmitted helminth (STH) infections, causing a disease burden of ∼4 million disability-adjusted life years, with a global prevalence of 406-480 million infections. Until a decade ago, epidemiological surveys largely assumed and as the relevant human hookworm species implicated as contributing to iron-deficiency anemia. This assumption was based on the indistinguishable morphology of the spp. eggs in stool and the absence of awareness of a third zoonotic hookworm species, . The expanded use of molecular diagnostic assays for differentiating hookworm species infections during STH surveys has now implicated , a predominant hookworm of dogs in Asia, as the second most common hookworm species infecting humans in Southeast Asia and the Pacific. Despite this, with the exception of sporadic case reports, there is a paucity of data available on the impact of this emerging zoonosis on human health at a population level. This situation also challenges the current paradigm, necessitating a One Health approach to hookworm control in populations in which this zoonosis is endemic. Here, we have summarized the available research studies and case reports on human infections in Southeast Asia and the Pacific after 2013 using a systematic review approach. We summarized eight research articles and five clinical case studies, highlighting the importance of future in-depth investigation of zoonotic infections using sensitive and cost-effective diagnostic tools.
Topics: Ancylostoma; Ancylostomiasis; Animals; Asia, Southeastern; Dog Diseases; Dogs; Feces; Humans; Neglected Diseases; One Health; Pacific Islands; Parasite Egg Count; Zoonoses
PubMed: 32342850
DOI: 10.4269/ajtmh.20-0060 -
Scientific Reports Feb 2020Hookworms are intestinal parasites that cause major public health problems, especially in developing countries. To differentiate eggs from different hookworm species, it...
Hookworms are intestinal parasites that cause major public health problems, especially in developing countries. To differentiate eggs from different hookworm species, it is necessary to use molecular methodologies, since the eggs are morphologically similar. Here, we performed the molecular identification of single hookworm eggs from six Brazilian states. Of the 634 eggs individually analyzed, 98.1% (622/634) represented Necator americanus, and surprisingly, 1.9% (12/634 eggs from the same patient) represented Ancylostoma caninum. DNA analysis of the A. caninum-positive stool sample revealed no contamination with animal feces. This is the first report of the presence of A. caninum eggs in human feces, which may have a direct implication for the epidemiology of hookworm infection caused by this species. This suggests the need for special attention regarding prophylaxis, as different reservoirs, previously not described, may have great relevance for the spread of A. caninum.
Topics: Ancylostoma; Ancylostomiasis; Animals; Brazil; DNA, Helminth; Feces; Genotype; Humans; Intestines; Necator americanus; Necatoriasis
PubMed: 32080267
DOI: 10.1038/s41598-020-59874-8 -
Parasites & Vectors Jan 2020Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%,...
BACKGROUND
Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs.
METHODS
Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura.
RESULTS
Among the 682 children, no positive samples were identified, and participants reported high standards of WASH.
CONCLUSIONS
To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.
Topics: Adolescent; Ancylostoma; Ancylostomiasis; Animals; Ascariasis; Ascaris lumbricoides; Child; Child, Preschool; Feces; Female; Helminths; Humans; Hygiene; Japan; Male; Necator americanus; Necatoriasis; Soil; Surveys and Questionnaires; Trichuriasis; Trichuris
PubMed: 31915050
DOI: 10.1186/s13071-019-3875-z