Ancylostoma duodenale [keywords]
- Ancylostoma ceylanicum hookworm infection in Japanese traveler who presented chronic diarrhea after return from Lao People's Democratic Republic. [JOURNAL ARTICLE]
- Parasitol Int 2016 Jul 20.
Ancylostoma (A.) ceylanicum, one of the most common species of hookworms infecting dogs and cats, also causes patent infections in humans and is now considered to be the second most common hookworm species infecting populations in southeast Asia. A Japanese patient who returned from a visit to Thailand and Lao People's Democratic Republic (PDR) was presented with intermittent watery diarrhea with eosinophilia. Hookworm eggs were found in feces samples, and adult worms were confirmed to be present in the jejunum with capsule endoscopy and double balloon enteroscopy. A diagnosis of A. ceylanicum infection was made based on the morphology of the adult worms along with findings of a PCR-based molecular study using larvae obtained from a fecal sample culture. The infection was considered likely to have been obtained during a 1-month stay in a Laotian village, where the patient had eaten local food, worn sandals on bare feet, and lived as a local native villager, though he had stayed in modern hotels during the visit to Thailand.
- Mating Ancylostoma Duodenale under Magnifying Endoscopy. [JOURNAL ARTICLE]
- Gastrointest Endosc 2016 Jul 19.
- Vaccination with a cocktail of Ancylostoma ceylanicum recombinant antigens leads to worm burden reduction in hamsters. [Journal Article]
- Acta Parasitol 2016 Sep 1; 61(3):556-61.
Hookworms, a group to which Ancylostoma ceylanicum belongs, are gastrointestinal nematodes that infect more than 700 million people around the world. They are a leading cause of anemia in developing countries. In order to effectively prevent hookworm infections research is conducted to develop an effective vaccine using recombinant antigens of the parasite. The aim of this study was to examine the influence of the hosts' on protection against ancylostomiasis and the shaping of the humoral immune response among Syrian hamsters after immunization with a cocktail of five A. ceylanicum recombinant antigens. Ace-ASP-3, Ace-ASP-4, Ace-APR-1, Ace-MEP-6 and Ace-MEP-7 were obtained in the pET expression system. Immunization with a vaccine cocktail resulted in a 33.5% worm burden reduction. The immunogenicity of the recombinant proteins were determined using ELISA. Statistical analysis showed that vaccinated hamsters developed stronger humoral responses to four of five recombinant antigens (the exception being Ace-ASP-3) compared to hamsters from the control group.
- Prevalence and risk factors associated with endoparasitosis of dogs and cats in Espírito Santo, Brazil. [Journal Article]
- Acta Parasitol 2016 Sep 1; 61(3):544-8.
The objective of this study was to determine the prevalence and risk factors for the occurrence of endoparasitosis in dogs and cats in Espírito Santo, Brazil. For the study, 345 dogs and 160 cats were examined. Faecal samples from the animals were collected, and owners were interviewed about their handling of their animals. For the diagnosis of the infections, the Willis-Molley, simple centrifugal flotation and formalin-ether sedimentation techniques were performed. The data found in the tests were tabulated and analysed with a chi-square test (p <0.05), and calculation of odds ratios (OR) with confidence intervals of 95% were then performed to determine the association between the variables and the outcome of stool examinations. The prevalence of parasites was 59% for dogs and 54% for cats. The genus Ancylostoma was the most prevalent (45%). Supplying filtered water, not feeding raw foods, standardisation of a defecation site and cleaning up the faeces reduced the chances of developing intestinal parasites. An increased frequency of deworming was also shown to be a protective factor; specifically animals which received anthelmintic more than once a year had a lower predisposition for intestinal parasites.
- Epidemiological survey of zoonotic helminths in feral cats in Gran Canaria island (Macaronesian archipelago-Spain). [Journal Article]
- Acta Parasitol 2016 Sep 1; 61(3):443-50.
The presence of zoonotic parasites in feral cats have been widely considered all over the world. In Gran Canaria (Macaronesian archipelago, Canary Islands, Spain) the number of feral cats has grown out of control in urban and rural areas. 48 of Felis catus captured in different Gran Canaria areas were studied. Animals were necropsied and several organs were systematically examined in order to collect and identify macroscopic parasites. In addition, coprological tests were done in 28 cats. There were no statistically significant differences in the prevalence rate among sex, age or capture area, showing an overall prevalence of helminths of 77.1%. The most common tapeworms were Dipylidium caninum (64.6%) and Taenia taeniaeformis (31.3%), followed by the nematodes Toxocara cati (20.8%), Ancylostoma tubaeforme (18.8%), Aelurostrongylusabstrusus (10.4%) and Trichuris vulpis (2.08%). We also find several eggs of Alaria alata in the small intestine of one cat (2.08%), being the first description of this trematode in cats in the Canary Islands. Aproximatelly, 40% of the studied cats harboured more than one parasite. High rates of zoonotic species found in these animals suggest the need of controling parasitic infections and preventive measures against them.
- Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting. [Journal Article]
- Sci Rep 2016.:29895.
Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency.
- Odanacatib, a Cathepsin K Cysteine Protease Inhibitor, Kills Hookworm In Vivo. [Journal Article]
- Pharmaceuticals (Basel) 2016; 9(3)
Hookworm infection is chief among soil-transmitted helminthiases (STHs) for the chronic morbidly inflicted. Deworming via mass drug administration (MDA) programs most often employs single doses of benzimidazole drugs to which resistance is a constant threat. To discover new drugs, we employ a hamster model of hookworm infection with Ancylostoma ceylanicum and use albendazole (ABZ; 10 mg/kg orally) as the gold standard therapy. We previously showed that a single oral 100 mg/kg dose of the cathepsin cysteine protease (CP) inhibitor, K11777, offers near cure of infection that is associated with a 95% reduction in the parasite's resident CP activity. We confirm these findings here and demonstrate that odanacatib (ODN), Merck's cathepsin K inhibitor and post-clinical Phase III drug candidate for treatment of osteoporosis, decreases worm burden by 73% at the same dose with a 51% reduction in the parasite's CP activity. Unlike K11777, ODN is a modest inhibitor of both mammalian cathepsin B and the predominant cathepsin B-like activity measureable in hookworm extracts. ODN's somewhat unexpected efficacy, therefore, may be due to its excellent pharmacokinetic (PK) profile which allows for sustained plasma exposure and, possibly, sufficient perturbation of hookworm cathepsin B activity to be detrimental to survival. Accordingly, identifying a CP inhibitor(s) that combines the inhibition potency of K11777 and the PK attributes of ODN could lead to a drug that is effective at a lower dose. Achieving this would potentially provide an alternative or back-up to the current anti-hookworm drug, albendazole.
- Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced gastrointestinal nematode infections in dogs. [Journal Article]
- Vet Parasitol 2016 Jul 30.:117-22.
The efficacy of oral afoxolaner plus milbemycin oxime combination chewables against induced gastrointestinal nematode infections in dogs was evaluated in six separate studies. Two studies were performed to evaluate the efficacy of the product against Toxocara canis, two studies evaluated the efficacy against Toxascaris leonina, one study evaluated the efficacy against Ancylostoma braziliense, and one study evaluated the efficacy against Ancylostoma caninum. In the A. caninum study, the efficacy of milbemycin oxime alone and afoxolaner alone was also evaluated. Dogs in all studies were inoculated with infective eggs or larvae and confirmed to have patent infections based on a fecal examination prior to allocation to study group and treatment. Each study utilized a randomized block design with blocks based on pre-treatment body weight. All dogs were assigned to blocks based on body weight, and then each dog within a block was randomly assigned to treatment group. There were two groups of 10 dogs each in the T. canis, T. leonina, and A. braziliense studies: 1) an untreated (control) group and 2) a group treated with afoxolaner plus milbemycin oxime chewables (NexGard Spectra(®), Merial). This group was treated at a dose as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime (2.5mg+0.5mg per kg body weight, respectively) once on Day 0 using whole chews. There were four groups of 10 dogs each in the A. caninum study: 1) untreated (control), 2) NexGard Spectra(®) as described above, 3) milbemycin oxime alone (dose of at least 0.5mg per kg of body weight) and 4) afoxalaner alone (dose of at least 2.5mg per kg body weight). For parasite recovery and counts, dogs were euthanized humanely and necropsied seven days after treatment. The efficacy of the afoxolaner plus milbemycin oxime combination was ≥98% against T. canis, ≥95.8% against T. leonina, and 90.2% against A. braziliense. Efficacy of the combination against A. caninum was 99.7%, while the efficacy of milbemycin oxime alone was 99.6% and the efficacy of afoxolaner alone was 2.1%. Dogs treated with afoxolaner plus milbemycin oxime chewables had significantly (p≤0.0002) fewer nematodes than the untreated controls in all studies. There were no adverse events or other health problems that were related to treatment with Nexgard Spectra(®) in these studies. The results of these controlled studies demonstrate the high efficacy of the afoxolaner plus milbemycin oxime chewables against a broad range of canine intestinal nematode infections.
- Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections. [Journal Article]
- Parasit Vectors 2016; 9(1):376.
Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections.All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models.Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 μM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 μM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 μM) and adults (50 μM), and H. polygyrus L3 (200 μM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively.Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a starting point for drug discovery for STH.
- Ancylostoma (Ancylostoma) buckleyi (Nematoda: Ancylostomatidae): new wild host and distribution expansion. [Journal Article]
- Rev Bras Parasitol Vet 2016 Jun 7; 25(2):231-4.
Here we report the occurrence of Ancylostoma (Ancylostoma) buckleyi (Le Roux and Biocca, 1957) (Nematoda: Ancylostomatidae) in the small intestine of Pampas foxes (Lycalopex gymnocercus) (Mammalia: Canidae). This fox is the most abundant native carnivore in southern South America, where it inhabits grasslands, open woodlands and areas highly modified by extensive ranching and agricultural activities. Material from 80 foxes in rural areas of southern Buenos Aires province, Argentina was examined. The intestinal tracts were carefully removed from each carcass and subsequently isolated by ligatures (pylorus and rectum). Examination of the intestinal content was performed using the sedimentation and counting technique. Four foxes (5%) were found to be parasitized with adult specimens of A. buckleyi. This is the first report of Ancylostoma (A.) buckleyi in Argentina and adds L. gymnocercus as new host of this nematode species.