Albendazole resistance induced in Ancylostoma ceylanicum is not due to single-nucleotide polymorphisms (SNPs) at codons 167, 198, or 200 of the beta-tubulin gene, indicating another resistance mechanism.

Mass drug administration has been implicated as the major cause of drug resistance in nematodes of ruminants. Single-nucleotide polymorphisms (SNPs) at codons 167, 198, and 200 of the beta-tubulin isotype 1 gene are associated with albendazole resistance mechanisms. Although drug resistance is suspected to occur in nematodes of the same order, at present, there is no evidence of a strong correlation between these canonical SNPs and albendazole resistance in hookworms. In the absence of a hookworm strain that is naturally resistant to albendazole, we produced an albendazole-resistant Ancylostoma ceylanicum strain by selective drug pressure. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to identify the presence of SNPs previously associated with drug resistance in other nematodes. However, none of the benzimidazole resistance-associated SNPs known in other nematodes were found. A beta-tubulin isotype 1 gene mini-cDNA library was constructed to obtain the complete cDNA gene sequence for the analysis of the entire gene to identify distinct SNPs associated with resistance. Some SNPs were found, but the resulting sequences were not reproducibly detected among the different clones, preventing their association with the resistance mechanism. The parasitological and hematological parameters of the albendazole-resistant strain were characterized and compared to those of the sensitive strain. Although the albendazole-resistant strain was less adapted to its host, with fewer worms recovered, all other parameters analyzed were similar between both strains. The results of the present study indicate that the mechanism of albendazole resistance of the resistant strain described herein must differ from those that have previously been characterized. Thus, new mechanistic studies are needed in the future.

A nanocrystal-based formulation improves the pharmacokinetic performance and therapeutic response of albendazole in dogs.

OBJECTIVES: Here, we aimed to assess the pharmacokinetic performance and therapeutic response (anthelmintic efficacy) of an albendazole (ABZ) nano-sized formulation in dogs. METHODS: In the pharmacokinetic study, ABZ self-dispersible nanocrystals (SDNCS) and a control formulation were administered orally to healthy dogs (n = 6). The concentrations of the sulphoxide metabolite in plasma were determined by high-performance liquid chromatography. For the anthelmintic efficacy trial, SDNCS and a commercially available formulation of ABZ were given to naturally parasitised dogs. The number of Ancylostoma caninum eggs in the faeces was determined using the McMaster technique. KEY FINDINGS: The area under the curve, Tmax and Cmax for the SDNCS were improved compared to the control. The efficacy study showed no statistical differences between the SDNCS and the commercial formulation at the doses of 25 and 12.5 mg/kg. However, significant differences (P < 0.05) between the treatments were found at 6.25 mg/kg (a quarter of the reference dose) with a reduction in the faecal nematode egg counts of 62.0 ± 21.1% and 100 ± 0% for the control and SDNCS, respectively. CONCLUSIONS: The improved pharmacokinetic performance observed for the novel formulation of ABZ correlated with an improved in vivo therapeutic response against a model intestinal nematode parasite in dogs.

Efficacy of a single oral administration of milbemycin oxime against natural infections of Ancylostoma braziliense in dogs.

The objective of this randomized, blinded, placebo controlled laboratory study was to confirm the efficacy of a single oral administration of two marketed formulations of milbemycin oxime (Interceptor(®) Flavor Tabs(®) and Sentinel(®) Flavor Tabs(®)) at a minimum dose of 0.5 mg/kg (0.23 mg/lb) against natural infections of Ancylostoma braziliense in dogs. Thirty-six hookworm infected dogs, a minimum of 10 weeks of age and of various breeds and genders were used. Fecal egg counts were done on three separate days prior to treatment for randomization purposes. Dogs were ranked by descending order of the fecal egg count arithmetic means and randomly assigned to either the two milbemycin treatment groups or the placebo control group in blocks of three dogs each, 12 dogs per group. Dogs were dosed according to the product label with blinding maintained by separation of function. Worm counts were done at necropsy 7 days after treatment. Reduction in A. braziliense worm counts in the milbemycin groups were compared to the placebo control group using analysis of variance of the A. braziliense logarithmic mean worm counts and percent efficacy was based on geometric means. Efficacy was defined as the ability of the test products to significantly (p≤0.05) reduce parasite load by 90% or greater in treated dogs when compared to adequately infected placebo control dogs. The placebo control group had a geometric mean worm count of 19.2. The Interceptor treated group had a geometric mean worm count of 0.38 representing a 98% reduction in parasite load and the Sentinel treated group had a geometric mean worm count of 0.98 representing a 95% reduction in parasite load. Both reductions were highly significant (p<0.0001). In this study, milbemycin oxime, when administered as two marketed formulations at a minimum dose of 0.5 mg/kg (0.23 mg/lb), was efficacious for removing adult A. braziliense in naturally infected dogs.

Prednisolone and cyclosporine A: effects on an experimental model of ancylostomiasis.

Corticosteroids and cyclosporine A (CsA) are important clinical immunosuppressive drugs used in the maintenance of organ transplants and in suppressing undesired autoimmune or allergic immune responses. To study the effect of CsA and prednisolone on the course of an Ancylostoma ceylanicum infection, hamsters were treated with commercially available prednisolone or CsA. For both drugs, half the recommended dose was sufficient to inhibit the proliferation of more than 70% of hamster lymph node cells. There was no difference in the recovery of adult worms; however, animals treated with prednisolone presented with low egg counts in the feces. Infection with A. ceylanicum resulted in an increase in specific antibodies against adult worm antigens, but hamsters treated with either drug presented with lower IgG titers. We observed that A. ceylanicum infection caused peripheral cellular immune suppression, which is characterized by a reduction in the total white cell count, neutropenia and lymphopenia. We also observed a lymphoplasmacytic pattern and few eosinophils in the mucosal inflammatory infiltrate for all the animals. The animals treated with prednisolone showed changes in the architecture of the intestine, including the loss of the mucosa, intense congestion and inflammation. In spleen, we observed hyperplasia of white pulp in all infected animals; in addition, there was a loss of tissue architecture in the animals treated with prednisolone. In conclusion, this work shows that an A. ceylanicum infection leads to acute peripheral cellular immune suppression in hamsters but not humoral immune suppression and that CsA treatment does not interfere with the process of infection. However, prednisolone treatment causes intestinal injury, what could hamper the parasite attachment to the intestinal wall, and as a result affects copulation and, consequently, decreases the number of eggs eliminated in the feces. Moreover, the possibility that the drug can also be exerting an effect on female fertility should be considered.

Dinâmica da infecção e reinfecção por ancilostomídeos seguido ao tratamento anti-helmíntico em crianças residentes em seis comunidades dos municípios de Novo Oriente de Minas e Caraí na região nordeste de Minas Gerais, Brasil

A ancilostomíase é causada por parasitas nematoides das espécies Necator americanus e Ancylostoma duodenale. É uma das formas de infecção crônica mais comum em humanos com estimativa de 740 milhões de casos especialmente em áreas rurais pobres dos trópicos e subtrópicos segundo a Organização Mundial de Saúde. As principais manifestações clínicas da doença resultam da perda crônica de sangue intestinal causada pela fixação dos vermes adultos à mucosa e submucosa dos intestinos. Quando a perda de sangue excede as reservas nutricionais, há deficiência de ferro e desenvolvimento de anemia, relacionada ao baixo rendimento escolar em crianças, apatia, adinamia e queda da produtividade em adultos. O enfoque atual para o tratamento da ancilostomíase e outras helmintoses transmitidas pelo solo consiste em administrações periódicas de anti-helmínticos da classe dos benzimidazólicos, tanto albendazol quanto mebendazol. Contudo, estudos têm demonstrado que a reinfecção ocorre rapidamente após o tratamento, o que na maioria das vezes resulta em administrações regulares de anti-helmínticos predispondo ao risco de aparecimento de resistência às drogas e manutenção de níveis endêmicos da doença.

Diante disso, nosso objetivo nesse trabalho foi avaliar a evolução da intensidade de infecção pelo ancilostomídeo em crianças entre 1 a 10 anos de idade de seis comunidades em dois municípios na região nordeste de Minas Gerais, Brasil, após o tratamento com a droga mais comumente utilizada, o Albendazol, num períodode dois anos, além da possibilidade de avaliar a velocidade com que a reinfecção ocorre. Nossos resultados mostraram que a intensidade da infecção pelo ancilostomídeo medida em ovos por grama de fezes foi reduzida pela administração do medicamento, com queda parcial na prevalência que se manteve estável durante o seguimento. Houve uma super utilização do albendazol além do esperado pelo protocolo em grande parte devido ao encontro de outros parasitas cujo tratamento também se baseia no uso dessa droga. A velocidade de reinfecção não pôde ser mensurada em virtude de limitações metodológicas do protocolo. Pudemos inferir com nossos resultados, a tendência encontrada na literatura de que isoladamente o tratamento farmacológico em massa interfere na intensidade das infecções, mas não controla os níveis de doença, conforme foi observado nos 24 meses de seguimento. São necessários novos estudos com melhor abordagem metodológica e tempo de seguimento para avaliar com mais precisão o efeito da terapia farmacológica sobre a velocidade em que a reinfecção se faz.

Dinâmica da infecção e reinfecção por ancilostomídeos seguido ao tratamento anti-helmíntico em crianças residentes em seis comunidades dos municípios de Novo Oriente de Minas e Caraí na região nordeste de Minas Gerais, Brasil / Dynamics of hookworm infection and reinfection followed by anthelmintic treatment in children residents in six communities in the municipalities of Novo Middle of Mines and Karai in the northeastern region of Minas Minas, Brazil

A ancilostomíase é causada por parasitas nematoides das espécies Necator americanus e Ancylostoma duodenale. É uma das formas de infecção crônica mais comum em humanos com estimativa de 740 milhões de casos especialmente em áreas rurais pobres dos trópicos e subtrópicos segundo a Organização Mundial de Saúde. As principais manifestações clínicas da doença resultam da perda crônica de sangue intestinal causada pela fixação dos vermes adultos à mucosa e submucosa dos intestinos. Quando a perda de sangue excede as reservas nutricionais, há deficiência de ferro e desenvolvimento de anemia, relacionada ao baixo rendimento escolar em crianças, apatia, adinamia e queda da produtividade em adultos. O enfoque atual para o tratamento da ancilostomíase e outras helmintoses transmitidas pelo solo consiste em administrações periódicas de anti-helmínticos da classe dos benzimidazólicos, tanto albendazol quanto mebendazol. Contudo, estudos têm demonstrado que a reinfecção ocorre rapidamente após o tratamento, o que na maioria das vezes resulta em administrações regulares de anti-helmínticos predispondo ao risco de aparecimento de resistência às drogas e manutenção de níveis endêmicos da doença...

Tratamento da estrongiloidíase humana e outras parasitoses intestinais com dose única de ivermectina / Treatment of human strongyloidiasis and other intestinal parasitosis with a single dose of ivermectin

Os autores trataram 70 pacientes portadores de estrongiloidíase, ascaríase, tricuríase e ancilostomíase com dose única de ivermectina (200 ug/kg). A cura parasitológica obtida foi de 95 porcento para estrongiloidíase, de 100 poecento para ascaríase e tricuríase e de 60 porcento para ancilostomíase. As reaçöes adversas foram observadas em 3 porcento dos pacientes - cefaléia, náuseas e vômitos.(au)

Efficacy of an ivermectin and pyrantel pamoate combination against adult hookworm, Ancylostoma braziliense, in dogs.

A chewable tablet incorporating ivermectin and pyrantel was tested in 12 Beagle dogs for efficacy against the adult hookworm, Ancylostoma braziliense. The dogs were administered infective larvae of A braziliense orally. Twenty-one days after infection the dogs were weighed and allocated randomly to receive either an oral treatment with ivermectin and pyrantel in a beef-based chewable tablet or no treatment. The chewable tablet was a commercially available product, which was made to deliver ivermectin at 6 micrograms/kg and pyrantel at 5.0 mg/kg to each dog. Seven days after treatment the dogs were euthanased, necropsied, and examined for adult hookworms. At necropsy, no adult A braziliense was observed in any of the 6 treated dogs and all 6 dogs that had been left untreated were infected with adult A braziliense (range, 48 to 161). It was concluded that this combination product is 100% efficacious against adult A braziliense.

Efficacy of a chewable formulation of ivermectin against a mixed infection of Ancylostoma braziliense and Ancylostoma tubaeforme in cats.

The efficacy of a beef-based, chewable formulation of ivermectin against a mixed infection of Ancylostoma braziliense and A tubaeforme was determined in cats. Ivermectin administered orally at approximately 24 micrograms/kg of body weight was 92.8% effective against adult A braziliense and 90.7% effective against adult A tubaeforme. The number of eggs per gram of feces had decreased 98.1% by 7 days after treatment. Clinical signs of hookworm disease also decreased after treatment. Location of adult parasites within the small intestine, percentage of infecting larvae that developed to the adult stage, and egg size in cats with infections of A braziliense and A tubaeforme were similar to those reported for cats with separate infections of either species.

Tratamento das parasitoses intestinais por nematelmintos com albendazol: análise de 74 casos / Treatment of intestinal parasitical diseases by nematodes with albendazol: analysis of 74 cases

Os autores descrevem sua experiência com albendazol no tratamento de 74 pacientes com parasitoses intestinais por nematelmintos. Eles concluem que o albendazol tem grande eficácia e é uma droga bem tolerada. Ele deve ser preferido especialmente quando um ou mais nematelmintos estäo associados ao Strongyloides stercoralis.

Anquilostomiasis: un problema de nuestros días / Ancylostomiasis: an actual problem

Se realizó una revisión bibliográfica retrospectiva y prospectiva y se enfocó de manera real la problemática que ocasiona en el país las parasitosis intestinales, con especial referencia a la anquilostomiasis. Se estudiaron los factores que inciden y condicionan su vigencia, aspectos críticos que hacen que se mantenga la prevalencia como factor significativo, posibilidades de la aplicación del inmunodiagnóstico e inmunoprofilaxia (vacunación) los enfoques terapéuticos actuales y si es necesario incluir campañas de tratamiento profilactico dentro del Sistema Nacional de Salud

[Therapeutic trials of a new anti-helminthic in Colombian Amazonia: flubendazole]. / Essai thérapeutique d'un nouvel anti-helminthique en amazonie colombienne: le flubendazole.

After a coprologic survey made at Araracuara, a village in colombian Amazonia showing high prevalences of nematodosis, 83 villages (including 55 children below twelve) were given Flubendazole during three consecutive days. The total dose was 600 mg. for children below 12, and 900 mg. for adults. The product efficiency was 88% for Trichuris, 82% for Hookworm, 77% for Ascaris and 43% for Strongyloïdes. The tolerance was excellent in all cases, in spite of heavy parasital infection. The Flubendazole's effect seems to be particularly interesting by its polyvalency.