Efficacy of single-dose 500 mg mebendazole in soil-transmitted helminth infections: a review.

Soil-transmitted helminthiasis (STH) is caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Mebendazole is one of the recommended preventive chemotherapy agents for STH. This review summarizes the efficacy data from 29 studies with single-dose 500 mg mebendazole in STH treatment and compares the results with those of a recently conducted phase 3 study of a 500 mg mebendazole chewable tablet against A. lumbricoides and T. trichiura infections. Studies that reported efficacy results against at least one STH infection were selected from the literature and efficacy data by each STH type were abstracted and pooled. Single-dose 500 mg mebendazole treatment resulted in a cure rate of 92.6% (range: 72.5-100%) for A. lumbricoides, 27.6% (range: 8.4-100%) for T. trichiura and 25.5% (range: 2.9-91.1%) for hookworms. Egg reduction rate for A. lumbricoides was 97.9% (range: 89.8-100%), for T. trichiura it was 72.9% (range: 31.6-93.0%) and for hookworms it was 72.0% (range: -6.5% (denoting an increase in egg count) to 98.3%). Similar results were observed in the studies that were placebo-controlled. In the phase 3 study, the cure rate and egg reduction rate reported was 83.7% and 97.9%, respectively, for A. lumbricoides and 33.9% and 59.7%, respectively, for T. trichiura. In conclusion, single-dose 500 mg mebendazole showed a high cure rate against A. lumbricoides and a substantial reduction in faecal egg count for all STH types. These results are consistent with the recently conducted phase 3 study of a new 500 mg chewable mebendazole tablet.

In vitro studies on the relative sensitivity to ivermectin of Necator americanus and Ancylostoma ceylanicum.

Experiments were carried out to compare the sensitivity of Ancylostoma ceylanicum and Necator americanus to ivermectin (IVM) and pyrantel in vitro. Loss of motility and inhibition of ingestion by IVM were compared and A. ceylanicum was found to be approximately 40-50 times more sensitive to IVM than N. americanus. Both species showed a similar sensitivity to pyrantel. Uptake of [3H]IVM across the cuticle was compared and shown to be unlikely to account for the differences in sensitivity to IVM between the two species.

Inibiçäo da vida externa de larvas de ancilostomídeos e de Strongyloides stercolaris por substâncias vegetais / Inhibitory assays of larval stage of Ancylostomatidae and Strongyloides Stercolaris by vegetable substances

Os AA apresentam os resultados obtidos com a utilizaçäo de extratos vegetais de 24 espécies na inibiçäo do desenvolvimento larvar de ancilostomídeos e de Strongyloides stercoralis. As partes vegetais utilizadas na elaboraçäo dos extratos foram as mais diversas; os solventes utilizados foram o hexano e o álcool; destes, nove extratos alcoólicos e dois extratos hexânicos revelaram atividade inibitória do desenvolvimento larvar

Estudio de dosis única de mebendazol para el tratamiento de Trichuris trichiura y Nécator americanus en campañas de control quimioterapetico en las comunidades / Study of single mebendazole dosages in the management of Trichuris trichiura and Necator americanus in chemotherapeutic control campaigns in the community

Se realiza un estudio de parasitismo intestinal en la comunidad "Argelia Libre", de la Isla de la Juventud, mediante el uso de 4 técnicas coproparasitológicas: Kato Katz, Ritchie, Directo y willis. Se dividen los pacientes con geohelmintos en 2 grupos de tratamiento: el grupo A, el cula se trató con 500 mg de mebendazol en dosis única, y el grupo B, con el esquema clásico de 100 mg cada 12 horas por 3 días. Se expresan los resultados del tratamiento en tasas de curación y porcentaje de reducción del conteo de huevos. Al comparar el esquema A con el B, no se encontraron diferencias significativas (p > 0.05). Debido a su más bajo costo y su más fácil administración, se recomienda el esquema de dosis única para el tratamiento quimioterapéutico masivo de las geohelmintiasis en las comunidades

Response of adult Necator americanus to some known anthelminthics in hamsters.

Adult Necator americanus infection in laboratory hamsters (the hamster-hookworm model) was examined as an anthelminthic screening system. Three reference anthelminthics--pyrantel (PYTL), mebendazole (MBZ) and ivermectin (IVRN)--were used to assess the sensitivity of adult N. americanus and also to investigate the value of the hamster-hookworm model for predicting clinical results. Serial drug dosages were used, and the ED50 was determined from the resulting cure rates. In addition, percentage worm reductions were calculated by reference to the worm burdens in control groups. The results showed that the hamster-hookworm model was able to differentiate anthelminthics on their efficacy. Absolute activity (100% worm reduction) followed treatment with 8 mg kg-1 MBZ, 38-40 mg kg-1 PYTL and 18 mg kg-1 IVRN. Based on ED50 data of PYTL and MBZ, adult N. americanus appeared to be two to five times more sensitive than pre-adult stages. However, with IVRN the reverse appeared true. MBZ appeared to be most active and PYTL least active in terms of curing infected animals, but there were no obvious differences between the rates of worm reductions following single or multiple doses of anthelminthics. It is considered that the hamster-hookworm model will prove of value in identifying and characterizing possible new anthelminthics.

Estudio comparativo de flubendazol, oxantel-pirantel, albendazol y mebendazol en el tratamiento de helmintos transmitidos por el suelo / Comparative study of flubendazol, oxantel-pirantel, albendazol and mebendazol in treatment of helminths transmited by the soil

Se trataron 141 personas que tenian infeccion por Ascaris lumbricoides, Trichuris trichiura o Necator americanus. Las drogas empleadas fueron: Flubendazol, con tres dosificaciones: 500 mg dosis unica; 300 mg/dia por 2 dias; y 200 mg/dia por 3 dias. Oxantel-Pirantel, 400 mg de cada una en dosis unica o 600 mg de cada una, tambien en dosis unica. Mebendazol con tres dosificaciones: 500 mg dosis unica; 300 mg/dia por 2 dias; y 200 mg/dia por tres dias. Los resultados indican que todas las drogas empleadas tuvieron una efectividad para el tratamiento de la ascariasis con una curacion entre el 84.6 y el 100% y un porcentaje de reduccion del 88.5 al 100%. El flubendazol a la dosis de 300 mg/dia por 2 dias fue la droga mas efectiva para la tricocefalosis y la uncinariasis, curacion y reduccion de huevos del 100% para ambas. Todas las drogas fueron bien toleradas y casi no se observaron efectos secundarios. Si se requeire una droga para tratamientos en masa con dosis unica, se debe seleccionar el flubendazol, a la dosis de 500 mg; con ella se cubren los tres helmintos con una alta efectividad.

The response of adult and free-living stages of Necator americanus, in vitro, to anthelmintics.

The in vitro response of adults (males and females) and free-living stages of Necator americanus one of the human hookworms, to a wide variety of 20 broad and narrow spectrum anthelmintics was tested. Almost all the broad spectrum anthelmintics influenced males, females and free-living stages at different levels and showed good activity with EC50 values varying from about 0.0002 and 0.0007 mg/l for pyrantel pamoate and tricofenol piperazine respectively to about 8.47 and 7.6 mg/l for morantel tartrate and amoscanate respectively. Certain drugs (emetine, praziquantel and suramin) exerted their effect either on male or female or free-living stages at 10.0 mg/l level. It is concluded that either sex or life-cycle stage alone may not be an effective criteria for screening of anthelmintics which have been employed at large; and females of nematodes (in particular those of N. americanus) should be taken into account for proposing EC50 as they were found to require relatively highest EC50 level in almost all the instances studied presently.

The response of adult and free-living stages of Necator americanus, in vitro, to anthelmintics

Se probó la respuesta in vitro de Necator americanus a 20 antihelmínticos. Con valores de EC50 desde 0.0002 hasta 0.0007 mg/L, los antihelmínticos de espectro amplio afectaron a machos, hembras y estadíos libres. Ciertas drogas (emetine, praziquantel y suramin) afectaron selectivamente a los grupos mencionados al nivel de 10.0 mg/L. Las hembras requirieron mayores niveles de tratamiento, lo que tiene importantes implicaciones en la aplicación de antihelmínticos

Response of laboratory-adapted human hookworm and other nematodes to ivermectin.

The activity of ivermectin was examined in Necator americanus, a human hookworm, adapted to the laboratory hamster. A dose of 30 mg kg-1 X 1 or 10 mg kg-1 X 2 was required for complete clearance of pre-adult N. americanus; however, hamsters carrying adult N. americanus were completely cured of infection by doses of 15 mg kg-1 or 7.5 mg kg-1 X 2. The doses of ivermectin required for complete elimination of N. americanus were much higher than those reported for other intestinal nematodes. The probable reasons for these higher doses are discussed. Tests were also carried out with other rodent parasites, namely Nematospiroides dubius, Strongyloides ratti and Trichuris muris. Doses as low as 0.3 mg kg-1 X 1 completely eliminated adult N. dubius from mice, whereas++ S. ratti needed a repeated dose (0.3 mg kg-1 X 2). None of the mice was cured of T. muris infection even at doses of 10 mg kg-1 X 2, although some degree of cure was apparent at the toxic dose. It thus appears that ivermectin is in no way superior in its activity against N. americanus and T. muris than the existing anthelmintics.

Response of preadult Necator americanus to some known anthelmintics in hamsters.

Hamsters infected with laboratory-adapted preadult Necator americanus were dosed with 6 reference anthelmintics. Their efficacy was measured in terms of percentage cure of infected animals as well as percentage worm reduction following treatment. Mebendazole and pyrantel were equally effective in this system. Other anthelmintics, including anti-hookworm compound, bephenium hydroxynaphthoate, were less effective. The comparative results revealed that the N. americanus model is sensitive and reliable for identifying and characterizing new anti-parasite preparations.

Antigen stripping from the nematode epicuticle using the cationic detergent cetyltrimethylammonium bromide (CTAB).

The cuticular antigens of adult Nematospiroides dubius were selectively removed using the cationic detergent cetyltrimethylammonium bromide (CTAB). Nonionic, zwitterionic or anionic detergents were ineffective in comparison. The biochemical profile of the antigens removed by detergent was identical to that of surface antigens removed by homogenization, with the added advantage that detergent-stripped antigens lacked many of the background antigens (excretory/secretory--ES and somatic) seen in homogenates. In addition, the detergent was shown to act in a non-invasive manner as electron micrographs failed to reveal any gross damage to the nematode outer cuticle. The observed selective release of significant quantities of relatively clean nematode surface antigen by CTAB in a non-invasive or destructive manner provides the impetus for definitive studies on the relevance of surface antigens (in the absence of ES or somatic antigens) to the overall immunogenicity of this and other parasites.

Larvicidal activity of albendazole against Necator americanus in human volunteers.

This study evaluated the efficacy and tolerance of a single oral 400-mg dose of albendazole on Necator americanus larvae, and compared its efficacy when administered between meals or with a meal. Twenty-nine healthy and hookworm-free male volunteers were exposed on the forearm to approximately 45 8-day-old N. americanus larvae. All subjects developed discrete maculopapular eruptions at the site of larval application. Following a random double-blind study design, each subject received at the end of the 6th post-infection day either the investigational drug or a placebo as follows: Group I (n = 8)-placebo; Group II (n = 11)-400 mg albendazole with a meal; Group III (n = 10)-400 mg albendazole 3 or more hours after or before a meal. On day 56 post-infection, the stools of all subjects who received placebo were positive for N. americanus eggs (by zinc sulfate flotation technique), compared with 48% positivity (10/21) in those who received albendazole (P = 0.01). By day 63 post-infection, an additional three subjects in the treatment group became positive, for an overall 62% rate of positivity (13/21), i.e., albendazole prevented patent infection in 38%. Administration of albendazole with a meal did not alter drug efficacy. In those subjects in whom patent infections were not prevented, egg output was one-fourth that of the placebo group. There was no difference in viability of eggs appearing in feces of treated and untreated subjects as judged by larval development in Harada-Mori cultures. Our data indicate that albendazole is active against pre-intestinal stages of N. americanus in human infections.

Clinical evaluation of a new anthelmintic - C. 9333 Go./CGP 4540 in human hookworm infection.

A new antihookworm compound, C.9333 Go./CGP 4540, was evaluated clinically in 65 adult patients with hookworm infection. Several dosage schedules were evaluated to determine an effective, well tolerated and convenient regime. The lowest effective dose was 125 mg administered at four-hourly intervals for three doses. The compound was generally well tolerated; mild giddiness was observed in nine patients and severe giddiness was present in one patient. Clinical and biochemical monitoring revealed no other toxicity of the compound.

A comparative study of the relative efficacy of pyrantel pamoate, bephenium hydroxynaphthoate and tetrachlorethylene in the treatment of Necator americanus infection in Ceylon.

The clearance of hookworm (Necator americanus) ova by a single dose of tetrachlorethylene (T.C.E.) was compared with that produced by single and multiple dose regimes of bephenium hydroxynaphthoate and pyrantel pamoate. Single doses of bephenium and pyrantel were inferior to T.C.E. Three daily doses of bephenium or pyrantel produced effects comparable with a single dose of T.C.E. Because of the low cost and lack of side effects, T.C.E. remains the drug of choice in the treatment of N. americanus in infections; the only disadvantage of T.C.E. is its unnoticed deterioration under tropical conditions.