Single Oral Dose Of Albendazole Research Articles

Albendazole metabolites excretion in human saliva as a biomarker to assess treatment compliance in mass drug administration (MDA) anthelmintic programs.

Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the trueeffectiveness of albendazole(ABZ) in those MDA programs.The aims of this work wereto characterize the pattern ofalbendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection)useful to accurately estimate the coverage/compliance in MDA campaigns.The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however,this ABZ-metabolite was recovered longer in saliva.Thein vivomeasurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.

The efficacy of a single oral dose of albendazole against soil-transmitted helminthiasis in Ogun State, Nigeria

Soil Transmitted Helminths (STHs) are Neglected Tropical Diseases of global public health importance. This study evaluated the efficacy of albendazole (ALB) amongst primary school children aged 6 – 16 years in STH-endemic communities in Ogun State, Nigeria. Demographic characteristics were obtained and stool samples were collected and analysed by Kato-Katz at baseline and 15 and 21 days post-treatment. All study participants were treated with a single ALB 400 mg tablet. A total of 282 participants were screened at baseline, of which 151 were found to be excreting STH (51.4%) of which A. lumbricoides was the most prevalent STH (n = 137, 48.6%), followed by hookworm (n = 60 children, 21.3%) and T. trichiura (n = 3; 1.1%). The prevalence across the four schools varied from 31.3% to 73.9% for A. lumbricoides, from 6.8% to 56.3% for hookworm, and from 0.0% and 2.2% for T. trichiura infections. Of the 151 children excreting any STH infection at baseline, 131 (86.8%) provided a stool sample 15 and 21 days after treatment. The mean fecal egg counts across these complete cases at baseline was 5,096 (± 13,735) eggs per gram (EPG) for A. lumbricoides, 2,202 (±7,849) for hookworms and 288 (±375) for T. trichiura. Fifteen days after drug administration the therapeutic efficacy, measured as the reduction in mean fecal egg count (FEC) following drug administration (ERR), was 99.7% (95CI: 99.4-99.9) for A. lumbricoides and 69.2% (95CI: 28.7-92.8) for hookworms. The hookworm ERR at day 14 was reduced due to the continued high egg output of one highly infected individual. One week later, 21 days following drug administration, ERR for hookworm also reached satisfactory levels (99.4% (95CI: 98.7-99.8)). This study highlights that ALB still shows satisfactory efficacy to Ascaris and hookworm infections in Ogun State, Nigeria.

INFANTILE HOOKWORM INFECTION: CLINICAL CASE REPORT

Hookworms are endemic nematodes from tropical regions. Infection is more common in preschool and school children, but it is less frequent in infants under 6 months, because of the transmission mechanism that implies contact between contaminated soil and skin. The clinical disease is characterized by manifestations related to iron-deficiency anemia, secondary to a chronic digestive blood loss. An unusual way of presentation is the massive digestive bleeding that causes severe anemia. Case report: A four month shuar girl with no significant medical history, referred from General Puyo hospital, presented upper digestive bleeding of 3 months duration. At month of age, the girl presented self-limited melenas and skin pallor that worsen two weeks before the admission. The girl was hypo active, with a pale complexion, and had edema of feet. Her blood count showed hemoglobin 2.8 g/dl, hematocrit 9%, mean corpuscular volume 73 fl, red cell distribution width 18%, reticulocyte count 1%, eosinophils 4%. Coprological analysis reported tarry stools, positive fecal occult blood test, and hookworm eggs determined by Kato – Katz as a moderate infection. It was diagnosed iron-deficiency anemia secondary to an upper digestive bleeding caused by hookworms. The infection was treated with a single oral dose of albendazole 400mg plus blood transfusion. After 5 days of treatment, hemoglobin increased and edema was reduced. Melenas disappeared completely. Finally the discharge was indicated for outdoor control. Conclusion: Hookworm infestation is an endemic disease whose presence and impact in infants has been underestimated because it is not necessary as a cause of digestive bleeding. This disease should be considered in contexts of endemic areas in children who meet a clinical profile similar to that described.

The effects of Mannheimia haemolytica and albendazole on marbofloxacin pharmacokinetics in lambs.

The study aimed to define the effects of M. haemolytica and a single oral dose of albendazole on the single-dose pharmacokinetics of marbofloxacin in lambs. The pharmacokinetic-pharmacodynamic integration of marbofloxacin was applied to describe a 3mg/kg intramuscular dose in lambs. The 6 healthy and 12 naturally infected with M. haemolytica lambs (Akkaraman, males weighing 10-15kg and aged 2-3months) were used in this study. In the marbofloxacin group, 6 healthy lambs received marbofloxacin. In the albendazole group after 2weeks washout period, the same animals received marbofloxacin on 1h after albendazole. In the diseased marbofloxacin group, 6 lambs naturally infected with M. haemolytica received marbofloxacin. In the diseased albendazole group, 6 lambs naturally infected with M. haemolytica received marbofloxacin on 1h after albendazole. The marbofloxacin and albendazole were administered each as a single dose of 3mg/kg intramuscular and 7.5mg/kg oral, respectively, in the respective groups. Plasma concentration of marbofloxacin was measured with HPLC-UV and pharmacokinetic parameters were analyzed by non-compartmental model. Albendazole did not change the pharmacokinetic profiles of marbofloxacin in healthy and diseased lambs. However, M. haemolytica affected the pharmacokinetics of marbofloxacin in diseased lambs, AUC0-24/MIC90 ratio was not found to be higher than 125, but Cmax/MIC90 ratios was found to be higher than 10 for an MIC value of 0.25μg/mL in all groups. The marbofloxacin dose described in this study may not be effective for the treatment of infections due to M. haemolytica in lambs, with MIC ≤ 0.25μg/mL.

The optimal timing of post-treatment sampling for the assessment of anthelminthic drug efficacy against Ascaris infections in humans

The egg reduction rate (ERR) is the current standard mean to assess the efficacy of drugs against human soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura and hookworm). Although the timing of post-treatment sampling is pivotal for a readily interpretation of drug efficacy, there is lack empirical data that allows recommending the optimal time point for a follow-up egg counting. In the present study, we re-analyzed both the kinetics of worm expulsion and egg output for Ascaris lumbricoides following a single oral dose of albendazole in a series of studies previously conducted in Kenyan communities. The results indicate that it takes up to 10 days post-treatment before the expulsion of both adult male and female Ascaris worms is completed, approximately 20% of the worms being expelled between day 7 and 10 post-treatment. The sequential analysis of the egg out put, indicated a poor ERR (89.4%) at day 7 post-treatment, but a 100% ERR at day 14 and 21 post-treatment. Based on our findings we recommend to wait at least 14 days after an albendazole treatment before conducting the follow-up egg count. Any sampling before this time point may result in biased ERR estimates, due the release of residual eggs from moribund or degenerating worms.

Assessment of in vitro and in vivo anthelminthic potential of extracts of Allium sativum bulb against naturally occurring ovine gastrointestinal nematodiosis

Background: The rapid development of anthelminthic resistance has limited the success of traditional control programmes, thereby forcing researchers to search for ethno-veterinary alternatives.Objective: The objective is to assess the anthelminthic potential of various extracts of the bulb of Allium sativum in naturally infected sheep.Animals and methods: In vitro anthelminthic activities of crude aqueous and methanolic extracts of the bulb of A. sativum were investigated against the egg (500 eggs/ml) and larvae of naturally infected sheep. The aqueous extract of A. sativum was also investigated for in vivo anthelminthic activity in three groups (n = 15 each) of naturally infected Chokla sheep with a negative control group receiving no treatment, a positive control group was given a single oral dose of albendazole at 7.5 mg/kg bodyweight, and a group administered a single oral dose of an aqueous extract at 5 g/animal. Data were analysed using the general linear model.Results: Aqueous extract showed better efficacy in egg hatch assay and larval development test. However, in larval paralysis test, reverse trend was seen as methanolic extract was more potent than the aqueous counterpart. A significant amount of 57% faecal egg count reduction was observed in in vivo trail using the aqueous extract on day 21 post-treatment, although in initial stages it showed 30% and 83% effectiveness on days 7 and 14 post-treatment, respectively. No deleterious ill effect was found in any of the haematological and biochemical parameters.Conclusions: Bulb of A. sativum possesses good anthelminthic efficacy and further research is thereby warranted before recommending it for nematode control programme in ovines.

Efficacy and side effects of albendazole currently in use against Ascaris, Trichuris and hookworm among school children in Wondo Genet, southern Ethiopia

Monitoring the efficacy of anthelminthic drugs is essential. The objective of this study was to assess the efficacy of a single oral dose of 400mg albendazole (ABZ) against the major soil-transmitted helminth (STH) infection in school children, Wondo Genet, southern Ethiopia. A single fresh stool sample was collected from 298 school children and examined using a duplicate smear of the Kato–Katz method. Children positive for STH infections were treated with single oral dose of 400mg ABZ and re-examined for intestinal helminth infections 21days post-treatment. The participants were interviewed for symptoms related with the drug uptake 24h after ABZ treatment. Children positive for Schistosoma mansoni infections were treated with Praziquantel (40mg/kg of body weight) after an ABZ treatment follow up survey. 51.3%, 49.7%, 44.6% and 88.3% had hookworm, Ascaris lumbricoides, Trichuris trichiura and any intestinal helminth infection, respectively. Cure rates were 97.4% for hookworm, 96.6% for A. lumbricoides and 30.8% for T. trichiura infections. Egg reduction rates (ERRs) were 99.8% for hookworm, 99.9% for A. lumbricoides and 83.1% for T. trichiura infections. Mild and transient symptoms were observed among the participants which were quite frequent. In conclusion, a 400mg single oral dose of ABZ was effective against hookworm and A. lumbricoides but less efficacious against T. trichiura infection. The drug resulted in high ERRs for hookworm, A. lumbricoides and T. trichiura. Administration of the drug in repeated doses or in combination with other drugs might be necessary.

Low Efficacy of Single-Dose Albendazole and Mebendazole against Hookworm and Effect on Concomitant Helminth Infection in Lao PDR

BackgroundAlbendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke.MethodologyWe conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n = 100) and mebendazole (n = 100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21–23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment.Principal FindingsSingle-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2–0.8; P = 0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively).Conclusions/SignificanceBoth albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic.Clinical Trial RegistrationCurrent Controlled Trials ISRCTN29126001

Effects of albendazole on Litomosoides chagasfilhoi (Nematoda: Filarioidea) females in vivo

Gerbils (Meriones unguiculatus) experimentally infected with Litomosoides chagasfilhoi were treated with a single oral dose of 40 or 80 mg of albendazole, respectively. Observation of the microfilaremia after the treatment showed that both single oral doses of albendazole decreased the microfilaremia in L. chagasfilhoi infection. The body wall was composed of a cuticle, a hypodermis, and a muscular layer, and treated nematodes showed no morphological alterations. The ultrastructural alterations produced by treatment with 40 mg of albendazole included a higher number of membrane invaginations in the basal labyrinth of the uterine epithelium and the presence of myelin figures in this region. Inside the uterus, most embryos and microfilariae were disintegrated. The treatment with 80 mg of albendazole did not produce alterations in the uterine wall, and the number of vesicles near the microfilariae sheath was smaller than that observed in the untreated and in the 40-mg treatment groups. However, all the microfilariae observed in the uterus were extensively damaged with cytoplasmic vacuolization and cellular degeneration. No alterations in the intestinal cells were observed after treatment with 40 or 80 mg of albendazole. The present study contributes to the knowledge of albendazole's effects in filariids and demonstrates the potential embryotoxic and microfilaricidal consequences of this drug.

Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole.

Albendazole (ABZ) is used in several anthelminthic drug programs. ABZ side-effects are generally mild, but ABZ-induced pancytopenia may be serious. In filariasis programmes, it may be necessary to administer ABZ to breastfeeding women. Few data are available on safety of ABZ for breastfed infants. In addition, the pharmacokinetics of ABZ and its metabolites in human milk is insufficiently investigated. The aim was to study pharmacokinetics of ABZ and its metabolites [ABZ sulphoxide (ABSX) and ABZ sulphone] in the breast milk lactating women after one single oral dose of ABZ. Thirty-three lactating women (age 18-40 years) participated in the study. They received a single oral 400-mg dose of ABZ. Five milk samples were taken at 0, 6, 12, 24 and 36 h. One serum sample was taken after 6 h. Samples were analysed using high-performance liquid chromatography and pharmacokinetic analysis was performed. ABZ was detectable in milk samples 6 h after the oral dose. The mean concentration of serum ABZ was 63.7 +/- 11.9 ng ml(-1). The pharmacokinetic parameters for ABSX were calculated as follows: 351.9 +/- 32.4 ng ml(-1), 6.9 +/- 0.5 h, 12.4 +/- 2.2 h and 5190.3 +/- 482.8 ng*h ml(-1) for C(max), T(max), t((1/2)) and AUC(0-36), respectively. The milk-to-serum ratios (range) for ABZ and ABSX were 0.9 (0.2-6.5) and 0.6 (0.1-1.5), respectively. After an oral dose of 400 mg, ABZ and ABSX attain low concentrations in breast milk that are unlikely to be considered harmful for the breastfed infant.

Tribendimidine and Albendazole for Treating Soil-Transmitted Helminths, Strongyloides stercoralis and Taenia spp.: Open-Label Randomized Trial

BackgroundTribendimidine is an anthelminthic drug with a broad spectrum of activity. In 2004 the drug was approved by Chinese authorities for human use. The efficacy of tribendimidine against soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) has been established, and new laboratory investigations point to activity against cestodes and Strongyloides ratti.Methodology/Principal FindingsIn an open-label randomized trial, the safety and efficacy of a single oral dose of albendazole or tribendimidine (both drugs administered at 200 mg for 5- to 14-year-old children, and 400 mg for individuals ≥15 years) against soil-transmitted helminths, Strongyloides stercoralis, and Taenia spp. were assessed in a village in Yunnan province, People's Republic of China. The analysis was on a per-protocol basis and the trial is registered with controlled-trials.com (number ISRCTN01779485). Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and, moderately, against hookworm. The efficacy against T. trichiura was low. Among 57 individuals who received tribendimidine, the prevalence of S. stercoralis was reduced from 19.3% to 8.8% (observed cure rate 54.5%, p = 0.107), and that of Taenia spp. from 26.3% to 8.8% (observed cure rate 66.7%, p = 0.014). Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account “new” infections discovered at treatment evaluation, which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches, the difference between the drug-specific net Taenia spp. cure rates was highly significant in favor of tribendimidine (p = 0.001). No significant adverse events of either drug were observed.Conclusions/SignificanceOur results suggest that single-dose oral tribendimidine can be employed in settings with extensive intestinal polyparasitism, and its efficacy against A. lumbricoides and hookworm was confirmed. The promising results obtained with tribendimidine against S. stercoralis and Taenia spp. warrant further investigations. In a next step, multiple-dose schedules should be evaluated.

Clinical Quiz

A healthy 15-year-old girl was referred to our Centre with two episodes of painless fresh rectal bleeding each lasting for a few days. The blood was not mixed with stool. Stools were described as normal and there was no recent change in her bowel habits. There was no abdominal pain or other symptoms referable to the GI tract. Her father had a similar problem that he attributed to hemorrhoids. Physical examination was normal. She had routine investigations including complete blood count, blood urea nitrogen and serum electrolytes, liver function tests and inflammatory markers. All were within normal values. Colonoscopy was performed and biopsies taken. The histopathology of transverse colonic biopsy is shown in (Fig. 1).FIG. 1: Transverse colonic biopsy histopathology.What is the diagnosis? Ulcerative colitis. Rectal polyp. Enterobius vermicularis infestation. Meckel's diverticulum. ANSWER C. Enterobius vermicularis (Threadworm) Infestation. Figure 2 shows a segment of colonic mucosa. The surface epithelium is intact with mild patchy mucus-cell depletion. The lamina propria is edematous with a moderate increase in chronic inflammatory cells, especially eosinophils. One E. vermicularis worm is present (Fig. 2, arrow). The patient was treated with a single dose of albendazole that was repeated after 2 months. The patient made a full recovery with no further rectal bleeding.FIG. 2A: segment of colonic mucosa. One Enterobius vermicularis worm is present (arrow).Enterobius vermicularis is a nematode with worldwide distribution, although it is most prevalent in temperate and cold climates. Children are most often infected, but infestation can spread rapidly among family members. Infection spreads by direct transmission of ova from person to person or indirectly on clothing or house dust (1). Although nocturnal anal pruritus is usually the most common presenting symptom, there have been a few reports of E. vermicularis-induced eosinophilic colitis presenting with bloody diarrhea (2,3). Ova can be detected in the perianal region by applying a clear adhesive tape to the perianal skin and examining this microscopically. A single oral dose of albendazole is the treatment of choice, although pyrantel pamoate and piperazine are also effective. Treatment of the entire family is usually indicated (4). A second dose might be needed, as re-infestation can occur as early as 2 months after initial treatment (1).

Effects of albendazole against larval and adult Angiostrongylus cantonensis in rats

Effects of albendazole against larval and adult stages of Angiostrongylus cantonensis in rats were examined. (1) A single oral dose of albendazole of 10, 50 or 100 mg/kg at 7 or 14 days post-infection (PI) showed that the use of drug at 7 days PI was more effective in the larval infection. Rats treated 7 days PI showed significant reductions in the relative wet weight of heart and lungs (g/100 g body wt.), the mean total number of recovered worms and the mean body length of worms, as compared to those in the non-treated control. Similarly, visual morbidity assessment of the lung-tissues revealed a marked reduction in pathological changes in the rats treated 7 days PI. (2) Following two or three successive oral doses of 100 mg/kg at weekly intervals from 6 weeks PI, the first-stage larvae in rat feces completely disappeared 2 weeks post-treatment (PT) and this disappearance lasted during the experiment. In rats treated once, however, larval output reappeared from 3 weeks PT. Both histological sections of the rat lung-tissues and the recovered female worms showed degenerative changes in the female reproductive systems.

Differential efficacy of mebendazole and albendazole againstNecator americanus but not forTrichuris trichiura infestations

The effect of single oral doses of albendazole 600 mg and mebendazole 1 g given to 56 and 60 men, respectively, with T. trichiura and/or N. americanus infestation has been studied. Both albendazole and mebendazole cured more than 90% of T. trichiura infestations, but only albendazole (95%) and not mebendazole (21%) had a high cure rate for N. americanus infestations. Thus, albendazole is the preferred benzimidazole derivate for the mass treatment of subjects with T. trichiura and/or N. americanus infestations.

Interaction of Fasciola hepatica with albendazole and its metabolites.

Adult Fasciola hepatica recovered from sheep 12 and 24 h after a single oral dose of albendazole (20 mg/kg) contained significant amounts of two oxidized metabolites of albendazole (ABZ), a sulphoxide (SX) and a sulphone (SO), but not ABZ. Flukes incubated in vitro with 10 microM SX or SO contained these metabolites at a level two to three times the level observed in flukes recovered from sheep 24 h after a curative oral dose of ABZ. The concentration of ABZ in flukes was 10-fold greater than either SX or SO after a 24 h in vitro incubation in 10 microM of the respective drug. Flukes exposed to ABZ in vitro contained two-fold higher SX levels than SX-treated flukes due to a combination of spontaneous oxidation in media and fluke-mediated oxidation of ABZ. Measurement of end-products of glucose metabolism following 24 h incubation in 10 microM of either ABZ, SX or SO did not show a significant difference between treated and untreated flukes.