Efficacy Of Albendazole Research Articles

The threat of reduced efficacy of anthelmintics against gastrointestinal nematodes in sheep from an area considered anthelmintic resistance-free

BackgroundThe worldwide increased difficulty to combat gastrointestinal nematode (GIN) infection in sheep, due to progressing anthelmintic resistance (AR), calls for an enhanced and standardized implementation of early detection of AR. This study provides a snapshot of the current AR status against benzimidazoles and macrocyclic lactones in southern Italy, generated with standardized techniques.MethodsOn 10 sheep farms, the efficacy of albendazole (ALB) and either eprinomectin (EPR) or ivermectin (IVM) was evaluated based on the faecal egg count reduction test (FECRT) performed with the Mini-FLOTAC. For each tested drug, 40 sheep were rectally sampled at D0 and sampled again 14 days after the treatment (D14). The FECRT was calculated from individual samples and pooled samples which consist of 5 individual samples. Efficacy was classified as ‘reduced, ‘suspected’ and ‘normal’. Coprocultures were set for D0 and D14 faecal samples of each group. From farms with FECR < 95%, an in vitro egg hatch test (EHT) and a follow-up FECRT using fenbendazole (FBZ) were conducted.ResultsBased on the FECR, high efficacy (from 95.7% to 100%) was observed for ALB and IVM in eight farms (Farms 3–10). On Farm 1 and Farm 2, the efficacy for the macrocyclic lactones was classified as ‘normal’, but ‘reduced’ efficacy was observed for ALB on Farm 1 (FECR = 75%) and ‘suspected’ efficacy on Farm 2 (FECR = 93.3%) with the predominant GIN genus Trichostrongylus followed by Haemonchus at D14. The FEC results of pooled samples strongly correlated with those of individual samples, for FEC at D0 (rs = 0.984; P < 0.0001) and at D14 (rs = 0.913; P < 0.0001). The classifications of efficacy in Farm 1 (FECR = 86.0%) and Farm 2 (FECR = 93.0%) in the follow-up FECRT with FBZ coincide with the main FECRT trial. The in vitro EHT confirmed AR in both farms (Farm 1: 89%; Farm 2: 74%).ConclusionsIn regions like southern Italy, where the negative impacts from AR have played a minor role, efficient monitoring of AR is important in order to evaluate potential risks and being able to promptly respond with countermeasures.

Efficacy of Albendazole Against Soil-transmitted Helminthiasis among Children in Asia: Systematic Review

BACKGROUND: The World health organization reported that 875 million children worldwide require antihelminth preventive chemotherapy annually. Vast majority of STH infections (67%) and YLDs (68%) occurred in Asia.&#x0D; METHODS: A systematic search was performed for relevant titles, abstract, and keywords from Cochrane Library, PubMed, and Scopus around October 2018 based on the PICO strategy. Out of 173 papers that were evaluated, final assessment for eligibility had yielded a total of five papers to be included for analysis covering period from 2013 to 2018.&#x0D; RESULTS: Of the five selected studies, three were randomized controlled trial, one was cohort and another one was described more like a quasi-experimental trial. All infection intensity showed improvement post-intervention. Four of the five studies used Kato Katz as diagnostic method with one combined it with Baermann techniques. One used McMaster egg counting method. All except one study tested albendazole efficacy in their study either alone or in combination with other chemotherapy such as diethyl carbazide or combining with education pamphlet. Egg reduction rate was reported as low as 63% and as high as 99.9%.&#x0D; CONCLUSION: In general, albendazole is efficacious enough to control STH.

Albendazole solid dispersions against alveolar echinococcosis: a pharmacotechnical strategy to improve the efficacy of the drug.

Alveolar echinococcosis is a neglected parasitic zoonosis caused by Echinococcus multilocularis. The pharmacological treatment is based on albendazole (ABZ). However, the low water solubility of the drug produces a limited dissolution rate, with the consequent failure in the treatment of the disease. Solid dispersions are a successful pharmacotechnical strategy to improve the dissolution profile of poorly water-soluble drugs. The aim of this work was to determine the in vivo efficacy of ABZ solid dispersions using poloxamer 407 as a carrier (ABZ:P407 solid dispersions (SDs)) in the murine intraperitoneal infection model for secondary alveolar echinococcosis. In the chemoprophylactic efficacy study, the ABZ suspension, the ABZ:P407 SDs and the physical mixture of ABZ and poloxamer 407 showed a tendency to decrease the development of murine cysts, causing damage to the germinal layer. In the clinical efficacy study, the ABZ:P407 SDs produced a significant decrease in the weight of murine cysts. In addition, the SDs produced extensive damage to the germinal layer. The increase in the efficacy of ABZ could be due to the improvement of water solubility and wettability of the drug due to the surfactant nature of poloxamer 407. In conclusion, this study is the basis for further research. This pharmacotechnical strategy might in the future offer novel treatment alternatives for human alveolar echinococcosis.

Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association

The search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5 mg/kg), TML (150 mg/kg, twice every 24 h) or the co-administration of both compounds. Blood samples were collected between 0 and 51 h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16 ± 0.07 μg/mL and 3.63 ± 1.21 μg.h/mL) compared with those that received ABZ alone (0.45 ± 0.15 μg/mL and 9.50 ± 2.84 μg.h/mL). TML was detected in the bloodstream between 1 and 48 h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.

New codon 198 \u03b2-tubulin polymorphisms in highly benzimidazole resistant Haemonchus contortus from goats in three different states in Sudan

BackgroundBenzimidazole (BZ) resistance in gastrointestinal nematodes is a worldwide problem for livestock production, particularly in small ruminants. Assignment of the emergence of resistance using sensitive and reliable methods is required to adopt the correct strategies for control. In Sudan, BZ resistant Haemonchus contortus populations were recently reported in goats in South Darfur. This study aimed to provide additional data regarding albendazole efficacy and to describe the prevailing molecular BZ resistance mechanisms.MethodsFaecal egg count reduction and egg hatch tests (EHT) were used to evaluate albendazole efficacy in three different areas of South Darfur using naturally (Rehed Al-Birdi and Tulus) and experimentally infected (Tulus and Um Dafuq) goats. Using samples from Central, East and South Darfur, pyro- and Sanger sequencing were used to detect the polymorphisms F167Y, E198A and F200Y in H. contortus isotype 1 β-tubulin in DNA extracted from pooled third-stage larval (L3) samples (n = 36) on days 0 and 10 during trials, and from pooled adult male H. contortus (treated goats, n = 14; abattoirs, n = 83) including samples from populations previously found to be resistant in South Darfur.ResultsAlbendazole efficacies at 5, 7.5 and 10 mg/kg doses were 73.5–90.2% on day 14 in natural and experimental infections while 12.5 mg/kg showed > 96.6% efficacy. EC50 in the EHT were 0.8 and 0.11 µg/ml thiabendazole in natural and experimental infection trials, respectively. PCRs detected Haemonchus, Trichostrongylus and Cooperia in L3 samples from albendazole-treated goats. Haemonchus contortus allele frequencies in codons 167 and 200 using pyrosequencing assays were ≤ 7.4% while codon 198 assays failed. Sanger sequencing revealed five novel polymorphisms at codon 198. Noteworthy, an E198L substitution was present in 82% of the samples (L3 and adults) including all post-treatment samples. Moreover, E198V, E198K and potentially E198I, and E198Stop were identified in a few samples.ConclusionsTo our knowledge, this is the first report of E198L in BZ resistant H. contortus and the second where this is the predominant genotype associated with resistance in any strongyle species. Since this variant cannot be quantified using pyrosequencing, the results highlight important limitations in the general applicability of pyrosequencing to quantify BZ resistance genotypes.

Anti-echinococcal activity of menthol and a novel prodrug, menthol-pentanol, against Echinococcus multilocularis

Alveolar echinococcosis is one of the most dangerous parasitic zoonoses. This disease, widely distributed in the northern hemisphere, is caused by the metacestode stage of the tapeworm Echinococcus multilocularis. All surgical and non-surgical patients should perform chemotherapy with benzimidazoles, mainly with albendazole. However, the efficacy of albendazole is variable due to its deficient pharmacokinetic properties. Therefore, the need to find new therapeutic alternatives for the treatment of alveolar echinococcosis is evident. Menthol is a natural compound of low toxicity, used in industries such as cosmetics and gastronomy and generally recognized as safe by the Food and Drug Administration. In addition, menthol has important pharmacological effects and is effective against a wide variety of organisms. The development of prodrugs allows improving the pharmacokinetic properties of the parental drug. To improve lipophilicity and therefore the bioavailability of menthol, a novel prodrug called menthol-pentanol was developed by masking the functional polar group of menthol by linking n-pentanol by a carbonate bond. The aim of the current work was to evaluate the in vitro and in vivo efficacy of menthol and menthol-pentanol against E. multilocularis. Menthol-pentanol had a greater protoscolicidal effect than menthol. In addition, the prodrug demonstrated a similar clinical efficacy to albendazole. The increase in lipophilicity of the prodrug with respect to menthol was reflected in an increase in its antiparasitic activity against E. multilocularis. Thus, menthol-pentanol appears as a promising candidate for further evaluation as a potential alternative for the treatment of alveolar echinococcosis.

Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis

The study investigated chitosan coated nanostructured lipid carriers (NLCs) for oral delivery of albendazole in treatment of trichinellosis. NLCs comprised precirol and oleic acid with Tween and Span 80. Dicetylphosphate was used as charging agent to allow chitosan coating. Trichinella spiralis infected mice were used and albendazole suspension, coated or uncoated NLCs were orally administered at different stages of infection. NLCs were spherical with size of 188 and 200 nm for coated and uncoated NLC, respectively. Treatment during intestinal phase reduced worm count with NLCs showing better rank. This was reflected further by reduced larvae count and improved histopathological features. Starting treatment in the migrating phase reduced larval count by 62.9, 99.6 and 89.5 % after administration of suspension, coated and uncoated NLCs, respectively. The same rank was recorded for the encysted phase. NLCs enhanced the efficacy of albendazole against Trichinella spiralis compared with suspension with chitosan coated NLCs being superior.

Study on the prevalence of intestinal parasitic infections and the assessment of the efficacy of albendazole in soil-transmitted helminths in school-going children in East Sikkim.

Background:The problem of intestinal parasitic infections (IPIs) in children is one of the most worrisome problems worldwide. The latest estimates indicate that more than 880 million children are in the need of treatment for these parasites.Objective:The aim of this study was to measure the prevalence of IPIs in school-going children in East Sikkim, India, and to assess the efficacy of single-dose albendazole (ALB) in children infected with soil-transmitted helminths (STHs).Subjects and Methods:A total of 300 stool samples were collected from the schoolchildren of government schools of East Sikkim. Samples were processed for the identification of IPIs by direct microscopy and formalin-ether concentration method. Fecal egg counting was carried out for STH by Stoll's egg counting technique, pre- and posttreatment with single-dose ALB. The second stool samples were collected 10–14 days posttreatment of ALB. Cure rate (CR) and the fecal egg reduction rate (ERR), the two most widely used indicators for assessing the efficacy of an anthelmintic, were used in this study. The data were analyzed and the results were interpreted statistically.Results:The overall prevalence of the IPIs was 33.9%. Helminthic infection was 4.6% and protozoan infection was 29.3%. Among helminthes Ascaris lumbricoides and among protozoans Entamoeba spp. were the dominant intestinal parasites. For drug efficacy, A. lumbricoides had CR 55.5% and ERR 81.4%. Moreover, for Trichuris trichiura, CR and ERR was 100%. The study has shown less efficacy against A. lumbricoides infections compared to T. trichiura.Conclusion:The study provides useful insight into the current prevalence of IPIs in school-going children in government schools in East Sikkim region. Keeping in view of less efficacy of ALB, it is necessary to keep the monitoring of development of drug resistance simultaneously.

Effect of dexamethasone on albendazole cysticidal activity in experimental cysticercosis by Taenia crassiceps in BALB/c mice: In vitro and in vivo evaluation

Taenia solium is a parasite whose larvae (cysticerci) can locate in the central nervous system of humans and cause neurocysticercosis (NC). The introduction of cysticidal drugs such as albendazole (ABZ) for the treatment of NC has significantly improved its prognosis. However, treatment is not always effective, and the high levels of corticosteroids used to prevent inflammatory complications in this disease could be, partly, the cause of this observation. In this context, this study investigated, using the experimental mouse model of intraperitoneal infection with Taenia crassiceps, the influence of corticosteroid administration on the therapeutic efficacy of ABZ. We evaluated and compared the effects of ABZ, dexamethasone (DXM) and their combination (ABZ + DXM) on cyst viability, both in vitro and in vivo. Serum levels of IL-4, IFN-gamma, IL-6 and IL-10 were evaluated in the in vivo study. Results showed that the treatment with ABZ, in vitro and in vivo, was associated with a high number of parasites deaths. Concomitant treatment with DXM did not alter ABZ in vitro cysticidal activity but reduced its effectiveness significantly in the in vivo experimental model. Cytokine serum levels did not change significantly in treated mice compared to the controls. The results of this study are relevant as they indicate a negative effect of corticosteroids on the efficacy of cysticidal therapy. In human neurocysticercosis, control of inflammation is of great importance to most patients in order to avoid complications. Corticosteroids are generally used for this purpose and the results of this study demonstrate the need to find other therapeutic strategies. Further studies are needed to better understand the mechanisms involved.

Enhanced Oral Bioavailability and Anti-Echinococcosis Efficacy of Albendazole Achieved by Optimizing the "Spring" and "Parachute".

Maximizing the pharmacological efficacy of albendazole (ABZ), an anti-echinococcosis drug, is essential in the long-term treatment of patients with echinococcosis. As a weakly alkaline drug, ABZ has a pH-dependent solubility that decreases dramatically from gastric fluid (pH 1.4) to intestinal fluid (pH 6.5), where it is absorbed. In this study, we endeavored to develop an optimized tablet formulation of ABZ to improve its dissolution and oral bioavailability from two aspects: a faster initial dissolution in the gastric pH condition (i.e., the "spring") and a more prolonged drug supersaturation in the intestinal pH condition (i.e., the "parachute"). To achieve this goal, ABZ-HCl salt was selected first, which demonstrated a higher intrinsic dissolution rate under pH 1.4 compared with the ABZ free base that is used in the commercial product Albenda. Second, by comparing the ABZ supersaturation kinetics under pH 6.5 in the presence of various polymers including poly(vinylpyrrolidone) (PVP), PVP/VA, hydroxypropyl methylcellulose (HPMC), and HPMC acetate succinate (HPMC-AS), HPMC-AS was found to be the most effective crystallization inhibitor for ABZ, likely due to the hydrophobic interaction between ABZ and HPMC-AS in an aqueous environment. The newly designed tablet formulation containing ABZ-HCl and HPMC-AS showed ∼3 times higher oral bioavailability compared with that of Albenda in Beagle dogs. More significantly, the anti-echinococcosis efficacy of the improved formulation was 2.4 times higher than that of Albenda in a secondary hepatic alveolar echinococcosis Sprague-Dawley rat model. The strategy of simultaneously improving the spring and parachute of an oral formulation of ABZ, by using a highly soluble salt and an effective polymeric crystallization inhibitor, was once again proven to be a viable and readily translatable approach to optimize the unsatisfactory oral medicines due to solubility and bioavailability limitations.

Detection of Gastrointestinal Nematode Populations Resistant to Albendazole and Ivermectin in Sheep

Simple SummaryGastrointestinal parasite infections represent a major welfare problem in small ruminants reared in extensive systems, which may be exacerbated by anthelmintic resistance. In this study, we evaluated the efficacy of two commonly used anthelmintic drugs in sheep reared in the Mexican temperate zone. We found that the genera Cooperia spp. and Trichostrongylus spp. were the nematodes predominant in all experimental animals. We also found that the sheep flock naturally infected with gastrointestinal nematodes in the temperate zone (i.e., central valley) of the State of Mexico exhibit anthelmintic resistance with marked and potentially detrimental effects on sheep welfare and production. Both albendazole and ivermectin proved to be only partly effective for the treatment of both Cooperia spp. and Trichostrongylus spp. Therefore, we suggest that nematode infections should be systematically monitored in order to implement integrated management strategies to control nematodiasis more effectively, limit anthelmintic resistance and promote sheep welfare and production.Gastrointestinal parasite infections represent a major welfare problem in small ruminants reared in extensive systems, which may be exacerbated by anthelmintic resistance. Therefore, we aimed to study the efficacy of albendazole and ivermectin in sheep. Eighty-six animals were selected from commercial farms in the temperate area of the State of Mexico at the age of seven months. These animals were randomly distributed into three groups: Group A, treated with albendazole, Group I, treated with ivermectin and Group C, left untreated. Faecal samples were collected before the anthelmintic was administered and 15 days post-treatment. Both Group A and Group I displayed a significant decrease of faecal egg counts when pre- and post-treatment values were compared (p = 0.003 and p = 0.049, respectively), and a significantly lower faecal egg count when compared with Group C after the treatment (p < 0.05). However, the faecal egg count reduction test showed that gastrointestinal nematodes (GIN) developed anthelmintic resistance to both albendazole and ivermectin. The results of the polymerase chain reaction (PCR) allowed the identification of Cooperia spp., and Trichostrongylus colubriformis. The allele-specific PCR results confirmed that T. colubriformis was resistant to albendazole. In conclusion, this study showed the presence of resistant GIN to albendazole and ivermectin in sheep reared in Mexican temperate zones. Therefore, nematode infections should be systematically monitored in order to implement integrated management strategies to prevent the spread of anthelmintic resistance.

Improvement of Antialveolar Echinococcosis Efficacy of Albendazole by a Novel Nanocrystalline Formulation with Enhanced Oral Bioavailability.

Alveolar echinococcosis (AE) is a chronic infectious parasitic disease that is fatal and still being neglected. Currently, the AE treatment recommended by the WHO is complete excision of the lesions, followed by the oral administration of albendazole (ABZ), the only effective first-line anti-AE drug, for two years. Unfortunately, complete excision of AE lesions is impossible in most cases, leaving the long-term use of ABZ as the only alternative. However, only about one-third of patients experience complete remission or cure with such treatments, largely because of the low oral bioavailability of ABZ caused by its very low solubility. To improve the oral bioavailability of ABZ, a novel nanocrystalline (NC) formulation of ABZ was obtained by spray-drying ABZ with a triblock copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Poloxamer 188), and its physical structure was confirmed by scanning electron microscopy (SEM), small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXRD), and polarized optical microscopy (POM). The significantly reduced ABZ crystallite size coupled with prolonged ABZ supersaturation significantly improved the drug dissolution performance compared with that of the commercial ABZ oral product (Albenda), and the NC formulation showed an approximately 4.2-fold higher AUC than Albenda in a pharmacokinetic comparison in Beagle dogs as measured by the plasma concentration of albendazole sulfoxide, the active antiparasitic metabolite. Even more encouragingly, after 30 days of once-daily oral administration of the NC and Albenda formulations to SD rats with hepatic alveolar echinococcosis, the NC formulation demonstrated a cyst inhibition effect 3.7-fold greater than that of Albenda. We therefore conclude that the NC formulation could potentially be developed into an improved anti-AE drug therapy.

Evaluation of the curative effect of Balanites aegyptiaca fruits ethanolic extract on Haemonchosis experimentally induced in Egyptian Baladi goats: phytoanalytical, parasitological and hematological studies.

This study aimed to screen phytochemical components and antioxidant activity of Balanites aegyptiaca ethanolic extract (BAF-EE) as well as to evaluate its curative effect on experimentally induced haemonchosis in goats. Phytochemical constitutes of BAF-EE were screened and identified using Gas Chromatography-mass Spectrometry (GC-MS) analysis and antioxidant effect was determined. Infective third larval stage (L3) of Haemonchus contortus (H. contortus) were obtained by culturing feces of goat harboring monospecific infection of the parasite. Twelve male goats were randomly divided into four groups (n = 3) as: G1 (infected-untreated) which served as control positive, G2 (infected-BAF-EE treated), G3 (infected-albendazole treated) and G4 (uninfected-BAF-EE treated) that served as control negative. Experimental infection was conducted with a single oral dose of 10,000 L3 at 0-time, whereas treatment with BAF-EE and albendazole were given at a single oral dose of 9g and 5mg/kg BW, respectively in the 5th week post infection (PI). Egg count per gram of feces (EPG) was conducted once a week and blood samples were drawn on zero time, 3rd week PI and then biweekly for 9weeks, for conduction of hemogram. At the end of the experiment, all animals were slaughtered and adult worms in their abomasa were counted. GC-MS analysis confirmed 28 compounds in the extract which revealed presence of saponins, flavonoids, terpenoids, phenolics and alkaloids, and exhibited in vitro antioxidant activity. Clinical signs observed on the infected animals were signs of anemia, which were gradually disappeared post treatment (PT). A maximum reduction in EPG (88.10%) and worm burden (94.66%) was recorded on 4th week PT due to efficacy of BAF-EE in contrast to 98.29% and 96.95% efficacy of albendazole. All infected groups showed a significant decrease in hemoglobin (Hb) and packed cell volume (PCV) and presence of microcytic hypochromic anemia compared with G4. Goats treated with B. aegyptiaca and albendazole, exhibited significant increase in Hb and PCV 2weeks PT and anemia changed to be normocytic hypochromic or microcytic normochromic in G2 and G3, respectively. Total white blood cells (WBCs) were elevated significantly in all infected groups which attributed to increase in lymphocytes, monocytes and eosinophils on expense of neutrophils. After treatments, WBCs and previously mentioned cells tended to decease. This study demonstrated that BAF-EE has anthelmintic effect against H. contortus and can improve hemogram and health condition of infected goats.

Evaluation of the therapeutic efficacy of albendazole-loaded silver nanoparticles against Echinococcus granulosus infection in experimental mice.

The drug of choice for treatment of hydatid disease, albendazole (ABZ) is a poorly water-soluble drug; thus, enhancing its solubility is required. Among metal nanoparticles (NPs), silver (Ag) NPs showed antimicrobial efficacies. Therefore, this study was conducted to evaluate nanosilver particles (Ag NPs) free or combined with albendazole against Echinococcus granulosus infection in vivo. In this study, besides the normal control group (GI) (n = 5), 80 mice were infected with 2000 viable protoscoleces intraperitoneally then divided equally (n = 20) into the infected control (GII), ABZ-treated (GIII), nanosilver-treated (GIV) and ABZ-loaded-Ag NPs-treated (GV) groups. On the 90th post-infection day, treatment was started and continued for 8weeks then the experiment was terminated. Each mouse was subjected to measurement of hydatid cysts' sizes and weights, serum IFN-γ, liver enzymes; histopathological and transmission electron microscopy studies. In all treated groups, there were significant reductions of hydatid cysts' sizes and weights; however, the highest efficacy rate (63.9%) was detected in group V associated with obvious ultrastructure alterations of the cysts. The liver tissues of group II showed intense granulomatous reactions, congestion, fibrosis, necrosis and steatosis associated with significant increases in serum IFN-γ and liver enzymes. Interestingly, the best antiparasitic effect and the most significant reduction of IFN-γ towards the normal values were found in GV. Moreover, Ag NPs had reduced the toxic effects of ABZ such as necrosis, steatosis and the elevated serum liver enzymes. Therefore, loading ABZ on Ag NPs could be a potential method to improve ABZ efficacy against hydatid disease.

Epidemiology of strongyle nematode infections and first report of benzimidazole resistance in Haemonchus contortus in goats in South Darfur State, Sudan

BackgroundSince pastoralists in South Darfur, Sudan, had complained about lack of albendazole (ABZ) efficacy to control nematodes in goats, the frequency of infection with gastrointestinal helminths was studied before in vivo faecal egg count reduction tests (FECRT) were conducted using ABZ orally either at the dose recommended for sheep, 5 mg/kg body weight (bw) or at 10 mg/kg bw. Experiments included goats naturally infected with gastrointestinal nematodes or experimentally infected with local Haemonchus contortus isolates. Three study areas (Nyala, Beleil and Kass) were visited in autumn or winter.ResultsOut of 478 screened goats, 82.4% were infected with gastrointestinal helminths and 82% were shedding eggs of strongyle nematodes with 90% of the strongyle larvae representing Haemonchus spp. A FECRT using naturally infected goats (n = 225: 71 untreated, 104 and 50 treated with 5 and 10 mg ABZ/kg bw, respectively) detected reduced ABZ efficacy in Nyala and Kass. Paired and unpaired FECRT calculations detected reductions of 72–92% with samples taken at 8 days post treatment with 5 mg ABZ/kg bw and of 85–94% with 10 mg ABZ/kg bw. The FECRT based on day 14 post treatment samples showed reductions of 69–77% with 5 mg/kg and of 75–87% with 10 mg ABZ/kg bw. In Beleil, ABZ efficacy was 95%. In the egg hatch test EC50 values for Nyala and Kass ranged from 0.12–0.24 μg thiabendazole/ml, corresponding to benzimidazole resistant phenotypes. Only Haemonchus spp. larvae were present after treatments in coprocultures. When the efficacy was evaluated experimentally using isolates of H. contortus from Nyala and Kass, the 5 mg ABZ/kg dose revealed reductions of 76–78% on day 8 and of 62–70% on day 14 with the unpaired method. Using 10 mg ABZ/kg, the FECR was still only 77–82%.ConclusionsBoth, in vivo and in vitro methods detected resistant H. contortus populations in goats from South Darfur State. The time point 14 days post treatment was more sensitive for detection of ABZ resistance than 8 days post treatment. This is the first report on the occurrence of anthelmintic resistance in Sudan confirming that anthelmintic resistance selection is occurring in African subsistence farming systems.

Efficacy of Albendazole and Mebendazole With or Without Levamisole for Ascariasis and Trichuriasis.

BACKGROUND:Helminthiasis in school-aged children potentially causing physical growth and intellectual development retardation. Trichuriasis was the most common type of helminthiasis in children.AIM:To investigated the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis and ascariasis.METHODS:This study was conducted as a double-blind, randomised clinical trial by comparing the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis. The sample of this study were 180 elementary school students at Deli Serdang Regency State Elementary School, Medan, Indonesia. The study was conducted from April to June 2015.RESULT:The cure rate of helminthiasis on the 7th day was 81.7% after albendazole therapy, 88.3% after albendazole levamisole therapy, and 83.3% after mebendazole combined with levamisole therapy (p = 0.577). Cure rate on the 14th day was 88.3%, 95%, and 91.7% for albendazole, albendazole combined with levamisole, and mebendazole combined with levamisole therapy, respectively (p = 0.418). On the 21th day, the cure rate was 88.3%, 96.7%, and 91.7% (p = 0.230). Combination of albendazole and levamisole showed the highest cure rate, despite the statistically insignificant difference for all groups (p > 0.05). Combination of albendazole combined with levamisole showed better cure rate for mild trichuriasis (95.8%) than albendazole therapy (46.2%) and mebendazole combined with levamisole (83.3%), (p < 0.05).CONCLUSION:Single-dose albendazole, a combination of albendazole and levamisole, and a combination of mebendazole and levamisole had similar efficacy in reducing egg count in helminthiasis. Combination of albendazole and levamisole showed better cure rate for mild trichuriasis and mixed infections. Side effects were similar in all treatment groups.

Microscopic alterations in Fasciola hepatica from sheep treated with albendazole.

Currently, albendazole is one of the most commonly used drugs because of its affordability. The objective was to evaluate the histopathology of Fasciola hepatica specimens. For this, the efficacy test was performed on sheep treated with albendazole at the dose recommended for F. hepatica, in which the helminths recovered at necropsy were counted and separated for histology. Spermatogenic cells from parasites recovered from treated and control sheep were examined by microscopy. The fecal egg-count reduction test revealed 97.06% efficacy of albendazole in the treatment of F. hepatica. Changes in testicular tubule cells started 48 hours after treatment and became evident within 72 hours, at which point it became difficult to identify cell types. Primary and secondary spermatogonia became increasingly rare and intercellular vacuolization was more evident. Signs of apoptosis, with pycnotic nuclei and evidence of keriorrexia were observed at all times. Cell debris was identified 96 hours after treatment. The results indicated that parasitic spermatogenesis was severely affected by albendazole and demonstrated the importance of the use of histopathology for the diagnosis of therapeutic efficacy in field strains.

Efficacy of anthelmintic towards gastrointestinal nematode infection in thin-tailed sheep at smallholder farms in Sukomulyo Village, Malang Regency

Intensive anthelmintic administration was estimated to cause drug resistancy. Research was conducted to determine the efficacy of albendazole and levamisole anthelmintic in thin-tailed sheep infected with gastrointestinal nematode at smallholder farms in Sukomulyo Village, Malang Regency. A total of 65 sheeps naturally infected with nematode worms were administered albendazole (35 tails) and levamisole (30 tails). Observation of egg per grams (EPG) was conducted using modified McMaster method. To determine treatments’ efficacy, EPG was conducted before and 2 weeks after treatments’ administration. The results showed that in farms that routinely given albendazole, mean treatment efficacy was 83.73% meanwhile in farms that were never receive albendazole was 92.23%. There were no farms that ever receive levamisole before. Mean treatment’s efficacy for levamisole was 95.84%. In conclusion, albendazole and levamisole still effective as anthelmintic towards gastrointestinal nematode infection in thin-tailed sheep. However, the possibility of drug resistance needs to be carefully observed, especially for albendazole.

Albendazole, levamisole and ivermectin are effective against monogeneans of Colossoma macropomum (Pisces: Serrasalmidae).

This study evaluated the efficacy of albendazole, ivermectin, levamisole, mebendazole and praziquantel on monogeneans of Colossoma macropomum, based on in vitro and in vivo assays. In vitro assays indicated that albendazole (500, 100, 1,500 and 2,000mg/L), ivermectin (200, 250, 300 and 350mg/L) and levamisole (50, 75, 100 and 125mg/L) were 100% effective against Anacanthorus spatulatus, Notozothecium janauachensis, Mymarothecium boegeri and Linguadactyloides brinkmanni, while mebendazole (125, 150, 175 and 200mg/L) and praziquantel (5, 10, 15 and 20mg/L) were ineffective. Fish mortality in 24hr therapeutic baths with 500mg/L of albendazole was 6.6%, but the behaviour of the animals remained unchanged, while 200mg/L of ivermectin caused lethargy, signs of hypoxia and 100% mortality within 2hr, and 125mg/L of levamisole caused no mortality. The efficacy of 500mg/L of albendazole was 48.6% in the 24hr baths, while that of 125mg/L levamisole was 88.2%. Although ivermectin showed in vitro efficacy, the lowest concentration used in baths was highly toxic to fish. Therefore, we recommend the use of 125mg/L of levamisole to control and treat monogenean infestations on C.macropomum in fish farming.

Pharmacokinetic assessment of methimazole-mediated modulation of albendazole biotransformation and efficacy in goats

To assess the hypothesis that hepatic microsomal oxidation inhibitor methimazole (MTH) could increase bioavailability of albendazole (ABZ), a study was undertaken to understand the pharmacokinetics and efficacy of ABZ in goats with and without co-adminstration of ABZ with MTH at 7.5 and 3.0 mg/kg body weight, respectively. Significant increased values (P<0.05) of time to reach concentration maximum (calculated), area under concentration-time curve (0-∞), elimination half-life (t1/2β) and total area under the first movement of plasma drug concentration time curve were observed for ABZ-SO (albendazole sulphoxide) in goats following coadministration of ABZ and MTH. Faecal egg count reduction and lower 95% confidence limit revealed resistance and susceptible for ABZ alone and co-administration of ABZ and MTH, respectively. The dominant nematode exhibiting resistance was Haemonchus spp. ED 50 for egg hatch was 0.196 indicating resistance to benzimidazole. The study suggested that coadministration of ABZ and MTH affects pharmacokinetic disposition of ABZ, which could possibly result in potentiation of anthelmintic activity of ABZ as observed through faecal egg count reduction test.