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Jennifer Keiser - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of Albendazole Albendazole sulfoxide and Albendazole sulfone determined from plasma blood dried blood spots and mitra samples of hookworm infected adolescents
Antimicrobial Agents and Chemotherapy, 2019Co-Authors: Jessica D Schulz, Anna Neodo, Jean T Coulibaly, Jennifer KeiserAbstract:Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify Albendazole's disposition. Quantification methods were developed and validated using liquid chromatography-tandem mass spectrometry to analyze Albendazole and its metabolites Albendazole sulfoxide and Albendazole sulfone in wet samples (plasma and blood) and blood microsamples (dried-blood spots [DBS]; Mitra). The use of DBS was limited by a matrix effect and poor recovery, but the extraction efficiency was constant throughout the concentration range. Hookworm-infected adolescents were venous and capillary blood sampled posttreatment with 400 mg Albendazole and 25 mg/kg oxantel pamoate. Similar half-life (; t; 1/2; = ∼1.5 h), time to reach the maximum concentration (; t; max; = ∼2 h), and maximum concentration (; C; max; = 12.5 to 26.5 ng/ml) of Albendazole were observed in the four matrices. The metabolites reached; C; max; after ∼4 h with a; t; 1/2; of ca. 7 to 8 h. A statistically significant difference in Albendazole sulfone's; t; 1/2; as determined by using DBS and wet samples was detected.; C; max; of Albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher; C; max; of Albendazole sulfone were obtained in the two microsampling devices (22 ng/ml) versus the wet matrices (14 ng/ml). In conclusion, time-concentration profiles and PK results of the four matrices were similar, and the direct comparison of the two microsampling devices indicates that Mitra extraction was more robust during validation and can be recommended for future Albendazole PK studies.
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exposure of heligmosomoides polygyrus and trichuris muris to Albendazole Albendazole sulfoxide mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes
International Journal for Parasitology-Drugs and Drug Resistance, 2017Co-Authors: Noemi Cowan, Anna Neodo, Charles Meier, Jennifer KeiserAbstract:Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of Albendazole, Albendazole sulfoxide, Albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of Albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and invivo. Oral and intraperitoneal treatments (100 mg/kg) were studied. Drug quantities in helminths and host compartments (stomach, the contents and mucosa of the small and large intestine, and the plasma) were determined using HPLC-UV/vis and anthelmintic activities were recorded using phenotypic readout. The influence of 1-aminobenzotriazole (ABT), an irreversible and unspecific cytochrome P450 inhibitor, on Albendazole disposition in mice harboring H. polygyrus was evaluated. In vivo, Albendazole was found in quantities up to 10 nmol per ten H. polygyrus and up to 31 nmol per ten T. muris. ABT did not change the levels of Albendazole or its metabolites in the plasma of mice harboring H. polygyrus or in H. polygyrus, whereas drug levels in the gastrointestinal tract of host mice doubled. Mebendazole and oxantel pamoate quantities per ten T. muris were as high as 21 nmol and 34 nmol, respectively. Albendazole revealed a very dynamic distribution and high rate of metabolism, hence, H. polygyrus and T. muris are exposed to Albendazole and both metabolites via multiple pathways. Diffusion through the cuticle seems to be the crucial pathway of oxantel pamoate uptake into T. muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied.
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In Vitro and In Vivo Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Noemi Cowan, Mireille Vargas, Jennifer KeiserAbstract:The current treatments against Trichuris trichiura, Albendazole and mebendazole, are only poorly efficacious. Therefore, combination chemotherapy was recommended for treating soil-transmitted helminthiasis. Albendazole-mebendazole and Albendazole-oxantel pamoate have shown promising results in clinical trials. However, in vitro and in vivo drug interaction studies should be performed before their simultaneous treatment can be recommended. Inhibition of human recombinant cytochromes P450 (CYPs) CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was tested by exposure to Albendazole, Albendazole sulfoxide, mebendazole, and oxantel pamoate, as well as Albendazole-mebendazole, Albendazole sulfoxide-mebendazole, Albendazole-oxantel pamoate, and Albendazole sulfoxide-oxantel pamoate. A high-pressure liquid chromatography (HPLC)-UV/visible spectroscopy method was developed and validated for simultaneous quantification of Albendazole sulfoxide, Albendazole sulfone, mebendazole, and oxantel pamoate in plasma. Albendazole, mebendazole, oxantel pamoate, Albendazole-mebendazole, and Albendazole-oxantel pamoate were orally applied to rats (100 mg/kg) and pharmacokinetic parameters calculated. CYP1A2 showed a 2.6-fold increased inhibition by Albendazole-oxantel pamoate (50% inhibitory concentration [IC50] = 3.1 μM) and a 3.9-fold increased inhibition by Albendazole sulfoxide-mebendazole (IC50 = 3.8 μM) compared to the single drugs. In rats, mebendazole's area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) were augmented 3.5- and 2.8-fold, respectively (P = 0.02 for both) when coadministered with Albendazole compared to mebendazole alone. Albendazole sulfone was slightly affected by Albendazole-mebendazole, displaying a 1.3-fold-elevated AUC compared to Albendazole alone. Oxantel pamoate could not be quantified, translating to a bioavailability below 0.025% in rats. Elevated plasma levels of Albendazole sulfoxide, Albendazole sulfone, and mebendazole in coadministrations are probably not mediated by CYP-based drug-drug interaction. Even though this study indicates that it is safe to coadminister Albendazole-oxantel pamoate and Albendazole-mebendazole, human pharmacokinetic studies are recommended.
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Efficacy and reinfection with soil-transmitted helminths 18-weeks post-treatment with Albendazole-ivermectin, Albendazole-mebendazole, Albendazole-oxantel pamoate and mebendazole
Parasites & vectors, 2016Co-Authors: Benjamin Speich, Jan Hattendorf, Marco Albonico, Wendelin Moser, Said M. Ali, Shaali M. Ame, Jennifer KeiserAbstract:Preventive chemotherapy with Albendazole or mebendazole is the current strategy to control soil-transmitted helminth (STH) infections (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura). STH reinfections, in particular A. lumbricoides and T. trichiura occur rapidly after treatment with the standard drugs. However, their low efficacy against T. trichiura, made an accurate assessment of reinfection patterns impossible. In 2013 a randomised controlled trial was conducted on Pemba Island, Tanzania. School-aged children diagnosed positive for T. trichiura, were randomly allocated to (i) Albendazole-ivermectin; (ii) Albendazole-mebendazole; (iii) Albendazole-oxantel pamoate; or (iv) mebendazole. Here we report the efficacy [cure rates (CR) and egg-reduction rates (ERR)], reinfection rates and new infections determined 18 weeks post-treatment. For a total of 405 children complete baseline and follow-up data were available. Similar to the efficacy determined after 3 weeks, 18 weeks after treatment Albendazole-oxantel pamoate showed a significantly higher efficacy against T. trichiura (CR: 54.0 %, 95 % CI: 43.7–64.0; ERR: 98.6 %, 95 % CI: 97.8–99.2) compared to the other treatment arms. Children treated with Albendazole-oxantel pamoate or Albendazole-ivermectin had fewer moderate infections compared to children treated with Albendazole. The reinfection rates 18 weeks post-treatment among all treatment arms were 37.2 % for T. trichiura (95 % CI: 28.3–46.8), 34.6 % for A. lumbricoides (95 % CI: 27.3–42.3) and 25.0 % for hookworms (95 % CI: 15.5–36.6). The moderate reinfection rates with STHs 18 weeks post-treatment support the concept of regular anthelminthic treatment in highly endemic settings. Combination chemotherapy might achieve decreased morbidity in children since in the Albendazole plus oxantel pamoate and Albendazole plus ivermectin treatment arms only few moderate T. trichiura infections remained. Further trials should investigate the long term efficacy of Albendazole-oxantel pamoate (i.e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections. Current Controlled Trials ISRCTN80245406
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efficacy and safety of Albendazole plus ivermectin Albendazole plus mebendazole Albendazole plus oxantel pamoate and mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, Albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive Albendazole (400 mg) plus ivermectin (200 μg/kg); Albendazole (400 mg) plus mebendazole (500 mg); Albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and Albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for Albendazole plus ivermectin, 10 (9·3%) for Albendazole plus mebendazole, 20 (18·2%) for Albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for Albendazole plus ivermectin, 6 (5·6%) for Albendazole plus mebendazole, 12 (10·9%) for Albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for Albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of Albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
Benjamin Speich - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of co administered ivermectin plus Albendazole for treating soil transmitted helminths a systematic review meta analysis and individual patient data analysis
PLOS Neglected Tropical Diseases, 2018Co-Authors: Vicente Y. Belizario, Benjamin Speich, Stefanie Knopp, Marta S Palmeirim, Eveline Hurlimann, Serene A Joseph, Michel VaillantAbstract:Background The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (Albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus Albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. Methods and findings We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-Albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-Albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-Albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to Albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over Albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-Albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and Albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-Albendazole compared to those treated with Albendazole alone (RR = 1.29, 95% CI = 0.81–2.05). Conclusions Our findings suggest a good tolerability and higher efficacy of ivermectin-Albendazole against T. trichiura compared to the current standard single-dose Albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.
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Efficacy and reinfection with soil-transmitted helminths 18-weeks post-treatment with Albendazole-ivermectin, Albendazole-mebendazole, Albendazole-oxantel pamoate and mebendazole
Parasites & vectors, 2016Co-Authors: Benjamin Speich, Jan Hattendorf, Marco Albonico, Wendelin Moser, Said M. Ali, Shaali M. Ame, Jennifer KeiserAbstract:Preventive chemotherapy with Albendazole or mebendazole is the current strategy to control soil-transmitted helminth (STH) infections (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura). STH reinfections, in particular A. lumbricoides and T. trichiura occur rapidly after treatment with the standard drugs. However, their low efficacy against T. trichiura, made an accurate assessment of reinfection patterns impossible. In 2013 a randomised controlled trial was conducted on Pemba Island, Tanzania. School-aged children diagnosed positive for T. trichiura, were randomly allocated to (i) Albendazole-ivermectin; (ii) Albendazole-mebendazole; (iii) Albendazole-oxantel pamoate; or (iv) mebendazole. Here we report the efficacy [cure rates (CR) and egg-reduction rates (ERR)], reinfection rates and new infections determined 18 weeks post-treatment. For a total of 405 children complete baseline and follow-up data were available. Similar to the efficacy determined after 3 weeks, 18 weeks after treatment Albendazole-oxantel pamoate showed a significantly higher efficacy against T. trichiura (CR: 54.0 %, 95 % CI: 43.7–64.0; ERR: 98.6 %, 95 % CI: 97.8–99.2) compared to the other treatment arms. Children treated with Albendazole-oxantel pamoate or Albendazole-ivermectin had fewer moderate infections compared to children treated with Albendazole. The reinfection rates 18 weeks post-treatment among all treatment arms were 37.2 % for T. trichiura (95 % CI: 28.3–46.8), 34.6 % for A. lumbricoides (95 % CI: 27.3–42.3) and 25.0 % for hookworms (95 % CI: 15.5–36.6). The moderate reinfection rates with STHs 18 weeks post-treatment support the concept of regular anthelminthic treatment in highly endemic settings. Combination chemotherapy might achieve decreased morbidity in children since in the Albendazole plus oxantel pamoate and Albendazole plus ivermectin treatment arms only few moderate T. trichiura infections remained. Further trials should investigate the long term efficacy of Albendazole-oxantel pamoate (i.e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections. Current Controlled Trials ISRCTN80245406
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efficacy and safety of Albendazole plus ivermectin Albendazole plus mebendazole Albendazole plus oxantel pamoate and mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, Albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive Albendazole (400 mg) plus ivermectin (200 μg/kg); Albendazole (400 mg) plus mebendazole (500 mg); Albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and Albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for Albendazole plus ivermectin, 10 (9·3%) for Albendazole plus mebendazole, 20 (18·2%) for Albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for Albendazole plus ivermectin, 6 (5·6%) for Albendazole plus mebendazole, 12 (10·9%) for Albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for Albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of Albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
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Albendazole and mebendazole administered alone or in combination with ivermectin against trichuris trichiura a randomized controlled trial
Clinical Infectious Diseases, 2010Co-Authors: Benjamin Speich, Stefanie Knopp, Khalfan A Mohammed, Simba I Khamis, Alipo Naim Khamis, Jan Hattendorf, Russell J StothardAbstract:Background. Single-dose Albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of Albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of Albendazole (400 mg) plus placebo, Albendazole plus ivermectin (200 mug/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with Albendazole-ivermectin (38%), mebendazole (19%), and Albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by Albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and Albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both Albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN08336605
Stefanie Knopp - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of co administered ivermectin plus Albendazole for treating soil transmitted helminths a systematic review meta analysis and individual patient data analysis
PLOS Neglected Tropical Diseases, 2018Co-Authors: Vicente Y. Belizario, Benjamin Speich, Stefanie Knopp, Marta S Palmeirim, Eveline Hurlimann, Serene A Joseph, Michel VaillantAbstract:Background The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (Albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus Albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. Methods and findings We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-Albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-Albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-Albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to Albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over Albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-Albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and Albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-Albendazole compared to those treated with Albendazole alone (RR = 1.29, 95% CI = 0.81–2.05). Conclusions Our findings suggest a good tolerability and higher efficacy of ivermectin-Albendazole against T. trichiura compared to the current standard single-dose Albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.
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Albendazole and mebendazole administered alone or in combination with ivermectin against trichuris trichiura a randomized controlled trial
Clinical Infectious Diseases, 2010Co-Authors: Benjamin Speich, Stefanie Knopp, Khalfan A Mohammed, Simba I Khamis, Alipo Naim Khamis, Jan Hattendorf, Russell J StothardAbstract:Background. Single-dose Albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of Albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of Albendazole (400 mg) plus placebo, Albendazole plus ivermectin (200 mug/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with Albendazole-ivermectin (38%), mebendazole (19%), and Albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by Albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and Albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both Albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN08336605
Jan Hattendorf - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and reinfection with soil-transmitted helminths 18-weeks post-treatment with Albendazole-ivermectin, Albendazole-mebendazole, Albendazole-oxantel pamoate and mebendazole
Parasites & vectors, 2016Co-Authors: Benjamin Speich, Jan Hattendorf, Marco Albonico, Wendelin Moser, Said M. Ali, Shaali M. Ame, Jennifer KeiserAbstract:Preventive chemotherapy with Albendazole or mebendazole is the current strategy to control soil-transmitted helminth (STH) infections (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura). STH reinfections, in particular A. lumbricoides and T. trichiura occur rapidly after treatment with the standard drugs. However, their low efficacy against T. trichiura, made an accurate assessment of reinfection patterns impossible. In 2013 a randomised controlled trial was conducted on Pemba Island, Tanzania. School-aged children diagnosed positive for T. trichiura, were randomly allocated to (i) Albendazole-ivermectin; (ii) Albendazole-mebendazole; (iii) Albendazole-oxantel pamoate; or (iv) mebendazole. Here we report the efficacy [cure rates (CR) and egg-reduction rates (ERR)], reinfection rates and new infections determined 18 weeks post-treatment. For a total of 405 children complete baseline and follow-up data were available. Similar to the efficacy determined after 3 weeks, 18 weeks after treatment Albendazole-oxantel pamoate showed a significantly higher efficacy against T. trichiura (CR: 54.0 %, 95 % CI: 43.7–64.0; ERR: 98.6 %, 95 % CI: 97.8–99.2) compared to the other treatment arms. Children treated with Albendazole-oxantel pamoate or Albendazole-ivermectin had fewer moderate infections compared to children treated with Albendazole. The reinfection rates 18 weeks post-treatment among all treatment arms were 37.2 % for T. trichiura (95 % CI: 28.3–46.8), 34.6 % for A. lumbricoides (95 % CI: 27.3–42.3) and 25.0 % for hookworms (95 % CI: 15.5–36.6). The moderate reinfection rates with STHs 18 weeks post-treatment support the concept of regular anthelminthic treatment in highly endemic settings. Combination chemotherapy might achieve decreased morbidity in children since in the Albendazole plus oxantel pamoate and Albendazole plus ivermectin treatment arms only few moderate T. trichiura infections remained. Further trials should investigate the long term efficacy of Albendazole-oxantel pamoate (i.e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections. Current Controlled Trials ISRCTN80245406
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efficacy and safety of Albendazole plus ivermectin Albendazole plus mebendazole Albendazole plus oxantel pamoate and mebendazole alone against trichuris trichiura and concomitant soil transmitted helminth infections a four arm randomised controlled t
Lancet Infectious Diseases, 2015Co-Authors: Benjamin Speich, Jan Hattendorf, Isaac I Bogoch, Rainer Alles, Jorg Huwyler, Marco Albonico, Jurg Utzinger, Jennifer KeiserAbstract:Summary Background Existing anthelmintic drugs (eg, Albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. Methods In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6–14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive Albendazole (400 mg) plus ivermectin (200 μg/kg); Albendazole (400 mg) plus mebendazole (500 mg); Albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. Findings We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6–77·4]; egg reduction 99·2%, 98·7–99·6) and Albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0–36·0]; egg reduction 94·5%, 91·7–96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1–13·8]; egg reduction 58·5%, 45·2–70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1–13·8; egg reduction 51·6%, 35·0–65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for Albendazole plus ivermectin, 10 (9·3%) for Albendazole plus mebendazole, 20 (18·2%) for Albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for Albendazole plus ivermectin, 6 (5·6%) for Albendazole plus mebendazole, 12 (10·9%) for Albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. Interpretation Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for Albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of Albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Funding Medicor Foundation and Swiss National Science Foundation.
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Albendazole and mebendazole administered alone or in combination with ivermectin against trichuris trichiura a randomized controlled trial
Clinical Infectious Diseases, 2010Co-Authors: Benjamin Speich, Stefanie Knopp, Khalfan A Mohammed, Simba I Khamis, Alipo Naim Khamis, Jan Hattendorf, Russell J StothardAbstract:Background. Single-dose Albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of Albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of Albendazole (400 mg) plus placebo, Albendazole plus ivermectin (200 mug/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with Albendazole-ivermectin (38%), mebendazole (19%), and Albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by Albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and Albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both Albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN08336605
Marta S Palmeirim - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of co administered ivermectin plus Albendazole for treating soil transmitted helminths a systematic review meta analysis and individual patient data analysis
PLOS Neglected Tropical Diseases, 2018Co-Authors: Vicente Y. Belizario, Benjamin Speich, Stefanie Knopp, Marta S Palmeirim, Eveline Hurlimann, Serene A Joseph, Michel VaillantAbstract:Background The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (Albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus Albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. Methods and findings We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-Albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-Albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-Albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to Albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over Albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-Albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and Albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-Albendazole compared to those treated with Albendazole alone (RR = 1.29, 95% CI = 0.81–2.05). Conclusions Our findings suggest a good tolerability and higher efficacy of ivermectin-Albendazole against T. trichiura compared to the current standard single-dose Albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.
