Efficacy, safety and acceptability of a new chewable formulation versus the solid tablet of mebendazole against hookworm infections in children: An open-label, randomized controlled trial

Marta S Palmeirim, Felix Bosch, Shaali M Ame, Said M Ali, Jan Hattendorf, Jennifer Keiser, Marta S Palmeirim, Felix Bosch, Shaali M Ame, Said M Ali, Jan Hattendorf, Jennifer Keiser

Abstract

Background: Soil-transmitted helminths (STHs) infect almost 1·5 billion people worldwide. The control of STH infections is based on preventive chemotherapy using either albendazole or mebendazole. Before being widely used, a sufficient body of evidence on efficacy, safety and acceptability is warranted for the new chewable child-friendly formulation of mebendazole that was recently developed.

Methods: We conducted a randomised controlled superiority trial in four primary schools and kindergartens on Pemba Island, Tanzania. We considered eligible children aged 3 to 12 years with a hookworm infection intensity of at least 50 eggs per gram (EPG) of stool and no chronic diseases. Participants were allocated to treatment arms (ratio 1:1) using a computer generated random sequence. Our primary outcome was geometric mean based egg reduction rate (ERR) against hookworm assessed 14-21 days post-treatment. This trial complete and is registered with ClinicalTrials.gov, number NCT03995680 (June 24, 2019).

Findings: 397 children were eligible and randomised into the solid (198) or chewable (199) tablet arms, of whom 393 were analysed. We found no significant difference between both formulations in terms of ERR (solid 70·8% versus chewable 68·5%, difference in ERRgeometric mean 2·3%-points, 95% CI -7·8 to 12·6, p = 0.65) and CR (11·2 versus 12·7%, 95% CI -4·9 to 7·9, p = 0.65) against hookworm infections. Adverse events were mild in both treatment arms.

Interpretations: Though we could not demonstrate superiority in terms of efficacy of the new formulation, the difference between arms was small and therefore, the chewable formulation could be safely used as an alternative to swallowable tablets, in particular in young children who may have swallowing difficulties. This might help increase compliance and, consequently, enhance the effect of preventive chemotherapy.

Conflict of interest statement

We declare no competing interests.

© 2020 The Author(s).

Figures

Fig. 1
Fig. 1
Trial profile. *hookworm-negative participant who was wrongly randomised and treated.

References

    1. WHO. Soil-transmitted helminth infections. 2020. .
    1. GBD 2016 DALYs and HALE Collaborators Global, regional, and national disability-adjusted life years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the global burden of disease Study 2016. Lancet. 2017;390:1260–1344.
    1. Bethony J., Brooker S., Albonico M. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet. 2006;367(9521):1521–1532.
    1. Hotez P.J., Brooker S., Bethony J.M., Bottazzi M.E., Loukas A., Xiao S. Hookworm infection. Engl J Med. 2004;351(8):799–807.
    1. Sarkar R., Rose A., Mohan V.R. Study design and baseline results of an open-label cluster randomized community-intervention trial to assess the effectiveness of a modified mass deworming program in reducing hookworm infection in a tribal population in southern India. Contemp Clin Trials Commun. 2017;5:49–55.
    1. Kattula D., Sarkar R., Rao Ajjampur S.S. Prevalence & risk factors for soil transmitted helminth infection among school children in South India. Indian J Med Res. 2014;139(1):76–82.
    1. Hall A., Hewitt G., Tuffrey V., De Silva N. A review and meta-analysis of the impact of intestinal worms on child growth and nutrition. Matern Child Nutr. 2008;4(s1):118–236.
    1. Bethony J., Brooker S., Albonico M. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet. 2006;367(9521):1521–1532.
    1. WHO . World Health Organization; Geneva: 2017. Guideline: preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups.
    1. WHO . World Health Organization; Geneva: 2019. Mebendazole 500mg chewable tablets - WHO-PQ recommended summary of product characteristics.
    1. Silber S.A., Diro E., Workneh N. Efficacy and safety of a single-dose mebendazole 500mg chewable, rapidly-disintegrating tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment in pediatric patients: a double-blind, randomized, placebo-controlled, phase 3 study. Am J Trop Med Hyg. 2017;97(6):1851–1856.
    1. Friedman A.J., Ali S.M., Albonico M. Safety of a new chewable formulation of mebendazole for preventive chemotherapy interventions to treat young children in countries with moderate-to-high prevalence of soil transmitted helminth infections. J Trop Med. 2012;2012
    1. Corrigan O.I., Timoney R.F. Some aspects of the influence of formulation on the bioavailability of drugs from solid dosage forms. Ir J Med Sci. 1974;143(4):197–207.
    1. Moser W., Schindler C., Keiser J. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis. BMJ (Clin Res ed) 2017;358:j4307.
    1. WHO . World Health Organization; Geneva: 2012. Eliminating soil-transmitted helminthiasis as a public health problem in children: progress report 2001–2010 and strategic plan 2011–2020.
    1. Vitamin Angels. Global Impact. 2016
    1. WHO . World Health Organization; Geneva: 2007. Action against worms.
    1. WHO . World Health Organization; Geneva: 2013. Assessing the efficacy of anthelminthic drugs against schistosomiasis and soil-transmitted helminths.
    1. Speich B., Ame S.M., Ali S.M. Oxantel pamoate-albendazole for Trichuris trichiura infection. Engl J Med. 2014;370(7):610–620.
    1. Levecke B., Montresor A., Albonico M. Assessment of anthelmintic efficacy of mebendazole in school children in six countries where soil-transmitted helminths are endemic. PLoS Negl Trop Dis. 2014;8(10):e3204.
    1. Palmeirim M.S., Ame S.M., Ali S.M., Hattendorf J., Keiser J. Efficacy and safety of a single dose versus a multiple dose regimen of mebendazole against hookworm infections in children: a randomised, double-blind trial. EClinicalMedicine. 2018;1:7–13.
    1. Moser W., Schindler C., Keiser J. Drug combinations against soil-transmitted helminth infections. Adv Parasitol. 2019;103:91–115.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe