Assessment of Anthelmintic Efficacy of Mebendazole in School Children in Six Countries Where Soil-Transmitted Helminths Are Endemic

Submitted by Nuzia Santos ([email protected]) on 2015-03-23T13:11:01Z No. of bitstreams: 1 2014_162.pdf: 1256054 bytes, checksum: c9c4ed7e49598b8545d512d7ac49c7fe (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-23T13:11:12Z (GMT) No. of bitstreams: 1 2014_162.pdf: 1256054 bytes, checksum: c9c4ed7e49598b8545d512d7ac49c7fe (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-23T13:21:51Z (GMT) No. of bitstreams: 1 2014_162.pdf: 1256054 bytes, checksum: c9c4ed7e49598b8545d512d7ac49c7fe (MD5)Made available in DSpace on 2015-03-23T13:21:51Z (GMT). No. of bitstreams: 1 2014_162.pdf: 1256054 bytes, checksum: c9c4ed7e49598b8545d512d7ac49c7fe (MD5) Previous issue date: 2014Ghent University. Department of Virology, Parasitology and Immunology. Merelbeke, BelgiumWorld Health Organization. Department of Control of Neglected Tropical Diseases. Geneva, SwitzerlandFondazione Ivo de Carneri. Milan, ItalyPublic Health Laboratory-Ivo de Carneri, Chake Chake, United Republic of TanzaniaUniversity of Nottingham. School of Life Sciences. Nottingham, United KingdomGeorge Washington University Medical Center. Microbiology, Immunology, and Tropical Medicine. Washington, D.C., United States of AmericaUniversity of Yaounde. Centre for Schistosomiasis and Parasitology. Yaounde, CameroonWorld Health Organization. Department of Control of Neglected Tropical Diseases. Geneva, SwitzerlandPasteur Institute. Clinical Laboratory. Phnom Penh, CambodiaCommonwealth Scientific and Industrial Research Organisation. Division of Animal, Food and Health Sciences. St. Lucia, AustraliaUniversidad Nacional de Salta. Instituto de Investigaciones en Enfermedades Tropicales. ArgentinaUniversity of Queensland. Queensland Institute for Medical Research. Brisbane, AustraliaJimma University. Department of Medical Laboratory Sciences and Pathology. Jimma, EthiopiaFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Belo Horizonte, MG, BrazilPasteur Institute. Clinical Laboratory. Phnom Penh, CambodiaUniversity of Yaounde. Centre for Schistosomiasis and Parasitology. Yaounde, CameroonNational Institute of Malariology, Parasitology and Entomology. Department of Parasitology. Ha Noi, VietnamNational Institute of Malariology, Parasitology and Entomology. Department of Parasitology. Ha Noi, VietnamJimma University. Department of Medical Laboratory Sciences and Pathology. Jimma, EthiopiaGhent University. Department of Virology, Parasitology and Immunology. Merelbeke, BelgiumBACKGROUND: Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained for similarly conducted trials of a single oral dose of albendazole (ALB; 400 mg). METHODOLOGY: The efficacy of MEB, as assessed by FECR, was determined in six trials involving 5,830 school children in Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam. The efficacy of MEB was compared to that of ALB as previously assessed in 8,841 school children in India and all the above-mentioned study sites, using identical methodologies. PRINCIPAL FINDINGS: The estimated FECR rate [95% confidence interval] of MEB was highest for A. lumbricoides (97.6% [95.8; 99.5]), followed by hookworm (79.6% [71.0; 88.3]). For T. trichiura, the estimated FECR rate was 63.1% [51.6; 74.6]. Compared to MEB, ALB was significantly more efficacious against hookworm (96.2% [91.1; 100], p<0.001) and only marginally, although significantly, better against A. lumbricoides infections (99.9% [99.0; 100], p = 0.012), but equally efficacious for T. trichiura infections (64.5% [44.4; 84.7], p = 0.906). CONCLUSIONS/SIGNIFICANCE: A minimum FECR rate of 95% for A. lumbricoides, 70% for hookworm, and 50% for T. trichiura is expected in MEB-dependent PC programs. Lower FECR results may indicate the development of potential drug resistance

The efficacy albendazole and mebendazole, as a function of infection intensity at the pre-treatment survey.

<p>The estimated efficacy measured by means of fecal egg reduction (FECR) rate (straight line) and 95% confidence intervals (dashed line) of a single oral dose of 400 mg ALB (black) and a single dose of 500 mg MEB (red) as a function of infection intensity at the pre-treatment survey (means of FEC) for <i>Ascaris lumbricoides</i>, and <i>Trichuris trichiura.</i></p

Study participation, occurrence of soil-transmitted helminth infections, and stool sample submission compliance during the mebendazole-intervention.

<p>These surveys were conducted in six soil-transmitted helminth-endemic countries (i.e. Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam) between December 2011 and April 2012. Subjects who were not able to provide a stool sample for the follow-up, or who were experiencing a severe intercurrent medical condition or had diarrhea at the time of the first sampling, were excluded from the trial.</p

Comparison of efficacy between a single dose of albendazole and mebendazole against <i>Trichuris trichiura</i> infection.

<p>Forest plot comparing the anthelmintic drug efficacy measured by means of fecal egg reduction (FECR) rate of a single oral dose of 400 mg albendazole (ALB) and a single oral dose of 500 mg mebendazole (MEB) against <i>T. trichiura</i> infection.</p

Number of infected subjects and characteristics of the study across seven albendazole trials.

<p>Number of infected subjects (N), sex ratio (number of female subjects/number of male subjects), mean age, mean FEC, and intensity of infection across seven albendazole trials for <i>Ascaris lumbricoides</i>, <i>Trichuris trichiura</i>, and hookworm infection separately.</p><p>Number of infected subjects and characteristics of the study across seven albendazole trials.</p

Efficacy of a single dose of mebendazole against soil-transmitted helminths.

<p>Three forest plots summarizing the anthelmintic drug efficacy measured by means of fecal egg reduction (FECR) rate of a single oral dose of 500 mg mebendazole against <i>Ascaris lumbricoides</i>, <i>Trichuris trichiura</i>, and hookworm infections, respectively.</p

Number of infected subjects and characteristics of the study across six mebendazole trials.

<p>Number of infected subjects (N), sex ratio (number of female subjects/number of male subjects), mean age, mean FEC, and intensity of infection across six mebendazole trials for <i>Ascaris lumbricoides</i>, <i>Trichuris trichiura</i>, and hookworm infection separately.</p><p>Number of infected subjects and characteristics of the study across six mebendazole trials.</p

Comparison of efficacy between a single dose of albendazole and mebendazole against hookworm infection.

<p>Forest plot comparing the anthelmintic drug efficacy measured by means of fecal egg reduction (FECR) rate of a single oral dose of 400 mg albendazole (ALB) and a single oral dose of 500 mg mebendazole (MEB) against hookworm infections.</p