Assessment of anthelmintic efficacy of mebendazole in school children in six countries where soil-transmitted helminths are endemic

Abstract

Background: 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.

Trial registration: ClinicalTrials.gov NCT01087099 NCT01379326.

Figure 1. Study participation, occurrence of soil-transmitted helminth infections, and stool sample submission compliance during the mebendazole-intervention.

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.

Figure 2. Efficacy of a single dose of mebendazole against soil-transmitted helminths.

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 Ascaris lumbricoides, Trichuris trichiura, and hookworm infections, respectively.

Figure 3. Comparison of efficacy between a single dose of albendazole and mebendazole against Ascaris lumbricoides infections.

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 A. lumbricoides infection.

Figure 4. Comparison of efficacy between a single dose of albendazole and mebendazole against Trichuris trichiura infection.

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 T. trichiura infection.

Figure 5. Comparison of efficacy between a single dose of albendazole and mebendazole against hookworm infection.

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.

Figure 6. The efficacy albendazole and mebendazole, as a function of infection intensity at the pre-treatment survey.

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 Ascaris lumbricoides, and Trichuris trichiura.