부산대학교 도서관

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. Author Summary: Soil-transmitted helminths (STHs; roundworms, whipworms, and hookworms) infect millions of children in sub-tropical and tropical countries, resulting in malnutrition, growth stunting, intellectual retardation, and cognitive deficits. To fight against STH, large-scale deworming programs are implemented in which anthelmintic drugs (either albendazole (ALB) or mebendazole (MEB)) are administered. Currently, these large-scale programs are intensifying, highlighting the need to closely monitor the efficacy of anthelmintic drugs to detect changes in drug efficacy that may arise through the evolution of anthelmintic drug resistance in the parasites. We have previously defined the minimum expected efficacy of ALB based on the fecal egg count reduction (FECR) rate, but these reference values are lacking for MEB. Therefore, we therefore evaluated the FECR rate of MEB against STHs in six STH endemic countries. In addition, we compared the results of the FECR rate for MEB with those we obtained previously for ALB. The results confirm that MEB treatment was highly efficacious against roundworms, and to a lesser extend against hookworms, but not against whipworms. Compared to ALB, MEB is less efficacious against hookworm, but equally efficacious against roundworms and whipworms. Based on this study we propose the minimum expected FECR rate for MEB-dependent large-scale deworming programs. [ABSTRACT FROM AUTHOR]