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https://www.arca.fiocruz.br/handle/icict/53146
INDIVIDUAL RESPONSES TO A SINGLE ORAL DOSE OF ALBENDAZOLE INDICATE REDUCED EFFICACY AGAINST SOIL-TRANSMITTED HELMINTHS IN AN AREA WITH HIGH DRUG PRESSURE
Author
Affilliation
Department of Pathobiology and Population Sciences. Royal Veterinary College. Hatfield, United Kingdom/London Centre for Neglected Tropical Disease Research. Imperial College London. London, United Kingdom.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Center for Tropical Diseases. Sacro Cuore Don Calabria Hospital. Negrar, Italy/ Department of Life Sciences and Systems Biology. University of Turin. Turin, Italy.
Laboratory Division. Public Health Laboratory-Ivo de Carneri. Chake Chake, United Republic of Tanzania.
Jimma University Institute of Health. Jimma University. Jimma, Ethiopia.
Jimma University Institute of Health. Jimma University. Jimma, Ethiopia.
Department of Medical Parasitology and Infection Biology. Swiss Tropical and Public Health Institute. Basel, Switzerland/University of Basel. Basel, Switzerland.
Laboratory of Molecular and Cellular Immunology. Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Nursing school. Federal University of Minas Gerais. Belo Horiozonte, MG, Brazil.
Department of Control of Neglected Tropical Diseases. World Health Organization. Geneva, Switzerland.
Jimma University Institute of Health. Jimma University. Jimma, Ethiopia.
Laboratory of Molecular and Cellular Immunology. Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Laboratory of Molecular and Cellular Immunology. Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Lao Tropical and Public Health Institute. Ministry of Health. Vientiane, Lao People's Democratic Republic.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Center for Tropical Diseases. Sacro Cuore Don Calabria Hospital. Negrar, Italy/ Department of Life Sciences and Systems Biology. University of Turin. Turin, Italy.
Laboratory Division. Public Health Laboratory-Ivo de Carneri. Chake Chake, United Republic of Tanzania.
Jimma University Institute of Health. Jimma University. Jimma, Ethiopia.
Jimma University Institute of Health. Jimma University. Jimma, Ethiopia.
Department of Medical Parasitology and Infection Biology. Swiss Tropical and Public Health Institute. Basel, Switzerland/University of Basel. Basel, Switzerland.
Laboratory of Molecular and Cellular Immunology. Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Nursing school. Federal University of Minas Gerais. Belo Horiozonte, MG, Brazil.
Department of Control of Neglected Tropical Diseases. World Health Organization. Geneva, Switzerland.
Jimma University Institute of Health. Jimma University. Jimma, Ethiopia.
Laboratory of Molecular and Cellular Immunology. Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Laboratory of Molecular and Cellular Immunology. Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Lao Tropical and Public Health Institute. Ministry of Health. Vientiane, Lao People's Democratic Republic.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Department of Virology. Parasitology and Immunology. Ghent University. Merelbeke, Belgium.
Abstract
Background: Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment.
Methodology/principal findings: We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People's Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites.
Conclusions/significance: We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB.
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