Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods.


Journal

PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488

Informations de publication

Date de publication:
08 2019
Historique:
received: 04 02 2019
accepted: 16 05 2019
entrez: 2 8 2019
pubmed: 2 8 2019
medline: 14 1 2020
Statut: epublish

Résumé

Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance. ClinicalTrials.gov NCT03465488.

Sections du résumé

BACKGROUND
Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz.
METHODS
An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy.
PRINCIPAL FINDINGS AND CONCLUSIONS
The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03465488.

Identifiants

pubmed: 31369562
doi: 10.1371/journal.pntd.0007471
pii: PNTD-D-19-00219
pmc: PMC6675043
doi:

Substances chimiques

Anthelmintics 0
Soil 0
Tubulin 0
Albendazole F4216019LN

Banques de données

ClinicalTrials.gov
['NCT03465488']

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0007471

Subventions

Organisme : World Health Organization
ID : 001
Pays : International

Déclaration de conflit d'intérêts

The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, their affiliations did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

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Auteurs

Johnny Vlaminck (J)

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

Piet Cools (P)

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

Marco Albonico (M)

Center for Tropical Diseases, Sacro Cuore Don Calabria Hospital, Negrar, Italy.
Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.

Shaali Ame (S)

Laboratory Division, Public Health Laboratory-Ivo de Carneri, Chake Chake, United Republic of Tanzania.

Mio Ayana (M)

Jimma University Institute of Health, Jimma University, Jimma, Ethiopia.

Giuseppe Cringoli (G)

Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy.

Daniel Dana (D)

Jimma University Institute of Health, Jimma University, Jimma, Ethiopia.

Jennifer Keiser (J)

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.

Maria P Maurelli (MP)

Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy.

Leonardo F Matoso (LF)

Laboratory of Molecular and Cellular Immunology, Research Center René Rachou-FIOCRUZ, Belo Horizonte, Brazil.
Nursing school, Federal University of Minas Gerais, Brazil.

Antonio Montresor (A)

Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland.

Zeleke Mekonnen (Z)

Jimma University Institute of Health, Jimma University, Jimma, Ethiopia.

Greg Mirams (G)

Techion Group Ltd, Dunedin, New Zealand.

Rodrigo Corrêa-Oliveira (R)

Laboratory of Molecular and Cellular Immunology, Research Center René Rachou-FIOCRUZ, Belo Horizonte, Brazil.

Simone A Pinto (SA)

Laboratory of Molecular and Cellular Immunology, Research Center René Rachou-FIOCRUZ, Belo Horizonte, Brazil.

Laura Rinaldi (L)

Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy.

Somphou Sayasone (S)

Lao Tropical and Public Health Institute, Ministry of Health, Vientiane, Lao People's Democratic Republic.

Eurion Thomas (E)

Techion Group Ltd, Aberystwyth, United Kingdom.

Jozef Vercruysse (J)

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

Jaco J Verweij (JJ)

Laboratory for Medical Microbiology and Immunology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.

Bruno Levecke (B)

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

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Classifications MeSH