Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 27 06 2020
accepted: 21 09 2020
entrez: 19 10 2020
pubmed: 20 10 2020
medline: 15 12 2020
Statut: epublish

Résumé

Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance. We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique. None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05). This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.

Sections du résumé

BACKGROUND
Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance.
METHODS
We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique.
RESULTS
None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05).
CONCLUSIONS
This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.

Identifiants

pubmed: 33075062
doi: 10.1371/journal.pone.0240174
pii: PONE-D-20-19842
pmc: PMC7571678
doi:

Substances chimiques

Antimalarials 0
Artemisinins 0
Drug Combinations 0
Protozoan Proteins 0
Quinolines 0
artenimol 6A9O50735X
piperaquine A0HV2Q956Y

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0240174

Subventions

Organisme : World Health Organization
ID : 001
Pays : International

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Himanshu Gupta (H)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.

Beatriz Galatas (B)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Arlindo Chidimatembue (A)

Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Silvie Huijben (S)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.

Pau Cisteró (P)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.

Gloria Matambisso (G)

Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Lidia Nhamussua (L)

Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Wilson Simone (W)

Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Quique Bassat (Q)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.
ICREA, Pg. Lluís Companys, Barcelona, Spain.
Spanish Consortium for Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu (University of Barcelona), Barcelona, Spain.

Didier Ménard (D)

Institut Pasteur, Paris, France.
INSERM U1201, Paris, France.
CNRS ERL9195, Paris, France.

Pascal Ringwald (P)

World Health Organization (WHO), Global Malaria Programme, Geneva, Switzerland.

N Regina Rabinovich (NR)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Pedro L Alonso (PL)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Francisco Saúte (F)

Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.

Pedro Aide (P)

Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.
National Institute of Health, Ministry of Health, Manhica, Mozambique.

Alfredo Mayor (A)

ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça, Manhica, Mozambique.
ICREA, Pg. Lluís Companys, Barcelona, Spain.

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Classifications MeSH