Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.
Artemisinin partial resistance
Malaria
Pfkelch13 genotype
Plasmodium falciparum
Ring-stage Survival Assay
Senegal
Targeted-amplicon deep sequencing
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
26 May 2023
26 May 2023
Historique:
received:
01
02
2023
accepted:
15
05
2023
medline:
29
5
2023
pubmed:
27
5
2023
entrez:
26
5
2023
Statut:
epublish
Résumé
Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively. The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur.
METHODS
METHODS
Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach.
RESULTS
RESULTS
All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively.
CONCLUSION
CONCLUSIONS
The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.
Identifiants
pubmed: 37237307
doi: 10.1186/s12936-023-04588-1
pii: 10.1186/s12936-023-04588-1
pmc: PMC10223908
doi:
Substances chimiques
Antimalarials
0
artemisinin
9RMU91N5K2
artenimol
6A9O50735X
Artemisinins
0
Protozoan Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
167Subventions
Organisme : Cochin institute
ID : ANR Chrono ANR-19-CE35-0009
Organisme : International Centers of Excellence for Malaria Research (ICEMR), West Africa
ID : U19AI089696
Organisme : Institut Pasteur, Paris, the French Government (Agence Nationale de la Recherche), Laboratoire d'Excellence (LabEx) "French Parasitology Alliance for Health Care"
ID : ANR-11-15 LABX-0024-PARAFRAP
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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