| Title: |
Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea ; Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea: Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea |
| Authors: |
Mihreteab, Selam; Platon, Lucien; Berhane, Araia; Stokes, Barbara; Warsame, Marian; Campagne, Pascal; Criscuolo, Alexis; Ma, Laurence; Petiot, Nathalie; Doderer-Lang, Cécile; Legrand, Eric; Ward, Kurt; Zehaie Kassahun, Assefash; Ringwald, Pascal; Fidock, David; Ménard, Didier |
| Contributors: |
Malaria Control Program Asmara, Eritrea; Génétique du paludisme et résistance - Malaria Genetics and Resistance; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); ED 515 - Complexité du vivant; Sorbonne Université (SU); Ministry of Health, Communicable Diseases Control Division Asmara, Eritrea; Columbia University Irving Medical Center (CUIMC); Göteborgs Universitet = University of Gothenburg (GU); Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Biomics (plateforme technologique); Biologie de Plasmodium et Vaccins - Malaria Parasite Biology and Vaccines; Dynamique des interactions hôte pathogène (DIHP); Université de Strasbourg (UNISTRA); World Health Organization Country Office for Eritrea Asmara, Erythrée (OMS / WHO); Organisation Mondiale de la Santé - World Health Organization, Regional Office for Africa Brazzaville, Republic of the Congo (OMS / WHO AFRO); Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO)-Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); Global malaria program Genève, Suisse; Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg); Hôpitaux Universitaires de Strasbourg (HUS); Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry numbers, ACTRN12618001223224. opens in new tab, ACTRN12618000353291. opens in new tab, and ACTRN12619000859189.; ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011) |
| Source: |
ISSN: 0028-4793. |
| Publisher Information: |
CCSD; Massachusetts Medical Society |
| Publication Year: |
2023 |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; BackgroundAlthough the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin in Plasmodium falciparum on the continent is troubling, given the lack of alternative treatments.MethodsIn this study, we used data from drug-efficacy studies conducted between 2016 and 2019 that evaluated 3-day courses of artemisinin-based combination therapy (artesunate–amodiaquine or artemether–lumefantrine) for uncomplicated malaria in Eritrea to estimate the percentage of patients with day-3 positivity (i.e., persistent P. falciparum parasitemia 3 days after the initiation of therapy). We also assayed parasites for mutations in Pfkelch13 as predictive markers of partial resistance to artemisinin and screened for deletions in hrp2 and hrp3 that result in variable performance of histidine rich protein 2 (HRP2)–based rapid diagnostic tests for malaria.ResultsWe noted an increase in the percentage of patients with day-3 positivity from 0.4% (1 of 273) in 2016 to 1.9% (4 of 209) in 2017 and 4.2% (15 of 359) in 2019. An increase was also noted in the prevalence of the Pfkelch13 R622I mutation, which was detected in 109 of 818 isolates before treatment, from 8.6% (24 of 278) in 2016 to 21.0% (69 of 329) in 2019. The odds of day-3 positivity increased by a factor of 6.2 (95% confidence interval, 2.5 to 15.5) among the patients with Pfkelch13 622I variant parasites. Partial resistance to artemisinin, as defined by the World Health Organization, was observed in Eritrea. More than 5% of the patients younger than 15 years of age with day-3 positivity also had parasites that carried Pfkelch13 R622I. In vitro, the R622I mutation conferred a low level of resistance to artemisinin when edited into NF54 and Dd2 parasite lines. Deletions in both hrp2 and hrp3 were identified in 16.9% of the parasites that carried the Pfkelch13 R622I mutation, which made them potentially undetectable by HRP2-based rapid diagnostic ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://hal.science/hal-04738651v1; info:eu-repo/semantics/altIdentifier/pmid/37754284; PUBMED: 37754284; PUBMEDCENTRAL: PMC10539021 |
| DOI: |
10.1056/NEJMoa2210956 |
| Availability: |
https://hal.science/hal-04223624; https://hal.science/hal-04223624v1/document; https://hal.science/hal-04223624v1/file/nejmoa2210956.pdf; https://doi.org/10.1056/NEJMoa2210956 |
| Rights: |
https://hal.science/licences/copyright/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D0DC0492 |
| Database: |
BASE |