Molecular markers of antimalarial drug resistance in pfk13, pfmdr1, pfdhfr, and pfdhps genes of Plasmodium falciparum in a rural municipality in Cubal, Benguela Province, Angola (2022-2023)
Mediavilla, Alejandro (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
García, Xana (Vall d'Hebron Institut de Recerca (VHIR))
Martínez-Vallejo, Patricia (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Molina-de la Fuente, Irene (Instituto de Salud Carlos III)
Febrer-Sendra, Begoña (Universidad de Salamanca)
Silgado, Aroa (Hospital Universitari Vall d'Hebron)
Kheta, Francisco (Programa Nacional de Controlo da Malária (Angola))
Rubio Maturana, Carles (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Martins, José F. (Programa Nacional de Controlo da Malária (Angola))
Nindia, Arlette (Hospital Nossa Senhora da Paz (Angola))
Martínez-Campreciós, Joan (Hospital Universitari Vall d'Hebron)
Aznar, Maria Luisa (Hospital Universitari Vall d'Hebron)
Oliveira-Souto, Inés (Hospital Universitari Vall d'Hebron)
Molina Romero, Israel (Hospital Universitari Vall d'Hebron)
Sulleiro Igual, Elena (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Berzosa, Pedro (Instituto de Salud Carlos III)

Data:	2026
Resum:	Background: Malaria remains a major cause of morbidity and mortality in Angola, where Plasmodium falciparum accounts for most infections. The widespread use of artemether-lumefantrine (AL) as first-line treatment and sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy (IPTp) exerts selective pressure on local parasite populations. Molecular surveillance of drug resistance markers is essential to monitor susceptibility and anticipate changes that may influence treatment and prevention strategies. This study analyzed pfk13, pfmdr1, pfdhfr, and pfdhps polymorphisms in P. falciparum isolates from Cubal, Benguela province, to assess parasite genetic evolution under AL and SP pressure. Methods: A cross-sectional study was conducted between 2022 and 2023 at Hospital Nossa Senhora da Paz (Cubal). A total of 139 real-time PCR-confirmed P. falciparum infections were included. Dried blood spot samples underwent sequencing of the genes involved in resistance. Mutation and haplotype frequencies associated with antimalarial resistance were determined. Results: Among 120 pfk13 sequences, mutations were detected in 12 isolates (10%), including five nonsynonymous variants, but none corresponded to validated or candidate markers of artemisinin resistance. In pfmdr1 (100 sequences), Y184F was the most prevalent mutation (43%), N86Y was rare (1%), and D1246Y was not detected. Seven additional pfmdr1 variants were identified. Of the 101 isolates correctly sequenced for pfdhfr/pfdhps, 77. 2% carried the triple pfdhfr N51I/C59R/S108N mutation. In pfdhps, A437G was nearly fixed (98%), K540E showed moderate prevalence (23. 8%), and A581G was absent. The most common pfdhps haplotypes were ISGKAA (64. 4%) and ISGEAA (22. 8%). Combined pfdhfr/pfdhps profiles classified 58. 4% of isolates as "partially resistant" (IRNG) and 17. 8% as "fully resistant" (IRNGE), with no "super-resistant" haplotypes. Additional single mutations not associated with SP resistance were also detected. Conclusions: This study provides an updated molecular profile of antimalarial resistance in a rural area of Angola. No validated or candidate pfk13 markers of artemisinin resistance were identified. However, the predominance of pfmdr1 haplotypes linked to reduced lumefantrine susceptibility raises concerns regarding AL efficacy. Although SP remains suitable for IPTp, the presence of the "fully resistant" haplotype (IRNGE) of pfdhfr/pfdhps highlight potential risks to long-term effectiveness. These findings reinforce the need for integrated molecular surveillance and periodic therapeutic efficacy studies to guide malaria control policies in rural Angola.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Plasmodium falciparum ; Antimalarial resistance ; pfk13 ; pfmdr1 ; pfdhfr/pfdhps ; Artemether-lumefantrine ; Sulfadoxine-pyrimethamine ; Treatment ; Chemoprevention ; Angola.
Publicat a:	Malaria journal, March 2026, ISSN 1475-2875

DOI: 10.1186/s12936-026-05856-6

Postprint 32 p, 1.1 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats