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Peer-reviewedCC BYThe American journal of tropical medicine and hygiene

Geographical Variation in Antimalarial Drug Resistance Marker Prevalence across the Southern African Elimination Eight Region.

32 more authors
26 affiliations
  1. 1Laboratory for Antimalarial Resistance Monitoring and Malaria Operational Research, Centre of Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases, Johannesburg, South Africa.
  2. 2Wits Research Institute for Malaria, University of Witwatersrand, Johannesburg, South Africa.
  3. 3University of Pretoria Institute for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa.
  4. 4EPPIcenter Research Program, Department of Medicine, University of California, San Francisco, California, USA.
  5. 5Malaria Elimination Initiative, Global Health Group, University of California, San Francisco, California, USA.
  6. 6ISGlobal, Barcelona, Spain.
  7. 7SADC Malaria Elimination Eight Secretariat, Windhoek, Namibia.
  8. 8Programa Nacional do Controlo da Malária, Luanda, Angola.
  9. 9Instituto Nacional de Investigação em Saúde, Luanda, Angola.
  10. 10National Malaria Programme, Manzini, Eswatini.
  11. 11Department of Environmental Health Sciences, University of Eswatini, Mbabane, Eswatini.
  12. 12Department of Biochemistry, Microbiology, and Biotechnology, School of Science, University of Namibia, Windhoek, Namibia.
  13. 13Malaria Operational Research Program, Multidisciplinary Research Services, University of Namibia, Windhoek, Namibia.
  14. 14Ministry of Health and Social Services, National Vector-Borne Disease Control Program, Windhoek, Namibia.
  15. 15KwaZulu-Natal Provincial Malaria Control Program, Jozini, South Africa.
  16. 16National Department of Health, Pretoria, South Africa.
  17. 17National Health Research and Training Institute, Ndola, Zambia.
  18. 18National Malaria Elimination Centre, Ministry of Health, Lusaka, Zambia.
  19. 19Centro de Investigação em Saúde de Manhiça, Manhiça, Mozambique.
  20. 20Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.
  21. 21Programa Nacional do Controlo da Malária, Maputo, Mozambique.
  22. 22Sequencing Core Facility, National Institute for Communicable Diseases, Johannesburg, South Africa.
  23. 23Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique.
  24. 24Spanish Consortium for Research in Epidemiology and Public Health, Madrid, Spain.
  25. 25Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
  26. 26Department of Epidemiology & Biostatistics, University of California, San Francisco, California, USA.

Abstract

Global efforts to control and eliminate malaria are threatened by antimalarial drug resistance. The WHO recommends molecular surveillance of resistance markers as a complementary approach to therapeutic efficacy studies. Here, the first regional analysis of antimalarial resistance markers across six southern African countries spanning diverse transmission intensities and geographies is reported. Dried blood spots, collected from rapid diagnostic test-positive individuals in Angola, Eswatini, Namibia, and Zambia in 2023, Mozambique in 2022, and South Africa between 2022 and 2024 using a standardized collection method, were analyzed using a Plasmodium falciparum-targeted amplicon sequencing protocol. The distribution of resistance markers was spatially heterogeneous. Validated markers of artemisinin partial resistance (ART-R) were rare. However, more than 30% of samples from eastern Namibia and Zambia's Western and Central Provinces carried the candidate kelch13 P441L ART-R marker. Other ART-R markers (kelch13 R515K, P553L, P574L, A675V) were detected at a prevalence rate <1.3% in all countries except Mozambique, where these markers were absent. The wild-type multidrug resistance 1 N86 allele, potentially associated with reduced lumefantrine susceptibility, was near fixation (>99%) across all countries, whereas the chloroquine resistance marker K76T, in the chloroquine resistance transporter (crt) was nearly absent in most districts. The sulfadoxine-pyrimethamine resistance dihydropteroate synthase (dhps)-dihydrofolate reductase quintuple mutation was approaching fixation (>95%) in 35% of districts. Northern Angola was a clear outlier, with a lower dhps K540E prevalence (≤20%) but a higher crt K76T prevalence (48% to 56%). This pronounced spatial heterogeneity underscores the need for timely high-resolution local resistance data generation and sharing to safeguard antimalarial drug efficacy and guide malaria control and elimination strategies across the region.

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BibTeX
@article{raman2026geographical,
  title = {{Geographical Variation in Antimalarial Drug Resistance Marker Prevalence across the Southern African Elimination Eight Region.}},
  author = {Jaishree Raman and Andrés Aranda-Díaz and Maxwell Mabona and Mukosha Chisenga and Maria Florinda João and Domingos Jandondo and Pedro Rafael Dimbu and Nomcebo Nhlengethwa and Sabelo V Dlamini and Lydia Eloff and Stark Katokele and Davis R Mumbengegwi and Qedusizi Nyawo and Mbavhalelo Shandukani and Sydney Mwanza and Moonga Hawela and Simone Boene and Arlindo Chidimatembue and Bernardete Rafael and Eduard Rovira-Vallbona and Brighton Mangena and Sonja B Lauterbach and Takalani I Makhanthisa and Hazel Gwarinda and Blaženka D Letinić and Faith De Amaral and Isobel Routledge and Beatriz Arregui-Gallego and Mishalan Moodley and Jonathan Featherston and Power B Tshikae and Arshad Ismail and Jose Franco Martins and Quinton Dlamini and Baltazar Candrinho and Petrina Uusiku and Ednah Baloyi and Busiku Hamainza and Alfredo Mayor and Bryan Greenhouse and Amy Wesolowski and Chadwick Sikaala and John Chimumbwa and Jennifer L Smith},
  journal = {The American journal of tropical medicine and hygiene},
  year = {2026},
  month = oct,
  doi = {10.4269/ajtmh.26-0299},
  url = {https://europepmc.org/article/MED/42838037},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Geographical Variation in Antimalarial Drug Resistance Marker Prevalence across the Southern African Elimination Eight Region.
AU  - Jaishree Raman
AU  - Andrés Aranda-Díaz
AU  - Maxwell Mabona
AU  - Mukosha Chisenga
AU  - Maria Florinda João
AU  - Domingos Jandondo
AU  - Pedro Rafael Dimbu
AU  - Nomcebo Nhlengethwa
AU  - Sabelo V Dlamini
AU  - Lydia Eloff
AU  - Stark Katokele
AU  - Davis R Mumbengegwi
AU  - Qedusizi Nyawo
AU  - Mbavhalelo Shandukani
AU  - Sydney Mwanza
AU  - Moonga Hawela
AU  - Simone Boene
AU  - Arlindo Chidimatembue
AU  - Bernardete Rafael
AU  - Eduard Rovira-Vallbona
AU  - Brighton Mangena
AU  - Sonja B Lauterbach
AU  - Takalani I Makhanthisa
AU  - Hazel Gwarinda
AU  - Blaženka D Letinić
AU  - Faith De Amaral
AU  - Isobel Routledge
AU  - Beatriz Arregui-Gallego
AU  - Mishalan Moodley
AU  - Jonathan Featherston
AU  - Power B Tshikae
AU  - Arshad Ismail
AU  - Jose Franco Martins
AU  - Quinton Dlamini
AU  - Baltazar Candrinho
AU  - Petrina Uusiku
AU  - Ednah Baloyi
AU  - Busiku Hamainza
AU  - Alfredo Mayor
AU  - Bryan Greenhouse
AU  - Amy Wesolowski
AU  - Chadwick Sikaala
AU  - John Chimumbwa
AU  - Jennifer L Smith
PY  - 2026
DA  - 2026/10/06
JO  - The American journal of tropical medicine and hygiene
DO  - 10.4269/ajtmh.26-0299
UR  - https://europepmc.org/article/MED/42838037
AB  - Global efforts to control and eliminate malaria are threatened by antimalarial drug resistance. The WHO recommends molecular surveillance of resistance markers as a complementary approach to therapeutic efficacy studies. Here, the first regional analysis of antimalarial resistance markers across six southern African countries spanning diverse transmission intensities and geographies is reported. Dried blood spots, collected from rapid diagnostic test-positive individuals in Angola, Eswatini, Namibia, and Zambia in 2023, Mozambique in 2022, and South Africa between 2022 and 2024 using a standardized collection method, were analyzed using a Plasmodium falciparum-targeted amplicon sequencing protocol. The distribution of resistance markers was spatially heterogeneous. Validated markers of artemisinin partial resistance (ART-R) were rare. However, more than 30% of samples from eastern Namibia and Zambia's Western and Central Provinces carried the candidate kelch13 P441L ART-R marker. Other ART-R markers (kelch13 R515K, P553L, P574L, A675V) were detected at a prevalence rate <1.3% in all countries except Mozambique, where these markers were absent. The wild-type multidrug resistance 1 N86 allele, potentially associated with reduced lumefantrine susceptibility, was near fixation (>99%) across all countries, whereas the chloroquine resistance marker K76T, in the chloroquine resistance transporter (crt) was nearly absent in most districts. The sulfadoxine-pyrimethamine resistance dihydropteroate synthase (dhps)-dihydrofolate reductase quintuple mutation was approaching fixation (>95%) in 35% of districts. Northern Angola was a clear outlier, with a lower dhps K540E prevalence (≤20%) but a higher crt K76T prevalence (48% to 56%). This pronounced spatial heterogeneity underscores the need for timely high-resolution local resistance data generation and sharing to safeguard antimalarial drug efficacy and guide malaria control and elimination strategies across the region.
SN  - 0002-9637
SN  - 1476-1645
ER  -