Temporal genomic analysis of Plasmodium falciparum reveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia
Fola, A. A.; Kobayashi, T.; Shields, T.; Hamapumbu, H.; Musonda, M.; Katowa, B.; Matoba, J.; Stevenson, J. C.; Norris, D. E.; Thuma, P. E.; Wesolowski, A.; Moss, W. J.; Juliano, J. J.; Bailey, J. A.
Show abstract
The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Identification of novel genetic variants in the malaria vaccine candidate PfRh5: structure-guided insights into potential function 96%
- Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering 96%
- Disparate co-evolution and prevalence of sulfadoxine and pyrimethamine resistance alleles and haplotypes at dhfr and dhps genes across Africa 95%
Similar papers in this journal
- Emergence and Rising Prevalence of Artemisinin Partial Resistance Marker Kelch13 P441L in a Low Malaria Transmission Setting in Southern Zambia 97%
- Artemisinin Partial Resistance Mutations in Zanzibar and Tanzania Suggest Regional Spread and African Origins, 2023 95%
- Sensitive, highly multiplexed sequencing of microhaplotypes from the Plasmodium falciparum heterozygome 94%
Similar papers in this journal
- Genomic Surveillance Reveals Clusters of Plasmodium falciparum Antimalarial Resistance Markers in Eswatini, a Low-Transmission Setting 95%
- Varying Malaria Rapid Diagnostic Test Accuracy by Regional Transmission Level and Demographics in Tanzania 94%
- Analytical sensitivity analysis and clinical impact modeling of Rapigen rapid diagnostics tests for malaria 92%
Similar papers in this journal
- Analysis of nucleic acids extracted from rapid diagnostic tests reveals a significant proportion of false positive test results associated with recent malaria treatment 95%
- Estimating the potential impact of surveillance test-and-treat posts to reduce malaria in border regions in sub-Saharan Africa: a modelling study 94%
- Estimating malaria antigen dynamics and the time to negativity of next-generation malaria rapid diagnostic tests 93%
Similar papers in this journal
- Characterisation of populations at risk of sub-optimal dosing of artemisinin-based combination therapy in Africa 95%
- Impact of seasonal malaria chemoprevention timing on clinical malaria incidence dynamics in the Kedougou region, Senegal 94%
- Resurgence of malaria in Uganda despite sustained indoor residual spraying and repeated long lasting insecticidal net distributions 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.