Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing

• Published in: Scientific reports 2023-07, Vol.13 (1), p.11416-11416, Article 11416
• Main Authors: Osborne, Ashley, Phelan, Jody E., Kaneko, Akira, Kagaya, Wataru, Chan, Chim, Ngara, Mtakai, Kongere, James, Kita, Kiyoshi, Gitaka, Jesse, Campino, Susana, Clark, Taane G.
• Format: Article
• Language: English
• Subjects: 631/114/2163; 631/326/417/2550; Antimalarial agents; Antimalarials - pharmacology; Antimalarials - therapeutic use; Asymptomatic; Decision making; Drug Combinations; Drug resistance; Drug Resistance - genetics; Female; Haplotypes; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Humans; Infections; Kenya - epidemiology; Malaria; Malaria - parasitology; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Medicin och hälsovetenskap; multidisciplinary; Next-generation sequencing; Parasite resistance; Parasites; Plasmodium falciparum; Pregnancy; Pyrimethamine; Pyrimethamine - pharmacology; Pyrimethamine - therapeutic use; Quinolones; Science; Science (multidisciplinary); Sulfadoxine; Sulfadoxine - pharmacology; Sulfadoxine - therapeutic use; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-38481-3

Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt , Pfmdr1 , Pfdhps , Pfdhfr , and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype ( Pfdhfr/Pfdhps : N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1 , associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.