PubMedJournal of parasitology research2026-06-12
Polymorphism of pfmdr1 Gene Mutation Conferring Resistance to Artemisinin-Based Combination Therapy in Plasmodium falciparum in Patients at Gulu Regional Referral Hospital in Northern Uganda.
Amito Florence Peace FP, Angwech Harriet H, Ojok Lonzy L, Wokorach Godfrey G et al.
Malaria is one of the most devastating infectious diseases in humans, and antimalarial drugs have been used to combat it with minimal success. Worldwide, malaria treatment is threatened by the emergence and spread of artemisinin resistance, which is associated with mutations in the PfK13 propeller domain. In Sub-saharan Africa, data relating to the prevalence of Plasmodium falciparum malaria infection in association with the Kelch 13 mutations are mainly from research settings outside disease-endemic areas. This study is aimed at establishing the prevalence of P. falciparum malaria infection in association with Kelch 13 mutations among patients presenting with fever at Gulu Regional Referral Hospital (GRRH) in northern Uganda.
This cross-sectional study enrolled all participants presenting with fever at GRRH between April 2022 and January 2024. Data on adults and children aged ≥ 6 months with fever and confirmed diagnosis of malaria using mRDT, microscopy, and PCR were collected. Parasite DNA was extracted using the Chelex method and sequenced for multidrug resistance genes, and Sanger customized CRF forms were used to capture variables on social demographics, clinical presentation, and treatment. Data were analyzed using IBM SPSS Version 25, and the sequenced data were analyzed using molecular evolutionary genetic analysis (MEGA) Version 11.1.10. All sequences from a single population were aligned using the National Center for Biotechnology Information (NCBI) database.
In total, 353 participants were recruited, and the overall prevalence of P. falciparum malaria was 60.6% (n = 214), with the highest number of cases registered in Gulu City (24.9%). Women were the most affected participants (37.1%). The most common clinical presentations among the participants were fever (91.8%; n = 324), chills (90.7%; n = 320), and headaches (72.0%; n = 254). Genotyping results of the mutant genes showed that of all 214 P. falciparum isolates examined, the pfmdr1 SNP at Codon 1034 1042 (29.6%, n = 94) had the highest prevalence, followed by the pfmdr SNP at Codon 86 184 (28%, n = 89), and the SNP fragment at codon 1246 (25.8%, n = 82) recorded the lowest prevalence. Kelch 13 propeller gene, known to be associated with artemisinin resistance, was also isolated in 16.7% (n = 53) of the samples. There was a 90.1% (n = 318) prevalence of the SNPs 86 184, 1034 1042 of the pfmdr1 gene, and K13 propeller gene, with no significant difference between the sexes (p = 0.756). The SNP at Codon 1246 of pfmdr1 showed a significant difference between the location and mutation (p = 0.017). The median parasite load in patients with mutations in 86 184, 1034 1042, and K13 propeller genes varied significantly among patients who received treatment p ≤ 0.0001, p = 0.0061, and p = 0.012, respectively.
The presence of pfmdr1 mutant genes suggests resistance of P. falciparum to most antimalarial drugs used in treatment. Therefore, it is important to monitor the prevalence of Kelch 13 mutations and P. falciparum to contribute to global efforts to control and eliminate malaria.
