Plasmodium falciparum merozoite invasion ligands, linked antimalarial resistance loci and ex vivo responses to antimalarials in The Gambia

Abstract

Background Artemether/lumefantrine is the most commonly used artemisinin-based combination treatment (ACT) for malaria in sub-Saharan Africa. Drug resistance to ACT components is a major threat to malaria elimination efforts. Therefore, rigorous monitoring of drug efficacy is required for adequate management of malaria and to sustain the effectiveness of ACTs. Objectives This study identified and described genomic loci that correlate with differences in ex vivo responses of natural Plasmodium falciparum isolates from The Gambia to antimalarial drugs. Methods Natural P. falciparum isolates from The Gambia were assayed for IC50 responses to four antimalarial drugs (artemether, dihydroartemisinin, amodiaquine and lumefantrine). Genome-wide SNPs from 56 of these P. falciparum isolates were applied to mixed-model regression and network analyses to determine linked loci correlating with drug responses. Genomic regions of shared haplotypes and positive selection within and between Gambian and Cambodian P. falciparum isolates were mapped by identity-by-descent (IBD) analysis of 209 genomes. Results SNPs in 71 genes, mostly involved in stress and drug resistance mechanisms correlated with drug responses. Additionally, erythrocyte invasion and permeability loci, including merozoite surface proteins (Pfdblmsp, Pfsurfin), and high-molecular-weight rhoptry protein 2 (Pfrhops2) were correlated with responses to multiple drugs. Haplotypes of pfdblmsp2 and known drug resistance loci (pfaat1, pfcrt and pfdhfr) from The Gambia showed high IBD with those from Cambodia, indicating co-ancestry, with significant linkage disequilibrium between their alleles. Conclusions Multiple linked genic loci correlating with drug response phenotypes suggest a genomic backbone may be under selection by antimalarials. This calls for further analysis of molecular pathways to drug resistance in African P. falciparum.

Risk Factors of Malaria Transmission Dynamics Among Sand Mining Workers in the Kombos West Coast Region, The Gambia

“…(19,40) Therefore, it is important for future studies to assess the protective impact of incorporating particular internal features. (14,42) The results of the current investigation indicated a relationship between malaria transmission and the state of the ceiling (55.40%) and inside walls (61.96%). Similar findings were found in another study, which indicated that contemporary, upgraded dwellings had a 47% lower risk of malaria infection than traditional ones.…”

“…(15) According to a different research, changes in land cover have a major impact on Africa's highland temperatures and the spread of malaria vectors. (6,14,15) Additionally, it raises the danger of malaria in the highlands as well as the pace at which sporogony develops and adult vectors survive. (27) The number of Anopheles mosquitoes can be significantly decreased by taking steps to remove standing water and mosquito breeding grounds.…”

“…Effective treatment for malaria is hampered by patients' ignorance, a itudes, and beliefs as well as by their inability to obtain and adhere to artemisinin-based combination therapy (ACT). (5,14) Furthermore, a number of studies have demonstrated that using a repellent for malaria stops the disease from spreading. (23,41) Additional research emphasizes the necessity of enhancing personal mosquito repellent techniques for the prevention and control of plasmodium infections.…”

“…For instance, there is a chance that sand miners in Tanjeh and Brufut, The Gambia, would get malaria. (14,15) Additional research has demonstrated that mining regions are more susceptible to malaria, with persistent evidence of malaria vectors flourishing there, as observed in the West Kenyan highlands. (4,16) Changes in land use can have an influence on the spread of malaria, and socioeconomic and behavioural variables are among the risk factors for malaria in mining regions.…”

Overview of malaria prevention and treatment management in The Gambia: a descriptive study

“…Since this dose, although effective as a gametocide, is not sufficient to produce toxicity in individuals who have G6PD variation, it is not important to know the G6PD status of the patient in this case. (Gadji et al, 2023, Mbye et al, 2022. (Babucarr Jassey et al) Due to the possibility of death within hours of hospital admission, severe malaria is a medical emergency.…”