Trial reportPathogens and global health2014
Host candidate gene polymorphisms and associated clearance of P. falciparum amodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon.
Trial report in Pathogens and global health, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations.RNA (New York, N.Y.) · 2022Review
- Antimalarial Drug Resistance Profiling of Plasmodium falciparum Infections in Ghana Using Molecular Inversion Probes and Next-Generation Sequencing.Antimicrobial agents and chemotherapy · 2020Article
- Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination.Parasites & vectors · 2019Review
- Monitoring the Efficacy and Safety of Artemisinin-Based Combination Therapies: A Review and Network Meta-analysis of Antimalarial Therapeutic Efficacy Trials in Cameroon.Drugs in R&D · 2019Review
- Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to Plasmodium falciparum.PloS one · 2017Article
- A Method for Amplicon Deep Sequencing of Drug Resistance Genes in Plasmodium falciparum Clinical Isolates from India.Journal of clinical microbiology · 2016Article
- From within host dynamics to the epidemiology of infectious disease: Scientific overview and challenges.Mathematical biosciences · 2015Review
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn this post-hoc analysis, we determined the influence of single nucleotide polymorphisms in host candidate immune genes on the outcome of drug resistant malaria in Cameroon.
methodsHuman DNA from 760 patients from a previous clinical trial was subjected to mass spectrometry-based single nucleotide polymorphism (SNP) genotyping. Allele frequencies of candidate immune genes were calculated for 62 SNPs on 17 human chromosomes for their possible involvement in clearance of drug-resistant parasites with the triple mutations of pfcrt76T, pfmdr86Y, and pfmdr1246Y (TY) and pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps437G (IRNG) which were determined by dotblot or PCR-restriction analysis. Differences in SNP frequencies and association analysis were carried out by comparing Chi-square odds ratios (ORs) and stratified by Mantel-Haenzel statistics. An adjusted P value (OR) <0·0008 was considered significant.
resultsPost-treatment drug failure rates were amodiaquine (36·4%); sulpadoxine/pyrimethamine-amodiaquine combination (15·4%); and sulphadoxine/pyrimethamine (18·1%). SNPs in IL22, IL-4R1, and CD36 appeared to have been associated with clearance of resistant parasites [p = 0·017, OR (C allele):1·44, 95% CI (OR): 1·06-1·95]; [P = 0·014, OR = 1·31, 95% CI (OR): 1·07-1·83]; [P = 5·78×10(-5), OR = 0·27, 95%CI (OR): 0·13-0·54], respectively, with high fever (>39°C for 48 hours) [IL-22, P = 0·01, OR = 1·5, 95% CI (OR): 1·8-2·1] and also in high frequency among the Fulani participants [P = 0·006, OR = 1·83, 95% CI (OR): 1·11-3·08)]. The CD36-1264 null allele was completely absent in the northern population.
conclusionIndependent association of SNPs in IL22 and IL-4 with clearance of amodiaquine- and sulphadoxine/pyrimethamine-resistant parasites did not reach statistical significance, but may suggest that not all drug-resistant mutants are adversely affected by the same immune-mediated mechanisms of clearance.
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