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Host candidate gene polymorphisms and associated clearance of P. falciparum amodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon.

Title: Host candidate gene polymorphisms and associated clearance of P. falciparum amodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon.
Authors: Ali IM; Evehe MS; Netongo PM; Atogho-Tiedeu B; Akindeh-Nji M; Ngora H; Domkam IK; Diakite M; Baldip K; Ranford-Cartwright L; Mimche PN; Lamb T; Mbacham WF
Source: Pathogens and global health [Pathog Glob Health] 2014 Oct; Vol. 108 (7), pp. 323-33. Date of Electronic Publication: 2014 Nov 12.
Publication Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Taylor & Francis Country of Publication: England NLM ID: 101583421 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-7732 (Electronic) Linking ISSN: 20477724 NLM ISO Abbreviation: Pathog Glob Health Subsets: MEDLINE
Imprint Name(s): Publication: 2016- : Abingdon : Taylor & Francis; Original Publication: London, UK : Maney Pub.
MeSH Terms: Genetic Predisposition to Disease*; Interleukin-4/*genetics ; Interleukins/*genetics ; Malaria, Falciparum/*genetics ; Malaria, Falciparum/*immunology ; Plasmodium falciparum/*immunology; Amodiaquine/pharmacology ; Antimalarials/pharmacology ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/drug effects ; Pyrimethamine/pharmacology ; Sulfadoxine/pharmacology ; Cameroon ; Child, Preschool ; Drug Combinations ; Drug Resistance ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Polymorphism, Single Nucleotide ; Interleukin-22
Abstract: Background: In 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.; Methods: Human 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) 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.; Conclusion: Independent 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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Contributed Indexing: Keywords: Amodiaquine,; Drug resistance markers,; Fever clearance,; Immune response; Interleukin-22,; Parasite clearance,; Sulphadoxine/pyrimethamine,
Substance Nomenclature: 220236ED28 (Amodiaquine); 0 (Antimalarials); 0 (Drug Combinations); 207137-56-2 (Interleukin-4); 0 (Interleukins); Z3614QOX8W (Pyrimethamine); 88463U4SM5 (Sulfadoxine); 0 (Interleukin-22); 0 (IL4 protein, human); 37338-39-9 (fanasil, pyrimethamine drug combination)
Entry Date(s): Date Created: 20141113 Date Completed: 20150701 Latest Revision: 20260128
Update Code: 20260130
PubMed Central ID: PMC4241784
DOI: 10.1179/2047773214Y.0000000159
PMID: 25388906
Database: MEDLINE

Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't