Host candidate gene polymorphisms and associated clearance of P. falciparum amodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon. (October 2014)

• Record Type: Journal Article
• Authors: Ali, Innocent Mbulli; Evehe, Marie-Solange Bebandue; Netongo, Palmer Masumbe; Atogho-Tiedeu, Barbara; Akindeh-Nji, Mbuh; Ngora, Honore; Domkam, Irenee Kamogne; Diakite, Mahamadou; Baldip, Khan; Ranford-Cartwright, Lisa; Mimche, Patrice Nsangou; Lamb, Tracey; Mbacham, Wilfred Fon
• Is Part Of: Pathogens and global health. Volume 108:Number 7(2014)
• Page Start: 323
• Page End: 333
• Publication Date: 2014-10
• Subjects: Communicable diseases -- Periodicals; Public health -- International cooperation -- Periodicals; World health -- Periodicals; 362.1969
• DOI: 10.1179/2047773214Y.0000000159
• Languages: English
• ISSNs: 2047-7724

Abstract

<abstract> <title> <x content-type="archive" xml:space="preserve">Abstract</x> </title> <sec> <title>Background:</title> <p>In this <italic>post-hoc</italic> analysis, we determined the influence of single nucleotide polymorphisms in host candidate immune genes on the outcome of drug resistant malaria in Cameroon.</p> </sec> <sec> <title>Methods:</title> <p>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 <italic>pfcrt</italic>76T, <italic>pfmdr</italic>86Y, and <italic>pfmdr</italic>1246Y (TY) and <italic>pfdhfr51I</italic>, <italic>pfdhfr59R</italic>, <italic>pfdhfr108N</italic>, and <italic>pfdhps437G</italic> (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 <italic>P</italic> value (OR) <0·0008 was considered significant.</p> </sec> <sec> <title>Results:</title> <p>Post-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 [<italic>p</italic> = 0·017, OR (C allele):1·44, 95% CI (OR): 1·06–1·95]; [<italic>P</italic> = 0·014, OR = 1·31, 95% CI (OR): 1·07–1·83]; [<italic>P</italic> = 5·78×10<sup>−5</sup>, OR = 0·27, 95%CI (OR): 0·13–0·54], respectively, with high fever (>39°C for 48 hours) [IL-22, <italic>P</italic> = 0·01, OR = 1·5, 95% CI (OR): 1·8–2·1] and also in high frequency among the Fulani participants [<italic>P</italic> = 0·006, OR = 1·83, 95% CI (OR): 1·11–3·08)]. The CD36-1264 null allele was completely absent in the northern population.</p> </sec> <sec> <title>Conclusion:</title> <p>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.</p> </sec> </abstract>