Molecular epidemiology of malaria in Yaounde, Cameroon : 5. Analysis of the omega repetitive region of the Plasmodium falciparum CG2 gene and chloroquine resistance

A novel #Plasmodium falciparum$ gene, denoted cg2 gene, has been recently discovered, and a distinct genotype, characterized by 12 point mutations and 3 size polymorphisms, has been shown to be associated with chloroquine resistance in laboratory-adapted parasite strains. One of the polymorphic regions, denoted the omega region, consists of 16 tandem repeat units in chloroquine-resistant strains, while the chloroquine-sensitive strains have either less than or equal to 15 or greater than or equal to 17 repeat units. In this study, the in vivo and in vitro responses were compared with the number of repeat units in the omega region of the cg2 gene for 75 Cameroonian isolates determined either by DNA sequencing or agarose gel electrophoresis. The 16-repeat units that characterise the resistant strains were found in 10 chloroquine-sensitive isolates (50% inhibitory concentration (IC50) is less than 100 nM) and 30 chloroquine-resistant isolates (IC50 is greater than or equal to 100 nM). Thirty-five isolates (28 chloroquine-sensitive isolates and 7 chloroquine-resistant isolates) displayed less than or equal to 15 or greater than or equal to 17 repeat units. Of the 18 patients (11 with isolates carrying 16 repeat units and 17 with isolates carrying less than or equal to 15 or greater than or equal to 17 repeat units) showed an adequate clinical response. The sensitivity, specificity, and predictive value were 81% (83%), 74% (61%), and 75% (58%), respectively compared with in vitro (or in vivo) responses. Neither the level of IC50 nor the key #P. falciparum$ multidrug resistance gene (pfmdr 1) allele at position 86 was associated with the number of omega repeat units... (D'après résumé d'auteur