TY - JOUR
T1 - Source of drug resistant Plasmodium falciparum in a potential malaria elimination site in Saudi Arabia
AU - Al-Farsi, Hissa M.
AU - Al-Hashami, Zainab S.
AU - Bin Dajem, Saad M.
AU - Al-Sheikh, Adel Ali H.
AU - Al-Qahtani, Ahmed
AU - Beja-Pereira, Albano
AU - Idris, Mohamed A.
AU - Babiker, Hamza A.
N1 - Funding Information:
We thank the participants in this study and the staff of the Ministry of Health authorities in Jazan for their cooperation in this study. We tank Dr Lisa Ranford-Cartwright, Glasgow University, UK, for comments. This study was supported by Sultan Qaboos University, Oman, project IG/MED/BIOC/09/03 and King Abdulaziz City for Science and Technology (KACST), Saudi Arabia, grant (LR-4-13). Appendix A
PY - 2012/8
Y1 - 2012/8
N2 - A major challenge to the success of malaria control program in Saudi Arabia is the high influx of expatriates and holy visitors from malaria endemic countries. In the present study we examined whether drug resistant parasite genotypes reported in Jazan region, southwest of Saudi Arabia are imported or developed locally. We examined 178 Plasmodium falciparum isolates for alleles of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), associated with Sulfadoxine-Pyrimethamine (SP) resistance, and three microsatellites flanking each gene. In addition, we examined a neutral polymorphic gene (Pfg377). We compared the dhfr and dhps haplotypes in Jazan, using network analysis, to an existing similar data set of 94 P. falciparum isolates from eastern Sudan. In Jazan, double mutant dhfr allele (51I, 108N) occurred with a prevalence of 33%. The vast majority (99%) of dhps were wild-type alleles. The mean expected heterozygosity (He) of microsatellites around mutant dhfr alleles (He=0.312; n=60) was lower (P≤0.05) than that around the wild-type allele (He=0.834; n=116). Also, the mutant dhfr isolates showed high He for dhps (He=0.80) and the non-drug resistance locus Pfg377 (He=0.63) indicative of selection for mutant dhfr only. The predominant double mutant dhfr haplotype in Jazan (73%), was prevalent among P. falciparum in east Africa. Network analysis suggests the mutant haplotype of dhfr gene was possibly introduced into Jazan from East Africa. The absence of mutations in dhps as well as triple mutant dhfr haplotype associated with SP failure support the current use of SP as a partner with artesunate as a first line therapy in Saudi Arabia. However, the close relationship between the major mutant dhfr haplotype in Sudan and Saudi Arabia, favour the hypothesis of recent migration as a source of the major resistant dhfr lineage. Thus, regular monitoring of the dhfr and dhps haplotypes is of high priority to guard possible importation of high level SP resistant lineages.
AB - A major challenge to the success of malaria control program in Saudi Arabia is the high influx of expatriates and holy visitors from malaria endemic countries. In the present study we examined whether drug resistant parasite genotypes reported in Jazan region, southwest of Saudi Arabia are imported or developed locally. We examined 178 Plasmodium falciparum isolates for alleles of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), associated with Sulfadoxine-Pyrimethamine (SP) resistance, and three microsatellites flanking each gene. In addition, we examined a neutral polymorphic gene (Pfg377). We compared the dhfr and dhps haplotypes in Jazan, using network analysis, to an existing similar data set of 94 P. falciparum isolates from eastern Sudan. In Jazan, double mutant dhfr allele (51I, 108N) occurred with a prevalence of 33%. The vast majority (99%) of dhps were wild-type alleles. The mean expected heterozygosity (He) of microsatellites around mutant dhfr alleles (He=0.312; n=60) was lower (P≤0.05) than that around the wild-type allele (He=0.834; n=116). Also, the mutant dhfr isolates showed high He for dhps (He=0.80) and the non-drug resistance locus Pfg377 (He=0.63) indicative of selection for mutant dhfr only. The predominant double mutant dhfr haplotype in Jazan (73%), was prevalent among P. falciparum in east Africa. Network analysis suggests the mutant haplotype of dhfr gene was possibly introduced into Jazan from East Africa. The absence of mutations in dhps as well as triple mutant dhfr haplotype associated with SP failure support the current use of SP as a partner with artesunate as a first line therapy in Saudi Arabia. However, the close relationship between the major mutant dhfr haplotype in Sudan and Saudi Arabia, favour the hypothesis of recent migration as a source of the major resistant dhfr lineage. Thus, regular monitoring of the dhfr and dhps haplotypes is of high priority to guard possible importation of high level SP resistant lineages.
KW - Evolutionary origin
KW - Plasmodium falciparum
KW - Pyrimethamine-sulfadoxine resistance
KW - Saudi Arabia
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U2 - 10.1016/j.meegid.2012.03.011
DO - 10.1016/j.meegid.2012.03.011
M3 - Article
C2 - 22709478
AN - SCOPUS:84861926547
SN - 1567-1348
VL - 12
SP - 1253
EP - 1259
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
IS - 6
ER -
