Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya

• Published in: Malaria Journal
• Main Authors: Iriemenam Nnaemeka C, Shah Monica, Gatei Wangeci, van Eijk Anna M, Ayisi John, Kariuki Simon, Vanden Eng Jodi, Owino Simon O, Lal Ashima A, Omosun Yusuf O, Otieno Kephas, Desai Meghna, ter Kuile Feiko O, Nahlen Bernard, Moore Julie, Hamel Mary J, Ouma Peter, Slutsker Laurence, Shi Ya Ping
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2012
• Subjects: Malaria in pregnancy; SP resistance; Kenya; dhfr; dhps; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-11-134; https://doaj.org/article/579336a824c14346bc8fe9cba07508d8

Abstract Background Resistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population prevalence of the SP resistance molecular markers in pregnant women is limited. Methods Temporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed. Results The prevalence of quintuple mutant ( dhfr N51 I /C59 R /S108 N and dhps A437 G /K540 E combined genotype) increased from 7 % in the first study (1996–2000) to 88 % in the third study (2008–2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4 % in 1998 to 44.4 % three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996–2000 study, more mutations in the combined dhfr / dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002–2008 and 2008–2009 studies. In addition, in the 2008–2009 study, 5.3 % of the parasite samples carried the dhps triple mutant (A437 G /K540 E /A581 G ). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples. Conclusions There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype ...