Frequency Of Sulfadoxine Pyrimethamine Resistance Associated Gene Mutations In Plasmodium Falciparum Clinical Isolates From Kwale County, Kenya

ABSTRACT

Malaria persists to be one of the world’s complex and dynamic disease. The disease is more devastating in sub-Saharan Africa as it constitutes high cases of childhood mortality and morbidity. Management of the disease remains a problem as a result of the spread of parasites that are resistant to the available drugs. Due to the broadened spread of resistance to Sulfadoxine Pyrimethamine (SP), the artemether-lumefantrine which is a more effective and well-tolerated anti-malarial drug replaced the SP as the first-line regimen in treatment of uncomplicated malaria in Kenya. However, SP remains the suggested drug to treat and prevent malaria in expectant women and children under the age of five. This study sought to assess the presence of mutation in dihydrofolate reductase and dihydropteroate synthase genes associated with SP resistance a decade after Sulfadoxine-Pyrimethamine was withdrawn as the first-line anti-malarial drug of choice in Kenya. Smear-positive samples (N = 134) collected from a 2013 cross-sectional study in infants managed at Msambweni District Hospital were evaluated for mutations in dhfr and dhps (SP).The findings obtained were matched up with molecular data from infants in Western Kenya in a study carried out in 2003/05. In all the 134 samples, mutations at codons N51I, C59R, S108N had a high predominance at 80.6%, 72.4% and 93.3% respectively. The double mutant of Pfdhps A437G/ K540E had an occurrence rate of 82.1% and 78.4% respectively. Compared to the molecular data of 2003/05 study, the Pfdhfr triple mutant (S108N/N51I/C59R) genotype decreased to 63.4% in 2013 up from 68%. However, this reduction was not significant (p=0.387). There was no significant change in the prevalence of Pfdhps double mutant (A437G/K540E) genotype (p=0.485). The percentage of isolates which had the Pfdhps A437G/K540E/ Pfdhfr N51I/C59R/S108N quintuple mutant linked with SP-resistance did not change significantly over the two study periods under consideration (53.5% in 2003/05 versus 53.7% in 2013, p = 0.967).The high prevalence of SP resistance marker in the coastal Kenya could be attributed to circulation and SP drugs being sold over the counter which has maintained a selection pressure for the mutations and fixation in the key mutations in the inhabitants. Also the mutation could have a little effect on the fitness of fit of the parasite such that withdrawal of drug pressure did not offer any survival disadvantage hence the continued spread of resistant parasites. Further investigations should be done to determine the linkage between SP drug resistance associated mutations and efficacy of IPTi-SP since the mutation levels are still high. It is also recommended that doctors using SP for IPTi and IPTp should be more cautious and their use monitored to ensure cases of poor response are managed with a different drug