Status of Plasmodium Falciparum Resistance to Sulfadoxine Pyrimethamine in Kwale County, Kenya
Abstract
Background: Malaria persists to be one of the major significant diseases in the world. A range of antimalarial drugs are readily accessible but management of the disease remains a problem. Despite the broadened spread of resistance to Sulfadoxine Pyrimethamine (SP), it still remains the suggested drug to treat and prevent malaria in expecting women and children below five years. This study sought to assess the current trend of SP resistance markers a decade after it was withdrawn as the first-line anti-malarial in Msambweni, Kwale County, Kenya.
Materials and Methods: Smear-positive samples (N=134) collected from June 2013 cross-sectional study amid infants visiting Msambweni District Hospital were evaluated for mutations in dhfr and dhps genes. Extraction of DNA was done using Chelex method followed by PCR amplification of dhfr and dhps genes. Specific enzymes were used to cleave the successfully amplified DNA to establish the samples as either mutated or wild type.
Results: Pfdhps/pfdhfr A437G/K540E/N51I/C59R/S108N quintuple mutant linked with SP-resistance did not change significantly (p=0.967).
Conclusion: This survey proves fixation of key mutations in the Pfdhfr and Pfdhps genes conferring resistance to SP. Further research involving more samples and endemic sites need to be conducted to endow the stakeholders with information on the emergence and increase of SP resistance.
References
World Health Organization (WHO). Monitoring health for the SDGs Sustainable Development Goals,
World Health Statistics; 2017.https://www.who.int>gho>publications.
Ministry of Health Malaria Surveillance guidelines; National guidelines for the diagnosis, treatment and
prevention of malaria in Kenya, 2014.repository.eac.int>bitstream>handle.
Kenya Malaria Indicator Survey (KMIS). Division of Malaria Control [Ministry of Public Health and
Sanitation], Kenya National Bureau of Statistics, and ICF Macro. 2011.https://www.knbs.or.ke.
Okiro EA, Alegana VA, Noor AM et al. Changing malaria intervention coverage, transmission and hospitalization in Kenya. Malaria Journal 2010; 9: 285.
Moody A. Rapid diagnostic tests for malaria parasites. Clin Microbial Rev 2002; 15(4): 66-78.
Kublin JG, Dzinjalamala FK, Kamwendo D et al. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum Malaria. Journal of Infectious Diseases
; 185: 380-388.
Khan B, Omar S, Kanyara JN et al. Antifolate drug resistance and point mutations in Plasmodium
falciparum in Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 1997; 91(4): 456-460.
Djimde A, Ogobara PD, Doumbo K et al. Molecular marker for chloroquine-resistant falciparum malaria.
N Engl J Med 2001; 344(4): 257-263.
Amin A, Zurovac D, Kangwana B et al. The challenges of changing national malaria drug policy to artemisininbased combinations in Kenya. Malaria Journal 2007; 6: 72.
Sridaran S, McClintock SK, Syphard LM et al. Anti-folate drug resistance in Africa: meta-analysis of reported
dihydrofolate reductase (dhfr) and dihydropteroatesynthase (dhps) mutant genotype frequencies in African
Plasmodium falciparum parasite populations. Malar J 2010; 9: 247.
Thaithong S, Chan SW, Songsomboon S et al. Pyrimethamine resistant mutations in Plasmodium
falciparum. Mol Biochem Parasitol 1992; 52(2): 149-157.
Gregson A, Plowe CV. Mechanisms of resistance of malaria parasites to antifolates. Pharmacological
Reviews 2005; 57(1): 117-145.
Warhurst DC, Kariem FM, Miles MA. Simplified preparation of malarial blood samples for polymerase
chain reaction. Lancet 1991; 337: 303-304.
Duraisingh MT, Curtis J, Warhurst D. Plasmodium falciparum: detection of polymorphism in the
dihydrofolate reductase and dihydropteroate synthase genes by PCR and restriction digestion. Experimental
Parasitology 1998; 8(1): 1-8.
Spalding MD, Eyase FL, Akala HM et al. Increased prevalence of the Pfdhfr/phdhps quintuple mutant
and rapid emergence of Pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya. Malar J
; 9: 338.
Iriemenam NC, Shah M, Gatei W et al. Temporal trends of sulfadoxine-pyrimethamine (SP) drug-resistance
molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Malar J 2012;
: 134.
Juma DW, Omondi AA, Ingasia L et al. Trends in drug resistance codons in Plasmodium falciparum
dihydrofolate reductase and dihydropteroate synthase genes in Kenyan parasites from 2008 to 2012. Malaria
Journal 2014; 13: 250.
Okombo J, Kamau AW, Marsh K et al. Temporal trends in prevalence of Plasmodium falciparum drug resistance alleles over two decades of changing antimalarial policy in coastal Kenya. Int J Parasitol Drugs Drug Resist 2014; 4(3): 152-163.
Mbonye AK, Birungi J, Yanow SK et al. of Plasmodium falciparum resistance markers to sulfadoxine
pyrimethamine among pregnant women receiving intermittent preventive treatment for malaria in
Uganda. Antimicrob Agents Chemother 2015; 59: 5475-5482.
Alifrangis M, Lusingu JP, Mmbando B et al. Five-year surveillance of molecular markers of Plasmodium
falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in
the P. falciparum dihydropteroate synthase gene. Am J Trop Med Hyg 2009; 80: 523-527.
Amin AA, Snow RW. Brands costs and registration status of antimalarial drugs in the Kenyan retail sector.
Malar J 2005; 4: 36.
Manyando C, Njunju EM, D’Alessandro U et al. Safety and efficacy of co-trimoxazole for treatment and
prevention of Plasmodium falciparum malaria: a systematic review. PLoS One 2013; 8(2): 56916.
