FREQUENCY OF SULFADOXINE PYRIMETHAMINE RESISTANCE ASSOCIATED GENE MUTATIONS IN PLASMODIUM FALCIPARUM CLINICAL ISOLATES FROM KWALE COUNTY, KENYA
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Date
2020-01
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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with SP resistance a decade after Sulfadoxine-Pyrimethamine was withdrawn as the first-line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.