Prevalence of Molecular Markers Associated With Chloroquine Resistance in P. Falciparum After Withdrawal of the Drug in Harbu, Ethiopia.
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Date
2011-06
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Addis Ababa University
Abstract
In Ethiopia, chloroquine was the first line anti-malarial drug used for the treatment of
uncomplicated falciparum malaria for more than 40 years, until very high treatment failure
rates were demonstrated through studies conducted in 1997/98. Following these findings,
the national drug policy for uncomplicated falciparum malaria treatment was shifted to
sulfadoxine/pyrimethamine (SP). Unfortunately, SP resistance became widely prevalent
soon after its introduction and was replaced by artemether-lumefantrine (AL) in 2004. In
order to assess the impact of this policy change on the prevalence of molecular markers
linked to chloroquine resistance in Harbu, South Wollo, Amhara Region, a total of 144
blood samples were collected from P. falciparum mono-infected study participants using
whatman filter paper in 2005 (N=72) and 2008 (N=72). PCR based dot blot-hybridization
technique was performed to determine the change in prevalence of molecular marker genes,
Pfcrt 76 Thr and Pfmdr1 86 Tyr that confer chloroquine resistance in P. falciparum
isolates from 2005 and 2008. The study showed a slight reduction in the prevalence of
Pfcrt 76 mutation (Lys 76 Thr) from 100% in 2005 to 98.21% in 2008 (95% CI, -0.017-
0.053; P= 0.29), whereas, Pfmdr1 86 mutation (Asn 86 Tyr) showed a statistically
significant reduction of 15.9%, from 81.97% in 2005 to 66.07% in 2008 (95% CI, 0.001-
0.315; P= 0.049). The prevalence of wild allele of Pfcrt 76 Lys increased to1.79% in 2008
from 0% in 2005 (95% CI,-0.053- 0.017; P= 0.29). Similarly, the wild allele of Pfmdr1 86
Asn was also increased from 14.75% in 2005 to 23.21% in 2008 (95% CI, -0.227- 0.057;
P= 0.24). Overall, the findings of the present study showed a decline in prevalence of
chloroquine resistance conferring genes in spite of use of chloroquine for treatment of P.
vivax in the study area. This is a good indication of the re-emergence of chloroquine
sensitive P. falciparum in the study area. Therefore, it would be advisable to withdraw the
use of chloroquine for vivax malaria treatment for a much faster re-emergence of
chloroquine sensitive P. falciparum parasites, in order to maximize the likelihood of
chloroquine reintroduction.
Key words: Plasmodium falciparum; Chloroquine resistance; Pfcrt; Pfmdr1; PCR; Dot
blot-hybridization.
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Keywords
Plasmodium falciparum, Chloroquine resistance, Pfcrt; Pfmdr1; PCR; Dot, blot-hybridization.