Different mutation patterns of Plasmodium falciparum among patients in Jimma University Hospital, Ethiopia

Background: The emergence of drug resistance is a major problem in
malaria control. Combination of molecular genotyping and
characterization of mutations or single nucleotide polymorphisms (
SNPs) correlated with drug resistance can provide information for
subsequent surveillance of existing and developing drug resistance
patterns. The introduction of artemether/lumefantrine (AL) as
first-line treatment, never used before in Ethiopia, allowed the
collection of baseline data of molecular polymorphisms before a
selection due to AL could occur. Method: 97 patients with
uncomplicated falciparum malaria were recruited from April to June
2006 and treated with either AL, quinine (Q) or
atovaquone/proguanil (AP) in Jimma University Hospital, Ethiopia.
Mutations or SNPs associated with resistance to these drugs were
analysed by RFLP (pfdhfr, pfmdr1) and sequencing of the target
genes (pfcytb, pfserca). Results: SNPs previously reported to be
associated with resistance to the study drugs were identified in
recrudescent and treatment sensitive isolates. A total of seven
recrudescences were obtained. The pfmdr1 N86Y mutation was found in
84.5% of isolates. The triple mutation 51I,59R,108N of the pfdhfr
gene occured in high frequency (83.3%) but no pfcytb mutation was
detected. Sequencing showed a variety of previously described and
new mutations in the pfserca gene. Conclusion: The prevalence of
mutations was in accordance with the expected patterns considering
recent drug regimens. The broad introduction of AL and the
cessation of former drug regimens might probably change the current
distribution of polymorphisms, possibly leading to decreased
sensitivity to AL in future. Continuous surveillance of molecular
patterns in this region is, therefore, recommended.