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.


METHODS
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.


CONCLUSIONS
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.
Eshetu
Teferi
T
Department of Infectious Diseases and Tropical Medicine, Ludwig Maximilians University, Leopoldstrasse 5, München, Germany.
Berens-Riha
Nicole
N
Fekadu
Sintayehu
S
Tadesse
Zelalem
Z
Gürkov
Robert
R
Hölscher
Michael
M
Löscher
Thomas
T
Miranda
Isabel Barreto
IB
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D053626:Atovaquone / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D045303:Cytochromes b / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use; D005002:Ethiopia; D005260:Female; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D002727:Proguanil / Q000494:pharmacology / Q000627:therapeutic use; D011803:Quinine / Q000627:therapeutic use; D012008:Recurrence; D017422:Sequence Analysis, DNA; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D055815:Young Adult
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D053626:Atovaquone; D045303:Cytochromes b; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D002727:Proguanil; D011803:Quinine; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C109496:atovaquone, proguanil drug combination