Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia.
BACKGROUND
Drug resistant malaria poses an increasing public health problem in Indonesia, especially eastern Indonesia, where malaria is highly endemic. Widespread chloroquine (CQ) resistance and increasing sulphadoxine-pyrimethamine (SP) resistance prompted Indonesia to adopt artemisinin-based combination therapy (ACT) as first-line therapy in 2004. To help develop a suitable malaria control programme in the district of West Sumba, the seasonal distribution of alleles known to be associated with resistance to CQ and SP among Plasmodium falciparum isolates from the region was investigated.


METHODS
Plasmodium falciparum isolates were collected during malariometric surveys in the wet and dry seasons in 2007 using two-stage cluster sampling. Analysis of pfcrt, pfmdr1, pfmdr1 gene copy number, dhfr, and dhps genes were done using protocols described previously.


CONCLUSIONS
The 76T allele of the pfcrt gene is nearing fixation in this population. Pfmdr1 mutant alleles occurred in 72.8% and 53.3%, predominantly as 1042D and 86Y alleles that are mutually exclusive. The prevalence of amplified pfmdr1 was found 41.9% and 42.8% of isolates in the wet and dry seasons, respectively. The frequency of dhfr mutant alleles was much lower, either as a single 108N mutation or paired with 59R. The 437G allele was the only mutant dhps allele detected and it was only found during dry season.


CONCLUSIONS
The findings demonstrate a slighly higher distribution of drug-resistant alleles during the wet season and support the policy of replacing CQ with ACT in this area, but suggest that SP might still be effective either alone or in combination with other anti-malarials.
Eijkman Institute for Molecular Biology, Jakarta, Indonesia. puji@eijkman.go.id
Puji B S
PB
Asih
William O
WO
Rogers
Agustina I
AI
Susanti
Agus
A
Rahmat
Ismail E
IE
Rozi
Mariska A
MA
Kusumaningtyas
Krisin
Sekartuti
Rita M
RM
Dewi
Farah N
FN
Coutrier
Awalludin
A
Sutamihardja
Andre J A M
AJ
van der Ven
Robert W
RW
Sauerwein
Din
D
Syafruddin
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D016054:DNA, Protozoan / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005787:Gene Frequency; D006801:Humans; D007214:Indonesia; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology; D012621:Seasons; D013413:Sulfadoxine / Q000494:pharmacology
D000962:Antimalarials; D016054:DNA, Protozoan; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine