title: Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia.
abstract: Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Nor Azrina
authors: http://orcid.org/0000-0002-6714-3001
authors: NA
authors: Norahmad
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Mohd Ridzuan
authors: MR
authors: Mohd Abd Razak
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Noor Rain
authors: NR
authors: Abdullah
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Umi Rubiah
authors: UR
authors: Sastu
authors: Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Mallika
authors: M
authors: Imwong
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Prem Kumar
authors: PK
authors: Muniandy
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Muhammad Nor Farhan
authors: MN
authors: Saat
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Amirrudin
authors: A
authors: Muhammad
authors: Sabah Vector Borne Disease Control Programme, Sabah State Health Department, Kota Kinabalu, Sabah, Malaysia.
authors: Jenarun
authors: J
authors: Jelip
authors: Sabah District Health Office Kota Marudu, Kota Marudu, Sabah, Malaysia.
authors: Moizin
authors: M
authors: Tikuson
authors: Sabah District Health Office Kota Marudu, Kota Marudu, Sabah, Malaysia.
authors: Norsalleh
authors: N
authors: Yusof
authors: Sabah District Health Office Kota Marudu, Kota Marudu, Sabah, Malaysia.
authors: Christina
authors: C
authors: Rundi
authors: Vector Borne Disease Sector, Disease Control Division, Ministry of Health, Federal Government Administrative Centre, Putrajaya, Malaysia.
authors: Rose Nani
authors: RN
authors: Mudin
authors: Herbal Medicine Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Ami Fazlin
authors: AF
authors: Syed Mohamed
mesh_terms: D000328:Adult; D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008296:Malaysia; D010963:Plasmodium falciparum / Q000235:genetics* / Q000502:physiology*; D017354:Point Mutation; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine