title: Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014.
abstract: Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors-total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.
authors: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Xiang Yong
authors: XY
authors: Oong
authors: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Kim Tien
authors: KT
authors: Ng
authors: School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
authors: Tommy Tsan-Yuk
authors: TT
authors: Lam
authors: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Yong Kek
authors: YK
authors: Pang
authors: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Kok Gan
authors: KG
authors: Chan
authors: Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Nik Sherina
authors: NS
authors: Hanafi
authors: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Adeeba
authors: A
authors: Kamarulzaman
authors: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Kok Keng
authors: KK
authors: Tee
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D019143:Evolution, Molecular; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D009981:Influenza B virus / Q000235:genetics*; D007251:Influenza, Human / Q000453:epidemiology* / Q000235:genetics*; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase