Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014

Xiang Yong Oong; Kim Tien Ng; Tommy Tsan-Yuk Lam; Yong Kek Pang; Kok Gan Chan; Nik Sherina Hanafi; Adeeba Kamarulzaman; Kok Keng Tee

doi:10.1371/journal.pone.0136254

Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014

PLoS One. 2015 Aug 27;10(8):e0136254. doi: 10.1371/journal.pone.0136254. eCollection 2015.

Authors

Xiang Yong Oong¹, Kim Tien Ng¹, Tommy Tsan-Yuk Lam², Yong Kek Pang¹, Kok Gan Chan³, Nik Sherina Hanafi⁴, Adeeba Kamarulzaman¹, Kok Keng Tee¹

Affiliations

¹ Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
² School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
³ Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
⁴ Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Amino Acid Substitution
Evolution, Molecular*
Female
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
Humans
Influenza B virus / genetics*
Influenza, Human / epidemiology*
Influenza, Human / genetics*
Malaysia / epidemiology
Male
Middle Aged
Multiplex Polymerase Chain Reaction
Mutation, Missense*
Neuraminidase / genetics*
Phylogeny*
Reverse Transcriptase Polymerase Chain Reaction

Substances

Hemagglutinin Glycoproteins, Influenza Virus
Neuraminidase

Grants and funding

This work was supported by grants from the Ministry of Education, Malaysia: High Impact Research H-500001-00-A000012-000001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.