Molecular Epidemiology of Rubella Virus Strains Detected Around the Time of the 2012–2013 Epidemic in Japan

Abstract

A nationwide rubella epidemic occurred from 2012 to 2013 in Japan, resulting in around 17,000 rubella cases and the birth of 45 infants with congenital rubella syndrome. The aim of this study was to genetically characterize the rubella viruses (RVs) circulating around the time of the epidemic in Japan. In total, 221 RV strains detected from 14 prefectures in Japan between 2010 and 2014 were sequenced in the 739 nucleotide-window region within the E1 gene. The virus strains were chronologically and geographically characterized into groups based on phylogenetic analysis. Among the 221 strains analyzed, 192 (87%), 26 (12%), and 3 (1%) strains were classified into genotypes 2B, 1E, and 1J, respectively. The majority (n = 184) of the genotype 2B strains belonged to lineage 2B-L1 and shared nucleotide homology with the strains detected in Southeast and East Asian countries. Phylogenetic analyses demonstrated that at least six distinct clusters of RV strains (clusters 1–6) induced outbreaks in Japan between 2010 and 2014. Among them, strains from clusters 3, 4, and 6 circulated almost simultaneously during 2012–2013. The cluster 3 strains circulated locally, whereas strains from cluster 4 spread nationwide. The findings suggest that RVs were introduced into Japan many times from neighboring countries. The 2012–2013 epidemic was a complex of outbreaks induced by at least three clusters of RV strains.

Predicting congenital rubella syndrome in Japan, 2018–2019

“…Although Japan is on its way to achieving substantial herd immunity to prevent rubella epidemics , adult men aged 39-56 years are known to have missed vaccination in childhood, and those aged 28-38 years have only had the opportunity for one vaccination dose. As a consequence, the country remains prone to imported cases and experienced a rubella epidemic during 2012-14 (Mori et al, 2017). Moreover, owing to the absence of an identifiable increase in the proportion of rubella antibody-positive individuals following the 2012-14 epidemic (Nishiura et al, 2015), another epidemic began in August 2018.…”

Clinical value of enzyme immunoassay that detects rubella‐specific immunoglobulin M immediately after disease onset

“…The vaccination history of the subject was investigated by public health officers. The viral genotypes were determined by a phylogenetic analysis based on the 739‐nucleotide window region within rubella virus E1 gene using reported primer sets . A total of 300 RT‐PCR‐positive rubella patients were examined for rubella‐specific IgM titer.…”

Rubella Virus Genotype 1E in Travelers Returning to Japan from Indonesia, 2017

“…We amplified the E1 protein-coding region genome of the virus and sequenced the molecular window region (739 nt) ( 7 ). We classified this rubella strain into genotype 1E and deposited it into GenBank (RVs/Osaka.JPN/41.17[1E], accession no.…”

“…LC333396). We generated a phylogenetic tree including 61 strains using the maximum-likelihood method ( Figure ); it revealed that rubella virus can be classified into 5 distinct lineages (L0–L4), as previously described ( 7 , 8 ). 1E-L1 strains are mainly detected in China and Russia.…”

“…To verify rubella elimination, interruptions in transmission of indigenous or imported rubella virus strains must be confirmed through effective surveillance systems ( 9 ). However, it is difficult to distinguish imported strains from endemic strains and to confirm the control status on the basis of genotype information because the genotypes of global epidemic strains converge to genotypes 1E and 2B ( 3 , 7 , 8 , 10 ). Therefore, several studies were conducted to subdivide the genotypes on the basis of detailed phylogenetic analysis ( 7 , 8 ).…”