Rubella Epidemics and Genotypic Distribution of the Rubella Virus in Shandong Province, China, in 1999–2010

BACKGROUND: The rubella vaccine was introduced into the immunization program in 1995 in the Shandong province, China. A series of different rubella vaccination strategies were implemented at different stages of measles control in Shandong province. METHODOLOGY/PRINCIPAL FINDINGS: The average reported incidence rate of rubella cases remained at a low level in Shandong province after 1999. However, rubella epidemics occurred repeatedly in 2001/2002, 2006, and 2008/2009. The age of the onset of rubella cases gradually increased during 1999–2010, which showed that most cases were found among the 10 years old in 1999 and among the 17 years old in 2010. Phylogenetic analysis was performed and a phylogenetic tree was constructed based on the World Health Organization standard sequence window for rubella virus isolates. All rubella viruses isolated in Shandong province were divided into 4 genotypes: 1E, 1F, 2A, and 2B. Genotype 1E viruses accounted for the majority (79%) of all these viruses. The similarity of nucleotide and amino acid sequences among genotype 1E viruses was 98.2–100% and 99.1–100%, respectively. All Shandong genotype 1E strains, differed from international genotype 1E strains, belonged to cluster 1 and interdigitated with the viruses from other provinces in mainland China. The effective number of infections indicated by a Bayesian skyline plot remained constant from 2001 to 2009. CONCLUSIONS/SIGNIFICANCE: The gradual shift of disease burden to an older age group occurred after a rubella-containing vaccine was introduced into the childhood immunization schedule in 1995 in Shandong province. Four genotypes, including 1E, 1F, 2A, and 2B, were found in Shandong province during 2000–2009. Genotype 1E, rather than genotype 1F, became the predominant genotype circulating in Shandong province from 2001. All Shandong genotype 1E viruses belong to the genotype 1E/cluster 1; they have constantly circulated, and co-evolved and co-circulated, with those from other provinces.