This study summarizes the rubella surveillance data and documents epidemic rubella cycles occurring approximately every 6 to 8 years (1993 to 1994, 2001, and 2007). Similar epidemic cycles have been observed in other countries, for example, in the United States before 1969 (24
). Seroepidemiological surveys revealed seronegativity rates of around 20% among women of childbearing age in China (17
), and this study shows that the percentage of rubella cases in individuals between 15 and 29 years of age increased between 2004 and 2007. Routine rubella vaccination was not included in the national immunization program of China until 2007; before this, vaccination was implemented on a voluntary basis in a few large cities (9
). This may partly be responsible for the shift of disease burden to susceptible young adults, specifically to women of childbearing age in the prevaccination era, which could lead to an increase in the rate of CRS relative to the number of rubella cases.
This study investigated the genotype distribution of rubella viruses in China over a 28-year period to establish an important genetic baseline in China during the prevaccination era. Molecular epidemiology and phylogenetic analyses have become important tools in monitoring virus circulation and the progress of elimination efforts, and these baseline data should be useful in the near future for classifying viruses found in China as either indigenous or imported (13
). For example, based on the data presented here, genotype 1G viruses, which are commonly found in Africa and Europe, would probably be considered to have been imported if found in China (3
Among the viruses of 5 genotypes detected in China between 1979 and 2007 (1a, 1E, 1F, 2A, and 2B), those of genotypes 1a, 1F, 2A, and 2B were rarely found in recent years. Genotype 1a rubella viruses that were present during 1984 in Shandong province were not found after that year. Genotype 2A viruses, which are not closely related to the vaccine virus BRDII, have not been found since 1980. Genotype 1F viruses were first detected in 1999 in Anhui province and were likely the predominant viruses in this province during 1999 to 2000. However, viruses of this genotype have not been isolated in China or elsewhere since 2002 (in Henan). Furthermore, viruses of genotypes 2A and 1F have yet to be found outside China. Genotype 2B rubella viruses were not found frequently enough to be considered significant in indigenous transmission. Genotype 2B viruses that were not considered to be imported were found in only 1 outbreak between 1999 and 2007 (Anhui province in 2000). It would be interesting to collect samples from other Chinese provinces to determine if genotype 2B viruses are more prevalent than our data suggest.
The data presented here show that viruses of different genotypes have cocirculated in China. Genotype 1a and 2A viruses were found during 1979 to 1984, genotype 1F and 2B viruses were found during 1999 to 2000, and genotype 1F and 1E viruses were found during 2001 to 2007. Clearly, data on viruses from more locations and more years would be beneficial; the number of cocirculating viruses reported here should be considered a minimum. The more recent data presented here indicate that the number of cocirculating strains decreased after 2003. Only genotype 1E viruses were found since then (a total of 81 viruses). However, the dominance of genotype 1E viruses may not be an entirely stable situation, because recent data from 2008 indicate circulating genotypes other than 1E (data not shown).
This study provides good evidence that replacement of rubella viruses of a given genotype can occur. Rubella viruses of genotype 1F and 2B were likely replaced by viruses of genotype 1E in Anhui province. Anhui is a small, densely populated province (population, about 65,000,000; area, about 150 × 300 miles). This province has good virological surveillance, resulting in the determination of the genotypes of 10 viruses from 4 outbreaks in 1999 to 2000 (1F and 2B) and 12 viruses from 3 outbreaks in 2001 to 2007 (1E) (Table and Fig. ). Genotype 1E viruses first appeared in Anhui in 2001, an epidemic year in China. Although there are fewer viruses from Shandong, the data are consistent with a similar shift to genotype 1E in this province. Genotype 1E viruses were predominant in China during 2001 to 2007, being found in 13 provinces (101 viruses from 30 rubella outbreaks). A shift to genotype 1E similar to that observed in Anhui province may have occurred throughout China during 2001 to 2007.
Genotype 1E viruses were first identified in 1997 in the United States, Canada, the Caribbean, and Italy (20
). In addition to North America and Europe, 1E viruses have now been isolated in South America, Africa, and Asia (27
). Shifts of predominant viruses to a new genotype, such as those that occurred in Anhui and likely in all of China, have also occurred in some other countries where rubella is endemic, such as Japan, Italy, and Brazil (14
Three BRDII vaccine-associated cases were found in Shandong in 2001 in this study, and isolation of the RA27/3 vaccine virus from vaccinees has been reported previously (8
). Vaccine virus isolations can easily occur when outbreaks and vaccination campaigns occur simultaneously; therefore, future isolations of RA27/3 and BRDII vaccine viruses are expected as vaccination increases in China.
It is also interesting that the molecular epidemiological pattern of rubella viruses in China appears to be quite different from those of the measles virus (30
), mumps virus (6
), human enterovirus 71 (32
), and coxsackievirus A16 (31
). Virological surveillance for measles virus and mumps virus since 1995 shows that the genotype H1 of measles virus and genotype F of mumps virus are the only genotypes found thus far in China, and subgenotype C4 of human enterovirus 71 and genotype B1 of coxsackievirus A16 have been continuously circulating in China since they were first detected in 1998 and 1999, respectively.
Although rubella virological surveillance has been successfully implemented in China, more viruses need to be collected from other provinces to establish a complete genetic baseline for the entire country. Ongoing molecular epidemiological surveillance of circulating rubella viruses is needed, especially when routine vaccination programs are initiated. Vaccination will considerably reduce the number of susceptible individuals and, consequently, decrease or eliminate endemic viruses, allowing detection of imported viruses.