Characterization of G2P[4] rotavirus strains causing outbreaks of gastroenteritis in the Northern Territory, Australia, in 1999, 2004 and 2009

Outbreaks of rotavirus diarrhea cause a large disease burden in the Alice Springs region of the Northern Territory, Australia. The introduction of the rotavirus vaccine Rotarix® has been associated with an increase in detection of G2P[4] strains in many countries. However, G2P[4] emergence has also been observed in vaccine-naive countries, suggesting a general global increase in the circulation of G2P[4] strains.A G2P[4] rotavirus outbreak occurred in 2009, 28months after the introduction of the Rotarix® vaccine and 43 children were hospitalized. Pre-vaccine introduction, G2P[4] strains were observed associated with large outbreaks in 1999 and 2004. To determine the genetic relationship between these strains whole genome sequence analysis was conducted on representative strains from each of the G2P[4] outbreaks, in 1999, 2004 and 2009. Phylogenetic analysis revealed the majority of genes from 2009 outbreak strain clustered with contemporary global strains, while the VP7 gene clustered with contemporary and older strains and was antigenically distinct to the majority of contemporary global G2P[4] strains; suggesting the strain was an intragenogroup reassortant. The 1999 and 2009 strains appear to share similar evolutionary origins, and both had a high degree of genetic identity to previously identified Australian and global strains. Conversely, the 2004 outbreak strain was more divergent in comparison to Australian and global strains.The 1999 and 2004 outbreaks likely occurred due to the accumulation of immunologically naïve children in the population following low levels of G2P[4] rotavirus disease in the community in the years prior to each outbreak. The 2009 outbreak was associated with moderate vaccine coverage in the population and vaccine efficacy against the strain was low. The circulation of this unusual strain in the population combined with low vaccine coverage and diminished vaccine efficacy likely contributed to the outbreak occurring in this population.