Chapter 7. Molecular epidemiology of measles and rubella

Mick Mulders


Overview

The genetic analysis of measles and rubella viruses has been well-documented as a valuable tool for characterizing outbreaks and tracking transmission pathways [1-12]. In addition, the identification of genotypes for confirmed cases is an important performance indicator for laboratory activities undertaken in support of national and global goals for measles and rubella elimination. The data collected can be used to assess the sensitivity of the surveillance to detect imported cases. In addition, the accumulated molecular surveillance data from the laboratory provide evidence for the impact of immunization programmes, including the interruption of endemic virus circulation, an essential criterion for the verification of elimination.

The descriptions of the temporal and geographic details of cases and outbreaks, as well as molecular characterization of the viruses are a vital component of the verification of elimination. The ability to identify a genotype is particularly important when the source of infection is unknown. However, there is an ongoing challenge to obtain adequate clinical samples to meet the goal for high quality virologic surveillance that is required for GMRLN laboratories. WHO recommends that molecular surveillance be conducted during all phases of measles and rubella control to provide an accurate description of the global distribution of genotypes.

There may be viruses with novel genotypes in circulation, particularly for rubella, since virologic surveillance for rubella has lagged that for measles. However, it is anticipated that as elimination programmes for measles and rubella progress, more of the recognized genotypes will join those considered to be inactive or extinct. The geographic associations that had initially proven to be epidemiologically useful for many of the measles genotypes are no longer valid since there are fewer genotypes circulating and most of these have a global distribution. For this reason, additional regions of the measles and rubella genomes have been identified or are under evaluation for inclusion in phylogenetic analyses to improve the ability to discern genetic differences among viruses within a genotype that reflect epidemiologic relationships.

The sections that follow will include the methodologies and links to protocols that are recommended for genotype determination by sequence analysis. In addition, the guidelines and limitations for the interpretation of molecular epidemiologic data will be discussed. Instructions for reporting genotypes, proposing new genotypes and nominating a virus variant as a named strain are included, along with detailed steps for accessing and navigating the measles nucleotide surveillance (MeaNS) and the rubella nucleotide surveillance (RubeNS) databases.