Measles near whole genome sequence data from an outbreak in 2013-2014 in the Netherlands
Measles is a highly contagious infectious disease and stays a major cause of global childhood morbidity and mortality. Molecular surveillance of measles virus (MV) is used for tracing transmission chains, by distinguishing between repeated introductions or endemic circulation. WHO guidelines used in the global measles surveillance network recommend sequencing of a 450 nucleotide region at the C-terminal end of the N gene (N450). However, given the low genetic variability of MV, whole genome sequencing would potentially increase the resolution of genomic sequencing to track transmission chains. In this study, we describe an amplicon-based nanopore sequencing protocol for generating near complete whole MV genome sequences (15,813 nucleotides; WGS). We applied this protocol to samples collected during an outbreak of measles in the Netherlands in 2013-2014, involving an estimated 30,000 cases, to quantify the sequence variation of WGS during this outbreak. While this was considered a clonal outbreak based on N450 sequencing, different genetic clusters were identified by phylogenetic analysis, defined by mutations present in the WGS, but not in the N450 region. Furthermore, differences in WGS in viruses detected early in the outbreak suggested that the outbreak started with at least 2 introductions. Notably, the number of single nucleotide polymorphisms between viruses detected early and late in the outbreak varied among clusters. Some of these clusters were supported by epidemiological data. These results can aid in interpreting sequence variation in MV during transmission chains and outbreaks in countries or regions approaching measles elimination.