Global Update on Measles Molecular Epidemiology

Abstract

Molecular surveillance of circulating measles variants serves as a line of evidence for the absence of endemic circulation and provides a means to track chains of transmission. Molecular surveillance for measles (genotyping) is based on the sequence of 450 nucleotides at the end of the nucleoprotein coding region (N450) of the measles genome. Genotyping was established in 1998 and, with over 50,000 sequence submissions to the Measles Nucleotide Surveillance database, has proven to be an effective resource for countries attempting to trace pathways of transmission. This review summarizes the tools used for the molecular surveillance of measles and describes the challenge posed by the decreased number of circulating measles genotypes. The Global Measles and Rubella Laboratory Network addressed this challenge through the development of new tools such as named strains and distinct sequence identifiers that analyze the diversity within the currently circulating genotypes. The advantages and limitations of these approaches are discussed, together with the need to generate additional sequence data including whole genome sequences to ensure the continued utility of strain surveillance for measles.

Keywords: elimination; genotyping; measles; molecular surveillance.

Figure 1

Phylogenetic tree with 28 measles N450 reference sequences. Data from MeaNS [8]. The evolutionary history was inferred using the maximum parsimony method. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (500 replicates) are shown next to the branches. The tree is drawn to scale, with branch lengths calculated using the average pathway method and are in the units of the number of changes over the whole sequence. Scale bar indicates number of nucleotides.

Figure 2

Year of last detection of measles genotypes. The last year of documented circulation reported to MeaNS [8] for all 24 genotypes is shown. Viruses with a date of 2024 are currently circulating. All other viruses have had transmission interrupted in the year depicted. Note that the chart does not specify the first year of detection of any genotype.

Figure 3

Number of submissions per genotype reported to MeaNS [8] 2019–2023.

Figure 4

Global distribution of major DSIds according to the WHO region, 2019–2023. The genotype is indicated by the color and pattern in each pie chart. The size of the pie chart indicates the number of submissions to MeaNS [8]. Only the eight most frequently detected DSIds are listed.

Figure 5

Phylogenetic tree of named strains of genotypes B3 and D8. Data from MeaNS [8], accessed 9 April 2024. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (500 replicates) are shown next to the branches. The tree is drawn to scale, with branch lengths calculated using the average pathway method and are in the units of the number of changes over the whole sequence. Scale bar indicates number of nucleotides.

Figure 6

Proportion of MeaNS submissions corresponding to the five most frequently reported named strains of genotypes B3 (shades of orange) and D8 (shades of blue), 2019–2023. Data from MeaNS [8], accessed 9 April 2024. NS = named strain.

Figure 7

Example for reporting to NVC [27]: Genotype B3 cases in the US 2021–2023. (Top) Chart format. Columns represent epidemiological weeks. Columns in grey are combined weeks without sequenced cases. The number in each cell indicates the number of identical sequences from cases with onset in that week. (Bottom) Curve format. The data and colors are the same as on top. Colors correspond to different DSIds.

Figure 8

Comparison of N450, MF-NCR and WGS. BEAST analysis of (A) N450 sequences, (B) MF-NCR sequences and (C) WGS of the same samples. X-axis indicates time scale. Purple bars indicate 95% confidence interval for time points of branching patterns. Black dots indicate high statistical support for branch points. Analysis of longer sequences improves statistical support for branching patterns and narrows confidence intervals. Data are based on published sequences [28], but annotations are simulated to show how the certainty of the tree shape and measurements are likely to change.

Figure 9

From [28], with permission of the authors. Use of WGS in combination with epidemiological data. Measles outbreak among Afghan refugees in the USA in 2021. (A) Red square indicates part of tree magnified in B. (B) X-axis indicates time. Blue bars denote 95% confidence intervals. Red arrows highlight epidemiologically linked cases. Grey arrows highlight cases without epidemiological links. (C) High number of nucleotide differences can rule out epidemiological linkage but low numbers do not always serve as proof of linkage. * WGS not available.