means and rubens for verification - who · means genotype diversity manual for the laboratory...
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MeaNS and RubeNS for verification
Kevin Brown
5 December 2017
Genotype disappearance?
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Genotype 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
B2 1 12 52 7 0 0 0 0 0 0
B3 15 93 385 335 1082 583 1409 548 668 1211
D4 425 338 666 2025 927 134 37 66 46 15
D5 114 17 0 0 0 0 0 0 0 0
D8 76 37 96 246 832 1694 1222 1299 1482 1453
D9 26 28 41 225 91 79 91 33 88 17
D11 0 6 1 0 0 0 0 0 0 0
G3 0 0 25 51 1 15 5 0 0 0
H1 157 144 158 29 66 181 4850 3167 2592 493
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Measles sequences by genotype
Manual for the laboratory diagnosis of measles and rubella virus infection
WHO – EPI, WHO/IVB/07.01: 2nd edition 2007 3 MeaNS and RubeNS for verification data to mid 2016
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Genotype B3 phylogeny over last 5
years
4,021
sequences
4 MeaNS and RubeNS for verification WHO naming convention: MVi or MVs/city.ISO/wk.year/number [genotype]
Genotype B3 phylogeny over last 5 years
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Genotype D8 phylogeny over last 5 years
6,784
sequences
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Genotype D8 phylogeny over last 5 years
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MeaNS Genotype Diversity
Manual for the laboratory diagnosis of measles and rubella virus infection
WHO – EPI, WHO/IVB/07.01: 2nd edition 2007 8 MeaNS RubeNS Update 2015
Genotype data in MeaNS clearly shows a reduction in the number of
genotypes
Is this simply sampling bias?
Interpreting diversity in sequences maybe counter-intuitive
In outbreaks get less diversity
Multiple importations – greater diversity
Overall, appears to be a decrease in diversity with linked transmission
chains across countries and regions
Indicates the success of the global program
Monitoring diversity can be useful at a regional or country level
Need more sequences/sampling in some regions for monitoring
diversity to be useful at a global level
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Named strains Analysis (2012) suggested that ‘sub-genotyping’ was unlikely to be of great benefit
Although N450 is a ‘hypervariable’ region in the genome, the substitution rate
indicates that there should be less than 1 substitution/year
Sequences with identical N450 could be used for tracking outbreaks.
Would not expect >2 substitutions/6 months
Therefore:
Try to identify the earliest example of a sequence with a specific N450
Use this sample’s WHO name to be the designated named strain name
The named strain name does NOT indicate where the virus has come from
The N450 sequence of the named strain must be available in a public database
ie GenBank so that it can be used globally.
Anyone can nominate a strain to be a recognised ‘named strain’
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MeaNS database Measles Nucelotide Surveillance database Database for storing measles sequences
Started in 2006
Seeded with data from ELSM study in Europe/UK data/Genbank
data
Hosted by PHE Colindale
MeaNS and RubeNS for verification
Tools for:
Genotyping
Comparison/phylogeny with viruses in
other countries
Finding identical ‘strains’ (N450)
Completing information for ASU
Reporting ability to WHO (regional
offices and HQ)
Ability to upload to GenBank
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~ 37,000 sequences in MeaNS
Summary tools
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Country summary
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ASU update
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Downloaded csv file
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Each unique N450 is given a sequence id
If it is a named strain that will be also
labelled
This can be used to identify identical
strains within country
Can use pivot charts to analyse further
Mapping of genotypes or strains
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Measles in UK, 2012
Mapping of discarded cases
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Measles in UK, 2016
RubeNS www.who-rubella.org
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19 Measles sequence diversity 19 MeaNS and RubeNS for verification
genotype
Line listing for ASU
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