means and rubens for verification - who · means genotype diversity manual for the laboratory...

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

MeaNS and RubeNS for verification 8

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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