8th Global Measles and Rubella LabNet
Meeting, Sept 2010
Key Recommendations
GLOBAL MEASLES AND RUBELLA MANAGEMENT MEETING
15-17 March 2011
Salle B, WHO Headquarters, Geneva, Switzerland
David Featherstone
EPI / IVB
WHO Geneva
2
Outline
What are the challenges for the LabNet?
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Implications for achieving Elimination Quality Indicators
Reporting data
Quality Assurance
New Laboratory Procedures
Funding
Summary
WHO Vaccine Preventable Disease Lab Network
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3
Global LabNet Meeting
Participants
WHO Vaccine Preventable Disease Lab Network
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Implications for LabNet in achieving Elimination
Indicators (WER No 49, 2010, 85, 490-495)
ELISA IgM testing:
– ≥ 2/100,000 (non-measles rash/fever cases) per year & ≥ 80%
serum samples collected
 Workload increase estimated extra ~50,000 cases / yr
 Mainly Pakistan and India moving to case based
surveillance
 India planning 3 new labs 2011 (~$100,000)
 LabNet has proven surge capacity
– Measles IgM cost ~ $ 3 -11 per sample (depending on batch
size)
– Rubella IgM cost ~ $ 4.50 -17 per sample
WHO Vaccine Preventable Disease Lab Network
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Implications for LabNet in achieving Elimination
Indicators (WER No 49, 2010, 85, 490-495)
Virus detection:
– Measles elimination: The absence of endemic
measles cases:
– Re-establishment of endemicity: continuous
transmission of indigenous measles virus for a
period of > 12 months:
– >80% of laboratory-confirmed measles outbreaks
have adequate samples for virus characterization
in an accredited lab
WHO Vaccine Preventable Disease Lab Network
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Current challenges for improving molecular
surveillance
African region:
– Building molecular capacity in Uganda and CIV
Molecular surveillance gaps:
– Sequencing capacity available but limited sample
collection for virus detection
– Enhanced molecular surveillance using Oral fluid

Trials in India, Benin, CIV, Kenya, Malawi and Zimbabwe
WHO Vaccine Preventable Disease Lab Network
Molecular surveillance recommendations
Reference and sequencing laboratories
– determine their capacity to reach surveillance indicators
– determine the additional resources needed
Laboratory and field surveillance programmes
– collaborate to enhance molecular surveillance
Greater molecular capacity needed with documented
accuracy
– training programmes
– molecular proficiency programme established
Data Reporting
Data Issues: Measles and Rubella Laboratory Tested
Cases Reported to WHO HQ 2010*
WHO
region
Member states
reporting
(expected)
Rubella
2010
Specimens
received
Tested
Positive
Tested
Positive
AFR
31 (46)
18,151
18,151
6,757
12,605
1,963
AMR
30 (35)
11,582
5,347
22
5,678
134
EMR
21 (21)
12,242
11,615
3,873
9,760
1,042
EUR
46 (53)
27,110
22,325
4,994
21,590
936
SEAR
11 (11)
5,284
4,968
1,697
3,524
1,547
WPR
12 (27)
16,897
15,658
4,141
13,617
3,606
Total
153 (193)
91,266
78,064
21,484
66,774
9,228
Data source: surveillance DEF file
Data in HQ as of 8 Jan 2011
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Measles
2010
* As of Jan 2011
WHO Vaccine Preventable Diseases Lab Network
Data Issues: Measles and Rubella Laboratory Tested
Cases Reported to WHO HQ 2010*
WHO
region
Member states
reporting
(expected)
Specimens
received
Tested
Positive
6,757
Rubella
2010
Tested
Positive
South Africa outbreak
18,359 laboratory
12,605
1,963
confirmed
2010
AFR
31 (46)
18,151
18,151
AMR
30 (35)
11,582
5,347
EMR
21 (21)
12,242
11,615
3,873
9,760
1,042
EUR
46 (53)
27,110
22,325
4,994
21,590
936
SEAR
11 (11)
5,284
4,968
1,697
3,524
1,547
WPR
12 (27)
16,897
15,658
Total
153 (193)
91,266
78,064
Data source: surveillance DEF file
Data in HQ as of 8 Jan 2011
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Measles
2010
* As of Jan 2011
WHO Vaccine Preventable Diseases Lab Network
~ 50,000
(2008)
22 / year
5,678
134
China not
reporting 3,606
4,141
13,617
21,484
66,774
9,228
22,037 from Country
reports
Data reporting: Recommendations
LabNet encouraged to work with their national
surveillance programmes to reconcile
laboratory and field surveillance data
Data sent to WHO according to agreed upon
reporting requirements
Sequencing data reporting
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WHO Global genotype databases: Current Status
Viruses submitted dating from 1954 to 2011
Data as of 28 Feb 2011
WHO
Database
No. of
viruses
Genotypes
Countries
and
Territories
WHO
Regions
Proportion with
GenBank entries
Measles
8912
23
+ 1 prov.
131
6
37%
Rubella
773
9
+ 4 prov.
44
6
36%
MeaNS database (HPA/WHO)
N – 450bp – 5542 sequences
N – full – 5 sequences
H – full – 503 sequences
WHO Vaccine Preventable Disease Lab Network
Measles Genotype data submitted to WHO Database
1600
Total number of countries
submitting virus data per year
Number of countries submitting
virus data per region
58
1400
55
6
64
1200
55
4
57
8
1000
9
WPR
SEAR
EUR
Number of viruses submitted
10
14
800
2
24
31
600
11
3
39
3
4
EMR
AMR
AFR
21
30
13
22
400
20
26
3
4
200
17
12
9
0
2002
2003
2004
2005
2006
2
2007
Year of onset
WHO Vaccine Preventable Disease Lab Network
10
3
9
2008
9
2
19
2009
10
3
17
2010
10
2011
2010 incidence
2010 Distribution of
measles genotypes
West Africa inset
West Europe inset
Genotype:
Incidence:
(per 100'000)
B2
<0.1
B3
≥0.1 - <1
D4
≥1 - <5
D5
≥5
D8
No data reported
D9
H1
Chart proportional to
number of genotypes
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1
The boundaries and names shown and the designations used on this map do not imply the
expression of any opinion whatsoever on the part of the World Health Organization concerning
the legal status of any country, territory, city or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border
lines for which there may not yet be full agreement.
China: Measles isolates and genotyping results, 2009
2009: 270 cases H1a measles virus reported to database
D9 (1 case)
D4 (1 case)
Yunnan
d11
(17 cases)
Unpublished data provided by
Xu Wenbo
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Recognition of new genotypes
d11 MVi/Menglian.Yunnan.CHN/47.09/1. Virus to be provided by China CDC.
Genotype B3 sequences from Libya, Tunisia and Sudan should be considered
as a third cluster in genotype B3. Virus to be provided by Institut Pasteur de
Tunis.
Reference viruses for Rubella genotypes 1h, 1i, and 1j have been identified.
These viruses to deposited in the WHO rubella virus strain banks
The recent changes in the list of recognized rubella and measles genotypes
should be published in the WER
A steering committee to be formed to review and refine the protocols for
accepting and distributing sequence information via MeaNS and the WHO
Database
WHO should develop a mechanism for rapidly notifying LabNet of important
developments such as detection of a new lineage or genotype
WHO Vaccine Preventable Disease Lab Network
Higher resolution sequencing
D6 strains in Germany and Belarus
Data Provided by Luxemburg Laboratory
N gene
NPH gene
1 month
Recommendation:
Select laboratories to
evaluate and identify
when appropriate to
6 months
implement
UKR
BEL
UKR
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Quality Assurance
LabNet Proficiency test performanceMeasles IgM Panels
Panel No.
≥ 90% correct
(Pass)
00801 n=46 (2001)
96%
00702 n=17 (2002)
88%
01002 n=66 (2003)
95%
00703 n=99 (2004)
90%
00704 n=115 (2005)
94%
00508 n=142 (2006)
98%
00607 n=164 (2007)
98%
00705 n=173 (2008)
99%
00805 n= 171 (2009)
98%
00905 n= 220 (2010)
99%
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Quality Assurance Recommendations
More comprehensive analysis of IgM proficiency testing
and reporting
Introduction of proficiency test for molecular techniques
More comprehensive training & post training
assessments
WHO Vaccine Preventable Disease Lab Network
New Procedures
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Point of care rapid measles assay
The measles rapid point of
care (POC) shows
promising sensitivity and
specificity compared with
detection of IgM in serum
WHO Vaccine Preventable Disease Lab Network
POC to be further validated
using oral fluid samples
collected under routine
field conditions
Documentation of new procedures
Alternative samples to serum
for measles and rubella
M & R PCR QC
programme
QC for Oral fluid
Real time PCR; M & R
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Standards for
measles serosurvey
New sequencing primers
for measles and rubella
Rapid Point of
care assays
Validated and in process of implementation
WHO Vaccine Preventable Disease Lab Network
In process of validation
Funding
Current LabNet Estimated Costs
$1,600,000
$1,400,000
$1,200,000
Estimated shortfall
$1,300,000
Shortfall
Funds Identified 2011
$1,000,000
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$800,000
$600,000
$400,000
$200,000
$0
Lab Support
Meetings
Consumables
Kits
WHO Vaccine Preventable Disease Lab Network
Training
Travel
Equipment
Funding recommendations
LabNet should endeavour to find additional
resources and new partners
Countries encouraged to include laboratory
support in their surveillance budgets
Additional funds for training, to:
– Maintain the current high level of LabNet
performance
– Strengthen sequencing capacity
Summary
LabNet has capability to meet increased
surveillance needs
– Some capacity will need to be developed
Capacity building and extra testing comes at a
cost, not all of which is realised
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Thank you to all our LabNet Supporters
CDC
WHO
Korean CDC
National MsOH
IFFIM
Luxemburg Gov't
Merck
Measles Initiative
HPA
Labs belonging to LabNet
WHO Vaccine Preventable Disease Lab Network
Programmes sharing
resources
Polio
JE
YF