This document discusses WHO's plans for expanding global respiratory syncytial virus (RSV) surveillance. A pilot phase from 2016-2018 tested the feasibility of leveraging existing influenza surveillance networks. The pilot was successful and identified several key findings. The next phase from 2019-2021 will expand surveillance to more countries, focus on children under 2, include RSV typing and genetic sequencing, and estimate disease burden. The objectives of RSV genomic characterization are outlined. Issues around sequencing protocols, bioinformatics, and data sharing are discussed. The document argues expanded and systematic RSV strain surveillance is critical for vaccine development and monitoring effectiveness.

1. WHO global RSV surveillance
schema for future planning
Moving from RSV detection to
systematic sequence analysis.
Maria Zambon
Public Health England

3. WHO Pilot phase (2016-18)
3-y project to pilot a
strategy to leverage
capacities and test
feasibility of GISRS for
RSV surveillance
– without interfering
with influenza
surveillance
- Evidence-base to
inform guidelines for
RSV vaccine
introduction
- Seasonality, global
circulation of RSV
- Disease burden
- High risk groups
- Epi and lab standards
- Case definition
performance
- Incremental costs
- Feasibility
- Platform for special
studies
- Case definition
- Fever
- Apnea / sepsis
- 0-<6m, 6m-<5y, 5-
<65y, 65+y
- Case based clinical
data
- 1000 specimens per
year
- All year round
Rha et al. S Africa
36% RSV missed with SARI
Saha et al. India
50% missed if fever included

4. Pilot Countries

5. • Feasible to leverage influenza surveillance for RSV
– No adverse impact on GISRS
– Well accepted
– Collateral benefits for influenza surveillance
• Enough case-load to screen for RSV
• RSV burden highest in infants
• Extended SARI / ARI case definition – high sensitivity
– Inclusion of fever significantly decreases the sensitivity to
detect RSV
– Apnea, sepsis – high specificity in infants <6mo age
• Five scientific papers ready for submission
• RSV surveillance strategy being revised
– https://apps.who.int/iris/bitstream/handle/10665/259853/9789241513203-
eng.pdf;jsessionid=6D73862F7358CF21C81B467046BD7F5F?sequence=1
Learnings from the Pilot

6. ….. onto phase II (2019-21)
Phase I Phase II Rationale
Geographical
representation
2-3 countries / WHO
region
+ 1 to 2 GAVI-eligible / early
adopter countries
• GAVI VIS (2021-25)
• Wider geographical representation
Age groups All age groups Focus on <2y • RSV burden highest in infants
• RSV vaccine for infants via MI
Virus detection RSV detection, typing
optional
RSV typing & establish
framework for sequence
analysis
• Global circulation of RSV-A, RSV-B
• Association with disease severity
• Future monitoring of VE
Genetic
sequencing
Not included Pilot in a few national
laboratories
• GSD scarce, largely from the US
• Demonstrate feasibility of WGS
• Baseline to map changes post-vaccine
• Geographical sequence variability
• Relate viral genotype to age, clinical
severity, virulence
ICD code-
based RSV
surv.
Methodology developed
based on German data
Validate methodology in
other country contexts
• Sustainability, complementarity
Surveill. based
BoD estimates
Explored availability of
denominator-related
data
Estimate RSV associated
hospitalization burden
• BoD estimates to inform RSV vaccine
policies

7. WHO : The objectives of RSV genomic
characterization
• Characterize representative global viral diversity, particularly in LMICs
• Better understand the global evolutionary phylogeographic dynamics of
RSV
• Demonstrate the feasibility of large-scale whole genome sequencing of
RSV
• Help to establish a baseline of RSV diversity prior to the introduction of RSV
vaccines
• Source suitable reference viruses for molecular testing and phylogenetic
analyses
• Identify RSV strains with potential resistance to monoclonal antibodies
• Identify RSV strains with potential resistance to novel antiviral drugs

8. RSV Molecular surveillance
What questions do we have
• Is there genetic drift in areas of genome used for
detection
• Is there genetic or antigenic drift in areas important for
antibody or CMI
• Do genetic changes correlate with important antigenic
changes
• Are there any important virulence determinants
• Do any changes impact on interventions
• What changes impact on human antibody reactivity
• Host cell selection
• partial vs complete genome

9. Molecular Surveillance
How much sequence is necessary ?
• Sample selection
• RNA virus evolution (G).
• No recombination, but insertion & deletion
• Antigenic variation
• Targets of interventions (F & others)
• Monitor detection targets (N and others)
• CMI
• Virulence determinants ?
• Host cell selection… ?

10. RSVdetectionPCRs–primerlocations
Needforsystematicreview
PHE RSV A 1838-1900
PHE RSV B 1819-2034
CDC RSV 3254-3337
Commercial ??
Other in house ?????

11. Planning of Phase 2
Y1 2019-2020
EQA to all labs for typing
Ref labs work together to define framework for sequence analysis
Samples shared from Phase 1
Reference labs sequence materials from Phase1
Y2 2020-2021
Ref labs lessons learnt from Sequencing Phase 1 materials
Establish data analysis platforms and quality metrics for future global
virologic surveillance
Begin sequencing Phase 2 materials
Y3 2021-2022
Continued Reference lab sequence analysis of representative samples Phase 2
Sample size calculations for sequencing
Country sequencing expanded as appropriate

12. Issues
• Resourcing arrangements
• Sequencing Protocols
• Bioinformatics analysis pipelines
• Quality assurance for sequence data
• Repository for sequence data
• Data curation
• Phylogenetic methods
• Data tools for analysis
• Reference viruses
• Data sharing agreements

13. Final Remarks
• Strain diversity information critical for product
development and product efficacy
• Moving from project based to systematic
sampling
• Embedded in national surveillance systems
• Characterisation approaches need to be
sustainable and much more real time
• Interventions targeted at H & LMICs, but data
on strain diversity not representative.

14. How is Europe Interacting
• Quality assurance schemes
• European projects ( RESCEU)
• Seninel
• ECDC ?