DoD Global, LaboratoryBased Influenza Surveillance Program

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DoD Global, Laboratory-BasedInfluenza
Surveillance Program

• Sequence Analysis
• and
• Vaccine Effectiveness Overview

Maj Thomas Gibbons, PhD, Virologist Chris Myers,
PhD, Molecular Biologist Angela Owens, MPH,
Epidemiologist Jason Garner, MS, Molecular
Biologist Anthony Hawksworth, Epidemiologist
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Background

• Seasonal Influenza
• Sentinel site surveillance
• - DoD military sites worldwide
• - Countries collaborating with DoD overseas
  research sites

• Population-based surveillance
• DoD recruit training sites (8)
• Select Navy ships
• Border Infectious Disease Surveillance (BIDS)

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Background

• Collection Methods
• - Patients must have Fever 100.5ºF and cough or
  sore throat (for less than 72 hrs)
• - Specimen collection kits are provided to
  collect 6-10 specimens/week
• - Surveillance Questionnaire (vaccination,
  symptom, and travel history)
• Laboratory Methods
• - Reverse Transcriptase Polymerase Chain
  Reaction (RT-PCR)
• Universal Influenza A and Influenza B
• - Viral Culture
• Influenza A, Influenza B, Adenovirus,
  Parainfluenza,
• Respiratory Syncytial Virus (RSV), and
  Enterovirus
• - 100 of influenza isolates are subtyped and
  sequenced

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2007-2008 Season (as of 19 Feb 08)
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Vaccine EffectivenessDescriptive Review
Preliminary Data

• Period of Review
• 30 Sept 2007 09 Feb 2008 (non-recruits)
• 01 Aug 2007 09 Feb 2008 (recruits)
• Population
• US military recruits (population-based
  surveillance)
• US Active Duty members (sentinel site
  surveillance)
• DoD beneficiaries (sentinel site surveillance)
• Outcome
• Laboratory-confirmed influenza
• Reverse Transcriptase polymerase chain reaction
  (RT-PCR)
• Viral culture
• Covered by Vaccination
• Vaccination date gt14 days prior to clinic visit
  date
• Patients with vaccination date prior to August
  classified as unvaccinated

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Sentinel Site SurveillancePreliminary Data

• 2,570 specimens 562 (21.9) influenza isolates
• 36.1 (203 of 562) identified vaccination status
• 77.3 (157 of 203) identified as covered by
  vaccine
• 68.1 (n107) LAIV 30.0 (n47), Injection, 1.9
  (n3) Not Specified

• Influenza Subtype
• A-type pending 31.8 (n50)
• A/H1 39.5 (n62)
• A/H3 24.2 (n38)
• B-type pending 4.5 (n7)

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Population-Based SurveillancePreliminary Data

• 205 lab-confirmed influenza A cases Aug 07 Feb
  08
• 59 (29) A/H1
• 74 (36) A/H3
• 72 (35) type pending (weeks 4 and 5)

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• Vaccine effectiveness calculation
• Only consider periods when all trainees on base
  are vaccinated
• Trainees assumed covered by vaccination 14 days
  after arrival/receiving the vaccine
• Proportion unvaccinated at each site estimated
  as those within their first 14 days of arrival
• e.g., in 8-week training programs, 2/8 (25) of
  the population was assumed to be unvaccinated
  at any given time
• Previous estimates of 86-94 VE against
  lab-confirmed influenza using this method during
  past 4 seasons
• 2007-2008 Results from Basic Trainees
• 102 lab-confirmed cases (40 H1, 61 H3, 1 type
  pending) in this analyses
• 34 cases among vaccinated, rate 2.9/10,000
  trainee-weeks
• 68 cases among unvaccinated, rate 18.6/10,000
  trainee-weeks
• VE 85 (95 CI, 77-90)
• Other assumptions (7 days for coverage 10 less
  vaccination) resulted in VE estimates of 89 and
  75, respectively
• VE by subtype
• VE (H1) 54 Mostly Clade 2b strains
• VE (H3) 92 Brisbane strain variants

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Population-Based Surveillance, 2007-2008

• Overall VE remains strong among basic trainees
• On the low end of previous four years of VE
  estimates
• Reduced effectiveness against Influenza A/H1
  subtype

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Influenza B Field IsolatesHA1 HA Phylogenetic
Analysis
Population US Active Duty, DoD beneficiaries,
and non-D0D personnel Timeframe July 2007 to
present Location US, Africa, Antarctica,
Asia, South Pacific

• 78.0 (39 0f 50) isolates collected in Nepal,
  Thailand, the Philippines
• 66.7 (4 of 6) isolates collected in 2008 within
  US are of the Yamagata lineage
• 58.0 (29 of 50) isolates belong to B/Victoria
  lineage 99.0-99.7 sequence identity

Victoria Lineage
Yamagata Lineage
2006-07 vaccine strain
Current Reference Strain
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Influenza A (H1N1) Field IsolatesHA1 HA
Phylogenetic Analysis
T90K R149K E276K
Population US Active Duty, DoD beneficiaries,
and non-D0D personnel Timeframe July 2007 to
present Location US, Africa, Middle East,
Asia, South Pacific
Clade 2

• 9.8 (5 of 51) isolates characterized as Clade 1
  all collected from Honduras
• Clade 2 isolates collected from US (Alaska, HI,
  SD, TX), Guam, Saipan, Philippines, South Korea,
  Nepal, Japan, Thailand, Qatar, Kenya
• Clade 2 subgroup highlighted by change at
  position 46

Y101H R212K K144E T269N
T90R
S46N
T90K
Y256F
Clade 1
2006-07 vaccine strain
2007-08 vaccine strain
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Influenza A (H1N1) Field Isolates continued
Population US military recruits and
Border Infectious Disease Surveillance
(BIDS) Timeframe July 2007 to present
Location US

• Clade 2 isolates collected from US (CA, IL, MO,
  SC, TX)
• Majority of isolates are Clade 2B

2006-07 vaccine strain
2007-08 vaccine strain
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Influenza A (H3N2) Field IsolatesHA1 HA
Phylogenetic Analysis
L3F K83N L157S K173N
Population US Active Duty, DoD beneficiaries,
and non-D0D personnel in allied countries.
Timeframe July 2007 to present Location
US, Central America, Asia, Africa, South Pacific

• 85.3 (58 of 68) of representative H3N2 isolates
  possess changes G50E, D122N, K140I, I223V
• H3N2 isolates collected in 2008 within the US
  possess additional changes L3F, K83N, L157S and
  K173N
• 14 overseas and domestic H3N2 isolates collected
  in 2007 of the 2007-8 season antigenically
  characterized by CDC as A/Brisbane/10/2007-like
  via HAI assays

G50E D122N K140 II223V
N144D
R142G
current vaccine strain
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Influenza A (H3N2) Field Isolates continued
Population US military recruits and BIDS
Timeframe July 07 to present Location US

• All sequenced representative isolates possess
  changes G50E, D122N, K140I, and I223V
• All sequenced isolates collected in 2008 within
  the US possess additional changes L3F, K83N,
  L157S and K173N
• All BIDS sequenced isolates have either N96K or
  E280K mutations

current vaccine strain
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Acknowledgements

• Global Emerging Infections Surveillance and
  Response System (GEIS)
• Centers for Health Promotion and Preventive
  Medicine (CHPPM) / Army Medical Surveillance
  Activity (AMSA)
• Air Force Clinical Informatics Branch
• Centers for Disease Control and Prevention (CDC)
• Landstuhl Regional Medical Center
• Sentinel sites in the DoD Global Influenza
  Surveillance Program

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Contact Information

• Air Force Institute for Operational Health
• - Sentinel Site Surveillance
• Influenza_at_brooks.af.mil
• Naval Health Research Center
• - Population-Based Surveillance
• NHRC-FRI_at_med.navy.mil

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BACKUP SLIDES
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2007-2008 Season (as of 19 Feb 08)