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DoD Global, Laboratory-Based Influenza Surveillance Program

DoD Global, Laboratory-Based Influenza 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

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DoD Global, Laboratory-Based Influenza Surveillance Program

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  1. 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

  2. NRTC Great Lakes CGTC Cape May Fort Leonard Wood MCRD San Diego Fort Jackson Frt Benning MCRD Parris Island Lackland AFB Background • Seasonal Influenza • Sentinel sitesurveillance • - 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)

  3. 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

  4. 2007-2008 Season (as of 19 Feb 08)

  5. 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 >14 days prior to clinic visit date • Patients with vaccination date prior to August classified as unvaccinated

  6. 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% (n=107) LAIV; 30.0% (n=47), Injection, 1.9% (n=3) Not Specified • Influenza Subtype • A-type pending: 31.8% (n=50) • A/H1: 39.5% (n=62) • A/H3: 24.2% (n=38) • B-type pending: 4.5% (n=7)

  7. 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)

  8. 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

  9. 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

  10. 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

  11. 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

  12. A_California_NHRC_04_2008(H1N1).seq A_Missouri_NHRC_01_2008(H1N1).seq F263L A_California_NHRC_33_2007(H1N1).seq A_Illinois_NHRC_33_2007(H1N1).seq A_Illinois_NHRC_35_2007(H1N1).seq A_Illinois_NHRC_36_2007(H1N1).seq A_Illinois_NHRC_37_2007(H1N1).seq A_Illinois_NHRC_38_2007(H1N1).seq A_Illinois_NHRC_39_2007(H1N1).seq A_Illinois_NHRC_40_2007(H1N1).seq A_Illinois_NHRC_41_2007(H1N1).seq A_Illinois_NHRC_42_2007(H1N1).seq A_Illinois_NHRC_45_2007(H1N1).seq A_Illinois_NHRC_52_2007(H1N1).seq A_Missouri_NHRC_02_2008(H1N1).seq A_Missouri_NHRC_03_2008(H1N1).seq A_Missouri_NHRC_04_2008(H1N1).seq A_Missouri_NHRC_05_2008(H1N1).seq A_Illinois_NHRC_51_2007(H1N1).seq D45N R192K E276K A_Illinois_NHRC_50_2007(H1N1).seq T90K, Y101H, V169A, N190D,R212K, K144E, W254R, T269N, H324P A_Illinois_NHRC_46_2007(H1N1).seq A_Illinois_NHRC_44_2007(H1N1).seq A_Illinois_NHRC_43_2007(H1N1).seq R149K T197K A193T, G240R A_South Carolina_NHRC_15_2008(H1N1).seq A_Texas_NHRC_11_2007(H1N1).seq S46N, I56K, K90R, R192M, A193T SolomonIslands_Vaccine.pro A_NewCaledonia_20_1999(H1N1)official.pr 3.5 2 0 Amino Acid Substitutions (x100) Influenza A (H1N1) Field Isolatescontinued 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

  13. L3F K83N L157S K173N Influenza A (H3N2) Field IsolatesHA1 HA Phylogenetic Analysis 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

  14. A_Georgia_NHRC_24_2008(H3N2).seq A_South Carolina_NHRC_18_2008(H3N2).seq V20L A_South Carolina_NHRC_14_2008(H3N2).seq A_South Carolina_NHRC_09_2008(H3N2).seq A_South Carolina_NHRC_23_2008(H3N2).seq A_Georgia_NHRC_21_2008(H3N2).seq A_Missouri_NHRC_13_2008(H3N2).seq S199P A_South Carolina_NHRC_11_2008(H3N2).seq K173Q A_South Carolina_NHRC_01_2008(H3N2).seq A_Georgia_NHRC_17_2008(H3N2).seq A_South Carolina_NHRC_24_2008(H3N2).seq A_Georgia_NHRC_23_2008(H3N2).seq R150K A_Georgia_NHRC_25_2008(H3N2).seq A_South Carolina_NHRC_02_2008(H3N2).seq A_California_NHRC_20_2008(H3N2).seq A_Georgia_NHRC_02_2008(H3N2).seq A_Georgia_NHRC_07_2008(H3N2).seq A_Georgia_NHRC_13_2008(H3N2).seq A_Georgia_NHRC_18_2008(H3N2).seq L3F, K83N, L157S, K173N A_Oklahoma_NHRC_03_2008(H3N2).seq A_South Carolina_NHRC_07_2008(H3N2).seq A_California_NHRC_03_2008(H3N2).seq A_California_NHRC_34_2007(H3N2).seq I58V A_California_NHRC_06_2008(H3N2).seq A_Oklahoma_NHRC_02_2008(H3N2).seq K173E A_California_NHRC_01_2008(H3N2).seq A_California_NHRC_35_2007(H3N2).seq G50E, D122N, K140I, H195Y, I223V N7D A_California_NHRC_07_2008(H3N2).seq N96K G5R A_California_NHRC_11_2008(H3N2).seq A_California_NHRC_05_2008(H3N2).seq E280K A_California_NHRC_02_2008(H3N2).seq A_California_NHRC_36_2007(H3N2).seq A_Wisconsin_67_2005(HA).pro 2.3 2 0 Amino Acid Substitutions (x100) 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

  15. 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

  16. Contact Information • Air Force Institute for Operational Health - Sentinel Site Surveillance Influenza@brooks.af.mil • Naval Health Research Center - Population-Based Surveillance NHRC-FRI@med.navy.mil

  17. BACKUP SLIDES

  18. 2007-2008 Season (as of 19 Feb 08)

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