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DoD Global, Laboratory-Based Influenza Surveillance Program

Vaccines and Related Biological Products Advisory Committee Meeting February 18,2009. DoD Global, Laboratory-Based Influenza Surveillance Program. Naval Health Research Center San Diego, CA Patrick Blair, PhD, Commander, MSC, USN Chris Meyers, PhD Anthony Hawksworth .

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DoD Global, Laboratory-Based Influenza Surveillance Program

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  1. Vaccines and Related Biological Products Advisory Committee Meeting February 18,2009 DoD Global, Laboratory-Based Influenza Surveillance Program Naval Health Research Center San Diego, CA Patrick Blair, PhD, Commander, MSC, USN Chris Meyers, PhD Anthony Hawksworth USAF School of Aerospace Medicine Brooks City-Base, TX Victor MacIntosh, MD, MPH Lieutenant Colonel, USAF, MC Thomas Gibbons, PhD Major, USAF, BSC Alicia C. Guerrero, MPH Distribution Statement A: Approved for public release; distribution is unlimited. 311 HSW/PA No. 09-066, 17 Feb 09

  2. Outline • Introduction & history • Overview of sentinel & population-based surveillance • Description & highlights: epidemiology, laboratory, vaccination, molecular analysis • Discussion

  3. Origin of the program • 1976 US Air Force begins influenza surveillance Aims: • Isolate and identify circulating influenza virus • Detect emerging variants • Evaluate effectiveness of vaccine

  4. Sentinel (etiology) based surveillance USAF School of Aerospace Medicine (USAFSAM)* Brooks City-Base, Texas Population based surveillance** Naval Health Research Center (NHRC) San Diego, California DoD laboratory-based influenza surveillance program • *Formerly the program was located in the Air Force Institute for Operational Health (AFIOH) • **Recruits, Shipboard and Border Populations

  5. Collection methods (USAFSAM) Patient criteria: fever ≥ 100.5ºF and cough or sore throat (< 72 hr duration) Case definition for Influenza-like Illness ->USAFSAM & sentinel sites Collection kits are provided to sentinel sites Instructed to collect 6-10 specimens / week Preferred specimen is nasal wash Surveillance questionnaire (e.g. vaccine, symptom and travel history) Specimen collection

  6. DoD Global Influenza Surveillance.................IN ACTION

  7. DoD-GEIS Funding & Guidance Epi Services Laboratory DoD Global Influenza Surveillance.................IN ACTION

  8. DoD-GEIS Funding & Guidance Epi Services Laboratory Program guidance, routine reports and notifications Supplies FedEx, etc, Support Participating Sites Collect & ship Samples DoD Global Influenza Surveillance.................IN ACTION

  9. DoD-GEIS Funding & Guidance Epi Services Laboratory Program guidance, routine reports and notifications Conventional/Molecular Laboratory Methods Supplies FedEx, etc, Support Participating Sites Collect & ship Samples Flu Isolated DoD Global Influenza Surveillance .................IN ACTION

  10. DoD Global Influenza Surveillance .................IN ACTION DoD-GEIS Funding & Guidance Epi Services Laboratory Program guidance, routine reports and notifications Conventional/Molecular Laboratory Methods Supplies FedEx, etc, Support Participating Sites Collect & ship Samples All Molecular Sequences Vaccine Decisions Flu Isolated CDC Selected Samples

  11. 2007-2008 & 2008-2009 SeasonsResults by Week Collected 2007 2008 2009 2007- 08 season 2008- 09 season

  12. Comparison of seasons2007-2008 (full seasonal year) & 2008-2009 2007-2008 Season 2008-2009 Season Specimens processed: 2,155 Countries: 13 For example: Saipan Deployed sites: Kyrgyzstan, Kuwait, Iraq, Afghanistan Guam early season B Yamagata S. Korea Dec 2008 A/H3 from Osan AB, then A/H1 from Army hospital in Seoul • Specimens processed: 6,751 • Countries:20 For example: Antarctica Embassy sites in Asia (US Staff) Nepal • Ft. Gordon Cluster, Dec 2007 A/H1 • Ellsworth AFB, vaccine strain contribution July 2007 A/H3

  13. A Subtype & B Lineage Results by Week Collected(USAFSAM)CURRENT SEASON – ALL SITES

  14. Influenza Subtype Results for Season 2008-2009 Across DoD Commands

  15. Pacific Sites South Korea

  16. NHRC USACHPPM-S NMRC-D USACHPPM-EUR USAMRU-K AFRIMS DoD Military-based Sites Non DoD Beneficiaries Global, Lab-Based Influenza Surveillance Sites (USAFSAM) Developing Partners

  17. Vaccination Rates • AF AD 95.8% ANG 92.0% AFR 84.0% • All recruits are vaccinated – all services AD = Active Duty ANG = Air National Guard AFR = Air Force Reserve

  18. NRTC Great Lakes CGTC Cape May Fort Leonard Wood MCRD San Diego Fort Jackson Frt Benning MCRD Parris Island Lackland AFB Naval Health Research Center (NHRC), San Diego Influenza Surveillance among US Military Basic Trainees • NHRC conducts population-based surveillance for febrile respiratory illness (FRI) at 8 US military basic training centers • FRI rates tabulated weekly • Specimens and clinical data are collected systematically from consenting trainees • PCR and viral culture testing for influenza A/B, adenovirus, etc. • Clinical data include vaccination status, type of vaccine, and vaccination date

  19. NHRC Influenza Surveillance, 2008-09 • 70 lab-confirmed influenza A cases Oct 08 – Jan 09 • 67 (96%) A/H1 • HA sequencing of A/H1 isolates from recruits shows they are similar to an A/H1 strain circulating in the U.S. that has 5 amino acid mutations from the current A/H1 vaccine strain • 3 (4%) A/H3

  20. NHRC Influenza Surveillance, 2008-09 • Vaccine effectiveness calculation • Only considered periods when all trainees on base were vaccinated • Majority of recruit vaccination Oct-Jan was LAIV, > 90% • 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 81-94% VE against lab-confirmed influenza using this method during past 5 seasons • 2008-09 Results • 62 lab-confirmed cases (all A/H1) in this analysis • 26 cases among vaccinated, rate = 1.0/10,000 person-weeks • 36 cases among unvaccinated, rate = 5.1/10,000 person-weeks • VE (A/H1) = 79% (95% CI, 66-87%) • Other assumptions (7 days for coverage; 10% less vaccination) resulted in VE estimates of 83% and 66%, respectively • Vaccine appeared to be effective against A/H1 among U.S. military recruits

  21. Preliminary Vaccine Data USAFSAM • 2,155 specimens; 551 (25.6%) influenza isolates • 37.6% (207 of 551) identified vaccination status (quest avail) • 62.3% (129 of 207) characterized as vaccinated • 77.5% (n=100) LAIV; 22.5% (n=29) Injection % Distribution of Influenza Subtypes/Lineage by Vaccination Status (as of 07 Feb 2009)

  22. Laboratory method • Molecular analysis • Nucleic acid extraction • PCR analysis – A/H1, A/H3 and B • Sequencing of HA1 region for positive flu’s • Sequence analysis performed - data to CDC • Tissue culture analysis • Influenza A, B, PIV 1,2,3, RSV, Adeno • All positive tissue culture archived for additional testing • Archiving • Repeat or additional testing as requested by provider • CDC request for egg culture production and possible use as vaccine seed virus

  23. A/Japan---1 A/Japan/717y/2009 A/Japan/718y/2009 A/Japan/723y/2009 A/Japan/719y/2009 A/Kw-4,J-2,H-1,Kr-32,Kn-1 A/Korea/468k/2009 A/Korea/489s/2009 A/Korea/967s/2009 A/New Jersey-1 A/Korea/219s/2009 A/Korea/490s/2009 A/Korea---1 A/Korea/482s/2009 A/Japan/670k/2009 A/Korea-2 A/Korea/469k/2009 A/Korea/491s/2009 A/Japan--1 A/Korea/250s/2009 A/Japan/721y/2009 A/Korea--1 A/Korea/218s/2009 A/Kuwait/689b/2009 A/Kuwait/553a/2009 A/Korea/593s/2009 A/Korea/397s/2009 A/Korea/972s/2009 A/Korea-----1 A/Korea/485s/2009 A/Saipan/907/2009 A/Korea/488s/2009 A/Korea/92s/2009 A/Japan-1 A/Japan/864k/2009 A/Korea/597s/2009 A/Korea/976s/2009 A/Korea/974s/2009 A/Korea-1 A/Korea-25 A/Korea/467k/2009 A/Korea/473k/2009 A/Korea/474k/2009 A/Korea/475k/2009 A/Korea/477s/2009 A/Korea/478s/2009 A/Korea/398s/2009 A/Korea------1 A/Hawaii--1 A/Kr----1,NJ--1 A/Washington/257m/2009 A/Alaska/710/2009 A/Texas/402w/2009 A/Texas/382w/2009 A/Texas/601w/2009 A/Texas-1 A/Texas/641w/2009 A/Texas/615w/2009 A/TX-5, Kw--4 A/Texas/385w/2009 A/Texas/622w/2009 A/Texas/437w/2009 A/Arkansas/505/2009 A/Texas/519r/2009 A/Illinois/589/2009 A/Texas/590s/2009 A/Texas/293r/2009 A/Illinois/925/2009 A/Kuwait-1 A/H-3,Nv-1 A/South Carolina/588b/2009 A/South Dakota/661/2009 A/South Carolina/715b/2009 A/New Jersey/944/2009 A/Texas/683w/2009 A/Texas/697w/2009 A/Texas/698w/2009 A/Oklahoma/938t/2009 A/Guam-1 A/Illinois-1 A/Texas/392w/2009 A/Germany/535/2009 A/Kuwait/552a/2009 A/Nevada--1 A/Kenya-6 A/California/669t/2009 A/Kenya--1 A/Kenya---1 A/Kenya----1 A/Kenya------1 A/Kenya-5 A/Kenya-----1 A/Honduras----1 A/Honduras---1 A/Brisbane/59/2007 A/Honduras-1 A/Honduras--1 A/Honduras-3 A/Solomon Islands/3/2006 A/New Caledonia/20/1999 A/Beijing/262/95 6.8 Amino Acid Substitutions (x100) 6 4 2 0 K162M E169G Influenza A/H1 HA (HA1) Phylogenetic Analysis • Overall amino acid sequence identity for the 184 specimens sequenced 98.1 – 100% • 3 at 98.1% • 88 at 99.1% or more • 93 greater than 98.1% but • less than 99.1% • Parallel amino acid changes • at 141 and 185 S141N I184M G185A S141R S141K L69S S257I G152E G185V H192R D272G A189T All annotated aa changes are comparisons of submitted specimens to A/Brisbane/59/2007 and do not relate to previous vaccine strains N183S G185S I213V 2008 – 09 Vaccine strain Previous Vaccine strains January 09 (collection date) “_” Parallel Mutation Site G185N

  24. A/Kuwait/688b/2009 A/Kenya-4 A/Korea/330s/2009 A/Korea-1a A/Korea/487s/2009 A/Kenya-1h A/Korea/595s/2009 A/Kenya-1g A/Korea/60k/2008 A/Japan-1b A/Germany/555/2009 A/Japan-1a A/Germany/543/2009 A/Germany/554/2009 A/Germany/546/2009 A/South Dakota/662/2009 A/California/455t/2009 A/Guam-1 A/Germany/542/2009 A/Germany/551/2009 A/Germany/541/2009 A/Alaska/464/2009 A/Germany/537/2009 A/Germany/540/2009 A/Germany/532/2009 A/Germany/536/2009 A/Kenya-1i A/Kenya-3c A/Kenya-7 A/Kyrgyzstan-1b A/Kyrgyzstan-1a A/Germany/531/2009 A/Ku-7,Af-2,G-7,Kr-3 A/Germany/539/2009 A/Germany/547/2009 A/Germany/556/2009 A/Germany/533/2009 A/Germany/534/2009 A/Germany/549/2009 A/Kenya-1a A/Kenya-1b A/Kenya-1c A/Kenya-1d A/Kenya-11 A/Kenya-1e A/Kenya-2 A/Kenya-3 A/Germany/545/2009 A/Kenya-1f A/Kenya-3a A/Korea-15 A/Kuwait/494aa/2009 A/Kyr-6,Kw-1 A/Germany/544/2009 A/Brisbane/10/2007 A/Wisconsin/67/2005 A/California/7/2004 A/Wyoming/03/2003 A/Panama/2007/1999 A/Sydney/5/1997 5.9 4 2 0 Amino Acid Substitutions (x100) Influenza A/H3 HA (HA1) Phylogenetic Analysis • Overall amino acid sequence identity for the 118 specimens sequenced 97.9 – 99.4% • 15 at 97.9% • 73 at 99.1% or more • 30 greater than 97.9% but • less than 99.1% • Parallel amino acid changes • at 173 T48A I267V 2008 – 09 Vaccine strain Previous Vaccine strains January 09 (collection date) December 08 (collection date) ^ Create glycosylation motif & Loss of glycosylation motif “_” Parallel Mutation Site N278K K173Q K173E ^S45N V112I &N144S L3F, I25L, T131N, R142G, K173N, K158R All annotated aa changes are comparisons of submitted specimens to A/Brisbane/10/2007 and do not relate to previous vaccine strains P194L K173E K173Q

  25. B/Guam/6719/2008 B/Guam/6722/2008 B/Guam/6962/2008 B/Guam/7123/2008 B/Guam/7126/2008 B/Guam/6724/2008 B/Guam/6720/2008 B/Guam/6961/2008 B/Guam/6963/2008 B/Guam/7180/2008 B/Guam/6844/2008 B/Guam/7063/2008 B/Texas/7753/2008 B/Texas/7807/2008 B/Guam/6843/2008 B/Guam/6845/2008 B/Guam/6850/2008 B/Florida/4/2006* B/Guam/7262dA/2008 B/Kenya/7511/2008 B/Kenya/7583/2008 B/Kenya/7523/2008 B/Kenya/7524/2008 B/Kenya/7584/2008 B/Kenya/6884/2008 B/Kenya/6902/2008 B/Honduras/6829/2008 B/Kenya/6892/2008 B/Honduras/7427 B/Honduras/7426 B/Kenya/6899/2008 B/Kenya/6910/2008 B/Kenya/7531/2008 B/California/447L/2009* B/Oklahoma/312t/2009 B/Washington/7231b/2008 B/Shanghai/361/2002 B/Sichuan/379/99 B/Beijing/184/93 B/Texas/497w/2009* B/Oklahoma/512t/2009* B/Arkansas/599/2009* B/Kuwait/232b/2008 B/Texas/7632/2008 B/Texas/405w/2009* B/Texas/406w/2009* B/Texas/668s/2009* B/Texas/663s/2009* B/Germany/529/2009* B/Arkansas/600/2009* B/Malaysia/2506/2004** B/Hong Kong/330/2001 6.8 6 4 2 0 Amino Acid Substitutions (x100) Influenza B HA (HA1) Phylogenetic Analysis • Overall amino acid sequence identity for the 35 B Yamagata lineage specimens sequenced to date • 98.2 – 99.7%* • Overall amino acid sequence identity for the 11 B Victoria lineage specimens sequenced to date • 97.3 – 97.9%** 2008 – 09 Vaccine strain Previous Vaccine strains January Yamagata Lineage Victoria Lineage

  26. A Ten Seasonal Year Review1998-1999 through 2008-2009

  27. Acknowledgements • Armed Forces Health Surveillance Center • DoD-Global Emerging Infections Surveillance and Response System (GEIS) • NHRC, USAFSAM • Overseas Research Laboratories & Host Countries (AFRIMS, USAMRU-K & NMRCD-Lima) • Military Health System • Landstuhl Regional Medical Center • Tripler Army Medical Center • Medical & public health staff • USACHPPM-S, USACHPPM-EUR Contact Us! influenza@brooks.af.mil (210) 536-3471 or DSN 240-3471 https://gumbo2.brooks.af.mil/pestilence/influenza/

  28. Questions & Discussion

  29. Backup Slides

  30. Backup slide - NHRC VE Calculation Methods • Vaccine effectiveness calculation • Only considered periods when all trainees on base were 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 • From Dec 08 – Jan 09, there were 319,002 person-weeks at the 6 centers included in the analyses • Estimated 248,107 vaccinated and 70,895 unvaccinated • Influenza rates (cases/10,000 person-weeks) were: • Vaccinated: 26/248,107 = 1.0 • Unvaccinated: 36/70,895 = 5.1 • Results in a VE of 79%

  31. Preliminary Vaccine Data USAFSAM

  32. Proposed VE Study – USAFSAM • VE Case Control Study • Period of Review • 27 Sept 2008 – 07 Feb 2009 • Population • Patient Medical Encounters – AF Clinics • Cases : lab confirmed influenza patients • Controls 1:4 match based on DMIS (clinic), date of encounter, and age group • Selected from non-ILI visits • Excluded cases: deployed AD, BMTs, Lackland AD aged 18-19. • Vaccination Status • Matched cases and controls against the AFCITA database. Questionnaire data not used.

  33. Preliminary VE Analysis USAFSAM Among cases of lab confirmed influenza matched to non-ILI patient controls matched by age, base clinic visited and date of visit Influenza cases and controls by Vaccination status Influenza cases and controls by Vaccination withFluMist *Statistically significant, p<0.05

  34. A/Korea/7995s/2008 A/Korea/8072k/2008 A/Korea/7859o/2008 A/Korea/7858o/2008 A/Korea/7855o/2008 A/Korea/7854o/2008 A/Korea/7853o/2008 A/Korea/7851o/2008 A/Korea/7723o/2008 A/Korea/7722o/2008 A/Korea/7719o/2008 A/Korea/7714o/2008 A/Korea/248s/2009 A/Korea/115o/2008 A/Korea/60k/2008 A/Korea/90s/2009 A/Korea/93s/2009 A/Korea/330s/2009 A/Korea/487s/2009 A/Brisbane/10/2007 A/Wisconsin/67/2005 A/California/7/2004 A/Wyoming/03/2003 A/Panama/2007/1999 A/Sydney/5/1997 5.2 4 2 0 Amino Acid Substitutions (x100) HA1 Phylogenetic Analysis South Korean Influenza A/H3 Specimens with completed vaccine questionnaires* All annotated aa changes are comparisons of submitted specimens to A/Brisbane/10/2007 and do not relate to previous vaccine strains HA1 Protein sequence identity = 97.9 – 99.4% 2008 – 09 Vaccine strain Previous Vaccine strains *15/19 previously vaccinated L3F I25L T131N R142G K158R K173Q P194L

  35. A/Japan/7338x/2008 A/California/455t/2009 A/Guam/7178/2008 A/Japan/154y/2008 A/Guam/7124/2008 A/Alaska/464/2009 A/Guam/7261/2008 A/Kuwait/494aa/2009 A/Kuwait/291aa/2009 A/Guam/7396/2008 A/Guam/6981/2008 A/Guam/7054/2008 A/Kuwait/688b/2009 A/Brisbane/10/2007 A/Wisconsin/67/2005 A/California/7/2004 A/Wyoming/03/2003 A/Panama/2007/1999 A/Sydney/5/1997 4.6 4 2 0 Amino Acid Substitutions (x100) HA1 Phylogenetic Analysis Non-South Korean Influenza A/H3 Specimens with completed vaccine questionnaires* All annotated aa changes are comparisons of submitted specimens to A/Brisbane/10/2007 and do not relate to previous vaccine strains HA1 Protein sequence identity = 99.1– 99.4% 2008 – 09 Vaccine strain Previous Vaccine strains *4/13 previously vaccinated

  36. DoD authority/policy for global influenza surveillance 1IOM. 1992. Emerging Infections: Microbial Threats to Health in the United States. Washington, DC: National Academy Press. 2CISET (Committee on International Science, Engineering, and Technology). 1995. Infectious Disease a Global Threat: Report of the National Science and Technology Council. Working Group on Emerging and Re-emerging Infectious Disease. Washington, DC: Committee on International Science, Engineering, and Technology 3NSTC (National Science and Technology Council, Executive Office of the President). 1996. Presidential Decision Directive NSTC-7: Emerging Infections. Washington, DC: National Science and Technology Council, Executive Office of the President. 4DoD-GEIS (Department of Defense Global Emerging Infections Surveillance and Response System). 1998. Addressing Emerging Infectious Disease Threats: A Strategic Plan for the Department of Defense. Washington, DC: Walter Reed Army Institute of Research. 5Bailey S. 1999. Policy for DoD Global, Laboratory-Based Influenza Surveillance. Memorandum for Surgeon General of the Army, Surgeon General of the Navy, Surgeon General of the Air Force, Deputy Director for Medical Readiness, J-4, the Joint Staff. U.S. Department of Defense, Health Affairs, Washington, DC, February 3, 1999.

  37. Vignette:Ft Gordon Dec 2007 Vignette 1: Investigation of an Influenza A Outbreak at an Advanced Military Training Site, Ft. Gordon, GA An influenza outbreak occurred among active duty (n=28) and dependents (n=2) stationed at Fort. Gordon U.S. Army Garrison in Georgia in December of 2007. Fort Gordon houses several active duty units and includes training facilities for Advanced Individual Training in Signal Corp military occupational specialties, the Dwight D. Eisenhower Army Medical Center (EAMC) and is home to the Southeast Regional Medical Command. There are approximately 30,000 military and civilian employees on post. In January of 2008, the USAFSAM laboratory received 33 influenza A isolates for molecular characterization from Fort Gordon US Army Garrison in Georgia. Molecular analysis revealed that the Ft. Gordon strains were antigenically unique compared to other US strains previously sequenced by the USAFSAM laboratory. USAFSAM matched these record results with SADR data and results were forwarded to USACHPPM for a comprehensive follow up epidemiologic investigation. Thirty cases were contacted for interview via email and telephone and interviewed between April and May 2008. The active duty members averaged 19 yrs of age, with 67% (20) males and 33% females (10). The predominant symptoms among interviewed cases were fever >90% cough 88%, fatigue 88% and congestion 71%. A large majority of cases were hospitalized, 88% with an average of about 2 self reported bed days upon admission to Eisenhower Army Medical Clinic.

  38. Vignette: Submission of Vaccine Strain Ellsworth AFB July 2007 Vignette 2: Submission of Vaccine Strain from Ellsworth AFB, SD The 2008-09 trivalent influenza vaccine contains an A/Brisbane/59/2007 (H1N1)-like virus, an A/Brisbane/10/2007 (H3N2)-like virus, and a B/Florida/4/2006-like virus. One of these strains, the Brisbane/59-like, was identified through the DoD Lab-Based, Global Influenza Surveillance Program at the USAF School of Aerospace Medicine (SAM) and served as the seed virus for the H1 component of the live, attenuated influenza virus (LAIV) vaccine (aka FluMist®). A prior Air Force member and current Army National Guard member and their beneficiaries were assigned to Ellsworth Air Force Base, South Dakota for their primary care. Four members of this family were seen at the base clinic in July 2007 presenting with influenza-like illness (i.e. fever, cough, sore throat). A travel history was noted, which may explain the presence of influenza illness in the northern hemisphere during non-influenza season. Specimens were collected and sent to the laboratory at USAFSAM, where they were processed through the standard procedures of viral culture and molecular characterization. Two of the patients were reported to have Influenza A by USAFSAM. Specimens underwent further molecular characterization at the USAFSAM laboratory, and were then sent to CDC for antigenic characterization. One of them was selected as a seed virus by MedImmune, Inc. for the LAIV. Although the strain was selected for the LAIV and not the traditional, injectable trivalent influenza vaccine (TIV), this contribution to the LAIV is still significant since use of the LAIV is on the rise in military populations.

  39. NHRC USACHPPM-S NMRC-D USACHPPM-EUR USAMRU-K AFRIMS DoD Military-based Sites Non DoD Beneficiaries Global, Lab-Based Influenza Surveillance Sites (USAFSAM) Developing Partners

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