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Slide 1 of 25 Influenza Surveillance in the DoD: 2009 - 2010 Armed Forces Health Surveillance Center (AFHSC) United States Air Force School of Aerospace.

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Presentation on theme: "Slide 1 of 25 Influenza Surveillance in the DoD: 2009 - 2010 Armed Forces Health Surveillance Center (AFHSC) United States Air Force School of Aerospace."— Presentation transcript:

1 Slide 1 of 25 Influenza Surveillance in the DoD: 2009 - 2010 Armed Forces Health Surveillance Center (AFHSC) United States Air Force School of Aerospace Medicine (USAFSAM) Naval Health Research Center (NHRC) DoD Global Influenza Network Partners (GEIS Operations) Presentation to the Vaccines and Related Biological Products Advisory Committee VRBPAC 22 February 2010 CAPT Kevin L. Russell, MD, MTMH, FIDSA** **Representing the DoD CONUS and OCONUS lab-based influenza surveillance activities

2 Slide 2 of 25 Briefing Outline PURPOSE : Provide a concise update to the VRBPAC on DoD influenza surveillance activities, 2009-2010 1.AFHSC a)Defense Medical Surveillance System—Health care utilization b)Laboratory network 2.Strain Circulation and Molecular Analyses a)pH1N1, H3N2, B 3.Vaccine Effectiveness a)AFHSC, NHRC, USAFSAM 4.Vaccine Safety 5.Population-Based Serology Studies

3 Slide 3 of 25 CAPT Russell//301-319-3041 DSN 285- AFHSC Operating Structure DIRECTOR Armed Forces Health Surveillance Center Dep Dir, AFHSC/ Director, GEIS DoD Serum Repository AFHSC HQ Support Science Advisor Executive Officer Resource Mgr Chief, Information Officer Chief, Epi and Analysis Chief, Communications, Standards, & Training Chief, GEIS Operations Data Management Epidemiology/ Analysis Surveillance Operations & Communications Surveillance Standards & Training AI/PI Surveillance GEIS Core Liaisons USPHS DHS WHO

4 Slide 4 of 25 Pre- Induction Post- Discharge MEPS 11.1 million persons 23.1 million records Hospitalizations 2.7 million records Ambulatory Data 162 million records Health Risk Assessments (Army) 575,000 records Immunizations 51.6 million records Casualty Data 40,600 AD Deaths Pre / Post-Deployment Health Assessments 6,336,114 forms Reportable Diseases 215,000 records Deployments 4.0 million records Serum Specimens (DoD Serum Repository) 46.1 million specimens Personnel Data 9.0 million persons 102.5 million records Focus: Active Duty & Reserve Component / Surveillance DMSS: Longitudinal Database

5 DoD Lab-based Influenza Surveillance - 2009

6 Slide 6 of 25 Breadth of AFHSC Influenza Surveillance Division of Epidemiology and Analysis – 1.4M AD records (health care utilization, immunizations, deployment, reportable diseases, etc) 12 data feeds into DMSS, additional in house Medical Surveillance Monthly Reports (MSMR), Adhoc requests, Studies/analyses, Routine reports/summaries Weekly influenza reports Vaccine safety and effectiveness studies Division of GEIS Operations – Approximately 500 locations in over 75 countries globally Military ; Local government/academic – Extensive characterization capabilities within the DoD Culture, HAI, PCR (battery), Sequencing – Rapid sharing of results with CDC and/or regional WHO reference centers Two DoD laboratories reported first four cases of 2009 A/H1N1 in the U.S. More than 40,000 samples collected and analyzed in 2009

7 Slide 7 of 25 DoD Global Influenza Activity (1 Sept 2009 – 31 Jan 2010) New = previous two weeks

8 Slide 8 of 25 Global Influenza Circulation October pH1N1 H3N2 sH1N1 Flu B

9 Slide 9 of 25 Global Influenza Circulation November pH1N1 H3N2 sH1N1 Flu B

10 Slide 10 of 25 Global Influenza Circulation December pH1N1 H3N2 sH1N1 Flu B

11 Slide 11 of 25 Global Influenza Circulation January pH1N1 H3N2 sH1N1 Flu B

12 Slide 12 of 25 Global Influenza Circulation February pH1N1 H3N2 sH1N1 Flu B

13 Slide 13 of 25 Summary of Circulating Strain Activity Laboratory confirmed influenza rates among US service members have declined since peaking in the Fall of 2009 Regional differences in virus co-circulation – Samples from European sites have all been 2009 A/H1N1 – Samples collected during the Fall of 2009 from Southeast Asia showed co- circulation of Influenza B, A/H3N2, and 2009 A/H1N1 viruses The 2009 A/H1N1 virus is the predominant virus currently circulating

14 Slide 14 of 25 Distribution of Sequenced A/H1N1 within the DoD, 2009 - 2010 CONUS OCONUS United States AfghanistanKorea AlaskaKuwait GuamKyrgyzstan HondurasUnited Arab Emirates IraqUkraine Japan CONUS OCONUS United States AfghanistanKorea AlaskaKuwait GuamKyrgyzstan HondurasUnited Arab Emirates IraqUkraine Japan 298 26 4 4 Distribution of Sequenced A/H1N1 Specimens within the DoD, 2009 - 2010 1 1 3 3 57 97 80 2 2 3 3 3 3 9

15 Amino Acid Substitutions (x100) 0 2.6 2 A/Florida/375/2009 A/South Carolina/3203/2009 A/Nevada/3460/2009 * A/Iraq/18529/2009 A/Nevada/143/2009 A/North Carolina/4358/2009 A/Texas/331/2009 A/Japan/3624/2009 A/Arizona/4156/2009 A/South Carolina/2260/2009 A/California/3770/2009 A/Florida/2412/2009 A/Connecticut/2033/2009 A/Georgia/3826/2009 A/United Arab Emirates/2757/2009 A/Guam/3656/2009 A/Korea/3163/2009 A/Colorado/1102/2009 A/Japan/4856/2009 A/Arizona/20285/2009 A/Florida/19340/2009 A/Korea/3619/2009 A/Arizona/3825/2009 A/Korea/1772/2009 A/Arizona/4887/2009 A/Texas/427/2009 A/Maryland/2635/2009 A/Maryland/2520/2009 A/Texas/732/2009 A/New Jersey/3792/2009 A/Colorado/653/2009 A/Iraq/4045/2009 A/Iraq/4051/2009 A/Ohio/4320/2009 A/Afghanistan/2953/2009 A/Ohio/674/2009 A/Japan/4372/2009 A/Japan/4081/2009 A/California/1763/2009 A/Japan/16700/2009 A/Japan/1888/2009 A/Maryland/3894/2009 A/Oklahoma/1631/2009 A/Maryland/2519/2009 A/Virginia/2393/2009 A/South Carolina/3652/2009 A/New Jersey/4768/2009 A/Texas/2465/2009 A/Illinois/4597/2009 A/Japan/3627/2009 A/Illinois/4877/2009 A/Massachusetts/2573/2009 A/Japan/4639/2009 A/Japan/4375/2009 A/Japan/4079/2009 A/Japan/4861/2009 A/Delaware/3213/2009 A/Delaware/3296/2009 A/District of Columbia/4386/2009 A/Nebraska/527/2009 A/Nebraska/4107/2009 A/Japan/3711/2009 A/Ohio/3660/2009 A/Texas/3852/2009 A/Korea/1751/2009 A/California/1879/2009 A/Korea/19735/2009 A/Texas/2253/2009 A/Kyrgyzstan/2926/2009 A/Nebraska/2630/2009 A/Massachusetts/3702/2009 A/Iraq/4697/2009 A/Iraq/4075/2009 A/Honduras/3234/2009 A/California/3784/2009 A/Kansas/1106/2009 A/Japan/3754/2009 A/North Dakota/19325/2009 A/Ohio/4319/2009 A/Oklahoma/3982/2009 A/North Carolina/4957/2009 A/Alabama/2395/2009 A/New Mexico/20448/2009 A/Massachusetts/3912/2009 A/Korea/3918/2009 A/Korea/4837/2009 A/Virginia/4518/2009 A/Utah/307/2009 A/Alaska/4171/2009 A/Alaska/3051/2009 A/Texas/4576/2009 A/United Arab Emirates/1461/2009 A/Washington/4363/2009 A/Washington/2184/2009 A/Iraq/1309/2009 A/Korea/19741/2009 A/Mississippi/261/2009 A/South Dakota/339/2009 A/Iraq/2133/2009 A/California/7/2009/pH1N1 NYMC X181A A/California/07/2009 S203T P83S I321V 2009 Vaccine *Reference Antigen July 09 (10) August 09 (5) September 09 (26) October 09 (299) November 09 (154) December 09 (74) “^” Create glycosylation motif “&” Loss of glycosylation motif “_” Parallel Mutation Site Protein identity compared to A/California/07/2009- like virus, 97.9 – 99.4% (n=568) 99.1 - 99.4%: (2-3 changes) 36% (201/568) 98.5 – 98.8%: (4-5 changes) 60% (341/568) 97.9 – 98.2%: (6-7 changes) 4% (25/568) Parallel amino acid changes at 27 sites – 20/27 within predicted epitope sites A/Iraq/18529/2009v selected as CDC HI reference antigen All annotated aa changes are comparisons of submitted specimens to HA1 region of A/California/7/2009 (H1N1) – like virus and do not relate to previous vaccine strains. Q293H I321 L32I K36E E112K H273Y N129D K22R V47I V47A T270A T270K T120A K283E A261D A197S A197T I116M D97N A48V A48S N156K V19I S157L A197S I295V D35Y V272A I295T T72A T72I N31D P137L P137H V199A V199I F114V D222E K54E 2009-10 DoD Influenza A/H1N1 HA1 - Phylogenetic Analysis

16 Protein identity compared to (n=7): A/Perth/16/2009 98.2 – 99.1% A/Brisbane/10/2007 97.4 – 98.2% 99.1 - 99.4%: A/Perth – 1A/Brisbane- 0 98.5 – 98.8%: A/Perth – 5A/Brisbane- 0 97.4 – 98.2%: A/Perth – 1A/Brisbane- 7 Parallel amino acid change at 261 (predicted epitope stie) 2009 – 10 Vaccine strain Previous Vaccine Strains July 09 August 09 October 09 December 09 “^” Create glycosylation motif “&” Loss of glycosylation motif “+” Receptor Binding Site (RBS) “_” Parallel Mutation Site +V223I &N133D +P227H T212A K158N K173Q N189K P194L E62K &N144K All annotated aa changes are comparisons of submitted specimens to HA1 region of A/Brisbane/10/2007-like viruses and do not relate to previous vaccine strains/ Amino Acid Substitutions (x100) 0 6.2 246 A/Perth/16/2009 A/South Carolina/10319/2009 A/Mississippi/15624/2009 A/Japan/3909/2009 A/Kuwait/4551/2009 A/Kuwait/4554/2009 A/Afghanistan/2950/2009 A/Kuwait/4562/2009 A/Brisbane/10/2007 A/Wisconsin/67/2005 A/California/7/2004 A/Wyoming/03/2003 A/Panama/2007/1999 A/Sydney/5/1997 R261Q 2009-10 DoD Influenza A/H3 HA1 - Phylogenetic Analysis

17 Amino Acid Substitutions (x100) 0 5.9 24 B/California/2650/2009 B/California/2986/2009 B/District of Columbia/20691/2009 B/Texas/19095/2009 B/Maryland/18932/2009 B/Korea/18724/2009 B/Brisbane/60/2008 B/Japan/3280/2009 B/Malaysia/2506/2004NH B/Hong Kong/330/2001 B/Florida/4/2006 B/Shanghai/361/2002 B/Sichuan/379/99 B/Beijing/184/93 Yamagata Lineage Victoria Lineage All DoD Flu B specimens fall within Victoria Lineage Protein sequence identity for DoD specimens (n=7) compared to B/Brisbane/60/2008 - 99.7% Predicted loss of glycosylation motif for 6/7 specimens All annotated aa changes are comparisons of submitted specimens to HA1 region of B/Brisbane/60/2008-like virus and do not relate to previous vaccine strains. B/ 2009-10 Vaccine strain September 09 October 09 November 09 “^” Create glycosylation motif “&” Loss of glycosylation motif L58P &N197D 2009-10 DoD Influenza B HA1 - Phylogenetic Analysis

18 Slide 18 of 25 Vaccine Effectiveness AFHSC – Retrospective analysis, case/control (1:4) of seasonal influenza vaccine against clinically apparent, laboratory-confirmed 2009 A/H1N1 associated illness Modest VE (22%): Many active duty with multiple prior vaccinations and unique experience with respiratory pathogen exposure Naval Health Research Center (NHRC) – Population-based, flu-confirmed, febrile-respiratory illness surveillance of recruits at 8 training centers (since 2003)**( Russell 2004; Strickler 2007) 03/04--94%; 04/05--86%; 05/06--92%; 06/07--87%; 07/08--81%; 08/09--79%; 09/10--insufficient cases after vaccination instituted USAF School of Aerospace Medicine (USAFSAM) – Population-based of observed as compared to expected influenza cases as determined by vaccination coverage**( Orenstein 1985; Farrington 1993) Estimate of vaccine effectiveness (not clinical VE) No VE demonstrated

19 Slide 19 of 25 Vaccine Effectiveness Unfortunately Unable to examine pandemic 2009 H1N1 vaccine effectiveness due to high seasonal vaccination coverage (~92%) and small case count occurring after pandemic vaccination

20 Slide 20 of 25 H1N1 Vaccine Safety Collaboration between MILVAX and AFHSC, in conjunction with the FDA's CBER and the CDC's Immunization Safety Office AFHSC’s DMSS searched weekly to identify all H1N1 vaccinations Outcomes – Anaphylaxis – Bell’s palsy – Idiopathic thrombocytopenia – Acute disseminated encephalomyelitis – Guillain-Barré Syndrome – Acute transverse myelitis – Optic neuritis Rapid cycle statistical analysis of aggregated data – Comparison to past 3 seasonal influenza vaccine campaigns – Identify in near real-time increased occurrences of outcomes

21 Slide 21 of 25 H1N1 Vaccine Safety Potential cases verified by FDA and DoD neurologists and immunologists Safety surveillance conducted on over 1 Million Service members receiving the Novel A(H1N1) vaccine There continues to be no increase in safety concerns compared to previous seasonal influenza vaccine campaigns

22 Slide 22 of 25 Susceptibility Studies Utilize DoD serum repository Determine existing rates of seroconversion – True incidence of 2009 H1N1 – HAI and Microneutralization – From 01 May—Feb 2010 Associate with – Known 2009 H1N1 infection – Medical care – Complications – Co-morbidities – Prior vaccinations

23 Slide 23 of 25 Summary The DoD maintains a global laboratory-based influenza surveillance program – military and civilian populations – underserved regions of the world Molecular analysis of 2009 A/H1N1 specimens indicate an overall protein identity of 97.9 – 99.4% compared to the vaccine strain Molecular analysis of A/H3 specimens supports a change of vaccine composition for the next season from A/Brisbane to A/Perth like strain We were unable to perform 2009 H1N1 vaccine VE determinations – Seasonal vaccination studies suggest at most mild protection toward 2009 H1N1 No increase in vaccine safety concerns

24 Slide 24 of 25 Acknowledgements AFHSC Dr. Kelly Vest Dr. Jose “Toti” Sanchez Dr. Angelia Eick LT Matthew Johns MAJ Ronald Burke CDR David Blazes COL Robert DeFraites MILVAX Ms. Hayley Hughes LTC Patrick Garman USAFSAM Ms. Alicia Guerrero Ms. Genny Maupin Major Thomas Gibbons Lt Col Victor Macintosh Col Paul Sjoberg NHRC Mr. Anthony Hawksworth Dr. Chris Myers CDR Patrick Blair CDR Dennis Faix

25 Slide 25 of 25 Questions COL Robert DeFraites, MD, MPH, Director, AFHSC Tel: 301-319-3245, E-mail: CAPT Kevin L. Russell, MD, MTMH, Director, DoD-GEIS Tel: 301-319-3041, E-mail:

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