DoD Global, Laboratory-Based, Influenza Surveillance Program United States Air Force School of Aerospace Medicine (USAFSAM) Wright-Patterson Air Force Base, OH 2014-2015 Influenza Season Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

DoD collaborative program initiated 1999 Introduction DoD collaborative program initiated 1999 Funding: Armed Forces Health Surveillance Center – Division of the Global Emerging Infections Surveillance & Response System Operations (AFHSC/GEIS) Provide lab-based influenza surveillance 2014-15 season: 55 CONUS/36 OCONUS sites worldwide Collect respiratory specimens & questionnaires from individuals with influenza-like illness Process specimens in USAFSAM’s Epidemiology Laboratory Service Mission & Priorities Identify circulating viruses / detect new strains Share data and specimens with the Centers for Disease Control and Prevention (CDC) & the World Health Organization (WHO) Evaluate influenza vaccine effectiveness Weekly comprehensive surveillance report Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Beginnings 1976-1997: General Respiratory Surveillance/Research AF Influenza Program “Project Gargle”1 Letterman Army Institute of Research2 DoD overseas medical research labs (Brazil, Egypt, Indonesia, Kenya, Peru, Thailand) 3 1996: Presidential Decision Directive (NSTC-7) 4 1997: Global Emerging Infections Surveillance & Response System Operations (GEIS) 5 1998: Addressing Emerging Infectious Disease Threats: A Strategic Plan for the DoD6 Influenza surveillance named as the #1 priority 1999: Assistant Secretary of Defense, DoD (Health Affairs) Policy Memorandum7 Formal implementation of the DoD influenza surveillance program Outlines program functions and surveillance goals Appointed the Air Force Surgeon General as Executive Agent and management responsibility was given to what is now USAFSAM Note: References available in speakers notes section. Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Service Influenza Policy DoD ASD-HA: Sentinel Sites for the 2014-2015 Influenza Surveillance Program (24 July 2014) Service Specific Policy Air Force: Instruction 48-105: Surveillance, Prevention, and Control of Diseases and Conditions of Public Health or Military Significance (15 July 2014) Army: OP-ORD 13-63 (2013-2014 Influenza Vaccination Program) Reference e: ASD(HA) Memo ANNEX C: Sentinel site list Navy & Marine Corps: Message No. 6320 (Policy for the Use of Influenza Vaccine for the 2013-2014 Influenza Season) Reference f: ASD(HA) Memo Coast Guard: None Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Influenza-like illness (ILI) case definition Fever ≥ 100.5°F AND Program Overview Laboratory-based surveillance network with >80 sites across the DoD globally Sites aim to collect 6-10 respiratory specimens/week from active duty, dependents, and retirees who present to MTF clinics and meet a specific case definition: Influenza-like illness (ILI) case definition Fever ≥ 100.5°F AND Cough or sore throat Symptom onset < 72 hours Specimens shipped to and processed by the USAFSAM Epidemiology Laboratory Service (USAFSAM/PHE) (Shipping/testing costs covered) Test for influenza A & B and other respiratory viruses Select influenza viruses sequenced by molecular team Clinical and syndromic data analyzed by epidemiologists Weekly reporting to participating sites and DoD & civilian public health entities Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Program Overview CONUS Sites: 55 Air Force: 33 Army: 11 Navy & Marine Corps: 7 Coast Guard: 6 JTF CAPMED/DHA: 2 OCONUS Sites: 36 Air Force: 18 Army: 9 Navy & Marine Corps: 7 Coast Guard: 2 Submit to USAFSAM Submit to LRMC Submit to TAMC Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Military members and their families: Influenza and Military Populations Even with modern medical advances, influenza and influenza- like illness can cause high morbidity rates, undermining readiness Military members and their families: Are stationed where new strains are likely to appear Are highly mobile across the globe and could quickly spread a pandemic strain May live in areas that represent “gaps” in the CDC influenza surveillance network Training environments are well suited for the spread of emerging respiratory pathogens Highly immunized military plus electronic vaccination data registry facilitate rapid assessment of vaccine protection against emerging strains Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Examples 1918 Spanish Flu at Ft. Riley 1976 Swine Flu at Ft. Dix 2009 H1N1 at Randolph AFB Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Evolves rapidly & responsible for most epidemics and pandemics Refresher Influenza A Evolves rapidly & responsible for most epidemics and pandemics Divided into subtypes (Example: H5N1, H3N2) based on two surface proteins: Hemagglutinin (HA) Neuraminidase (NA) Influenza B Gradually changing virus Classified by strains based on their lineage: Currently Yamagata or Victoria Found primarily in humans Immunity-related changes to influenza A virus Changes to regions of the HA surface protein (called antigenic shift & drift) can affect human antibody responses to the virus Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Antigenic Drift & Shift Small gradual changes that occur over time and create a new strain that may not be recognized by immune system Reason that new influenza vaccine is manufactured and distributed each year Antigenic Shift Abrupt major change that produces a novel virus (not previously seen in humans) Result of direct animal-to-human transmission or mixing of human and animal viral genes within the same individual (reassortment) Most people have little or no protection against the new virus USAFSAM monitors these changes using molecular sequence analysis on influenza specimens. What does that look like? Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Distribution A: Approved for public release; distribution is unlimited Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

NORTHERN SEASONAL INFLUENZA VACCINE PRODUCED Surveillance Process and Vaccine Development FDA’s VRBPAC* meets to decide strains for annual flu vaccine USAFSAM DoD Global Lab-Based Sentinel Surveillance Sentinel Sites Participating Non-Sentinel Sites CDC/Viral Surveillance National Respiratory & Enteric Virus Surveillance System Labs (U.S.) WHO Influenza Labs NORTHERN SEASONAL INFLUENZA VACCINE PRODUCED DoD System Civilian System *Food and Drug Administration, Vaccines and Related Biological Products Advisory Committee Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Seed Viruses and Reference Strains from DoD Surveillance Contribution Reasons to participate: Constant changes to the influenza virus require ongoing collection and characterization of the strains Strains can undergo rapid changes, leading to pandemics of influenza; surveillance of viruses will detect these changes Updates to seasonal influenza vaccine based on surveillance findings National and international responses to emerging pandemic strains are triggered by surveillance data The DoD surveillance network helps fill surveillance gaps for parts of the world that civilian surveillance systems do not reach Offer surge / outbreak support RT-PCR results available in 48 hours after arrival at laboratory. Viral culture and, if negative, additional molecular testing may be performed Support for testing of novel viruses (e.g., MERS-CoV) Seed Viruses and Reference Strains from DoD Surveillance A/PR8/1945, an A strain isolated from a recruit in May 1943, plus B/Lee (Army) A/Texas/1/77(H3N2) (USAF) A/Philippines/2/82(H3N2) (USAF) A/Panama/2007/99 (H3N2) (USAF) A/California/4/2005 (H3N2) (USN) A/South Dakota/06/2007(H1N1) (USAF Base, Army Case) A/Texas/05/2009 (H1N1) (USAF) A/Iraq/18529/2009 (H1N1) (USAF) A/California/07/2009 (H1N1) (USN) Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Novel respiratory virus Early detection essential for control of emerging, reemerging, and novel infectious diseases (natural or intentional) Highly interconnected and transitive environment Expanding detection capabilities to a network of state and reference laboratories are critical Viral respiratory illness caused by a coronavirus not previously identified in humans Understanding of the virus and the disease continuing to evolve First reported September 2012 in the United Kingdom from a patient who recently traveled to Saudi Arabia and Qatar Secretary of Health and Human Services has declared that circumstances exist to justify authorization of emergency use of in vitro diagnostic tests for detection USAFSAM’s Epidemiology Laboratory Service has this testing capability, along with other DoD reference laboratories Middle East respiratory syndrome coronavirus (MERS-CoV) Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Surveillance Program Goals Prevent Influenza Infections Reduce Morbidity & Mortality Force Health Protection Identify current strains & outbreaks Analyze vaccine effectiveness Track genetic changes of viruses in circulation (molecular sequence analysis) Detect and monitor antiviral resistance Monitor severity trends Contribute to annual vaccine selection Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Site Specifics Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Cough AND/OR sore throat WITH symptom onset/duration < 72 hours Decision Tree for Influenza-Like Illness SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Cough AND/OR sore throat WITH symptom onset/duration < 72 hours Yes Fever ≥ 100.5 ̊ F ILI No Not ILI ILI Case Definition: Fever ≥ 100.5°F (38°C) with Cough OR Sore Throat ≤ 72 hours Not ILI: Not recommended to collect a specimen. However, there is flexibility for clinical judgment. If you suspect influenza or other respiratory viral infection, you can collect a specimen for testing. ILI: Collect nasal wash specimen (preferred method) or nasopharyngeal swab and submit to USAFSAM in viral transport medium (VTM) for testing. Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

What to do if…. There is an increase in ILI patients SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE There is an increase in ILI patients Continue submitting up to 10 per week, giving priority to the sickest or hospitalized patients and those presenting with respiratory distress (shortness of breath) Fewer than six patients meet the ILI case definition in a given week Send specimens for those who meet the ILI case definition You want to make sure specimens arrive at USAFSAM on a weekday Consider sampling patients early in the week You are in a busy clinic and would like to simplify case selection It may be convenient to designate 1 day a week for patient sampling to meet the 6-10 samples per week, for example, “Flu Mondays” A specimen has already been submitted for a patient in the past 14 days One specimen per patient is recommended; use clinical judgment in these situations Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Nasal Wash (NW) Kits USAFSAM NW collection kit includes: SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE USAFSAM NW collection kit includes: Sterile saline, collection cup, & bib VTM Biohazard bag Influenza Surveillance Questionnaire USAFSAM also provides: Shipping containers Shipping costs via FedEx To request collection kits: Use the current version of the “Supply Order Form” available (under Shipping/Training) at: https://gumbo2.area52.afnoapps.usaf.mil/epi- consult/influenza/lab NOTE: If an urgent public health need arises, contact the program via email for more kits at: usafsam.phrflu@us.af.mil Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Collection instructions are on the back of each questionnaire Nasal Wash SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Nasal wash collection method is preferred as it captures adequate volumes of original specimen for: Diagnostic testing Sequence analysis Specimen sharing Collection instructions are on the back of each questionnaire Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Influenza Surveillance Questionnaire SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Use the current season 2014-2015 questionnaire included in each nasal wash kit and available on the influenza surveillance program website Complete the questionnaire for each patient specimen Submit a hard copy of the questionnaire with each specimen Make a copy of each questionnaire for your records https://gumbo2.area52.afnoapps.usaf.mil/epi-consult/influenza/welcome Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Potential for specimen to be tested on multiplex respiratory panel Why are questionnaires important? SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Provide valuable epidemiological data such as vaccination and travel history Identify severe illness and hospitalized cases, which could signal important changes in the virus Can be used as a worksheet when you need to report hospitalized influenza case information in DRSi Potential for specimen to be tested on multiplex respiratory panel Specimen must test negative for influenza on PCR and meet ILI case definition Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

You can order the test in AHLTA/CHCS Ordering the Test SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE You can order the test in AHLTA/CHCS Order the RESPIRATORY CULTURE PNL (EPI), or panel with a similar name designated by your installation, in AHLTA/CHCS where available. If you have questions, consult your lab officer Two (or three) types of tests are performed as part of this panel: INFLUENZA VIRUS A/B PCR Reflex test (Multiplex Respiratory Panel) – Criteria must be met prior to performing this test (negative PCR, questionnaire submitted and meets ILI case definition) VIRAL CULTURE RESPIRATORY Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Storage & Shipping Best: Freeze specimen at -70°C and ship on dry ice: SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Best: Freeze specimen at -70°C and ship on dry ice: Specimens frozen at -20°C are not acceptable due to loss of viability of the viruses Please contact USAFSAM if dry ice or a -70°C freezer is not available at your site prior to the start of the season Use dry ice blocks or pellets rather than “snow” form For each 24-hour period of travel, each standard shipping box should contain a minimum of: 5 lb of dry ice for CONUS sites 15 lb of dry ice for OCONUS sites Acceptable: A specimen may be shipped on frozen gel packs at refrigerated temperature (2-8°C) only if received at the USAFSAM lab within 48 hours of collection from patient: Specimens received over 8°C or over 48 hours from collection cannot be accepted Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Epidemiology Laboratory Service 2510 Fifth Street, Bldg 20840 Shipping SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Use the FedEx number 425177729 (for surveillance testing only) and ship FedEx Priority Overnight to: USAFSAM/PHE Epidemiology Laboratory Service 2510 Fifth Street, Bldg 20840 WPAFB, OH 45433-7951 If you have laboratory or shipping questions, request your lab staff to call customer service at: (937) 938-4140, DSN 798-4140 For the comprehensive USAFSAM/PHE Laboratory Guide, please visit: https://kx2.afms.mil/kj/kx5/EPILab/Pages/home.aspx or https://gumbo2.area52.afnoapps.usaf.mil/epi-consult/influenza/lab Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Responses to Frequently Asked Questions SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Be sure to ship FedEx Priority or Standard Overnight® Do not ship FedEx First Overnight VTM tube should have at least two identifiers on the label, i.e., SSN/FMP, DOB, or name Package each specimen individually in biohazard bags with the questionnaire in the front pocket Specimens can be received M-F with limited Saturday hours If specimens must be shipped for Saturday delivery, please call USAFSAM lab at 937-938-4140 or DSN 798- 4140 to make arrangements before shipping A Continuity Binder can help when passing procedures on after personnel PCS or rotate Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Checking Results Test name: Influenza virus A/B PCR Test Name on Multiplex Usually available within 48 hours from receipt into laboratory Coronavirus (229E, HKU1, NL63, & OC43) Positive results: Influenza A or B Pandemic influenza A/H1N1 Human metapneumovirus Seasonal influenza A/H1 Parainfluenza 1-4 Influenza A/H3 RSV Influenza B Rhinovirus/enterovirus Negative result: Bordetella pertussis No influenza detected Chlamydophila pneumoniae Mycoplasma pneumoniae Test name: Final viral culture respiratory Positive result: Influenza A and B Detected (Organism specified) Adenovirus Enterovirus Not detected Parainfluenza 1-3 Respiratory syncytial virus (RSV) No respiratory virus isolated (after 10 days) Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Website Resources Site-specific surveillance dashboard Submission data SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Site-specific surveillance dashboard Submission data POC information Shipping/storage Welcome packet Weekly reports Other sentinel site resources Novel virus information Historical data Program publications https://gumbo2.area52.afnoapps.usaf.mil/epi-consult/influenza Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Influenza Dashboard SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE https://gumbo2.area52.afnoapps.usaf.mil/epi-consult/influenza/dashboard/ Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

Weekly Surveillance Report SELECT CASES COLLECT SPECIMENS COMPLETE QUESTIONNAIRES ORDER TEST STORAGE & SHIPPING CHECK RESULTS CHECK WEBSITE Distributed via email and websites: Sentinel sites AF bases Offices of the Surgeon General (all Services) Public health organizations DoD Health Affairs AFHSC/GEIS Collaborators CDC collaborators CDC Epi-X Distribution (local and state health departments) All who are interested Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014

USAFSAM Epidemiology Laboratory Service (PHE) The End <INSERT YOUR INSTALLATION POINT OF CONTACT INFO HERE> USAFSAM Epidemiology Laboratory Service (PHE) Email: usafsam.phecussv@us.af.mil Website: https://kx2.afms.mil/kj/kx5/EPILab/Pages/home.aspx Commercial (937) 938-4140 DSN 798-4140 USAFSAM Epidemiology Consult Service (PHR) Email: usafsam.phrflu@us.af.mil Website: https://gumbo2.area52.afnoapps.usaf.mil/epi-consult/influenza/ (CAC-required) Commercial (937) 938-3196 DSN 798-3196 Distribution A: Approved for public release; distribution is unlimited. Case Number: 88ABW-2014-3876, 19 Aug 2014