1. Laboratory Surveillance of Non-Influenza Respiratory Viruses in the State of Maryland For Public Health Preparedness 1 William A. Murtaugh Centers for Disease Control and Prevention/Association of Public Health Laboratories Emerging Infectious Diseases Laboratory Training Fellow Maryland Department of Health and Mental Hygiene Laboratories Administration Capstone Advisor: Maria Paz Carlos, Ph.D, DVM

2. Outline 1. Overview 2. Objectives 3. Methods 4. Results 5. Implications for Public Health Preparedness 6. Limitations and challenges of laboratory surveillance for respiratory viral pathogens 7. Conclusions 2

3. Respiratory Viral Disease Infants and Children - Majority of hospitalizations due to infectious disease Adults – Reinfection Range of disease severity, Influenza-like Illness (ILI) Common viral agents: non-influenza respiratory viruses Respiratory syncytial virus (RSV) Parainfluenza virus (PIV) subtypes I, II, and III Adenovirus (AdV) No Vaccines against these viruses! 3

4. A Cornerstone of Public Health Preparedness State of Maryland Department of Health and Mental Hygiene Laboratories Administration Division of Virology and Immunology 201 W. Preston St. Baltimore, MD Identify, characterize and study distribution patterns of viral pathogens of public health importance Data used by local health department, medical, regulatory and law enforcement professionals throughout the state. Examples of collaborations and partnerships: CDC, FDA, EPA, FBI. Primary Stakeholder: Citizens of Maryland Results presented in state, national and international conferences, scientific papers and journals. Participation in the CDC NREVSS and WHO Influenza Surveillance Programs A comprehensive surveillance program is valuable during a pandemic, as seen during the 2009 H1N1 Influenza Pandemic. 4

5. 5 Seasonal Influenza RSV PIV - 1 PIV - 3 PIV - 2 Oct. Nov. Dec. Jan. Feb. Mar. Apr. May AdV Seasonal Trends in the Northern Hemisphere WHO declared dates of 2009 H1N1 Influenza Pandemic: April 24, 2009 – August 10, 2010 2009 H1N1 Influenza Pandemic → → 2008 2008 2008 2009 2009 2009 2009 2009 PIV-1 = Fall (Sept. – Nov.) PIV-2 = Fall (Sept. – Nov.) PIV-3 = Spring (Mar. – May) AdV = Jan. – Dec. RSV = Winter (Oct. – May) Influenza virus = Winter (Oct. – May)

6. Objectives To Provide a retrospective analysis of laboratory tests for three non-influenza viral pathogens: RSV, PIV (types I, II, and III), and AdV. Characterize the burden and severity of non-influenza respiratory viral disease throughout the year and particularly during the influenza season. Explain the public health implications of continual monitoring of circulating respiratory viral strains 6

7. Methods July 2002 through June 2011 (9 years) (n=1041) respiratory specimens tested by cell-culture. Annual Summary: tests performed, virus identified, positivity rates October 2008 through May 2011 (n=4912) 2008-2009 Influenza Season 2009 H1N1 Influenza Pandemic 2010-2011 Influenza Season Positive specimens stratified by geographic distribution, respiratory disease severity, age and sex. 7

8. 2002-2011 Annual Summary of Non-Influenza Respiratory Viral Pathogens 8 Year Respiratory Virus by Virus Isolation Total No. Isolated Total Tested % Positive Respiratory Syncitial VirusParainfluenza VirusesAdV No. Tested No. Positiv e % Positive No. Tested PIV- 1 PIV- 2 PIV- 3 % Positive No. Tested No. Positive % Positive 2002400.001080111.8510210.9832141.40 20038200.006723110.7417521.1479290.75 20049200.005393010.7410600.0047370.54 200540940.989034110.6621331.411315250.85 200648930.614893041.43489163.27264895.32 2007528142.655280020.3852861.14235284.36 200877660.777761020.39776182.32277763.48 20093244260.8032442416171.763244371.1412032443.70 2010955252.629555561.68955212.20629556.49 201164450.786441251.2464471.09206443.11 Total7223831.1588584426401.2472321111.53305100413.04

9. 9 Temporal Trend Analysis October 2008 – May 2011

10. Temporal Trend Analysis October 2008 – May 2011 PIV RSVAdV

11. Geographic Distribution of Cases October 2008 through May 2011) Total Non-Influenza RVPs Detected N=200

12. Geographic Distribution of Cases 12 2008-2009 Influenza Season (October 2008 – May 2009) Total Non-Influenza RVPs Detected N=26

13. Geographic Distribution of Cases 13 2009 H1N1 Influenza Pandemic (April 2009 – August 2010) Total Non-Influenza RVPs Detected N=151

14. Geographic Distribution of Cases 14 2010-2011 Influenza Season Total Non-Influenza RVPs Detected N=23

15. All Non-influenza RVPs - Disease Severity by Sex 15

16. All Non-influenza RVPs - Disease Severity by Age 16

17. Number of Deceased Cases by Viral Pathogen Identified during the 2008-2009 Influenza Season (n=1) and the 2009 H1N1 Influenza Pandemic (n=10) 17 a. Ageb. Sex

18. Implications for Public Health Preparedness Aid state epidemiologists with outbreak investigations Private or municipal site closings Community mitigation Create situational awareness - clarify disease burden, identify risk factors Characterize changes in virulence Timing is everything…State public health labs have a direct connection to state and federal public policy makers. Without them, the exchange of critical information is delayed. Quality etiologic evidence, which inform proper policies and guidelines, are required to prioritize limited public health resources and justify the rationale of implementation. 18

19. Implications for Public Health Preparedness Isolation of cases Use and timing of antiviral prophylaxis (improper use of antibiotics) – *NREVSS study Immunization strategies or vaccine development Detection of drug resistance Importance of cell-culture! 19

20. Limitations and Challenges of Laboratory Surveillance for Respiratory Viral Pathogens Resource limitations Confirming the etiology of influenza-like illnesses (ILI) can take a significant amount of time and resources. Sensitivity of cell-based methods of viral detection depends on the quality of specimen (viability). “garbage in, garbage out” Specimen submitters not representative of all counties Testing volume can be difficult to predict or control 20

21. Conclusions This retrospective laboratory surveillance data emphasize the temporal impact of non-influenza respiratory viruses. Overlapping seasonal patterns and general presentation of ILI symptoms can make clinical interpretation confusing, as well as implementing effective treatment and infection control measures difficult. In collaboration with epidemiologists, the public health laboratory surveillance efforts serves as a critical tool to define the impact of circulating respiratory viruses in outbreak, morbidity/mortality cases the community, and during a pandemic. 21

22. Acknowledgements I would like to thank Ms. Beth Resnick, Director of the Public Health Practice and Training Program at the JHSPH for her support of my research and training activities. A special thank you to all the Virus Isolation Laboratory Scientists at DHMH Laboratories Administration Division of Virology and Immunology for their assistance, inspiration and guidance. The Virus Isolation Group: Heather Peters Benjamin Healey Mandy Tran Marci Ziese Barbara Anderson I am sincerely appreciative of Dr. Jack DeBoy and Dr. Robert Meyers. Lastly, many thanks to Dr. Maria Paz Carlos, the Chief of the Division of Virology and Immunology and my mentor, for her patience, understanding, and unending support of my personal and professional development. 22

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24. References 24 13. American Academy of Pediatrics. Respiratory Syncitial Virus. In: Pickering LK, ed. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th Ed. pp. 560-569. Elk Grove Village, IL: American Academy of Pediatrics. 2009 14. American Academy of Pediatrics. Parainfluenza Viral Infections,. In: Pickering LK, ed. Red Book: 2009 Report of the Committee on Infectious Diseases. 26th Ed. p. 454-455. Elk Grove Village, IL: American Academy of Pediatrics. 2009 15. NREVSS: List of Participating Labs. National Center for Immunization and Respiratory Disease. 4 March 2010. http://www.cdc.gov/surveillance/nrevss/labs/list.html. Accessed 15 Oct. 2011. 16. World Health Organization. Manual for the laboratory diagnosis and virological surveillance of influenza. WHO Press. 2011. pp.25 17. Leland, D., et al. Role of Cell Culture for Virus Detection in the Age of Technology. Clinical Microbiology Reviews. Vol. 20:1. pp. 49-78. 2007. 18. Mahony, J., et al. Detection of Respiratory Viruses by Molecular Methods. Clinical Microbiology Reviews. Oct. 2008. Volume 21, No. 4, p. 716-744. 19. Hall, C., Respiratory Syncytial Virus and Parainfluenza Virus. N Engl J Med. 21 June 2001, 344, p. 1917-1928. 20. Panozzo, C., et al. Use of Respiratory Syncytial Virus Surveillance Data to Optimize the Timing of Immunoprohylaxis. Pediatrics 2010; 126; e116-e123. June 2010. 21. CDC. The 2009 H1N1 Pandemic: Summary Highlights, April 2009-April 2010. Centers for Disease Control and Prevention. 10 Aug. 2010. http://www.cdc.gov/h1n1flu/cdcresponse.htm. Accessed 19 Sept. 2011