Respiratory Syncytial Virus (RSV) in Older Adults: A Hidden Annual Epidemic. Webinar Agenda

Transcription

1 Respiratory Syncytial Virus (RSV) in Older Adults: A Hidden Annual Epidemic Wednesday, November 2, :00 PM ET Webinar Agenda Agenda Welcome and Introductions William Schaffner, MD, NFID Medical Director Personal and Societal Burden of RSV: Clinical Presentation, Diagnosis, Current and Future Prevention & Treatment Strategies Edward E. Walsh, MD, University of Rochester Medical Center Questions & Answers This webinar is supported by an unrestricted educational grant from Novavax, Inc. NFID policies restrict funders from controlling program content. 1

2 Disclosures Marla Dalton (NFID staff) owns stock, stock options, or bonds from Merck & Co., Inc. William Schaffner (NFID medical director, presenter) served as an advisor or consultant for Dynavax, Merck & Co., Inc., Novavax, Inc., Pfizer Inc. and Sanofi Pasteur; and served as a speaker for Genentech Edward E. Walsh (presenter) has received research support from Gilead Inc. All other activity planners/reviewers and staff for this activity have no relevant financial relationships to disclose Learning Objectives At the conclusion of this webinar, participants will be able to: Describe the epidemiology of RSV Discuss the clinical presentation and outcome of RSV infection in older adults Explain RSV diagnostic challenges Summarize RSV treatment and prevention strategies 2

3 About NFID Non profit 501(c)(3) organization dedicated to educating the public and healthcare professionals about causes, treatment, and prevention of infectious diseases across the lifespan Reaches consumers, health professionals, and media through: Coalition building activities Public and professional educational program Scientific meetings, research, and training Longstanding partnerships to facilitate rapid program initiation and increase programming impact Flexible and nimble organization NFID Resources 3

4 Personal and Societal Burden of RSV: Clinical Presentation, Diagnosis, Current and Future Prevention & Treatment Strategies Edward E. Walsh, MD Professor of Medicine University of Rochester School of Medicine Rochester, NY RSV is a pneumovirus in the Paramyxovirus family Similar to Parainfluenza and measles viruses An ss enveloped RNA virus with 10 genes First discovered in 1956, RSV is best known for causing annual winter time epidemics of bronchiolitis in infants Also linked to asthma 4

5 Epidemiology and Impact of RSV in Elderly Adults 4 winter seasons Prospective surveillance of healthy elderly, adults with cardiopulmonary disease Adults hospitalized with acute cardiopulmonary conditions Diagnosis of influenza and RSV by culture, one tube nested RT PCR, serology Falsey et al. NEJM. 2005;352:

6 Rates of Illness and Infection by Cohort, Group Enrolled Illnesses Healthy Old High Risk Hospitalized Falsey et al. NEJM. 2005;352:1749. Incidence of Influenza A and RSV in Older Adults N=420 N=553 N=375 N=467 Flu A RSV RSV: 5.5 per 100 / season ( ) Flu A: 2.1 per 100 / season ( ) 10% of infections were asymptomatic Falsey et al. NEJM. 2005;352:

7 Percent Admissions Due to RSV and Flu A % Admissions Flu A RSV Average RSV 10.5 % Flu A 11.6 % Falsey et al. NEJM. 2005;352:1749. Admitting Diagnosis RSV Influenza A Pneumonia 7% 6% 7% COPD CHF Asthma Bronchitis 13% 39% 8% 9% 46% MI Other 35% 23% Falsey et al. NEJM. 2005;352:

8 Functional Impact in Healthy Elderly % Housebound Bedbound Unable to do ADLs RSV Flu A Falsey et al. NEJM. 2005;352:1749. Outcome of Hospitalized Subjects % Pneumonia ICU Ventilator Death Flu RSV Falsey et al. NEJM. 2005;352:

9 Risk Factors for Hospitalization with RSV P Risk Factor Odds Ratio value Male sex Pulmonary disease Coronary Artery Disease 1.0 NS Congestive heart failure 1.9 NS Diabetes 0.9 NS Functional score (per integer 1 12) Neutralizing titer <10 log Walsh et al. J Infect Dis. 2004;189: Risk Factors for Hospitalization with RSV 508 hospitalized adults age 65 years PCR over 3 winters in Nashville, TN Virus Incidence (%) % ICU Mortality RSV 6.1% 10% 6% Influenza 6.5% 13% 9% hmpv 4.5% 6% 0% Widmer et al. JID. 2012;206:

10 Age Specific Annual Deaths in US: P & I and Circulatory & Respiratory Age (years) All Flu RSV < > Total Thompson et al. JAMA. 2003;289: Projections of US RSV Burden Using surveillance data from Rochester, NY Hospitalizations: 177,000 Deaths: 14,000 10

11 FLU Optimal model had a 2 3 week lag for RSV deaths in adults Von Asten et al. JID. 2012;206: Deaths Attributable During Study Period, Poisson regression model to estimate mortality from RSV & flu in elderly adults in The Netherlands During 9 years influenza ~1.6 fold > RSV Virus years years 85 years 65 years Flu A 1,935 6,282 7,201 15,519 RSV 1,305 5,171 7,425 13,902 Flu B 2,209 3,907 6,116 Von Asten et al. JID. 2012;206:

12 RSV and Flu Incidence and Morbidity in Adults 65+ Based on Modeling Author Location Thompson US Mullooly Oregon, US Zhou US van Asten Netherlands Matias US Fleming UK Chan Hong Kong Goldstein NYC Outcome Measure Results RSV/Flu % Respiratory & circulatory deaths per 100,000 Annual pneumonia & influenza hospitalizations per 10,000 Annual hospitalizations per 100,000 RSV 26.5 Flu A+B 98.5 RSV 23.4 Flu 55.6 RSV 86.1 Flu 309 Total deaths RSV 13,902 Flu A + B 21,635 Annual deaths from respiratory illness Annual hospitalizations (ratio of RSV:Flu) Annual hospitalizations per 10,000 Annual hospitalizations per 100,000 RSV 9,673 Flu % 42% 28% 64% 59% RSV 14,039 (0.8:1) 80% RSV 5.2 (M) 6.1 (F)** Flu A 19.5 (M) 17.3 (F) RSV 15.3 Flu % 12% Office RSV and Influenza, % of samples < >65 Age Group RSV Flu Zambon MC. Lancet. 2001;358:

13 New Data from Flu Vaccine Efficacy Studies Using Test Negative Control Groups 1,568 adults age >50 years presenting with medicallyattended respiratory illness, 6 seasons at Marshfield Clinic Virus No. % Influenza RSV Rhinovirus hmpv Coronavirus Sundaram et al. CID. 2013; 57: Symptoms in Outpatients RSV Influenza A Healthy n=48, % High Risk n=54, % Healthy n=18, % High Risk n=16, % Nasal Cough Sputum Dyspnea Wheeze Constitutional Fever Sundaram et al. CID. 2014;

14 Clinical Findings of RSV in Comparison to Other Viruses also Affecting Elderly Adults Flu A RSV HMPV hcov 0 Symptoms of RSV and Flu A in Hospitalized Patients Are Very Similar Favors Flu Abrupt High Fever Myalgia GI Symptoms Favors RSV Gradual Rhinorrhea Wheezing Sputum 14

15 Marshfield Clinic Data 2014 ARI symptoms RSV+ n (%) RSV n(%) P value Cough 202 (99.0) 1857 (91.9) <.001 Wheezing 135 (66.8) 997 (49.4) <.0001 Nasal congestion 182 (89.7) 1570 (77.7) <.0001 Fever 124 (61.1) 1303 (64.8).29 Fatigue 184 (90.2) 1824 (90.3).98 Headache 134 (65.7) 1403 (69.5).27 Muscle aches 116 (56.9) 1283 (63.7).05 ARI=acute respiratory illness. Sundaram et al. CID. 2014; RSV Culture + 15

16 Diagnosis of RSV in the Elderly Comparison of Standard Methods and RT PCR Sensitivity Antigen BD EIA 9% Antigen VIDAS 23% Antigen DFA 27% Culture 39% PCR 73% Serology 95% 16

17 Adult RSV Infection 17

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19 Management O2, fluids, standard supportive care Make a correct and accurate diagnosis WHY Antivirals (small molecules and antibodies) perhaps in the not so distant future Antibacterials????? 19

20 How Were These Patients Treated? Almost all (92%) received antibiotics but very few had evidence of bacterial infection Virus Infiltrates Bacteremic chest X ray Influenza A 30% <1% RSV 31% 3% hmpv 27% 1% Coronavirus (229E/OC43) 12%/37% 0%/0% What Is the Incidence of Bacterial Co Infection During Viral Infection? Historical data from 1918 influenza pandemic: 95% of deaths due to bacterial pneumonia influenza pandemic estimates of 40 50% of deaths were bacterial 2009 H1N1 pandemic suggesting severe fatal pneumonia was often bacterial Descriptions of bacterial pneumonia during RSV, parainfluenza virus & metapneumovirus infections in adults 20

21 Bacterial Complications of RT Viral Illness in Rochester, NY 842 hospitalizations during 3 winter seasons 348 viral infection (41%) 212 virus alone (61%)* 64 bacteria specific dx + 72 elevated serum PCT 0.25 ng/ml *74% by RT PCR. Falsey et al. J Infect Dis. 2013;208: Virus (N) Bacteriaspecific dx PCT 0.25 ng/ml Bacteriaspecific or PCT 0.25 ng/ml Influenza A (83) (40%) Influenza B (7) (43%) RSV (55) (31%) hmpv (38) (39%) HCoV OC43 (56) (39%) HCoV 229E (16) (44%) PIV 1 3 (24) (50%) Rhinovirus (30) (30%) Mixed viral (38) (47%) TOTAL (348) (39%) Falsey et al. J Infect Dis. 2013;208:

22 Vaccines Antivirals Diagnostics Antibiotic Reduction Serum Neutralizing Titers and Illness Severity Hospitalized vs Non-Hospitalized No. of Subjects < MNA Hospitalized Non- Hospitalized Walsh et al. J Infect Dis. 2004: 189:

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