Respiratory Syncytial Virus Severe Morbidity and Mortality

Transcription

1 Respiratory Syncytial Virus Severe Morbidity and Mortality Marika K Iwane, PhD MPH CDC Division of Viral Diseases Respiratory/Picornavirus Team PAHO-Panama City May 29, 2014 National Center for Immunization & Respiratory Diseases Division of Viral Diseases

2 Outline Background on RSV Issues to consider if plan to study RSV

3 Global Priorities Pre-Vaccine Burden of RSV severe disease & mortality RSV seasonality Special populations Infants Mother/infant pairs High risk - underlying conditions, elderly Other data - RSV prophylaxis, nosocomial cases

4 Global Epidemiology of RSV Most common cause of ALRI in <5y Major cause of severe illness and hospitalizations in <5y Global meta-analysis <5y (Nair et al 2010) 33.8 M (19-42) RSV ALRI cases in % of all ALRI 3.4 M RSV hospitalizations 66, ,000 RSV deaths ~3-9% of all ALRI deaths 99% in developing countries

5 Infants RSV Epidemiology ~70% infected in 1 st year of life Almost all by 2 nd birthday Almost all are symptomatic ~20%+ or more have LRTI Highest hospitalization rates Reinfection can occur throughout life Subsequent infections usually milder Multiple RSV strains can co-circulate

6 RSV Clinical Characteristics Apnea, irritability, poor feeding in infants Fever may be absent Cold-like symptoms (nasal congestion, cough, etc) LRTI is the hallmark of RSV Bronchiolitis (wheezing) & pneumonia Often cannot distinguish bronchiolitis from pneumonia, esp young children RSV associated with later wheezing/asthma, directionality unclear 6

7 Risk Factors for Severe RSV Disease in Children Young age (<3m, <6m) Smaller airways, less developed immune systems Premature birth Underlying medical conditions Chronic lung disease Congenital heart disease Immune disorders

8 Risk Factors for Severe RSV Disease in Adults Older age Underlying medical conditions Cardiopulmonary Immunodeficiency

9 Population-based Surveillance for Severe RSV Population-based - for rates, clinical, epi High access to care hospitals Less access to care hospitals + community Select sites with high catchment Adjust for lower catchment, by age (HUS) Adjust for non-enrollment, by age Denominators also needed by age Census (annualized rates) Person-time followup Sensitive lab tests (PCR)

10 Rates of RSV Severe ALRI Meta-analysis, Nair et al 2010 Lancet RSV Severe ALRI rates/1000/yr Age <1 y Age <2 y Age <5 y Guatemala (San Marco, ) Brazil (Rio de Janeiro, ) Developing countries, Industrialized countries, Rates ~3x higher for <1y vs <5y Rates ~10x higher for ALRI vs Severe ALRI, <5y

11 RSV Hospitalization Rates by Age, Guatemala IEIP McCracken et al, JID 2013

12 Case Definitions Impact RSV Estimates Surveillance case definitions If require fever, then will miss RSV cases Important to assess impact of case defs Sites using broad definitions can assess India site, enroll & swab all hospitalizations: narrow case defs substantially RSV rates (e.g., ILI SARI) RSV supplement in JID 2013, IEIP data Peer reviewers questioned some case definitions, bias

13 Case Definitions Atypical age patterns in 2 countries Age (mo) RSV Hosps per 1000/yr (at least 1 of the following conditions: reported fever, reported chills, measured temperature of >38.2 C or <35 C, or an abnormal white blood cell count or differential) and lower respiratory tract disease (at least 1 of the following conditions: abnormal breath sounds, documented tachypnea, cough, sputum production, or dyspnea) a reported temperature of 38 C and one of the following : cough; sore throat; tachypnea ; abnormal breath sounds, including dry or moist rales or wheezing; dyspnea; hemoptysis; and chest pain or chest radiographic documentation of parenchymal lung abnormalities.

14 Meta-analysis of RSV Epidemiology in Latin America data from 74 studies PAHO began centralizing RSV info in 2009 Weekly virologic data gathered from MOHs or National Influenza Centers by country or region Most were pediatric studies from Brazil, Argentina, Chile, Mexico, Uruguay RSV seasonality Temperate climates - winter, tropical climates ~ rainy season Usual age patterns - highest %RSV+ among <1 yo Bardach A, Rey-Ares L, Cafferata ML, Cormick G, Romano M, Ruvinsky S, Savy V, Rev Med Virol 2014; 24:76 89.

15 Issues Related to RSV Seasonality RSV varies by region and year RSV may overlap with other viruses Data impacted by Participation US NREVSS voluntary, mostly clinical care results, assume pediatric # laboratories, # specimens, consistency of reporting Detection (Se) differs by age, test, specimen Diagnostic practices year round Analysis/methods - onset and offset

16 RSV Seasonality US, Florida, Puerto Rico SE FL & Puerto Rico > FL other > US other

17 RSV Mortality Data Lacking Why are RSV mortality data so limited? RSV testing for clinical care is not routine Study populations are not sufficiently large Relatively small number of RSV studies Some case definitions less sensitive for RSV Statistical models suffer from data limitations

18 Nair et al RSV Mortality insufficient data are available from which to make valid estimates of global mortality from RSV-associated ALRI 3 methods to obtain range of deaths in <5y 1. Case fatality ratios (CFR) of hospitalized RSV+ applied to severe ALRI (0.3-2% 66,000) 2. CFR of hospitalized with hypoxemia applied to severe ALRI (14% 155,000) 3. Excess deaths during RSV season in Indonesia assumed due to RSV (199,000)

19 Direct Measure of RSV Deaths Obtain specimens prior to death Surveillance for severely ill In hospitals In the community Obtain specimens post-mortem Kenya etiology of mortality study in <5y NP/OP swabs, needle biopsies, full autopsy, respiratory tract tissue, blood Argentina study NP swabs, other?

20 Indirect Measures of RSV Mortality Define when RSV is circulating Mortality databases and verbal autopsy data Case defs - Can respiratory deaths be identified Important neonates, young infants, other infants Assess diagnostic/coding practices (admin data) Assume need multiple years, large population

21 Indirect Measures of RSV Mortality (cont d) Can we model RSV deaths? Can we assume some % due to RSV? Surveillance for severely ill How to decide who might die from RSV? What are the clinical criteria for severity? Clinical scales are lacking Hypoxemia, mechanical ventilation, ICU admission? Do other pathogens co-circulate with RSV?

22 Summary RSV mortality estimation is in early stages Does surveillance need to be modified and enhanced for RSV severe disease/death? Opportunities in PAHO countries RSV testing of existing specimens? Seasonality of RSV & other viruses, and determinants Assess current data for case definitions Assess cause-of-death assignment Are data collected on risk factors - gestational age and underlying medical conditions? Other studies

23 Thank you!

24 Extra slides

25 Vaccine Development RSV vaccine priority groups Neonates and infants (<6 mos) Infants and children >6 mos (seropositive and negative) Siblings and parents of neonates Young adult women Older adults (>65y) PIV and HMPV vaccine development

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27 Etiology and Transmission Enveloped RNA Paramyoxviridae virus A and B group strains (G glycoprotein) Single stranded Spread by direct or close contact Large droplets or objects/surfaces Time from infected to symptoms: 4-6 days (range 2-8 days) Viral shedding: 3-8 days (up to 4 weeks)

28 Laboratory Testing Rapid tests of respiratory specimens (nasal swab/wash) Antigen assays Sensitivity ~70-90% in young children Sensitivity ~30% in adults PCR assays: higher sensitivity and specificity Up to 60%-70% in adults Cell culture of respiratory specimens 3-5 days Unstable virus, sensitivity probably lower than antigen Serology 28

29 Treatment Broad spectrum antiviral: Ribavirin (1980s) Improvement in oxygen levels but not in long-term outcomes Expensive and difficult to administer (aerosol) No proven benefit from steroids, bronchodilators or passive immunization Supportive care Oxygen Assisted ventilation Hydration with fluids