RSV disease global burden

Transcription

1 RSV disease global burden Prof Harish Nair MBBS PhD FRCPE FFPH Chair of Paediatric Infectious Diseases and Global Health Usher Institute of Population Health Sciences and Informatics University of Edinburgh WSPID, Shenzen, 5 December 2017

2 Disclosures Funding from Bill and Melinda Gates Foundation and Innovative Medicines Initiative for RSV-related work Funding from Sanofi Pasteur for RSV and non-rsv related work Honorarium from Medimmune for participating in SAB meeting Co-founder of ReSViNET network has received funding from several pharmaceutical industries to organise high level expert group meetings 2

3 Outline Background Global acute RSV Burden by age and region Incidence Hospitalisation Mortality 3

4 Background Child pneumonia - the leading cause of child mortality in M (18% of all <5y child deaths) 1 In 2015, estimated 921k child deaths due to pneumonia (15% of all <5y child deaths) 1 Deaths per 1000 live births In future, as PCV and Hib conjugate vaccine coverage is scaled up, the proportional contribution of viral aetiologies (RSV, flu, hmpv) to pneumonia mortality will be substantial 1. Liu et al., Lancet 2016

5 Natural history of RSV infection in young children

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7 Updated systematic review records identified through database search 4 records identified through other sources 5198 duplicates removed 9911 records screened 990 full-text articles assessed for eligibility 8921 records excluded because not relevant to topic 740 full-text articles excluded 76 unpublished studies 250 articles included 90 studies reported incidence/hospitalisation data 103 studies reported inhospital CFR data 218 studies reported proportion RSV+ hospitalised - 83 were Chinese data 7

8 Case definitions Community-based (active) case ascertainment Cough / difficulty breathing AND RSV positive RSV-associated ALRI: tachypnoea (IMCI cut-offs) RSV-associated severe ALRI: chest wall indrawing AND / danger signs Hospital-based (passive) case ascertainment Hospitalised RSV-ALRI: Hospitalisation with a physician confirmed diagnosis of ALRI and RSV positive on laboratory confirmation IMCI: Integrated management of childhood illnesses 8

9 RSV disease severity- conceptual diagram Shi et al., Lancet

10 Location of incidence, hospital admission and in-hospital mortality studies (n=157) Shi et al., Lancet

11 Incidence of RSV-(severe) ALRI in LMIC children <2 years Incidence of RSV-ALRI (per 1000 per year) days 28-<3m 3-5m 6-11m 12-23m Age group RSV-ALRI severe RSV-ALRI Shi et al., Lancet 2017

12 Estimates of RSV-(severe) ALRI in developing countries in 2015 Incidence (per 1000 children per year) [# studies] # episodes (millions) 0-5 mo 6-11 mo 0-59 mo 0-5 mo 6-11 mo 0-59 mo RSV-ALRI 82.5 (50.4, 135.2) [14] 98.8 (58.8, 166.1) [10] 50.8 (32.4, 79.7) [14] 5.1 (3.1, 8.3) 6.1 (3.6, 10.2) 30.5 (19.5, 47.9) RSVsevere ALRI 36.1 (10.1, 129.1) [8] 28.7 (9.1, 90.3) [7] 10.2 (3.5, 29.9) [8] 2.2 (0.6, 7.8) 1.5 (0.7, 3.3) 6.1 (2.1, 17.9) Shi et al., Lancet

13 Methods to estimate country-level RSV-ALRI incidence Meta-analysis of incidence rates Meta-analysis of risk ratios Risk factors from survey data Risk factor Survey Odds ratio Prematurity (GA<37 wk) Other 1.96 ( ) Low birth weight DHS 1.91 ( ) Siblings DHS 1.6 ( ) Maternal smoking Other 1.36 ( ) Paediatric HIV UNAIDS 3.74 ( ) Crowding DHS 1.94 ( ) Shi et al., Lancet

14 National RSV-ALRI incidence estimates Country Incidence of RSV-ALRI (per 1000 children per year) No. of episodes of RSVassociated ALRI (millions) (UR) India 56.7 ( ) 7.0 ( ) China 31 ( ) 2.6 ( ) Nigeria 55.6 ( ) 1.7 ( ) Pakistan 63.9 ( ) 1.6 ( ) Indonesia 50.1 ( ) 1.2 ( ) Shi et al., Lancet

15 Hospitalisation rate for RSV-ALRI in children <2 years Even though peak hospitalisation in children <6 months; substantial burden on hospital in-patient services in 6-11 months Shi et al., Lancet

16 Global estimates of hospitalised RSV-ALRI Region (% global U-5 pop.) High income (12%) Upper middle income (26%) Lower middle income (47%) Low income (16%) Hospitalisation rate (per 1000 children per year) # episodes (millions) in mo 6-11 mo mo 0-5 mo 6-11 mo mo 26.3 (22.6, 30.5) 23.0 (16.1, 32.9) 22.9 (17.7, 29.7) 7.4 (2.4, 22.6) 13.0 (7.2, 23.7) 18.5 (9.8, 34.7) 11.3 (6.1, 21.0) 3.4 (0.6, 19.5) 1.6 (1.1, 2.3) 2.2 (1.3, 3.9) Episodes in 0-59 mo 3.3M (2.5, ) M (1.2, 2.8) 0.4 (0.1, 1.7) 0.2 (0.2, 0.2) 0.4 (0.3, 0.6) 0.7 (0.6, 1.0) 0.08 (0.03, 0.2) 0.1 (0.05, 0.2) 0.3 (0.2, 0.6) 0.4 (0.2, 0.7) 0.03 (0, 0.2) 0.1 (0.07, 0.2) 0.3 (0.2, 0.6) 0.5 (0.3, 0.7) 0.03 (0, 0.1) Global 1.4 (1.1, 2.0) (0.4, 1.7) (0.5, 1.5) Shi et al., Lancet

17 RSV-ALRI in-hospital CFR in children <5 y Region (% global U- 5 pop.) # studies h-cfr [%] (95% CI) 0-5 mo High income (12%) (0.0, 12.8) Upper middle income (26%) Lower middle income (47%) (1.2, 2.6) (2.0, 3.6) Low income (16%) (0.4, 6.8) Developing (1.8, 2.7) h-cfr [%] (95% CI) 6-11 mo 0.9 (0.2, 4.0) 2.4 (1.1, 5.4) 2.8 (1.8, 4.4) 9.3 (3.0, 28.7) 2.4 (1.9, 3.2) h-cfr [%] (95% CI) mo 0.7 (0.1, 5.2) 0.5 (0.1, 3.5) 2.7 (1.7, 4.3) 4.7 (0.7, 33.7) 2.2 (1.6, 3.0) Industrialised ( ) 0.1 ( ) 0.1 ( ) Shi et al., Lancet

18 RSV-ALRI in-hospital mortality in children <5y Region # studies Mortality 0-5 mo (UR) Mortality 6-11 mo (UR) Mortality mo (UR) Mortality 0-59 mo (UR) High income ( ) 900 ( ) 700 ( ) 3300 ( ) Upper middle income ( ) 8000 ( ) 1500 ( ) ( ) Lower middle income ( ) ( ) ( )) ( ) Low income ( ) 3400 ( ) 1400 ( ) 8200 ( ) Developing (A) ( ) ( ) ( ) ( ) Industrialised (B) 2 <50 (0-2000) <50 (0-300) 100 (0-300) 200 ( ) Global (A+B) ( ) Shi et al., Lancet

19 Overall RSV-ALRI mortality in infants: background ~80% of ALRI deaths in <5 yr children occur outside hospital (Nair et al., Lancet 2013) Overall mortality can be estimated using modelling - requires data on pneumonia mortality in <5 yr children and RSV transmission Data from vital registration incomplete Therefore, need to use other data from other sources- verbal autopsy, mortality surveys, medical certification of deaths Data for minimum three complete years Sufficient number ( 100) of pneumonia deaths RSV transmission- clear seasonality, adjust for shared seasonality with influenza Shi et al., Lancet

20 Approach to RSV-ALRI mortality estimates 20

21 Overall RSV-ALRI mortality in <5y children : methods Overall RSV-ALRI mortality for <5y children using an excess mortality model (data from 3 sites Bangladesh, Indonesia and Argentina) Attributing all excess ALRI mortality during RSV season to RSV overestimates RSV mortality Exclusion of secondary bacterial infection post RSV-ALRI underestimates RSV mortality Inflation factor ranged from 1.5 (Argentina) to 2.9 (Indonesia) applied mean inflation factor (2.2) Adjusted for shared seasonality with influenza (90% of excess mortality during RSV season attributable to RSV) Shi et al., Lancet

22 Overall RSV-ALRI mortality in <5y children: modelled estimates Overall RSV mortality in <5 children in (95-149)k >99% mortality in developing countries 73% of in-hospital RSV-ALRI mortality in infants; 46% in infants <6 months No national ALRI mortality estimates for infants; so not possible to directly model overall RSV-ALRI mortality estimates for this age group However, if proportional RSV-ALRI mortality (by age group) outwith hospital were same as in-hospital, then overall RSV mortality in infants could be as high as 86k (69k to 109k) 22

23 How can we improve global mortality estimates? Community mortality data Site-specific mortality multiplier need site-specific overall and inhospital RSV mortality PREREQUISITE Community mortality surveillance with hospital arm POSSIBLE DATA SOURCES Gates funded RSV mortality studies- Argentina, India, Pakistan and Zambia CHAMPS ADVANTAGES Hospital and community mortality are from same site and are from true deaths reliable multiplier Data on 30-day post RSV mortality for post-rsv secondary bacterial infection (CHAMPS) 23

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25 Summary RSV associated with about 25% of ALRI episodes in children <5 years 37% of RSV-severe ALRI and 42% of RSV hospitalisations in infants 0-5 months Overall RSV-ALRI mortality in children <5 years (95-149)k (13% of global ALRI mortality) 50% (~60 k) occurs in hospital 43k (73%) RSV-ALRI in-hospital deaths in infants; 63% in infants <6 months Relatively robust in-hospital RSV mortality estimates Overall RSV mortality estimates limited by number of data points and lack of national level pneumonia mortality estimates in infants 25

26 Acknowledgements RSV Global Epidemiology Network S Madhi, K O Brien, E Simoes, B Gessner, F Polack, J Nokes, A Brooks, D Feikin, M Venter, J Moyes, E Azziz-Baumgartner, A Gordon, G Bacalla, J Montgomery, S Broor, M Chadha, S Hirve, A Krishnan, R Singleton, S Thamtithiwat, M Oliveira, M Echhavaria, R Fasce, Y Hongjie, M Lucero, C Kartasasmita, C Lupisan, S Howie, H Oshitani, L Yoshida, C Turner, K Strum-Ramirez, J McCracken, A Ali, H Zar, Z Rasmussen, L Bont, W Clara, J Jara, P Byass, A Scott, D Thea, C Romero, P Buchy, A Gentile, Q Bassat, A Ali Bill and Melinda Gates Foundation Innovative Medicines Initiative

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