RSV disease burden estimates in young children and development of clinical case definition for RSV-ALRI

Transcription

1 RSV disease burden estimates in young children and development of clinical case definition for RSV-ALRI Harish Nair MB BS, PhD, DCH, DNB (Paeds.) Centre for Global Health Research, The University of Edinburgh Board member, ReSViNET Public Health Foundation of India Geneva, 24 March 2015

2 Outline Background Updated burden estimates for 2012 (work in progress) Prevalence of hypoxemia in RSV-ALRI (work in progress) Clinical signs as predictors of RSV-ALRI WHO ALRI Case definitions as predictors of RSV-ALRI Conclusions

3 Background ALRI = Pneumonia + Bronchiolitis 33.4 million cases of RSV-associated ALRI (6 studies) 3.4 million cases of RSV-associated severe ALRI (29 studies) 53,250 to 199,000 deaths due to RSV-associated ALRI ALRI = acute lower respiratory infection, RSV = respiratory syncytial virus Lancet 2010; 375:

4 Need for revised estimates Mortality upper bound based on Lombok data and assumptions that may not be correct IHME estimates- 234,000 RSV pneumonia deaths in 2010 New collaborations with groups in developing countries (CDC s IEIP sites, LAC sites, China CDC) Post 2009 SARI surveillance intensified and viral testing has increased Clear case to review available data and revise disease burden estimates

5 Case definitions RSV-associated ALRI (active, community based) - Child with cough, difficulty breathing and tachypnoea with laboratory confirmed RSV infection RSV-associated hospitalised ALRI- hospitalisation based on physician confirmed diagnosis of pneumonia / bronchiolitis with laboratory confirmed RSV infection RSV-associated severe ALRI (active, community based) - child with lower chest wall indrawing with / without tachypnoea with laboratory confirmed RSV infection RSV-associated hospitalised (very) severe ALRI hospitalised ALRI with lower chest wall indrawing and / (hypoxemia /danger signs) with laboratory confirmed RSV infection

6 Progress so far 79 studies providing incidence rates (9 community based) 68 studies reporting in-hospital case fatality ratio (CFR) 159 studies reporting proportion of hospitalised ALRI positive for RSV Ø 57 articles from Chinese literature (Ting Shi)

7 Alternative method to estimating RSV-ALRI hospitalisations in children Lancet 2013; 381(9875):

8 Analysis plan No. of new cases in 0-59 month by severity by regional, global (and national?) estimates Incidence data- 79 studies Proportion data- 167 studies Hospitalised RSV-ALRI estimates stratified by narrow age bands in infants Mortality data Lower bound In-hospital CFR- 68 studies Upper bound more robust by including data from 3-5 sites from various regions Risk factors for RSV-ALRI episodes Risk factors for RSV-ALRI mortality- RSV GOLD

9 Developing a clinical case definition for RSVALRI Primarily for surveillance purposes Part of Gates / WHO project on Optimal use of clinical signs for diagnosis and prognosis of childhood pneumonia

10 Literature search Total records n= 1444 Duplicates removed n= 402 Records screened by title and abstract n=1042 Records excluded n= 1007 Full text articles examined for eligibility n=33 Articles excluded n= 28 Studies used for analysis n=5

11 An example Backward stepwise logistic regression model Durrani, 2008 Pediatr Int Prediction model including all 3 signs sensitivity 80 (71-87)%, specificity 68 (54-79)%, PPV 82 (74-89)%, positive likelihood ratio 2.5 ( ), AUC 0.66( )

12 Analysis plan Individual patient data analysis of the data within RSV GEN Develop clinical case definitions by age group, altitude and also by settings (developing vs industrialised, community vs hospital) Potential variables to be included in the analysis now finalised Analysis to be completed by October 31, 2015

13 Summary Widely varying sensitivities and specificities for the (single) clinical signs for predicting RSV-ALRI Helpful to look at the discriminative power of combination of signs Data available within RSV-GEN would help towards this analysis

14 Acknowledgements Bill and Melinda Gates Foundation John McCracken (UVG, Guatemala) U of Edinburgh Ting Shi, Evelyn Balsells, Harry Campbell RSV GEN collaborators and their team