U pdate on A(H7N9) epidemiology

1. Update on A(H7N9) epidemiology GM Leung, BJ Cowling, JT Wu School of Public Health, The University of Hong Kong in collaboration with China CDC MIDAS Meeting May 7, 2013

2. Person, place, time • First case identified in March (illness onset on February 19) • 130 cases to date, mostly among residents of urban areas Cowling BJ, Jin L et al, submitted

3. Cowling BJ, Jin L et al, submitted

4. Age+sex distribution • Apparent increase in risk of H7N9 with age (above) • Substantially higher risk in men than women • Very different age pattern compared to H5N1 Cowling BJ, Jin L et al, submitted

6. Exposure pattern explains sex effect? Cowling BJ, Jin L et al, submitted

7. Undetected mild H7N9 cases More extreme rise in incidence of serious H7N9 cases (above) compared to changes in live poultry exposures (below) implies increasing seriousness with age and undetected mild infections in adults? Cowling BJ, Freeman G, et al, in press

8. Yu H, Cowling BJ, Wu JT, et al, submitted

9. 2 observations from 3 of the cities that closed markets: 1. Closure was effective – reduced incidence rate by 92%. 2. Mean incubation period =2.4 days Yu H, Cowling BJ, Wu JT, et al, submitted

10. Estimated from line list of 126 cases (April 30) • Mean incubation period 2.8d (top left) • Mean onset-to-admission period 3.5d (top right) Cowling BJ, Jin L et al, submitted

11. Case hospitalization fatality risk • Overall HFR of 48% (not 20%!) • For H7N9, the HFR increases with age. Cowling BJ, Jin L et al, submitted

12. A(H7N9) - A new threat for poultry trade biosecurity • Low pathogenic among poultry, i.e. cannot be visually detected because of the lack of overt symptoms (unlike H5N1) • Highly pathogenic among humans, i.e. Risk of exposure may escalate without signs as the virus spreads silently among poultry • Countermeasures • Closure of live poultry markets • Screening of poultry exports and imports • Inspection of flocks and facilities at farms

13. Risk assessment of infection importation Avian influenza surveillance of poultry import in Hong Kong (RPCR = 30, Rsero = 20) How many infected poultry will reach the market? Border Outbreak with m seeds RPCR RT-PCR RSero serology RPCR RT-PCR RSero serology Single consignment (800-1,000 poultry) ready for export 5 days of quarantine For sale at local markets Outcome measures: Probability of importing an infected consignment Expected number of infected poultry per consignment that “leak” into the market Method: Simulate the outbreak with a stochasticSEIR-type model Calculate the detection probability Weight the epidemic curves from (1) with the probability from (2).

14. Results • Randomly selecting 60 chickens in a single homogeneous consignment for RT-PCR and 40 for serology can detect an outbreak with at least 95% probability if prevalence >5.4% or seroprevalence > 9%. • Final outcomes depend on transmission dynamics only via the epidemic doubling time and the seed size. • The expected number of infected and infectious poultry imported are smaller than 16 and 8, respectively, regardless of the epidemiologic details of the outbreak. • Serology is important even though it can only detect seropositive birds that may not necessarily be infectious. • RT-PCR resources can be optimized by choosing a pool size that maximizes the product of sample size and pooled sensitivity

15. Implications • Need poultry-to-human reproductive number to translate our risk outcomes into precise risks of human cases, i.e. ongoing investigation of poultry-to-human transmission is critical to filling this important knowledge gap in risk assessment. • Sample size requirement for multi-flock consignments scale with the number of constituent flocks. • A generic risk model that can be: • Used to evaluate the performance of screening for detecting poultry consignments that are infected with low pathogenicity avian influenza, such as the currently expanding A(H7N9) epizootic • Adapted and applied to different critical control points of the poultry supply chain for optimizing avian influenza surveillance.

16. The Team