Ying Qin1, Peter W Horby2, Tim K Tsang3, Enfu Chen4, Lidong Gao5, Jianming Ou6, Tran Hien Nguyen7, Tran Nhu Duong7, Viktor Gasimov8, Luzhao Feng1, Peng Wu3, Hui Jiang1, Xiang Ren1, Zhibin Peng1, Sa Li1, Ming Li1, Jiandong Zheng1, Shelan Liu4, Shixiong Hu5, Rongtao Hong6, Jeremy J Farrar9, Gabriel M Leung3, George F Gao10, Benjamin J Cowling3, Hongjie Yu1. 1. Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China. 2. Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom Singapore Infectious Disease Initiative. 3. WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region. 4. Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou. 5. Hunan Provincial Center for Disease Control and Prevention, Changsha. 6. Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China. 7. National Institute of Hygiene and Epidemiology, Hanoi, Vietnam. 8. Ministry of Health of Azerbaijan, Baku. 9. Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom Singapore Infectious Disease Initiative ISARIC, Centre for Tropical Medicine, University of Oxford, Churchill Hospital, United Kingdom. 10. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences Office of Director-General, Chinese Center for Disease Control and Prevention, Beijing, China.
Abstract
BACKGROUND: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. METHODS: We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). RESULTS: We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). CONCLUSIONS: The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.
BACKGROUND: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. METHODS: We compared the characteristics of sporadic and clustered cases of humanH5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). RESULTS: We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). CONCLUSIONS: The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.
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