H7N9 Fatality Rates May Be Lower Than Once Thought

Troy Brown

June 24, 2013

The case fatality risk for patients hospitalized with avian influenza A H7N9 virus may be lower than previously estimated, but the virus may reappear when the weather cools, according to data from researchers at the Chinese Center for Disease Control and Prevention (China CDC) in Beijing.

Hongjie Yu, MD, director of the Division of Infectious Disease, Key Laboratory of Surveillance and Early-Warning on Infectious Disease at the China CDC in Beijing, and colleagues present their findings in 2 articles published online June 24 in the Lancet.

In the first article, they used data as of May 28, 2013, from hospitalized patients with laboratory-confirmed H7N9 to estimate the risk for death, mechanical ventilation, and intensive care unit (ICU) admission. Sentinel influenza-like illness (ILI) surveillance data were used to estimate the symptomatic case fatality risk.

A total of 123 patients were hospitalized with laboratory-confirmed H7N9; of those, 37 (30%) died and 69 (56%) recovered. Of hospitalized patients, 71 (58%) were aged at least 60 years and 87 (71%) were men.

After accounting for incomplete data regarding 17 patients who were still hospitalized, the estimated fatality risk for all ages was 36% (95% confidence interval, 26% - 45%) on hospital admission.

Of the 108 patients for whom detailed clinical data were available, 71 (66%) required mechanical ventilation and 83 (75%) required ICU admission. The risks for ICU admission (P = .08) and mechanical ventilation (P = .0067) were higher for patients aged 60 years or older than for those who were younger.

Similarly, there were high risks for mechanical ventilation or fatality (69%; 95% CI, 60% - 77%), as well as ICU admission, mechanical ventilation, or fatality (83%; 95% CI, 76% - 90%) for all age groups, but the fatality risk was higher in those aged 60 years or older than for younger patients (P = .0019).

Using sentinel ILI data, the researchers estimated the symptomatic case fatality risk at between 160 (95% CI, 63 - 460) and 2800 (95% CI, 1000 - 9400) per 100,000 symptomatic cases. This estimate "suggests that avian influenza A H7N9 is not as severe as influenza A H5N1, but more severe than 2009 influenza A H1N1 pandemic virus," the authors write.

"[M]any mild cases might have occurred."

The median time to death for the 37 patients who died was 11 days (interquartile range, 6 - 23 days). The median time to recovery for the 69 patients who recovered was 18 days (interquartile range, 14 - 29 days).

H7N9 vs H5N1: Similarities and Differences

In the second paper, the same researchers compared the epidemiological characteristics of the H7N9 virus (130 patients reported to the China CDC before May 24, 2013) with those of the influenza A H5N1 virus (43 patients), which has been seen in China since 2003.

The median age was 62 years for those with H7N9 and 26 years for those with H5N1. "The differences in age distribution of patients with laboratory-confirmed infection with H7N9 and H5N1 are intriguing; presumably, immunity associated with different histories of influenza virus exposures has an important role in addition to differences in exposure patterns," the authors write.

For both viruses, 74% of patients in urban areas were men. In rural areas, the percentages of men with either virus were lower: 62% of H7N9 cases and 33% of H5N1 cases, respectively,. About three quarters of patients (75% of those with H7N9 and 71% of those with H5N1) reported recent poultry exposure.

"Whereas most patients with confirmed H7N9 and H5N1 infection reported exposure to live poultry, the type of exposure was very different in urban and rural locations...the male-to-female ratio is much higher in urban than in rural areas for both viruses," the authors write. "This result is consistent with sex-based differences in exposure, rather than differences in immunity."

The mean incubation period was 3.1 days for H7N9 and 3.3 days for H5N1. The average number of contacts that were traced for each case of H7N9 was 21 in urban areas and 18 in rural areas compared with 90 and 63 contacts, respectively, for H5N1.

On hospital admission, the fatality risk was 36% (95% CI, 26% - 45%) for H7N9 and 70% (95% CI, 56% - 83%) for H5N1.

"If H7N9 follows a similar pattern to H5N1, the epidemic could reappear in the autumn," the authors write. "This potential lull should be an opportunity for discussion of definitive preventive public health measures, optimisation of clinical management, and capacity building in the region in view of the possibility that H7N9 could spread beyond China's borders."

In an accompanying comment, Cécile Viboud, PhD, and Lone Simonsen, PhD, from the Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, discuss the 2 articles. Dr. Simonsen is also from the Department of Global Health, School of Public Health and Health Services at George Washington University in Washington, DC.

"It is reassuring that head-to-head comparison of the fatality risk of admitted patients infected with avian influenza A H7N9 or H5N1 suggests a substantially milder disease course for H7N9," write Dr. Viboud and Dr. Simonsen. "Use of these estimates of case fatality risk to extrapolate the potential severity of a full pandemic would be tempting; however, whether global dissemination of these zoonotic influenza viruses would result in a catastrophic pandemic like that in 1918, or worse, or would mirror the mild 2009 pandemic is impossible to predict."

The first study was funded by the Chinese Ministry of Science and Technology; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; National Institute of Allergy and Infectious Disease; and National Institutes of Health. The second study was funded by the Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and National Institutes of Health. One coauthor has received research funding from MedImmune and consultant fees from Crucell NV. One coauthor has received speaker honoraria from HSBC and CLSA. The other authors have disclosed no relevant financial relationships. Dr. Simonsen is a member of the Severity Assessment Plan Technical Working Group initiated by the World Health Organization in 2013 and reports support from the RAPIDD program of the Science and Technology Directorate (US Department of Homeland Security). Dr. Viboud has disclosed no relevant financial relationships.

Lancet. Published online June 24, 2013. Abstract

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