A Comparative Discussion of the Influenza A(H7N9) and Influenza A(H5N1) Outbreaks

The first human cases of infection from a reassortant avian influenza  A(H7N9) virus were reported from the People’s Republic of China (China) on March 31, 2013.[1] Since then more than 145 confirmed and probable human cases of H7N9 infection have been officially reported. Of the cases reported through December 31, 2013, about 71% are male and 29%, female. Among the reported cases, the ages range from 2 years old to 91 years old. The median age is 60.

Besides two imported case in Taiwan, one in April and one in December 2013, all other H7N9 have occurred within the country of China. A recent summary of human H7N9 cases is presented on pages 102 and 103 in Update on the situation of avian influenza A(H7N9) infection by the Hong Kong Centre for Health Protection.[2] Another current summary is available from the European Center for Disease Prevention and Control.[3] The last official World Health Organization (WHO) tabulation of cases was published in October 25, 2013.[4]

 

Geographic Distribution

Beside the two imported cases identified in Taiwan, the remaining 145+ cases have been reported from 13 provinces and municipalities in an area covering more than 1.3 million square kilometers in eastern China.[3] The wide geographic spread of these cases, in less than 12 months, and the fact that most of these cases are sporadic cases suggests that the infection source for H7N9 is widespread throughout eastern China.
Map: Heat map of the geographic distribution of human H7N9 cases in China between February and December 2013.

Initial investigations in early 2013 suggested that some of the H7N9 infections were caused by exposure to poultry. In a tabulation of samples testing positive for H7N9, chickens and environmental samples (most from live bird markets) frequently tested positive.[5] These data indicate that chickens are the most likely host reservoir for the virus although a few ducks and pigeons have also tested positive for H7N9. H7N9 infection in poultry sources is unlike Influenza A(H5N1) infection  which often causes extreme morbidity and mortality in poultry populations. H7N9 does not seem to be fatal for poultry stock, as evidenced by the dispersed geographic distribution of positive H7N9 animal and environmental samples.

 

H7N9 Clusters

A human cluster of cases is generally defined by WHO as two or more cases of confirmed, probable, or suspected infections with onset of illness occurring within the same two-week period and who are in the same geographical area and/or are epidemiologically linked.

At least six human H7N9 clusters, including both confirmed and probable cases, have been identified among the reported H7N9 cases from China. Three family clusters occurred between February and April 2013. These clusters include a father and two sons in Shanghai Province in February and March, 2013, a husband and wife from Shanghai Province in March and April, 2013, and a father and daughter from Jiangsu Province in April 2013. In addition, one neighborhood cluster including one adult and two children occurred in Houshayu in Shunyi District, Beijing Municipality in April, 2013.[6][7]

Another confirmed family cluster in Zaozhuang, Shangdong was reported in April 2013. This cluster includes a 36-year-old man and his 4-year-old son.[8] Most recently, a family cluster consisting of 57 year-old man and his 30-year-old son-in-law was reported from Zhejiang Province in December 2013.[9]

 

Comparison of Human H7N9 and H5N1 infections

At least two published papers provide epidemiological comparisons between H5N1 and H7N9 cases. Influenza A(H5N1) is another emerging infectious disease. It was first identified in 1997 and since that infected more 650 individuals from 15 countries around the world.

A paper published in June 2003 in Lancet entitled Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases compares 43 reported H5N1 cases from China with 130 H7N9 cases through May 24, 2013. Another article, entitled Age-specific and sex-specific morbidity and mortality from avian influenza A(H7N9), reports on 136 H7N9 cases by age and sex with comparisons to H5N1 cases. Both of these articles are published in journals behind a pay wall. The details and results the analysis are not publicly available, although there are significant differences between the outbreaks of H7N9 and H5N1.

In less than 12 months since the initial H7N9 cases were reported, more than 145 peoples have been infected. The official WHO count of human H5N1 infections did not reach 145 cases until 24 months after WHO starting reporting cases in December of 2003. It was the resurgence of the H5N1 virus in a family cluster from Fujian, China in January 2003 [10] that reignited the concern for this emerging disease, although WHO did not officially start tracking H5N1 cases until January of 2004. For comparison, the initial 11 month period from January to December in 2004 (corresponding with the 11 months that have passed since the reporting of the initial H7N9 cases) only 48 human H5N1 cases were reported.

Age and Gender Differences
People of different ages are differentially infected by these two novel influenza viruses. The median age of infection for H5N1 cases is 18 years old. For H7N9, the median age is 60 years old. About 79% of H5N1 cases are less than 30 years in age. Of all of the H7N9 cases, 70% are older than 50 years.

Graph: Comparison of differential infection by Age Group of H7N9 and H5N1. 

These two influenza viruses seem to attack by gender differentially as well. Females are more likely to be infected with H5N1 than males. In contrast, males are more than twice as likely to be infected by H7N9 as females.

Graph: Comparison of differential gender infection of H7N9 and H5N1.

Mortality Comparison 
Through December 31, 2013 the case-fatality ratio for H7N9 is .31; for all WHO-confirmed H5N1 cases the CFR is .53. The differential infection rate by age groups between H7N9 and H5N1 cases limits any meaningful comparison for mortality rates among these two novel infectious influenza viruses.

 

Discussion

The lack of human H7N9 clusters indicates that the sporadic human infections are not a result of widespread human-to-human transmission. Additionally, the lack of H7N9 infections among health care workers indicates that human-to-human transmission is rare. The far-reaching geographic distribution of sporadic human H7N9 cases in China suggest the infection source is widely spread, and possibly ubiquitous, in Eastern China. The limited temporal data available suggests that H7N9 infections will follow cyclical seasonal pattern of seasonal influenza similar to the season pattern of H5N1 infections.

Graph: Percent of all H7N9 and H5N1 cases by month of infection.

As with H5N1, poultry exposure is the primary source of H7N9 infection. In contrast to HPAI H5N1 infections in poultry populations, H7N9 does not cause large-scale morbidity and mortality in domestic poultry populations. This makes surveillance for both human cases and animal outbreaks more challenging.

In 2003, influenza H5N1 reemerged as a potential pandemic threat. In 2013, another reassortant virus, H7N9, began infecting humans and this virus may also have the potential to spawn a pandemic. Finally, just few weeks ago another novel influenza virus A(H10N8) infected a woman in China. This is first known case of a human H10N8 infection. With three novel influenza virus with possible epidemic or pandemic potential, public health officials and government agencies need to expand surveillance and promote additional influenza research and vaccine development.


Acknowledgements and Notes
I thank all of the internet sources, posters at FluTrackers.com, and other internet disease trackers for their online efforts to follow and track H7N9 and other emerging infectious diseases. Thanks are also due to open source journals and researchers who post full copies of their papers and data sets.

The data and information used here have been derived from numerous publicly available sources including WHO, various ministries of health, internet bloggers, Internet forums, and other media reports available online through December 31, 2013. For some individual cases, specific details are lacking or conflicting information is presented in online reports. There are also discrepancies in case statistics reported by various public health organizations and government agencies. However, the information and graphics presented here are based on data which is believed to be reasonably accurate and current through December 31, 2013.



[1] www.who.int/csr/don/2013_04_01/en/index.html

[2] www.chp.gov.hk/files/pdf/cdw_compendium_2013.pdf 

[3] http://www.ecdc.europa.eu/en/publications/Publications/Communicable-disease-threats-report-4-jan-2014.pdf

[4] http://www.who.int/entity/influenza/human_animal_interface/influenza_h7n9/10u_ReportWebH7N9Number.pdf
 
[5] http://www.flutrackers.com/forum/showthread.php?t=213227

[6] http://www.flutrackers.com/forum/showpost.php?p=494384&postcount=1

[7] http://www.nejm.org/doi/suppl/10.1056/NEJMoa1304617/suppl_file/nejmoa1304617_appendix.pdf

[8] http://www.flutrackers.com/forum/showthread.php?p=497695

[9] http://www.who.int/csr/don/2013_12_10/en/index.html
 
[10] http://www.dh.gov.hk/textonly/english/useful/useful_ld/useful_ld_h5n12003.html