Thursday, January 1, 2015

Human Cases of Avian Influenza Infections in 2014

In 2014, 366 human cases of avian influenza infection from four subtypes, A(H7N9), A(H5N1), A(H5N6) and A(H10N8) were reported from 7 countries, China, Egypt, Taiwan, Malaysia, Cambodia, Indonesia, and Vietnam. The case-fatality risk ranged from possibly as low as .22 to as high as .67 among these subtypes in 2014. There is no evidence among any of these subtypes of sustained human-to-human transmission.

Influenza viruses that easily circulate among human populations are referred to as seasonal influenza viruses and can cause severe illness in 3 to 5 million individuals annually.[1] Avian influenza Type A viruses that cause infection in birds are referred to as avian influenza viruses. These viruses occur naturally among wild birds worldwide and can infect domestic poultry and other bird and animal species.[2] These avian influenza viruses circulating in bird populations do not usually infect humans. However, sometimes humans can become infected with avian influenza subtypes which have the potential to reassort into pandemic viruses. Avian influenza viruses that have infected humans include A(H5N1), A(H7N7), A(H7N9), A(H9N2), and others.

Four subtypes of avian Influenza, A( H7N9), A(H5N1), A(H10N8), and A(H5N6) caused sporadic human infections in 2014. In 2014, avian influenza H7N9 infected 317 people in the People’s Republic of China (China). Also in 2014, 44 human cases of H5N1 were reported from 5 countries. Also, a few sporadic cases of H10N8 and H5N6 were reported from China.

Avian Influenza A(H7N9)

The first case of human infection with the novel reassortant avian-origin influenza A (H7N9) virus was reported from China in 2013.[3] By the end of 2013, a total of 158 human cases were reported from China by the World Health Organization (WHO). In 2014, 312 additional cases of H7N9 were reported through December 31, 2014 by WHO.[4] Three of these cases were individuals infected in China but reported and treated in Taiwan (2) and Malaysia (1). All of the remaining cases were reported from China. In addition to the cases reported by WHO, local health agencies in Zhejiang and Guangdong provinces in China have announced 5 additional cases through December 31, 2014 that have yet to be reported by WHO.

In total, since the beginning of H7N9 outbreak in China in 2013, at least 475 individuals have been infected. Ages of infected individuals range from less than 1 year old to 91 years old with a median age of 58 years old. Infections among males exceed infections among females by about 2:1.

An overall case-fatality risk is difficult to derive based on published information. WHO has only reported 105 confirmed H7N9 deaths which would result in a case-fatality risk of .22. While there have been some reports of recoveries of cases in China, the outcome of more than 250 cases is unknown. A recent published report indicates that there have been at least 170 deaths in China through July 2014.[5] This would results in a case-fatality risk of .39 as of July 2014. A more recent article estimates the hospital fatality rate during the second wave in 2014 at 48% for hospitalized H7N9 cases.[6] It is not possible to directly derive the number of fatal cases of H7N9 from this article to compute an overall case-fatality risk.

In 2013, H7N9 cases were concentrated in eastern China. The provinces of Zhejiang, Shanghai, and Jiangsu accounted for about 75% of all reported cases that year. More than 30% (101) of all 2014 H7N9 cases were reported from Guangdong Province, a province that only reported 10 cases in 2013. Zhejiang Province continues to report a high number of H7N9 infections. Shanghai reported fewer infections in 2014, while several other provinces in eastern China reported increases in cases over the previous year or their first confirmed cases. Of concern is that Xinjiang Uygur Autonomous Region reported eight cases H7N9 in 2014. Xinjiang Uygur Autonomous Region is located in western China, far from the provinces in eastern China where the H7N9 outbreak has been concentrated.

Table 1. Number of H7N9 Cases by Province in China 2013-2014.

Figure 1. Geographic Distribution of A(H7N9), A(H5N1), A(H10N8), and A(H5N6) in China (2003-2014)

Origin of A(H7N9)
The circulation of A(H9N2) influenza genotypes in chicken populations in China resulted in the novel H7N9 virus that is infecting humans.[7,8] Research indicates that multiple strains of H7N9 and H9N2 influenza viruses are circulating in poultry in Guangdong Province, continually creating an environment that is “rich for reassortment of these viruses and that poses an ongoing risk for human infection.”[9] Other researchers suggest that H7N9 infecting humans originated in waterfowl in Taihu Lake region in Zhejiang Province where some of the first human cases were recorded.[10]

A(H7N9) Co-infections with Seasonal Influenza
Not only is reassortment of H7N9 subtype in bird populations a concern, but reassortment between H7N9 and seasonal influenza could lead to more efficient or sustained human-to-human transmission and possibly a pandemic. There are reports from China detailing three cases of human co-infection of A(H7N9) with seasonal influenza subtypes of A(H3N2), A(H1N1)pdm09, and influenza B virus that widely infect humans.[11,12] Dual influenza infections raise the risk of reassortment of human and avian subtypes. Adding to the concern is that a small percentage, about 10%, of contacts of H7N9 cases showed elevated levels of H7N9 antibody in study from Jiangsu Province and “offer evidence that human-to-human transmission of H7N9 virus may occur among contacts of infected persons.”[13]

Confusing the issue of H7N9 co-infection with seasonal influenza is a recent published report that estimates that thousands of symptomatic cases of H7N9 occurred in 2013 and 2014 in the provinces of Shanghai, Zhejiang, and Jiangsu. [14, see table]. Each symptomatic human case of H7N9 represents a potential for pandemic reassortment.

Family Clusters of A(H7N9)
Most reported H7N9 cases are sporadic cases of community acquired infections with limited evidence of human-to-human transmission. Transmission of novel influenza viruses in family groups can be a signal of increasing efficiency of human-to-human transmission. However, only minimal information on family clusters of H7N9 cases is publicly available. During the initial stages of the outbreak in China in 2013, a few small family clusters were reported.[15] In 2014, at least four separate family clusters of H7N9 cases occurred in Zhejiang and Guangdong provinces.[16,17] The pediatric cases in the clusters from Guangdong Province only exhibited mild symptoms and virus isolates from patients in the same cluster shared high sequence similarities. Community acquired infection from poultry or live bird markets poultry or a contaminated environment could account for these clusters. These data are evidence that efficient or sustained person-to-person transmission of H7N9 has not yet occurred.

Avian Influenza A(H5N1)

Avian influenza A(H5N1) was first detected in humans in Hong Kong in 1997. Since 2003, WHO has officially reported a total of 676 confirmed human cases of H5N1 from 16 countries.[18] The most recent WHO timeline of significant events associated with the H5N1 was updated on December 4, 2014.[19] The last WHO report summarizing H5N1 cases was also published on December 4, 2014.[20] Since that date, the Ministry of Health in Egypt has announced an additional 17 human cases of H5N1 through December 31, 2014, raising the total of confirmed world-wide H5N1 infections to 693. The count of confirmed H5N1 cases in 2014 is 44.

Sixteen countries have reported human H5N1 cases to WHO.[18] Through 2012, H5N1 cases were restricted to countries in the Eastern Hemisphere. On January 3, 2014, a woman from Canada infected with H5N1 died, but because she exhibited symptoms in late December 2013 she is counted as a 2013 case by WHO. This case from Canada is the first to be reported from the Western Hemisphere. In 2014, 29 cases were reported from Egypt, 9 from Cambodia, and 2 each from China, Indonesia, and Vietnam.

Figure 2. All countries reporting human H5N1 cases since 2003. 

Compared to 2013, the number of H5N1 cases in 2014 has increased by about 12%. Of the 44 reported cases in 2014 20 were male and 22 were female, the gender of two children were not identified. Females (52%) outnumber males (48%) among reported cases in 2014. Overall, females represent about 53% of all of the WHO-reported H5N1 cases where gender was noted. The male-female sex ratio for H5N1 cases is very different than the ratio for human H7N9 cases.

In 2014, the age of H5N1 cases ranged from one year old to 75 years old with a median age of 12. In 2013, children under 10 years old were the most commonly infected individuals. In 2014, young children were again frequently infected. This contrasts with H7N9 infection which occurs primarily among elderly individuals.

Figure 3. Comparison of H7N9 and H5N1 by Age Groups. 

Of the 44 cases in 2014, 20 are reported to have died. The case-fatality risk for H5N1 cases is .45 for the 2014 calendar year as of December 31, 2014. Because numerous cases reported in December in Egypt are still hospitalized, additional deaths among these cases may occur. Notably, with 29 confirmed H5N1 cases in 2014, Egypt has now overtaken Indonesia as the country with the greatest number of overall confirmed H5N1 cases.

Figure 4. Comparison of the Number of Reported H5N1 Cases by Country.

Most of the H5N1 cases in 2014 were reported from Egypt (66%). Although a number of these cases were reported from the same general location, it is not possible to speculate whether they represent clusters of cases that would signal human-to-human transmission. While H5N1 continues to be a potential pandemic threat, the limited number of cases in 2014 suggests that H5N1 has not yet achieved the ability to efficiently transmit between humans.

Avian Influenza A (H10N8)

The first reported human case of a novel influenza A(H10N8) subtype was reported in November 2013 in China. A 73-year-old woman from the Donghu District, Nanchang, Jiangxi Province experienced onset on November 28, 2013 and was hospitalized on November 30, 2013. She died nine days later on December 6, 2013. The woman had visited a live bird markets several days before onset.[21] 

In 2014, two additional human cases of H10N8 have been reported, both from China. The first is a 55-year-old woman who was hospitalized on January 15, 2014. This woman is from Nanchang, Jiangxi Province. [21] This woman visited a live bird market on January 4, 2014.

The second human H10N8 case in 2014 was a 75-year-old man from Nanchang, Jiangxi Province. He experienced onset on February 2, was hospitalized, and died on February 8, 2014.[22] A retrospective serological study in Guangdong Province indicates that 3 animal workers (out of 827) may have had subclinical H10N8 infections prior to November of 2013.[23]

Since 1965, H10N8 seems to have been circulating among wild and domestic birds in at least seven countries (China, Italy, United State of America, Canada, South Korea, Sweden and Japan).[21] Recent analysis suggests that the reported human cases of H10N8 in China resulted from exposure in live bird markets and that H10N8 had been circulating in these markets for months.[24,25] There is a potential for more sporadic infections of H10N8 in the future, especially because WHO notes that influenza viruses are unpredictable.

Avian Influenza A(H5N6)

Chinese authorities first reported the avian influenza A( H5N6) virus in poultry in April 2014.[26] During that same time, China also reported the first human case of influenza A(H5N6). A respiratory tract sample from a 49-year-old man from Nanchong, Sichuan Province tested positive for H5N6. He later died of died of severe pneumonia.[27,28] In December 2014, a second human infection of H5N6 was confirmed. A 58-year-old man from Guangzhou, Guangdong Province experienced onset on December 1 and was hospitalized on December 9, 2014. The individual is currently in critical condition. Contact tracing of this second case has failed to identify any additional cases.[29,30] H5N6 has also been detected outside of China in domestic poultry flocks in Laos and Vietnam [26,31]. WHO states “given that the disease {H5N6} seems already widespread in poultry, further sporadic human cases or small clusters of infection would not be unexpected.” [27]

Other Avian Influenza Viruses (H5N8 and H5N2)

In 2014 other Highly Pathogenic Avian Influenza (HPAI) subtypes of H5N2 and H5N8 were reported from various locations around the world including, East Asia, Europe, and North America [32,33,34]. These reported infections occurred in wild migratory birds as well as commercial poultry from flocks. No confirmed human infections of H5N8 or H5N2 have been reported through the end of 2014 although the possibility of future human infections from these two avian influenza viruses cannot be discounted.


Almost 400 people were infected with novel avian influenza viruses in 2014 primarily in China. The case-fatality risk for human avian influenza infection in 2014 is not clear but varies depending on the subtype. There is uncertainty about the extent of subclinical infections of these avian influenza viruses in the general population which would affect the spread of these viruses if one reassort into a pandemic strain. As yet, there is no evidence that any of these novel avian influenza viruses that infected humans in 2014 can efficiently infect and transmit between humans. Continued global surveillance to detect virological, epidemiological, and clinical changes associated with circulating influenza viruses is vital to human and animal health.

Acknowledgements and Notes
I thank all of the international and national public health agencies and ministries of health, posters at, and other internet disease trackers for their online efforts to announce and track human cases of various avian influenza strains. 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, 2014. For some individual cases, specific details are lacking or conflicting information is presented in online reports. However, the information and graphics presented here are based on data which is believed to be reasonably accurate and current through December 31, 2014.

[3] Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

[4] Human infection with avian influenza A(H7N9) virus – China

[7] Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus

[11] Human co-infection with novel avian influenza A H7N9 and influenza A H3N2 viruses in Jiangsu province, China

[24] Human Infection with Influenza Virus A(H10N8) from Live Poultry Markets, China, 2014

[31] Outbreaks of bird flu reported in Vinh Long, Tra Vinh, Quang Ngai

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