What is happening with H7N9 in China?

Based on illness onset dates from January through the end of November 2016, China officially reported about 115 human cases H7N9 infection. Over the course of several days in early January 2017, China notified the World Health Organization of more than 100 additional human cases of H7N9 presumably having been infected in December 2016. It appears that almost as many people were infected in December as all of the preceding months in 2016.

The graph below shows the distribution of H7N9 cases by onset date where available and then by reporting date. The graph clearly shows the large increases in the number of infected individual reported recently. Should this increase be a cause for alarm?

Increases in human cases of avian influenza always increase the risk for sustained human to human transmission of the disease. Reviewing the minimal data that is available for the 107 recent cases reported by China, some observations can be made. About 36% of these new cases are female and 67% are male. This gender ratio is similar to the earlier cases in 2016. The age range of these cases is 23 to 91 years with a median age of 54 years old, also similar to the age distribution of earlier cases in 2016. There is no evidence from these recent cases that different age groups are being disproportionately infected.

Finally, the case fatality risk (CFR) for these recent cases is about .31. This is higher than the CFR for earlier cases in 2016 and the overall CFR for all cases since the initial outbreak in 2013. Many of the nonfatal cases are reported to have severe pneumonia, which suggests that more of these individuals may not recover.

There is nothing in the publicly available reports of these cases which would indicate the extent of human to human transmission, if any. The best indirect way to assess the potential for human to human transmission is to evaluate human clusters. In the available data, there is no information about relationships among various infected individuals, nor are onset dates available to assess chains of transmission.

 The only information we currently have available to interpret potential clusters is the geographic distribution of cases. The map below plots the geographic distribution of human cases recently reported by China compared with all of the H7N9 cases with onset dates or reported dates since January 1, 2016. About half of these newly reported cases are spread out among various provinces in eastern China and probably represented isolated sporadic infections. 

However, the remaining 50+ cases were reported from just four cities. The map below shows the four cities with 9 or more H7N9 cases reported in the January announcements, Suzhou, 21 cases, Wuxi 11 cases, and Changzhou 10 cases, all in Jiangsu Province. The fourth city is Hangzhou in Zhejiang Province with 9 cases. All of these cities are large population centers, so we will need more case details to determine if there is human to human transmission in these areas.

Information on contact tracing would be useful as well. None of the reported cases appears to be asymptomatic. Less 10 cases since the initial human H7N9 outbreak have been reported as asymptomatic. Are mild cases being overlooked?

If the number of reported H7N9 cases continues to grow dramatically over the next several weeks, it may signal a local H7N9 epidemic in China. We need to be watching H7N9 in China very closely.

A Review of Human Influenza A(H7N9) Infections in 2016

Note: Between January 1 and January 9 2017, China officially reported  to WHO at least another 107 human cases of H7N9 most with onset dates in 2016. The information presented below relates to  the first 125 cases reported with onset dates in 2016.  updated January 11, 2017

The first officially reported human case of infection from a reassortant avian influenza A(H7N9) virus was from the People’s Republic of China (China) in March of 2013, although human H7N9 infection may have occurred in or near Hong Kong as early as 2007 (FAO ID event 220957). Since 2013 the World Health Organization (WHO) has officially reported 808 human cases of H7N9 as of December 23, 2016. In the past few days, an additional 13 H7N9 cases have been reported by public health officials in China but have not yet been published by the WHO. Of these 821 cases, 696 have onset or reporting dates prior to December 31, 2015. The total number of reported H7N9 cases in 2016 is 125.

Geographic Distribution 

All 125 human cases of H7N9 in 2016 were reported from China. These cases have been reported from 18 provinces and special administrative regions. More specific geographic location information was available for 117 of these cases, the remaining 8 cases were only reported from a specific province; Anhui 2, Hebei 2, Fujian 1, Hubei 1, Shandong 1, and Zhejiang 1. The map below depicts the provinces and special administrative regions with reported 2016 cases. Dots indicate the locations of individual or multiple cases reported in 2016. In 2016, these cases all occurred in the Western portion of China.

Table: Comparison of the frequencies of human H7N9 infections reported in China between 2013-2015 and 2016 by province/special administrative regions.

Map: Geographic distribution of human H7N9 cases in China in 2016.

Age Statistics 

From 2013 to 2015, the median age of H7N9 infected males was 57.5 years with ages ranging from 1 to 91 years old. For females during that period the median age was 54.5 with ages ranging from less than year to 85 years old. The age distributions by gender for 2016 is similar. The chart below compares age categories for 2013-2015 and 2016. In 2016, infected individuals were somewhat younger than previous years.

Graph: Comparison of the frequencies of human H7N9 cases by age categories.

Gender

Between 2013 and 2015, 471 of the reported cases were male (68%) and 220 of the reported cases were female (32%). The genders of the remaining cases were not published. Among the 125 cases reported in 2016, 72% (85) were male and 28% (33) were female. Seven cases do not have a reported gender.

It seems that males are far more likely to contract H7N9 infections than females. Because almost all cases are associated with exposure to infected poultry, it is possible that different gender roles expose males more frequently to affected poultry than females. 

Fatalities

Between 2013 and 2015, 143 of the 696 reported H7N9 cases were reported as fatal. These data would suggest a minimum case fatality risk (CFR) of .21.

The CFR, as defined here, is the conditional probability of death from an H7N9 infection, a ratio between H7N9-caused deaths and recoveries/asymptomatic cases. Because follow-up reporting is lacking in many of these cases, the actual number of deaths versus the number of recoveries is uncertain. Very few of the cases in the period from 2013 to 2015 were officially reported as recovered (only 133).

In 2016, 29 of the 125 cases were reported as fatal. At face value, the CFR for 2016 is .23 but it is likely to be higher since many of the recently reported cases are currently being treated.

H7N9 Clusters

Most of the reported human H7N9 infections in 2016 result from zoonotic transmission of the virus from domestic poultry. Public health reports in 2016 rarely indicate the possibility of human-to-human transmission among confirmed H7N9 cases which would signal a cluster of cases. 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 link.

Based on family ties or restricted geographic area, potential human H7N9 clusters in 2016 include the following. In February 2016 infected individuals in several locations may represent multiple clusters, two siblings in Suzhou Jiangsu, several family members in Wuxi Jiangsu, and several unrelated individuals in Fuzhou Fujian. Several family members from Tahie Jiangxi were reported as H7N9 cases in April. Two cases from Hebei in July of 2016 may represent a cluster. Recently, two infected individuals from Kunshan Jiangsu were reported in November and three cases in Hefei Anhui in December, with no other details are available.

Discussion

Most of the human H7N9 case reported in 2016 are sporadic infections. As noted above, a few clusters of cases suggest that human-to-human transmission may have occurred but did not result in sustained human-to-human transmission. H7N9 cases seems to occur on an annual cyclical basis that follows the pattern of season human influenza infections. As depicted in the chart below, H7N9 cases were frequent from week numbers 1-23 and started increasing again in week number 46. The seasonal fluctuation in human infections indicates that more H7N9 cases can be expected in the coming months. While the number of H7N9 cases declined in 2016 compared to earlier years, the potential for a deadly epidemic or a possible H7N9 pandemic continues to exist.

 

 Chart: Epidemic curve of human H7N9 cases in 2016.

Note: The information presented and discussed here is based on a compilation of publicly available data sources including WHO, Food and Agriculture Organization of the United Nations, and various public health agencies supplemented by media reports as available.