Wednesday, March 1, 2017

The Current Status of the 2016 – 2017 H7N9 Outbreak in China as of March 1, 2017 (Is the Outbreak Just About Over?)

For the purposes of this discussion the current outbreak of H7N9 began November 1, 2016 and is still continuing. More than 460 human cases have been reported from China. Of these cases, 426 have symptom onset dates reported by the World Health Organization (WHO) for cases with onset before February 10, 2017.

Graphing the symptom onset dates for these H7N9 cases provides a count of new daily infections of H7N9. Also included in the graph are the remaining 37 cases based on their reporting date rather than symptom onset date which is not available at this time for cases reported after February 11. The graph, an epidemic curve, shows that the greatest number of H7N9 infections occurred on February 1, 2017, based on a five day moving average.

Even if The 37 cases for which symptom onset dates are not available are distributed over the 17 days following February 11, they are an insufficient number of new cases to exceed the five-day moving average which peaked above 10 cases per day on February 1, 2017. The number of human H7N9 infections in this outbreak now seems to be declining. The decline in human cases can be attributed to closing of some local poultry markets by Chinese authorities. Hopefully, the number of H7N9 infections will continue to decrease.

While there is little evidence of human-to-human transmission in this outbreak, every human H7N9 infection is a potential opportunity for the influenza virus to reassort and become transmissible between humans.

The Current Status of the 2016 – 2017 H7N9 Outbreak in China as of March 1, 2017 (Geographic Distribution)

As noted in the previous post, there have been at least 460 human cases of H7N9 reported in the current H7N9 outbreak between November 1, 2016 and February 27, 2017. Of great concern is a possibility that many of these cases are a result of human-to-human transmission. There is little publicly available information about the relationships, if any, among these hundreds of cases. To date, only four two-person clusters have been reported by the World Health Organization (WHO, January 17 and February 20) with family members comprising three of the clusters. For all four of these clusters, the WHO notes that human-to-human transmission cannot be ruled out.

One important clue to the nature of the outbreak is the geographic distribution of the reported cases. An indirect signal of human-to-human transmission can be multiple cases occurring in a localized geographic area within a short period of time. The recent WHO line listing of H7N9 cases from China (Influenza at the Human Animal Interface: Summary and Assessment, February 14, 2017), only provides the province or region for each of the reported cases. Line lists of cases provided by the Centre for Health Protection (CHP) Weekly Influenza Report provide additional geographic locational information to the prefecture level (administrative level 2) for individual cases. The Food and Agricultural Organization of the United Nations (FAO) line list of H7N9 cases occasionally provides the geographic locale of the county or administrative level 3 for some individual cases.

The most accurate locational information for individual cases is reported in local public health reports on Chinese websites. This information has been translated to English by members at FluTrackers. Sharon Sanders at FluTrackers has linked to these translated reports in the FluTrackers running list of H7N9 cases. Unfortunately, local publication of data of confirmed H7N9 cases in China are infrequent, so geographic details about individual cases beyond administrative level 2, the prefecture level, are limited to only a handful of the reported cases in this outbreak.

However, even with limited geo-locational information for individual H7N9 cases, the geographic distribution of cases can be plotted and is very informative. The map below provides a heat map of the distribution of cases in eastern China computed from the prefecture level data. Overlaid on this map are plotted locations of individual cases. The map shows the concentrations of cases in the 2016-2017 H7N9 outbreak in the provinces of Jiangsu, Zhejiang, Anhui, and Guangdong. In southern Jiangsu, hot spots include Suzhou, Wuxi, Taizhou, and Changzhou. In northern and eastern Zhejiang, the hot spots are Hangzhou, Ningbo, and Wenzhou. Hefei is the hot spot in central Anhui province and in central Guangdong, Guangzhou is the location with the most reported infections.

This map also shows that cases are widely scattered throughout many provinces during the current outbreak. The widely dispersed nature of these cases provides indirect support that human-to-human transmission is not occurring in these areas and the infections are resulting primarily from animal-to-human transmission. Even the increased number of cases in the hot spot locations does not mean that human-to-human transmission is occurring. The prefecture level cities mentioned above have very large populations most exceeding several million people. Were human-to-human transmission occurring in these areas we would expect many more reported cases.

The Current Status of the 2016 – 2017 H7N9 Outbreak in China as of March 1, 2017 (Case Count)

Since November 2016, more than 460 human cases of H7N9 have been reported or imported from China. To put this number in perspective, confirmed cases of H7N9 were first reported in March 2013, four years ago. Of all the cases of human H7N9 infections reported to date, more than one-third (about 36%), have occurred in the last four months. This raises a concern that H7N9 is not only causing outbreaks in China but could lead to epidemics and perhaps even a pandemic.

It is difficult to tabulate exactly how many H7N9 cases have occurred since November 1 of 2016, because case reporting and enumeration seem to vary among various public health reporting agencies. Media and blog reports have interpreted variation among these counts of H7N9 cases as a failure of public health officials in China to accurately track H7N9 cases, often leading to exaggerated claims of the rates of infection in China.

It is possible to arrive at a close approximation of the actual number of recent cases by using different data sources. Official counts of human cases of H7N9 are individually presented by the Food and Agricultural Organization of the United Nations (FAO), the Centre for Health Protection (CHP), and the World Health Organization (WHO). The discrepancies between these different agencies can be attributed to differential reporting periods. The FAO updates its list of human H7N9 infections every few days or whenever newly confirmed cases are reported. The CHP only updates its case information every seven days in the Weekly Influenza Report. The WHO only provides irregular updates, often only in aggregate fashion in the Disease Outbreak News. Later the WHO usually provides case details in its Influenza at the Human Animal Interface: Summary and Assessment that is only published on a monthly basis.

In order to compare these three data sets we need to have a starting point. The current outbreak in China started in November 2016. Prior to that time only a few sporadic cases were reported in the preceding weeks. Between November 1, 2016 and February 16, 2017 (the last date of FAO reported cases), the FAO has noted 437 cases of human H7N9. On November 1, 2016, the WHO count of human H7N9 cases was 800. The most recent WHO Disease Outbreak News H7N9 reports a total of 1223 confirmed H7N9 cases, indicating a total of 423 cases since November 1, 2016. The WHO case counts however only includes cases reported through February 14, 2017.

Prior to November 1, 2016, the CHP reported a total of 798 cases. Since then, the CHP has reported 461 H7N9 cases through February 27, 2017. Adjusting the FAO number of cases to include 35 cases noted by CHP with reporting dates after February 16, would bring the total FAO case count through February 27 to 472 for the period from November 1, 2016 – February 27, 2017. Adding the 43 additional cases noted by CHP (and not yet reported by WHO) to the WHO-reported count of 421 gives a total of 465 confirmed cases for the period of November 1, 2016- February 27, 2017. The variations between the adjusted counts of these three agencies is minimal, the average is 466 cases. Based on these data, the WHO count of H7N9 cases through February 27 should eventually be reported to be about 1267 cases.

The differences between the H7N9 case counts among these three agencies are primarily a function of differential reporting dates, and not the result of confusion about the number of cases by Chinese public health officials.

Another question to ask is how accurate is this count of H7N9 cases from China. In the past, China has been accused of underreporting infectious diseases to the WHO. Could there be hundreds of more human H7N9 cases that are not being reported to the WHO?

We can compare the sex ratio and median age of the 461 cases noted by the CHP in this outbreak with the sex ratio and median age reported for the previous 792 confirmed H7N9 cases prior to November 1, 2016. For the cases prior to November 1, 2016, males represent 68% of the cases, and females represent 32% of the cases. In the current outbreak, males represent 71% of the cases and females represent 29% cases. These numbers are within the range of statistical variation.

For the cases prior to November 1, 2016, males had a median age of 58 and females had a median age of 55. For the cases in the current outbreak, males have a median age of 58 and females a median age of 56. The median age for both males and females is comparable from the cases in this outbreak to all of the previous H7N9 cases reported.

Thus, there is no reason to assume that China has been underreporting H7N9 cases during this outbreak. Hypothetically, in order for China to be underreporting current H7N9 cases, the public health authorities would have to be implementing a sophisticated real-time algorithm that would allow cases to be underreported, yet still maintain the male to female ratio and the average median age for the remaining cases. Because China is reporting new H7N9 cases every few days, it does not seem possible for China to be purposefully underreporting cases of H7N9 in this outbreak. Internet claims of hundreds of unreported human H7N9 cases in China are unfounded.