First Human Case of A(H5N1) Imported into the Western Hemisphere

Influenza A(H5N1) jumped to humans for the first time in 1997 and since then more than 650 confirmed cases of H5N1 have been reported. These cases have been reported from 15 countries in Asia, Africa, Europe, but none from countries in the Western Hemisphere.

On January 8, Canadian public health officials announced that a woman, in her late 20s, from Red Deer, Alberta, died from H5N1 on Jan 3, 2014. She had returned from the People’s Republic of China via Beijing after visiting for three weeks within China. She apparently fell ill on the return flight to North America. Although it is likely she was infected in China in late December 2013, this is the first confirmed case of H5N1 reported in North America. (link below)

Should you be concerned if you live in North America?

This single case does not indicate that there is an H5N1 outbreak in North America. A single imported case in Canada should not spark pandemic hysteria. Even though over the years researchers have speculated that H5N1 could be the next pandemic virus, this case does not signal the start of a pandemic.

Of more immediate concern for people in North America is seasonal Influenza. Seasonal influenza is particularly virulent this 2013-2014 flu season. Rather than worrying about H5N1, people should educate themselves about different ways of protecting themselves from the seasonal flu varieties that are now widely circulating.

The best course of action is to monitor your local public health agencies for updates and heed any recommendations for minimizing exposure to all infectious disease.

Canada - H5N1 death in Alberta after travel from China - died from meningoencephalitis

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

A Review of Human Influenza A(H5N1) Cases in 2013

In 2013, 38 human cases of Influenza A(H5N1)  were reported from around the world. This number represents an 18% increase over the number of reported cases in 2012. Six countries reported cases in 2013, Bangladesh, Cambodia, China, Egypt, Indonesia, and Vietnam. Cambodia reported about 71% (27) of all cases reported in 2013.   In 2013, children younger than 10 years old represent about 63% of all cases. No human clusters were reported in 2013. Relative to other countries, Cambodia experienced the greatest percentage increase in human infections in a short period of time. The continued low frequency of reported infections does not eliminate H5N1 as a pandemic threat.  

Influenza A(H5N1), (often referred to “bird flu” or avian influenza or HPAI), is an emerging infectious disease. It was first detected in humans in Hong Kong in 1997. Since 2003, the World Health Organization (WHO) has been monitoring human outbreaks of H5N1. Through December 31, 2013, WHO has officially reported a total of 648 confirmed human cases of H5N1. The most current WHO summary report on H5N1 is Influenza at the human-animal interface: Summary and assessment as of 20 December 2013.  The most recent WHO time line of significant events associated with the H5N1 virus was last updated on December 17, 2012 (link).The following summary of human cases of H5N1 in 2013 is generally organized according to the outline presented previously in “H5N1 in 2012: The Year in Review”. (link)

Since 2003, 15 countries have reported human H5N1 cases to WHO (link). The count of WHO-confirmed H5N1 cases in 2013 is 38.  Compared to 2012, the number of H5N1 cases increased by about 18%. In 2013, 6 countries reported human cases of H5N1, Bangladesh (1 case), Cambodia (26), China (2), Egypt (4), Indonesia (3), and Vietnam (2). These same six countries were the only countries to report H5N1 cases in 2012. 

Geographic Distribution

More than 60% of the H5N1 cases reported in 2012 occurred in Egypt and Indonesia. In 2013, more than 60% of the H5N1 cases were reported from Cambodia. Between 2003 and 2012, Cambodia had only reported 21 cases. In  the 12 month period of  2013, Cambodia reported  26 H5N1 cases, more than doubling  the count of previously reported cases. Indonesia continues to lead the world in cumulative number of reported human H5N1 cases with 195.  Egypt is second with 173 reported cases.  Based on the total number of cases reported, Cambodia now exceeds China and Thailand in total count of cases. It now ranks fourth behind Indonesia, Egypt, and Vietnam.

Map: WHO map of countries (Administrative level 1) with human H5N1 cases in 2013.

 Map: All countries reporting human H5N1 cases since 2003. 

Map: The approximate geolocations of H5N1 cases in Cambodia from 2003-2013.

Gender Statistics

Of the 38 reported cases in 2013 19 were male and 19 were female, although in the past females outnumbered males among reported cases. Overall, females represent about 53% of all of the WHO-reported H5N1 cases where sex was noted.  In 2013, 12 of the males died as did an equal number of females (12). 

Age Statistics

In 2013, the age of H5N1 cases ranged from less than one year old to 58 years old with a median age of 6. Children under 10 years old were the most commonly infected individuals. Twenty-four (63%) of the 38 cases were less than 10 years old in age.

Graph: Comparison of H5N1 infections in 2012 and 2013 by age group.

Twenty-two of the 24 children in 2013 were reported from Cambodia.  Only two other children were reported, a four-year-old from Vietnam and a one-year-old from Bangladesh.  Among all H5N1 cases, the greatest number cases are children in the 0-10-years-old age group.

Graph: All H5N1 cases by age group, 2003 to 2013.

Mortality Statistics

Of the 38 cases in 2013, 24 died. The  case-fatality ratio (CFR) is .625 for the 2013 calendar year. Over the past several years the CFR has not appreciably decreased.  Although there is inter-year variability, the overall CFR for the 648 WHO reported cases is .59.

As in previous years, children continued to have a slightly better survival rate than infected adults.  The CFR for the 24 children under 10 years old is .54, while the CFR for the 14 individuals older than 10 years is .78.

With the 26 cases and 14  deaths, Cambodia now has the second highest CFR rate at .70. Among the countries reporting at least 25 H5N1 cases, only Indonesia, with a CFR of .84, exceeds the CFR in Cambodia.

Table: H5N1 mortality by age group in 2013.

Seasonality

As noted previously, human H5N1 cases do not randomly occur throughout the year, but the number of cases fluctuates in a pattern similar to that of seasonal influenza in the northern hemisphere (link). Below is a current graph of the month of onset for almost all of the worldwide confirmed cases since 2009.  

Graph: Monthly H5N1 case count, 2009 to 2013. 

H5N1 Clusters

All 38 cases reported to WHO in 2013 represent sporadic cases. No clusters, as defined by WHO, were identified in 2013.  A cluster is defined as two or more cases of confirmed, probable, or suspected Influenza A(H5N1) 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. (link)

Discussion

In summary, the 38 H5N1 cases reported in 2013 is a slight increase over 2012, but less than the highest yearly total of 115 cases in 2006.  The concentration of 27 cases in Cambodia including 24 infected children is unusual, and the lack of reported clusters in 2103 is notable as well. As noted in 2012,  there has been an observable trend of an increasing number of H5N1 infections among young children. That trend has continued in 2013 with 63 % of the cases being younger than 10 years old. Previous analyses suggested that this age group had a high recovery rate. However, the infected children in 2013 had much lower survival rate. The reason for low recovery rates in children in Cambodia deserved further research.

Gain of function research in 2011 demonstrated that, in theory, only a few genetic changes are necessary for H5N1 to become an aerosolized pandemic virus.  While media attention in 2013 has focused on the Middle East respiratory syndrome coronavirus and  the novel influenza virus  A(H7N9), H5N1 continues to a pandemic threat, even if it is not receiving media attention.

 

 

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 H5N1 cases. 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. However, the information and graphics presented here are based on data which is believed to be reasonably accurate and current through December 31, 2013.

Tracking the MERS-CoV Outbreak

The World Health Organization (WHO) is charged with tracking outbreaks of novel diseases around the world. For novel disease outbreaks such as H5N1, H7N9, SARS, Middle East respiratory syndrome coronavirus (MERS-CoV),  etc., WHO does report cumulative updates of the counts and locations of cases providing that the member states comply with International Health Regulations (IHR) about timely reporting of cases.

However, WHO does not provide a publicly available line list of cases of these novel disease outbreaks.  Such line lists of cases with epidemiological and geographic information help researchers and the general public assess the potential danger of these novel outbreaks.   Through December 2, 2013, more than 170 confirmed and probable human cases of  MERS-CoV have been reported from 11 countries including France, Italy, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Spain, Tunisia,  the  United Arab Emirates and the United Kingdom. Members of FluTrackers.com have been compiling a line list of confirmed MERS-CoV cases since early in 2013.[1]

I have posted a concordance list of the WHO confirmed cases with the individually reported and tracked MERS-CoV cases by FluTrackers members at this link.[2] This concordance list provides a basis for the general public to obtain more detailed information about individual cases in order to assess for themselves the nature and geographic distribution of this novel coronavirus.

[1] 2012/2013 Case List of MoH/WHO Novel Coronavirus nCoV Announced Cases

[2] WHO MERS-CoV Case Concordance List (as of December 2, 2013)