Saturday, January 31, 2015

The CDC is Watching for Human Avian Influenza Infections

So far, North America has been lucky. Community acquired infections of avian  influenza have not yet occurred, although an imported case of H5N1 was identified in Alberta Canada in 2013 and two imported cases of H7N9, a husband and wife, were reported from British Columbia in just this past week.

Because of recent outbreak of highly pathogenic avian influenza (H5 subtypes) in wild birds and domestic flocks in North America, the Center for Disease Control has issues guidance for health care workers for identifying and testing patients with potential avian influenza infections. As of January 31, 2015, no H5 subtype human avian influenza infections have been recorded from these outbreaks which have been reported from six western states along the Pacific Flyway (Washington, Oregon, Idaho, Nevada, Utah, and California ). (link)


The CDC guidance will help health care workers to assess patients with influenza symptoms that might be at infected with an H5 subtype of avian influenza.   The CDC identifies the following  items as risk factors for potential avian influenza infections. Individuals
who have had recent contact (<10 days prior to illness onset) with sick or dead birds in any of the following categories:
Domestic poultry (e.g., chickens, turkeys, ducks)
Wild aquatic birds (e.g., ducks, geese, swans)
Captive birds of prey (e.g., falcons) that have had contact with wild aquatic bird
Contact may include: direct contact with birds (e.g., handling, slaughtering, defeathering, butchering, preparation for consumption); or direct contact with surfaces contaminated with feces or bird parts (carcasses, internal organs, etc.); or prolonged exposure to birds in a confined space.

The CDC also states that exposures that occur in geographic regions in the United States where newly detected avian influenza A H5 viruses have been identified are of most concern ( e.g. Washington, Oregon, Idaho, Nevada, Utah, and California).

Health care workers need to be familiar with this CDC guidance in order to adequately assess patients who might be infected with avian influenza. Last year a suspected Ebola patient was not correctly diagnosed and was sent home causing an Ebola scare in Texas. The patient later died.  Human infections from H5 subtypes are virulent often resulting death. There is some evidence that H5 subtypes can be transmitted from human-to-human, so early detection is important.

If you experience influenza symptoms and meet any of the risk factors for avian influenza be sure to mention it to your doctor or health care professional at the time of your visit.

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 casesin 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.

Discussion

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 FluTrackers.com, 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.

References
  
[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





Monday, December 1, 2014

How will we know when the number of Ebola infections starts to decline?



According to the World Health Organization (WHO), three West African countries continue to experience intense transmission of Ebola. More than 16,000 cases of Ebola have been reported from Guinea, Liberia, and Sierra Leone in the past several months since the outbreak started earlier this year (link). There is some evidence that the rate of new Ebola infections in these countries is not growing as fast as previously estimated which is good news. The WHO situation report published on November 26, 2014 (link) states “Case incidence is stable in Guinea, stable or declining in Liberia, but may still be increasing in Sierra Leone”.

However, there is great uncertainty over the quality of the reporting data emanating from West Africa on this Ebola outbreak. Also, based on the fluctuating numbers of newly reported cases in each of these three countries, it is difficult to assess the increases or decreases in the incidence of cases in these three countries. Assuming that the case numbers reported in the WHO situation reports are representative the number of infections in each of these countries, the average number of new cases per day can be graphed on a timeline. Below, the average number of new cases per day is compared with the cumulative moving average of cases since the start of the outbreak within each of the three countries.

These graphs clearly show that the trajectory of the number of new cases in each country generally support the WHO statement. At this time, the number of new  daily cases  in Guinea appears to be declining towards the cumulative moving average. Recent new case counts for Liberia have fallen below the long term cumulative moving average. For Sierra Leone, the reported average number of Ebola cases is above the cumulative moving average,  This is a clear indication that rate of Ebola infections in Sierra Leone have not yet started to decline.

Eventually, declines in the number of new Ebola infections in these three countries will only be apparent when the daily average of newly reported Ebola cases drops below-and stays below-the cumulative moving average. At that time the cumulative moving average will begin to decline as well. Comparing the number of daily new cases in these countries in relation to the cumulative moving daily average will help identify when there is a downturn in the number of new Ebola infections in these countries. 






Graph Notes:

1. Data used to construct these graphs is derived from the country totals provided by WHO in the Ebola situation and data updates current through November 28, 2014 (link). The new daily cases counts includes all Ebola cases reported from the country including, confirmed, probable, and suspected cases.

2. The average number of new Ebola cases per days is computed as the total number of newly reported cases since the last report divided by the number of reporting days. The average number of new cases per day is recalculated after each WHO report.

Sunday, November 23, 2014

WHO provides additional data on MERS cases from Saudi Arabia in October

Earlier this month, I noted that the World Health Organization (WHO) did not report information on five MERS cases from Saudi Arabia from October  (see Has WHO overlooked 5 MERS cases in Saudi Arabia?), although theses cases were counted in the world-wide total in the Disease Outbreak News posted on November 7, 2014 (link).

Two days ago, the WHO provided additional details about these five cases (link)  that are not available on the statistics page of the Saudi Arabia Ministry of Health website. The reporting of these additional case details is important to understanding the nature of human MERS infections.

Since, the last WHO update on MERS from Saudi Arabia (through October 30, 2014), the Saudi Arabia Ministry of Health website has reported almost 20 new MERS cases (link),. Hopefully, WHO will publish details about these cases soon as well.

Tuesday, November 4, 2014

Has WHO overlooked 5 MERS cases in Saudi Arabia?



Previously, I discussed discrepancies between the MERS case counts for the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) (link). The WHO case count differed from the number posted on the Saudi Arabia Ministry of Health website by 15 cases. At least 12 cases previously announced by the Saudi Arabia Ministry of Health had not yet been posted in Disease Outbreak News by the WHO through October 21, 2014.

Yesterday the WHO reported in aggregate 12 new MERS cases from Saudi Arabia from the period October 18 to October 26, 2014 (link). These 12 cases do not equate to the 12-case differential noted in my previous post. The most recent WHO report regarding cases from Saudi Arabia (October 16 link) only enumerates cases through October 11, 2014. However, between October 12 and October 16, the Saudi Arabia Ministry of Health website announced five additional MERS cases, Taif (3), Riyadh (1), and Al Karj (1).

Hopefully, the WHO will report these cases in the future or discuss why they are not included in the total count for MERS cases from around the world.

Links to five Saudi Arabia MERS Cases (October 12-16)




Thursday, October 30, 2014

Comparison of WHO and ECDC MERS case counts



As of October 16, 2014, the World Health Organization (WHO) reported a total of 877 cases of Middle East respiratory virus syndrome (MERS) from WHO member states (through October 11, 2014 link).  The European Centre for Disease Prevention and Control (ECDC),  a European disease monitoring organization established in 2005 (link), has reported a total of 906 MERS cases from around the world through October 21, 2014 (link). Both WHO and ECDC provide updates on the MERS outbreak, however neither these agencies provides a publicly available line list of cases.

Because it appears that the next MERS wave has started on the greater Arabian Peninsula in the Middle East, is worth discussing the apparent discrepancy in the number of MERS cases between the WHO and the ECDC.  

The table below compares the current counts of MERS cases for WHO and the ECDC through specific dates.  The differences in the case counts are discussed below by country.  WHO and the ECDC enumerate cases based on the reporting country (under IHR), rather than the source country of infection.  Also included in the table below is a column with the case counts that have been tabulated by FluTrackers.com (link). The FluTrackers’ case counts are not directly comparable to the WHO or ECDC data because the FluTrackers’ counts are based on the country of the source of infection not the reporting country.

There are minor discrepancies between the WHO case counts and the ECDC case counts as noted in the detailed discussions below. It would be beneficial if both of these organizations would make their line list of cases publicly available on the internet.
 

Discussion of table discrepancies between WHO and ECDC

Jordan

The case count noted by WHO for Jordan does not appear to include the seven retrospectively confirmed cases from the first MERS cluster in Jordan in 2012 (link).

Philippines

The WHO does not recognize any cases from the Philippines. At least two possible MERS cases have been reported from the Philippines. The first was a male nurse who tested positive for MERS in United Arab Emirates and later tested negative in the Philippines in April, 2014 (link). The second was a female nurse who was tested in Saudi Arabia and arrived in the Philippines after the positive test results were announced by Saudi Arabia (link). It is not clear which case, if either, of these two cases is included as a case from the Philippines by the ECDC.

Qatar

On October 12, 2014, the Supreme Health Council of Qatar officially announced the first MERS case in Qatar in 2014 (link), so  the WHO may report his case in the future.

Saudi Arabia

As of October 21, 2014 the Saudi Arabia Ministry of Health web page reports a total of 771 MERS cases. The ECDC count for MERS cases from Saudi Arabia is 771, matching the Saudi Arabia Ministry of Health total.

The last official WHO update prior to October 21, 2014 was published on October 16, 2014 (link). At that time, the WHO case count for Saudi Arabia was apparently 756. There is a disparity of 15 MERS  cases between the WHO case count and the ECDC case count for Saudi Arabia. This difference appears to be a function of differential reporting dates rather than major disparities in the case counts. Between  October 11 and October  21, the Saudi Arabia Ministry of Health reported a total of 12 MERS cases that will probably be reported and incorporated in the WHO count in the near future.  

This would bring the WHO total through October 21 to 768.

The reason for the difference of three cases between the WHO data and the ECDC data is uncertain. Any number of additions and deletions (due to duplicates and false positives) in the case counts could affect this differential in the case counts.

Turkey

The first MERS case in Turkey was only reported on October 17, 2014 (link). The WHO later reported this case on October 24, 2014 (link).

United Arab Emirates

It is not clear how the ECDC determined an additional four cases from United Arab Emirates compared to the WHO counts.