H7N9 Preparedness: What The CDC Is Doing

A CDC scientist uses a pipette to transfer H7N9 virus into vials for sharing with partner laboratories for public health research purposes.

 

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While it remains to be seen just how much of a threat the H7N9 virus will pose to global health, the CDC – quite prudently – is taking steps to prepare, should this virus eventually pose a pandemic threat.

A few excerpts from a CDC posting from today, and then I’ll return with a bit more, including what you should be doing now to prepare as well:

 

H7N9 Update; CDC Pandemic Preparedness Activities Progress

April 26, 2013 – The number of human infections with avian influenza A (H7N9) in China has risen to 109; with 23 deaths.* There are still no reports of H7N9 in the United States. While there is no evidence of sustained human-to-human spread of this virus, CDC is taking routine pandemic preparedness measures to prepare for that possibility.

 

This update contains information on CDC laboratory activities to date, an update on the H7N9 outbreak in China and background information on RT-

PCR tests.

CDC Activities to Date Include:

Growing and Sharing the Virus

The first H7N9 virus isolate from China was received by CDC on Thursday, April 11, 2013. The virus was immediately inoculated into hundreds of eggs to grow more of the virus. The virus replicated well in eggs – not unusual for an avian influenza virus – and CDC was able to begin packaging vial samples of virus to distribute to other laboratories on Monday April 15, 2013. At this time, CDC has sent H7N9 isolates to 5 laboratories, including the United States Department of Agriculture. Only laboratories with the proper permits can receive the H7N9 virus isolate.

Conducting Studies with the Virus

CDC is using the H7N9 virus isolate to learn more about how the virus causes disease and its potential to spread among humans. Studies using cell cultures and animals will provide information about the severity of associated disease, as well as the pathology of the infection (what the virus does to the body either directly or indirectly). Additionally, animals are used to conduct studies on how the virus spreads. So far these studies have confirmed that this virus spreads between animals through close contact, which was expected. Studies to determine whether this virus can be spread in respiratory droplets through the air are ongoing.

Collecting Antiserum

Animal studies also allow for the collection of antiserum (antibodies) to these viruses so that the animals’ immune responses to the virus can be examined and other studies on immunity can be performed. Methods to detect immune responses in human serum are under development and will be used to study population immunity to the H7N9 virus. These studies are just getting underway; results are not expected for some time. The antibody tests also will be used to see if the candidate H7 vaccine viruses in development are a good match to the wild virus detected in China.

Creating a Test to Detect This Virus

CDC has completed work on new laboratory diagnostic test materials to identify human infections with the new avian influenza A (H7N9) virus. Influenza diagnostic tests already in use at qualified public health laboratories identify the new H7N9 virus as “unsubtypable” influenza A viruses, but cannot specifically identify the H7N9 subtype. The CDC H7N9 test materials are intended for use with real-time RT-PCR (reverse-transcriptase polymerase chain reaction), a highly accurate and sensitive laboratory test for detecting and identifying flu viruses in respiratory specimens by type and subtype. Providing this test to qualified public health laboratories will allow for more rapid testing of H7N9, though any H7N9-positive samples will continue to be sent to CDC for confirmation. Domestic and international shipping of these diagnostic test materials began this week.

<SNIP>

Developing a Vaccine Virus Candidate

CDC reports continued progress in developing an H7N9 candidate vaccine virus that could be used to manufacture H7N9 vaccine should that become necessary.

Testing for Antiviral Susceptibility

CDC also has tested the H7N9 virus isolate it received from China to see if it is susceptible to the influenza antiviral drugs oseltamivir/Tamiflu® and zanamivir/Relenza®. Laboratory testing at CDC indicates that this first virus isolate received on April 11 is sensitive (susceptible) to  these  `neuraminidase inhibitors’ (NAIs) the two antiviral drugs now recommended to treat seasonal flu.

 

Testing showed the virus would be resistant to the adamantanes, another class of antiviral drugs that are not currently recommended for use because of widespread resistance.

<SNIP>

Supporting Investigation in China

CDC received a request for bi-lateral assistance from China and a CDC team is in country now supporting the domestic outbreak investigation and response.

 

You’ll also find an update on the outbreak in China.

 

Update on H7N9 in China

While some mild illness has been reported in H7N9 patients, most have had very severe illness. China is reportedly treating H7N9 cases and recommending treatment of their symptomatic contacts with oseltamivir.

 

Since this H7N9 virus is a novel influenza virus with pandemic potential, the source of the human infections and how this virus spreads is being carefully investigated. H7N9 has been detected in Chinese poultry. While the investigation is ongoing, the current working assumption is that most people have been infected with the virus after having contact with infected poultry or contaminated environments. A New England Journal of Medicine (NEJM) article authored by Chinese public health officials released on Wednesday, April 24, 2013 reports that 77% of the first 82 H7N9 patients had some animal exposure.

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While there will be some in the media who may make a lot more out of these steps than is deserved, the CDC is simply taking the prudent, early steps one would expect them to take in the face of an unknown viral threat.

 

Government preparation is important, but a nation’s resilience in the face of a major crisis – whether it be local or global - truly comes from the bottom up, not from the top down.

 

Which is why businesses, organizations, families and individuals ought to be taking a page from the CDC’s play book and dusting off, reviewing, and updating their own Pandemic and Disaster Plans.

 

Not just because of the H7N9 virus, but because a wide range of disasters can happen anyplace and at anytime.

 

Earthquakes, tornadoes, hurricanes, floods, industrial accidents, and yes . . . even terrorist attacks, such as we saw last week in Boston  . . . can all disrupt, or threaten our lives.

 

Being prepared doesn’t mean going to extremes.

 

You don’t have to dig a bunker, or set aside 10 years worth of canned goods. Nor should you overly focus on any one particular threat, or scenario.

 

Instead, the smart money is on taking basic preparedness steps against `All Hazards', including those you may not automatically assume are a threat where you live.

 

Everyone should have a well thought out disaster and family communications plan, along with a good first aid kit, a `bug-out bag’, and sufficient emergency supplies to last a bare minimum of 72 hours.

 

Based on the  events in Japan (or after Hurricane Katrina in New Orleans, or the earthquake in Haiti) 3 days of supplies many not be enough for a truly worst case scenario.

 

The County of Los Angeles Emergency Survival Guide calls for having 3 to 10 days worth of food and water. Personally, I believe that 2-weeks of supplies isn’t an unreasonable goal, particularly if you live in earthquake or hurricane country.

 

The L.A. guide may be downloaded here (6.5 Mbyte PDF).

 

For more information on preparedness, I would invite you  to visit:

 

FEMA http://www.fema.gov/index.shtm

READY.GOV http://www.ready.gov/

AMERICAN RED CROSS http://www.redcross.org/

 

And lastly, you may wish to revisit some of my earlier preparedness essays, including:

 

In An Emergency, Who Has Your Back?

The Gift of Preparedness 2012

An Appropriate Level Of Preparedness

 

Because, by the time you recognize that a disaster is at your doorsteps, it is probably too late to prepare for it.

WHO: H5N1 Monthly Update

Credit WHO

 

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While far outpaced by the newly emerging H7N9 avian flu virus, H5N1 remains endemic among poultry and migratory birds in a number of countries, and continues to occasionally jump to humans.

Over the past 6 weeks the World Health Organization  has been notified of 6 infections, from four different countries; Egypt, Vietnam, Cambodia, and China.

 

For the past few months the WHO has been updating the H5N1 situation on a monthly basis.  Here is the latest report, covering cases reported between March 12, 2013 and today.

 

 

Influenza at the human-animal interface

Summary and assessment as of 26 April 2013

Human infection with avian influenza A(H5N1) viruses and associated animal health events

From 2003 through 26 April 2013, 628 laboratory-confirmed human cases with avian influenza A(H5N1) virus infection have been officially reported to WHO from 15 countries, of which 374 died.

 

Since the last update on 12 March 2013, 6 new laboratory-confirmed human cases with influenza A(H5N1) virus infection were reported to WHO from Bangladesh (1), Cambodia (1), Egypt (2 ) and Viet Nam (2). The investigations into these concluded that they were sporadic cases and that the appearance of sporadic cases is expected and will likely occur in the future.

 

Since the beginning of 2013, Cambodia has reported ten human cases with influenza A(H5N1) virus infection including eight fatal cases. These cases come from five provinces all located in southern Cambodia. These cases do not seem to be linked directly, and most had contact with sick poultry in their villages. The clade 1.1 viruses that have been isolated from cases are very similar to those isolated from poultry in the region. Investigations around these cases did not detect additional cases.

 

This evidence suggests sporadic infections from exposure to infected poultry or contaminated environments, rather than human-to-human transmission. It has been suggested that the A(H5N1) virus is circulating endemically in poultry in Cambodia1, as such, additional sporadic human cases might be expected.

 

Public health risk assessment of avian influenza A(H5N1) viruses: Any time influenza viruses are circulating in poultry, sporadic infections or small clusters of human cases are possible especially in people exposed to infected poultry kept in households or contaminated environments. However, currently, this A(H5N1) virus does not appear to transmit easily among people and therefore the likelihood of community level spread of this virus remains low. Therefore, the public health risk associated with this virus remains unchanged.

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You’ll find additional details on some of these recent cases in the following blogs:

• H5N1: Meanwhile, In Vietnam . . .

• Vietnam Reports H5N1 Fatality

• IEDCR Reports H5N1 Fatality In Bangladesh

• Meanwhile, Cambodia Reports Their 10th H5N1 Case

• FAO/ECTAD Report: H5N1 Case In Egypt

Eurosurveillance: H7N9 Virus-Host Interactions & Age Shift

H7N9 Age Curve - Credit CIDRAP 

 

 

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One of the ongoing mysteries surrounding the H7N9 outbreak in China is the disproportionate skewing of known cases towards elderly males – even though all ages in the community are assumed to be equally immunologically naive to this emerging virus.

 

This excellent chart by Laidback Al clearly shows the disproportionate impact H7N9 is having on the elderly, while the largest segment of the Chinese population –  middle-aged adults - are far less represented in the case counts.

 

 

Source FluTrackers Demographic and Geographic Overview of H7N9

For some additional discussion on this unusual patterning of cases, you may wish to revisit H7N9: The Riddle Of The Ages and last Monday’s WHO H7N9 Study: Preliminary Age & Sex Distribution.

 

While many epidemiologists are investigating exposure differences to poultry or other birds that might explain this age/sex shift, researchers from Canada are exploring a different scenario.

One that harkens back to a mystery still unresolved from the 2009 pandemic – the observation (particularly in Canada) that people who received the 2008 flu shot seemed to be more susceptible to catching the H1N1 pandemic strain the following spring.

The so-called `Canadian Problem’.

 

Fair warning, this letter from the Eurosurveillance  Journal offers up a hypothesis based on an extremely complex and poorly understood phenomenon. 

 

None of what follows is exactly `light’ reading.

 

Rather than mangle the author’s words by excerpting portions here, I would invite you to follow the link and read it in its entirety.

 

After you return, I’ll take a stab at trying to make it easier to understand (wish me luck).

 

Eurosurveillance, Volume 18, Issue 17, 25 April 2013

Letters

Virus-host interactions and the unusual age and sex distribution of human cases of influenza A(H7N9) in China, April 2013

D M Skowronski, N Z Janjua, T L Kwindt, G De Serres

 

What follows is a layman’s explanation of some poorly understood areas of our immune system. Real scientists may want to avert their eyes. 

 

Normally, after you’ve been infected by most viruses, you develop neutralizing antibodies that can recognize that pathogen and protect you from being infected again. Variances in individual immune systems and time since exposure can weaken these defenses.

 

But this is the reason why influenza viruses must continually mutate, else they’d run out of susceptible hosts.

 

But sometimes, the system doesn’t work as designed.

 

Sometimes - and for reasons that aren’t well understood - an earlier viral infection can set the host up for a more serious infection when exposed at a later date to a similar virus.

 

The classic example is with Dengue (DENV), which comes in four flavors (serotypes) – and which typically produces a mild illness with the first infection, regardless of which serotype is acquired.

 

The problem usually comes later, when a person is infected with a different serotype.

 

They often (but not always) experience a more severe illness, which can even progress into DHF (Dengue Hemorrhagic Fever).

 

The prevailing theory is that the host’s immune system - which already has neutralizing antibodies to the first DENV infection - mistakenly identifies the second DENV infection as being the same strain.

 

Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read: ineffective) antibodies to the field of battle.

Sometimes called OAS or Original Antigenic Sin, this is the immunological equivalent of taking a knife to a gun fight.

 

Original Antigenic Sin was coined in 1960 by Thomas Francis, Jr. in the article On the Doctrine of Original Antigenic Sin) that postulates that when the body’s immune system is exposed to and develops an immunological memory to one virus, it may be less able to mount a defense against a subsequent exposure to a second slightly different version of the virus.

OAS has been described in relation to influenza viruses, Dengue Fever, and HIV. You can find a terrific background piece on OAS from 2009 by Robert Roos in my blog entitled CIDRAP On Original Antigenic Sin.

 

And if mistakenly sending the wrong antibodies into the fray isn’t bad enough, sometimes non-neutralizing antibodies can actually enhance a virus’s ability to enter a host’s cells via a process called ADE or Antibody-dependent enhancement.

 

The result can be either an increased susceptibility to infection, a more severe course of illness, or both.

 

In this paper, the authors are suggesting that researchers look beyond simple socio-cultural behaviors to explain the age shift with H7N9, and consider what potential immunological effects that decades of exposures to a variety of influenza viruses might be having on an older population.

 

It is, as they say, complicated.  And not without controversy.

 

For more on this fascinating, but unresolved `Canadian problem’ - which the authors suggest may have some bearing on the epidemiology of H7N9 - you may wish to revisit:

 

ICAAC: Ferreting Out The `Canadian Problem’

 

EID Journal: Revisiting The `Canadian Problem’

 

Flu Vaccines & The Temporary Immunity Hypothesis

H7N9: Zhejiang, Jiangsu, Jiangxi Report New Cases

 

 

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In addition to the news this morning that the H7N9 virus has moved into Southern China (see H7N9: Fujian Province Reports First Case), end-of-day reporting from provincial health departments indicate a second case in Jiangxi province, three new cases in Jiangsu, and one new case in Zhejiang.

 

My thanks to the newshounds on FluTrackers whose daily case count thread helped me to put this list together.

 

First stop, Jiangxi province.

 

Jiangxi new case of human infection of H7N9 avian influenza confirmed cases

Jiangxi Provincial Health Department www.jxwst.gov.cn 2013 26 Source: Office of the Office

 

Health Department of Jiangxi Province, April 26 briefing, Jiangxi new case of human infection of H7N9 avian influenza confirmed cases.

 

Patient Xiong, female, 76 years old, farmers, Nanchang County. The patients suffered from fever, cough and other symptoms to Nanchang hospital and hospital treatment. April 26, the patient specimens were Jiangxi Province Center for Disease Control detection of human infection of H7N9 avian influenza virus nucleic acid positive.

 

The epidemiology survey results show that the patient's home keeping chickens and ducks, the recent death. Provincial Health Department expert group based on clinical manifestations, laboratory testing and epidemiological findings, the diagnosis of the human infection in patients with confirmed cases of the H7N9 avian influenza. Currently, patients in critical condition, the hospital is under active treatment.

 

10 close contacts of the cases have been measures to be taken under medical observation and found no abnormalities.

 

Up to now, Jiangxi Province, were found in human infection with the H7N9 avian flu case in two cases. Not found an epidemiological association between the two cases.

 

Next Zhejiang reports one new case, as well.

 

 

Zhejiang new cases of H7N9 avian influenza

April 26, 2013 18:48:31
 

Network April 26 hearing Zhejiang Provincial Health Department Bulletin, April 26 as of April 26 at 15:00, Zhejiang new case of human infection with H7N9 avian influenza.

 

Patients Lee, male, aged 38, farmer, Huzhou, onset on April 17, Hangzhou, a hospital for treatment.

 

Detected by the provincial CDC, the patient specimens of human infection of H7N9 avian influenza virus nucleic acid positive. Provincial Health Department organized experts on the patient's clinical manifestations, epidemiological data and laboratory test results are discussed, and diagnosis of human infection of H7N9 avian influenza confirmed cases. Currently, the patient is seriously ill, the hospital is under active treatment.

 

At present, the province has confirmed 45 cases of human infection with the H7N9 avian influenza patients, 6 patients died of his wounds, two cases have been cured.

 

 

And last stop, Jiangsu Province, where we get a particularly syntax-challenged translation of three new cases and a fatality from a previously announced case.

 

April 26th case of human infection of H7N9 avian influenza cases in Jiangsu discharged newly diagnosed two cases of human infection with the H7N9 avian influenza and another suspected cases were diagnosed with confirmed cases

---

Published :2013-4-26

Jiangsu Province Health Department Bulletin, April 26 The the Jiangsu case of human infection of H7N9 avian influenza discharged newly confirmed cases of human infection of H7N9 avian influenza cases, 1 suspected cases were diagnosed as confirmed cases.

 

Patients with single, male, 26 years old, live in Yancheng City Pavilion Lakes. April 14, was diagnosed with human infection of H7N9 avian influenza confirmed cases. After active treatment, is now available clinical cure, meet the discharge standards, was discharged on April 26.

 

The patients Qianmou, male, 49 years old and currently residing in Lishui area. On April 26, the provincial expert group diagnosed cases of human infection of H7N9 avian influenza confirmed cases. The case through early check early treatment measures found in a hospital in Nanjing, where mild.

 

Patients Zhou, male, 36 years old and currently residing in Xuzhou Xinyi City. On April 26, the provincial expert group diagnosed cases of human infection of H7N9 avian influenza confirmed cases. A hospital in Nanjing where serious condition.

 

Patients Zhang, male, aged 60, now living Binhu District. On April 5, the provincial expert group diagnosed cases of human infection of H7N9 avian influenza suspected cases. April 26, the H7N9 avian influenza virus isolated from the patient specimens. On April 26, the provincial expert group diagnosed cases of human infection of H7N9 avian influenza confirmed cases. Treatment in a hospital in Wuxi, a critical condition.

 

In addition, the case of human infection of H7N9 avian influenza confirmed cases in Wuxi City, Zhang, female, 32 years old, many times by the provincial expert group consultation, to rescue invalid death on April 24.

 

By my (possibly confused) count, this adds 6 new cases today (1 Fujian, 1 Jiangxi, 1 Zhejiang, 3 Jiangsu), which bring us to 118 cases (+1 asymptomatic PCR positive case in Beijing) on the Chinese Mainland, and 1 exported case to Taiwan.

H7N9: ECDC Epidemiological Update – April 26th

Credit ECDC

 

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The ECDC has a new epidemiological update out this morning, which includes the imported case to Taiwan. While not surprising, the `money quote’ from this assessment is:

An increasing incidence of sporadic cases and expansion of geographic spread in China and possibly neighbouring countries are expected over the coming weeks. Individual imported human cases to Europe cannot be ruled out and countries need to prepare for detecting and diagnosing such cases.

 

Follow the link for all of the charts and graphs.

 

 

Epidemiological update of 26 April: avian influenza A(H7N9) virus in China

26 Apr 2013

ECDC

Since 31 March 2013, one hundred and twelve (112) cases of human infection with avian influenza A(H7N9) virus have been reported from eight provinces in eastern China. Onset of disease has been between 19 February and 18 April 2013 in: Zhejiang (44), Shanghai (33), Jiangsu (24), Henan (4), Anhui (4), Beijing (1), Shandong (1) and Taiwan (1). The date of disease onset is currently unknown for fourteen patients.

 

Most cases have developed severe respiratory disease. Twenty three patients have died (case-fatality ratio=21%). The median age is 62 years with a range between 4 and 91 years; 33 out of 112 patients are female.

 

The Chinese health authorities are responding to this public health event by enhanced surveillance, epidemiological and laboratory investigation and contact tracing. The animal health sector has intensified investigations into the possible sources and reservoirs of the virus. The authorities reported to the World Organisation for Animal Health (OIE) that avian influenza A(H7N9) was detected in samples from pigeons, chickens and ducks, and in environmental samples from live bird markets ('wet markets') in Shanghai, Jiangsu, Anhui and Zhejiang provinces. Authorities have closed markets and culled poultry in affected areas.

 

The source and mode of transmission have not been confirmed. The outbreak is caused by a reassortant avian influenza virus with low pathogenicity for birds, hence it does not cause the signal 'die-offs' in poultry associated with highly pathogenic strains of avian influenza viruses. Genetic analyses of the isolates have shown changes which suggest that the H7N9 virus may have greater ability to infect mammalian species, including humans, than most other avian influenza viruses. Pathogenicity for humans appears to be high and higher age appears to be a risk factor for disease.

 

The most likely scenario is that the influenza A(H7N9) virus is spreading undetected in poultry populations and occasionally infecting humans who have close contact with poultry or poultry products but this will have to be validated as further data become available.

 

At the present time there is no evidence of sustained human-to-human transmission. Close to 2 000 close contacts of confirmed cases are reported to have been followed up. There is one family cluster with two confirmed cases for which human-to-human transmission cannot be ruled out but where common exposure is the most likely explanation. In addition, the virus has been detected in one asymptomatic carrier in Beijing.

 

An increasing incidence of sporadic cases and expansion of geographic spread in China and possibly neighbouring countries are expected over the coming weeks. Individual imported human cases to Europe cannot be ruled out and countries need to prepare for detecting and diagnosing such cases.

 

Critical developments that would change this assessment would be evidence of sustained human-to-human transmission and detection of avian influenza A(H7N9) in bird populations in Europe.

 

ECDC has published the Supporting diagnostic preparedness for detection of avian influenza A(H7N9) viruses in Europe guidance for laboratories on 24 April 2013.

 

ECDC is preparing an EU case definition for A(H7N9).

 

ECDC is closely monitoring developments and is continuously re-assessing the situation in collaboration with WHO, US CDC, China CDC and other partners.

 

This epidemiological update does not change the conclusions and recommendations of the updated risk assessment published on April 12.

Related links:

• ECDC Rapid Risk Assessment on avian influenza A(H7N9) virus in China, 12 April 2013
• Diagnostic preparedness in Europe for detection of influenza A(H7N9) viruses 
• Epidemiological update 18 April 2013: avian influenza A(H7N9) virus in China
• More on avian influenza on ECDC website

External links:

• WHO: question and answers on human infection with influenza A(H7N9) virus, China (updated 5 April 2013)
• Chinese Center for Disease Control and Prevention: question and answers about human infection with A(H7N9) avian influenza virus (published 31 March 2013)
• Updates on avian influenza A(H7N9) by Chinese Center for Disease Control and Prevention

 

 

H7N9: Fujian Province Reports First Case

 

Fujian Province – Wikipedia

 

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Despite the announcement two days ago by the Chinese government that case information would be released on a weekly basis, I’m pleased to report we continue to see case reports from individual provinces. 

 

Yesterday Jiangxi province was added to the geographic range of this virus, and today, we learn the virus has spread even further south with this  confirmed case reported in Fujian Province.

 

 

Fujian confirmed the first case of human infection with the H7N9 avian influenza

April 26, 2013 18:14:55

Source: Xinhua

Xinhua Fuzhou, April 26 (Reporter Mengzhao Li) Fujian Provincial Health Bureau informed that on the 26th, Fujian Province confirmed case of human infection with H7N9 avian influenza. The case is Fujian first case of human infection of H7N9 avian influenza confirmed cases.

 

Patients Luomou, male, 65 years old, Yongding County, Longyan City, Fujian Beizhen. On April 18 patients no obvious incentive to repeated coughing, chest tightness, with active low heat. At 14:50 on the 23rd, "cough sputum, fever, shortness of breath two days" chief complaint Check the Second Hospital of Longyan City, the condition has improved.

 

At 11:00 on the 26th the China CDC review of test results for the H7N9 avian influenza virus nucleic acid positive. Fujian Provincial Health Bureau a comprehensive case the clinical manifestations of the Group of Experts, the results of laboratory testing and epidemiological investigation, diagnosis confirmed cases of human infection of H7N9 avian influenza.

 

After investigation, the close contacts of the cases of 37 people, to take timely measures of medical observation. Up to now, all close contacts of the cases were not unusual.