BACKGROUND

SITUATION

AS OF1900 HRS EDT

23 APRIL 2013

RISK ASSESSMENT

H7N9 IN POULTRY AND BIRDS

HUMAN CASES

CHINESE GOVERNMENT Ministry of Agriculture Ministry of Health of the People

’s Republic of China Chinese Center for Disease Cont

rol and Prevention Hong Kong Department of Heal

th | Centre for Health Protection

National Health and Family Planning Commission

INTERNATIONAL ORGANIZATIONSFAOOIEWHO World Health Organization West

ern Pacific Region Disease Outbreak News Human infection with influenza

A(H7N9) virus Global Initiative on Sharing All I

nfluenza Data (GISAID)

US GOVERNMENT CDC – Health Info

EUROPEAN UNIONECDC

PORTALS, BLOGS, AND RESOURCES Avian Flu Diary CIDRAP FluTrackers.com Flu Wiki Health Map ProMed Mail Virology Down Under

NEW SOURCES People’

s Daily Online – China High Alert H7N9

China Daily Forbes Bloomberg AlertNet Reuters NY Times

YALE- TULANE ESF-8 SPECIAL REPORT

A(H7N9) VIRUS

SCREENING PATIENTS RETURNING FROM CHINA

SITUATION MAP

TIPS FOR THOSE VISITING CHINA

RESPONSE ACTIVITIES

AS OF 23 APRIL 2013CONFIRMED DEAD

108 2211

H7N9 OUTBREAK CHARACTERIZATION

• H7N9 infections in people and poultry in China

• Sporadic infections in humans; many with poultry exposure

• No sustained or community transmission

• Investigation ongoing

SOURCE: CDC

First confirmed casein Shandong Provincewas reported on23 April 2013.

SOURCE: Bloomberg News

BACKGROUND

TRANSMISSION:

• Thousands of close contacts of confirmed H7N9 patients are being followed to see if any human-to-human spread of H7N9 has occurred. With perhaps rare exceptions, people are not getting sick from other people.

• Of the many hundreds of people who were in close contact with the H7N9 patients, all the care-givers, neighbors, and family members, there are only a very few cases where these contacts have become ill as well. These are the little clusters of illness authorities are paying special attention to. Otherwise it it still seems that this does not happen easily, or there would be evidence of many such cases. There has not been sustained person-to-person transmission.

THE SOURCE: While the novel A(H7N9) virus has been detected in birds and environmental specimens at a bird markets in Shanghai and the other affected provinces, the source of infection in most of the cases still remains to be determined

SOURCES:• WHO Chinese Center for Disease Control and Prevention 4 April 2013• Global Alert Response, (1 APRIL 2013) http://www.who.int/csr/don/2013_04_01/en/• New technology speeding progress on bird flu vaccine (Reuters)• Global Concerns Regarding Novel Influenza A (H7N9) Virus Infections• Chinese Centers for Disease Control and Prevention H7N9 Information

On 31 March 2013, the World Health Organization (WHO) was notified by China’s Health and Family Planning Commission of three cases of human infection with the influenza A(H7N9) virus. Since then, additional cases have been reported. Most reported cases have severe respiratory illness and, in some cases, have died.

• H7N9 virus is an avian influenza) virus. Human infections with avian influenza (AI, or “bird flu”) are rare, but have occurred in the past, most commonly after exposure to infected poultry. This is the first time that A(H7N9) has been found in humans

• Cases presented with respiratory tract infection with progression to severe pneumonia and breathing difficulties.

• At this time there are no cases of H7N9 outside of China.

• There are no vaccines available at this time.

• China has intensified human and animal surveillance. It has also implemented public health measures that include the culling of birds and the closure of some live poultry and bird markets

ANTIVIRAL DRUGS: So far, all three viruses seem to be susceptible to the influenza antiviral drugs oseltamivir and zanamivir, but they are resistant to the amantanes

VACCINE: There is no licensed H7N9 vaccine currently available but government-backed researchers at Novartis and at and a unit of the J. Craig Venter Institute, which is using synthetic biology, have already begun testing a "seed" strain of the virus made from the genetic code posted on the Internet .

Researchers in protective suits test samples of a suspected case of the H7N9 avian influenza virus at the provincial center for disease control and prevention in Hangzhou, capital of east China's Zhejiang Province, April 17, 2013. An emergent testing team on 24-hour stand-by was set up in the center after the recent spread of the H7N9 virus. Infections within the province will be officially confirmed by the center. (Xinhua/Xu Yu)

Place1 Cases1 Deaths1 Place1 Cases1 Deaths1

Beijing 1* 0 Zhejiang 42 6

Shanghai 33 12 Anhui 4 1

Jiangsu 24 3 Henan 3 0

Shandong 1 0 *Does not include asymptomatic 4 year old boy

SITUATION

ALL CONFIRMED HUMAN INFECTIONS WITH A(H7N9) ARE SPORADIC CASES, AND THERE IS NO EVIDENCE OF ONGOING HUMAN-TO-HUMAN TRANSMISSION.1

However, this is still a future possibility:• Every time the virus encounters and infects a new human

host, it has the opportunity to mutate.2

• The haemagglutinin (H) surface protein on the virus has shown mutations that precede a change in binding preference from bird to human cells.2,4

• A PB2 protein substitution is also indicative of mammalian adaptation of the virus4

ALL CONFIRMED CASES AND DEATHS WITHIN CHINA1

• Cases in 30 prefectures/districts across 7provinces

Cases Type Most Recent Total1

Deaths 22

Laboratory-Confirmed Cases

108

Sources: 1. WHO Update - 23 April 2013 2. www.Nature.com/news 3. South China Morning Post 4. www.NEJM.org 5. WHO's Western Pacific Region Office (WPRO)

Note: All case and death totals are as of 8 am EST, April 22, 2013

H7N9 HAS NEVER BEFORE BEEN DETECTED IN HUMANS4

• WHO has published Real-time RT PCR (rRT-PCR） Protocol for the Detection of A(H7N9) Avian Influenza Virus

• All age groups expected to be susceptible.4 However, the age distribution is skewed toward the elderly. 5

CLUSTERS:

There have been 3 clusters officially reported:• A father and his two sons became ill. The father and the younger son died.

Authorities say blood tests show that both the father and the older son had H7N9. That son has now recovered from pneumonia.

• A parent and a child, where the daughter was caring for the parent who was very sick, and became sick herself with the H7N9.

• A husband-and-wife cluster. In both of those, people were sick with severe pneumonia, and so were linked clinically.

SOURCES:

SITUATION

• Chinese Centers for Disease Control – H7N9 Update – 23 April 2013 • WHO Update – 23 April 2013• Virology Down Under • WPRO: Human

infections with avian influenza A(H7N9) virus in China: preliminary assessments of the age and sex distribution

As of 23 April 2013 there have been a total of 108 cases have been laboratory confirmed with influenza A(H7N9) virus in mainland China, including 14 recovered and discharged, 72 in hospitalization and 22 deaths. There is no evidence of ongoing human-to-human transmission.

SOURCE: Virology Down Under

• Shanghai was the first municipality to report cases but recent activity has been concentrated in Zhejiang province.

CASES: • Cases have been confirmed in the

following provinces and municipalities: Shanghai, Beijing Jiangsu, Anhui, Henan , Zhejiang, and Shandong. All locations are in Eastern and Northern China.

• Experts from the WHO's Western Pacific Region Office (WPRO) wrote that among the 63 H7N9 cases reported from Mar 31 through Apr 16, the median age was 64, and 45 patients (71%) were male. Thirty-nine of the 63 patients (62%) were at least 60 years old. This is different to the Chinese population which has a large proportion of young and middle-aged adults and a greater number of women among the elderly.

• Three main reasons may be considered for the current case distribution: (1) Differential exposure between males and females due to gender-

associated practices and norms(2) Biological differences between males and females in the clinical course

post exposure/infection(3) Differential healthcare-seeking/access behavior between male and

females, leading to surveillance/detection bias.• At this time further investigation is required.

AGE DISTRIBUTION

The ages for the cases where age is reported range from 2 to 89 years old. The age distribution is skewed toward the elderly. Only four pediatric cases have been reported. They include two males, a 2-year-old and 4-year–old from Shanghai, and a 4-year old boy and a 7-year old girl from Beijing. The 4-year-old boy was asymptomatic. None of these children have died SOURCE: FluTrackers.com

SITUATION

• The novel H7N9 viruses possess several characteristic features of mammalian influenza viruses, which are likely to contribute to their ability to infect humans and raise concerns regarding their pandemic potential.

• H7N9 viruses features H7 HA and N9 NA surface proteins, a combination that had been previously seen only in birds.

• H7N9 acquired its surface protein genes from the H7N3 and H7N9 avian influenza strains, and its remaining genes from H9N2 influenza viruses that had recently circulated in poultry in China.

• If H7N9 virus infection is primarily zoonotic, as reports currently suggest, transmission is expected to occur through exposure to clinically normal but infected poultry, in contrast to HPAI H5N1 virus infection, which typically causes rapid death in infected chickens.

• The hemagglutinin (HA) sequence data suggest that these H7N9 viruses are a low-pathogenic avian influenza A virus and that infection of wild birds and domestic poultry would therefore result in asymptomatic or mild avian disease, potentially leading to a “silent” widespread epizootic in China and neighboring countries. The HA sequence data also featured:

‒ Mutations that have been shown to improve the virus’ ability to bind to human cells, the first step in the infection process.

‒ A mutation associated with improved virus reproduction within human cells, which helps the infection spread throughout the body and cause disease.

• The NA sequences contained a mutation associated with more severe disease in mammals.

• Three of the four H7N9 viruses sequenced are likely to be treatable using NA inhibitors, a class of anti-influenza drugs that includes oseltamivir (Tamiflu) and zanamivir (Relenza). Analysis of all four sequences suggests that the novel strain will not be treatable with ion channel inhibitors, another major class of anti-influenza drugs.

• Ongoing surveillance is crucial to assessing the emergence and prevalence of H7N9 viruses resistant to available antivirals.

SOURCE OF THE VIRUS: Investigations into the possible sources of infection and reservoirs of the virus are ongoing. Until the source of infection has been identified, it is expected that there will be further cases of human infection with the virus in China.

GENETIC CHARACTERISTICS: The sequences of the first three viruses were posted to GISAID by China and are publicly available.

SOURCES:• NIH: Supported Researchers Glean Clues from H7N9 Influenza Genetic Sequences • Kageyama T et al

. Genetic analysis of novel A(H7N9) influenza viruses isolated from patients in China, February to April 2013. Eurosurveillance 18(15) (2013).

• GISAID H7N9 virus sequencing

Total number of confirmed human cases A(H7N9)

109*

* Incudes asymptomatic 4 Year old boy - Beijing

Total number of deaths attributed A(H7N9)

22

Current Case Fatality Rate 19%

Average time from illness onset to first confirmation of H7N9 (days):

9 days

Average age of the H7N9-confirmed cases

58 years

Median age of the H7N9 confirmed cases

62 years

The mode of the ages among confirmed cases (including deaths; years):

54, 56 and 74

The mode of the ages among the deceased (years):

64, 74, 77

Males 67% of the cases 71% of the fatalities

Females 23%of the cases 29% of the fatalities

NUMBER OF DEATHS / NUMBER OF CONFIRMED CASES

SOURCE: VIROLOGY DOWN UNDER, DR. IAN M MACKAY

SHANGHAI

1233

BEIJING

01

ANHUI

13

JIANGSU

324

ZHEJIANG

540

HENAN

03

DISTRIBUTION OF CASES GEOGRAPHICALLY

Total number of confirmed cases

Total number of deaths

Source: WHO Update - 23 April 2013

SHANDONG

01

PRESENT SITUATION IN CHINA

• China's Ministry of Agriculture, says its has taken samples from poultry markets, farms and slaughterhouses across the country.

• So far, 84,444 samples have been taken, 47,801 have been tested and 40 samples confirmed as H7N9 positive.

• Of these, 38 positive samples came from live poultry markets in the Shanghai municipality and Anhui, Zhejiang and Jiangsu provinces. Besides that, one sample, was found in a feral pigeon and another in and a carrier pigeon from a farm in Jiangsu.

• The Harbin Veterinary Research Institute under the Chinese Academy of Agricultural Sciences (CAAS) on Tuesday, 23 April, 2012 reported that the H7N9 virus isolated from live poultry markets in China is closely related to the viruses that caused the recent human infections.

• For the first time, the institute identified the direct avian origin of the H7N9 influenza viruses that caused the human infections, which may provide an important basis for controlling the virus in the future.

SITUATION - H7N9 IN POULTRY AND BIRDS

SOURCES• OIE: Questions and Answers on Influenza A(H7N9)• CAAS: Isolation and characterization of H7N9 viruses from live poultry markets—Implication of the source of current H7N9 infection in humans

Event summary: Low pathogenic avian influenza (poultry) in China

• 12 outbreaks • Event reported to OIE - 4 April

2013 • Lab confirmation – 4 April 2013• Situation is ongoing.

SOURCE: WAHID Interface

• Situation is ongoing. Situation is ongoing

RISK OF HUMAN TO HUMAN TRANSMISSION• There is insufficient evidence to quantify the risk of A(H7N9) developing

into a virus that transmits from human to human • At the present time there is no evidence of sustained human-to-human

transmission Infective period for A(H7N9) cases not known but patients likely to

excrete the virus in body fluids Pathogenicity for humans appears to be high and higher age appears to

be a risk factor for disease.

RISK OF FURTHER CASES IN CHINA Most human cases of H7N9 likely due to animal exposure Further cases are expected

RISK OF INTERNATIONAL SPREAD Risk of international spread via humans currently low As virus cannot sustain human-to-human transmission, extensive

spread unlikely regardless of infected travelers WHO does not advise special screening at points of entry with regard

to this event or any travel restrictions No cases have been reported outside of China

OTHER MODES OF TRANSMISSION No epidemiological evidence of transmission to humans through

the consumption of food Low or no risk of transmission through blood transfusion or

organ/tissue donations Importation through food and agricultural products from China

unlikely due to importation restrictions Risk of spread through migratory birds unknown Virus been detected in a feral pigeon and

RISK ASSESSMENT

TWO RISK ASSESSMENTS HAVE BEEN PUBLISHED:

European Centre for Disease Prevention and Control (12 April 2013)

http://www.ecdc.europa.eu/en/publications/Publications/influenza-A(H7N9)-China-rapid-risk-assessment-4-april-2013.pdf

World Health Organization (13 April 2013): http://www.who.int/influenza/human_animal_interface/influenza_h7n9/RiskAssessment_H7N9_13Apr13.pdf

GENERAL INFORMATION: At this time, there are still gaps in information and evidence available.

Investigations into possible sources of infection and reservoirs of the virus are ongoing.

This is the first time that human infection with influenza A(H7N9) virus has been identified and the first time that human infection with a low pathogenic avian influenza A virus has been associated with a fatal outcome.

For precautionary reasons, those working in or visiting China should avoid visiting live bird and animal markets and direct contact with bird and animal feces, untreated bird feathers, and other animal and bird waste

REPONSE ACTIVITIES

CHINESE GOVERNMENT • Chinese government notifies the World Health Organization

of the emergence of an A(H7N9)• Chinese health authorities are conducting investigations to

learn the source of the infections with this virus• Chinese scientists first sequence the viral genome and

identified the origin of this new virus.• The Chinese health authorities are responding to this public

health event by enhanced surveillance, epidemiological and laboratory investigation and contact tracing.

• All influenza network laboratories in the 31 provincial regions on China's mainland are now capable of testing for the H7N9 bird flu virus

• China's Ministry of Agriculture gathers samples from poultry markets, farms and slaughterhouses across the country. So far, 84,444 samples have been taken, 47,801 have been tested and 39 samples confirmed as H7N9 positive. Surveillance continues.

• President Xi Jinping urged government authorities to take effective measures to contain the spread of the H7N89. Xi said local authorities should prioritize public safety and health, as well as strengthen disease control and prevention. He also called for efforts to conduct epidemiological studies of the disease, strictly control infection sources, promote public awareness of disease prevention and accelerate the development of vaccines.

WORLD HEALTH ORGANIZATION

US GOVERNMENT• CDC holds a telebriefing on H7N9 Influenza Cases• CDC issues a Health Advisory,

Human Infections with Novel Influenza A (H7N9).• CDC post a Travel Notice about avian influenza A (H7N9) on

www.cdc.gov/travel• CDC provides

Interim Guidance on Case Definitions to be Used for Novel Influenza A (H7N9) Case Investigations in the United States

• CDC offers antiviral guidance for possible H7N9 cases• CDC post H7N9: Frequently Asked Questions Friday, April 19,

2013 11:45:00 AM• CDC post Interim

Recommendations: Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2013Friday, April 19, 2013 12:33:00 PM

• CDC post CDC post Background on Human Infections with other Avian Influenza Viruses Monday, April 22, 2013 11:35:00 AM

• WHO is in contact with national authorities and is following the H7N9.

• The WHO-coordinated international response is also focusing on work with WHO Collaborating Centers for Reference and Research on Influenza and other partners to ensure that information is available and that materials are developed for diagnosis and treatment and vaccine development. WHO publishes background and summary of H7N9 5 April 2013

• The WHO Collaborating Center for Reference and Research on Influenza at the Chinese National Influenza Center in Beijing, China, has made available the real-time RT-PCR protocol for the detection of avian influenza A(H7N9) virus. 8 April 2013 (updated on 15 April 2013)

• WHO post Risk Assessment 13 April 2013 • WHO post

Standardization of the influenza A(H7N9) virus terminology as of 16 April 2013pdf, 92kb

• At the invitation of the National Health and Family Planning Commission of China, WHO has convened a team of experts who are currently visiting areas affected by avian influenza A(H7N9) in China in order to provide recommendations on the prevention and control of the disease.

OVERVIEWWhat is H7N9 virus? The virus appears to be a reassortment of three avian influenza viruses.

How does H7N9 flu spread? Thus far, there is no evidence of human-to-human transmission. Some affected patient had exposures to poultry before falling ill. There is concern that H7N9 does not cause severe illness in birds and hence can potentially spread undetected from poultry to sporadic human cases.

What are the symptoms? Predominant presenting symptoms have been severe respiratory tract infections which progressed to pneumonia.

SCREENING

KEY POINTS• Clinicians should consider the possibility of novel influenza A (H7N9) virus infection

in persons presenting with respiratory illness within 10 days of an appropriate travel or exposure history.

• Although the majority of novel influenza A (H7N9) cases have resulted in severe respiratory illness in adults, infection with this virus may cause mild illness in some and may cause illness in children as well.

• Influenza diagnostic testing in patients with respiratory illness for whom an etiology has not been confirmed may identify human cases of avian influenza A virus infection or new cases of variant influenza in the United States.

• Patients with novel influenza A (H7N9) virus infections should have a positive test result for influenza A virus via reverse-transcription polymerase chain reaction (RT-PCR) testing but be unsubtypeable. Clinicians suspecting novel influenza A (H7N9) should obtain appropriate specimens and notify their local or state health department promptly. State health departments should notify CDC of suspected cases within 24 hours. For more information, see the Health Alert Notice issued April 5, 2013.

References: (picture) www.abcnew.com, www.upmc-biosecurity.org, www.uptodate.com, http://emergency.cdc.gov/HAN/han00344.asp, http://www.cdc.gov/flu/avianflu/guidance-labtesting.htm

Who should be tested ? Patients with flu symptoms and the following exposure criteria:

1. Recent travel to countries with human H7N9 cases, especially if there was close contact with animals (e.g. wild birds, poultry or pigs) or where H7N9 viruses are known to be circulating in animals. Thus far, China is the only country with recent reported human cases.

Use Standard Precautions plus Droplet, Contact, and Airborne Precautions, including eye protection until more is known about the transmission characteristics.

Commercial rapid influenza diagnostic tests may not detect avian or variant A viruses. Hence a negative test does not exclude H7N9 infection.

Send a nasopharyngeal swab or aspirate placed in viral transport medium to state or local health department. Currently, all confirmatory testing for H7N9 will be done by CDC.

TREATMENT

INFECTION CONTROL

Do not base treatment decision solely on the result of a negative rapid influenza diagnostic test result.

For patients in following categories, start empiric treatment with oral oseltamivir or inhaled zanamivir as soon as possible without waiting for laboratory confirmation:1. Patients hospitalized with suspected influenza, including H7N9 cases2. High risk persons (age <5 or ≥65, certain underlying medical conditions)

Antiviral treatment is most effective if started as soon as possible after the onset of influenza illness. But treatment in moderate, severe, or progressive disease that began after 48 hours may still have some benefit.

DIAGNOSTIC TESTS

FACT SHEET: AVIAN INFLUENZA A (H7N9) VIRUSSCREENING PATIENTS RETURNING FROM CHINA

2. Recent contact with confirmed human H7N9 cases

Information on incubation period is incomplete but other avian influenza had incubation period ranging 3-9 days.

FACT SHEET: AVIAN INFLUENZA A (H7N9) VIRUS

TIPS FOR THOSE VISITING CHINA

OVERVIEWWhat is H7N9 flu? It is a contagious disease in humans and other animals that can sometimes lead to serious illness and death.

How does H7N9 flu spread? An animal with H7N9 virus can give it to another animal or human through feces, saliva, or nasal secretions.

What are the symptoms? Some of the following: fever, cough, sore throat, runny nose, body aches, headaches, chills, fatigue.

PREVENTION

KEY POINTSH7N9 is a new bird flu virus.

Rare but serious human cases have occurred in China. So far, there is no evidence of sustained human-to-human transmission.

References: (picture) http://www.ottawacitizen.com http://www.cdc.gov/flu/avianflu/h7n9-virus.htm, http://www.who.int/csr/don/2013_04_10/en/ http://wwwnc.cdc.gov/travel/notices/watch/avian-flu-h7n9-china.htm

Do not touch birds or other animals. ‒ Do not touch animals whether they are alive or dead.‒ Avoid live bird or poultry markets.‒ Avoid other markets or farms with animals (wet markets).

Eat food that is fully cooked. – Eat meat and poultry that is fully cooked (not pink) and served hot.– Eat hard-cooked eggs (not runny).– Don’t eat or drink dishes that include blood from any animal.– Don’t eat food from street vendors.

Practice hygiene and cleanliness: – Wash your hands often.– If soap and water aren’t available,

clean your hands with hand sanitizer containing at least 60% alcohol.

– Don’t touch your eyes, nose, or mouth. If you need to touch your face, make sure your hands are clean.

– Cover your mouth and nose with a tissue or your sleeve (not your hands) when coughing or sneezing.

– Try to avoid close contact, such as kissing, hugging or sharing eating utensils or cups, with people who are sick.

IF YOU BECOME ILL….See a doctor if you become sick during or after travel to China.

‒ See a doctor right away if you become sick with fever, coughing, or shortness of breath.

‒ If you get sick while you are still in China, visit the US Department of State website to find a list of local doctors and hospitals. Many foreign hospitals and clinics are accredited by the Joint Commission International. A list of accredited facilities is available at their website (www.jointcommissioninternational.org).

‒ Delay your travel home until after you have recovered or your doctor says it is ok to travel.

‒ If you get sick with fever, coughing, or shortness of breath after you return to the United States, be sure to tell your doctor about your recent travel to China.