BACKGROUND

SITUATION

AS OF11500 HRS EDT

3 MAY 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

GENETIC CHARACTERISTICS

RESPONSE ACTIVITIESAS OF 2 MAY 2013CONFIRMED DEAD

129 27

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

SOURCE: Bloomberg News

Taiwan reported its first case of H7N9 on 24 April

BACKGROUND• ANTIVIRAL DRUGS: H7N9 can be treated with the antiviral

drugs oseltamivir (Tamiflu®) and zanamivir ( Relenza® ) but is resistant to the adamantanes, another class of antiviral drugs.

• VACCINE: There is no licensed H7N9 vaccine currently available but US government-backed researchers at Novartis and at and a unit of the J. Craig Venter Institute have begun testing a "seed" strain of the virus.

• SURVEILLANCE. 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.

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

• SOURCE OF THE VIRUS: Investigations into the possible sources of infection and reservoirs 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.

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 3 cases of the A(H7N9) virus in humans. Since then new cases continue to emerge:

• H7N9 virus is an avian influenza) virus. This is the first time that A(H7N9) has been found in humans

• Cases present with respiratory tract infection that progresses to severe pneumonia and breathing difficulties.

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

SOURCE: Minnesota Center of Excellence for Influenza Research & Surveillance (MCEIRS) Resources

BACKGROUND

HHS: 2013 H7N9 INFLUENZA EMERGENCY USE AUTHORIZATION (POTENTIAL EMERGENCY)

SOURCE: Virology Down underFluTrackers 2013 Human Case List of Confirmed and Highly Suspected/Probable Influenza A(H7N9) Cases-

• On April 19, 2013 Secretary Kathleen Sebelius determined that avian influenza A(H7N9) poses a significant potential for a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad.

• On the basis of this determination the Secretary declared that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection of the avian influenza A(H7N9) virus.* http://www.phe.gov/emergency/news/healthactions/phe/Pages/H7N9-influenza-virus.aspx

• On April 22, 2013, the FDA issued an Emergency Use Authorization (EUA) for the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel-Influenza A/H7 (Eurasian Lineage) Assay.

• This test is for the presumptive detection of novel influenza A (H7N9) virus in conjunction with the FDA cleared CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel in real-time RT-PCR (rRT-PCR) assays in patients with signs and symptoms of respiratory infection. This device will be distributed by CDC to the public health and other qualified laboratories.

*Note that Secretary’s determination and declaration were issued based on revised authorities under the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA)

Diagnostic TestLetter ofAuthorization

Fact Sheet for Healthcare Providers

Fact Sheet for Patients

Labeling (PDF)

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel-Influenza A/H7 (Eurasian Lineage) Assay

[Authorization ] Healthcare Patients Labeling

For Access to available H7N9 Kits (for Domestic Use) and H7N9 Kits (for International Use) Please Register with the IRR. If You are Already Registered, and Currently Have Access to RT-PCR Kits, Login and Enter a Search for H7N9 to View Available H7N9 Kits

NOTE: Due to the Determination of a Significant Potential for a Public Health Emergency and Declaration for H7N9, orders not associated with H7N9 and non-emergency orders may be delayed

Cases Type Most Recent Total1

Deaths 27

Laboratory-Confirmed Cases 129**

** Number includes asymptomatic case of 4 year old from Beijing and the Taiwan case

CHINA

Place1 Cases1 Deaths1 Place1 Cases1 Deaths1

Anhui 4 1 Jiangsu 27 6

Beijing 2* 0 Jiangxi 5 0

Fujian 3 0 Shandong 2 0

Henan 4 0 Shanghai 33 13

Hunan 2 1 Zhejiang 46 6

*Include asymptomatic 4 year old boy

TAIWAN

Taiwan 1 0

SITUATION

• The emergence of H7N9 in China continues to be a concern.

• The number of cases and fatalities continues to increase.

• H7N9 continues to expand its geographical range. It is now being reported in 10 of China’s provinces.

• Taiwan reported its first case. Taiwanese health officials reported that its first case was imported by a local businessman who regularly traveled between back and forth between China's Jiangsu province and Taiwan

• Genetic and epidemiological findings show that patients are likely to be infected through exposure to infected poultry or its contaminated environment such as wet markets but the exact source and mode of spread still has not been identified.

• Patients range fro 2 to 91 years of age, however two thirds of the cases have been 50 years old or older, 69% percent of the cases are male and 65% of all fatalities are male.

• It is unclear how many people might have carried the disease without showing any signs of illness. So far a 4 year old boy in Beijing has been identified as a carrier but is is unknown how many others there might be.

SOURCES: CIDRAPVirology Down UnderFluTrackers: 2013 Human Case List of Confirmed and Highly Suspected/Probable Influenza A(H7N9) CasesWHO: Human infection with avian influenza A(H7N9) virus – updateChina Ministry of Health: H7N9, China: Number of Confirmed birdflu cases reported from April 25 to May 1 2013

Total number of confirmed human cases A(H7N9)*

129* Incudes asymptomatic 4 Year old boy - Beijing

Total number of deaths attributed A(H7N9)

23

Current Case Fatality Rate 19% (12% Men;6% women)

Discharged from the hospital 15

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

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

64, 74, 77, 86

Males 69% of the cases 65% of the fatalities

Females 21%of the cases 35% of the fatalities

NUMBER OF DEATHS / NUMBER OF CONFIRMED CASES

SOURCE: VIROLOGY DOWN UNDER, DR. IAN M MACKAY

GENETIC CHARACTERISTICS

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

• H7N9 features H7 hemagglutinin (HA) and N9 neuraminidase (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.

• 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.

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• Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylo

genetic, structural, and coalescent analyses

• The hemagglutinin (HA) sequence data suggest that the H7N9 virus is a low-pathogenic avian influenza A virus and that infection of wild birds and domestic poultry results in asymptomatic or mild avian disease, potentially leading to a “silent” widespread epizootic in China and neighboring countries.

Influenza A H7N9 as viewed through an electron microscope. Both filaments and spheres are observed in this photo. CDC

The Lancet (1 May 2013):

FINDINGS: • The novel avian influenza A H7N9 virus originated from multiple

reassortment events. • The HA gene might have originated from avian influenza viruses of

duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway.

• The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens.

• Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus.

• Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades.

INTERPRETATION: The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future

PRESENT SITUATION IN CHINA

• 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.

• Because H7N9 infection is unlikely to show visible signs of disease in poultry, the use of reliable and accurate laboratory tests, complying with OIE Standards and guidance from OFFLU, will underpin surveillance and control of the H7N9 virus in poultry.

• Destruction of infected poultry by Veterinary Services as well as poultry that have been in contact with infected birds is recommended.

• There is no evidence to suggest that the consumption of poultry or eggs fit for human consumption could transmit the AI virus to humans.

• It is safe to eat properly prepared and cooked meat and eggs. Specific precautions when plucking poultry are recommended.

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

• 16 outbreaks • Event reported to OIE - 4 April 2013 (weekly

follow ups since)• Lab confirmation – 4 April 2013• Situation is ongoing.

SOURCE: WAHID Interface

The Ministry of Agriculture of the People’s Republic of China asked the Director General of the World Organization for Animal Health (OIE) to send OIE experts to assess the situation with influenza A(H7N9) in animals. At the conclusion of this mission the team confirmed that :

• Many of the human cases of H7N9 appear to have a link with live bird markets.

• To date no human cases or animal infections of H7N9 have been detected on poultry farms.

• H7N9 does not cause visible disease in poultry or birds

• Veterinary Services must be especially involved in preventing its further spread in poultry, particularly through the supervision of the implementation of biosecurity measures on farms.

The experts believe that live bird markets may play a key role in human and animal infections with H7N9. Llive bird markets provide an environment for amplification and maintenance of the H7N9 virus.

OIE – 30 April 2013

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 in poultry

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.

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