BACKGROUND

SITUATION

AS OF 1600 HRS EDT15 APRIL 2013

RISK ASSESSMENT

AVIAN INFLUENZA

HUMAN CASES

CHINESE GOVERNMENT ORGANIZATIONS Ministry of Health of the People’s Republic of China Chinese Center for Disease Control and Prevention Hong Kong Department of Health | Centre for Health Protection National Health and Family Planning Commission

INTERNATIONAL ORGANIZATIONSFAOOIEWHO

World Health Organization Western Pacific Region Disease Outbreak News Human infection with influenza A(H7N9) virus Global Initiative on Sharing All Influenza 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 Forbes AlertNet Reuters NY Times

YALE- TULANE ESF-8 SPECIAL REPORT

A(H7N9)

SCREENING PATIENTS RETURNING FROM CHINA

MAP

TIPS FOR THOSE VISITING CHINA

RESPONSE

AS OF 15 APRIL 2013

CONFIRMED DEAD

64 14 ECONOMIC IMPACTS

CDC to update clinicians, health departments on #H7N9 flu. Call in April 18, 2PM ET: http://goo.gl/DLm1J

BACKGROUND

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

It is equally unclear how the virus was introduced into the markets.

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

SOURCE: Global Alert Response, (1 APRIL 2013) http://www.who.int/csr/don/2013_04_01/en/ Flu.Gov (April 2013) Avian Influenza A (H7N9) Virus http://www.flu.gov/about_the_flu/h7n9/index.html#

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.

• At this time, no cases of H7N9 outside of China have been reported. The new H7N9 virus has not been detected in people or birds in the United States.

• This new H7N9 virus is an avian (bird) influenza (flu) 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 this bird flu subtype (H7N9) has been found in people. This virus is very different from other H7N9 viruses previously found in birds.

• Many of the human cases of H7N9 are reported to have had contact with poultry. However, some cases reportedly have not had such contact.

• Close contacts of confirmed H7N9 patients are being followed to see if any human-to-human spread of H7N9 has occurred. No sustained person-to-person spread of the H7N9 virus has been confirmed at this time.

• There is no licensed vaccine available at this time..

A man infected with H7N9 bird flu receives treatment at an intensive care unit in a hospital in Kaifeng, Henan province, on Sunday.( Li Bo / Xinhua )

CASE UPDATES• The National Health and Family Planning Commission continues to

notify WHO as there are are additional laboratory-confirmed cases of human infection with influenza A(H7N9) virus.

• Cases have been confirmed in the following provinces and municipalities: Shanghai, Beijing Jiangsu, Anhui, Henan and Zhejiang. All locations are in Eastern and Northern China.

• The age of confirmed cases ranges from 4-87 years old.

• Cases presented with respiratory tract infection with progression to severe pneumonia and breathing difficulties. More than 1,000 close contacts of the identified cases are being closely monitored.

• Two confirmed cases have been associated with possible family clusters. Close contacts of confirmed cases and health care workers caring for cases have been monitored for infection. So far, among the contacts who have been tested by polymerase chain reaction, none has been shown to have infection.

SITUATION

Chinese Centers for Disease Control – H7N9 Update GISAID H7N9 virus sequencing Global Concerns Regarding Novel Influenza A (H7N9) Virus InfectionsCenters for Disease Control and Prevention – Travelers’ Health World Health Organization Global Alert and Response Virology Down Under Chinese Centers for Disease Control and Prevention H7N9 Information WHO H7N9 Risk Assessment

As of 15 April 2013 there have been a total of 64 confirmed cases and 14 deaths.

On 15 April, Beijing Municipal Health Bureau reported that a four-year-old boy, who was tested positive for H7N9 flu virus, was asymptomatic.

SITUATION

VIRUS CHARACTERIZATION• This is the first time human infection with this influenza

subtype, avian influenza A(H7N9) virus, has been detected.

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

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 pharmaceutical manufacturers are currently using synthetic biology techniques to develop a candidate vaccine strain.

The schematic above (provided by CDC) shows the structure of an influenza virus particle. There are two major proteins found on the virus surface, hemagglutinin (that is the  ”H” when the virus type is designated) and neuraminidase (the “N”)

GENETIC CHARACTERISTICS

• The novel H7N9 viruses have genetic characteristics that are of concern.

• 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.

• 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 gene sequences also indicate that these viruses may be better adapted than other avian influenza viruses to infecting mammals.

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

REPONSE ACTIVITIES

CHINESE GOVERNMENT ACTIVITIES• 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 government has instituted enhanced surveillance,

strengthened laboratory utilization, and training of health care professionals for detection, reporting, and treatment.

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

US GOVERNMENT ACTIVITIES5 April: • CDC holds a telebriefing on H7N9 Influenza Cases• CDC issues a Health Advisory,

Human Infections with Novel Influenza A (H7N9).8 April:• The US Centers for Disease Control and Prevention (CDC)

activates its Emergency Operations Center (EOC) in Atlanta at Level 2 to support the response to the H7N9 influenza outbreak in China, CDC officials said in an e-mailed statement today.

• CDC post a Travel Notice about avian influenza A (H7N9) on www.cdc.gov/travel

11 April:• China provides US CDC with virus sample for vaccine

development

NUMBER OF DEATHS / NUMBER OF CONFIRMED CASES

NO EVIDENCE OF H7N9 TRANSMISSION FROM PERSON-TO-PERSON1,2,3 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 29 prefectures/districts across 6 provinces

Cases Type Most Recent Total1

Deaths 14

Laboratory-Confirmed Cases

64

Sources: 1. China CDC 2. www.Nature.com/news 3. South China Morning Post 4. www.NEJM.org

Note: All case and death totals are as of 8pm EST, April 14, 2013

H7N9 HAS NEVER BEFORE BEEN DETECTED IN HUMANS4

• Rapid diagnostic tests are currently unavailable4

• All age groups expected to be susceptible4

Place1 Cases1 Deaths1 Place1 Cases1 Deaths1

Beijing 2 0 Zhejiang 16 2

Shanghai 24 9 Anhui 3 1

Jiangsu 17 2 Henan 2 0

NUMBER OF DEATHS / NUMBER OF CONFIRMED CASES

Total number of confirmed human cases A(H7N9)

60

Total number of deaths attributed A(H7N9)

13

Current Case Fatality Rate

22%

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

10 days

Average age of the H7N9-confirmed cases

59 years

Median age of the H7N9 confirmed cases

64 years

Modal age of the H7N9 confirmed cases

74 years

Average age of deceased

62 years

Males 71% of the cases 71% of the fatalities

Females 29%of the cases 71% of the fatalities SOURCE: Virology Down Under

SHANGHAI

924

BEIJING

02

ANHUI

13

JIANGSU

217

ZHEJIANG

216

HENAN

02

DISTRIBUTION OF CASES GEOGRAPHICALLY

Total number of confirmed cases

Total number of deaths

Source: China CDC http://www.chinacdc.cn/en/research_5311/H7N9update/201304/t20130414_79862.html

RISK ASSESSMENT

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.

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

• There is no evidence of sustained human-to-human transmission. However the two possible family clusters suggest that limited human-to-human transmission may occur where there is close contact between cases and other individuals, as occurs in families and, potentially, healthcare settings.

• At this time, there is no information to indicate international spread of this virus. However, it is possible that an infected person, who may or may not have symptoms, could travel to another country. If the virus cannot sustain human-to-human transmission, as appears to be the current situation, then extensive community spread is unlikely.

• WHO does not advise special screening at points of entry with regard to this event, nor does it recommend that any travel or trade restrictions be applied.

RISK OF HUMAN TO HUMAN TRANSMISSION

Insufficient evidence to determine risk of A(H7N9) human to human transmission.

Risk of healthcare-associated transmission when caring for infected patients not yet determined

Infective period for A(H7N9) cases not known but patients likely to excrete the virus in body fluids

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 has not been detected in wild birds at this time

RISK ASSESSMENT

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

AVIAN INFLUENZA A(H7N9)

WHAT IS AVIAN INFLUENZA (AI)?

WHAT IS INFLUENZA A(H7N9)?

WHAT IS THE SOURCE OF INFLUENZA A(H7N9)?

SOURCE: OIE – Questions and Answers on Influenza A(H7N9)

PRESENT SITUATION IN CHINA

• To date, a total of 60 cases have been laboratory confirmed with influenza A(H7N9) virus in mainland China, including 14 deaths.

• The China Animal Disease Control Centre and the country’s animal health services, including the OIE Reference Laboratory in Harbin, are still investigating animal sources and possible reservoirs of the influenza virus A(H7N9).

Chinese health workers collect bags of dead chickens at the Huhai wholesale market on April 5. China on high alert over bird flu In Shanghai, more than 100,000 live birds have been killed in the past week at live-poultry markets across the city in an effort to contain the problem - CNN

The first human cases of type A influenza virus of the strain H7N9. was found in March 13, 2013. This strain of virus usually infects birds, and the report was followed by reinforced surveillance in bird populations in China.

The virus has been found in a pigeon in a market in Shanghai. It is not yet known how persons became infected. The possibility of animal-to-human transmission is being investigated, as is the possibility of person-to-person transmission.

Wild birds can normally carry avian influenza viruses in their respiratory or intestinal tracts but they do not commonly get sick. They have historically been reservoirs of influenza viruses

Avian influenza (AI) is an infectious viral disease of birds (especially wild water fowl such as ducks and geese), often causing no apparent signs of illness. AI viruses can sometimes spread to domestic poultry and cause large-scale outbreaks of serious disease.

Outbreaks of AI in poultry often raise global public health concerns due to their effect on poultry populations, their potential to cause serious disease in people, and their pandemic potential.

At this time there is no evidence of ongoing human-to-human transmission.

Influenza A H7N9 viruses are a group of influenza viruses that normally circulate among birds. The influenza A(H7N9) virus is one subgroup among the larger group of H7 viruses. Although some H7 viruses (H7N2, H7N3 and H7N7) have occasionally been found to infect humans, no human infections with H7N9 viruses have been reported until recent reports from China.

Influenza - or, as it is often known, flu - is a large family of different viruses (more than 70 major types), some of which affect humans and many of which affect other animals, especially birds.

AVIAN INFLUENZA A(H7N9)

HOW IS INFLUENZA A(H7N9) TRANSMITTED AND SPREAD AMONG BIRDS?

WHAT ARE THE REPORTING REQUIREMENTS FOR INFLUENZA A(H7N9)?

HAVE WILD BIRDS BEEN IDENTIFIED AS A CARRIER OF THE INFLUENZA A(H7N9) VIRUS?

Map of outbreak locations. SOURCE: OIE

Thus far, most patients with this infection have had severe pneumonia. Symptoms include fever, cough and shortness of breath. However, information is still limited about the full spectrum of disease that infection with influenza A(H7N9) virus might cause.

OIE Terrestrial Animal Health Code reporting guidelines

Confirmed Case: A patient with novel influenza A (H7N9) virus infection that is confirmed by CDC’s Influenza Laboratory or a CDC certified public health laboratory using methods agreed upon by CDC and CSTE.

Probable Case: A patient with illness compatible with influenza for whom laboratory diagnostic testing is positive for influenza A, negative for H1, negative for H1pdm09, and negative for H3 by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and therefore unsubtypeable.

An investigation by Chinese authorities is ongoing. H7N9 viruses have been detected in poultry in the same area where human infections have occurred. Many of the human cases of H7N9 are reported to have had contact with poultry. However some cases reportedly have not had such contact. Close contacts of confirmed H7N9 patients are being followed to see if any human-to-human spread of H7N9 might have occurred.

All the patients had preexisting medical conditions, and two had a history of direct contact with poultry.

Since April 4, it has been reported that H7N9 viruses similar to those isolated from the three patients described here have been isolated from pigeons and chickens, indicating that the novel H7N9 viruses might currently be circulating in poultry.

All AI viruses can be transmitted among birds through direct contact with secretions from infected birds, especially feces or through contaminated feed, water, equipment, and human clothing.

Several factors can contribute to the spread of all AI viruses including: the movements of people and goods, marketing practices (live bird markets), farming practices and the presence of the viruses in migratory wild birds.

We do not yet know enough about these infections to determine whether there is a significant risk of community spread. This possibility is the subject of epidemiological investigations that are now taking place.

Does this influenza virus pose a pandemic threat?Any animal influenza virus that develops the ability to infect people is a theoretical risk to cause a pandemic. However, whether the influenza A(H7N9) virus could actually cause a pandemic is unknown. Other animal influenza viruses that have been found to occasionally infect people have not gone on to cause a pandemic.

ECONOMIC IMPACTS

CURRENT SITUATION• China exports 1821.9 Hundred Million dollars of goods per month. • China produces 12.1 million metric tons of broiler meat.• SARS caused year-over-year growth to fall to 7.9% from 10.8% in Q1 2003--

H7N9 may cause a similar drop.

TRADE BANS• Vietnam has banned Chinese poultry imports.• Shanghai’s, Huhai’s, Hangzhou’s, Nanjin’s, and several other poultry

markets have been closed. • More bans may proliferate.

TRAVEL • No travel bans are in place. • Japanese airports are on alert for arriving travelers from China who exhibit

flu-like symptoms.

FOOD SECURITY• Chicken meat is a popular source of protein among poor workers. • In order to decrease the risk of H7N9 spread many birds were slaughtered

and will continue to be slaughtered. This could lead to food shortages and a lack of protein, especially for the poor. Consumers are also avoiding poultry and egg, despite authorities assuring that it is safe to eat if properly cooked.

MARKET REACTION• Soybeans and poultry shares are down on the Chinese market, but

pharmaceutical stocks are up, as well as the sales of medicinal herbs. Overall the Shanghai index is down .7%, the Hang Seng index 2.7%, and Bloomberg US-China Equity Index 1.8% due to fears of reduced economic growth The market has reacted similarly to travel companies, hotels, educational services, retail, and consumer staples due to beliefs that people will avoid congregating and traveling.

• Sales of chicken are down, while sales of masks and hand sanitizer are up.

http://www.thepoultrysite.com/http://www.grains.org/index.php/2012-04-30-15-22-26/4162-h7n9-affects-chinese-poultry-markethttp://www.chinaeconomicreview.com/big-bad-birdhttp://www.guardian.co.uk/world/2013/apr/05/bird-flu-shanghai-poultry-market-cull

RAMIFICATIONS: If H7N9 continues to spread or simply generates large amount of China’s recovery from the current global economic situation could be retarded.

MITIGATION: The WHO’s measured response to the disease has prevented market panic or intense travel fears. Continued consideration of economic ramifications before issuing alerts will help to minimize the amount of economic losses incurred.

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 POINTSH7N9 is a new avian flu virus.

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

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.

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.

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

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 flu can give it to another animal or human through feces, saliva, or nasal secretions. For now, there is no evidence of human to human transmission.

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 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.