In light of the recent outbreaks in China, the Yale-Tulane ESF #8 Planning and Response Program has produced a special report the A(H7N9) virus. The group that produced this summary and analysis of the current situation are graduate students from Yale and Tulane Universities. It was compiled entirely from open source materials.

1. YALE- TULANE ESF-8 SPECIAL REPORT
A(H7N9) VIRUS
CHINESE GOVERNMENT
First confirmed case
in Shandong Province
BACKGROUND  Ministry of Agriculture
 Ministry of Health of the
was reported on People’s Republic of China
23 April 2013.  Chinese Center for Disease H7N9 OUTBREAK
SITUATION Control and Prevention CHARACTERIZATION
 Hong Kong Department of
Health | Centre for Health
Protection
HUMAN CASES  National Health and Family
Planning Commission
INTERNATIONAL ORGANIZATIONS
SITUATION MAP FAO
OIE
WHO
 World Health Organization
H7N9 IN POULTRY AND BIRDS Western Pacific Region
 Disease Outbreak News
 Human infection with influenza
SOURCE: Bloomberg News A(H7N9) virus
RISK ASSESSMENT  Global Initiative on Sharing All
AS OF 23 APRIL 2013 Influenza Data (GISAID)
CONFIRMED DEAD US GOVERNMENT • H7N9 infections in
1 RESPONSE ACTIVITIES CDC – Health Info people and
108 1
22 EUROPEAN UNION poultry in China
SCREENING PATIENTS RETURNING ECDC
FROM CHINA PORTALS, BLOGS, AND RESOURCES • Sporadic
 Avian Flu Diary infections in
 CIDRAP
 FluTrackers.com humans; many
TIPS FOR THOSE VISITING CHINA  Flu Wiki with poultry
 Health Map
 ProMed Mail exposure
 Virology Down Under
NEW SOURCES • No sustained or
AS OF1900  People’s Daily Online – China community
High Alert H7N9
HRS EDT  China Daily transmission
 Forbes
23 APRIL 2013  Bloomberg
 AlertNet • Investigation
 Reuters ongoing
 NY Times
SOURCE: CDC

2. BACKGROUND
On 31 March 2013, the World Health Organization (WHO) was notified by TRANSMISSION:
China’s Health and Family Planning Commission of three cases of human
infection with the influenza A(H7N9) virus. Since then, additional cases • Thousands of close contacts of confirmed H7N9 patients are being
have been reported. Most reported cases have severe respiratory illness followed to see if any human-to-human spread of H7N9 has occurred.
and, in some cases, have died. With perhaps rare exceptions, people are not getting sick from other
people.
• 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 • Of the many hundreds of people who were in close contact with the
commonly after exposure to infected poultry. This is the first time that H7N9 patients, all the care-givers, neighbors, and family members,
A(H7N9) has been found in humans 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
• Cases presented with respiratory tract infection with progression to severe attention to. Otherwise it it still seems that this does not happen easily,
pneumonia and breathing difficulties. or there would be evidence of many such cases. There has not been
sustained person-to-person transmission.
• At this time there are no cases of H7N9 outside of China.
THE SOURCE: While the novel A(H7N9) virus has been detected in birds
• There are no vaccines available at this time. and environmental specimens at a bird markets in Shanghai and the other
affected provinces, the source of infection in most of the cases still
• China has intensified human and animal surveillance. It has also remains to be determined
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
SOURCES: virus at the provincial center for disease control and prevention in Hangzhou, capital of east
• 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/
China's Zhejiang Province, April 17, 2013. An emergent testing team on 24-hour stand-by was set
• New technology speeding progress on bird flu vaccine (Reuters) up in the center after the recent spread of the H7N9 virus. Infections within the province will be
• Global Concerns Regarding Novel Influenza A (H7N9) Virus Infections officially confirmed by the center. (Xinhua/Xu Yu)
• Chinese Centers for Disease Control and Prevention H7N9 Information

3. SITUATION
Cases Type Most Recent Total1
Deaths 22
Laboratory-Confirmed 108
Cases
ALL CONFIRMED HUMAN INFECTIONS WITH A(H7N9) ARE Note: All case and death totals are as of 8 am EST, April 22, 2013
SPORADIC CASES, AND THERE IS NO EVIDENCE OF ONGOING
HUMAN-TO-HUMAN TRANSMISSION.1 H7N9 HAS NEVER BEFORE BEEN DETECTED IN
However, this is still a future possibility: HUMANS4
• Every time the virus encounters and infects a new human • WHO has published Real-time RT PCR (rRT-PCR） Protocol
host, it has the opportunity to mutate.2 for the Detection of A(H7N9) Avian Influenza Virus
• The haemagglutinin (H) surface protein on the virus has • All age groups expected to be susceptible.4 However, the
shown mutations that precede a change in binding age distribution is skewed toward the elderly. 5
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
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
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

4. SITUATION
AGE DISTRIBUTION
As of 23 April 2013 there have been a total of 108 cases have been
• Experts from the WHO's Western Pacific Region Office (WPRO) wrote that among
laboratory confirmed with influenza A(H7N9) virus in mainland China,
the 63 H7N9 cases reported from Mar 31 through Apr 16, the median age was 64,
including 14 recovered and discharged, 72 in hospitalization and 22 and 45 patients (71%) were male. Thirty-nine of the 63 patients (62%) were at
deaths. There is no evidence of ongoing human-to-human transmission. 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
CASES: among the elderly.
• Cases have been confirmed in the
• Three main reasons may be considered for the current case distribution:
following provinces and
(1) Differential exposure between males and females due to gender-
municipalities: Shanghai, Beijing
associated practices and norms
Jiangsu, Anhui, Henan , Zhejiang,
(2) Biological differences between males and females in the clinical course
and Shandong. All locations are in
post exposure/infection
Eastern and Northern China.
(3) Differential healthcare-seeking/access behavior between male and
• Shanghai was the first municipality to females, leading to surveillance/detection bias.
report cases but recent activity has • At this time further investigation is required.
been concentrated in Zhejiang
province.
CLUSTERS: SOURCE: Virology Down Under
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:
• Chinese Centers for Disease Control – H7N9 Update – 23 April 2013
• WHO Update – 23 April 2013 The ages for the cases where age is reported range from 2 to 89 years old. The age
• Virology Down Under
distribution is skewed toward the elderly. Only four pediatric cases have been
• WPRO: Human infections with avian influenza A(H7N9) virus in China: preliminary assessments of the age and
sex distribution 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

5. SITUATION
SOURCE OF THE VIRUS: Investigations into the possible sources of infection • If H7N9 virus infection is primarily zoonotic, as reports currently
and reservoirs of the virus are ongoing. Until the source of infection has been suggest, transmission is expected to occur through exposure to
identified, it is expected that there will be further cases of human infection clinically normal but infected poultry, in contrast to HPAI H5N1 virus
with the virus in China. infection, which typically causes rapid death in infected chickens.
• The hemagglutinin (HA) sequence data suggest that these H7N9 viruses
GENETIC CHARACTERISTICS: The sequences of the first three viruses
are a low-pathogenic avian influenza A virus and that infection of wild
were posted to GISAID by China and are publicly available.
birds and domestic poultry would therefore result in asymptomatic or
• The novel H7N9 viruses possess several characteristic features of mild avian disease, potentially leading to a “silent” widespread
mammalian influenza viruses, which are likely to contribute to their ability epizootic in China and neighboring countries. The HA sequence data
to infect humans and raise concerns regarding their pandemic potential. also featured:
‒ Mutations that have been shown to improve the virus’ ability to
• H7N9 viruses features H7 HA and N9 NA surface proteins, a combination
bind to human cells, the first step in the infection process.
that had been previously seen only in birds.
‒ A mutation associated with improved virus reproduction within
human cells, which helps the infection spread throughout the
• H7N9 acquired its surface protein genes from the H7N3 and H7N9 avian body and cause disease.
influenza strains, and its remaining genes from H9N2 influenza viruses
that had recently circulated in poultry in China. • 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.
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

6. NUMBER OF DEATHS / NUMBER OF CONFIRMED CASES
Total number of confirmed 109*
human cases A(H7N9)
* Incudes
asymptomatic
4 Year old boy
- Beijing
Total number of deaths 22
attributed A(H7N9)
Current Case Fatality Rate 19%
Average time from illness 9 days
onset to first confirmation of
H7N9 (days):
Average age of the H7N9- 58 years
confirmed cases
Median age of the H7N9 62 years
confirmed cases
The mode of the ages among 54, 56 and 74
confirmed cases (including
deaths; years):
The mode of the ages among 64, 74, 77
the deceased (years):
Males 67% of the
cases 71% of
the fatalities
Females 23%of the
cases 29% of
the fatalities
SOURCE: VIROLOGY DOWN UNDER, DR. IAN M MACKAY

7. DISTRIBUTION OF CASES GEOGRAPHICALLY
Total number
of confirmed
cases
Total number
of deaths
1 0
1 0
3 0 24 3
33 12
3 1
40 5
Source: WHO Update - 23 April 2013

8. SITUATION - H7N9 IN POULTRY AND BIRDS
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.
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. • Situation is ongoing
Situation is ongoing.
SOURCE: WAHID Interface
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

9. RISK ASSESSMENT
GENERAL INFORMATION:
 At this time, there are still gaps in information and evidence available. RISK OF FURTHER CASES IN CHINA
 Most human cases of H7N9 likely due to animal exposure
 Investigations into possible sources of infection and reservoirs of the virus  Further cases are expected
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. OTHER MODES OF TRANSMISSION
 No epidemiological evidence of transmission to humans through
 For precautionary reasons, those working in or visiting China should avoid the consumption of food
visiting live bird and animal markets and direct contact with bird and
 Low or no risk of transmission through blood transfusion or
animal feces, untreated bird feathers, and other animal and bird waste
organ/tissue donations
 Importation through food and agricultural products from China
unlikely due to importation restrictions
RISK OF HUMAN TO HUMAN TRANSMISSION  Risk of spread through migratory birds unknown
• There is insufficient evidence to quantify the risk of A(H7N9) developing  Virus been detected in a feral pigeon and
into a virus that transmits from human to human
• At the present time there is no evidence of sustained human-to-human
transmission TWO RISK ASSESSMENTS
 Infective period for A(H7N9) cases not known but patients likely to HAVE BEEN PUBLISHED:
excrete the virus in body fluids
 Pathogenicity for humans appears to be high and higher age appears to European Centre for Disease
be a risk factor for disease. Prevention and Control (12 April
2013)
http://www.ecdc.europa.eu/en/publications/P
ublications/influenza-A(H7N9)-China-rapid-
RISK OF INTERNATIONAL SPREAD risk-assessment-4-april-2013.pdf
 Risk of international spread via humans currently low
 As virus cannot sustain human-to-human transmission, extensive World Health Organization (13
spread unlikely regardless of infected travelers April 2013):
 WHO does not advise special screening at points of entry with regard http://www.who.int/influenza/human_animal_i
to this event or any travel restrictions nterface/influenza_h7n9/RiskAssessment_H
 No cases have been reported outside of China 7N9_13Apr13.pdf

10. REPONSE ACTIVITIES
WORLD HEALTH ORGANIZATION CHINESE GOVERNMENT
• Chinese government notifies the World Health Organization
• WHO is in contact with national authorities and is following the of the emergence of an A(H7N9)
H7N9. • Chinese health authorities are conducting investigations to
• The WHO-coordinated international response is also focusing on learn the source of the infections with this virus
work with WHO Collaborating Centers for Reference and • Chinese scientists first sequence the viral genome and
Research on Influenza and other partners to ensure that identified the origin of this new virus.
information is available and that materials are developed for • The Chinese health authorities are responding to this public
diagnosis and treatment and vaccine development. WHO health event by enhanced surveillance, epidemiological and
publishes background and summary of H7N9 5 April 2013 laboratory investigation and contact tracing.
• The WHO Collaborating Center for Reference and Research on • All influenza network laboratories in the 31 provincial
Influenza at the Chinese National Influenza Center in Beijing, regions on China's mainland are now capable of testing for
China, has made available the real-time RT-PCR protocol for the the H7N9 bird flu virus
detection of avian influenza A(H7N9) virus. 8 April 2013 • China's Ministry of Agriculture gathers samples from poultry
(updated on 15 April 2013) markets, farms and slaughterhouses across the country. So
• WHO post Risk Assessment 13 April 2013 far, 84,444 samples have been taken, 47,801 have been
• WHO post Standardization of the influenza A(H7N9) virus tested and 39 samples confirmed as H7N9 positive.
terminology as of 16 April 2013 Surveillance continues.
pdf, 92kb • President Xi Jinping urged government authorities to take
• At the invitation of the National Health and Family Planning effective measures to contain the spread of the H7N89. Xi
Commission of China, WHO has convened a team of experts who said local authorities should prioritize public safety and
are currently visiting areas affected by avian influenza A(H7N9) health, as well as strengthen disease control and
in China in order to provide recommendations on the prevention prevention. He also called for efforts to conduct
and control of the disease. epidemiological studies of the disease, strictly control
infection sources, promote public awareness of disease
US GOVERNMENT prevention and accelerate the development of vaccines.
• 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

11. FACT SHEET: AVIAN INFLUENZA A (H7N9) VIRUS
SCREENING PATIENTS RETURNING FROM CHINA
KEY POINTS
2. Recent contact with confirmed human H7N9 cases
• Clinicians should consider the possibility of novel influenza A (H7N9) virus infection
in persons presenting with respiratory illness within 10 days of an appropriate Information on incubation period is incomplete but other avian influenza had
travel or exposure history. incubation period ranging 3-9 days.
• 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 INFECTION CONTROL
and may cause illness in children as well.
Use Standard Precautions plus Droplet, Contact,
• Influenza diagnostic testing in patients with respiratory illness for whom an and Airborne Precautions, including eye protection
etiology has not been confirmed may identify human cases of avian influenza A until more is known about the transmission
virus infection or new cases of variant influenza in the United States. characteristics.
• 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- DIAGNOSTIC TESTS
PCR) testing but be unsubtypeable. Clinicians suspecting novel influenza A (H7N9) Commercial rapid influenza diagnostic tests may not detect avian or variant A
should obtain appropriate specimens and notify their local or state health viruses. Hence a negative test does not exclude H7N9 infection.
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. 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
OVERVIEW CDC.
What is H7N9 virus? The virus appears to be a reassortment of three avian
influenza viruses. TREATMENT
How does H7N9 flu spread? Thus far, there is no evidence of human-to-human Do not base treatment decision solely on the result of a negative rapid influenza
transmission. Some affected patient had exposures to poultry before falling ill. diagnostic test result.
There is concern that H7N9 does not cause severe illness in birds and hence can
potentially spread undetected from poultry to sporadic human cases.
For patients in following categories, start empiric treatment with oral oseltamivir or
What are the symptoms? Predominant presenting symptoms have been severe inhaled zanamivir as soon as possible without waiting for laboratory confirmation:
respiratory tract infections which progressed to pneumonia. 1.Patients hospitalized with suspected influenza, including H7N9 cases
2.High risk persons (age <5 or ≥65, certain underlying medical conditions)
SCREENING
Who should be tested ? Patients with flu symptoms and the following exposure
Antiviral treatment is most effective if started as soon as possible after the onset of
criteria:
influenza illness. But treatment in moderate, severe, or progressive disease that
1. Recent travel to countries with human H7N9 cases, especially if there was began after 48 hours may still have some benefit.
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
References: (picture) www.abcnew.com, www.upmc-biosecurity.org, www.uptodate.com,
country with recent reported human cases. http://emergency.cdc.gov/HAN/han00344.asp, http://www.cdc.gov/flu/avianflu/guidance-labtesting.htm

12. FACT SHEET: AVIAN INFLUENZA A (H7N9) VIRUS
TIPS FOR THOSE VISITING CHINA
KEY POINTS
Practice hygiene and cleanliness:
H7N9 is a new bird flu virus.
– Wash your hands often.
Rare but serious human cases have occurred – If soap and water aren’t available,
in China. So far, there is no evidence of clean your hands with hand sanitizer
sustained human-to-human transmission. containing at least 60% alcohol.
– Don’t touch your eyes, nose, or mouth. If you need to touch your face,
OVERVIEW make sure your hands are clean.
What is H7N9 flu? It is a contagious disease in humans and other animals that – Cover your mouth and nose with a tissue or your sleeve (not your
can sometimes lead to serious illness and death. hands) when coughing or sneezing.
– Try to avoid close contact, such as kissing, hugging or sharing eating
How does H7N9 flu spread? An animal with H7N9 virus can give it to another
utensils or cups, with people who are sick.
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.
IF YOU BECOME ILL….
See a doctor if you become sick during or after travel to China.
PREVENTION ‒ See a doctor right away if you become sick with fever, coughing, or
Do not touch birds or other animals. shortness of breath.
‒ Do not touch animals whether they are alive or dead. ‒ If you get sick while you are still in China, visit the US Department of State
‒ Avoid live bird or poultry markets. website to find a list of local doctors and hospitals. Many foreign hospitals
‒ Avoid other markets or farms with animals (wet markets). and clinics are accredited by the Joint Commission International. A list of
Eat food that is fully cooked. accredited facilities is available at their website
– Eat meat and poultry that is fully cooked (not pink) and served hot. (www.jointcommissioninternational.org).
– Eat hard-cooked eggs (not runny). ‒ Delay your travel home until after you have recovered or your doctor says
– Don’t eat or drink dishes that include blood from any animal. it is ok to travel.
– Don’t eat food from street vendors.
‒ If you get sick with fever, coughing, or shortness of breath after you return
References: (picture) http://www.ottawacitizen.com to the United States, be sure to tell your doctor about your recent travel to
http://www.cdc.gov/flu/avianflu/h7n9-virus.htm, China.
http://www.who.int/csr/don/2013_04_10/en/
http://wwwnc.cdc.gov/travel/notices/watch/avian-flu-h7n9-china.htm