Yale - Tulane ESF-8 Special Report A(H7N9) Virus


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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.

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Yale - Tulane ESF-8 Special Report A(H7N9) Virus

  1. 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 influenzaSOURCE: 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. 2. BACKGROUNDOn 31 March 2013, the World Health Organization (WHO) was notified by TRANSMISSION:China’s Health and Family Planning Commission of three cases of humaninfection with the influenza A(H7N9) virus. Since then, additional cases • Thousands of close contacts of confirmed H7N9 patients are beinghave 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 marketsANTIVIRAL DRUGS: So far, all three viruses seem to be susceptible to theinfluenza antiviral drugs oseltamivir and zanamivir, but they are resistant tothe amantanesVACCINE: There is no licensed H7N9 vaccine currently available butgovernment-backed researchers at Novartis and at and a unit of the J. CraigVenter 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 influenzaSOURCES: 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/ Chinas 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. 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 boySources: 1. WHO Update - 23 April 2013 2. www.Nature.com/news 3. South China Morning Post 4. www.NEJM.org 5. WHOs Western Pacific Region Office
  4. 4. SITUATION AGE DISTRIBUTION As of 23 April 2013 there have been a total of 108 cases have been • Experts from the WHOs 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 womenCASES: 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 UnderThere 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. 5. SITUATIONSOURCE OF THE VIRUS: Investigations into the possible sources of infection • If H7N9 virus infection is primarily zoonotic, as reports currentlyand reservoirs of the virus are ongoing. Until the source of infection has been suggest, transmission is expected to occur through exposure toidentified, it is expected that there will be further cases of human infection clinically normal but infected poultry, in contrast to HPAI H5N1 viruswith 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. 6. NUMBER OF DEATHS / NUMBER OF CONFIRMED CASESTotal number of confirmed 109*human cases A(H7N9) * Incudes asymptomatic 4 Year old boy - BeijingTotal number of deaths 22attributed A(H7N9)Current Case Fatality Rate 19%Average time from illness 9 daysonset to first confirmation ofH7N9 (days):Average age of the H7N9- 58 yearsconfirmed casesMedian age of the H7N9 62 yearsconfirmed casesThe mode of the ages among 54, 56 and 74confirmed cases (includingdeaths; years):The mode of the ages among 64, 74, 77the deceased (years):Males 67% of the cases 71% of the fatalitiesFemales 23%of the cases 29% of the fatalities SOURCE: VIROLOGY DOWN UNDER, DR. IAN M MACKAY
  7. 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 5Source: WHO Update - 23 April 2013
  8. 8. SITUATION - H7N9 IN POULTRY AND BIRDSPRESENT SITUATION IN CHINA• Chinas 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 InterfaceSOURCES• 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. 9. RISK ASSESSMENTGENERAL 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 restrictionsRISK 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. 10. REPONSE ACTIVITIESWORLD 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 Chinas 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 • Chinas 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 diseaseUS 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. 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 avianinfluenza viruses. TREATMENTHow 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 influenzatransmission. 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 canpotentially spread undetected from poultry to sporadic human cases. For patients in following categories, start empiric treatment with oral oseltamivir orWhat 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) SCREENINGWho 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 ofcriteria: 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. 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 yourcan sometimes lead to serious illness and death. hands) when coughing or sneezing. – Try to avoid close contact, such as kissing, hugging or sharing eatingHow 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, orDo 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 ofEat 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 returnReferences: (picture) http://www.ottawacitizen.com to the United States, be sure to tell your doctor about your recent travel tohttp://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