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Date: Wed 1 May 2013
Source: MMWR Morb Mortal Wkly Rep 2013; 62 (early release); 1-6 [summ., edited]
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm62e0501a1.htm?s_cid=mm62e0501a1_e
Emergence of avian influenza A(H7N9) virus causing severe human illness -- China, February-April 2013
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On 29 Mar 2013, the Chinese Center for Disease Control and Prevention completed laboratory confirmation of 3 human infections with an avian influenza A(H7N9) virus not previously reported in humans (1). These infections were reported to the World Health Organization (WHO) on 31 Mar 2013, in accordance with International Health Regulations. The cases involved 2 adults in Shanghai and one in Anhui Province. All 3 patients had severe pneumonia, developed acute respiratory distress syndrome (ARDS), and died from their illness (2). The cases were not epidemiologically linked. The detection of these cases initiated a cascade of activities in China, including diagnostic test development, enhanced surveillance for new cases, and investigations to identify the source(s) of infection. No evidence of sustained human-to-human transmission has been found, and no human cases of H7N9 virus infection have been detected outside China. This report summarizes recent findings and recommendations for preparing and responding to potential H7N9 cases in the United States. Clinicians should consider the diagnosis of avian influenza A(H7N9) virus infection in persons with acute respiratory illness and relevant exposure history and should contact their state health departments regarding specimen collection and facilitation of confirmatory testing.
Epidemiologic investigation
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As of 29 Apr 2013, China had reported 126 confirmed H7N9 infections in humans, among whom 24 (19 per cent) died (1). Cases have been confirmed in 8 contiguous provinces in eastern China (Anhui, Fujian, Henan, Hunan, Jiangsu, Jiangxi, Shandong, and Zhejiang), 2 municipalities (Beijing and Shanghai), and Taiwan. Illness onset of confirmed cases occurred during 19 Feb-29 Apr 2013. The source of the human infections remains under investigation. Almost all confirmed cases have been sporadic, with no epidemiologic link to other human cases, and are presumed to have resulted from exposure to infected birds (3,4). Among 82 confirmed cases for which exposure information is available, 63 (77 per cent) involved reported exposure to live animals, primarily chickens (76 per cent) and ducks (20 per cent) (3). However, at least 3 family clusters of 2 or 3 confirmed cases have been reported where limited human-to-human transmission might have occurred (3).
The median age of patients with confirmed infection is 61 years (interquartile range: 48-74); 17 (21 per cent) of the cases are among persons aged 75 years or older and 58 (71 per cent) of the cases are among males. Only 4 cases have been confirmed among children; in addition, a specimen from one asymptomatic child was positive for H7N9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). Among the 71 cases for which complete data are available, 54 (76 per cent) patients had at least one underlying health condition (3). Most of the confirmed cases involved severe respiratory illness. Of 82 confirmed cases for which data were available as of 17 Apr 2013, 81 (99 per cent) required hospitalization (3). Among those patients hospitalized, 17 (21 per cent) died of ARDS or multiorgan failure, 60 (74 per cent) remained hospitalized, and only 4 (5 per cent) had been discharged (3).
Chinese public health officials have investigated human contacts of patients with confirmed H7N9. In a detailed report of a follow-up investigation of 1689 contacts of 82 infected persons, including health care workers who cared for those patients, no transmission to close contacts of confirmed cases was reported, although investigations including serologic studies are ongoing (3). In addition, influenza surveillance systems in China have identified no sign of increased community transmission of this virus. Seasonal influenza A(pH1N1) and influenza B viruses continue to circulate among persons in areas where H7N9 cases have been detected, and the Chinese Centers for Disease Control and Prevention has reported that rates of influenza-like illness are consistent with expected seasonal levels.
CDC, along with state and local health departments, is continuing epidemiologic and laboratory surveillance for influenza in the United States. On 5 Apr 2013, CDC requested state and local health departments to initiate enhanced surveillance for H7N9 among symptomatic patients who had returned from China in the previous 10 days (5). As of 29 Apr 2013, 37 such travelers had been reported to CDC by 18 states. Among those 37 travelers, none were found to have infection with H7N9; 7 had an infection with a seasonal influenza virus, one had rhinovirus, one had respiratory syncytial virus, and 28 were negative for influenza A and B. Among 31 cases with known patient age, 7 travelers were aged less than 18 years, 13 were aged 18-64 years, and 11 were aged 65 years or older. In addition, influenza activity in the United States is low and continues to decrease, with morbidity and mortality surveillance systems reporting activity below seasonal baseline levels. Although low numbers of influenza viruses are being detected, the majority in recent weeks have been influenza B.
Laboratory investigation
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As of 30 Apr 2013, Chinese investigators had posted 19 partial or complete genome sequences from avian influenza A(H7N9) viruses to a publicly available database at the Global Initiative on Sharing All Influenza Data (http://www.gisaid.org). Sequences are from viruses infecting 12 humans and 5 birds, and 2 are from viruses collected from the environment. These sequences indicate that all 8 genes of the H7N9 virus are of avian origin, with the closest phylogenetic relatives from 3 Eurasian influenza virus lineages (H7N3 from domestic ducks, H7N9 from wild birds, and H9N2 from birds widely distributed throughout East Asia). In addition, genetic changes in the sequences are present that have been associated with adaptations leading to enhanced virus binding to and replication in mammalian respiratory cells and increased severity of infection (2,4,6).
Immediately after notification by Chinese health authorities of the H7N9 cases, CDC began development of a new H7 diagnostic test for use with the existing CDC influenza rRT-PCR kit. This test has been designed to diagnose infection with Eurasian H7 viruses, including the recently recognized China H7N9 and other representative H7 viruses from Southeast Asia and Bangladesh. On 22 Apr 2013, this new H7 test was cleared by the Food and Drug Administration for use as an in vitro diagnostic test under an Emergency Use Authorization, thus allowing distribution and use of the test in the United States. The CDC H7 rRT-PCR test is now available to all qualified US public health and US Department of Defense laboratories and WHO-recognized National Influenza Centers globally and can be ordered from the Influenza Reagent Resource (http://www.influenzareagentresource.org). Access to the CDC H7 rRT-PCR test protocol is available at http:/www.cdc.gov/flu/clsis. Guidance on appropriate biosafety levels for working with the virus and suspect clinical specimens is being developed.
Animal investigation and US animal health preparedness activities
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As of 26 Apr 2013, reports from the China Ministry of Agriculture indicate that 68 060 bird and environmental specimens have been tested, 46 (0.07 per cent) were confirmed H7N9-positive by culture (7). The H7N9 virus has been confirmed in chickens, ducks, pigeons (feral and captive), and environmental samples in 4 of the 8 provinces and in Shanghai municipality. As of 17 Apr 2013, approximately 4150 swine and environmental samples from farms and slaughterhouses were reported to have been tested; all swine samples were negative. (Additional information available at http://www.chinacdc.cn). The China Ministry of Agriculture is jointly engaged with the National Health and Family Planning Commission in conducting animal sampling to assist in ascertaining the extent of the animal reservoir of the H7N9 virus. Sampling of animals is concentrated in the provinces and cities where human cases have been reported. Poultry markets in Shanghai and other affected areas have been closed temporarily, and some markets might remain closed.
The US Department of Agriculture (USDA) has set up a Situational Awareness Coordination Unit with a core team of subject matter experts and other USDA representatives, including the Animal and Plant Health Inspection Service (APHIS), the Agricultural Research Service (ARS), the Food Safety and Inspection Service, and the Foreign Agricultural Service. USDA and CDC are working collaboratively to understand the epidemiology of H7N9 infections among humans and animals in China. To date, no evidence of this strain of avian influenza A(H7N9) virus has been identified in animals in the United States. The US government does not allow importation of live birds, poultry, and hatching eggs from countries affected with highly pathogenic avian influenza. The current US surveillance program for avian influenza in commercial poultry actively tests for any form of avian influenza virus and would be expected to detect avian influenza A(H7N9) if it were introduced to the United States. A screening test for avian influenza is available from the National Animal Health Laboratory Network and the National Veterinary Services Laboratories (NVSL), which can be used together with confirmatory tests at NVSL to detect this strain of avian influenza A(H7N9) in poultry and wild bird samples.
Editorial note
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The epidemiology of H7N9 infections in humans so far reveals that most symptomatic patients are older (median age: 61 years), most are male (71 per cent), and most had underlying medical conditions. In comparison, among the 45 avian influenza A(H5N1) cases reported from China during 2003-2013, the median patient age is 26 years (8). This difference in median age might represent actual differences in exposure or susceptibility to H7N9 virus infection and clinical illness, or preliminary H7N9 case identification approaches might be more likely to capture cases in older persons. Ongoing surveillance and case-control studies are needed to better understand the epidemiology of H7N9 virus infections, and to determine whether younger persons might be more mildly affected, and therefore less likely to be detected via surveillance.
Available animal testing data and human case histories indicate that most human patients have poultry exposure; however, relatively few H7N9 virus-infected birds have been detected. During the month after recognition of H7N9, increasing numbers of infected humans have been identified in additional areas of eastern China, suggesting possible widespread occurrence of H7N9 virus in poultry. Enhanced surveillance in poultry and other birds in China is needed to better clarify the magnitude of H7N9 virus infection in birds and to better target control measures for preventing further transmission.
The emergence of this previously unknown avian influenza A(H7N9) virus as a cause of severe respiratory disease and death in humans raises numerous public health concerns. First, the virus has several genetic differences compared with other avian influenza A viruses. These genetic changes have been evaluated previously in ferret and mouse studies with other influenza A viruses, including highly pathogenic avian influenza A(H5N1) virus, and were associated with respiratory droplet transmission, increased binding of the virus to receptors on cells in the respiratory tract of mammals, increased virulence, and increased replication of virus (5). Epidemiologic investigations have not yielded conclusive evidence of sustained human-to-human H7N9 virus transmission; however, further adaptation of the virus in mammals might lead to more efficient and sustained transmission among humans. Second, human illness with H7N9 virus infection, characterized by lower respiratory tract disease with progression to ARDS and multiorgan failure, is significantly more severe than in previously reported infection with other H7 viruses. Over a 2-month period, 24 deaths (19 per cent of cases) have occurred, compared with only one human death attributed to other subtypes of H7 virus reported previously. Third, H7N9-infected poultry are the likely source of infection in humans, but might not display illness symptoms. Consequently, efforts to detect infection in poultry and prevent virus transmission will be challenging for countries lacking a surveillance program for actively identifying low-pathogenicity avian influenza in poultry. In the United States, an active surveillance program is in place that routinely identifies low-pathogenicity viruses. If this newly recognized H7N9 is detected, public health and animal health officials should identify means for monitoring the spread of asymptomatic H7N9 virus infections in poultry and maintain vigilance for virus adaptation and early indications of potential human-to-human transmission.
Beginning in early April 2013, CDC and US state and local health departments initiated enhanced surveillance for H7N9 virus infections in patients with a travel history to affected areas. A new CDC influenza rRT-PCR diagnostic test has been cleared by the Food and Drug Administration under an Emergency Use Authorization and is being distributed to public health laboratories to assist in evaluating these suspect cases. Clinicians should consider the possibility of H7N9 virus infection in patients with illness compatible with influenza who 1) have traveled within 10 days of illness onset to countries where avian influenza A(H7N9) virus infection recently has been detected in humans or animals, or 2) have had recent contact (within 10 days of illness onset) with a person confirmed to have infection with avian influenza A(H7N9) virus. Because of the potential severity of illness associated with avian influenza A(H7N9) virus infection, CDC recommends that all H7N9 patients (confirmed, probable, or under investigation for H7N9 infection) receive antiviral treatment with oseltamivir or zanamivir as early as possible. Treatment should be initiated even more than 48 hours after onset of illness. Guidance on testing, treatment, and infection control measures for H7N9 cases has been posted to the CDC H7N9 website (9).
On 5 Apr 2013, CDC posted a Travel Notice on the Traveler's Health website informing travelers and US citizens living in China of the current H7N9 cases in China and reminding them to practice good hand hygiene, follow food safety practices, and avoid contact with animals (10). CDC and WHO do not recommend restricting travel to China at this time. If travelers to China become ill with influenza signs or symptoms (such as, fever, cough, or shortness of breath) during or after returning from their visit, they should seek medical treatment and inform their doctor about their recent travel. Travelers should continue to visithttp://www.cdc.gov/travel or follow @CDCtravel on Twitter for up-to-date information about CDC's travel recommendations.
Given the number and severity of human H7N9 illnesses in China, CDC and its partners are taking steps to develop a H7N9 candidate vaccine virus. Past serologic studies evaluating immune response to H7 subtypes of influenza viruses have shown no existing cross-reactive antibodies in human sera. In addition, CDC has activated its Emergency Operations Center to coordinate efforts. In the United States, planning for H7N9 vaccine clinical trials is under way. Although no decision has been made to initiate an H7N9 vaccination program in the United States, CDC recommends that local authorities and preparedness programs take time to review and update their pandemic influenza vaccine preparedness plans because it could take several months to ready a vaccination program, if one becomes necessary.
CDC also recommends that public health agencies review their overall pandemic influenza plans to identify operational gaps and to ensure administrative readiness for an influenza pandemic. Continued collaboration between the human and animal health sectors is essential to better understand the epidemiology and ecology of H7N9 infections among humans and animals and target control measures for preventing further transmission.
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[The preceding report provides an account of the current H7N9 outbreak from a US perspective (the complete report and references are available at the source URL above). State and local health authorities are being encouraged to review pandemic influenza preparedness plans to ensure response readiness. Clinicians in the US should consider H7N9 virus infection in recent travelers from China who exhibit signs and symptoms consistent with influenza. Patients with H7N9 virus infection (laboratory-confirmed, probable, or under investigation) should receive antiviral treatment with oral oseltamivir or inhaled zanamivir as early as possible.
The report includes a map of the confirmed cases and deaths from avian influenza A(H7N9) in China as of 29 Apr 2013. At that point China had reported 126 confirmed cases of H7N9 infection, of which 24 (19 per cent) have resulted in death. The map displays the locations of the confirmed cases in 8 contiguous provinces in eastern China (Anhui, Fujian, Henan, Hunan, Jiangsu, Jiangxi, Shandong, and Zhejiang), 2 municipalities (Shanghai and Beijing), and Taiwan. http://www.promedmail.org/direct.php?id=20130502.1686919
