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Emerg Infect Dis. Asymptomatic, Mild, and Severe Influenza A(H7N9) Virus Infection in Humans, Guangzhou, China

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  • Emerg Infect Dis. Asymptomatic, Mild, and Severe Influenza A(H7N9) Virus Infection in Humans, Guangzhou, China

    [Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Edited.]


    Volume 20, Number 9?September 2014 / Dispatch

    Asymptomatic, Mild, and Severe Influenza A(H7N9) Virus Infection in Humans, Guangzhou, China

    Zongqiu Chen<SUP>1</SUP>, Hui Liu<SUP>1</SUP>, Jianyun Lu<SUP>1</SUP>, Lei Luo<SUP>1</SUP>, Kuibiao Li, Yufei Liu, Eric H.Y. Lau, Biao Di, Hui Wang, Zhicong Yang<SUP>2</SUP>, and Xincai Xiao<SUP>2</SUP>
    <SUP></SUP>
    Author affiliations: Guangzhou Center for Disease Control and Prevention, Guangzhou, China (Z. Chen, H. Liu, J. Lu, L. Luo, K. Li, Y. Liu, B. Di, H. Wang, Z. Yang, and X. Xiao); University of Hong Kong, Hong Kong, China (E.H.Y. Lau)


    Abstract

    Targeted surveillance for influenza A(H7N9) identified 21 cases of infection with this virus in Guangzhou, China, during April 1, 2013?March 7, 2014. The spectrum of illness ranged from severe pneumonia to asymptomatic infection. Epidemiologic findings for a family cluster of 1 severe and 1 mild case suggested limited person-to-person transmission of this virus.
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    During February?May 2013, the initial outbreak of human infection with avian influenza A(H7N9) virus in China resulted in 133 cases (1). Influenza A(H7N9) virus reemerged in southern China in October 2013 and had caused 85 laboratory-confirmed cases of infection in Guangdong Province as of March 7, 2014. In response to the outbreak, targeted surveillance programs were established in April 2013 in Guangzhou, the provincial capital of Guangdong Province. Here, we report results of this surveillance program through early 2014.


    The Study

    Since 2004, all clinical facilities in Guangzhou (population 13 million in 2013) have been required by the China National Health and Family Planning Commission to report any patient who meets the criteria of having pneumonia of unknown etiology (PUE): fever (>38?C), radiologic characteristics consistent with pneumonia, low-normal leukocyte count or low lymphocyte count in early-stage disease, and no alternative etiology (2). Upper or lower respiratory samples from these patients are collected for identification of possible causative pathogens. In response to the influenza A(H7N9) outbreak, PUE surveillance was enhanced in April 2013 by implementing laboratory testing specific for influenza A(H7N9) virus (3). Specimens are initially screened for influenza A and B viruses by real-time reverse transcription PCR (rRT-PCR); samples positive for influenza A are then subtyped as H1N1, H3N2, H5N1, or H7N9.

    Surveillance for influenza-like illness (ILI) was initially conducted in 4 sentinel hospitals in Guangzhou and expanded to 19 hospitals in November 2013. Each hospital collects 10?20 convenience throat swab specimens weekly from ILI patients visiting the hospitals within 3 days of illness onset. The same laboratory screening protocols were adopted as for PUE surveillance.

    Surveillance for influenza A(H7N9) virus was established in 24 live poultry markets (LPMs) in April 2013 and expanded to 42 LPMs in November 2013, covering all 12 districts in Guangzhou. From each LPM, 10?30 environmental samples are collected biweekly and tested by rRT-PCR. When human influenza A(H7N9) infection is confirmed, additional environmental sampling from epidemiologically linked LPMs is immediately launched to trace the possible source of infection. All poultry workers linked to influenza A(H7N9) virus?contaminated LPMs (i.e., LPMs with >1 virus-positive environmental samples identified) are placed under medical observation for 7 days. Throat swab specimens are collected within 24 hours for detection of influenza A(H7N9) infection and second swab specimens are collected if symptoms appear.

    Close contacts of influenza A(H7N9) case-patients are defined as any family member who shares residence, social contacts who visit, and health care workers who provide medical services without effective personal protection (4) during the period from 1 day before illness onset to isolation (5). All close contacts are monitored for 7 days for any symptoms, and throat swab specimens are collected to detect possible person-to-person transmission.
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    Figure 1

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    Figure 1. Weekly number of confirmed influenza A(H7N9) cases, percentage of pneumonia patients with pneumonia of unknown etiology (PUE), and percentage of patients with influenza-like illness (ILI) tested for influenza A(H7N9), Guangzhou, China,...
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    From April 1, 2013, through March 7, 2014, a total of 47,937 patients with pneumonia were reported in Guangzhou (Table 1). Of these, 1,923 (4.0%) met PUE criteria, and respiratory specimens were collected and tested. An influenza A(H7N9) case in Guangzhou was confirmed on January 10, 2014 (Figure 1); since then, an additional 15 patients with PUE were confirmed as influenza A(H7N9) case-patients. All were adults; 11 (69%) were >60 years of age. Recent poultry exposure history was available for 14 (88%) patients (Table 2).

    During the same period (April 1, 2013?March 7, 2014), a total of 4,149 throat swab specimens were collected from 349,712 ILI patients (Table 1); 3 (0.1%) specimens were positive for influenza A(H7N9) virus. All 3 patients were young urban residents who had mild upper respiratory symptoms (Table 2). As a safety measure, these patients were isolated and treated with oseltamivir. All 3 patients recovered quickly (within 5?7 days) and were discharged after test results for throat swab samples were negative for 2 successive days.

    During April?October 2013, 3 of 3,355 environmental samples collected from 24 LPMs were positive for influenza A(H7N9) virus, all on May 16. In contrast, of the 5,220 samples collected from 48 LPMs during November 2013 through March 7, 2014, a total of 141 (2.70%) samples were positive (Technical Appendix [PDF - 120 KB - 1 page]). A total of 375 poultry workers from 24 influenza A(H7N9) virus?contaminated LPMs were recruited and monitored, and 381 throat swab specimens were collected; repeat specimens were collected from 6 workers who showed symptoms. Asymptomatic influenza A(H7N9) virus infection was detected in 1 worker who managed a live poultry stall and had daily direct contact with live poultry. Two environmental samples collected from his stall on January 27, 2014, and a throat swab sample collected from the worker on January 28 were positive for influenza A(H7N9) virus. The worker was isolated, but test results for 3 consecutive throat swab specimens collected on January 30 and 31 and February 6 were negative, and in the absence of any symptoms or abnormal chest radiograph findings, he was discharged.
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    Figure 2

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    Figure 2. Timeline of illness for family cluster of 2 patients with confirmed influenza A(H7N9) virus infection, Guangzhou, China, 2014ICU, intensive care unit; rRT-PCR, real-time reverse transcription PCR; +, positive; ?, negative.
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    A total of 411 throat swab specimens were collected from 384 close contacts of influenza A(H7N9) case-patients . One contact, the 5-year-old daughter of a patient, was confirmed to be infected. In this family cluster (Figure 2), the father experienced a high fever on January 4 and was hospitalized on January 8; influenza A(H7N9) virus infection was confirmed by rRT-PCR on January 10. The man had managed a tofu stall (next to the poultry unloading area) in a retail wet market from which 2 environmental samples tested positive for influenza A(H7N9) virus on January 11. On January 14, fever developed in the patient?s daughter, and she was hospitalized. Throat swab specimens collected on January 14 and 15 were positive for influenza A(H7N9) virus. Her symptoms abated after January 16, and she was discharged on January 21 after 2 consecutive throat swab specimens tested negative. The daughter had not visited the contaminated market and had no known history of poultry exposure in the 12 days before illness onset. However, while her father had severe cough with heavy sputum during January 4?8, she had close, prolonged, and unprotected contact with her sick father, including kissing and embracing.


    Conclusions

    Human infection with influenza A(H7N9) virus has been characterized by severe illness, in particular, rapidly progressive pneumonia and acute respiratory distress syndrome (6). However, the 21 case-patients with laboratory-confirmed influenza A(H7N9) that we identified in Guangzhou showed a wider spectrum of illness, ranging from severe pneumonia to mild ILI to asymptomatic infection. Clinical signs and symptoms differed notably across age groups; all mild cases occurred in those <20 years of age, whereas most severe cases occurred in older patients, similar to findings from previous studies (7,8). The age variances may be attributed to more frequent poultry exposure, more co-existing chronic diseases, or delayed medical admission and antiviral treatment among older patients.

    Evidence shows the potential for influenza A(H7N9) virus transmission from person to person (9,10). Through targeted surveillance, we identified influenza A(H7N9) virus infection in a father and daughter, which indicates that person-to-person transmission may have occurred, consistent with findings in several other family clusters (7,11,12), but such transmission was likely to be limited to family members who had prolonged and intimate contact. No widespread mild influenza A(H7N9) infection was detected through ILI surveillance, which indicates that the likelihood of community-level transmission is low.

    Subclinical influenza A(H7N9) virus infections of poultry workers have been identified by serologic testing (13). However, the possibility of cross-reactivity with other antigenically similar viruses cannot be ruled out. Using rRT-PCR, our surveillance identified a poultry worker with asymptomatic influenza A(H7N9) virus infection, providing further evidence for an occupational risk for asymptomatic infection.

    Our study is limited by potential underreporting and by the increased use of PUE and ILI surveillance during the study period compared with previous periods. However, our results show that targeted surveillance during a period of elevated disease activity improved identification of mild or asymptomatic infections.
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    Dr Chen is an epidemiologist at the Department of Infectious Disease Control and Prevention, Guangzhou Center for Disease Control and Prevention, Guangdong, China. His research interests include surveillance of infectious diseases especially for influenza, prevention and control strategies for emerging infectious diseases, and preparedness for pandemic influenza.


    Acknowledgments

    We thank staff members of 12 district Center for Disease Control and Prevention offices in Guangzhou for their assistance in the field investigation and data collection.

    This work was supported by grants from the National Science and Technology Major Projects of China (no. 2012ZX100004213-005) and Science and Technology Program of Guangzhou, China (no. 201102A213222).


    References
    1. World Health Organization. Risk assessment: human infections with avian influenza A(H7N9) virus [cited 2014 Jan 21]. http://www.who.int/influenza/human_animal_interface/RiskAssessment_H7N9_21Jan14.pdf?ua=1
    2. Xiang N, Havers F, Chen T, Song Y, Tu W, Li L, Use of national pneumonia surveillance to describe influenza A(H7N9) virus epidemiology, China, 2004?2013. Emerg Infect Dis. 2013;19:1784?90 . DOI ? PubMed
    3. World Health Organization. Real-time RT-PCR protocol for the detection of avian influenza A(H7N9) virus. Beijing: WHO Collaborating Center for Reference and Research on Influenza at the Chinese National Influenza Center [cited 2013 Apr 15]. http://www.who.int/influenza/gisrs_laboratory/cnic_realtime_rt_pcr_protocol_a_h7n9.pdf
    4. China National Health and Family Planning Commission. Technical guidelines for prevention and control of nosocomial infections of avian influenza A(H7N9) (2013 edition) [in Chinese]. Beijing: Chinese Center for Disease Control and Prevention; 2013 [cited 2014 Apr 3]. http://www.moh.gov.cn/ewebeditor/uploadfile/2013/04/20130403184606651.doc
    5. China National Health and Family Planning Commission. Chinese guideline for prevention and control for human infection with A(H7N9) avian influenza (2014 edition) [in Chinese]. Beijing: Chinese Center for Disease Control and Prevention; 2014 [cited 2014 Jan 29]. http://www.moh.gov.cn/jkj/s3577/201401/8c1828375a7949cd85454a76bb84f23a.shtml
    6. Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med. 2013;368:2277?85 . DOI ? PubMed
    7. Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, Epidemiology of human infections with avian influenza A(H7N9) virus in China. N Engl J Med. 2014;370:520?32 . DOI ? PubMed
    8. Cowling BJ, Freeman G, Wong J, Wu P, Liao Q, Lau E, Preliminary inferences on the age-specific seriousness of human disease caused by avian influenza A(H7N9) infections in China, March to April 2013. Euro Surveill. 2013;18:20475 .PubMed
    9. Zhou J, Wang D, Gao R, Zhao B, Song J, Qi X, Biological features of novel avian influenza A (H7N9) virus. Nature. 2013;499:500?3 . DOI ? PubMed
    10. Zhang Q, Shi J, Deng G, Guo J, Zeng X, He X, H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science. 2013;341:410?4 . DOI ? PubMed
    11. Qi X, Qian YH, Bao CJ, Guo XL, Cui LB, Tang FY, Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation. BMJ. 2013;347:f4752 . DOI ? PubMed
    12. Liu T, Bi Z, Wang X, Li Z, Ding S, Bi Z, One family cluster of avian influenza A(H7N9) virus infection in Shandong, China. BMC Infect Dis. 2014;14:98 . DOI ? PubMed
    13. Yang S, Chen Y, Cui D, Yao H, Lou J, Huo Z, Avian-origin influenza A(H7N9) infection in influenza A(H7N9)?affected areas of China: a serological study. J Infect Dis. 2014;209:265?9 . DOI ? PubMed


    Figures

    Figure 1. Weekly number of confirmed influenza A(H7N9) cases, percentage of pneumonia patients with pneumonia of unknown etiology (PUE), and percentage of patients with influenza-like illness (ILI) tested for influenza A(H7N9),...

    Figure 2. Timeline of illness for family cluster of 2 patients with confirmed influenza A(H7N9) virus infection, Guangzhou, China, 2014ICU, intensive care unit; rRT-PCR, real-time reverse transcription PCR; +, positive; ?,...


    Tables

    Table 1. Investigation of weekly reported number of patients with pneumonia, PUE, and ILI and confirmed cases of influenza A(H7N9) virus infection, Guangzhou, China, April 1, 2013?March 7, 2014

    Table 2. Demographic, epidemiologic, and clinical characteristics of patients with severe and mild influenza A(H7N9) cases, Guangzhou, China, April 1, 2013?March 7, 2014


    Technical Appendix

    Technical Appendix. Geographic distribution of confirmed influenza A(H7N9) cases and live poultry markets sampled in Guangzhou, China. 120 KB
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    Suggested citation for this article: Chen Z, Liu H, Lu J, Luo L, Li K, Liu Y, et al. Asymptomatic, mild, and severe influenza A(H7N9) virus infection in humans, Guangzhou, China. Emerg Infect Dis [Internet]. 2014 Sep [date cited]. http://dx.doi.org/10.3201/eid2009.140424
    DOI: 10.3201/eid2009.140424

    <SUP>1</SUP>These first authors contributed equally to this article.

    <SUP>2</SUP>These senior authors contributed equally to this article.


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