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Chin Med J. Why H7N9 bird flu may cause scare in China?

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  • Chin Med J. Why H7N9 bird flu may cause scare in China?

    [Source: Chinese Medical Journal, full page: (LINK). Edited.]


    Why H7N9 bird flu may cause scare in China?

    Kong Xiangyi, Liu Yang, Guan Jian, Yang Yi and Wang Renzhi

    The first identified case of human infection with a novel influenza A (H7N9) virus occurred in eastern China during February and March, 2013. According to the Center for Disease Control and Prevention (CDC), Chinese mainland has recorded a total of 134 laboratory-confirmed cases of H7N9, among whom 45 died by August. It has spread to eight provinces including Beijing and Shanghai in mainland and, on April 29, it was confirmed to have spread to Taiwan,1 and might be slowly gaining pace daily, about 31% have died, 55% have recovered, and the rest are still sick and the fatality risk on admission to hospital was 36% (95% CI 26%?45%) for H7N9.2

    WHO considers this as a serious threat, and the government is urging people to take action to head off the spread of the disease. The flu is transmitted to humans from chickens. As the death toll increases, there have been growing concerns over public health and food safety. Under this circumstance, how serious is the H7N9 outbreak? This is the greatest question that people concern. Whether the virus might mutate and become more transmittable. The likelihood of a true pandemic is still small but not zero. Considering some particularly worrying findings or signs, we may explain why the scare of H7N9 bird flu in China is looming and why complacency on H7N9 must be warn against.

    High mortality of H7N9 bird flu

    H7N9 is definitely one of the most lethal influenza viruses so far. According to Keiji Fukuda, the assistant director general for health, security and the environment of WHO, ?This is an unusually dangerous virus for humans.?

    Fukuda said the WHO is still struggling to understand the disease, but he certainly seems to be sounding the alarm. The incubation period of the H7N9 virus is generally less than 7 days. Patients usually manifest with flu-like symptoms, such as fever and cough with little phlegm, which accompanied with headache, muscle aches and general malaise. The disease can progress rapidly, accompanied by acute respiratory distress syndrome, mediastinal emphysema, septic shock, disturbance of consciousness and acute kidney injury.3 This virus can invade epithelial cells in the lower respiratory tract and type II pneumonocytes of alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines.

    For acute serum samples of H7N9-infected patients, levels of the chemokines and cytokines IP-10, MIG, MIP-1β, MCP-1, IL-6, IL-8 and IFN-α could be increased. T cellmediated responses may play a key role in defense against H7N9. Myoglobin level, C-reactive protein level and traditional Chinese medicine duration may have a bearing on treatment outcomes of H7N9 infection.4 Till now, human population is naive to H7N9, and current seasonal vaccination could not provide protection.5 Clinical research found that refractory hypoxia and septic shock are the two direct reasons for rapid death of these patients. Clinicians should monitor closely the signs of hypoxia or shock and initiate proper treatment without delay.6

    Little verified human-to-human transmissions, but it is possible

    The key question for pandemic risk assessment is whether the virus would mutate so it could be transmitted between people, which implies a higher degree of contagiousness than from contact with birds. To date, both the Chinese government and the WHO have not recorded human-to-
    human transmission and the initial epidemiologic findings suggested that most confirmed H7N9 cases were epidemiologically unrelated. However, family outbreak of severe pneumonia induced by H7N9 infection including persons with epidemiologically linked suspected cases has been reported by some doctors in Fifth People?s Hospital of Shanghai.7 Limited nonsustained human-to-human H7N9 virus transmission could not be ruled out and may occur among blood-related family members.8

    Qi and colleagues9 reported the first probable case of human-to-human transmission of H7N9. They found the infection of a daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit between people. The transmissibility was incomplete and non-sustainable. Symptom guided laboratory investigations of contacts suggest H7N9 has yet to obtain the capacity to keep sustained human to human transmission, even though serological examination has not been performed in asymptomatic contacts to shut out silent transmission.10 In short, to forestall a possible pandemic of H7N9, judicious research efforts are needed to inform public health actions. There is perhaps little room for complacency.

    Hard to detect, estimate and control

    The strong evidence of humans became infected with the new strain of bird flu H7N9 was first found from chickens at a live market by Chinese scientists. So closing down the live poultry markets might by an effective way to reduce the risk of infection. One of the biggest problems is that the virus does not cause illness to birds, so it is impossible to know if they are infected, giving experts few signs as to where the flu might spread. China has slaughtered flocks of chickens to eradicate bird flu viruses, but H7N9 is now known to be present in chickens in 31 provinces of China. On the other hand, the H7N9 virus is extremely difficult to detect. ?It could be that the infected animals might not shed virus for more than a few days, so it is a matter of chance if you test and find it. It might be that they are not sampling enough animal species, and they may have to take a look at the less common species of birds being sold in Chinese markets.? said Ho Pak-leung, associate professor in the Department of Microbiology at the University of Hong Kong. Meanwhile, there is a concern about the swift rise in cases, for there may be more undetected cases if some people suffer less severe illness that are undetected and the geographical distribution of human cases suggests that the virus may have already spread too far to contain.

    In addition, although the WHO once recommended the antiviral drug as a standard treatment against the infection, the latest findings show that 3 seriously ill patients with H7N9 did not respond to medication, including tamiflu, oseltamivir or similar antiviral drugs,11 which further sparked people?s inward panic.

    Its genetic signature: a dangerousness prediction?

    The genetic research about H7N9 sounded another disconcerting note. The comprehensive genetic analysis of the virus has been published in Lancet, suggesting that the virus might have originated from the mixing of viruses from four different origins, including ducks. The genetic signatures make this virus a significant concern because it could enable the virus make a leap into the human population with minimal mutations. What is worse, in the two months after it was first detected, the H7N9 had already resulted in almost twice as many confirmed infections in China as H5N1 did in a decade, noted by Jane.12 Genetic analysis of the virus and such terrible mutations which render it capable to bind to the human influenza receptor, suggest that although it evolved in birds, it may infect mammals more easily than other bird flu viruses.13

    Epidemic could reappear in autumn and winter

    The warm season has passed, and only one new laboratoryconfirmed case of H7N9 in human beings has been identified from May to mid-July, 2013. H7N9 seems to have petered out in recent months and the outbreak seems to wane. Many people have relaxed their vigilance. However, if H7N9 follows a similar pattern to H5N1, the epidemic could reappear later this year when the warm season comes to an end and is likely to spread internationally. A population-based study of laboratory-confirmed cases has compared the epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China, which found that the increased risk for men was of a similar magnitude for H7N9 and H5N1.2 On July 20 and August 10, two new cases were reported from Hebei and Guangdong provinces, where no case was reported during the period of spring of 2013. The new cases sounded the alarm, thus, the continued public health response should not be slacked off.14

    The potential lull in H7N9 could provide health officials a chance to properly discuss and plan ahead for the return and wider spread of H7N9. And this should include policies to build healthcare capacity in view of the possibility that H7N9 could spread beyond China?s borders. Continuous monitoring of the transmission potential of H7N9 is serious in the upcoming months as intervention measures may be loose and seasonal factors could promote H7N9 transmission in colder months.15

    Chinese residents? daily routine and lifestyle further facilitate H7N9?s survival

    Due to improper market management process, the habit of purchasing freshly slaughtered poultry, negligent behavior of the workers and so on about Chinese residents? daily routine and lifestyle, breeding and transmission of H7N9 are easier in mainland of China. So strategies related to poultry markets management, health education and preventive measures against H7N9 need to be strengthened.16

    Based on previous studies, we found that live poultry purchasing habits, poultry handling, and living conditions amplify the risk of exposure to H7N9 contaminated environments in China. Moreover, it is really hard to change China?s live poultry purchasing habits and marketing mode within a short time. So poultry trade in epidemic area should be confined, and infected birds must be culled as more as possible. These enhanced regulation would be a more practicable and effective tactic to tackle H7N9 in China and the improved policies on environmental and food health are also needed for free-range poultry, especially in country.14

    In conclusion, H7N9 virus has attracted much attention. And these mentioned above are why H7N9 bird flu may cause scare in China. Chinese officials have actively responded to the infection, and introduced prevention and control measures. Many cities with closed poultry markets have banned poultry trading to halt the spread of H7N9.17 According to Beijing Times, the Beijing Municipal Bureau of Health called for vigilance among the general public and urged travelers returning from the Middle East who develop respiratory infections to see a doctor as soon as possible. Beijing has launched a 24/7 clinical service with police participating experts on call.

    Hospitals have been required to intensify inspections on respiratory cases, report any suspected cases and send samples to the city?s CDC. In addition, the health bureau of Beijing has asked all hospitals at level two or above in the city to monitor flu-like cases for two weeks in an attempt to keep down a possible epidemic of H7N9 as winter comes. When it comes to public perceptions and reactions to H7N9 in mainland of China, according to a survey conducted by Goodwin and Sun,18 despite moderately fret, participants largely trusted official messages, particularly from Chinese officials. According to a survey respondents could correctly identify symptoms of H7N9; 96% reported more than one recommended behavior change; other changes included avoiding crowds, fowl, and migrants, and cancelling travel.18 However, the researches on H7N9 are still inadequate.

    The country has to cope with the possible spread of the new virus shortly after it tackled the H7N9 bird flu scare. We strongly urge our health officials and doctors not to be lulled into a false sense of security by the sharp drop off in H7N9 cases in recent weeks. After all, though human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported and many mild cases might already have occurred, considering the severe acute respiratory syndrome (SARS) in 2003 and the H5N1 avian flu virus in 2003, continued vigilance and sustained intensive control efforts are needed to minimize the risk of human infection.19

    1. Chang SY, Lin PH, Tsai JC, **** CC, Chang SC. The first case of H7N9 influenza in Taiwan. Lancet 2013; 381: 1621.
    2. Cowling BJ, Jin L, Lau EH, Liao Q, Wu P, Jiang H, et al. Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a populationbased study of laboratory-confirmed cases. Lancet 2013; 382: 129-137.
    3. Wu S, Wu F, He J. Emerging risk of H7N9 influenza in China. Lancet 2013; 381: 1539-1540.
    4. Chen X, Yang Z, Lu Y, Xu Q, Wang Q, Chen L. Clinical features and factors associated with outcomes of patients infected with a novel influenza A (H7N9) virus: a preliminary study. PLoS One 2013; 8: e73362.
    5. Zhou J, Wang D, Gao R, Zhao B, Song J, Qi X, et al. Biological features of novel avian influenza A (H7N9) virus. Nature 2013; 499: 500-503.
    6. Cao B. What clinicians should know to fight against the novel avian-origin influenza A (H7N9) virus? Chin Med J 2013; 126: 2205-2206.
    7. Jie Z, Xie J, He Z, Song Y, Hu Y, Li F, et al. Family outbreak of severe pneumonia induced by H7N9 infection. Am J Respir Crit Care Med 2013; 188: 114-115.
    8. Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, et al. Preliminary report: epidemiology of the avian influenza A (H7N9) outbreak in China. N Engl J Med 2013. Epub ahead of print.
    9. Qi X, Qian YH, Bao CJ, Guo XL, Cui LB, Tang FY, et al. Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation. BMJ 2013; 347: f4752.
    10. Leung CC, Hui DS, Chan PK. Controlling novel avian influenza A (H7N9) at animal sources. BMJ 2013; 347: f5565.
    11. Hay AJ, Hayden FG. Oseltamivir resistance during treatment of H7N9 infection. Lancet 2013; 381: 2230-2232.
    12. Parry J. H7N9 virus is more transmissible and harder to detect than H5N1, say experts. BMJ 2013; 346: f2568
    13. Van Ranst M, Lemey P. Genesis of avian-origin H7N9 influenza A viruses. Lancet 2013; 381: 1883-1885.
    14. Song PP, Xia JF, Gao JJ, Xu LZ, Huang Y, Yao LN, et al. Measures to combat H7N9 virus infection in China: Live poultry purchasing habits, poultry handling, and living conditions increase the risk of exposure to contaminated environments. Biosci Trends 2013; 7: 168-171.
    15. Chowell G, Simonsen L, Towers S, Miller MA, Viboud C. Transmission potential of influenza A/H7N9, February to May 2013, China. BMC Med 2013; 11: 214.
    16. Yuan J, Di B, Ma XW, Liu JP, Chen YY, Li KB, et al. Risk evaluation on H7N9 avian influenza in Guangzhou, China (in Chinese). Chin J Epidmiol 2013; 34: 488-490.
    17. Dai C, Jiang M. Understanding H7N9 avian flu. BMJ 2013; 346: f2755.
    18. Goodwin R, Sun S. Public perceptions and reactions to H7N9 in Mainland China. J Infect 2013; 67: 458-462.
    19. Yu H, Cowling BJ, Feng L, Lau EH, Liao Q, Tsang TK, et al. Human infection with avian influenza A H7N9 virus: an assessment of clinical severity. Lancet 2013; 382: 138-145.

    (Received May 23, 2013)

    Edited by Cui Yi

    DOI: 10.3760/cma.j.issn.0366-6999.20131355

    Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. Beijing 100730, China (Kong XY, Liu Y, Guan J, Yang Y and Wang RZ)

    Correspondence to: Yang Yi, Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. No. 1 Shuaifuyuan Hutong, Dongcheng District, Beijing 100730, China (Email: