Community Acquired Infection

REVIEW ARTICLE
Year
: 2018  |  Volume : 5  |  Issue : 2  |  Page : 11--14

Current information of H9N2 virus zoonotic infection and its emerging pandemic potential: A review


Mohit Kamthania, Renu Kumari, Sirajuddin Ali, Ajaj Hussain, Abhimanyu Kumar Jha 
 Department of Biotechnology, Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh, India

Correspondence Address:
Mohit Kamthania
Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh
India

Abstract

H9N2 avian influenza viruses cause worldwide infections in animals including humans and show a threat as a pandemic infection. Since 1998 more than 59 cases including one death due to H9N2 infection had been reported worldwide and the majority of confirmed cases were young children. Due to the large host variety, tolerance to both poultry and mammals and widespread gene reassortment, H9N2 viruses played a crucial role in worldwide infection. In this review, we discuss the current worldwide infection of H9N2 avian influenza viruses as well as their host range, pathogenesis, epidemiology, diagnosis, control, and its pandemic potential.



How to cite this article:
Kamthania M, Kumari R, Ali S, Hussain A, Jha AK. Current information of H9N2 virus zoonotic infection and its emerging pandemic potential: A review.Community Acquir Infect 2018;5:11-14


How to cite this URL:
Kamthania M, Kumari R, Ali S, Hussain A, Jha AK. Current information of H9N2 virus zoonotic infection and its emerging pandemic potential: A review. Community Acquir Infect [serial online] 2018 [cited 2022 Jan 19 ];5:11-14
Available from: http://www.caijournal.com/text.asp?2018/5/2/11/285364


Full Text



 Introduction



Avian influenza virus belongs to the family orthomyxoviridae class A influenza virus.[1] The avian influenza virus genome consists of eight segments of negative-sense, single-stranded RNA encoding at least 10 proteins: two surface glycoproteins (hemagglutinin [HA] and neuraminidase [NA]), nucleoprotein, three polymerase essential proteins (PB2, PB1, and acidic polymerase), two matrix proteins (M1 and M2) and two nonstructural proteins (NS1 and NS2).[2] Avian influenza virus is categorized into subtypes based on the antigenic variations between the glycoprotein HA and NA. Influenza included 16 HA subtypes (H1 to H16) and nine NA subtypes (N1 to N9) A virus and viruses of all subtypes have been isolated from avian species.[3] Domestic poultry infection results in complex clinical syndromes of varying severity depending on the strain of the virus, the host species and the existence of secondary pathogens.[4] Highly pathogenic avian influenza viruses in chickens (H5 and H7 subtype), show high pathogenicity and contain polybasic cleavage sites which allow systematic virus replication in birds. However, low pathogenicity avian influenza viruses in chickens (H9N2 subtype), show low pathogenicity and contain mono, di or tri-basic cleavage site in HA which allows the cleavage of HA restricting the virus to respiratory and gastrointestinal tracts.[5]

Influenza A viruses give rise to different subtypes such as H1N1, H5N6, or H9N2 by different combinations of HA and NA surface proteins. Wild waterfowl and sea birds are the natural hosts of nearly all subtypes of influenza virus except H17N10 and H18N11 subtypes which are found in bats.[6] In 1966, first time, these viruses were isolated from Turkey (A/turkey/Wisconsin/1/1966).[7] Influenza virus transmits through aerosol, droplets, fecal-oral route and direct contact.[8] Studies show that respiratory and contact transmissions are probably the primary routes of transmission in case of H9N2 infection. In domestic poultry, the infection of H9N2 is commonly linked to reduced feed intake, less egg production, moderate respiratory symptoms, and low mortality rate.[9]

In the past 10 years, the epidemic infection of H9N2 in commercial poultry flocks results in severe clinical symptoms, high mortality rate, and huge loss in production.[10],[11] Human cases of influenza H9N2 virus infection have been observed in Hong Kong, China, Bangladesh, Pakistan, Egypt, Oman, and India.[12],[13],[14],[15],[16] H9N2 outbreaks in commercial chickens have been reported recently in Asia (India, Pakistan, China, Hong Kong, Korea, and Japan), the Middle East (Saudi Arabia, United Arab Emirates, Jordan, Iran, Iraq, Lebanon and Kuwait), and African countries (Egypt, Tunisia, Libya, and South Africa).[17] H9N2 influenza viruses emerge as drift variants due to constant mutations which acquire more virulence gradually.[18] In China, an influenza A (H9N2) virus (B51) was isolated in 2017 from migratory waterfowl. This B51 was the novel reassortment influenza virus that contains the gene segments from North American wild bird influenza viruses and human H7N4 virus.[19] H9N2 viruses provide internal genes to the H5N1, H7N9, H10N8 and H5N6 viruses.[20],[21],[22],[23]

A recent infection of H9N2 was detected in a 17-month-old boy from Melghat District, Maharashtra State, India. The strain of this H9N2 virus (A/India/TCM2581/2019) confirmed the mixed lineage of G1 and H7N3. This recent case of H9N2 infection in a 17-month-old boy in India can be a threat to human health in India and there is an urgent need for the surveillance in this case.[16]

 Pathogenesis



The subtypes of avian influenza viruses are determined by the antigenic difference between HA and NA surface glycoproteins; however, the HA largely determines the virulence of the virus in poultry.[24] A mutation in viral surface protein HA in Tunisian outbreaks strain isolated in 2011 allows the virus to bind to sialic receptor α[2],[6] of humans which made the virus highly pathogenic.[25],[26] The widespread subtype of influenza viruses in Chinese chickens was H9N2 which caused significant economic losses for the poultry industry, including those under long-term vaccination programs. Recent human infections with avian influenza virus have confirmed that H9N2 is the donor gene for H7N9 and H10N8 viruses which also infect humans. In China, the H9N2 virus was detected in a number of avian species including pigeon, duck, quail, pertussis, pheasant, chicken, egret, chukar, and silky chicken. Aerosol, droplet particles, oral-facial route and direct touch can transmit the H9N2 influenza virus. Transmission of contact relies on the transfer of particles directly to mucous membranes, or intermediate through fomite. After the infection, chickens showed no clinical sign generally but some of them showed ruffled feathers and depression. The virus inside the trachea replicates itself; this makes chickens more vulnerable to secondary infections, in particular, co-infections with Escherichiacoli or other pathogens. Furthermore, when ventilation is low, trachea, and bronchi are easily embolized by mucus which leads to severe respiratory disease and death.[27],[28] Live bird markets function as hubs for poultry traders and their birds are a major component of the disease transmission pathway, shown to keep avian influenza virus spread among poultry as well as facilitate zoonotic infections.[29],[30]

 Epidemiology



The H9N2 influenza outbreak began in northern Israel, from where the epizootic spread throughout the world. The diagnostics used the reverse transcription polymerase chain reaction (PCR) in addition to the standard serological studies. H9N2 virus causes low pathogenicity when it infects individually without other respiratory pathogens. However, it causes high mortality when co-infected with other pathogens. A previous study revealed that the co-infection of H9N2 (A/chicken/1618F/2016) with E. coli O78 in specific-pathogen-free chickens can increase the mortality rates to a percentage of 20%, which leads to economic losses up to 75% in chicken flocks.[31],[32],[33],[34] Influenza A subtype H9N2 viruses are now known to be prevalent in poultry. Previous studies suggest that the H5N1 viruses responsible for the highly pathogenic disease that occurred in Hong Kong in 1997 were reassortant from avian H9N2 viruses. Getting diagnostic tools for identifying H9N2 viruses is important for the preparedness for pandemic influenza.

 Diagnosis



H9N2 has been reported from indigenous poultry. Seroepidemiological study was undertaken among poultry workers in Pune, India, to understand the prevalence of antibodies against avian influenza H9N2. Serum samples of poultry workers were tested by hemagglutination inhibition and micro neutralization assays for the presence of antibodies against avian influenza H9N2 virus. Low prevalence of antibodies against H9N2 virus was found in this study but further serological studies are urgently required for poultry workers in India.[35] Bangladesh has reported high levels of highly pathogenic avian influenza H5N1 outbreaks in poultry.[36],[37] In the poultry in Bangladesh, a natural reassortant HPAI (H5N1) virus containing a H9N2-PBI gene was identified. Serological studies showed that a high rate of seropositivity was found among poultry workers in different enzootic countries including China, Egypt, Cambodia, Iran, Vietnam, Hong Kong, Pakistan, Thailand, and India.[5],[38]

Recently, a method to detect H9N2 avian influenza is developed in which monoclonal antibodies was developed against H9N2 virus and applied a double-antibody sandwich immunosorbent enzyme-linked assay (DAS-ELISA) to detect the H9N2 viral antigen. The specificity and sensitivity of DAS-ELISA was found to be >98%.[39] A highly sensitive real time immuno-PCR method is used for detecting H9N2 virus. The assay applies aptamers as ligands to capture and detect the virus.[26]

 Prevention and Control



H9N2 caused economic loss in several nations, including China, UAE, Morocco, Israel, South Korea, Iran, Egypt, and Pakistan, hence these countries adopted vaccination at either national or local level for prevention from H9N2.[5],[40] It is needed to understand the molecular determinant of H9N2 antigenicity, genetic drift, zoonotic potential, and viral fitness consequences for making a next generation vaccine against H9N2 virus. Stamping out by culling of influenza-infected birds was used as a first line of defense in countries without a history of H9N2 virus infection.[41],[42] Attenuated cold-adapted H9N2 influenza virus vaccine selected to control the influenza virus infection in chickens.[43]

Some other interventions have been used in the field to reduce or stop the spread of influenza virus infection in poultry. Live bird markets are the main hot spot to spread the infection due to availability of different species of poultry from across wide range of geographical area. Hence, different interventions including biosecurity, temporary/periodic closures of markets and hygienic conditions were used to control the infection. There are currently no clear methods for treating H9N2 avian influenza. To control the pandemic potential and human-to-human transmission of H9N2 globally, biosecurity in the poultry industry, isolation of infected poultry, decrease in microbial infection, screening programs for high-risk areas and decreasing the opportunities for reassortment are practical requirements.[44]

 Conclusion



In last decade, the outbreak of H9N2 has increased worldwide in different geographical ranges, causing damage to poultry production and great economic loss to poultry industries. Mostly, H9N2 virus causes low mortality and mild disease but recently increasing infections in humans and animals show that these viruses may cause pandemic infection in the near future. Due to the presence of human receptor binding protein in some H9N2 subtype which allow transmission between humans, and presence of internal gene cassettes in some other H9N2 subtypes, which allow efficient replication in humans, these intersubtypic H9N2 virus could cause a pandemic due to the zoonotic potential of these viruses. Hence, there is urgent need of a specific vaccine against these viruses and surveillance efforts are also required in infected areas of poultry.

Acknowledgment

The authors would like to appreciate all the participants collaborated in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza A viruses. Microbiol Rev 1992;56:152-79.
2Gu M, Xu L, Wang X, Liu X. Current situation of H9N2 subtype avian influenza in China. Vet Res 2017;48:49.
3Ciminski K, Thamamongood T, Zimmer G, Schwemmle M. Novel insights into bat influenza A viruses. J Gen Virol 2017;98:2393-400.
4Kash JC, Taubenberger JK. The role of viral, host, and secondary bacterial factors in influenza pathogenesis. Am J Pathol 2015;185:1528-36.
5James J, Sealy JE, Iqbal M. A global perspective on h9n2 avian influenza virus. Viruses 2019;11:620.
6Wu Y, Wu Y, Tefsen B, Shi Y, Gao GF. Bat-derived influenza-like viruses H17N10 and H18N11. Trends Microbiol 2014;22:183-91.
7Homme PJ, Easterday BC. Avian influenza virus infections. I. Characteristics of influenza A/Turkey/Wisconsin/1966 virus. Avian Dis 1970;1:66-74.
8Killingley B, Nguyen-Van-Tam J. Routes of influenza transmission. Influenza Other Respir Viruses 2013;7 Suppl 2:42-51.
9Jakhesara SJ, Bhatt VD, Patel NV, Prajapati KS, Joshi CG. Isolation and characterization of H9N2 influenza virus isolates from poultry respiratory disease outbreak. Springerplus 2014;3:196.
10Karimi-Madab M, Ansari-Lari M, Asasi K, Nili H. Risk factors for detection of bronchial casts, most frequently seen in endemic H9N2 avian influenza infection, in poultry flocks in Iran. Prev Vet Med 2010;95:275-80.
11Taha M, Ibrahim A, Osmsn N, Gaber A, Nasef S, Ahmed MS. Experimental co-infection of low pathogenic avian influenza virus (H9N2) and Escherichia coli in SPF broiler chickens. SVU Int J Vet Sci 2019;2:91-100.
12Pan Y, Cui S, Sun Y, Zhang X, Ma C, Shi W, et al. Human infection with H9N2 avian influenza in Northern China. Clin Microbiol Infect 2018;24:321-3.
13Butt KM, Smith GJ, Chen H, Zhang LJ, Leung YH, Xu KM, et al. Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J Clin Microbiol 2005;43:5760-7.
14Shanmuganatham K, Feeroz MM, Jones-Engel L, Smith GJ, Fourment M, Walker D, et al. Antigenic and molecular characterization of avian influenza A (H9N2) viruses, Bangladesh. Emerg Infect Dis 2013;19:1393-402.
15Ali M, Yaqub T, Mukhtar N, Imran M, Ghafoor A, Shahid MF, et al. Avian influenza A (H9N2) virus in poultry worker, Pakistan, 2015. Emerg Infect Dis 2019;25:136-9.
16Potdar V, Hinge D, Satav A, Simões EA, Yadav PD, Chadha MS. Laboratory-confirmed avian influenza A (H9N2) virus infection, India, 2019. Emerg Infect Dis 2019;25:2328-30.
17Al-Garib S, Agha A, Al-Mesilaty L. Low pathogenic avian influenza H9N2: World-wide distribution. Worlds Poult Sci J 2016;72:125-36.
18Vegad JL. Drift variants of low pathogenic avian influenza virus: Observations from India. Worlds Poult Sci J 2014;70:767-74.
19Li X, Sun J, Lv X, Wang Y, Li Y, Li M, et al. Novel reassortant avian influenza A (H9N2) virus isolate in migratory waterfowl in Hubei province, China. Front Microbiol 2020;11:220.
20Guan Y, Shortridge KF, Krauss S, Webster RG. Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong? Proc Natl Acad Sci U S A 1999;96:9363-7.
21Lam TT, Wang J, Shen Y, Zhou B, Duan L, Cheung CL, et al. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 2013;502:241-4.
22Chen H, Yuan H, Gao R, Zhang J, Wang D, Xiong Y, et al. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: A descriptive study. Lancet 2014;383:714-21.
23Shen YY, Ke CW, Li Q, Yuan RY, Xiang D, Jia WX, et al. Novel reassortant avian influenza A (H5N6) viruses in humans, Guangdong, China, 2015. Emerg Infect Dis 2016;22:1507-9.
24Almayahi ZK, Al Kindi H, Davies CT, Al-Rawahi B, Al-Jardani A, Al-Yaqoubi F, et al. First report of human infection with avian influenza A (H9N2) virus in Oman: The need for a One Health approach. Int J Infect Dis 2020;91:169-73.
25Tombari W, Nsiri J, Larbi I, Guerin JL, Ghram A. Genetic evolution of low pathogenecity H9N2 avian influenza viruses in Tunisia: Acquisition of new mutations. Virol J 2011;8:467.
26Hmila I, Wongphatcharachai M, Laamiri N, Aouini R, Marnissi B, Arbi M, et al. A novel method for detection of H9N2 influenza viruses by an aptamer-real time-PCR. J Virol Methods 2017;243:83-91.
27Xu KM, Smith GJ, Bahl J, Duan L, Tai H, Vijaykrishna D, et al. The genesis and evolution of H9N2 influenza viruses in poultry from Southern China, 2000 to 2005. J Virol 2007;81:10389-401.
28Sun Y, Liu J. H9N2 influenza virus in China: A cause of concern. Protein Cell 2015;6:18-25.
29Wan XF, Dong L, Lan Y, Long LP, Xu C, Zou S, et al. Indications that live poultry markets are a major source of human H5N1 influenza virus infection in China. J Virol 2011;85:13432-8.
30Fournié G, Guitian J, Desvaux S, Cuong VC, Pfeiffer DU, Mangtani P, et al. Interventions for avian influenza A (H5N1) risk management in live bird market networks. Proc Natl Acad Sci 2013;110:9177-82.
31Pan Q, Liu A, Zhang F, Ling Y, Ou C, Hou N, et al. Co-infection of broilers with Ornithobacterium rhinotracheale and H9N2 avian influenza virus. BMC Vet Res 2012;8:104.
32Hassan KE, Ali A, Shany SA, El-Kady MF. Experimental co-infection of infectious bronchitis and low pathogenic avian influenza H9N2 viruses in commercial broiler chickens. Res Vet Sci 2017;115:356-62.
33Ismail ZM, El-Deeb AH, El-Safty MM, Hussein HA. Enhanced pathogenicity of low-pathogenic H9N2 avian influenza virus after vaccination with infectious bronchitis live attenuated vaccine. Vet World 2018;11:977-85.
34Mahana O, Arafa AS, Erfan A, Hussein HA, Shalaby MA. Pathological changes, shedding pattern and cytokines responses in chicks infected with avian influenza-H9N2 and/or infectious bronchitis viruses. Virusdisease 2019;30:279-87.
35Pawar SD, Tandale BV, Raut CG, Parkhi SS, Barde TD, Gurav YK, et al. Avian influenza H9N2 seroprevalence among poultry workers in Pune, India, 2010. PLoS One 2012;7:e36374.
36Negovetich NJ, Feeroz MM, Jones-Engel L, Walker D, Alam SM, Hasan K, et al. Live bird markets of Bangladesh: H9N2 viruses and the near absence of highly pathogenic H5N1 influenza. PLoS One 2011;6:e19311.
37Turner JC, Feeroz MM, Hasan MK, Akhtar S, Walker D, Seiler P, et al. Insight into live bird markets of Bangladesh: An overview of the dynamics of transmission of H5N1 and H9N2 avian influenza viruses. Emerg Microbes Infect 2017;6:e12.
38Khan SU, Anderson BD, Heil GL, Liang S, Gray GC. A Systematic review and meta-analysis of the seroprevalence of influenza A (H9N2) infection among humans. J Infect Dis 2015;212:562-9.
39Ming F, Cheng Y, Ren C, Suolang S, Zhou H. Development of a DAS-ELISA for detection of H9N2 avian influenza virus. J Virol Methods 2019;263:38-43.
40Naeem K, Siddique N. Use of strategic vaccination for the control of avian influenza in Pakistan. Dev Biol (Basel) 2006;124:145-50.
41Marchenko VY, Goncharova NI, Evseenko VA, Susloparov IM, Gavrilova EV, Maksyutov RA, et al. Overview of the epidemiological situation on highly pathogenic avian influenza virus in Russia in 2018. Problems Particularly Dangerous Infect 2019;1:42-9.
42Awuni JA, Bianco A, Dogbey OJ, Fusaro A, Yingar DT, Salviato A, et al. Avian influenza H9N2 subtype in Ghana: Virus characterization and evidence of co-infection. Avian Pathol 2019;48:470-6.
43Wei Y, Qi L, Gao H, Sun H, Pu J, Sun Y, et al. Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine. Sci Rep 2016;6:30382.
44Offeddu V, Cowling BJ, Malik Peiris JS. Interventions in live poultry markets for the control of avian influenza: A systematic review. One Health 2016;2:55-64.