Additionally, public health efforts focus on monitoring human cases of H9N2 influenza, especially in regions with a history of zoonotic transmission. Improved biosecurity measures on farms and live bird markets are essential to prevent the spread of the virus between birds and from birds to humans. Research into antiviral medications and vaccines for humans is ongoing to enhance our ability to respond to potential outbreaks. In conclusion, H9N2 influenza poses a significant threat to both the poultry industry and public health. Its ability to infect a wide range of bird species, coupled with the potential for reassortment with other influenza viruses, underscores the importance of vigilant surveillance, effective biosecurity measures, and research into preventive and control strategies.

Addressing the challenges posed by H9N2 influenza requires a collaborative effort at the intersection of veterinary and human health to safeguard both animal and human populations from the impacts of this pervasive avian threat.^5-7

Fig-2: Structure of H9N2 virus:

H9N2 influenza virus, like other influenza A viruses, has a distinct structure that plays a crucial role in its function and interactions with host cells. The virus is named based on two key surface glycoproteins: hemagglutinin (H) and neuraminidase (N). Here is an overview of the structural components of the H9N2 virus:

Viral Envelop:

The outer layer of the virus also contains other viral proteins and lipids. The lipid envelope is derived from the host cell membrane during the viral budding process. This envelope helps the virus evade the host immune system and plays a crucial role in the virus's ability to infect new cells. The outer layer of the virus is primarily made up of two major glycoproteins: hemagglutinin (H) and neuraminidase (N). These glycoproteins are embedded in the viral envelope, which surrounds the viral particle.⁸

Hemagglutinin is a surface glycoprotein that facilitates the entry of the virus into host cells. H9 refers to a specific subtype of hemagglutinin found on the virus. Hemagglutinin plays a crucial role in binding the virus to host cells by recognizing and attaching to sialic acid receptors on the surface of host cells.⁹ Some of the key functions of the Hemagglutinin protein are;

Viral attachment to the host cell:

Hemagglutinin is responsible for the initial attachment of the virus to host cells. It binds to sialic acid receptors present on the surface of the host cell membranes. The specific binding of hemagglutinin to these receptors is a crucial step in the viral entry process.

Mediation of membrane fusion:

After binding to the host cell receptors, hemagglutinin facilitates the fusion of the viral envelope with the host cell membrane. This fusion allows the viral genetic material to enter the host cell cytoplasm, initiating the process of viral replication.

Determinant of host tropism:

The specificity of hemagglutinin for particular sialic acid linkages on host cells is a major determinant of host tropism. Different influenza virus subtypes, characterized by different hemagglutinin proteins, may have preferences for specific host species or cell types.

Antigenic determinant:

Hemagglutinin is a major target for the host immune system. It induces the production of neutralizing antibodies in the host. Changes in the amino acid sequence of hemagglutinin, known as antigenic drift, can lead to the emergence of new strains of influenza viruses that may not be effectively targeted by pre-existing immunity.^9-10

Neuraminidase is another surface glycoprotein that has enzymatic activity. It helps in the release of newly formed virus particles from infected cells by cleaving sialic acid from the host cell surface.¹¹The matrix protein lies beneath the viral envelope and helps maintain the shape of the virus particle. The nucleoprotein encapsulates the viral RNA genome and forms complexes with the viral RNA and polymerase Proteins. The genetic material of the H9N2 virus is composed of segmented, negative-sense, single-stranded RNA. The genome consists of eight segments that encode various viral proteins, including those mentioned above and additional proteins like polymerase basic proteins (PB1, PB2, and PA), non-structural proteins (NS1 and NS2), and the nuclear export protein (NEP).The viral envelope is embedded with viral glycoproteins and contains a lipid bilayer derived from the host cell membrane. Understanding the structure of the H9N2 virus is essential for developing strategies to combat its spread and infection. The specific interactions between viral surface proteins and host cell receptors are key targets for antiviral drugs and vaccines. Additionally, studying the molecular components of the virus aids in surveillance efforts and the development of diagnostic tools for detecting H9N2 infections in both avian and human populations.^12-13

How H9N2 transmitted from birds to human:

The transmission of the H9N2 influenza virus from birds to humans occurs through direct or indirect contact with infected birds or their environments. H9N2 is primarily an avian influenza virus, and it is considered a low-pathogenic avian influenza (LPAI) virus in birds, meaning it typically causes mild or no disease in infected birds. However, it has the potential to infect humans, and there have been documented cases of human infections.¹⁴ The main routes of transmissions are as follows.

Direct Contact:

Direct contact with infected birds, especially poultry, is a common mode of transmission. This can involve handling sick birds, touching surfaces contaminated with the virus, or exposure to respiratory secretions and feces of infected birds.¹⁵

Occupational exposure:

Individuals working in close proximity to live poultry, such as farmers, poultry workers, or veterinarians, are at an increased risk of exposure to the virus. Occupational exposure can occur through handling live birds, cleaning contaminated environments, or participating in activities that bring individuals into close contact with infected poultry.¹⁶

Live bird markets:

Live bird markets, where live poultry are bought and sold, can serve as hubs for the transmission of avian influenza viruses, including H9N2, to humans. People visiting or working in these markets may be exposed to the virus through contact with live birds, surfaces, or respiratory secretions.¹⁷

Air borne transmission:

Although less common, there is evidence to suggest that H9N2 can be transmitted through the air. Inhalation of respiratory droplets or dust containing the virus may pose a risk, especially in settings with crowded or confined conditions. It's important to note that while H9N2 has infected humans, these cases have generally resulted in mild respiratory illness. The concern lies in the potential for the virus to undergo genetic reassortment with other influenza viruses, avian and human, leading to the emergence of novel strains with increased transmissibility and pathogenicity.¹⁸

Respiratory influenza in children via H9N2:

H9N2 influenza virus primarily infects birds, and human cases are relatively rare. When human infections do occur, they are often associated with mild respiratory symptoms. However, the potential for H9N2 to cause influenza in children or pediatric populations exists, and the clinical presentation would be similar to other influenza viruses. Influenza viruses, including H9N2, can cause respiratory illness in humans by infecting the respiratory tract. Here's a general overview of how influenza viruses, including H9N2, can cause illness in children. The influenza virus enters the respiratory tract, usually through the nose or mouth.

Once inside the respiratory system, the virus attaches to and infects epithelial cells in the upper and lower respiratory tract. After infection, the child may develop symptoms such as fever, cough, sore throat, runny or stuffy nose, muscle or body aches, fatigue, and sometimes gastrointestinal symptoms like nausea or vomiting. The body's immune system responds to the infection by producing antibodies and activating immune cells. In many cases, the immune response can control and clear the infection.¹⁹

Complications:

While most cases of influenza, including those caused by H9N2, result in mild illness and recovery, complications can occur, especially in vulnerable populations like young children, the elderly, and individuals with underlying health conditions. Complications may include pneumonia, bronchitis, or exacerbation of pre-existing respiratory conditions.

It's important to note that the severity of the illness can vary, and some individuals, including children, may experience more severe symptoms. Additionally, influenza viruses can undergo genetic changes over time, potentially leading to new strains with different characteristics. Preventive measures, such as annual influenza vaccination, good hygiene practices (e.g., hand washing), and avoiding close contact with sick individuals, are crucial for reducing the risk of influenza in children and the general population.²⁰

The seasonal influenza vaccine is designed to protect against specific influenza virus strains, but it may not specifically target H9N2. However, vaccination can still provide some level of cross-protection and reduce the severity of illness. If a child shows symptoms of influenza, especially if they have underlying health conditions, it's important to seek medical attention promptly for proper diagnosis and management.²¹

Preventive measures to reduce the risk of H9N2 transmission from birds to humans:^14,22-24

Biosecurity measures- Implementation of strict biosecurity measures on poultry farms are required to prevent the spread of the virus. This includes restricted access i.e limit access to poultry farms to essential personnel only or prohibition for public. Implement controlled entry points and maintain visitor log book are also essential component of biosecurity measures. The second and foremost important factor is hygiene practices, this includes, ensure strict hygiene measures, such as use of protective clothing, disinfection of footwear, and hand washing facilities at frequent time interval. The flocks should keep separated to prevent the spread of the virus between them.

Surveillance:

Surveillance is an essential component. Regular surveillance in both avian and human populations to detect and monitor the presence of H9N2 and other influenza viruses. Routine surveillance programs required to monitor poultry populations for the presence of H9N2 and other avian influenza viruses. It will help for early detection of any unusual morbidity or mortality in poultry that could be indicative of an avian influenza outbreak.

Public Health education:

Making people aware about the pathogenicity of influenza virus is considered as an important factor to prevent the spread of viral infection. Educating individuals, especially those working with live poultry, about the risks associated with avian influenza and promoting hygiene practices to reduce the likelihood of transmission. NGOs and other community personnel should conduct public awareness campaigns to educate poultry farmers, workers, and the general public about the risks of avian influenza, including H9N2. They should encourage prompt reporting of sick or dead birds to veterinary authorities.

Treatment options for H9N2 infections:

As of my last knowledge update in January 2022, H9N2 influenza is primarily an avian influenza virus, and human infections with H9N2 are generally mild. The main concern with H9N2 is its potential to reassort with other influenza viruses, leading to the emergence of novel strains with increased transmissibility and pathogenicity. It's important to note that specific antiviral medications targeting H9N2 directly are not widely available or approved for human use.²⁵ Treatment for H9N2 infections in humans typically involves supportive care to alleviate symptoms and prevent complications. The following are general measures that may be taken.

Anti viral Medications:

Neuraminidase Inhibitors:

Antiviral drugs such as oseltamivir (Tamiflu) and zanamivir (Relenza), which are commonly used for treating influenza, may be considered. These medications work by inhibiting the neuraminidase enzyme on the surface of the virus, preventing the release of new viral particles from infected cells. The effectiveness of these drugs can vary, and their use should be guided by healthcare professionals.²⁶

Supportive Care:

Over-the-counter medications such as acetaminophen or ibuprofen may be used to reduce fever and alleviate pain. Adequate hydration and rest are essential for recovery. Maintaining hydration helps manage symptoms and prevents complications.²⁷

Hospitalization:

Severe cases of influenza, including those caused by H9N2 or other subtypes, may require hospitalization. This is especially important for individuals with underlying health conditions, the elderly and young children.²⁷

Monitoring for Complications:

Surveillance for secondary bacterial infections, pneumonia, or other complications is crucial. Antibiotics may be prescribed if a bacterial infection is suspected. It's important to recognize that the information provided here is based on the understanding of H9N2 influenza up to my last knowledge update in January 2022. If there have been developments or changes in treatment guidelines since then, I recommend consulting the most recent information from reputable health organizations such as the World Health Organization (WHO) or local health authorities. Additionally, because H9N2 has the potential to reassort with other influenza viruses, the emergence of new strains may necessitate ongoing research and development of antiviral medications and vaccines that specifically target these strains.

In any case, the management of H9N2 and other influenza infections should be guided by healthcare professionals based on the latest scientific evidence and public health recommendations.^28-29

Role of Government for preventive measures for H9N2:^30-32

Governments play a crucial role in eradicating viral infections by implementing public health strategies, policies, and interventions to prevent, control, and manage the spread of infectious diseases. Here are key roles that governments typically play in addressing viral infections.

Surveillance and Monitoring:

They establish and maintain robust surveillance systems to monitor the prevalence and spread of viral infections. They detect and respond to outbreaks promptly through effective data collection, analysis, and reporting.

Public Health Education and Awareness:

Educate the public about preventive measures, symptoms, and the importance of seeking medical attention. Disseminate accurate and timely information to combat misinformation and promote public awareness.

Vaccination Programs:

Develop and implement vaccination programs to immunize populations against preventable viral infections. Ensure vaccine accessibility, affordability, and coverage, particularly for high-risk populations.

Healthcare Infrastructure and Capacity Building:

Strengthen healthcare systems to enhance diagnostic, treatment, and quarantine capabilities. Build the capacity of healthcare professionals through training and resource allocation.

International Collaboration:

Collaborate with international organizations, neighboring countries, and global health partners to share information, resources, and best practices. Participate in global efforts to combat emerging infectious diseases through research, data sharing, and coordinated responses.

Border Control and Quarantine Measures:

To implement measures at borders and ports of entry to prevent the importation of infectious diseases. Establish quarantine protocols for individuals who may have been exposed to contagious viruses.

Research and Development:

Govt. invest in research to better understand viral diseases, develop diagnostic tools, antiviral medications, and vaccines. Support research initiatives that explore the genetic makeup, transmission dynamics, and potential treatments for emerging viruses.

Regulation and Legislation:

Enact and enforce regulations related to the containment of infectious diseases. Implement legal frameworks to facilitate public health responses, including quarantine measures and vaccination requirements.

Emergency Preparedness and Response:

Develop and regularly update emergency preparedness plans to respond effectively to outbreaks. Establish rapid response teams and allocate resources for timely and coordinated.

Community Engagement:

HEngage with communities to foster collaboration and trust in public health measures. Encourage community participation in vaccination campaigns, hygiene practices, and early reporting of symptoms.

Health Equity:

Address health disparities by ensuring that vulnerable and marginalized populations have access to healthcare services and preventive measures.

Communication Strategies:

Develop clear and consistent communication strategies to relay important health information to the public. Use various channels to reach diverse populations, considering cultural and linguistic factors.

Government efforts to eradicate viral infections are multifaceted and require a coordinated approach involving health agencies, policymakers, researchers, healthcare professionals, and the community. Effective governance, collaboration, and a commitment to evidence-based strategies are essential components of a successful public health response.

CONCLUSION:

In conclusion, H9N2 influenza presents a complex challenge at the intersection of animal and human health. While primarily an avian virus, its ability to infect humans and its potential for genetic reassortment with other influenza strains underscore the importance of vigilance and proactive measures. The global community must continue to prioritize surveillance, research, and collaborative efforts to mitigate the risks associated with H9N2. Biosecurity measures on poultry farms, strict regulation of live bird markets, and robust vaccination programs are essential components of preventive strategies.

Moreover, ongoing research into antiviral medications and vaccines specific to H9N2 is crucial for enhancing our preparedness and response capabilities. By fostering international cooperation, community engagement, and the implementation of evidence-based policies, governments can contribute to a comprehensive approach in eradicating or minimizing the impact of H9N2 and other potential zoonotic threats. The evolving nature of influenza viruses necessitates a dynamic and adaptive response to safeguard both animal and human populations from the consequences of these pervasive avian infections.

Future prospect of H9N2 prevention:

The future prospects of H9N2 influenza involve ongoing efforts to understand, monitor, and manage the virus's impact on both animal and human health. Several key aspects shape the future outlook for H9N2. Given its ability to infect humans, there is a need to closely monitor the zoonotic potential of H9N2. Vigilance is essential to detect any changes in the virus that may enhance its ability to transmit between humans. The One Health approach, which recognizes the interconnectedness of human, animal, and environmental health, will likely continue to guide strategies for addressing H9N2 and other zoonotic diseases. Flexibility and adaptability in strategies are important, as the virus may undergo changes over time. Regular updates to surveillance, prevention, and control measures will be necessary to address emerging challenges. The experience with H9N2 contributes to global preparedness for potential influenza pandemics. Lessons learned from monitoring and responding to H9N2 outbreaks can inform strategies for addressing novel influenza viruses with pandemic potential. In summary, the future prospects of H9N2 involve a dynamic and evolving landscape of research, prevention, and response strategies. Continuous monitoring, research, and collaboration are essential to stay ahead of potential threats and to safeguard both animal and human populations from the impacts of H9N2 influenza and similar emerging infectious diseases.

CONFLICTS OF INTEREST:

The authors declare no Conflict of Interest.

ACKNOWLEDGEMENT:

The authors are also thankful to Dean, College of Veterinary Science and Animal Husbandry, Anjora-491001, Durg, C.G., India, Principal and Management of Columbia Institute of Pharmacy, Raipur, C.G., and Principal, Faculty of Pharmacy, Kalinga University, Raipur, for providing necessary facilities to complete this research work.

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Received on 19.02.2024 Modified on 09.03.2024

Res. J. Pharmacology and Pharmacodynamics. 2024;16(2):127-133.

DOI: 10.52711/2321-5836.2024.00023