Avian flu & human physiology
Avian influenza (Bird flu or avian flu) is a dreaded disease with a pandemic potential. Since the first outbreak in 1997(Lahariya et al., 2006), 123 deaths have occurred over the last 10 years all over the world (Lu et al., 2006). World Health Organization has reported that over 217 cases were confirmed with avian influenza as of 19th May 2006 (WHO, 2006). The pathophysiological aspects of avian flu are pleiotropic. In this essay, I will be investigating the epidemiology of avian influenza, its antigenicity, and its impact on human physiology with reference to the immunological aspects, changes produced in the pulmonary and other extrapulmonary systems, and the recommended preventive measures.
Avian influenza is a disease of viral origin caused by an orthomyxo virus. Influenza viruses are of three types classified as A, B and C with subtypes H and N. Avian influenza virus belongs to the Influenza type A group. The classification into H and N types is based on the presence of proteins called Hemagglutinin (for H) and Neuraminidase (for N). There are 15 types of hemagglutinin protein (H1 to H15) and 9 subtypes of neuraminidase protein (N1 to N9). In May 1997, it was discovered that the virus H5N1 caused the influenza epidemic in Hong Kong. H5N1 virus was known to infect poultry, but was previously unknown to infect human beings. It was subsequently found to cross the species-barrier and cause fatal infections. It is seen mainly in people who are in contact with birds and poultry, like poultry farmers, bird-handlers and veterinary personnel.
Once the virus infects a human being, the individual will acquire immunity to that particular strain of virus. But the frequent variations in strains by different combinations of subtypes of proteins have resulted in repeated outbreaks of bird flu in different countries. Laboratory-confirmed cases of avian influenza have been reported from many countries like Vietnam, Cambodia, Hong Kong, Turkey, Thailand, Iraq, Indonesia and China (WHO, 2006). The isolation of avian influenza virus from these countries is a concern for the global community, because a re-emergence of this disease might end up resulting in a global pandemic.
Antigens from the virus play a major role in the pathogenesis of the disease. Apart from the H and N proteins, the virus particle comprises nucleocapsid protein, polymerase proteins, matrix protein and other non-structural proteins. The H and N proteins are the surface proteins and are the ones mostly implicated in the antigenicity. Hemagglutinin protein is the major antigen that neutralizes antibodies and facilitates the binding of the virus to the surface receptors present on the cells in the respiratory tract. Neuraminidase is involved in the release of newly formed virions from the cell surface.
IMPACT ON HUMAN PHYSIOLOGY
Despite the feco-oral transmission in birds, the disease gets transmitted through the respiratory route in humans via droplets. Usually the infective material is bird-droppings. Human to human spread through droplet transmission is a rare possibility even though there are case reports from many countries like Australia, New Zealand and Hawaii that suggest the chance of its existence. Mostly the disease affects the respiratory system and the symptoms are usually limited to the respiratory tract.
a) Respiratory system
Inhalation of aerosols containing particles of bird-droppings from infected birds results in the disease entry. For the virus particle to bind on to the respiratory epithelium, sialic acid is needed. The bronchioles and alveoli possess sialic acid linked to galactose by ?-2,3 linkages as well as ?-2,6 linkages. Hemagglutinin monomer of the avian virus particle binds to the sialic acid linked to galactose by ?-2,3 linkage where as, other influenza viruses bind to the sialic acid linked to galactose by ?-2,6 linkages. This could explain the difference in human-to-human transmission patterns seen in avian flu compared to other influenza types (Shinya and Kawaoka, 2006). The cellular proteases cause the cleavage of hemagglutinin monomer to different subunits. The virulence of avian influenza virus is dependent on the affinity of proteases to hemagglutinin (Zambon, 1999).
Replication of the virus happens in the respiratory epithelial cells, where the cell will take up the virus particle once hemagglutinin is cleaved by the protease enzyme. The cell engulfs it and the core genetic material of the virus is transported to the nucleus for the synthesis and replication of virions. Once the replication process is completed, the virions are released into the respiratory tract and will be carried by the droplets of respiratory secretions, during coughing and sneezing.
Mainly, the symptoms of avian flu are sore throat, cough, fever and muscle-ache (Viejo Banuelos, 2006) that start appearing after an incubation period of 2 to 4 days. Radiological findings include the presence of diffuse, multifocal or patchy infiltrates, which confirms the clinically apparent lower respiratory infection. Signs of tachypnea, respiratory crepitations and respiratory distress may also be present. In a severe situation, there may be respiratory failure, multi-organ failure with cardiac dysfunction and renal failure, which could turn fatal sometimes.
Cell mediated immunity, mediated through T lymphocytes, play a major role in the immunological response to infection. Sensitization of the lymphocytes result in the production of inflammatory cytokines like IL-6, IL-1?, IFN-? and MIP-1? (Zambon, 1999). The chemical mediators of inflammation confer the body with delayed immunity that gives protection against a future infection with the same strain of virus. The frequent mutations and antigenic drifts make this defense mechanism ineffective. Other subtypes like H9N2 and H7N7 are also capable of producing avian influenza apart from H5N1.
c) Extrapulmonary involvement
Reports show that extrapulmonary involvement also occurs in avian influenza by affecting the gastrointestinal system or the central nervous system. Predominantly, the gastrointestinal system is the organ that is affected in extrapulmonary presentation of avian influenza. It may present with gastrointestinal symptoms like severe diarrhea, vomiting, headache and fever. This may mimic the clinical picture of gastroenteritis (Apisarnthanarak et al., 2004). Bird flu has also presented with encephalitis and encephalopathy. These are characteristically seen in severe cases of influenza, but it is very unusual in avian influenza (Van-Tam and Watson, 2005)
Preventive measures & Influenza vaccine
No vaccines are commercially available for the prevention of avian influenza. Even if a vaccine is available for a strain, the antigenic drifts in the virus may result in new subtypes of bird flu viruses that can still produce a pandemic. The only option is to adopt necessary preventive measures to reduce the occurrence of disease till other effective measures are available. These preventive measures include culling of poultry and destroying or disinfection of poultry feeds, bird-droppings, contaminated manure and carcasses and use of necessary protective gear like mask and sterile gloves. Treatment with oseltamivir and zanamivir are effective in most of the cases.
Avian influenza is an unpredictable disease that can produce pandemics with serious implications. It can cause total derangement of the physiological systems of the body. Respiratory system is the major target of attack by avian influenza virus. Even though it is a disease that is usually limited to birds, the disease may cross the species-barrier and infect human beings, after antigenic drifts. Due to the unpredictable occurrence and the lack of effective vaccination, preventive measures still stand as the only option to reduce mortality due to this disease.
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Shinya, K. and Y. Kawaoka (2006). “[Influenza virus receptors in the human airway].” Uirusu 56(1): 85-9.
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WHO. WHO/ Cumulative number of confirmed human cases of Avian Influenza A/(H5N1) Reported to WHO. (Accessed on 7 March 2006 at http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_05_19/en/index.html)
Zambon, M. C. (1999). “Epidemiology and pathogenesis of influenza.” J Antimicrob Chemother 44 Suppl B: 3-9.