Virology and Epidemiology
Influenza virus is an enveloped orthomyxovirus (100 nm) that contains a negative single-stranded RNA genome divided into eight segments. This structure facilitates genetic re-assortment, which allows the virus to change its surface antigens and the influenza virus will take up genetic material from avian and pig influenza strains. The virus expresses seven proteins, three of which are responsible for RNA transcription. The nucleoprotein has three antigenic types that designate the three main virus groups, influenza A, B and C. Of the three types, influenza A and, more rarely, influenza B undergo genetic shift. The matrix protein forms a shell under the lipid envelope with haemagglutinin and neuraminidase proteins expressed as 10-nm spikes on the envelope, which interact with host cells. Virus immunity is directed against the haemagglutinin (H) and neuraminidase (N) antigens.
Annual epidemics of influenza are possible because the H and N antigens change, known as antigenic drift. This means that there are a sufficiently large number of individuals without immunity for the virus to circulate and, in some years, for an epidemic to occur. The virus may also undergo major genetic change, which is often due to gene re-assortment, known as antigenic shift. When this happens, as there are very few individuals with immunity, a worldwide pandemic may develop. Pandemics occur every 10-40 years, often originating in the Far East then circulating westwards. Such novel strains can often be traced to infected birds, poultry or pigs. Pandemic influenza A strains have a high attack rate and are associated with increased morbidity and mortality: 20 million people died in the 'Spanish 'flu' epidemic of 1919. The most recent pandemic virus, which arose in Mexico and was designated 'swine 'flu', was an H1N1 virus and had a high attack rate in the young. Viral pneumonia was most common in pregnant women and patients who were immunocompromised, but the global mortality rate was low. The risk of a pandemic is high when there are epizootics of avian 'flu circulating in domestic birds (e.g. H5N1) and genetic re-assortment occurs. Serotypes B and C are exclusively human pathogens that do not cause pandemics.
Avian strains are of great concern to poultry farmers, as avian 'flu may cause high mortality in their flocks. Infection can be transmitted to poultry from migratory wild birds. The virus can spread to humans and may be associated with high mortality (e.g. in the case of the H5N1 virus). Person-to-person spread is uncommon.
The incubation period lasts 1-4 days and patients are infectious for approximately 3 days, starting from 1 day before symptoms emerge. Headache, myalgia, fever and cough last for 3-4 days. Complications, which are more common in elderly people and patients with cardiopulmonary disease, include primary viral or secondary bacterial pneumonia.
Most diagnoses are made clinically. Rapid laboratory diagnosis is by direct immunofluorescence that can detect influenza A/B or C. Nucleic acid amplification tests (NAATs) are more sensitive and can identify the specific serotype, which can indicate whether a patient is infected with the pandemic strain. Public health laboratory services responding to pandemics must develop these novel tests quickly to track the progress of a new epidemic or pandemic strain. Virus isolation is still required for vaccine design, a process that is coordinated nationally by public health services and internationally by the WHO.
Treatment, Prevention and control
Treatment is usually symptomatic; secondary bacterial infections require appropriate antibiotics. Inactivated viral vaccines are prepared from the currently circulating viruses each year. Vaccination provides 70% protection and is recommended for individuals at risk of severe disease, such as those with cardiopulmonary disease or asthma. Influenza can be treated with the neuraminidase inhibitors zanamivir and oseltamivir, which shorten the duration of symptoms. They are indicated for patients who are at risk of severe complications and may have value in slowing the progression of a pandemic and reducing the associated mortality. Recent developments utilizing molecular cloning techniques have shortened the time taken to produce novel vaccines in response to a pandemic, which proved useful in the swine 'flu pandemic. Research continues to find a vaccine antigen that is effective but is not variable.
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