Virology and Epidemiology
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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