The Disease
Influenza is an acute contagious respiratory illness caused
by influenza viruses. It is one of the oldest and most common
diseases known to man. It can also be one of the deadliest.
Influenza was first described by Hippocrates in 412 BC at
Perinthus in North Greece, and the first well-described pandemic
of influenza-like disease occurred in 1580. Since that time,
31 influenza pandemics have been documented, with three occurring
in this century : in 1918; 1957 and 1968. There is evidence
that the virus which caused these epidemics originated from
animals or birds (1918-swine, 1957 and 1968 - birds). In 1976,
a new influenza virus from pigs caused human infections and
severe illness and in 1998, an H5N1 poultry strain of influenza
also caused human disease.
Each year, tens of thousands of Canadians become ill with
influenza, and 1000-7000 die from its complications.
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Picture taken from
Pathology of Influenza Infection
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The influenza virus invades the respiratory mucosal
cells of the upper and lower respiratory track. Viral
reproduction begins within 4-6 hours, after which infectious
virus is released to infect nearby cells. When the infected
person coughs, sneezes, or talks, virus laden particles
are sprayed into the air. |
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ONCE THE VIRUS IS INHALED< IT ENTERS THE LINING OF
THE NASOPHARYNX AND/OR THE BRONCHIAL TREE. THERE,
IT TARGETS COLUMNAR EPITHELIAL CELLS.
Picture taken from
Pathology of Influenza Infection
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The steps in the infectious cycle
are:
- Haemagglutinin on the viral surface
binds to sialic acid coating the cell surface .
- This complex triggers the cell
to engulf the virus, forming an endosome within
the cell
- The viral M2 protein acidifies
the endosome, breaking down both the virus and endosome
membranes, and releasing viral RNA
- Viral RNA enters the cell nucleus
and initiates viral replication.
- New viral particles are packaged
within the cell, and transported through the cell
membrane
-
Neuraminidase on the surface of new viruses cleaves
molecules of sialic acid , allowing release of
virus. Viral replication initiates the process
of cell death, which occurs several hours after
release of the virus.
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During the 48-hour incubation period after infection, virus
replication in the respiratory tract and transient asymptomatic
viremia may occur. In mild cases (in resistant or partially
immune hosts), the symptoms are like those of a common cold.
In more severe cases, symptoms typically start suddenly with
chills and fever (up to 39 to 39.5ºC) prostration and
generalized aches and pain (most pronounced in the back and
legs). Headache may be is prominent, often with photophobia
and retrobulbar aching. Respiratory tract symptoms may be
mild at first, with scratchy sore throat, substernal burning,
non productive cough, and some times coryza. Later, the lower
respiratory illness becomes dominant; cough can be persistent
and productive. In severe cases, sputum may be bloody. Nausea
and vomiting may occur in children. After 2 to 3 days, acute
symptoms subside and fever usually resolves
Abnormal lung clearance and altered bronchiolar air flow
can be demonstrated, and, in asthmatics, attacks are frequently
precipitated by weakness and fatigue. Fulminant pneumonia
is rare, but when it occurs, death may ensue in as little
as 48 hours.
Secondary bacterial infection of the bronchi and lungs,
most commonly pneumococcal or staphylococcal, is suggested
by persistence or recurrence of fever, cough and other respiratory
symptoms in the 2nd week. When pneumonia develops, cough and
fever worsen, purulent or bloody sputum may be produced, and
pleuritic chest pain may occur.
Encephalitis, myocarditis, and myoglobinuria are infrequent
complications of influenza and, if present, usually occur
during convalescence. Virus is rarely recovered from organs
outside the respiratory tract, and a specific role in the
pathogenesis of the extra- pulmonary diseases cannot be positively
established. However, an increased incidence of such disease
regularly follows influenza A pandemics. Reye's syndrome,
characterized by encephalopathy, fatty liver, hypoglycemia
and lipidemia, has been prominently associated with epidemics
of influenza B, particularly in children who have ingested
aspirin.
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Influenza infection can be diagnosed by serology using haemagglutinin-inhibition
tests to detect antibodies that develop during acute infections;
however, such antibodies require 10-14 days to develop. More
immediate diagnosis may be achieved by the direct detection
of viral antigens in nasal secretions by immunofluorescence,
polymerase chain reaction (PCR) or ELISA, using monoclonal
antibody to the nucleoprotein. Culture of the influenza viruses
is required for subtyping of strains, which is essential for
the detection of newly evolved strains, and thus for the selection
of new vaccine, and the detection of pandemics.
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Once a person has Influenza, treatment usually consists
of rest, drinking plenty of fluids, and taking medications
such as acetaminophen (Tylenol) to relieve fever and
discomfort. Children with febrile illnesses, including
influenza, should not take aspirin because of the risk
of developing Reye's syndrome.
Antibiotics are not effective against influenza viruses.
Four anti-influenza drugs are available to treat and
prevent influenza A. Two of these drugs, called amantadine
and rimantadine, are effective only against influenza
A. They act by binding to the M2 protein of influenza
A, and preventing the release of viral RNA into the
cell. Either of these medications can be used to prevent
influenza A if they are taken before exposure to the
virus or, after exposure but before symptoms develop.
They may also be used to treat influenza but they must
be given within 48 hours of developing the first symptoms.
Only Amantadine, which is also used to treat Parkinson's
disease, is available in Canada. It should not be taken
by people with seizure disorders, and may interact with
some other neurologic and psychiatric medications. The
most common side effects due to amantadine are dry mouth,
light-headness and difficulty concentrating. |
| The other two drugs are effective for the treatment
and prevention of both influenza A and influenza B.
These drugs called neuraminidase inhibitors, act by
blocking the function of the viral neuraminidase. One
of the drugs, zanamivir (Relenza®) is an inhaled
powder. A device called a disk inhaler is supplied with
the medication. The other drug, oseltamivir (Tamiflu®),
is a tablet. As with amantadine, both zanamivir and
oseltamivir must be started within 48 hours of onset
of symptoms to be effective for treatment. They are
also very effective in preventing influenza if they
are taken before exposure to the virus or, after exposure
but before symptoms develop. Very rarely, zanamivir
may cause irritability of airways, and wheezing after
the inhaler is used. The most common side effects of
oseltamivir are nausea, vomiting, and diarrhea, which
occur in 2-9% of people who take the medication. |
Zanamivir (Relenza®)
Picture taken from
National Foundation for Infectious Diseases
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