Page 327 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
316
least fourfold in paired serum samples taken early in the
illness and 10 days later is sufficient for diagnosis. Either
rivalent vaccines containing two A strains and two B strains
became available. The vaccine is usually reformulated each
the hemagglutination inhibition or complement fixation
year to contain the current antigenic strains.
(CF) test can be used to assay the antibody titer. Because
There are two main types of influenza vaccines available
the second sample is taken 10 days later, this approach is
used to make a retrospective diagnosis, often for epidemio-
logic purposes.
vaccine. The vaccine that has been used for many years is a
killed vaccine containing purified protein subunits of the
virus (hemagglutinin and neuraminidase). The virus is
Treatment in the United States, a killed vaccine and a live, attenuated
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inactivated with formaldehyde and then treated with a lipid
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Oseltamivir (Tamiflu) taken orally and zanamivir (Relenza)
solvent that disaggregates the virions. Note that the hemag-
inhaled into the nose are the two most commonly used
glutinin is the most important antigen because it elicits
drugs for the treatment of influenza. A third drug, perami-
vir (Rapivab) is administered intravenously and became
tered intramuscularly. A high-dose killed vaccine that
available in 2015. They are members of a class of drugs
contains four times as much hemagglutinin as the standard
called neuraminidase inhibitors, which act by inhibiting
vaccine is recommended for those over 65 years of age. In
the release of virus from infected cells. This limits the
2011, a killed influenza vaccine that can be administered
extent of the infection by reducing the spread of virus from
intradermally became available.
one cell to another. These drugs are effective against both
The other vaccine is a live, attenuated vaccine contain-
influenza A and B viruses.
Resistance to Tamiflu occurs but currently is not clini-
viruses. These temperature-sensitive mutants can repli-
cally significant. Some isolates of H1N1 influenza virus are
cate in the cooler (33°C) nasal mucosa where they induce
resistant to Tamiflu. However, H3N2 strains are still sus- ing temperature-sensitive mutants of influenza A and B
IgA, but not in the warmer (37°C) lower respiratory tract.
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ceptible to Tamiflu. Both H1N1 and H3N2 strains remained
The live virus in the vaccine therefore immunizes but
susceptible to Relenza. All influenza B strains are suscepti-
does not cause disease. This vaccine is administered by
ble to Tamiflu and Relenza.
Tamiflu pills are administered orally, whereas Relenza
ommended for children whereas the inactivated vaccine is
is delivered by inhaling the powder directly into the respi-
recommended for adults. The live vaccine should not be
ratory tract. Clinical studies showed they reduce the dura-
given to pregnant women or to immunocompromised
tion of symptoms by 1 to 2 days. They also reduce the
individuals.
amount of virus produced and therefore reduce the chance
Most of the vaccines described above are made in
of spread to others. These drugs are most effective when
chicken eggs, and anyone who has a significant allergy to
taken within 48 hours of the onset of symptoms. In 2015,
some concern regarding the efficacy of Tamiflu and
vaccines. However, in 2012, the U.S. Food and Drug
Relenza arose. Additional studies are needed to resolve
Administration (FDA) approved a killed influenza vaccine
this issue. egg proteins (e.g., anaphylaxis) should not receive these
(Flucelvax) made in calf kidney cell culture. This vaccine
Amantadine (Symmetrel) is approved for both the
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has two advantages: It can be given to those with egg
treatment and prevention of influenza A. However, 90% of
allergy, and it has a short turnaround time, so the latest
the H3N2 strains in the United States are resistant to
amantadine (and rimantadine, see later), and so these
Also in 2012, the FDA approved a recombinant vaccine
drugs are no longer recommended. These drugs block the
(Flublok) made by inserting the gene encoding the viral
M2 ion channel, thereby inhibiting uncoating. Resistance
hemagglutinin into an insect virus (baculovirus) that is
is caused primarily by mutations in the gene for the M2
propagated in insect cell culture. This vaccine contains
protein.
purified hemagglutinin as the immunogen. This vaccine
Note that amantadine is effective only against influenza
can also be given to those with egg allergy.
A, not against influenza B. Rimantadine (Flumadine), a
Note that the killed vaccine is not a good immunogen,
derivative of amantadine, can also be used for treatment
and prevention of influenza A and has fewer side effects
low. Protection lasts only 6 months. Yearly boosters are
than amantadine. It should be emphasized that the vaccine because little IgA is made and the titer of IgG is relatively
recommended and should be given shortly before the flu
is preferred over these drugs in the prevention of
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season (e.g., in October). These boosters also provide an
influenza.
opportunity to immunize against the latest antigenic
changes. The vaccine should be given to all persons 6
Prevention
The main mode of prevention is the vaccine, which con-
receive the vaccine. It is especially important that people
tains both influenza A and B viruses. Prior to 2013, the
with chronic diseases, particularly respiratory and cardio-
vaccine was trivalent and contained recent isolates of two A
vascular conditions, receive the vaccine. It should also be
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