Issue
Number 577
January 18, 2006
CONTENTS OF THIS ISSUE
- CDC publishes an MMWR Dispatch on Adamantane resistance
among influenza A (H3N2) viruses and interim guidelines for the use of
antiviral agents
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January 18, 2006
CDC PUBLISHES AN MMWR DISPATCH ON ADAMANTANE RESISTANCE AMONG INFLUENZA A
(H3N2) VIRUSES AND INTERIM GUIDELINES FOR THE USE OF ANTIVIRAL AGENTS
CDC published "High Levels of Adamantane Resistance Among Influenza A (H3N2)
Viruses and Interim Guidelines for Use of Antiviral Agents--United States,
2005-2006 Influenza Season" in the January 17 issue of MMWR Dispatch. CDC
publishes the web-based MMWR Dispatch only for the immediate release of
important public health information. The article will be published in a
print issue of MMWR in the future.
The January 17 MMWR Dispatch is reprinted below in its entirety, excluding
references.
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An estimated 200,000 persons are hospitalized each year and 36,000 persons
die from complications of influenza in the United States. The cornerstone of
influenza prevention is annual vaccination. However, antiviral drugs are an
important adjunct to vaccination for influenza prevention and control. Two
classes of antiviral medications are available currently: adamantanes or M2
ion channel inhibitors (i.e., amantadine and rimantadine) and neuraminidase
inhibitors (i.e., oseltamivir and zanamivir). The adamantanes are active
against only influenza A viruses and are used for both treatment and
chemoprophylaxis of influenza A, whereas the neuraminidase inhibitors are
active against both influenza A and B viruses. Zanamivir is not approved for
chemoprophylaxis of influenza in the United States. This report describes
new findings regarding the resistance to adamantanes of influenza A viruses
currently circulating in the United States and provides interim
recommendations that these drugs not be used during the remainder of the
2005-06 influenza season. Amantadine also is used to treat symptoms of
Parkinson disease and may continue to be used for this indication.
Resistance of influenza A viruses to adamantanes can occur spontaneously or
emerge rapidly during treatment. A single point mutation in the codons for
amino acids at positions 26, 27, 30, 31, or 34 of the M2 protein can confer
cross-resistance to both amantadine and rimantadine. Neither replication,
transmission, nor virulence of adamantane-resistant influenza A viruses are
impaired by the point mutations conferring resistance. A recent report on
the global prevalence of adamantane-resistant influenza A viruses indicated
a significant increase of drug resistance, from 1.8% during the 2001-02
influenza season to 12.3% during the 2003-04 season. In the United States,
the frequency of adamantane resistance increased from 1.9% during the
2003–04 influenza season to 11% during the 2004-05 season (CDC, unpublished
data, 2005). In contrast to adamantane resistance, neuraminidase-inhibitor
resistance remains rare worldwide.
The World Health Organization (WHO) Collaborating Laboratories and National
Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories in
the United States submit influenza isolates to CDC as part of routine
virologic surveillance. A subset of these isolates is further characterized
at CDC, which includes testing for antiviral susceptibility. Although
isolates are submitted by all U.S. states and territories, they are not
necessarily a representative sample of all influenza viruses circulating in
the United States.
Since the beginning of the 2005-06 influenza surveillance season, WHO and
NREVSS laboratories have tested a total of 38,932 specimens for influenza
viruses; 1,557 (4.0%) tested positive. Among the 1,557 influenza viruses,
1,499 (96.3%) were influenza A viruses, and 58 (3.7%) were influenza B
viruses. A total of 765 (51.0%) of the 1,499 influenza A viruses have been
subtyped; 760 (99.3%) were influenza A (H3N2) viruses, and five (0.7%) were
influenza A (H1N1) viruses. During October 1, 2005-January 14, 2006, a total
of 123 influenza A viruses collected from 23 states were tested at CDC for
adamantane resistance. Among the 120 influenza A (H3N2) viruses tested, 109
(91%) demonstrated the S31N substitution in the M2 protein that confers
resistance to amantadine and rimantadine. Conventional sequencing on a
subset of 20 viruses confirmed this substitution. Among the three influenza
A (H1N1) viruses tested, none contained any mutations associated with
resistance. As of January 14, all U.S. influenza viruses screened for
antiviral resistance at CDC had demonstrated susceptibility to neuraminidase
inhibitors. Procedures for virus propagation, RNA extraction, and
pyrosequencing for adamantane resistance have been described previously.
Editorial Note
The high levels of resistance to amantadine and rimantadine detected among
influenza A viruses tested during this season necessitate an interim change
in recommendations for the use of these drugs. On the basis of available
antiviral testing results, CDC recommends that neither amantadine nor
rimantadine be used for the treatment or chemoprophylaxis of influenza A
infections in the United States for the remainder of the 2005-06 influenza
season. During this period, oseltamivir or zanamivir should be prescribed if
an antiviral medication is indicated for the treatment of influenza, or
oseltamivir should be prescribed for chemoprophylaxis of influenza. On
January 14, 2005, a CDC Health Alert [available at
http://www.cdc.gov/flu/han011406.htm] with these recommendations was
sent via the Health Alert Network (HAN) to state and local health officers,
public information officers, epidemiologists, HAN coordinators, and
clinician organizations.
Testing of influenza isolates for resistance to antivirals will continue
throughout the 2005-06 influenza season, and recommendations will be updated
as needed. These findings of adamantane resistance pertain to human
influenza A (H3N2) viruses and not to avian influenza A (H5N1) viruses
isolated from birds or humans in Asia or Europe.
Recommendations for the use of the oseltamivir and zanamivir have not
changed. The Food and Drug Administration (FDA) recently extended
chemoprophylaxis approval of oseltamivir to include children aged 1-12
years; previously, chemoprophylaxis approval had been limited to children
aged 13 years and older.
When administered for treatment within 48 hours of illness onset,
neuraminidase inhibitors can reduce the duration of uncomplicated influenza
A and B illness by approximately 1 day when compared with placebo. Persons
at high risk for serious complications from influenza can benefit most from
neuraminidase inhibitors. CDC recommends that neuraminidase inhibitors be
used as treatment for any person experiencing a potentially life-threatening
influenza-related illness and for persons at high risk for serious
complications from influenza. CDC recommends that oseltamivir be used as
chemoprophylaxis for (1) persons who live or work in institutions caring for
persons at high risk for serious complications from influenza infection in
the event of an institutional outbreak and (2) persons at high risk for
serious influenza complications if they are likely to be exposed to others
infected with influenza. The FDA-approved indications for the use of
neuraminidase inhibitors are available at
http://www.cdc.gov/flu/professionals/treatment
Annual influenza vaccination remains the primary means of preventing
morbidity and mortality associated with influenza. Because the influenza
season has only recently begun in many areas of the United States, persons
for whom influenza vaccination is recommended should still be vaccinated.
Additional information regarding the prevention and control of influenza is
available at http://www.cdc.gov/flu New
information will be provided at this website as it becomes available.
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To obtain the complete text of this MMWR Dispatch online, go to:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d117a1.htm
To obtain this MMWR Dispatch in ready-to-print (PDF) format, go to:
http://www.cdc.gov/mmwr/pdf/wk/mm55d117.pdf |
