2008–2009 Influenza update: A better vaccine match
ABSTRACTLast year, the influenza vaccine did not match the circulating strains very well, and its overall protective efficacy was only 40%. All three antigens contained in the 2008–2009 vaccine are new. Surveillance data from the Southern Hemisphere during the summer of 2008 show that this vaccine is expected to match well the circulating strains in the Northern Hemisphere.
KEY POINTS
- Real-time reverse transcriptase polymerase chain reaction is the most accurate and clinically useful diagnostic test for influenza.
- All children age 6 months to 18 years should be vaccinated, and the live-attenuated vaccine is now approved for use in children 2 years old and older.
- We should continue to pursue traditional and innovative measures to increase influenza vaccination rates.
- Influenza vaccination during pregnancy reduces laboratory-confirmed influenza in infants up to 6 months of age by 63%.
- Hygienic measures (particularly hand-washing) aimed at younger children can prevent the spread of respiratory viruses in the community.
- Primary viral resistance to oseltamivir (Tamiflu) is rising, but almost all isolates remain susceptible to zanamivir (Relenza).
IF BIRD FLU BREAKS OUT, WE HAVE A VACCINE
In the event of an outbreak of avian influenza in humans, the US government now has a vaccine against H5N1, the causative virus. A two-dose regimen of a whole-virus H5N1 vaccine, which is derived from cell culture, induced neutralizing antibodies against diverse H5N1 virus strains in most subjects in one study.34 Another vaccine, which is egg-independent and adenoviral vector-based and contains conserved nucleoproteins, is broadly protective against globally dispersed H5N1 virus clades.35 The addition of the MF59 adjuvant to a subvirion H5N1 vaccine increased antibody response, but the addition of aluminum hydroxide did not.36
EXERCISE AND HYGIENE PREVENT FLU
Exercise has benefits beyond the usual ones: one study showed that exercising at low to moderate frequency (between once a month and three times a week) is associated with lower rates of influenza-related death.37
A recent meta-analysis38 confirmed that hygienic measures can prevent the spread of respiratory viruses in the community. The investigators calculated that hand-washing at least 10 times daily can prevent a large number of these infections (number needed to treat [NNT] = 4), and wearing surgical masks (NNT = 6), N95 masks (NNT = 3), gloves (NNT = 6), and gowns (NNT = 5) had incremental effects. On the other hand, the value of adding virucidal or antiseptic solutions to normal hand-washing was uncertain. Strict adherence to hand hygiene and masks (including by children) is needed to prevent influenza transmission in the home.39
AMANTADINE, RIMANTADINE ARE OUT; OSELTAMIVIR RESISTANCE IS GROWING
The CDC continues to recommend against using amantadine (Symmetrel) or rimantadine (Flumadine) to treat flu, owing to a high rate (> 90%) of resistance to these drugs.
A nonrandomized study suggests that zanamivir (Relenza) is more effective than oseltamivir (Tamiflu) for treating influenza B.40 A retrospective study in nine lung transplant recipients showed that oseltamivir is well tolerated and may reduce the risk of complications in these patients.41 Large, randomized, multicenter studies are under way to better assess oseltamivir’s preventive and therapeutic efficacy in transplant recipients.
In children, as in adults, oseltamivir is less effective against influenza B than influenza A,42 and both neuraminidase inhibitors, ie, oseltamivir and zanamivir, are equally effective in reducing the febrile period of influenza.43
During the 2007–2008 season, the rate of resistance to oseltamivir increased alarmingly.44 Resistance was restricted to A (H1N1) viruses carrying the H274Y mutation. In March 2008, the frequency of resistance among A (H1N1) viruses in the United States was 8.6%, 10 times higher than during the preceding influenza season. Resistance rates were much higher in several European countries, including Norway and France. During the Southern Hemisphere’s influenza season (May 2008 though September 2008), 46.5% of influenza A (H1N1) viruses received from 14 countries were resistant to oseltamivir. 45 It is worrisome that many of these resistant viruses were isolated from untreated patients. Fortunately, to date, 99% of these isolates remain susceptible to zanamivir.
Microbiologic tests to detect resistance are not currently available for clinical use. During an influenza pandemic, widespread use of neuraminidase inhibitors will likely promote further development of drug resistance. A mathematical model concluded that combined treatment and prophylaxis with antiviral agents will be necessary to control transmission during a pandemic, and that allocating different drugs to cases and contacts would be most effective in curtailing emergence of resistance.46
For now, either oseltamivir or zanamivir is acceptable for patients with flu symptoms and can be started pending results of PCR testing of nasopharyngeal swabs to make sure that the patient really has influenza. The drugs should be taken for 5 days.
