Prevention and treatment of influenza in the primary care office
ABSTRACTInfluenza, a common respiratory infection, is a source of significant rates of illness, death, and loss of productivity. Annual vaccination is safe and effective in preventing disease and in reducing its severity. Yet a majority of eligible US adults do not receive the annual vaccine, at least in part because of misunderstandings about adverse reactions and clinical effectiveness.
KEY POINTS
- Influenza vaccination is effective at preventing influenza-associated disease.
- Influenza vaccine is safe in people with a history of mild egg allergy.
- Many new vaccine formulations exist and may offer benefits to different patient groups.
- Neuraminidase inhibitors are recommended for treatment and postexposure prophylaxis in patients at high risk of influenza-related complications; however, they are not a substitute for vaccination.
EFFECTIVENESS OF INFLUENZA VACCINATION IN OLDER ADULTS
The effectiveness of influenza vaccination depends on the age and health status of the person being vaccinated, as well as on the quality of the match between the vaccine and the circulating influenza viruses.
In the 2012–2013 season, the adjusted vaccine effectiveness was 56% overall, 47% for influenza A H3N2, and 67% for influenza B. However, in people age 65 and older, the overall adjusted vaccine effectiveness was 27%, and only 9% for influenza A H3N2.15 Thus, even though the vaccine-virus match was considered good, the vaccine was suboptimally effective in the older group. This may be an argument for using the recently approved high-dose vaccine in that age group. Although the high-dose vaccine has been shown to be significantly more immunogenic in older adults, it is too early to know if it is clinically more effective in preventing influenza in this age group.
Despite the lower-than-expected effectiveness in preventing influenza in the 2012–2013 season in people age 65 and older, several well-designed studies found that influenza vaccination prevented severe disease, including one study that found vaccination to be 89% effective in reducing influenza-associated hospitalizations in the 2010–2011 flu season.4,16
The limited effectiveness of vaccination in the older age group reminds us of the importance of early recognition and treatment of patients at high risk of influenza-related complications (see Table 2). It is also a call for greater compliance with vaccination in younger people, with a goal of achieving the 80% vaccination rate that has been calculated as adequate to achieve herd immunity.17
MISAPPREHENSIONS THAT POSE BARRIERS TO VACCINATION
Concern about potential adverse effects is the most common reason for refusing influenza vaccination, even among health care workers.18 However, the only commonly encountered adverse effect of the intramuscular inactivated influenza vaccine is injection-site pain.
‘Catching the flu from a flu shot’
Many people think that they can “catch the flu from a flu shot” (or think that they actually did), but vaccine-acquired influenza is not possible with the inactivated influenza vaccine,19 and it is only a theoretical, undocumented consideration with the live-attenuated vaccine.
Various respiratory viruses other than influenza also cause viral upper-respiratory infections during the influenza season. These infections may coincide with influenza vaccination and are frequently misconstrued as a side effect of the influenza vaccine or as evidence of vaccine ineffectiveness.
Unnecessary concerns about simultaneous vaccinations
Patients and doctors are often concerned about simultaneous administration of multiple vaccines and choose to spread out indicated vaccinations over multiple visits. This practice increases patients’ risk of illness from vaccine-preventable diseases. Research shows that simultaneous administration does not alter the safety or effectiveness of vaccination.20–22 The CDC recommends simultaneous administration of all indicated live and inactivated vaccinations in order to reduce barriers to vaccination.20
Fear of Guillain-Barré syndrome
Guillain-Barré syndrome, an acute ascending polyneuropathy, has been blamed on influenza vaccination in cases that developed after the 1976 influenza A (H1N1) epidemic.
Most cases are self-limiting but require intensive treatment and supportive care. Full recovery occurs in 60% of cases, though some people experience persistent symptoms. The mortality rate is less than 5%.23
After the 1976 influenza pandemic, approximately 400 cases of Guillain-Barré syndrome arose in 45 million vaccine recipients, or about 1 case per 100,000 people.24 Multiple subsequent population analyses concluded that the actual incidence of Guillain-Barré syndrome attributable to influenza vaccination is negligible, at less than 1 case in 1 million vaccinations. Against this, we should compare the real risk of illness and death from influenza infection, which itself is a risk factor for Guillain-Barré syndrome.25
Should a person with a history of Guillain-Barré syndrome be revaccinated against influenza? The risk was evaluated in a large retrospective analysis of cases identified in the Kaiser Permanente Northern California Database from 1995 to 2006.26 Five hundred fifty cases of Guillain-Barré syndrome were identified, of which 18 had arisen within 6 weeks of the patient receiving a flu shot. Four hundred five doses of inactivated influenza vaccine were subsequently given to 105 patients who had a history of Guillain-Barré syndrome, two of whom had developed the syndrome within 6 weeks of receiving the shot. There were no documented episodes of recurrent Guillain-Barré syndrome in any of these patients. Only 6 of 550 patients with a history of the disease developed it again; none of these 6 had received the influenza vaccine in the preceding 2 months, and only 1 had been exposed to the measles-mumps-rubella vaccine in the 4 months before vaccination.
Nevertheless, expert opinion recommends lifelong avoidance of any immunization that had been given within 6 weeks before the onset of symptoms of Guillain-Barré syndrome.27
Overstated concern about egg allergy
Anaphylactic reactions can occur after influenza vaccination in people who have severe egg allergy, and concern about these reactions unfortunately prevents many otherwise eligible people with mild allergy from being vaccinated.
These reactions are much less common than feared. In a well-designed prospective cohort study of 367 patients with a history of egg allergy and positive skin-prick tests, including 132 with a history of severe allergy and 4 with a history of mild allergic symptoms arising in response to previous influenza vaccinations, none developed anaphylaxis.28
The same authors reviewed 26 studies in more than 4,000 egg-allergic patients, of whom more than 500 had a history of severe egg-associated reactions, and likewise found no cases of influenza vaccine-associated anaphylaxis. They concluded that the inactivated influenza vaccine is safer than the egg-derived mumps-measles-rubella vaccine, for which precautions for egg allergy no longer exist.28
People with a history of more serious reactions, ranging from stomach upset to anaphylaxis, can be safely vaccinated with a recombinant vaccine or referred to an allergist for further testing. People who experience hives as their only reaction to egg exposure should receive full-dose vaccination but then be observed for a half hour afterward.
The recombinant trivalent influenza vaccine Flublok was approved in 2013 for people age 18 to 49. It is the first commercially available influenza vaccine produced in a continuous insect cell line using a baculovirus vector. No eggs are used in its production, and it is approved for use in patients with egg allergy of any severity.
People who have a history of more serious reactions, including abdominal pain, nausea, vomiting, dizziness, or wheezing can be vaccinated with the recombinant vaccine or referred to an allergy specialist.
Despite this new option, understanding of alternative immunization guidelines for people with egg allergies, available on the CDC website29 remains important, as the availability of the recombinant trivalent influenza vaccine remains limited in the 2013–2014 influenza season.
Misconception about mercury toxicity
Thimerosal is an ethylmercury-containing preservative used in multidose antiviral vaccines, including some influenza vaccines.30 It is designed to prevent bacterial and fungal colonization of the vaccine vial while not reducing vaccine effectiveness or causing toxicity.
Contemporary understanding of mercury neurotoxicity is based largely on studies of methylmercury, including long-term, low-dose exposure in remote communities in the Faroe Islands and the Seychelles through regular consumption of fish and whale meat.31,32 These exposure studies had conflicting results: those in the Faroe Islands demonstrated toxicity, but the Seychelles studies actually showed better neurologic test scores at higher mercury levels, a trend the authors attributed to the beneficial effects of maternal fish consumption.
The results of the methylmercury studies have been extrapolated to ethylmercury (contained in thimerosal), although the two chemicals have vastly different pharmacologic properties. For example, methylmercury has a longer half-life and greater transport across the blood-brain barrier.33 A direct comparison found that ethylmercury is less toxic than methylmercury, although an increase in ethylmercury concentration of only 20% resulted in similar toxicity profiles.34 These studies were performed at concentrations of mercury thousands of times higher than those resulting from vaccination: nearly 150,000 times greater than those in an average adult or 15,000 times greater than those in a 1-year-old child from the typical 25-μg thimerosal dose allowed in contemporary influenza vaccines.
Despite much negative publicity, no link has been shown between thimerosal and autism.30 Multiple regulatory, scientific, and medical organizations including the US Food and Drug Administration (FDA), the WHO, the National Institutes of Health, the CDC, the American Academy of Pediatrics, and the American Congress of Obstetricians and Gynecologists (ACOG) have evaluated the data on the safety of thimerosal in vaccines and have agreed that it is safe. However, most of them urged vaccine manufacturers to eliminate mercury from vaccines as a precaution.30,35 Thimerosal has subsequently been eliminated from all childhood vaccines except for influenza vaccine, with no resulting decrease in childhood autism diagnoses.36
Considering that no harm from thimerosal at FDA-approved doses has been documented, and considering the real risk of influenza-related complications, particularly in young children and pregnant women, we recommend vaccination using whatever vaccine formulation is locally available for all patients, including children age 6 months and older and pregnant women. Nevertheless, given that mercury is being eliminated from childhood vaccines and that preservative-free single-dose vials are increasingly available in the United States, it seems reasonable to use thimerosal-free formulations for children, expectant mothers, and patients concerned about exposure if these formulations are readily available. Influenza vaccination should not be delayed if a thimerosal-free formulation is not readily available.
