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.
VIRAL RESISTANCE TO NEURAMINIDASE INHIBITORS
Viral resistance to neuraminidase inhibitors occurs through multiple mechanisms and may arise without selective pressure from exposure to these drugs.55
Oseltamivir possesses a hydrophobic moiety that requires viral neuraminidase to undergo a complex reconfiguration to expose the active site prior to binding. Any mutation affecting its ability to undergo this structural rearrangement can promote resistance by decreased oseltamivir access to the active site.
Zanamivir has a structural homology to the neuraminidase active site and requires no such reconfiguration. Additionally, mutations promoting resistance to zanamivir may actually decrease viral fitness; thus, resistance to zanamivir is significantly less common than to oseltamivir.55
About 2,000 influenza virus isolates currently circulating in the United States were tested for resistance; only 1% of the 2009 influenza A H1N1 isolates demonstrated resistance to oseltamivir, and none to zanamivir.56
The CDC regularly updates the resistance patterns of circulating influenza strains at www.cdc.gov/flu/weekly/index.htm.
SPECIAL CONSIDERATIONS
Pregnancy
Pregnant women may be at higher risk of severe influenza complications. This was especially true during the 2009 H1N1 pandemic, when pregnant women had a five times higher risk of death from influenza-related complications. Additionally, fever during pregnancy is an independent risk factor for adverse outcomes in the offspring.57 Maternal vaccination against influenza effectively protects the infant for the first 6 months of life, when vaccination is not recommended because of a poor immune response.58
Live-attenuated influenza vaccine is contraindicated during pregnancy. Given the documented risks to the mother from influenza and no documented harm from preservatives in multiuse vaccine vials, the Advisory Committee on Immunization Practices (ACIP) and ACOG do not state a preference for thimerosal-containing or thimerosal-free vaccine for any group, including pregnant women. Pregnant women should be vaccinated with whatever inactivated influenza vaccine formulation is available at the earliest opportunity in the beginning of the influenza season, regardless of the trimester of pregnancy.
Pregnant women are at high risk of influenza-related complications and should be considered for postexposure antiviral prophylaxis or early treatment with a neuraminidase inhibitor. However, both of the approved neuraminidase inhibitors are in pregnancy safety category C, indicating possible adverse effects in animal studies and a lack of safety data in pregnant humans. As with all category C medications, the risks and benefits must be considered, taking into account maternal comorbidities, vaccination status, effectiveness of the season’s influenza vaccine, and the virulence of circulating influenza strains.
As oseltamivir is associated with nausea and gastrointestinal side effects and as zanamivir has less systemic absorption, it may be reasonable to prescribe zanamivir for women already experiencing severe pregnancy-related nausea.
Immunocompromised people
Inactivated influenza vaccine is recommended and live-attenuated influenza vaccine is contraindicated for all immunocompromised people. Generally speaking, any form of immune compromise will decrease the immunogenicity of the vaccine. Additional considerations vary depending on the cause and severity of the immunocompromised status.
HIV-infected patients have higher seroconversion rates when vaccinated with the high-dose vaccine than with the standard-dose vaccine; however, as in adults over age 65, the clinical benefit has yet to be evaluated.59 The efficacy of vaccination is predictably related to the CD4 cell count, as T cells are necessary to mount a response.60 No documented benefit is gained from booster influenza vaccination in this group of patients.
Cancer patients should receive inactivated influenza vaccine every year. Postexposure chemoprophylaxis should be considered, and early treatment with a neuraminidase inhibitor is recommended in patients undergoing chemotherapy.
Solid-organ transplant recipients face a risk of organ rejection if they contract influenza infection, in addition to a higher risk of influenza-related complications.61 Transplant recipients should receive inactivated influenza vaccine as soon as it becomes available at the beginning of every influenza season. Additional research is necessary to evaluate the safety and effectiveness of the high-dose influenza vaccine in this patient group.
MORE OPTIONS, GREAT BENEFIT
Influenza remains a significant source of morbidity and mortality in the United States, and emerging pandemic strains as well as the aging population pose the risk of increased disease burden. New vaccine options offer hope of greater safety, improved efficacy, and higher vaccination rates though broader appeal to individuals. The actual differences in protection between various vaccine options are insignificant relative to the overall benefit of vaccination.
Health care providers should inquire about patients’ understanding and address their concerns about vaccination. Giving an available influenza vaccine within approved indications should not be delayed if alternative vaccine options are not readily available.
In addition to vaccination, patients at high risk of complications should be advised early in the influenza season to inform their doctors about potential exposure to influenza or the development of flu-like symptoms for consideration of early treatment or postexposure prophylaxis with a neuraminidase inhibitor.
