Essential Evidence

Last Updated on 2022-06-24 © 2022 John Wiley & Sons, Inc.

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Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia

Randall Forsch, MD, MPH, Assistant Professor, University of Michigan
Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia
Kenny Lin, MD, MPH, Professor of Family Medicine, Georgetown University

Overall Bottom Line

  • Yearly influenza vaccination is recommended by ACIP (US) for persons over the age of 6 months. A
  • Patients classically present with rapid onset of fever, cough, chills or rigors, sore throat, and myalgias. A clinical decision rule can be used to identify patients at low, moderate or high risk of influenza. B
  • Rapid antigen tests are most useful during the beginning and end of the flu season. C
  • Treatment is largely supportive; antiviral medications are recommended only if the likelihood of influenza is high and the patient presents within 24 hours of symptom onset. There is no evidence that they reduce serious complications or hospitalization. A
  • Predictors of adverse outcome in the elderly include increased age, previous hospitalization, comorbidities, gender, and number of outpatient visits in the previous year (Table 1). A

Screening and Prevention

Bottom Line

  • ACIP (United States) recommends influenza vaccination for all persons over the age of 6 months. A 42 43 13
  • While zanamivir and oseltamivir prevent flu in close contacts and family members (NNT = 25-36), the cost and concerns about developing resistance argue against routine or widespread use for this indication, particularly in vaccinated individuals. A 36 37 38 39 40

Primary prevention

  • Influenza vaccination is recommended by ACIP (US) for all persons over the age of 6 months. 13 A Cochrane review found a 3% absolute risk reduction in the likelihood of influenza symptoms (1% vs. 4%) when there was a good match to the circulating virus, but only a 1% reduction when the match was poor.
  • Vaccination reduced time off work but there is no evidence of an impact on hospitalization or complications. 56 Overall, there is good evidence that immunization is cost-effective. 84
  • Vaccination is usually recommended for anyone living in a nursing home or chronic care facility and anyone who lives with or cares for patients at high risk of complications. 42 43 However, it is unclear if offering vaccination to health care workers in long-term care facilities improves outcomes for residents. 68
  • Vaccination is recommended by the CDC and ACIP for pregnant women, and is not associated with any subsequent illness in offspring based on a Canadian registry study. 82
  • An RCT of 31,989 adults 65 years and older compared a standard dose influenza vaccine (15 mcg hemagglutinin) with a high dose vaccine (60 mcg hemagglutinin) over two flu seasons. Laboratory confirmed influenza was less likely in the high dose group (1.4% vs. 1.9%, p < 0.05, NNT = 220). This small benefit must be balanced against a possibly higher risk of serious adverse events (3 vs. 0) and higher cost. 65
  • A trial randomized 9003 healthy adults 50 and older to a recombinant quadrivalent flu vaccine or inactivated quadrivalent flu vaccine. The recombinant vaccine provided a small advantage in terms of preventing flu (NNT = 100) in the study year. 75
  • Influenza vaccination of healthy working adults under age 65 years can reduce the rates of febrile illness, lost workdays, and physician visits if there is a good match between the vaccine and the circulating virus. 56 However, it does not reduce overall cost to society. 35
  • Live attenuated intranasal vaccine is approved for persons aged between 5 and 50 years. Some studies have shown that it may be safe and effective for younger children. 32 33 34 However, it is not currently recommended due to evidence of poor effectiveness against H1N1 during the 2013-2014 and 2015-2016 influenza seasons. 73 78
  • Flu vaccine does not prevent asthma flares or acute otitis media in children. 30 31
  • Although baloxavir, 90 zanamivir 63 and oseltamivir prevent flu in close contacts and family members (NNT = 25-51), the cost and concerns about developing resistance argue against use for this indication, particularly in vaccinated individuals. 36 37 38 39 40
  • CDC guidelines recommend that persons with egg allergy who have had only hives after exposure to egg should receive the flu vaccine. Recombinant hemagglutinin influenza vaccine is egg-free and is recommended for adults 18 to 49 years. Many persons can safely receive influenza vaccination containing less than 1.2 mcg/ml egg protein, but appropriate precautions should still be taken and it should only be administered in a setting where patients can be observed for at least 30 minutes and emergency systems are in place in the event of a severe reaction. 48 28 Live attenuated vaccine does contain egg protein. A cohort study in 779 persons age 2 to 18 years with egg allergy in the UK found no systemic reactions (95% CI, 0%-0.47% in all, 0%-1.4% in those with previous anaphylaxis). However, 8.1% experienced lower RTI symptoms, including 29 persons with wheeze. 72
  • Statins may impair the immune response to the vaccine, but the clinical implications of this are uncertain. 70
  • A vaccine to H7N9 (avian influenza) is under development. 71
  • High-Risk Groups
  • A Cochrane review found no benefit of influenza vaccination in persons with cystic fibrosis, but the analysis was limited by a very small sample size (n = 179). 57
  • Another Cochrane review of influenza vaccine for patients with hematologic malignancies found a reduction in the likelihood of lower respiratory tract infection and hospitalization with vaccination. 59
  • For patients diagnosed with COPD, a Cochrane review found that influenza vaccine reduces the number of exacerbations (WMD −0.37; 95% CI, −0.64 to −0.11). 61
  • In children undergoing chemotherapy given the flu vaccine, they are able to generate an immune response (although weaker than in healthy children). Evidence of clinical effectiveness in this population is lacking. 83
  • A meta-analysis found that flu vaccine was associated with a lower risk of cardiovascular events in adults with coronary disease, particularly those with a history of acute coronary syndrome within the past 6 months (NNT = 8). 53
  • No trials were found in a Cochrane review of influenza vaccine for persons with bronchiectasis. 60
  • An RCT in South Africa found that trivalent inactivated influenza vaccine significantly reduced the attack rates of influenza among HIV negative women (1.8% vs. 3.6%), the infants of HIV negative women (1.9% vs. 3.6%), and among HIV infected women (7.0% vs. 17.0%). 66 Other Interventions Patient reminder and recall systems improve immunization rates (OR 2.2 for childhood influenza vaccination, 1.7 for adult influenza vaccination). 27 58 Antibacterial household products do not reduce the risk of infectious symptoms. 26   Handwashing (especially around young children), isolation and social distancing may be effective at preventing the spread of influenza. 46  A Cochrane review identified four studies of interventions to improve hand hygiene in healthcare settings, but only limited evidence of effectiveness. 41 A systematic review found no evidence that N95 respirators are more effective than surgical masks at preventing influenza transmission. While N95 masks have theoretical advantages, they are also less comfortable which may impair usage. 69 This was confirmed in a subsequent trial in 2862 healthcare personnel (8.2% vs 7.2%) laboratory confirmed flu. 86
  • There is no increase in flares when patients with rheumatoid arthritis, lupus, or spondylarthritis are given the flu vaccine. 85