Influenza: Still more important than Zika virus

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ABSTRACTInfluenza kills and hospitalizes many people every year. Although the 2015–2016 influenza season was relatively mild, we should remain vigilant in our efforts to reduce the impact of future epidemics or pandemics by implementing universal influenza vaccination and early initiation of antiviral therapy for suspected cases. We don’t expect influenza vaccine to prevent all cases of influenza, since immune response varies depending on age, underlying diseases, and immunosuppression.


  • Influenza vaccine remains the most effective way to prevent influenza. Healthcare providers should continue to vaccinate all people older than 6 months.
  • For the 2016–2017 influenza season, only the inactivated influenza vaccine, not the live-attenuated vaccine, is recommended, regardless of age group or underlying disease.
  • Early initiation of a neuraminidase inhibitor is advised for an influenza-like illness while awaiting a confirmatory diagnostic test.



The mass media and the medical literature have been saturated in the last few years by concerns about a variety of emerging viral epidemics such as Ebola and Zika. We must always remember that influenza will continue to affect many more patients worldwide.

The Cleveland Clinic Journal of Medicine periodically publishes updates on influenza, a topic befitting the large proportion of internists and internal medicine subspecialists who regularly read the Journal. This series began in 1975 with an article by Steven R. Mostow, MD,1 which followed three pandemics that changed the world’s attitude about influenza.

A lot has changed since then, including another pandemic in 2009–2010. Here, I review recent information relevant to daily practice.


The relatively mild 2015–2016 influenza season is no reason for complacency this season.

Influenza activity in 2015–2016 was milder than in most seasons in the last decade.2 Activity peaked in mid-March and resulted in fewer outpatient visits, hospitalizations, and deaths than in previous seasons. Influenza A (H1N1)pdm09 has remained the predominant circulating virus since 2009. Although the overall rate of influenza-related hospitalization was less than half that in previous years, the hospitalization rate of middle-aged adults was relatively high (16.8 per 100,000 population). Importantly, 92% of adults with influenza illness that required hospitalization had at least one underlying medical condition, alerting us as healthcare providers that there is plenty of room for improvement in preventing such hospitalizations.

We should remain vigilant. We should put forth our best efforts in vaccinating all individuals above the age of 6 months and in diagnosing influenza early in the course of the illness in order to prescribe antiviral therapy within 48 hours of onset of symptoms. These actions not only shorten the illness and prevent hospitalization and secondary bacterial infection, but also reduce contagion and thus reduce overall healthcare costs.

School closure as a measure to halt epidemics has been lately called into question,3 since there are not enough data to support doing this routinely. School closure in Western Kentucky during the 2013 influenza epidemic did not reduce transmission but caused additional economic and social difficulties for certain households.4


In the several decades since influenza vaccine became available, hundreds of studies have demonstrated the value of the “flu shot.” A few recent papers that support these well-established data:

  • In adults who sought medical care for acute respiratory illness, influenza vaccine was 58.4% effective in preventing laboratory-confirmed influenza illness in adults age 50 and older.­5
  • In the same age group, influenza vaccine was 56.8% effective in preventing laboratory-confirmed influenza hospitalizations.6
  • Influenza vaccination in patients with heart failure reduced all-cause hospitalizations, particularly cardiovascular hospitalizations (30% reduction) and hospitalizations for respiratory infections (16% reduction).7 This effect lasted up to 4 months after influenza vaccination.
  • Patients who were hospitalized with community-acquired, laboratory-confirmed influenza pneumonia were 43% less likely to have received the influenza vaccine than patients hospitalized with community-acquired pneumonia due to other pathogens.8


Influenza vaccination during pregnancy prevented one in five preterm deliveries in a developing country9 and reduced the risk of stillbirth by 50% in Australia.10

An interesting collateral benefit was demonstrated in a survey conducted in Minnesota, where children of mothers who self-reported prenatal influenza vaccination were more likely to complete their routine childhood vaccination series.11


A recently appreciated benefit is that influenza vaccine induces cross-reactive protective immune responses (“heterologous immunity”) to viral strains not included in the vaccine, even in immunosuppressed individuals such as kidney transplant recipients.12 Interestingly, patients were more likely to seroconvert for a cross-reactive “heterologous” antigen if they also seroconverted for the vaccine-specific “homologous” antigen.

In a study in mice, an influenza vaccine with an adjuvant protected mice not only from influenza virus challenge, but also from a Staphylococcus aureus superinfection challenge.13 This novel idea suggests that influenza vaccine protects not only against influenza virus infection, but also against a potentially fatal secondary bacterial infection. This has significant implications for curbing antibacterial use, with an expected reduction in antimicrobial resistance.

Another important benefit of influenza vaccination was recently demonstrated when ferrets were intranasally inoculated with the highly pathogenic influenza A(H5N1) strain and then received either influenza vaccine or prophylactic oseltamivir. Ferrets that received the vaccine were less likely to develop severe meningoencephalitis.14 Since influenza A(H5N1) is much more virulent than the current circulating influenza strains, and since it may be the cause of the next pandemic, preventing such a serious complication of influenza would be lifesaving.

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