Pharmacology Consult

Flu vaccine: The other ‘pneumonia shot’

Being an infectious disease pharmacist and having children has its advantages. Children contract many different infectious syndromes, which allows me to take advantage of that fact and use them as case examples. In July, my youngest son contracted influenza, which was complicated by pneumonia despite having been vaccinated last season. So, I was curious what the literature showed with respect to influenza vaccination decreasing the incidence of pneumonia.

Jeff Brock

Acute lower respiratory tract infections (LRTIs), such as pneumonia, are a leading cause of morbidity and mortality. Although we know that everyone is susceptible to the ill effects of influenza (eg, fever, body aches, cough, sore throat), complications that lead to hospitalizations and death can occur. These complications are highest in those aged older than 65 years, those aged younger than 5 years, and those who have medical conditions that increase the risk for complications (eg, immunosuppression, heart disease, chronic lung disease, etc.). According to the CDC, deaths related to pneumonia and influenza last season were at or above the epidemic threshold for 12 consecutive weeks — from Dec. 31, 2016, through March 18, 2017 — with two peaks occurring in week 3 (8.2%) and week 8 (8.1%) in 2017. Compared with other influenza seasons, this last season was considered moderate in nature, with mortality attributed to pneumonia and influenza ranging between 8.7% for the 2011-2012 season and 11.1% in 2012-2013.

Vaccination and influenza-related pneumonia

The question of whether influenza vaccines can decrease the risk of hospitalization for community-acquired pneumonia related to influenza was addressed by researchers who used data from the Etiology of Pneumonia in the Community (EPIC) study, which was conducted by the CDC from January 2010 through June 2012. In this case-control study, patients aged 6 months or older with laboratory-confirmed influenza and verified influenza vaccination status were included. A case patient was one that was hospitalized for pneumonia who tested positive for influenza within 72 hours, whereas the controls were those hospitalized for pneumonia who tested negative for influenza. Of those eligible for inclusion in this study, there were 2,767 patients hospitalized with pneumonia, and 162 (5.9%) of those patients had laboratory-confirmed influenza. Overall, 17% of those with influenza pneumonia had been vaccinated, whereas 29% of those who did not have influenza-related pneumonia had been vaccinated. In this study, influenza vaccination reduced the odds of being hospitalized with influenza pneumonia (adjusted OR = 0.43; 95% CI, 0.28-0.68) during the 2009 through 2012 influenza seasons, with an estimated vaccine efficacy of 56.7%.

Nursing home residents and hospital admissions

In a recent large cluster-randomized trial, researchers investigated whether high-dose (HD) influenza vaccine can provide better protection against severe influenza compared with standard-dose (SD) influenza vaccine in nursing home residents. The primary outcome of this study was hospital admissions related to pulmonary and influenza-like conditions using Medicare claims data. The nursing homes were certified by Medicare and located within 50 miles of a CDC influenza-reporting city. Facilities were randomly assigned to either the HD vaccine or SD vaccine. Influenza vaccines were administered to staff and residents in their usual way, including how they dealt with refusals or requests for different vaccines. Among the 823 facilities that were included in the analysis, 409 facilities received HD vaccine and 414 facilities received SD vaccine.

The staff vaccination rates did not differ between groups, with just over 50% of staff receiving influenza vaccine. The HD vaccine was found to be significantly more effective in preventing the primary study outcome of respiratory-related hospital admissions (0.185 per 1,000 resident days, or 3% to 4% over 6 months vs. 0.211 per 1,000 resident days, or 3% to 9% over 6 months). There was also a 20.9% reduction in hospital admissions related to pneumonia (adjusted RR = 0.791; 95% CI, 0.267-0.953; P = .013) among those receiving HD vaccine. The baseline hospital admission rate in this high-risk population was approximately one admission per 1,000 patient-days during the study period, so this means that to prevent one hospital admission, about 69 patients would need to be vaccinated with HD influenza vaccine. Of note, this study was conducted in 2013, during a relatively mild flu year, with H1N1 as the predominating strain, which tends not to impact those aged older than 65 years as much as a year in which H3N2 influenza is the predominating strain.

Maternal vaccination and infant respiratory infections

There is a substantial burden of acute LRTIs in children aged younger than 5 years. In the United States, the average rate of hospitalization related to influenza is greatest for infants aged younger than 6 months (104 hospitalizations per 10,000 children) compared with those aged 6 months to 12 months (50 per 10,000 children) and 1 to 3 years (19 per 10,000 children). Because influenza vaccine is poorly immunogenic in young infants (< 6 months of age), one way to provide protection from influenza for them is by passive protection through vaccination of pregnant women.

A randomized, double blind, placebo-controlled clinical trial completed in South Africa was recently published that evaluated the effect of maternal vaccination on infant hospitalizations for all-cause acute LRTIs. There were 2,049 infants enrolled, among whom 1,026 were born to mothers who received trivalent inactivated influenza vaccine (IIV). In the IIV-vaccinated group, 19 infants (3.4 per 1,000 infant-months) were hospitalized compared with 33 in the placebo group (6 per 1,000 infant-months). Vaccination during pregnancy reduced the risk for all-cause LRTI hospitalizations by 57.5%. In the placebo group, two-thirds of LRTI hospitalizations occurred in infants aged younger than 3 months, which highlights the risk for influenza complications in very young infants because they are unable to be vaccinated against influenza.

There were several earlier studies that looked at the effect of influenza vaccination on all-cause pneumonias that have shown modest decreases in the incidence of pneumonia among those vaccinated. The above-mentioned studies are important because they add to the evidence of the protective effect of influenza vaccine against LRTI, especially in two vulnerable populations — the older nursing home population and young infants — at least in years that have reasonably good vaccine effectiveness. However, last influenza season, the vaccine efficacy per the CDC was 34% for influenza A(H3N2) and 56% against the influenza B strains that were circulating. During influenza seasons with lower vaccine efficacy, it remains to be determined how well the vaccine will protect patients against LRTI, including influenza-related pneumonia.

When discussing the benefits of vaccination with our patients, it may be worthy to discuss that getting the influenza vaccine can reduce the risk for pneumonia and other LRTIs. For patients who are not willing to get the vaccine to prevent common influenza symptoms, this information may be enough to convince them to get the vaccine and possibly keep themselves or their young children out of the hospital with influenza complications. What we need is a universal influenza vaccine that is active against all strains of influenza that will also provide a durable immune response over time. Until such a vaccine is available, we will continue to deal with complications with this illness, even in those who have been immunized.

Disclosure: Brock reports no relevant financial disclosures.

Being an infectious disease pharmacist and having children has its advantages. Children contract many different infectious syndromes, which allows me to take advantage of that fact and use them as case examples. In July, my youngest son contracted influenza, which was complicated by pneumonia despite having been vaccinated last season. So, I was curious what the literature showed with respect to influenza vaccination decreasing the incidence of pneumonia.

Jeff Brock

Acute lower respiratory tract infections (LRTIs), such as pneumonia, are a leading cause of morbidity and mortality. Although we know that everyone is susceptible to the ill effects of influenza (eg, fever, body aches, cough, sore throat), complications that lead to hospitalizations and death can occur. These complications are highest in those aged older than 65 years, those aged younger than 5 years, and those who have medical conditions that increase the risk for complications (eg, immunosuppression, heart disease, chronic lung disease, etc.). According to the CDC, deaths related to pneumonia and influenza last season were at or above the epidemic threshold for 12 consecutive weeks — from Dec. 31, 2016, through March 18, 2017 — with two peaks occurring in week 3 (8.2%) and week 8 (8.1%) in 2017. Compared with other influenza seasons, this last season was considered moderate in nature, with mortality attributed to pneumonia and influenza ranging between 8.7% for the 2011-2012 season and 11.1% in 2012-2013.

Vaccination and influenza-related pneumonia

The question of whether influenza vaccines can decrease the risk of hospitalization for community-acquired pneumonia related to influenza was addressed by researchers who used data from the Etiology of Pneumonia in the Community (EPIC) study, which was conducted by the CDC from January 2010 through June 2012. In this case-control study, patients aged 6 months or older with laboratory-confirmed influenza and verified influenza vaccination status were included. A case patient was one that was hospitalized for pneumonia who tested positive for influenza within 72 hours, whereas the controls were those hospitalized for pneumonia who tested negative for influenza. Of those eligible for inclusion in this study, there were 2,767 patients hospitalized with pneumonia, and 162 (5.9%) of those patients had laboratory-confirmed influenza. Overall, 17% of those with influenza pneumonia had been vaccinated, whereas 29% of those who did not have influenza-related pneumonia had been vaccinated. In this study, influenza vaccination reduced the odds of being hospitalized with influenza pneumonia (adjusted OR = 0.43; 95% CI, 0.28-0.68) during the 2009 through 2012 influenza seasons, with an estimated vaccine efficacy of 56.7%.

Nursing home residents and hospital admissions

In a recent large cluster-randomized trial, researchers investigated whether high-dose (HD) influenza vaccine can provide better protection against severe influenza compared with standard-dose (SD) influenza vaccine in nursing home residents. The primary outcome of this study was hospital admissions related to pulmonary and influenza-like conditions using Medicare claims data. The nursing homes were certified by Medicare and located within 50 miles of a CDC influenza-reporting city. Facilities were randomly assigned to either the HD vaccine or SD vaccine. Influenza vaccines were administered to staff and residents in their usual way, including how they dealt with refusals or requests for different vaccines. Among the 823 facilities that were included in the analysis, 409 facilities received HD vaccine and 414 facilities received SD vaccine.

The staff vaccination rates did not differ between groups, with just over 50% of staff receiving influenza vaccine. The HD vaccine was found to be significantly more effective in preventing the primary study outcome of respiratory-related hospital admissions (0.185 per 1,000 resident days, or 3% to 4% over 6 months vs. 0.211 per 1,000 resident days, or 3% to 9% over 6 months). There was also a 20.9% reduction in hospital admissions related to pneumonia (adjusted RR = 0.791; 95% CI, 0.267-0.953; P = .013) among those receiving HD vaccine. The baseline hospital admission rate in this high-risk population was approximately one admission per 1,000 patient-days during the study period, so this means that to prevent one hospital admission, about 69 patients would need to be vaccinated with HD influenza vaccine. Of note, this study was conducted in 2013, during a relatively mild flu year, with H1N1 as the predominating strain, which tends not to impact those aged older than 65 years as much as a year in which H3N2 influenza is the predominating strain.

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Maternal vaccination and infant respiratory infections

There is a substantial burden of acute LRTIs in children aged younger than 5 years. In the United States, the average rate of hospitalization related to influenza is greatest for infants aged younger than 6 months (104 hospitalizations per 10,000 children) compared with those aged 6 months to 12 months (50 per 10,000 children) and 1 to 3 years (19 per 10,000 children). Because influenza vaccine is poorly immunogenic in young infants (< 6 months of age), one way to provide protection from influenza for them is by passive protection through vaccination of pregnant women.

A randomized, double blind, placebo-controlled clinical trial completed in South Africa was recently published that evaluated the effect of maternal vaccination on infant hospitalizations for all-cause acute LRTIs. There were 2,049 infants enrolled, among whom 1,026 were born to mothers who received trivalent inactivated influenza vaccine (IIV). In the IIV-vaccinated group, 19 infants (3.4 per 1,000 infant-months) were hospitalized compared with 33 in the placebo group (6 per 1,000 infant-months). Vaccination during pregnancy reduced the risk for all-cause LRTI hospitalizations by 57.5%. In the placebo group, two-thirds of LRTI hospitalizations occurred in infants aged younger than 3 months, which highlights the risk for influenza complications in very young infants because they are unable to be vaccinated against influenza.

There were several earlier studies that looked at the effect of influenza vaccination on all-cause pneumonias that have shown modest decreases in the incidence of pneumonia among those vaccinated. The above-mentioned studies are important because they add to the evidence of the protective effect of influenza vaccine against LRTI, especially in two vulnerable populations — the older nursing home population and young infants — at least in years that have reasonably good vaccine effectiveness. However, last influenza season, the vaccine efficacy per the CDC was 34% for influenza A(H3N2) and 56% against the influenza B strains that were circulating. During influenza seasons with lower vaccine efficacy, it remains to be determined how well the vaccine will protect patients against LRTI, including influenza-related pneumonia.

When discussing the benefits of vaccination with our patients, it may be worthy to discuss that getting the influenza vaccine can reduce the risk for pneumonia and other LRTIs. For patients who are not willing to get the vaccine to prevent common influenza symptoms, this information may be enough to convince them to get the vaccine and possibly keep themselves or their young children out of the hospital with influenza complications. What we need is a universal influenza vaccine that is active against all strains of influenza that will also provide a durable immune response over time. Until such a vaccine is available, we will continue to deal with complications with this illness, even in those who have been immunized.

Disclosure: Brock reports no relevant financial disclosures.