Flu vaccine in older people: decreased morbidity with annual shots

​​There have been several interesting studies recently on influenza, so will divide them into 2 days' worth of blogs.

This flu season has been a pretty bad one, peaking earlier than usual, with widespread flu activity pretty much throughout the US, some novel strains of influenza A discovered, 37 pediatric deaths so far, and the proportion of deaths attributed to pneumonia and influenza increasing sharply to 9.1% in the week ending 1/6/18 (see https://www.cdc.gov/flu/weekly/summary.htm​ )

A recent Spanish case-control study found that older adults getting repeated flu vaccine had half as much severe influenza as compared to nonsevere infections (see Casado I. CMAJ 2018 January 8;190:E3-12)

 

Details:

--130 with severe and 598 with nonsevere flu admitted to 20 Spanish hospitals during the 2013/14 and 2014/15 influenza seasons were matched with 333 and 1493 controls, respectively, 

--all were community-dwelling and >65yo. All flu episodes were laboratory-confirmed. patients had to be admitted for at least 24 hours. those vaccinated had the inactivated trivalent vaccine

--vaccine effectiveness was estimated in the current and 3 previous seasons in preventing influenza both for patients with nonsevere influenza and for those with severe influenza (those who were admitted to intensive care units or dying within 30 days after hospital admission)

--nonsevere: 56% were 65-79yo/43% >80yo, 53% male, 14% no chronic conditions/32% one/53% >1, 35% pulmonary dz, 33% diabetes, 30% cardiovasc dz, 8% pneumonia in past 2 yrs, 54% never smoked/37% prior smoker/8% current smoker, 72% visited hosp in past yr, LOS in hosp 11d, no of visits to primary care 30% had 0-2 visits/45% 3-10/24% >10, 89% who were positive for got antivirals

--severe: 54% were 65-79yo/46% >80yo, 50% male, 15% no chronic conditions/24% one/61% >1, 35% pulmonary dz, 37% diabetes, 46% cardiovasc dz, 10% pneumonia in past 2 yrs, 56% never smoked/37% prior smoker/7% current smoker, 73% visited hosp in past yr, LOS in hosp 15d, no of visits to primary care 39% had 0-2/45% 3-10/17% >10, 93% who were positive for flu got antivirals [bold= severe significantly different from nonsevere]

 

Results:

--influenza type: of 728 influenza-positive patients admitted: 45% A(H1N1)pdm09, 35% A(H3N2), 15% A (nonsubtyped), 5% B. A(H1N1)pdm09 was dominant in 2013/14 season, A(H3N3) in 2014/15

--overall, ICU admission in unvaccinated  vs vaccinated: 16% vs 6% (p<0.001).

--Compared with patients who were unvaccinated in the current and 3 previous seasons, adjusted effectiveness of influenza vaccination in the current plus any previous season was:

    --31% (13%-46%) in preventing admission to hospital for nonsevere influenza

    --70% (46%-83%) in preventing severe influenza

    --74% (42%-88%) in preventing admissions to ICU

    --70% (34%-87%) in preventing death.

--those with vaccination only in the current season had no significant effect on cases of severe influenza

--the number of doses of flu vaccine in the current and 3 previous seasons was associated with a progressive decrease in the risk of hospital admission for severe influenza (linear trend p<0.001)

--among inpatients with influenza, vaccination in the current and any previous season reduced the risk of severe outcomes, with adjusted odds ratio 0.45 (0.26-0.76).

--subgroup analysis, adjusted odds ratio of reduced severe outcomes was statistically significant in:

    -- both predominant flu types for the 2013/14 and 2014/5, females (73% reduction), those 65-79yo (57% reduction, though those >80yo had an almost significant 58% reduction, perhaps limited by smaller numbers of patients), all of the major chronic conditions other than pulmonary disease (all had about 60-70% reduction, pulmonary 46% but nonsignificant), and those treated with antivirals (50% reduction)

 

Commentary:

--pretty impressive study suggesting a few things:

    --influenza vaccination does seem to prevent more severe cases of flu in the elderly (several studies in different countries have also found that flu vaccine is associated with less severe infections, this one confirmed this finding in the elderly)

    --there seems to be a cumulative effect: the most benefit was clearly in those who had been vaccinated during the current and any previous season

--the postulated explanation for these results: protection against getting flu infection is related to B-cell responses/antibody production. but protection against getting severe disease may be mediated through T-cells/cellular immune response. and these T-cell immune responses "can target internal proteins common to heterologous viral strains": ie, there may be some protection for dissimilar viruses from the targeted ones in the vaccine. And, since the elderly mount impaired T-cell responses, it might well take a few years of priming to have an effective response (ie, that's perhaps why there was no evident effectiveness with immunization only the target year, and effectiveness seemed to increase with more years of consecutive vaccination)

--at this time, we are using the higher dose flu vaccine in those over 65yo. Not sure if these results would have been the same if this more potent vaccine were used.  greater immediate effectiveness (as has been shown) and perhaps even better severity reduction?? maybe without so many years of cumulative vaccine??

--there are clearly inherent biases in this type of study. For example, did those who chose to be vaccinated differ in important (and perhaps uncontrolled-for) ways? Were they more connected to the health care system (though they all saw their primary care clinicians a pretty similar amount, were those getting the flu shot more likely to take care of themselves in other ways? Eat better? Exercise more? Be less frail? perhaps having less denial or being more preventive-focused and therefore more likely to come to the ER earlier than the unvaccinated ones and not need ICU care as a result​??? Was there a bias as to which patients were admitted into the ICU (did those who had the flu shot have stronger relationships with their primary care or pulmonary clinicians, and their physicians were more likely to have them admitted to the ICU??)

 

So, this article highlights that flu vaccine does work in older adults in preventing more severe infection. And the effectiveness of the vaccine is pretty clearly augmented in those who get regular annual vaccines.  this is pretty new to me: i was under the assumption that immunity from the vaccine was pretty transient, with studies showing that the vaccine was more effective if given within 3 months of a flu outbreak. (see http://gmodestmedblogs.blogspot.com/2017/08/should-we-delay-giving-flu-vaccine.html​ ). And was unaware of other lasting effects which could modulate its future severity. but this study adds to our clinical imperative to try to vaccinate all elderly patients annually, and perhaps all other patients as well...

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