Monday, February 26, 2018

Two Studies On Impact Of Fever & Antipyretics On Flu Vaccine Immune Response In Children


As any parent will attest, it isn't unusual for a child (or sometimes an adult) to develop a mild fever after receiving the influenza (or other) vaccine. According to the CDC, in addition to soreness and swelling at the injection site, headache and minor muscle aches may also commonly occur. 
These symptoms generally last a day or so, and are widely believed to be a sign  the body's immune response. 
The question, often asked, it whether it is better to let these symptoms run their course, or to take an antipyretic (acetaminophen of an NSAID) to reduce fever and pain.  While adults can generally tough it through without taking anything, children may experience more discomfort.

We've looked at this debate a number of times over the years, and the answers have not always been consistent.  
Also in 2014's  Start Spreading the Flus, we looked at a study that appeared in the Proceedings of the Royal Society B, that calculated the use of fever suppression meds increased the number of annual cases by approximately 5%, resulting in more than 1,000 additional flu deaths each year in North America.
Simply put, the use of antipyretics not only produces a host environment conducive to better viral replication, it can allow someone who is still contagious to feel good enough go to work, or school, and further spread the virus.
We saw this tactic used during the 2009 pandemic among airline passengers trying to evade fever screenings at airports (see Why Airport Screening Can’t Stop MERS, Ebola or Avian Flu).

While it is always a good idea to avoid any medication whenever possible - as even OTC meds can cause rare but serious side effects (see Common anti-fever medications pose kidney injury risk for children)  - this can be a tough sell to a parent with a cranky, feverish child.
So the question remains, is it better to let a mild fever after a flu vaccination (or infection) run its course, or treat it with antipyretics?
And we have two recent studies on point, which unfortunately don't exactly come up with the same answer. First, from December of 2017:

Vaccine. 2017 Dec 4;35(48 Pt B):6664-6671. doi: 10.1016/j.vaccine.2017.10.020. Epub 2017 Oct 19.

The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children.

Walter EB1, Hornik CP2, Grohskopf L3, McGee CE4, Todd CA4, Museru OI5, Harrington L4, Broder KR5.

Antipyretics reduce fever following childhood vaccinations; after inactivated influenza vaccine (IIV) they might ameliorate fever and thereby decrease febrile seizure risk, but also possibly blunt the immune response. We assessed the effect of antipyretics on immune responses and fever following IIV in children ages 6 through 47 months.



Significant differences in seroconversion and post-vaccination seroprotection were not observed between children included in the different antipyretic groups and the placebo group for the vaccine antigens included in IIV over the course of the studies. Frequencies of solicited symptoms, including fever, were similar between treatment groups and the placebo group.


Significant blunting of the immune response was not observed when antipyretics were administered to young children receiving IIV. Studies with larger sample sizes are needed to definitively establish the effect of antipyretics on IIV immunogenicity.

Slightly newer, and with a different take, is this Feb 19th study from  Pediatric Infectious Diseases Journal.

Pediatr Infect Dis J. 2018 Feb 19. doi: 10.1097/INF.0000000000001949. [Epub ahead of print]
Impact of Fever and Antipyretic Use on Influenza Vaccine Immune Reponses in Children.
Li-Kim-Moy J, Wood N, Jones C, Macartney K, Booy R.



Comparing post-vaccination fever rates in pediatric influenza vaccine clinical trials is difficult due to variability in how fever is reported. The impact of vaccine-related fever and antipyretic use on trivalent influenza vaccine (TIV) immunogenicity in children is also unclear.

In this pilot study, we obtained individual-level data provided by GlaxoSmithKline (GSK) from three pediatric clinical trials of GSK versus comparator TIV. We explored a primary study (NCT00764790), the largest trial involving young children (6-35 months, n=3317), and further explored key findings in the two other trials (3-17 years, NCT00980005; 6m-17y NCT00383123). We analyzed post-vaccination fever and antipyretic use, and their association with immunogenicity through use of multivariable regression.

Post-vaccination fever data were re-analyzed from the primary study using the Brighton Collaboration standardized definition (vaccine-related fever ≥38°C, measured by any route, reported after each dose). Rates were substantially lower after first (2.7-3.4%) and second doses (3.3-4.1%), than those published (6.2-6.6%; combined dose data, any causality).
A pooled immunogenicity analysis combining the 3 studies (n=5902) revealed children with post-vaccination fever had significantly higher adjusted Geometric Mean Titers (GMT) than those without fever (ratio 1.21-1.39; p≤0.01). Conversely those with antipyretic use had significantly lower adjusted GMTs (ratio 0.80-0.87; p < 0.0006), dependent on virus strain.

Varying analyses and reporting methods can result in substantially different reported fever rates in studies. Standardized reporting of fever is needed to facilitate comparison between studies. Fever and antipyretic use may have important associations with influenza vaccine immunogenicity in children and need further prospective investigation.
Where these studies do agree is that more, and bigger, investigations are needed in order to accurately pin down the true impact of antipyretics on a flu vaccine's immune response in children.

No comments: