FluMist: me-too vaccine? Or latest and greatest?

September 2004

FluMist nasal vaccine. Talk about an enigma.

A highly effective innovative vaccine for influenza? A highly overpriced me-too vaccine?

God’s gift to children — not another shot? An asthmatic scourge about to be unleashed on young children?

Using it involves too much time for explanation? Using it saves a lot of time administering it?

Fewer side effects than the flu shot? High-risk because it’s a live vaccine?

Now that the price of cold-adapted intranasal influenza vaccine (CAIV, FluMist, MedImmune) has dropped from the stratosphere to a level manageable by most budgets, clinicians are beginning to rethink the value of this new tool to prevent the ubiquitous winter-time influenza scourge.

Sold in lots of 20, the cost this season for FluMist nonreturnable is $16 and for returnable is $23.50. This is within a reasonable range of injectable flu vaccine cost, which is priced in the range of $8 to $10 for thimerosal formulations and about $15 for thimerosal-free formulations. One problem that I see will be the limited number of doses of CAIV manufactured – about 500,000 to 1 million – this year.

If uptake accelerates as people begin learning about its advantages and disadvantages, this will average about one to two dose available for every primary care physician in the United States. Of course, the dreaded (by little and big kids age 35 years) shot should be (emphasis: should be?) in adequate supply this year, with at least 90 to 100 million doses manufactured.

So why would you consider using this vaccine in your pediatric patients?

Baby pincushions? No help here. The company nixed the notion of using their nonobnoxious nasal vaccine, which avoids a shot, in the group of children who most readily desire it — those younger than 60 months. I suspect that it was pre-emptive fear of rejection by the FDA of the entire product in all age groups.

Furthermore, to make our already pincushion schedule more onerous, the Advisory Committee on Immunization Practices (ACIP) and AAP have formally, albeit quite wisely, recommended influenza vaccines for all children 6 to 24 months of age, because of the heavy toll influenza wreaks in this young population. For them, the injectable influenza vaccine (TIV) is the only choice, and it does not lend itself as readily to mass vaccination as would a nasal spray. We are involved with more clinical trials this year to study the effectiveness of CAIV in young children.

Furthermore, trying to capture all the children in this age group for influenza vaccine will be a logistical nightmare. The clinician must immunize during both well and sick visits. Also, we must try to remind or capture each child over a five-month period as they age into the 6- to 24-month-old age range. Worse, then we will need to administer two injections within a short period a month apart. And the coup de grace: ALL contacts of high-risk groups and contacts of any child younger than 24 months old are recommended for influenza vaccine.

You will feel like a barking huckster at the county fair trying to entice entire families to “step right up! And get your shot!” Such pleasantry!

We really do need a universal influenza vaccine policy and an influenza vaccine (hopefully including nasal) that can be administered after 2 months of age. Who will have any time for well-child advice during the fall, trying to uncover contacts and explaining the tortuous recommendations?

FluMist advantages

So why use CAIV anyway for those older than 60 months?

1. Efficacy. Yes, there appears to be a modest difference. In noncomparative blinded trials involving 1,600 children, CAIV was 94% effective after two doses and 89% effective after a single dose for prevention of influenza. In comparison, five trials using TIV over the last decade showed the efficacy of TIV averaged about 65%, with a range of 31% to 83%.

Two recent European trials, each studying more than 2,000 children, compared a new, liquid-refrigerated version of CAIV with TIV. (Remember our available CAIV must be kept in a non–frost-free freezer.) The first study, which evaluated children aged 6 to 71 months with a history of recurrent upper respiratory infection, found CAIV 53% more effective than TIV (influenza attack rates of 2.3% vs. 4.8%, respectively). The second study, which evaluated children 6 to 17 years with a history of asthma, found CAIV 35% more effective than TIV (influenza attack rates of 4.1% vs. 6.4%, respectively). Reassuringly, neither study observed an increased rate of post-vaccine asthma or wheezing exacerbations among CAIV recipients (see below).

Second, antigenically drift strains. When influenza strains antigenically drift from those of the selected vaccine strain, which happens every three or four years, rates of protection with TIV seem to vary widely, as discussed above. For instance, protection was estimated to be only about 25% to 50% in last year’s epidemic (A/H3N2 Panama vs. Fujian). However, CAIV so far has continued to show 80%-plus protection in each year when an antigenic drift has occurred.

My colleagues and I are all aware that each annual injection of TIV causes a fair rate of local soreness and occasional malaise and achiness. In contrast, CAIV causes about 10% more rhinitis and 5% more fever than placebo, but only after the first dose, not after any subsequent doses. Neither type of influenza vaccine seems “to cause the flu.” Although a signal for asthma was seen in the northern California data from Black and Shinefield’s group, it occurred only in children 18 to 36 months old. Yet, when the diagnoses of asthma, wheezing and shortness of breath were all compiled, this relative risk disappeared. In fact, no signal for asthma was seen at all in children older than 36 months, and the relative risk for asthma post-vaccine for six weeks in children older than 60 months was reduced by 40%. (Could we even say it was temporarily protective for asthma post-vaccine in older children?)

Spreads like whooping cough?

First, the data from the Finnish day care trial looking at transmission had some limitations. Among about 100 day care children who received CAIV, only one child in the placebo group was documented to have acquired an influenza B vaccine strain and only for one day in three weeks. Although four influenza A (H3N2) strains were documented in the placebo recipients, the study could not verify whether they were the circulating wild-type or vaccine strains.

We are currently involved in a study to determine the rate and number of days that CAIV is shed. Earlier data suggested that CAIV in children is shed for seven days, rarely up to 21 days, and in adults for three days, occasionally up to seven days.

Second, one must remember that shedding does not mean transmission, which in turn does not mean influenza illness, particularly with a live-attenuated strain. The amount of virus shed (10- to 100-fold less than natural infection) also seems unlikely to be able to infect other children (Pediatrics 2004). CAIV reversion to wild type appears almost impossible with all of the genetic alterations of CAIV.

The ACIP stated that recipients of and administrators of CAIV should avoid CAIV only if they are exposed to severely immunocompromised patients (eg, those needing protective environment, current stem-cell transplants in hospital). For patients less immunocompromised, CAIV is considered safe if they are exposed to it. It is also considered safe for pregnant or nursing mothers to administer CAIV or to be exposed to it, although they should not receive it.

Anecdotally, for our entire office staff of 70, including six physicians, all but two received CAIV last year. We also administered CAIV to more than 500 patients last year. Why? We had observed early in some of our patients the antigenic drift of A/H3N2 from Panama to Fujian. Interestingly, within our 100% vaccinated office staff, no recipient of CAIV became ill with influenza, except for the two unlucky souls who had inadvertently received the injectable vaccine last year. True story, go figure?

Now, if only I can talk some of you guys out of a couple of doses of CAIV for this year?

For more information:

• Block SL. “Pediatric Drugs: September 2004.” In press.
• AAP Committee on Infectious Diseases. Recommendations for influenza immunization of children. Pediatrics. 2004;113:1441-1447.
• CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2004;(RR06):1-40.
• Zangwill KM. Safety and efficacy of trivalent inactivated influenza vaccine in young children: a summary for the new era of routine vaccination. Pediatr Infect Dis J. 2004;23:189-200.

• Stan L. Block, MD, has a pediatric practice in Bardstown, Ky., and is a member of the Infectious Diseases in Children Editorial Advisory Board.