Adolescent vaccines: the sting of making good choices

July 2005

Over the last decade, my sensible wife has been fond of pointedly admonishing our four lovely daughters (ages 17 to 26) prior to any weekend outing that they should “make good choices.” They merely laugh and then do what they darn well please. Curmudgeon Dad on the other hand has always extolled, “Don’t let me catch you doing something stupid, or you will be MY date for the next four weekends.” Now that injected a truly repulsive and deterrent thought into their cerebrum. And proudly, they have usually “made good choices” — for whatever reason.

Well folks, just like raising four daughters, don’t get comfortable thinking you have it made with the world of vaccines after age 4. Life has just become more complex for the pediatrician again. Adolescent vaccines have become like the world of “make good choices.” Along with the plethora of advice on healthy life style choices we must dispense for our pre-adolescent and adolescent patients during their routine checkup, we must now administer two new vaccines and possibly another three-shot series in the immediate future. First, let’s discuss our former objectives regarding adolescent vaccines before summer 2005.

Hepatitis B vaccine

You still need to certify that “the patient” has received all three doses of hepatitis B vaccine. But the exception is the Merck Recombivax, which requires only two doses (1 cc each) for the patient who is between ages 11 and 15. And, all regimens of hepatitis B must be delivered at the appropriate time intervals, ie, either at 0, 1-2, and greater than 6 months apart, or at 0 and greater than 6 months apart, respectively.

Varicella vaccine

Now, assume that “the patient” has slipped through your ever-vigilant radar screening (or, of course, some other “sorry doc’s” radar) for the varicella vaccine, and also has no history of verifiable varicella illness. The patient will need to receive two doses of varicella vaccine if they have reached the ripe old age of 13, but only one dose if captured at younger than 13 years.

Meningococcal vaccine (Menomune)

We occasionally administered the quadrivalent polysaccharide vaccine to some of our older adolescents — almost exclusively to entering college freshmen who requested it or who had received an entrance screening physical. The rule has now changed (see below).

Tetanus vaccine

As part of routine care, previously we have been administering a single dose of dT (adult diphtheria-tetanus) to our children at about age 9 to 11, in light of the recent CDC recommendations for a booster dose of tetanus five years after the four-year old booster. So, most of our current adolescents have received a tetanus booster of the old version. This rule has changed (see below).

Current new vaccines

Tetanus vaccine. (Whoops, did I mean the acellular pertussis vaccine? [no pun intended])

As investigators in several multicenter clinical trials, for about four years, we have been testing new acellular pertussis/tetanus/diphtheria vaccines in our patients of various ages. To make your office life more interesting, two new acellular pertussis/tetanus/diphtheria vaccines (Sanofi’s Adacel and GlaxoSmithKline’s Boostrix) have entered this sticky playing field. The immunogenicity, tolerability and safety of the vaccines have been excellent.

Both are administered as a single booster dose and contain a lower dose of pertussis antigens than those in the current vaccine used in the infant and preschool children series. The Adacel vaccine is approved for patients 11 to 64 and Boostrix is approved for those 10 to 19. (Although many adults act like teenagers, not many 40- to 60-year-olds appear in my practice currently.)

Most pediatricians have experienced the rationale creating the need for a booster dose of a pertussis vaccine to pre-adolescent and adolescent patients. By now, most of us have probably cared for an adolescent index case of pertussis or an adolescent as a vector for pertussis in an infant. In addition, pertussis is one of the few vaccine-preventable diseases whose incidence is steadily increasing across the United States. For more information, James Cherry, MD, has written an interesting treatise in Pediatrics 2005 about the need for a booster dose of pertussis in adolescents. He further explains that the acellular pertussis vaccine is much less reactogenic and, in turn, is probably less durable than the whole-cell pertussis vaccine series as the child ages.

But, I am also befuddled (beyond my usual state). It appears that I need to postpone the tetanus booster vaccine until age 11 in order to administer one of the new acellular pertussis/tetanus combinations? Do I even consider administering a new DTaP booster for an adolescent who has already received the older version of tetanus (dT) vaccine (without pertussis) within the last two to 10 years? Is every emergency department now supposed to administer one of the new DTaP vaccines for older patients in need of tetanus booster? Should all health care workers, like myself and my nurses, receive the Adacel vaccine?

Meningococcal vaccines

This is a vitally important vaccine for the world of pediatrics. Meningococcal invasive disease is among the most feared infectious diseases that we currently encounter with any regularity. It can be devastating to the patient, often killing or maiming before it can be recognized or before medical care is sought. Its prognosis is horribly unpredictable — even when treated correctly. I also believe that meningococcal mortality and morbidity have driven more good pediatricians totally out of practice because of lawsuits more than any other infectious disease, even though optimal care was provided for the patient.

The new quadrivalent protein conjugate meningococcal vaccine (Menactra, Sanofi Pasteur) has been approved for routine administration to patients 11 to 12 years old, and it has also been suggested for those 14 to 15 years old and those entering college.

Hundreds of our patients as young as 9 months and as “young as” 55 years, who have enrolled into several of the multicenter clinical trials recently performed in our office, have received this new conjugate vaccine. (My recent birthday reminded me how young 55 appears.) Immunogenicity and tolerability were quite good.

The new protein conjugate vaccine version is probably protective for a lifetime when administered after 15 months of age, based on historic and immunologic data. The polysaccharide version only protects for four or five years. Further testing and follow-up will hopefully substantiate this notion of permanent immunity. Remember that both meningococcal vaccines contain the four serotypes (A,C, W-135, Y) that account for only about two-thirds to three-quarters of all meningococcal disease. Unfortunately, since meningococcal serotype B is not included, we still cannot afford to be cavalier about the possibility of meningococcal disease occurring in our sicker or febrile previously healthy patients.

But the expected reduction in the overall incidence of meningococcal disease is truly welcomed by all, except for the “bean counters.” It appears that this new meningococcal vaccine at a cost of $82.50 is not very cost-effective, according to calculations made by Shepard and cohorts. It approaches a cost of $633,000 and $121,000 per meningococcal case prevented and life-year saved, respectively. But this calculation ignored the effects of herd immunity, which is usually more profound than predicted with this type of protein conjugate vaccine that also eliminates nasopharyngeal carriage.

The horns of a dilemma

We have about a 60% and 24% chance of capturing the child and adolescent, respectively, for routine immunizations, according to data from McInerny et al in Pediatrics 2005. Here is the dilemma. Clinicians must remember that we are currently testing the simultaneous administration of Menactra and Adacel in a clinical trial to determine whether any antibody interference between the two vaccines will occur. Thus, until we have these data, my assumption is that either of the adolescent DTaP vaccines should be administered at least a month apart from the conjugate meningococcal vaccine, when confronted with this possibility. However, a return second “well” visit a month or so later for another vaccination is anything but a slam dunk. And then more worrisome to me, we may be required to administer a third new vaccine for three doses over at least 6 months to half of our patients. For more information on this recommendation, see www.cdc.gov/nip/vaccine/mening/mcv4/mcv4_acip.htm.

HPV vaccine (Sodom and Gomorrah?)

We are currently entering our fifth year of clinical trial testing of two of the not-yet available human papilloma virus (HPV) vaccines for pre-adolescents, adolescents and adults. Lest you think that HPV does not concern you as a pediatrician, think again!

In the last few years, my gestalt is that up to 15% of our young ladies and mothers ages 17 to 25 have undergone colposcopy and/or treatment for significantly abnormal Pap smears showing either dysplasia or carcinoma in situ.

And guess what is the leading etiology of cervical dysplasia and cervical cancer? HPV. Myers and cohorts in American Journal of Epidemiology 2000 estimate that nearly half of all men and women will become infected with cervical HPV at sometime in their life. Over half of these patients will be infected with oncogenic strains. HPV is the second most prevalent sexually transmitted disease (STD), after herpes simplex. And possibly 86% of women infected with HPV never have an abnormal PAP smear.

Now the sad part is, the spread of HPV does not occur in a vacuum or by sharing sipping straws. It is mostly a STD, and condoms are only minimally protective according to the CDC Report to Congress by Gerberding. Even though males are supposed to show external signs of condylomata acuminata, during the last five years in our practice, I have seen only one adolescent male who has sought treatment for venereal warts. In previous years, we treated multiple male cases annually. Either the virulence has changed, or adolescent males are ignoring their minor dermatologic annoyance more so. This is not a needle in a haystack.

Thus, like many STDs (and unintended pregnancies), the women bear the brunt of the disease, and the men tend to go about their merry way, becoming carriers and major vectors for spread (sewing their oats, I suspect).

Now the good news. Two companies are quite near the FDA submission/approval process for a three-dose series of HPV vaccine, which looks quite effective, immunogenic and well-tolerated. Both contain serotypes 16 and 18, which are the predominant oncogenic serotypes causing cervical dysplasia/cancer. (The GSK version also contains verrucous-inducing serotypes 6 and 11 also.) Both HPV vaccines have already shown 80% to 90% effectiveness in preventing cervical cancer when compared with placebo.

Because of cost issues, probably only adolescent girls will receive the vaccine, starting at age 10 or 11. Sorry ladies.

Would I administer this vaccine to my daughters? Duhhh, as they tell their Dad.

Pediatricians: stung again?

So the vaccine schedule for our older patients appears as though it will become quite complex. But three additional important points have not been accounted for. Each of these new vaccines is terribly expensive, especially in large quantities, from a practitioner’s perspective.

First point, will supply be adequate, or will we be stuck with fits and sputtering spurts of vaccine availability, particularly with the usual Vaccines for Children (VFC) vs. privately insured dichotomy of uptake and coverage?

Second point, at what point can we be assured that reimbursement will be UNIFORMLY ADEQUATE from all insurance companies? I need to take care of patients and to have time to inform them of the need for each of these new vaccines. I do not need to be negotiating and fighting for reimbursement. A legislative mandate nationally is imperative.

Third point, the economic float needed to purchase these vaccines will undoubtedly place each practice’s economic bottom line precariously in the red for several months, until reimbursement can be obtained from the insurers. In the past, four doses of Prevnar for each child nearly economically decimated many a practice when it became standard in the vaccine schedule, a fact which also delayed uptake for many pediatric practices. (And my federal government wants me to purchase an electronic medical record system that could cost nearly $50,000 per doctor to obtain an actual user-friendly version? I suppose “M.D.” denotes a disposable “Million Dollars!”)

Now consider adding the cost of two new single-dose expensive vaccines to be administered to every older patient? Then add a three-dose series of another worthwhile but expensive HPV vaccine to every female patient. Additional total cost outlay per patient of nearly $400.

And, the vaccines may produce interference with each other and should thus be administered separately a month apart until we know differently. A “sticky” logistical nursing and recall nightmare for any busy practice! We also need a mechanism from each manufacturer to delay payment until actual administration of the vaccine, somewhat similar to a VFC mechanism. Otherwise, the routine use of these invaluable vaccines will be spotty and less than routine across the United States. As I can personally vouch for, McInerny in Pediatrics 2005 has shown that immunization levels correlate significantly with reimbursement levels.

Finally, I hope that our family practice colleagues will acquire and administer these three new vaccines routinely in their offices as they become standard of care. About half of all adolescents seek their routine care in family practice offices across the United States.

I worry about this issue because Prevnar has really never gained a foothold in most offices of family practitioners — creating a particularly vexing problem of two-tiered immunization distribution in rural America.

For more information:

• McInerny TK, Cull WL, Yudkowsky BK. Physician reimbursement levels and adherence to American Academy of Pediatrics Well-Visit and immunization recommendations. Pediatrics. 2005;115(4):833-838.
• Shepard CW, Ortega-Sanchez I, Scott RD, et al. Cost-effectiveness of conjugate meningococcal vaccination strategies in the United States. Pediatrics. 2005;115(5): 1220-1232.
• Cherry JD. The epidemiology of pertussis: a comparison of the epidemiology of the disease pertussis with the epidemiology of Bordetella pertussis infection. Pediatrics. 2005;115(5):1422-1427.
• Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of human papilloma virus type 16 vaccine. N Engl J Med. 2002;347(21):1645-1651.
• Harper DM, Franco EI, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomized controlled trial. Lancet. 2004;364(9447):1787-1765.

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