This has
been an exciting year for infectious disease.
Let’s hope an influenza epidemic does not make
2007 even more exciting.
We have
a slew of new vaccines for adolescents:
rotavirus, human papillomavirus and combined
tetanus-diphtheria-acellular pertussis (Boostrix,
GlaxoSmithKline; Adacel, Sanofi Pasteur). In
addition we have a recommendation for a second
varicella vaccine, which can now be given in
combination with measles-mumps-rubella as MMRV (ProQuad,
Merck).
We have
had our usual supply problems, including a
curtailment of the use of conjugate
meningococcal vaccines because of shortages;
this has now been rescinded and the vaccine can
now be offered to 11 to 12-year-olds. One of the
major problems that arose from this plethora of
new vaccines is how physicians can afford to
stock them. The cost of the new vaccines has
increased logarithmically compared with the
older ones, and there are more vaccines to give.
Thus, it may be necessary to lay out tens of
thousands of dollars to stock our offices with
vaccines. This is a problem that will be
discussed in these pages during the next couple
of months.
We had
expected live vaccines to produce an infection,
which would result in immunity similar to that
of natural infection, i.e. permanent immunity.
This generally appeared to be the case in the
past. A second dose of MMR is recommended to
protect those who might not have been immunized
successfully with the initial dose. If one
assumed a vaccine failure rate of only 1% from
one dose, then 40,000 susceptible patients (1%
of 4 million births) would accrue annually, or
400,000 in a decade. It is essential to keep the
pool of susceptible patients as small as
possible, thus the importance of giving multiple
doses.
Now
there is concern that some of these vaccines may
not confer durable immunity. In the case of
varicella, the second dose, which may be given
as MMRV, was recommended because of the number
of partially protected vaccinees following one
dose, but with an eye to waning immunity.
Varicella-zoster is a live herpes virus that
produces latent infection with cellular immunity
that clearly diminished with age, thus the need
for boosting immunity with a vaccine against
zoster at age 60; that vaccine was also licensed
this year. For this herpes virus, cellular
immunity may be more critical than immunity to
the older vaccines we have been using. The
durability of the immunity achieved with this
vaccine is being carefully watched. As a greater
proportion of children get vaccinated, we expect
to see more cases of modified varicella in the
future. This does not imply a loss of
vaccine-induced immunity.
The
second vaccine to arouse concern about waning
immunity is mumps. During the past year we have
had about 5,000 cases, which far exceeds what we
have seen for many decades. Outbreaks of mumps
have occurred sporadically, mainly in
educational settings, in the past. What is most
disconcerting is a large number of recent cases
occurred in people in their 20s, many of whom
had received the recommended two doses of MMR.
The predominance of cases in these people rather
than younger individuals certainly suggests
there may be waning immunity. In retrospect,
earlier estimates of the effectiveness of this
vaccine may have been overly optimistic. The
proportion of subclinical cases obfuscates the
calculation of vaccine efficacy and may make it
more difficult to appreciate virus spread.
Diminishing immunity to these childhood diseases
is of great concern as these diseases tend to be
much more severe in adulthood.
One
example of a disease in which immunity seems to
have diminished following vaccination is
pertussis. For reasons that are complex and as
yet unclear, we have witnessed a striking
increase in cases most of which are attributable
to cases in adolescents and adults. Thus, TDaP
has replaced dT as the vaccine of choice. It is
too soon to tell whether this has had an effect
on pertussis in the United States, but in
Canada, where vaccinating adolescents began in
2004, there is some suggestion that it may be
working. Although there appeared to be an
opportunity to test effectiveness in a suspected
outbreak of pertussis, PCR results used for
diagnosis could not be confirmed and thus the
planned intervention program was not carried
out. There continues to be a problem in
laboratory confirmation as we still lack an
approved serologic test and continue to be
plagued with unreliable PCR.
We now
have a newly licensed rotavirus vaccine, with a
second on the way. These have been tested
extensively and there has been no evidence of
increased risk of intussusception, which led to
the recall of the first rotavirus vaccine a few
years ago. In clinical trials, these vaccines
have been shown to reduce the risk of severe
diarrhea and are expected to decrease
hospitalization for gastroenteritis, a major
cause of hospitalization in infants.
Probably
the most important new vaccine is HPV. This has
been approved for girls as young as 9 years of
age and recommended for those women up to 26
years of age. It is important to immunize at a
young age, before sexual activity begins as
acquisition of HPV occurs rapidly after sexual
debut. In extensive field trials, the vaccine
has been shown to decrease the risk of infection
with the strains contained in both vaccines, 16
and 18, which are the two strains most commonly
involved in cervical cancer. The vaccine now
licensed contains additional strains, 6 and 11,
which are the principal ones causing genital
warts. A second vaccine has been submitted for
licensure, which contains only the two
cancer-producing strains. The vaccines have been
found to be immunogenic, decrease the risk of
infection and the development of early stages of
malignancy.
The
major story of the year is the continuing
epidemic of methicillin-resistant
Staphylococcus aureus. What is more, the
resistance to clindamycin, although variable
geographically, appears to be increasing. One
should know the resistance rate in one’s own
community before using it as a first choice.
Testing for inducible resistance using the
D-test should be routine as well as testing
additional antibiotics for sensitivity. What has
been most troubling is the appearance of the
disease in newborns. Both community and
hospital-associated disease are on the rise.
This has
been an exciting year in infectious disease
research. Let’s hope an influenza epidemic does
not make 2007 even more exciting … a reminder to
get ourselves, our families, our office staff
and out patients immunized. Have a happy holiday
season and a great (but not too exciting) New
Year. (Philip A.
Brunell, MD In Infectious Diseases in Children,
December 2006)