Immunization research, including vaccine development and
delivery, always provides a significant contribution to the
original science presentations at PAS. In the following
section, several investigations that focused on how the
increasingly complex vaccination schedule may affect pediatric
practice will be reviewed.
Conjugate Pneumococcal Vaccine and Unintended
Effects on Adherence to Vaccine Schedules
Karen Lee, MD, and co-investigators from several Boston
institutions, as well as from the National Immunization
Program of the Centers for Disease Control and Prevention
(CDC),[13] assessed (1) how well practitioners were
adhering to 2001 immunization guidelines, and (2) how the
advent of pneumococcal conjugate vaccine has affected delivery
of other immunizations. They surveyed pediatricians and nurse
practitioners in Massachusetts 1 year after the release of the
heptavalent pneumococcal conjugate vaccine.
Fifteen percent of respondents reported that they added
visits to accommodate the new schedule, with two thirds of
these added visits being immunization-only visits.
Thirty-eight percent of respondents reported moving other
vaccines within their usual delivery window, and 37% of the
practitioners were ultimately not adhering to guidelines for
when vaccines should be administered.
The investigators noted that the practice of splitting
vaccine administration into multiple visits, rather than
giving all that were eligible at the time the child presented
for a visit, strongly correlated with a provider not being
adherent to the recommended schedule. They concluded that the
addition of pneumococcal conjugate vaccine to the routine
immunization panel has resulted in an unintended rise in
patient visits (mostly immunization-only visits). The
take-home message from this research is to give all vaccines
for which a child is eligible at any visit. Otherwise,
patients will be much more likely to fall behind on the
recommended immunization schedule.
Increases in Missed Opportunities to Vaccinate
In a CDC surveillance project, Matilde Irigoyen, MD,
Columbia University, New York, NY, and colleagues[14]
evaluated the impact of change in the immunization schedule on
missed opportunities, both overall and vaccine-specific. This
was a CDC demonstration project specifically designed to
evaluate changes in missed opportunities. The study evaluated
immunization delivery in practices in New York City from
1996-2001, a time during which the number of injections
required to meet the recommended immunization series doubled.
The 21 surveyed practices contained over 22,000 children,
aged 6 months to 35 months. Data were collected by quarterly
chart review. For vaccine-specific rates of missed
opportunities (a child did not receive a vaccine for which he
or she was eligible), all vaccines except varicella
demonstrated an increase in missed opportunities for
administration. For example, roughly 6% of eligible children
missed polio vaccines in 1996, but 21% missed an eligible dose
in 2001, following the introduction of pneumococcal conjugate
vaccine to the routine schedule. Similar though less
pronounced patterns were noted for Hib, measles-mumps-rubella
(MMR), and diphtheria, tetanus and whole-cell pertussis (DTP)
immunizations.
Although hepatitis B vaccine missed opportunities were
equal in 1996 and 2001 at roughly 14%, this apparent lack of
change was deceptive. In fact, the rate of missed
opportunities for hepatitis B between 1996 and 2000 actually
improved a great deal during this time period but increased
back to the 14% range in 2000, a finding again linked to the
introduction of the pneumococcal conjugate vaccine. The
take-home message from this investigation, as well as from the
preceding study, is that immunization status should be
assessed at all visits and vaccines should be administered
when a child is first eligible.
Anaphylaxis After Vaccination
Kari Bohlke, MD, Center for Health Studies, Group Health
Cooperative in Seattle, Washington, and colleagues[15]
determined the rate of anaphylaxis after receipt of routine
childhood immunizations. Data were obtained from 1991-1997
from 4 West Coast health maintenance organizations
participating in the Vaccine Safety Datalink Project, a
program of the CDC.
The investigators searched the data first by International
Classification of Diseases (ICD)-9 codes for diagnosis of
anaphylaxis experienced by patients from birth to 17 years.
Children in the cohort received more than 7 million
vaccinations during the time period. After identifying
potential cases from ICD-9 codes, primary documents were
reviewed to confirm the diagnosis. Potential cases were
excluded if they occurred > 2 days after receipt of
vaccination.
Investigators identified only 5 cases of anaphylaxis in the
cohort (rate of 0.65 per million doses). No cases ended in
death, but all 5 cases required some treatment. Four of the
individuals received multiple vaccines prior to the
anaphylaxis episodes, but the investigators were able to
calculate the vaccine-specific risks of anaphylaxis. The
vaccine-specific risks were highest for DT at 21.2 cases per
million doses, with DTP-Hib combination vaccine and MMR having
the second-highest risks at roughly 3.5 cases per million
doses. DTP, hepatitis B, Hib, and oral poliomyelitis vaccine
(OPV) were all associated with 1 to 2 cases per 1 million
doses. The authors concluded that the risk of anaphylaxis is
extremely low after administration of vaccines, but they urged
practitioners to be prepared to deal with this rare
occurrence.
The Future of Rotavirus Vaccine
In an invited plenary session, Paul Offit, MD,[16]
Children's Hospital of Philadelphia, Pennsylvania, reviewed
vaccination issues for rotavirus disease, and the prospects
for a vaccine to replace Rotashield, the human-simian
combination vaccine that is now off the market owing to
association with intussusception. Rotavirus is responsible for
approximately 55,000 hospitalizations each year in US
children, and 20 to 40 deaths per year in the United States.
The morbidity and mortality rates are worse in the developing
world, making rotavirus a logical target for vaccines.
The previous rotavirus vaccine was a human-simian
"re-assortment" virus, basically a simian rotavirus backbone
with proteins from human-specific rotavirus strains attached
to induce antibody formation. The effectiveness trials
revealed that the vaccine was 70% to 100% effective against
"severe" disease. Intussusception was noted to be a potential
side effect of the vaccine during the trials (roughly 1 case
per 2200 recipients of vaccine compared with 1 case per 4600
placebo). Therefore, intussuception was included as a
potential complication of the vaccine in the package insert.
Most pediatricians are familiar with the rest of the story;
within 1 year following licensure, 15 cases of intussusception
were reported to the Vaccine Adverse Event Reporting Service.[17]
The case definition for intussusception for rotavirus vaccine
is intussusception within 42 days of vaccine receipt. Since
intussusception was not known to be a complication of natural
rotavirus infection, investigators wondered whether the
apparent increased rate of intussusception could be due to the
formulation -- the fact that the vaccine used a nonhuman
backbone. This question has led to development of a
bovine-based vaccine, again with human proteins added.
Although the data are unpublished, initial testing of the
new vaccine formulation included approximately 2000 infants
during the period from 1998-2000.[16] The company
that developed the vaccine has now expanded this cohort to
more than 60,000 children internationally to evaluate for rare
complications such as intussusception. Preliminary data from
this cohort have shown 12 cases of intussusception in 45,000
enrollees so far. Although the authors are blinded as to
whether the children with intussusception received the new
vaccine or placebo, only 4 of the 12 cases occurred during the
42-day period required to meet the case definition. Another
company is working on a human-strain, live, attenuated
rotavirus vaccine. Dr. Offit believes that these data
demonstrate that the new generation of rotavirus vaccines will
be safer, and that a safer and more effective vaccine for
rotavirus will available within the next few years.
