from Medscape Pediatrics

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.