In February 2005, the US Advisory Committee on Immunization Practices recommended the new meningococcal conjugate vaccine (MCV4) for routine use among 11- to 12-year-olds (at the preadolescent health-care visit), 14- to 15-year-olds (before high-school entry), and groups at increased risk. Vaccine distribution started in March; however, in July, the manufacturer reported inability to meet demand and widespread MCV4 shortages were reported. Our objectives were to determine early uptake patterns among target (11-12 and 14-15 year olds) and non-target (13- plus 16-year-olds) age groups. A post hoc analysis was conducted to compare seasonal uptake patterns of MCV4 with polysaccharide meningococcal (MPSV4) and tetanus diphtheria (Td) vaccines.
We analyzed data for adolescents 11-16 years from five managed care organizations participating in the Vaccine Safety Datalink (VSD). For MCV4, we estimated monthly and cumulative coverage during 2005 and calculated risk ratios. For MPSV4 and Td, we combined 2003 and 2004 data and compared their seasonal uptake patterns with MCV4.
Coverage for MCV4 during 2005 among the 623,889 11-16 years olds was 10%. Coverage for 11-12 and 14-15 year olds was 12% and 11%, respectively, compared with 8% for 13- plus 16-year-olds (
A surge in vaccine uptake between June and August was observed among adolescents for MCV4, MPSV4 and Td vaccines. The increase in summer-time vaccinations and vaccination of non-targeted adolescents coupled with supply limitations likely contributed to the reported shortages of MCV4 in 2005.
Menactra®, a quadrivalent meningococcal conjugate vaccine (MCV4) designed to prevent invasive disease due to
Distribution of MCV4 started in March, and ACIP recommendations became official on May 30, 2005 (upon publication in the Morbidity and Mortality Weekly Reports)[
The VSD is a collaborative project between CDC and eight US managed care organizations (MCOs) who have approximately six million members (2% of the US population)[
To examine MCV4 uptake during March-December 2005, we used 2005 vaccination data for adolescents 11-16 years of age from five of the eight MCOs (defined here as MCO A-E) who participated in ongoing data analyses for vaccine adverse events [
Based on ACIP's recommendations for MCV4, adolescents 11-12 and 14-15 years of age were defined as "target" age groups. Although the ACIP recommendations specified 15 years of age to approximate high school entry, we combined 14 and 15 year olds to represent high school entry because census data estimate that 64% and 22% of 9th graders are 14 and 15 years of age, respectively [
We calculated the number of MCV4 doses administered by month and age group. To calculate MCV4 coverage, the number of vaccinated adolescents was divided by the total number of adolescents enrolled in the age group per month. The monthly enrollment for each MCO was based on 2005 data for all except MCO E; we used 2004 data for MCO E because 2005 data were not available at the time of this analysis. The yearly enrollment by age for each MCO was estimated by averaging the 12 monthly totals. We used SAS 9.1 to calculate chi-square p-values, risk ratios and 95% confidence intervals for 11-12 year olds and 14-15 year olds to receive MCV4 compared to 13- plus 16-year-olds.
Additionally, in February 2006, we queried each of the five MCO principal investigators about whether or not: 1) the MCO experienced a "vaccine shortage" during 2005 and 2) if they were aware of any local or state legislation that could have impacted MCV4 during 2005.
We focused on the Td vaccine because it was the only vaccine recommended for adolescents during 2003-2004; unlike hepatitis B, measles mumps and rubella, and varicella vaccines, it is not recommended until age 11-12 and is not given in young children. For Td uptake, we combined preservative-free and non-preservative free tetanus and diphtheria toxoids, adsorbed, for adult use. To estimate MPSV4 and Td uptake, we combined 2003 and 2004 VSD data for adolescents 11-16 years of age from the same five MCOs (i.e A-E) used for examining MCV4 uptake. Two years of data were combined to maximize sample size and allow us to examine vaccination trends before MCV4 was licensed. Coverage for MPSV4 was not calculated since this vaccine was not routinely recommended for all 11-16 year old adolescents and eligibility (i.e. denominator) could not be accurately ascertained in this study. Similarly, Td coverage was not estimated because the indications for Td use (e.g. for use after tetanus-prone injury) were not known. 2005 data were not analyzed since the introduction of MCV4 likely affected the uptake patterns of MPSV4 (i.e. MCV4 substituted for MPSV4) and Td (e.g. uptake increased perhaps due to more immunization visits related to introduction of MCV4).
Therefore, for both MPSV4 and Td, we calculated the number of doses administered by month. MPSV4 uptake is presented for all adolescents 11-16 years combined because of low overall uptake. Td uptake is presented by single year of age from 11-16 years because 1) grouping distorted the patterns observed for single year of age and 2) Td recommendations did not parallel those of MCV4.
The number of adolescents 11-16 years of age in the five MCOs totaled 623,889 (Table
MCV4 uptake during 2005 among 11-16 year old adolescents by MCO and age group
| MCO | Study Population | All adolescents Number (%) Vaccinated | Percent Vaccinated by Age Group | |||||
|---|---|---|---|---|---|---|---|---|
| 11-12 | 14-15 | 13+16 | ||||||
| Yes† | No | 19724 | 3680 | (18.7) | 33.7* | 13.8* | 9.6 | |
| No | No | 31404 | 9518 | (30.3) | 31.9* | 32.0* | 27.0 | |
| No | Yes | 13456 | 1832 | (13.6) | 15.2* | 13.4 | 12.3 | |
| Unknown‡ | Yes | 261544 | 17934 | (6.9) | 6.4 | 7.7* | 6.4 | |
| Unknown‡ | Yes | 297761 | 31308 | (10.5) | 13.9* | 10.3* | 7.5 | |
| -- | -- | 623889 | 64272 | (10.3) | 12.3* | 10.5* | 8.2 | |
MCV4 - Meningococcal conjugate vaccine
MCO - Managed care organization
§Based on self-report by principal investigator at each MCO
†MCO is located in a state with legislation requiring meningococcal vaccination for adolescents in residential schools and postsecondary institutions that provide housing for students.
‡MCO did not provide a response; however, the state(s) these MCOs are located in did(do) not have any meningococcal vaccination legislation[
*
The coverage by MCO for all adolescents combined ranged from 7% to 30%; the lowest coverage was in the two largest MCOs (D and E). Coverage for the 11-12 and 14-15 year groups ranged from 6% to 34% and 8% to 32%, respectively (Table
Figure
During 2003-2004, a total of 1,837 MPSV4 vaccinations were administered to adolescents 11-16 years of age. Uptake for 11-16 year olds started to increase in May and peaked in June (Figure
During 2003-2004, a total 240,480 Td vaccinations were administered to adolescents 11-16 years of age. The number of vaccinations administered decreased with age, ranging from 29% among 11 year olds to 5% in the 16 year olds (data not shown). Overall, adolescents 11 and 12, 13 and 14, and 15 and 16 years of age appear to have similar seasonal patterns with the number of vaccinations rising substantially from May to June and peaking in August (Figure
MCV4 coverage during the first ten months after its licensure (March-December 2005) was about 11% among targeted adolescents. Non-targeted adolescents (13 and 16 year olds) received a sizeable portion (27%) of the total administered doses. Of the five MCOs, the two largest reported vaccine shortages and had the lowest coverage. The surge in MCV4 uptake during the summer months coupled with the uptake among non-targeted adolescents likely contributed to the vaccine ordering limits and reported shortages. Seasonal uptake patterns of MPSV4 and Td (prior to MCV4 availability) show a similar increase in uptake during the summer, though the month of the peak uptake varied.
Prior to the availability of national coverage data,[
Vaccine uptake among adolescents appears to have a seasonal pattern. MCV4 uptake started increasing in May and peaked in July. Examination of MPSV4 and Td also shows increases in uptake during summer months. The earlier peak for MPSV4 suggests that different factors may play a role; however, given the small number of MPSV4 vaccinations (compared to Td and MCV4), it is difficult to hypothesize possible reasons. It is possible that MCV4 would have peaked in August (before the start of school), like Td, if not for the vaccine limits placed by the manufacturer (in July). Michigan's vaccine registry data showed a similar surge in MCV4 uptake during summer months suggesting that this seasonal increase is not limited to adolescents enrolled in managed care [
Coverage was lower in the three MCOs reporting shortages (MCO C, D, and E) than in the other two. This included the two largest MCOs where implementation of a new vaccine recommendation is likely more challenging compared to smaller MCOs. Coverage differences within and between MCOs could have been affected by the nature of the shortage and/or the implementation plan at the MCO; we were unable to gather detailed information from all MCOs. The low coverage among the targeted adolescents in MCO D was likely related to their change in policy due to the shortage which instructed providers to defer vaccinating 11-12 and 14-5 year olds and preferentially vaccinate college freshman. School immunization laws have had a marked impact on both the incidence of vaccine preventable disease and immunization coverage in the United States. A limited number of studies suggest that much of the success of adolescent immunization programs in the United States is a direct result of these requirements[
In February 2005, the ACIP carefully considered supply, anticipated demand and disease epidemiology when recommending routine use of MCV4 for adolescents 11-12 and 14-15 years of age[
This study has some limitations. First, these results based on the VSD data may not be generalizable to uninsured adolescents and coverage during 2005 was likely lower in the overall US adolescent population; however, with standardized protocols, VSD data can be used to obtain timely vaccination coverage of recently and newly recommended vaccination. Second, we could not account for vaccinations that might have been administered outside the VSD MCO; however, considering the high price of MCV4 (list price in 2005 was $82), it is unlikely that many adolescents received this vaccine outside the plan. Third, this study is unable to account for the effect of any local events on seasonality of vaccination trends such as a case of meningococcal disease. Finally, we could have underestimated coverage among the target groups due to misclassification; some adolescents included in the 13+16 year-old, "non-target" age group, may in fact have been vaccinated according to recommendations if they were starting high school at those ages. However, the impact on our estimates is likely negligible given US school enrollment estimates.
These data from the VSD confirm the anecdotal reports of providers that vaccinations increase during summer months. This seasonal trend is likely related to vaccination requirements for summer recreational activities, upcoming school requirements and convenience for parents. Parents need to recognize that regular preventive visits provide an opportunity for obtaining timely vaccinations. In addition, the comparatively high proportion of vaccine doses administered to adolescents outside of the target groups illustrates the challenges associated with implementing complex vaccination recommendations. These factors combined with the limitations in vaccine supply resulted in a failure to meet MCV4 demand during the summer of 2005, and should be considered in the future as new vaccines are recommended to avoid potentially preventable shortages. Avoiding supply disruptions is essential to a key aspect of increasing vaccination in adolescents: reduction of missed opportunities for vaccinations during all healthcare visits.
The authors declare that they have no competing interests.
SL: Participated in study conception and design, data analysis and drafting the manuscript. DF: Participated in study conception and design, data analysis and drafting the manuscript. EW: Participated in design, data collection and analysis and drafting the manuscript. PM: Participated in design and data analysis and drafting the manuscript. GL: Participated in design and data analysis and drafting the manuscript. FZ: Participated in design and data analysis and drafting the manuscript. RD: Participated in design and drafting the manuscript. All authors read and approved the final manuscript.
The pre-publication history for this paper can be accessed here:
We would like to thank John Stevenson, Yuan Kong, and Dr. Greg Wallace for their assistance with this study. Additionally, we wish to thank the following members of the Vaccine Safety Datalink Study Project: James Baggs, Julianne Gee, (Centers for Disease Control and Prevention); Tracy Lieu, Katherine Yih, and Richard Fox, (Harvard Pilgrim);Roger Baxter, MD; Nicky Klein, and Ned Lewis, (Northern California Kaiser Permanente); Steve Jacobson, and Wansu Chen, (Southern California Kaiser Permanente);Lisa Jackson and Darren Malais, (Group Health Cooperative); Allison Naleway, John Mullooly, and Loie Drew, (Northwest Kaiser Permanente); Simon Hambridge, Jason Glanz, David McClur, and Christina Clarke, (Kaiser Permanente of Colorado);James Nordin, and Amy Butani, (Health Partners of Minneapolis); Edward Belongia, James Donahue, and Jeremy McCauley (Marshfield Clinic).