Meningococcal Catch-Up Vaccination in the US • CID 2008:46 (1 January) • 1
M A J O R A R T I C L E
Economics of an Adolescent Meningococcal
Conjugate Vaccination Catch-up Campaign
in the United States
Ismael R. Ortega-Sanchez,1,aMartin I. Meltzer,2,aColin Shepard,3,bElizabeth Zell,1Mark L. Messonnier,1
Oleg Bilukha,3,bXinzhi Zhang,3,bDavid S. Stephens,3,4and Nancy E. Messonnier,1for the Active Bacterial Core
National Centers for
Diseases, Centers for Disease Control and Prevention, and
1Immunization and Respiratory Diseases,
2Preparedness Detection and Control of Infectious Diseases, and
4Emory University School of Medicine, Atlanta, Georgia
licensed quadrivalent meningococcal conjugate vaccine for routine use among all US children aged 11 years. A 1-
time catch-up vaccination campaign for children and adolescents aged 11–17 years, followed by routine annual
immunization of each child aged 11 years, could generate immediate herd immunity benefits. The objective of
our study was to analyze the cost-effectiveness of a catch-up vaccination campaignwithquadrivalentmeningococcal
conjugate vaccine for children and adolescents aged 11–17 years.
We built a probabilistic model of disease burden and economic impacts for a 10-year period with
and without a program of adolescent catch-up meningococcal vaccination, followed by 9 years of routine im-
munization of children aged 11 years. We used US age- and serogroup-specific surveillance data on incidence and
mortality. Assumptions related to the impact of herd immunity were drawn from experience with routine me-
ningococcal vaccination in the United Kingdom. We estimated costs per case, deaths prevented, life-years saved,
and quality-adjusted life-years saved.
With herd immunity, the catch-up and routine vaccination program for adolescents would prevent
8251 cases of meningococcal disease in a 10-year period (a 48% decrease). Excluding program costs, this catch-
up and routine vaccination program would save US$551 million in direct costs and $920 million in indirect costs,
including costs associated with permanent disability and premature death. At $83 per vaccinee, the catch-up
vaccination would cost society ∼$223,000 per case averted, ∼$2.6 million per death prevented, ∼$127,000 per life-
year saved, and ∼$88,000 per quality-adjusted life-year saved. Targeting counties with a high incidence of disease
decreased the cost per life-year saved by two-thirds.
Although costly, catch-up and routine vaccination of adolescents can have a substantial impact
on meningococcal disease burden. Because of herd immunity, catch-up and routine vaccination cost per life-year
saved could be up to one-third less than that previously assessed for routine vaccination of children aged 11 years.
In June 2005, the Advisory Committee on Immunization Practices recommended the newly
In the United States, the rate of bacterial meningitis
and sepsis caused by Neisseria meningitidis is high
among adolescents and young adults, and they have an
increased risk of significant long-term sequealae (e.g.,
amputations and hearing loss) or death from infection
Received 23 May 2007; accepted 4 September 2007; electronically published
30 November 2007.
Reprints or correspondence: Dr. Ismael Ortega-Sanchez, Centers for Disease
Control and Prevention, 1600 Clifton Rd., NE MS-A-47, Atlanta, GA 30333
Clinical Infectious Diseases2008;46:1–13
This article is in the public domain, and no copyright is claimed.
[1–3]. This elevated risk is likely related to higher rates
of asymptomatic nasopharyngeal carriage and the 10–
30 times higher transmission rates among adolescents,
compared with young children ; behavioral risk fac-
tors also facilitate transmission among adolescents .
The findings and conclusions expressed are those of the authors and do not
necessarily represent the views of the Centers for Disease Control and Prevention
or the US Department of Health and Human Services.
aI.R.O.-S. and M.I.M. are first authors.
bPresent affiliations: International Training and Education Center on HIV-
Ethiopia, Seattle, Washington (C.S.); National Centers for Environmental Health
(O.B.) and Chronic Disease Prevention and Health Promotion (X.Z.), Centers for
Disease Control and Prevention, Atlanta, Georgia.
cMembers of the study group are listed at the end of the text.
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2 • CID 2008:46 (1 January) • Ortega-Sanchez et al.
States with and without adolescent vaccination and herd immunity. The
population is stratified into 3 age groups: !11 years, 11–17 years, and
?18 years, with age transitions. Meningococcal disease occurs in all
age groups, after which the patient could recover (or die; datanotshown).
In addition to direct protection, vaccination generates indirect protection
to unvaccinated persons (gray) by reducing the risk of disease. Despite
vaccination and/or herd immunity protection, meningococcal diseasemay
still occur—although at lower rates—as represented by the dotted lines.
Each new child aged 11 years who is promoted to the group of persons
aged 11–17 years could or could not receive vaccination. Eachadolescent
aged 17 years who is unvaccinated, vaccinated, or recovered, is age
promoted into the respective group of adults aged ?18 years.
Model used to assess meningococcal disease in the United
A meningococcal conjugate vaccine that protects against ser-
ogroups A, C, Y, and W135 (MCV4) and has been shown to
be safe and immunogenic in persons aged 11–55 years  was
approved by the US Food and Drug Administration in January
2005. Previous analyses of the direct benefits of vaccination
have concluded that routine vaccination of children aged 11
years would be more cost-effective than routine vaccination of
infants . The Centers for Disease Control and Prevention’s
routine MCV4 vaccination of all US children aged 11 years .
However, evidence that MCV4 vaccination has a potential for
substantial benefits for unvaccinatedgroups,aswellasstrategies
designed to maximize the likelihood of herd immunity, are
worthy of consideration. Herd immunity from meningococcal
vaccination is well documented in the United Kingdom, where
widespread use of a meningococcal conjugate vaccine against
serogroup C (MCC) in adults aged 18 years resulted in a 57%–
67% reduction in the rate of N. meningitidis infection among
unvaccinated persons of all ages [9–11]. Such reductions in the
rate of infection may also be attributable to the long-lasting
immunity associated with meningoccoccal conjugate vaccines
[4, 9, 11].
We analyzed the cost-effectiveness of a catch-up vaccination
campaign designed to vaccinate most children and adolescents
aged 11–17 years with MCV4 within 1 year, followed byroutine
vaccination of successive cohorts of children aged 11 years. We
estimated both the direct and herd immunity benefits of vac-
cination versus no vaccination.
We constructed a stochastic (Monte Carlo) model to estimate
the impact on disease outcomes of a 1-time catch-up vacci-
nation campaign among persons aged 11–17 years in year 1,
followed by a routine vaccination program for cohorts of chil-
dren aged 11 years. For each age group, to calculate the total
number of annual cases of N. meningitidis infection with or
without a catch-up vaccination program, the model randomly
selected annual rate of incidence from the available data, which
was then multiplied by the age-specific population. In the anal-
ysis of meningococcal cases with a catch-up vaccination pro-
gram, a herd immunity effect was included. Case fatalities and
long-term sequelae were then calculated using age- and se-
quelae-specific rates. Finally, the cost of disease in the catch-
up vaccine scenario versus no vaccination was calculated. The
model repeated these calculations by running iterations until
the means of outcomes (e.g., cases, deaths, and costs) varied
by ?1.5% after each additional 100 runs.
To allow the modeling of special situations (e.g., targeting
outbreaks), we defined a population of 10 million with age
distribution equal to the entire US population , which in-
cludes 1 million persons aged 11–17 years (Appendix A; online
only). This population was followed up for a lifetime (i.e., the
analytical horizon) to account for cases of acute meningococcal
disease and related complications. Figure 1 illustrates the mod-
eling of herd immunity and 2 main transitions: (1) age pro-
motion and (2) changes in immunity status attributable to
vaccination against and/or recuperation from meningococcal
To account for lifetime benefits derived from the prevention
of permanent disabilities or premature deaths, we used age-
specific life expectancy estimates . A 10-year time-frame
accounted for the vaccination program costs. We discounted
all costs and health benefits at a 3% annual rate . All costs
were in 2005 US dollars, and analyses and simulations were
performed using @RISK, version 4.5.2 (Palisade).
Cases of meningococcal disease, by age group, were
estimated by multiplying annual disease incidence by the age-
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Meningococcal Catch-Up Vaccination in the US • CID 2008:46 (1 January) • 3
specific population (table 1). Age-specific incidence data of
diseases attributed to meningococcal serogroups C, Y, and
W135 were obtained from the Active Bacterial Core Surveil-
lance  for the period 1991–2002 (MCV4 provides protec-
tion against serogoups A, C, Y, and W135. Because cases of
menigococcal disease due to serogroup A are rare in the United
States, we did not include serogroup A in our model). Because
of differences in the disease incidence by age , rates were
formulated for 9 age groups (table 1). Ourincidenceprobability
distributions incorporated differences in incidence over time
(Appendix A; online only) .
Case-fatality ratios (CFRs) werecalculatedusing
the number of meningococcal disease–related deaths caused by
vaccine serogroups recorded by Active Bacterial Core Surveil-
lance for the period 1993–2002 . Because meningococcal
disease–related deaths are relatively rare and the annual data
are insufficient, we used the mean number of deaths per age
group (table 1 and table B3; online only). To model variability
in CFRs, we assumed that CFRs from allserogroupsrepresented
an upper limit of CFRs associated with meningococcal sero-
groups C, Y, or W135 (i.e., all reported meningococcaldisease–
related deaths were from meningococcal serogroups C, Y, or
W135) (table 1). On the basis of the minimum number of
deaths recorded during the period 1993–2002 by an alternative
surveillance system , we established a lower limit equal to
34% of the mean CFRs.
We used published probabilities [7, 16–18, 20]
to estimate the number of cases in survivors with 5 main com-
plications associated with meningococcal infection (table 1).
Because multiple complications in a single case are rare [16,
20], we assumed that their probabilities were mutually exclu-
sive. Thus, cases with 11 sequela were not considered, nor were
rare complications, such as renal failure or septic arthritis [7,
16]. We excluded the probability of meningococcal disease–
related removal of toes and fingers. Although obviouslyinitially
problematic for the patient, we assumed that such removals
would have a relatively lower impact on a patient’s quality of
estimated by multiplying the rate of vaccine effectiveness by
the rate of vaccine coverage. We assumed a 93% (range, 39%–
99%) potential vaccine effectiveness for MCV4, whichissimilar
to the MCC effectiveness observed in the United Kingdom [9–
11, 21], and 70% vaccine coverage (range, 66%–95%) [7, 11]
for both the catch-up vaccination and routinevaccinationcom-
ponents of the program.
To estimate the indirect impact from vac-
cinating adolescents, we used age-specific data from 2 UK stud-
ies reporting reductions in the number of cases in unvaccinated
Effective vaccine protection in adolescentswas
persons [10, 11] (table 1). Because 16 adolescent cohorts could
be vaccinated (7 cohorts in the catch-up campaign and 9 co-
horts of children aged 11 years who were routinely vaccinated)
during a 10-year period, a persistent reduction in the risk of
infection among unvaccinated persons was estimated. We as-
sumed that both direct and indirect vaccine-inducedimmunity
were maintained for 10 years.
Quality of Life
We accounted for decreases in quality of life among survivors
of meningococcal disease with long-term sequelae. Because
there are no published measurements of loss of quality of life
for meningococcal sequelae, we used published health utility
scores for conditions closely resembling each of the menin-
gococcal disease–related long-term sequelae (table 1) [7, 22,
24, 26, 31]. Because meningococcal disease follows a rapid clin-
ical course, we did not estimate decreases in quality of life
associated with the acute illness.
Costs of the Disease
Previously published estimates of direct costs [7, 31] were up-
dated to 2005 values using the Gross Domestic Productdeflator
(table 2) . We assumed that each patient with an acute case
would be hospitalized. Medical, public response, and indirect
costs associated with meningococcal disease were used to es-
timate the cost of illness per case in each age group. Costs were
broken down into the 2 following categories: (1) medical, in-
direct, and public response costs per case associated with the
acute illness phase and (2) long-term costs derived from com-
plications, permanent sequelae, or premature death (table 2).
Vaccination Program Cost
We assumed a cost per fully immunized vaccinee of $83 (range,
$20–$110), with a single-dose cost including vaccine and ad-
ministration costs. Using rates of adverse events associatedwith
MCC vaccine , we estimated risk and costs for both mod-
erate and severe adverse events. Quality-of-life decreases from
vaccine-related adverse events were not assessed. We assumed
10% (range, 0%–25%) vaccine wastage [41, 42]. Because the
catch-up and routine components would require different vac-
cination time arrangements among parents and vaccinees,costs
of time lost to receive the vaccine were not included. Other
programmatic adjustments to implement a catch-up program
for adolescents were not assessed.
To calculate the net costs or net present values of a catch-up
and routine vaccination program, we extrapolated the model
results (based on a 10 million population) to the entire US
population . Net present value is calculated as the (dis-
counted) difference between the dollars spent on the vacci-
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indices, vaccine efficacy and coverage, and adverse events.
Meningococcal disease–associated probabilities, case-fatality ratios, herd immunity, quality of life-years (QALY) saved
Invasive meningococcal disease, mean incidenceaper 100,000 population, age groupABCs (1991–2002)
!1 year 4.61.9–9.5 Empirical…
1 year2.1 0.2–3.8Empirical…
2–4 years1.1 0.3–1.5 Empirical…
5–10 years0.7 0.1–1.3Empirical…
11–17 years 0.50.2–1.3 Empirical…
18–22 years1.0 0.0–2.4 Empirical…
23–32 years0.7 0.2–1.2 Empirical…
33–64 years 0.3 0.1–1.5 Empirical…
Case-fatality ratio,cage group
0.8 0.4–1.2 Empirical…
ABCs (1993–2002), 
!1 year4.5 1.5–9.6 Normal (T)…
1 year 1.90.7–2.9 Normal (T)…
2–4 years5.9 2.0–6.5
11–17 years10.8 3.7–12.7
18–22 years9.3 3.1–13.7Normal (T)…
Meningococcal-associated disease outcomes,dproportion of patients
With skin scarring7.60–19Normal (T)[16, 17]
With single amputation1.90.5–10Normal (T)[16–18]
With multiple amputation1.20.02–6Normal (T)[16, 18]
With hearing loss8.82–20Normal (T)[16, 19]
With long-term neurologic disability2.10.02–11Normal (T)[17, 18, 20]
Percentage reduction of attack rates in
unvaccinated groups,eage group
?24 to 93Normal (T)…
?37 to 87Normal (T)…
?28 to 79 Normal (T)…
?11 to 61Normal (T)…
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Meningococcal Catch-Up Vaccination in the US • CID 2008:46 (1 January) • 5
 NA NALognormal…
 35 20–49Lognormal…
Skin scarring1 0.8–1 Triangular [16, 21, 22]
Single amputation 0.700.31–0.8Triangular [7, 23]
Multiple amputation 0.610.31–0.71 Triangular[7, 23]
Hearing loss 0.720.64–0.82 Triangular[24, 25]
Long-term neurologic disability
0.06 0–0.39 Uniform
Efficacy estimate 93% 73%–99%Triangular[27, 28]
Coverage 70%16%–95% Lognormal (T)[7, 29]
Moderate (fever, rash, faints, seizures)0.0003… NA 
Severe (anaphylactoid reaction) 0.000002… NA
tables B2, and B3. NA, not applicable (the variable was not used in the Monte Carlo simulation); T, truncated distribution.
aFor each iteration, a year is randomly chosen from the period 1991–2002, and the corresponding age-specific incidence rate is imputed (table B2; online
only). Stochastic simulation was performed on the basis of the range of values from the iterations. Because these rates are annual, no adjustments for time
trends or cycles were introduced. Vaccine serogroups included in the rates are C, Y, and W135. No cases of meningococcal serogroup A were identified in the
United States during 1991–2002.
bUsing base-case estimates and lower, most likely, and upper values of variables, probability distributions were fitted for the decision analysis (tables B4 and
B5; online only). Distributions were selected by ranking the performance of candidate distributions in the replication of base-case values as the most likely
scenarios. Alternatively, using only triangular distributions, the model was recalibrated, and simulations were recalculated; some sensitivity in results were
observed (e.g., 10% and 15% increase in cost per life-year saved and QALY saved, respectively).
cMean age- and serogroup-specific case-fatality ratios were calculated from the standardized ABCs data for the US population during the period 1993–2002,
using the proportion of deaths attributable to menningococcal disease serogroups C, Y, and W135 (Appendix A; online only).
dIn nonfatal cases, probabilities of complications were assumed to be independent, and cases involving multiple complications were excluded.Smallremovals,
like toes and fingers, were not included in amputations.
eAge-specific reductions in gross attack rates in unvaccinated persons, as reported in Balmer et al.  and Ramsay et al.  for meningococcal conjugate
vaccine against serogroup C were used to estimate the herd immunity impact for quadrivalent meningococcal conjugate vaccine. For each iteration, the model
randomly chose 1 of these rates and proportionally calculated the number of additional cases indirectly prevented in unvaccinated persons. Balmer et al. 
did not report reduction in attack rates for !1 year and 119 years. Negative lower values were truncated to zero for the probability distribution. Data shown are
the mean base-case estimates and 95% CIs. Attack reduction rates for the 20–24 year age group were not reported.
fSome parameter values and distributions are similar to those we used elsewhere [7, 31]. Outcome-related QALY saved is based on EuroQol (for skin scarring
and upper-bound amputation ), HUI (for lower-bound single and multiple amputations  and hearing loss for death children ), SF-36 instrument and HUI-
2 (for postcochlear implant hearing loss ), and HUI-3 (for neurologic disability ). The total number of quality-adjusted life years lost was estimated by
multiplying the years of life living with the long-term sequela by the sequela-specific health utility score.
gEfficacy and adverse events values correspond to meningococcal conjugate vaccine against serogroup C, as cited by Shepard et al. .
A summary of Active Bacterial Core surveillance (ABCs) data used in the model are shown in online-only Appendix A and Appendix B, tables B1,
nation program and dollars saved because of disease episodes
averted through vaccination . Cost-effectivenessratioswere
calculated for 4 outcomes: cost per case prevented, death
averted, life-year saved (LYS), and quality-adjusted life-year
(QALY) saved. These ratios were calculated by dividing the net
present value by the number of disease outcomes prevented.
Consistent with recommendations , LYS and QALY saved
were also discounted, and productivity losses attributable to
death were not included in calculating dollars per LYS or QALY
Probabilistic sensitivity analyses (using the Monte Carlo pro-
cedure) were performed on values and distributions of inputs.
In addition, we re-ran the model to examine the impact of
varying the cost of vaccination ($50, $83, and $110 per ado-
lescent vaccinated) and the effect of the herd immunity (0%–
100% of that measured in the United Kingdom, in increments
of 20%). These 2 inputs were chosen for this type of sensitivity
analysis, because intervention costs impact budgets most di-
rectly and degree of herd immunity is yet to be measured in
the United States.
Some geographic areas in the United States repeatedly re-
corded a higher-than-average incidence of meningococcaldis-
ease . Thus, to model the economics of targeting just
those areas of relatively high incidence, we re-ran the model
using data from counties with incidence rates ?1.57 cases
per 100,000 population (Centers for Disease Control and Pre-
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Table 2. Cost of meningococcal-associated disease, vaccination, and vaccine-associated adverse events.
Invasive meningococcal disease
Public response cost
Value of work time lost
Sequelae-specific or lifetime costs per case in patients with
Skin scarring: medical careb
Other (prothesis and rehabilitation)
Value of permanent disabilityc
Other (prothesis and rehabilitation)
Value of permanent disabilityc
Value of permanent disabilityc
Long-term neurologic disability
Value of permanent disabilityc
Premature death,eage group
Cost to vaccinate an adolescentf
Moderate (fever, rash, faints, seizures)
Severe (anaphylactoid reaction)
50% on either side; 
5770 (2849–8547) Normal50% on either side; 
17,886 (8832– 26,497)
120% single amputation
b General (T)
[7, 25, 39]
83 (20–110) Assumption; 
Monte Carlo simulation; T, truncate distribution.
aUsing base-case estimates and lower and upper ranges, probability distributions are fitted for the decision analysis.
bSequelae-specific or long-term medical costs include costs for skin grafting procedures and wound care (skinscarring),rehabilitation,fittingand/ormaintenance
of prosthetic limb(s) (single or multiple amputations), cochlear implant surgery, and hearing device, including upgrades and maintenance (hearing loss).
cAssumes a 20% (single amputation), 30% (multiple amputation), 33% (hearing loss), and 100% (neurologic disability) reduction in lifetime labor market
earnings. Age-specific present value of lifetime labor market earnings (men and women) at a 3% discount rate for 2003 US dollars are taken from Grosse .
dNeurologic disability includes cost of long-term residential care and age-specific special education.
eAge-specific estimates of productivity losses because of premature death are based on human capital approach (i.e., societal value of an individual’s life is
equivalent to the value of productivity lost, as measured by the present value of the individual’s future income stream). Weighted mean wages for male and
female individuals in the United States (labor market earnings) and the value of unpaid labor (household production) using age-specific life expectancy  were
fBase-case vaccination costs include a weighted and hypothetical value of vaccine price, administration costs, wastage costs, and costs of adverse events
associated with vaccination with quadrivalent meningococcal conjugate vaccine.
Costs were adjusted for their social constant value in the economy using the Gross Domestic Product deflator. NA, estimates were not used in the
vention, Active Bacterial Core Surveillance, unpublished
data). The rate of 1.57 cases per 100,000 population corre-
sponds to the 75th percentile of reported rates and is higher
(96%) than the mean rate of 0.8 cases per 100,000 population
among the general population .
Without a vaccination program, an average of 1674 cases of
meningococcal disease attributable to serogroups C, Y, and
W135 would occur each year in the United States (figure 2).
A catch-up vaccination program for persons aged 11–17 years
in year 1, followed by routine vaccination of children aged 11
years in each of the following 9 years, would avert a mean of
156 cases annually (a 9% reduction) because of direct protec-
tion only. Including herd immunity would increase the annual
number of cases averted to 825 (a48% reduction).Thus,almost
four-fifths of all prevented cases would be attributable to herd
Ten-year projections of meningococcal disease outcomes
with and without a vaccination program are shown in table 3
(figure A1; online-only). Assuming full herd immunity, the
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Meningococcal Catch-Up Vaccination in the US • CID 2008:46 (1 January) • 7
values from Monte Carlo simulations). The number of cases in the base-case scenario (i.e., in patients who were vaccinated) is represented by
diamonds. For this scenario, the annual incidence of meningococcal disease attributable to serogroups C, Y, and W135 would be ∼0.8 cases per
100,000 population . The reduction in cases after a catch-up vaccination in persons aged 11–17 years in year 1 and routine vaccination of children
aged 11 years during the following 9 years is represented by 2 extreme scenarios: (1) a direct-protection-only (absence of herd immunity) scenario
(triangles), averting a mean of 156 cases (9%) per year (*a decrease in incidence to 0.72 cases per 100,000 population or 1530 cases annually); (2)
direct and full herd immunity protection (squares), averting a mean of 825 cases (48%) per year (**a decrease in incidence to 0.42 cases per 100,000
population or 922 cases annually). Full herd immunity assumed an impact in proportions equivalent to that of the UK experience with meningococcal
conjugate vaccine against serogroup C, as reported in Balmer et al.  and Ramsay et al. .
Expected number of cases of meningococcal disease attributable to serogroups C, Y, and W135 per year in the United States (median
catch-up and routine vaccination program would prevent 8251
cases (undiscounted) over 10 years. This reduction in cases
would result in saving 36,831 life-years (or 15,264 life-years
when discounted) or 69,383 QALYs (or 27,150 QALYs when
Net Returns and Costs
After discounting, meningococcal-associated disease (attribut-
able to vaccine-containing serogroups) would cause $999 mil-
lion in medical costs, $72 million in public response costs, $29
million in parents’ work time costs, and $1753 million infuture
productivity costs in a 10-year period in the UnitedStates(table
4). A fully implemented catch-up vaccination campaign, fol-
lowed by routine immunization in subsequent years, would
save, before program costs, a total of $1471.2 million over 10
years (table 4). At a cost of $83 per vaccinee, the catch-up and
routine vaccination program would cost ∼$3268 million in the
10-year period. Forty-five percent of these costs would be
needed to finance the catch-up vaccination component of the
program. Consequently, at $83 per vaccinee, the catch-up and
routine vaccination program would have a societal net cost of
$1797 million ($2717 million for payers), and at $110 per vac-
cinee—which is, increasingly, a more reasonable cost per vac-
cinee—the societal net costs would be $2912 million ($3832
million for payers).
After accounting for averted medical, public response, work
loss, and other costs from prevented episodes ofmeningococcal
disease, a catch-up and routine vaccination program (at $83
per vaccinee) would cost the public ∼$223,000 per caseaverted,
$2.6 million per death prevented (table 4), $127,000 per LYS,
and $88,000 per QALY saved (table 5). At $110 per vaccinee,
the payer and societal costs per LYS would increase to $206,000
and $185,000, respectively, and the societalcostperQALYsaved
would be $119,000. By contrast, at $20 per vaccinee, a vacci-
nation program would becost savingfromasocietalperspective
only (data not shown).
Changes in herd immunity.
percentiles) net costs per LYS at various levels of indirect pro-
tection provided to unvaccinated persons by the catch-up and
routine vaccination program for adolescents are presented in
figure 3. At a herd immunity equivalent to only 20% of that
reported by the United Kingdom, the catch-up and routine
The mean (and 5th and 95th
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8 • CID 2008:46 (1 January) • Ortega-Sanchez et al.
without catch-up and routine vaccination of persons aged 11–17 years.
Projected cumulative number of meningococcal disease outcomes in a 10-year period with and
Acute meningococcal cases
With skin scarring
With single amputation
With multiple amputations
With hearing loss
With long-term neurologic disability
Life-years lost (discounted)
QALYs lost (discounted)
127,572 (62,064– 203,483)
53,051 (25,744– 84,061)
58,188 (27,956– 94,474)
25,521 (12,208– 40,894)
outcomes are C, Y, and W135. It was assumed that there was full herd immunity impact equivalent in proportions to that in the UK
experience with meningococcal conjugate vaccine against serogroup C. QALY, quality adjusted life-year.
Data are no. of outcomes (95% CI), unless otherwise indicated. Serogroups included in the meningococcal disease
vaccination program has a mean societal cost of $414,000 per
LYS (5th and 95th percentiles, $232,000–$860,000). If the herd
immunity protection is proportionally similar to that in the
United Kingdom, a 70% decrease would be observed in the
mean cost per LYS (mean cost per LYS, $127,000; 5th and 95th
percentiles, $46,000–$377,000) (figure 3).
Changes in vaccination costs.
vaccination costs are shown in table 4. In general, if other
factors remain unchanged, a $30 increase in the mean cost of
vaccination (to $110) would increase the cost per LYS by
An adolescent vaccination campaign
targeting regions where the initial incidence of meningococcal
disease is ?1.57 cases per 100,000 population is more cost-
effective than a campaign covering all US adolescents.Targeting
these counties with high incidence of meningococcal disease
(top 25% of reported incidence range) would decrease the so-
cietal cost per LYS by two-thirds (figure 4). Furthermore, this
targeting strategy seems to be less sensitive to changes in vac-
cination costs than does the strategy of vaccinating all US ad-
olescents (i.e., in figure 4, the graph line for the former is less
steep than that for the latter).
The net societal costs for 3
Vaccination of adolescents in a combined publicly funded
catch-up and routine vaccination program with MCV4 would
result in net economic costs to society, even under the most
optimistic scenarios. However, such a program holds the
greatest promise for substantial and quick reduction in overall
meningococcal disease burden in the United States. Because
vaccination benefits would be largely a result of the reduction
of attack rates in unvaccinated groups (81% of averted cases),
the presence or absence of herd immunity is the critical de-
terminant. If a catch-up vaccination program induces herd im-
munity to the extent seen in the United Kingdom, this strategy,
although more expensive, would be more cost-effective than
the current adolescent vaccination or routineinfantandtoddler
In addition, a catch-up vaccination program targeted to
counties where meningococcal disease is highly endemic would
be 3 times more cost-effective than a catch-up and routine
vaccination program for all US adolescents. Because ∼40% of
cases are accrued to the top 25% of counties where menin-
gococcal disease is highly endemic (Centers for DiseaseControl
data), geographically targeted recommendations might maxi-
mize the cost-effectiveness of a conjugate meningococcal vac-
Two economic studies on meningococcal vaccination have
been previously published [7, 31]. In general, routine MCV4
vaccination programs for younger children are less cost-effec-
tive than such programs for adolescents . By contrast, a
catch-up and routine vaccination strategy or a strategy of only
MCV4 vaccination of children aged 11 years would be ∼2 times
more cost-effective than vaccination with meningococcal poly-
saccharide vaccine of first-year college students living in dor-
mitories. The limited duration of protection  and protection
to unvaccinated persons  may explain the reduced cost-
effectiveness of meningococcal polysaccharide vaccine, com-
pared with MCV4.
by guest on May 21, 2011
Meningococcal Catch-Up Vaccination in the US • CID 2008:46 (1 January) • 9
Projected cumulative costs with and without catch-up and routine vaccination program
Meningococcal disease–associated costs
Public response costs
Parent work loss
Future productivity costs
Total disease cost
Catch-up and routine vaccination costs
Cost for vaccination of an adolescent
$50 per vaccinee
$83 per vaccinee
$110 per vaccinee
Net cost ($83 per vaccinee)
Medical and public response
Cost per case lost or prevented
Medical public response
Cost per life lost or saved
Medical and public response
NA, not applicable.
An adolescent catch-up vaccination program with MCV4
would not only be costly to society, but would also be less cost-
effective when compared with other childhood vaccine inter-
ventions, such as the 1-dose varicella vaccination program. In
this respect, the adolescent catch-up MCV4 vaccination pro-
gram would be similar to the pneumococcal conjugate vacci-
nation program , although herd immunity was not con-
sidered in the study of pneumococcal conjugate vaccination.
Two recent studies involving adolescents have also considered
herd immunity impacts; these studies involved vaccination of
adolescents against pertussis  and vaccination of adolescent
girls against human papillomavirus . These studies have
shown that their vaccination programs have lower cost to so-
ciety per LYS or QALY saved (i.e., are more cost-effective),
compared with a catch-up vaccination program for all adoles-
cents or routine immunization of children aged 11 years .
The key feature of our analysis is the assumption of indirect
protection benefits attributed to MCV4. The analysis tried to
credit the vaccine’s value, not only for directly reducing mor-
tality and morbidity among vaccinated persons, but also for
the reduction in the attack rates among unvaccinated persons.
Although marked reductions in serogroup C carriage (150%)
 and attack rates among unvaccinated persons have been
observed in the first 4 years following vaccination with MCC
in the United Kingdom, long-term persistence of herd im-
munity is still uncertain.
Although our estimates with herd immunity correspond to
an optimistic scenario, our base-case analysis is conservative
when assessing the indirect protection of the vaccine, because
the model estimates reductions in attack rates that are some-
where between the estimates reported by Balmer et al.  and
Ramsay et al.  (table 1). When using only the most recent
and, thus, highest reduction rates , the number of cases
prevented increases by 4.8%, and cost per LYS and QALY saved
decrease by 18% (i.e., this vaccination strategy becomes less
costly or more cost-effective) (table 5, figure A2; online only).
Policymakers evaluating this analysis should also take into ac-
count the additional benefits of preventing morbidityandmor-
tality among unvaccinated persons, particularly among ado-
lescents, because in this age group, ∼46% of cases  and 52%
by guest on May 21, 2011
Cost-effectiveness of catch-up and routine and targeted meningococcal vaccination programs in the United States.
(no. of doses)
Cost per LYSa
per QALY saveda
Catch-up and routine vaccination of all US persons aged 11–17 yearsc
Base-case current analysis
Catch-up and routine vaccination of all US persons aged 11–17 years
(Ramsay’s estimates for the reduction of attack rates)
Catch-up and routine vaccination of persons aged 11–17 years in
areas of high endemicity
Routine vaccination of persons aged 11 years (with 10-years
duration of protective efficacy)c
Vaccination of first-year college students living in college
Meningitis cases prevented in infants by PCV7 under routine
vaccination against pneumococcal disease
Cost per life-year saved (LYS) and per quality adjusted life-year (QALY) saved from publications before 2003 were converted to 2005 US dollars using Gross Domestic Product deflator. All reported
studies used an annual discount rate of 3% for future costs, benefits, and health outcomes. MCV4, quadrivalent meningococcal conjugate vaccine; MPV4, quadrivalent meningococcal polysaccharide vaccine;
PCV7, heptavalent pneumococcal conjugated vaccine.
aValues were rounded to the nearest thousand.
bPayer’s perspective may include either medical and direct nonmedical costs or only medical costs.
cFor comparisons with the results in Shepard et al. , estimates were obtained after changing duration in vaccine protection and standardizing the discounting procedure.
by guest on May 21, 2011
Meningococcal Catch-Up Vaccination in the US • CID 2008:46 (1 January) • 11
children aged 11 years, under different herd immunity scenarios. Median values are represented by diamonds, and 5th and 95th percentiles are
represented by triangles (from Monte Carlo simulations). Scenarios with herd immunity assumed an impact in proportions equivalent to the reduction
in attack rates in vaccinated persons in the UK experience with meningococcal conjugate vaccine against serogroup C [10, 11].
Projected net cost per life-year saved (LYS) from combined catch-up vaccination of persons aged 11–17 years and routine vaccination of
persons aged 11–17 years and routine vaccination of children aged 11 years (squares) and (2) targeted catch-up vaccination of persons aged 11–17
years in areas where meningococcal disease is highly endemic (dots). Positive error bars (not shown) in the targeted strategy are overlapped with
the negative error bars (not shown) in the strategy involving all US adolescents. It was assumed that catch-up vaccination is targeted to the counties
with the highest (top 25%) incidence of meningococcal disease attributable to serogroups C, Y, and W135 (i.e., counties with 1.57 cases per 100,000
population, which is ∼96% higher than the incidence in the general population [∼0.8 cases per 100,000 population]). All strategies assumed a herd
immunity impact in proportions equivalent to that of the UK experience with meningococcal conjugate vaccine against serogroup C [10, 11].
Projected net cost per life-year saved (LYS) for 2 strategies under various vaccination cost scenarios: (1) catch-up vaccination of all US
of deaths associated with vaccine serogroups are attributableto
Although health-related quality-of-life effects from sequelae
were estimated, we have not attempted to place a value on the
pain and suffering of the patients, anxiety for the parents, and
psychological trauma insurvivorswithsequelae.Likewise,other
associated costs beyond public response to outbreaks(e.g.,pub-
lic fear and media hysteria)  were not included. Although
these costs are commonly observed , they are difficult to
by guest on May 21, 2011
12 • CID 2008:46 (1 January) • Ortega-Sanchez et al.
Initially, the limited vaccine supply will not allow a catch-
up vaccination of 20 million US adolescents (70% of the US
adolescent population). Therefore, alternative strategies that
have been considered are a phased catch-up vaccination pro-
gram for adolescents at highest risk and routine vaccination of
pre-adolescents; a catch-up vaccination program only in coun-
ties where meningococcal disease is highly endemic, in addition
to a routine vaccination program for pre-adolescents; or com-
bining the use of polysaccharide and conjugate vaccines for
catch-up and routinevaccination[48–50].However,thesestrat-
egies were not considered in our analysis, because the indirect
protection impact derived from the smaller proportion of ad-
olescents vaccinated with MCV4 would be overestimated by
the model. A different approach, including transmission dy-
namic models , specific disease carriage data, and various
critical assumptions, would be required for their proper
Although no evidence exists, concerns remain that menin-
gococcal serogroup B might replace vaccine serogroups in both
carriage and disease , which might lessen the expected direct
and herd immunity effects. For our analysis, we assumed that
the proportion of other non–vaccine-preventable serogroups
causing disease would remain stable, as has been observed so
far in the United Kingdom . Likewise, rates of MCV4-
associated adverse events were assumed to be similar to those
observed in the United Kingdom with MCC, and the duration
of immunity was estimated to be 10 years, with no decrease in
efficacy. However, postimplementation surveillance and re-
search should evaluate the effects of catch-up vaccination on
the incidence of meningococcal disease among unvaccinated
persons, frequency of documented or potentially new adverse
events, duration of vaccine efficacy, use of antimicrobial drugs,
and carriage and disease attributable to nonvaccineserogroups.
ACTIVE BACTERIAL CORE
Emerging Infections Programs: G. Rothrock, P. Daily, L. Gel-
ling, D. Vugia, and A. Reingold (California); S. Burnite and K.
Gershman (Colorado); N. Barrett, J. Hadler, P. Mshar, and C.
Petit (Connecticut); K. Arnold, S. Bulens, D. Stephens, W.
Baughman, and M. Farley (Georgia); D. Blythe, L. Sanza, A.
Schmidt, R. Hollick, and L. Harrison (Maryland); J. Rainbow,
C. Lexau, L. Triden, and R. Lynfield (Minnesota); R. McPher-
son, M. Bright, and M. Huber (Missouri); D. Morse, P. Smith,
N. Bennett, B. Anderson, S. Zansky, N. Spina, and G. Smith
(New York State Department of Health); L. Smithee, G. Istre,
and P. Quinlisk (Oklahoma); K. Stefonek, M. Barber, P. Cieslak,
and A. Thomas (Oregon Department of Health Services); A.
Craig, B. Barnes, C. Gilmore, W. Schaffner, and T. McMinn
(Tennessee Department of Public Health); and K. Cushing, A.
Cohn, J. Theodore, T. Clark, T. Skoff, S. Schmink, C. Pleatman,
C. Van Beneden, C. Wright, and L. Mayer (Centers for Disease
Control and Prevention).
We thank Dr. Walt Orenstein, for his insightful comments and collab-
oration, and Mary McCauley, for her comments on the manuscript.
Potential conflicts of interest.
All authors: no conflicts.
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