Published Ahead of Print 23 January 2013.
2013, 20(3):443. DOI:
Clin. Vaccine Immunol.
Brian H. Shirts, Ryan J. Welch and Marc Roger Couturier
Testing and Revaccination
and Rubella IgG and Costs Associated with
Seropositivity Rates for Measles, Mumps,
Updated information and services can be found at:
This article cites 10 articles, 4 of which can be accessed free at:
more»articles cite this article),
Receive: RSS Feeds, eTOCs, free email alerts (when new
Information about commercial reprint orders:
To subscribe to to another ASM Journal go to:
on June 10, 2014 by guest
on June 10, 2014 by guest
Seropositivity Rates for Measles, Mumps, and Rubella IgG and Costs
Associated with Testing and Revaccination
Brian H. Shirts,a,bRyan J. Welch,bMarc Roger Couturiera,b
Department of Pathology, University of Utah, Salt Lake City, Utah, USAa; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, USAb
Nevertheless, maintaining population immunity is important to
Prevention Advisory Committee on Immunization Practices
(ACIP) considers receipt of one documented dose of the MMR
vaccine as evidence of immunity to rubella and two docu-
mented doses of the MMR vaccine as evidence of immunity for
mumps and measles (2). In the absence of vaccination docu-
mentation, serological testing is accepted as laboratory evi-
dence of immunity (2).
We investigated immunization screening practices using ret-
rospective analysis of measles, mumps, and rubella IgG testing
performed at ARUP Laboratories (Salt Lake City, UT). Our goals
evidence of immunity among individuals screened, to evaluate
observed ordering practices, and to estimate potential cost-effec-
tiveness of vaccination versus serological screening.
This study was approved by the University of Utah Institu-
tional Review Board (IRB no. 7275). A deidentified data set was
created of all 159,257 tests for measles, mumps, and rubella IgG
antibodies ordered at ARUP Laboratories between 1 February
2011 and 31 January 2012. We linked measles, mumps, and/or
uals from 646 institutions in 44 states. Antibody titers were mea-
sured for more than one virus in 51,026 individuals and for all
performed at ARUP Laboratories according to the manufacturer’s
enzyme immunoassays (EIA) manufactured by SeraQuest (Miami,
FL) by following standard EIA protocols with sample index value
1.09 (equivocal), and ?1.09 (positive). Rubella testing was per-
formed using the Siemens rubella quantitative IgG chemilumines-
IgG seropositivity rates were high for all three viruses, regard-
highest for rubella and lowest for mumps, which correlates with
previous studies that show mumps titers decrease most rapidly
(3–8). It was assumed that the 10,210 individuals tested for all
than for acute infection, since natural infection with three viruses
would be extremely uncommon in the United States, and recom-
ince the introduction of the measles, mumps, and rubella sin-
gle injectable vaccine (MMR) in 1971, the incidence of each
significantly lower (P ? 0.001) than when all three titers were
tested, indicating that single orders may be testing for natural
infection rather than immunity (Table 2).
77.1% were tested for both measles and mumps IgG and 20.0%
were tested for measles, mumps, and rubella IgG. The high pro-
portion of testing that is ordered for measles and mumps IgG in
combination is likely a result of the ACIP guidelines, which con-
sider persons with a single dose of a rubella vaccine as immune;
this, combined with the disparate signs and symptoms of measles
and mumps, suggests that this test order combination is being
used as a marker for vaccine-induced immunity and not acute
are ordered, it can be calculated that if only measles and mumps
would be missed (individuals that would test positive for both
measles and mumps IgG but should be revaccinated as a result of
having a negative or equivocal rubella IgG titer; Table 1). Because
of the low positivity rate of mumps IgG relative to other viral
titers, it may by hypothesized that this alone could be used as a
determination of whether revaccination is needed. However, if
mumps IgG was ordered alone, 8.6% of individuals requiring re-
Received 13 August 2012 Returned for modification 10 October 2012
Accepted 14 January 2013
Published ahead of print 23 January 2013
Address correspondence to Marc Roger Couturier, firstname.lastname@example.org.
B.H.S. and R.J.W. contributed equally to this work.
Copyright © 2013, American Society for Microbiology. All Rights Reserved.
TABLE 1 Serostatus in individuals tested for measles IgG, mumps IgG,
and rubella IgG (n ? 10,210)
Rubella statusMumps status
% (n) who are measles IgG:
Positive (n ? 9,539)Positive
(n ? 671)
March 2013 Volume 20 Number 3Clinical and Vaccine Immunologyp. 443–445cvi.asm.org
on June 10, 2014 by guest
vaccination would be missed (summation of all patients that had
all three tests ordered that had a positive mumps IgG titer but a
negative measles IgG and/or rubella IgG; Table 1).
A simplified cost analysis was done to determine whether it is
appropriate to test for all three viral titers and follow up with vacci-
logical testing. Because ACIP guidelines require two doses of the
a single dose for rubella, individuals lacking immunity were parti-
tioned appropriately. To determine the cost of testing, the Medicare
reimbursement cost of $57.99 for all three tests was used (10). The
cost of the vaccine is $52.07 based on the CDC vaccine fee schedule
(11). For this analysis, only the 10,210 patients with all three tests
$85.81 per patient if testing was performed followed by appropriate
vaccination based on the negative viral titers (Table 3). This cost is
is administered without serological testing in cases where immunity
vaccination in certain cases without serological testing can also be
made due to the low incidence of vaccine-related complications, es-
pecially in individuals who may have been previously vaccinated (2,
care reimbursement rate, which may not be an accurate price for all
institutions. Each facility must determine its cost of testing and
whether it outweighs the cost of vaccination alone using this simple
According to the data presented, which is likely representative of
individuals without other evidence of immunity and represents a
large geographic sampling that can effectively account for regional
differences in vaccination rates, laboratory evidence of immunity to
tion. It is important to note that while serology can be used as evi-
sles, mumps, and rubella immunity in targeted populations. For in-
stance, the common practice of screening measles and mumps anti-
bodies as a surrogate for vaccine-induced immunity will identify a
majority of nonimmune individuals, whereas screening for only
mumps antibodies would be ill advised for identifying nonimmune
individuals. Institutions using the latter approach should strongly
balance financial expenses in determining institutional policy,
screening for immunity cannot be subjected to insensitivity of the
1. Centers for Disease Control and Prevention. 1987. Mumps—United
States, 1985–1986. MMWR Morb. Mortal. Wkly. Rep. 36:151–155.
2. Centers for Disease Control and Prevention. 1998. Measles, mumps, and
rubella—vaccine use and strategies for elimination of measles, rubella,
and congenital rubella syndrome and control of mumps: recommenda-
tions of the Advisory Committee on Immunization Practices (ACIP).
MMWR Morb. Mortal. Wkly. Rep. 47:1–57.
3. Date AA, Kyaw MH, Rue AM, Klahn J, Obrecht L, Krohn T, Rowland
J, Rubin S, Safranek TJ, Bellini WJ, Dayan GH. 2008. Long-term
persistence of mumps antibody after receipt of 2 measles-mumps-rubella
(MMR) vaccinations and antibody response after a third MMR vaccina-
tion among a university population. J. Infect. Dis. 197:1662–1668.
4. Davidkin I, Jokinen S, Broman M, Leinikki P, Peltola H. 2008. Persis-
tence of measles, mumps, and rubella antibodies in an MMR-vaccinated
cohort: a 20-year follow-up. J. Infect. Dis. 197:950–956.
5. Dayan GH, Quinlisk MP, Parker AA, Barskey AE, Harris ML, Schwartz
JM, Hunt K, Finley CG, Leschinsky DP, O’Keefe AL, Clayton J,
Kightlinger LK, Dietle EG, Berg J, Kenyon CL, Goldstein ST, Stokley
SK, Redd SB, Rota PA, Rota J, Bi D, Roush SW, Bridges CB, Santibanez
TA, Parashar U, Bellini WJ, Seward JF. 2008. Recent resurgence of
mumps in the United States. N. Engl. J. Med. 358:1580–1589.
6. LeBaron CW, Forghani B, Beck C, Brown C, Bi D, Cossen C, Sullivan
BJ. 2009. Persistence of mumps antibodies after 2 doses of measles-
mumps-rubella vaccine. J. Infect. Dis. 199:552–560.
7. LeBaron CW, Forghani B, Matter L, Reef SE, Beck C, Bi D, Cossen C,
Sullivan BJ. 2009. Persistence of rubella antibodies after 2 doses of mea-
sles-mumps-rubella vaccine. J. Infect. Dis. 200:888–899.
8. Peltola H, Jokinen S, Paunio M, Hovi T, Davidkin I. 2008. Measles,
gramme. Lancet Infect. Dis. 8:796–803.
TABLE 2 Seropositivity rates of measles IgG, mumps IgG, and rubella IgG stratified by test ordering patterns
Median age (% 18?
Seropositivity rate (%)
Measles IgGMumps IgGRubella IgG
Measles IgG (n ? 11,359)
Mumps IgG (n ? 22,049)
Rubella IgG (n ? 13,587)
Measles IgG, mumps IgG, rubella IgGb(n ? 10,210)
aTests listed are exclusive.
bSeropositivity of individual test orders was significantly less than when all tests were ordered when adjusted for age and sex (P ? 0.001).
TABLE 3 Weighted cost of serological testing for all three virus
antibody titers plus vaccination or vaccination alone
No. (%) of
Associated cost ($)
aIndividuals with negative or equivocal viral titers to rubella.
bIndividuals with negative or equivocal viral titers to measles.
cIndividuals positive for all three viral titers.
dWeighted average cost ? (cost of vaccination and testing ? percentage of individuals
requiring vaccination) ? (cost of testing ? percent of individuals not requiring
Shirts et al.
cvi.asm.orgClinical and Vaccine Immunology
on June 10, 2014 by guest
9. Immunization Action Coalition. 2011, posting date. Ask the experts:
measles, mumps and rubella. Immunization Action Coalition, St. Paul,
10. Centers for Medicare & Medicaid Services. 2012. Clinical diagnostic
laboratory fee schedule 2012. CMS, Baltimore, MD. http://www.cms.gov
12. Centers for Disease Control and Prevention. 2012. Recommended adult
immunization schedule—United States, 2012. MMWR Morb. Mortal.
Wkly. Rep. 61:1–7.
13. Centers for Disease Control and Prevention. 2011. General recommen-
dations on immunization—recommendations of the Advisory Commit-
tee on Immunization Practices (ACIP). MMWR Recomm. Rep. 60:1–64.
14. Centers for Disease Control and Prevention. 12 November 2009, posting
date. Acceptable presumptive evidence of immunity: mumps prevention
MMR-Associated Seropositivity and Vaccination Costs
March 2013 Volume 20 Number 3cvi.asm.org 445
on June 10, 2014 by guest