As the countdown for measles elimination has progressed,
increasing efforts have been made to confirm measles cases by
laboratory methods. As an additional measles serodiagnostic test,
a
staphylococcal protein A (SPA) adsorption test has recently been
adapted to measure measles-specific IgM (1,2). This test is based
on
the principle that SPA will bind IgG antibody and will permit its
removal from a serum specimen, allowing any residual measles IgM
antibody to be measured by routine hemagglutination-inhibition (HI)
testing (3).
The sensitivity and specificity of the SPA test were assessed
relative to sucrose gradient ultracentrifugation (SGU), the
standard
method for measuring measles-specific IgM, using 79 serum specimens
from patients clinically suspected of having measles (Table 1) (4).
The sensitivity of the SPA was 71% (45/63), and the specificity was
81% (13/16). In this study, a positive IgM detected by SPA was
almost
always confirmed as IgM by the SGU; of the 48 serum specimens
positive
by SPA, 45 (94%) were also positive by SGU. However, a negative
SPA
test did not mean IgM was absent; of the 31 specimens that tested
negative by the SPA test, 18 (58%) were positive by SGU.
Serum specimens from 36 measles cases confirmed by a four-fold
or
greater rise in complement-fixation or HI-antibody titer were used
to
determine when measles IgM becomes positive by SPA. Only six of 19
(32%) specimens collected 0-4 days after rash onset were positive
by
SPA compared with 12 of 17 (71%) specimens collected 5-21 days
following rash onset (X((2)) = 4.01, p = 0.045).
Reported by Viral Exanthems and Herpes Virus Br, Div of Viral
Diseases, Center for Infectious Diseases, Surveillance,
Investigations, and Research Br, Immunization Div, Center for
Prevention Svcs, CDC.
Editorial Note
Editorial Note: The techniques most commonly used to confirm
measles
infections serologically are the HI and the complement-fixation
(CF)
tests (3). A four-fold rise in measles-specific HI or CF antibody
titers between acute- and convalescent-phase serum specimens
confirms
measles infection. HI antibodies generally become detectable
within
the first several days following rash onset and peak approximately
2
weeks later (Figure 1) (5-7). Complement-fixation titers
frequently
follow the rise in HI titers, often by 1-3 days. However, there is
considerable individual variation; some persons reach peak HI and
CF
titers within the first few days after rash onset (5,8,9).
Measles-specific IgM antibodies may be detected shortly after rash
onset and peak within 10 days after rash onset; they are usually
undetectable by 30 days (10).
The SGU method (used most often to measure measles IgM) is
cumbersome and time-consuming and requires expensive and
sophisticated
equipment. The SPA adsorption test, although less sensitive than
SGU
for detecting IgM, is simple to perform and requires the addition
of
only one adsorption step to the serum-treatment procedure for the
measles HI assay. Laboratories that perform the HI assay should
consider adding the SPA technique for IgM measurement and should
establish internal quality control with known IgM positive and IgM
negative specimens. A positive test is presumptive evidence of
acute
measles infection. The three instances in which the SPA adsorption
test was positive and the SGU was negative may have been false
positives. However, it is possible that the SPA adsorption test
may
have detected IgM not detectable by SGU. A negative SPA adsorption
test, however, should not be interpreted as the absence of IgM.
The laboratory is more helpful for confirming measles cases
than
for ruling out measles as the cause of a rash illness. The
presence
of measles-specific IgM or the detection of a four-fold rise in
measles HI or CF antibody titers between acute- and
convalescent-phase
serum specimens confirms an acute measles infection. However, IgM
may
not be detected, even in specimens collected when antibody should
peak, and four-fold rises may go undetected, particularly if peak
titers were reached before an acute-phase specimen was drawn (11).
Laboratory confirmation should be sought for all suspected
cases
of measles occurring in the United States. However, decisions to
take
outbreak-control measures should be made on clinical and
epidemiological grounds, since laboratory confirmation may take
several weeks from rash onset, and the absence of laboratory
evidence
for measles infection may not rule out measles.
References
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NJ, eds. Diagnostic procedures for viral, rickettsial and
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Vesikari T, Vaheri A. Rubella: a method for rapid diagnosis of
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Black FL. Measles. In: Evans AS, ed. Viral infections of
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