Previous Article | Next Article 
Clinical and Diagnostic Laboratory Immunology, September 2000, p. 739-744, Vol. 7, No. 5
1071-412X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Comparison of Five Serologic Tests for Diagnosis of
Acute Infections by Chlamydia pneumoniae
Kenneth
Persson1,* and
Jens
Boman2
Department of Clinical Microbiology,
Malmö University Hospital, S-205 02 Malmö,1 and Department of
Clinical Virology, The University Hospital of Umeå, S-901 85 Umeå,2 Sweden
Received 24 January 2000/Returned for modification 5 April
2000/Accepted 14 June 2000
 |
ABSTRACT |
Serology is often used to diagnose acute infections by
Chlamydia pneumoniae. In this study paired sera from
patients with acute respiratory tract infection during an epidemic of
C. pneumoniae infections were examined by five different
antibody tests. These tests were the complement fixation (CF) test, the
microimmunofluorescence (MIF) test, a recombinant enzyme immunoassay
(rEIA) (Medac) based on a recombinant lipopolysaccharide of chlamydia
and measuring antibodies to a common chlamydial antigen, and two tests
that utilize preparations of C. pneumoniae organisms, the
SeroCp-EIA (Savyon) (with preserved lipopolysaccharide) and the LOY-EIA
(Labsystems) (without this antigen). Both of the last two tests should
measure specific antibodies to C. pneumoniae, although
cross-reacting antibodies may also be detected by the SeroCp-EIA. Acute
infection of C. pneumoniae was serologically confirmed in
44% of the cases by at least two different tests. Using an expanded
"gold standard," i.e., the presence of significant reactions in at
least two tests, the sensitivity of the CF test was 69%, that of the
MIF test was 88%, that of the rEIA was 89%, that of the LOY-EIA was
96%, and that of the SeroCp-EIA was 92%. Specificity was high for all
methods, but adjustments of diagnostic criteria were made to several of the tests. The basis for these adjustments and supportive data are
presented. Infections of C. pneumoniae were detected in
patients from 8 to 83 years of age. Two peaks in the incidence of such infections were observed: one among young teenagers and a second in
adults 30 to 45 years of age, corresponding to parents of young teen-agers. The tests were equally sensitive in different age groups.
Reinfections seemed to be rare.
| |
INTRODUCTION |
Serological diagnosis has been
important to unravel the clinical manifestations of acute infections by
Chlamydia pneumoniae. Isolation of the organism or detection
of its nucleic acid by PCR has extended the diagnostic arsenal. These
methods can provide early diagnosis, which might be helpful for
accurate treatment. Serology based on analysis of paired sera will
detect acute infection even after antibiotic treatment has been started
and might be useful to discriminate between infections by C. pneumoniae and Chlamydia psittaci.
The complement fixation (CF) test based on the common
lipopolysaccharide (LPS) antigen of chlamydia has been used for many years to detect acute infections by C. psittaci. After
C. pneumoniae was recognized and infection by this new agent
could be confidently diagnosed by the microimmunofluorescence (MIF)
test, many cases previously detected by the CF test and thought to be
cases of ornithosis were found to in fact be infections by C. pneumoniae (12, 18). Although the CF test can detect
acute infections by C. pneumoniae, its sensitivity has been
considered low for such infections, especially in reinfection
(13). The MIF test has been of paramount importance to
detect acute infections by C. pneumoniae and to describe the
prevalence of such infections. The performance of the test depends on
several factors, including the antigen preparations used and the
experience of the person reading the test. The test has been questioned
for different reasons. Some have found it unspecific during acute
infections due to cross-reactive antibodies (5, 17). Others
have questioned its ability to discriminate acute infections, either by
being nonreactive where other tests suggest infection (3, 7,
9) or by identifying cases which cannot be confirmed by other
means or which seem unlikely for other reasons (10, 11, 14,
15). Serological tests in an enzyme-linked immunoassay (ELISA)
format might overcome some of the potential problems with the MIF test.
Three new tests have been evaluated in this study and compared to the
MIF and CF tests for the serological diagnosis of acute infections by
C. pneumoniae. One of the new tests is based on an acylated
recombinant lipopolysaccharide from chlamydia (recombinant enzyme
immunoassay [rEIA]) and has been previously evaluated using the same
diagnostic criteria (19). The other tests utilize
preparations of C. pneumoniae organisms with (SeroCp-EIA) or
without (LOY-EIA) LPS.
| |
MATERIALS AND METHODS |
Patients.
During an epidemic of infections by C. pneumoniae, 261 consecutive patients with cases of acute
respiratory tract infection were chosen for the study. Patients were
eligible if paired sera were available and the symptoms indicated
respiratory tract infection. Most patients were treated as outpatients.
Twenty-one cases were excluded from the final assessment, as all tests
could not be performed due to lack of serum. Therefore, 240 cases were
finally studied. The study group consisted of 103 males and 137 females. The median age for the males was 31 years, with a range of 1 to 90 years, and that of the females was 40 years, with a range of 6 to
75 years. The sera were collected from late 1994 to the first months of
1996. Initially, the CF and MIF tests were used to detect cases of
acute infection. Later the sera were also examined by rEIA, LOY-EIA,
and SeroCp-EIA.
CF test.
The CF test was performed by standard procedures.
The chlamydial antigen for this test was obtained from the State Serum
Institute (Copenhagen, Denmark). A fourfold titer rise or a titer of 64 or higher was considered diagnostically significant.
MIF test.
The MIF test was performed by previously described
methods (4, 23). Slides with antigens of Chlamydia
trachomatis, C. psittaci, and C. pneumoniae
were obtained from Labsystems OY (Helsinki, Finland). In this test the
C. pneumoniae and C. trachomatis antigens have
been treated to remove the LPS antigen, which is, however, retained in
the C. psittaci antigen. Chlamydial immunoglobulin G (IgG),
IgA, and IgM antibodies were determined. All IgM reactions were
confirmed after the IgG antibodies had been removed with RF Absorbent
(Behringwerke, Marburg, Germany). Fourfold titer rises of IgG and/or
IgA and/or a titer of 
16 in IgM was considered diagnostically
significant. High titers of IgG or IgA that did not change between
acute- and convalescent-phase sera were not considered diagnostic per
se and will be discussed below.
rEIA.
The rEIA kits were kindly provided by the Medac
Company (Wedel, Germany). The test is based on a chemically modified
recombinant LPS from chlamydia (6). IgG, IgA, and IgM
antibodies to the chlamydial LPS are determined separately with this
test. IgG antibodies are removed before measuring IgM antibodies to
minimize the risk of false-positive reactions due to rheumatoid factor.
Serum pairs with differences in optical density values for IgG or IgA
of more than 0.3 or with values of >2.0 were titrated in two, three,
or four steps to determine the titer differences. Titers were
calculated according to the manufacturer's instructions. A threefold
change of titer of either IgG or IgA or a twofold change of both IgG
and IgA was considered diagnostically significant (19). IgM
titers of 200 or more were accepted as a diagnostic sign, although a
positive titer of 50 should be considered positive according to the manufacturer.
LOY-EIA.
The LOY-EIAs (Labsystems OY, Helsinki, Finland) for
C. pneumoniae IgG, IgA, and IgM antibodies are indirect
solid-phase EIAs based on an antigen from C. pneumoniae
devoid of LPS. The analysis with the LOY-EIA was performed by Tamara
Tuuminen, Labsystems OY, Helsinki, Finland, without knowledge of the
results from the other tests.
The results for IgG and IgA are expressed as enzyme immunounits (EIU),
which are calculated as: (
Asample 
Ablank)/(
Acalibrator Ablank) ×
n. The assays are
calibrated to correspond to the
inverted titers of the MIF assay
(Labsystems OY), with
n = 130
for the IgG EIA and
n = 30 for the IgA EIA. A level of 30 EIU
for IgG is
considered the limit of detection (corresponding to
a titer of 32 in
the MIF assay), and a level of 8 EIU in the IgA
EIA is the
corresponding limit of detection (titer of 8 in the
MIF
assay).
The criterion for a diagnostically significant change of EIU values for
IgG and IgA is a 1.5-fold change of EIU in the zones
below 130 EIU (for
IgG) and 50 EIU (for IgA). When the first sample
shows an EIU value of
130 or more for IgG and 50 for IgA, a 1.3-fold
change is considered
significant.
The results of the
C. pneumoniae IgM EIA are expressed as a
signal/cutoff (S/CO) ratio after subtraction of the blank value.
Samples with a S/CO ratio of less than 0.5 are considered negative
samples, those with a S/CO ratio of more than 1.1 are considered
positive, and samples with a S/CO ranging from 0.5 to 1.1 are
considered
equivocal.
SeroCp-EIA.
Kits for the SeroCp-EIA (Savyon Diagnostics
Ltd., St Ashdod, Israel) were kindly provided by the local
representative and the manufacturer. Kits for detection of IgG, IgA,
and IgM antibodies were used according to the recommendations of the
manufacturer and as delineated in the kit inserts.
A significant titer change of IgG and/or IgA antibodies was set to be a
twofold titer change after consulting the company.
After a preliminary
assessment of the IgM results, an adjustment
of the criterion for a
significant IgM titer was introduced. A
significant IgM reaction was
considered to be twice the cutoff
value and not >1.1 times the cutoff
at a dilution of 1:105 as
the insert of the manufacturer suggested. The
reasons for changing
the criterion are discussed
below.
| |
RESULTS |
Diagnostically significant reactions were found in 118 cases by at
least one test (Table 1). When MIF was
used as the "gold standard," the sensitivity for the CF test was
69% and those for the three different ELISAs were 87 to 95%, with
specificities of between 91 and 93% (Table
2). Some cases had significant titer changes detected by the ELISAs but not by MIF. It may be possible that
the MIF test is not the most sensitive test and that the gold standard
ought to be changed. Therefore, an expanded gold standard was adopted,
where a true positive case was defined as one for which there were
significant reactions by at least two tests. Such confirmed reactions
were found in 106 cases, while 12 cases (10%) were positive by only
one test and were considered to have false-positive reactions. Resolved
sensitivities, specificities, and predictive values are presented in
Table 3. The sensitivity was lowest for
the CF test at 69%, while it ranged between 87 and 96% for the other
tests. The LOY-EIA was somewhat more sensitive than MIF and rEIA but
not significantly different from the SeroCp-EIA. The specificities were
high at 99% for all tests except the SeroCp-EIA, which had some
unconfirmed IgM reactions also with the modified criteria used.
View this table:
[in this window]
[in a new window]
|
TABLE 2.
Sensitivity and specificity of the different serological
tests, using MIF as the gold standard, in acute infections
by C. pneumoniae
|
|
View this table:
[in this window]
[in a new window]
|
TABLE 3.
Performance of the different tests for the diagnosis of
acute infections by C. pneumoniae using an expanded gold
standard (i.e., with at least two tests showing significant reactions)
|
|
The patients with confirmed positive cases consisted of 45 males with a
median age of 32 years (range, 8 to 83 years) and 61 females with a
median age of 40 years (range, 12 to 75 years). The rate of infections
by C. pneumoniae in males was 45 of 103 (44%), and that in
females was 61 of 137 (45%). The age-specific distribution of
serologically confirmed acute infections is shown in Fig.
1. Two peaks were evident: one in young
teenagers and a second in adults 30 to 45 years of age, corresponding
to parents of teenagers.
View larger version (29K):
[in this window]
[in a new window]
|
FIG. 1.
Rates of serologically confirmed cases of acute
infections by C. pneumoniae in different age groups.
|
|
As seen in Table 1, most positive cases (56%) had reactions in all
five tests, while an additional 26% of the positive cases had
significant reactions in four tests, 11% had significant serological signs in three tests, and 7% were positive in two different tests.
CF test and rEIA.
The CF test and the rEIA are both based on
the chlamydial LPS antigen. The sensitivity of the CF test was 69%,
and that of the rEIA was 87%. One or both of the tests reacted in 97 of 106 (92%) of the confirmed positive cases. In 67 of the 73 cases
positive by the CF test (92%), the rEIA was also positive. One
unconfirmed significant reaction occurred by the CF test, and two such
reactions were observed with the rEIA.
In the rEIA significant antibody reactions were seen most often in IgA
(Tables
4 and
5). A titer of 200 was chosen as the
cutoff for significant IgM reactions. The manufacturer suggests
titers
over 50 as positive and diagnostically significant. With
a cutoff value
for positive IgM reactions at 100 in this material,
an additional 18 positive cases would have been obtained, none
of which was accompanied
by significant changes of IgG or IgA
in the same test and all of which
were unconfirmed by any other
test. Two more cases had IgM titers of
between 100 and 200 and
were also positive by other tests and would
thus have increased
sensitivity for the rEIA. Decreasing the cutoff
limit to 50 as
suggested by the insert would have increased the number
of true
positive cases obtained by the test by 8 but would also have
detected
19 unconfirmed cases.
MIF test, LOY-EIA, and SeroCp-EIA.
In the MIF test used here,
the LPS antigen has been removed from the C. pneumoniae and
C. trachomatis antigens but not from the C. psittaci antigen. The LOY-EIA is based on organisms of C. pneumoniae devoid of the LPS antigen, while the SeroCp-EIA uses
elementary bodies containing LPS. These three tests therefore measure
specific antibodies to C. pneumoniae but may pick up
cross-reactive antibodies to the LPS, depending on the preparation of antigen.
The sensitivity of the MIF test was 88%, and that of the LOY-EIA was
96%. The difference was statistically significant (chi-square
test
with Yates correction,
P = 0.04). The sensitivity of
the
LOY-EIA was also higher than that of the rEIA. As seen in Table
5,
the LOY-EIA most often showed significant reactions in IgM
and IgG,
while diagnostic changes were less common with
IgA.
The sensitivity of the SeroCp-EIA was 92%, and this test showed
significant reactions most often in IgM (89%) and much less
often in
IgG and IgA (36 and 31%, respectively). Seven unconfirmed
reactions
occurred, with IgA and IgM being the antibody classes
involved (Table
6). It was decided that the criteria for
the
SeroCp-EIA would be a twofold change in IgG and/or IgA and/or
a
titer of
200 for IgM. Had a titer change of 1.5 times been
used
instead for IgG and IgA, another four positive cases confirmed
by other
methods would have been picked up, although four unconfirmed
cases
would also have become positive. If the cutoff for IgM had
been lowered
to 100 in the SeroCp-EIA as suggested by the insert,
another four true
cases would have been detected but 25 positive
cases unconfirmed by
other tests would also have occurred. There
was agreement between the
MIF test and the SeroCp-EIA in 223 of
240 cases and between the MIF
test and the LOY-EIA in 222 of 240
cases.
When the rEIA or the MIF test was combined with the LOY-EIA, all
positive cases would have been detected (Table
1). Other
combinations
would have detected between 100 and 105 of the 106
positive cases. The
correlation between the IgG titers found in
the MIF test and those
determined by LOY-EIA was rather good (
rs = 0.82 [Spearman's correlation test]).
Single-serum testing.
With the diagnostic criteria chosen,
testing of the first serum showed a significant antibody reaction in
only 48 to 71% of the true positive cases in the different tests
(Table 7). In the cases of the MIF test,
rEIA, and LOY-EIA, this meant significant IgM reactions. Such reactions
in the first serum were detected in 72 to 87% of all IgM-positive
cases.
High MIF titers and acute C. pneumoniae infection.
High titers, of 256 or more, that were unchanged between acute- and
convalescent-phase sera were detected in 21 cases without confirmed
acute C. pneumoniae infection. Prior sera were available in
16 of these cases and had been collected on average 6 years before the
present disease (range, 1 to 17 years). All of these cases had prior
antibody titers. Eleven of the 16 cases had prior titers of 128 or
more, and 5 cases had titers of 32 or 64. Among the 106 positive cases,
18 had high unchanging titers of IgG antibodies to C. pneumoniae. Of these 18 cases, 13 had IgM antibodies in MIF and 5 had diagnostic findings by other tests. Four of these 13 cases with IgM
antibodies where prior sera were available had no or low antibody
titers in previous sera. Thus, only 5 of 26 cases with a stable titer
of 256 or more in MIF had current infection by C. pneumoniae
confirmed by other tests, while 21 cases with high titers remained
unconfirmed by other tests and also had prior antibodies in most
instances. Thirteen cases had stable IgG titers of 512 or more, of
which three had serological signs of acute infection by C. pneumoniae by other tests. Previous sera were available in seven
cases. Among the three cases with positive reactions in other tests,
previous sera were available in two cases, of which one lacked prior
antibody and the other had a low titer of 32 in prior serum. Previous
sera from 5 of the 10 cases with high MIF IgG titers only all had
antibody titers of 128 or more in prior sera.
Reinfections.
The CF test has been considered less sensitive
for reinfections by C. pneumoniae. It is reasonable to
assume that primary infections are more common in teenagers than among
adults. The proportions of positive cases by the CF test and the
LOY-EIA were compared for different age groups (Table
8). There was no statistically significant difference between these proportions (chi-square test). IgM
antibodies are not expected in reinfections. In this study there was no
significant difference in the rate of such antibodies detected by the
LOY-EIA test in different age groups (Table 8).
Of the 106 cases with serological signs of acute infection by
C. pneumoniae, 65 (61%) had IgG antibody titers of 32 or more
in the
first serum. Titers of 128 or more were detected in 25
(38%) of these
65 cases. We were able to examine previously collected
sera from 32 of
the 106 cases with acute infection. These sera
had been collected on
average 7 years earlier, with a range of
1 to 19 years. Most of these
prior 32 sera were antibody negative,
and only 3 had low titers of 32 or less. Of the 32 cases with
prior sera, 9 had a titer of 64 or more
in the acute-phase serum.
Only three of these nine cases had prior
antibodies at a low titer
of 32 or less, and six cases were antibody
negative. Reinfection
was therefore not demonstrated in any case with
titers of 64 or
more in prior
sera.
| |
DISCUSSION |
During an epidemic of acute respiratory tract infections by
C. pneumoniae, the diagnosis could be serologically
confirmed (i.e., positive by at least two tests) in 106 of 240 cases of acute respiratory tract infection (44%). In addition, 12 (10%) unconfirmed (i.e., positive in only one test) significant serological reactions were observed. This is an unusually high frequency of acute
infections by C. pneumoniae but reflects the epidemiological situation at that time. Currently, the rate of serological diagnoses of
C. pneumoniae infections is <2% in the same area. The
spectrum of positive cases would represent both primary infections and reinfections, as the youngest child with C. pneumoniae
infection was 8 years old and the oldest patient was 83 years of age.
The use of a proper gold standard is critical. Serological tests should
preferably be confirmed by tests that demonstrate the organism, like
cell culture or PCR, although these methods also have limitations. In
this study this was not possible, as no material was available for such
tests. New serological tests may, however, be compared to established
ones like the MIF and CF tests, although the latter is considered less
sensitive. In this study a commercial MIF test which should be
generally available was used. We have previously evaluated rEIA using
exactly the same diagnostic criteria for IgG and IgA as in this study
and found good agreement with MIF, although false-positive reactions were observed for parvovirus infections. Therefore, we lacked previous
experience only with the LOY-EIA and the SeroCp-EIA. An expanded gold
standard was finally adopted, where significant reactions in at least
two tests constituted a true-positive case. Of the 106 positive cases,
100 were confirmed by MIF and/or CF, which are both established
methods. Another five cases were confirmed by rEIA, which we have
evaluated previously and found to have a good specificity with the
criteria used. Thus, only 1 of 106 true-positive cases was included
where LOY-EIA and SeroCp-EIA confirmed one another with other tests
being negative.
The criteria for serodiagnosis of acute chlamydial infection are
important. For the CF test, a fourfold titer change or a titer of 64 or
more was considered significant. In the case of MIF, a fourfold titer
change of IgG and/or IgA antibodies and/or an IgM titer of at least 16 was considered diagnostic. High titers of IgG antibodies have been
suggested as a marker for current infection by C. pneumoniae
(13, 21), but this has been questioned by several authors
(10, 11, 14, 15). In a previous study, titers of 512 or more
in our test system did not predict acute respiratory infections, as
similar rates of such titers were observed among patients and controls
(19). In this study, with a prevalence of C. pneumoniae infections of 44%, only 5 of 26 cases (19%) with an
IgG titer of 256 or more in the MIF test had significant antibody reactions by other tests. Among the 21 cases with high IgG titers in
the MIF test but lacking significant reactions by other tests, all
cases had previous antibodies when prior sera were available (16 sera).
Thus, only about 20% of cases with high IgG titers in the MIF test
represented current infection as indicated by the other tests, while
the majority had high titers in prior sera, probably reflecting
previous infection, and lacked diagnostic signs of acute infections by
other tests.
Diagnostic criteria in the rEIA for infections of C. pneumoniae or C. psittaci have been established in a
previous study (19). It became obvious during this study
that the significance of IgM titers is problematic, and a titer of 200 or more was adopted as a diagnostic sign of acute infection. The use of
a lower titer would have affected specificity rather than sensitivity.
This adjustment of diagnostic criteria therefore seemed justified.
The diagnostic criteria for the LOY-EIA were suggested by the
manufacturer, and those for SeroCp-EIA were decided after consultation with the manufacturer. The criterion for a positive IgM reaction in the
SeroCp-EIA differs from that given in the insert of the kit. Had a
lower titer been used, several additional unconfirmed cases would have occurred.
Reinfections would be assumed to be more common at older ages, but the
CF test seemed to perform equally well for older patients. In fact, the
LOY-EIA demonstrated equal proportions of IgM-positive cases in
different age groups. Reinfection has been suggested to be indicated by
a titer rise of IgG antibodies without an IgM response in patients with
prior antibodies (13). In this study, 65 cases of C. pneumoniae infection (61%) had IgG antibodies by the MIF test in
the acute-phase serum and might be reinfections. Where prior sera were
available, only 3 of 32 such sera had low-titer antibodies, and 29 were
antibody negative. Reinfection could not be confirmed in any case with
a prior titer of 64 or more and seemed to be a rare event. In contrast,
reinfections have been considered rather common in several reports
(1, 2, 8). In those studies, patients with reinfections had
milder clinical symptoms than those with primary infection or were
asymptomatic. The patients in our study were all symptomatic, and all
had sought medical attention for their symptoms.
Recently, the rEIA has been evaluated by three other groups. For single
sera the test performance was poor in comparison to culture
(16). Even with paired sera, the test failed to detect acute
infection in the majority of the cases. Another study reported rather
good agreement between different serological tests and detection of
C. pneumoniae by PCR or culture (22). A poor
correlation was found between rEIA and PCR in a third study, but only a
few positive cases were detected (20).
The MIF test has been considered difficult to perform and has an
element of subjective assessment. In this study, all but one reaction
suggesting acute infections in the MIF test could be confirmed by other
tests. In fact, 84 of the 94 positive cases by MIF could be confirmed
by two or three other tests, and 9 cases were confirmed by one of the
other tests, while one reaction remained unconfirmed. The positive MIF
cases were confirmed by an independent LPS-based test in 86 of the 94 cases.
The usefulness of serology for diagnosis of acute infections by
C. pneumoniae has been questioned. Several authors have not been able to consistently find an antibody response in cases with C. pneumoniae infection demonstrated by culture or PCR
(3, 7, 9). Other studies have reported antibody responses
regularly in culture-positive or PCR-positive cases (4, 24).
These differing results cannot be explained at present. Differences in
the patients studied may be one factor, as some studies have involved
children with chronic conditions like asthma, and other studies have
focused on acute respiratory infections in adults. Acute infections are
expected to generate an antibody response with titer changes, while
detection of C. pneumoniae in long-term asymptomatic cases
may be unaccompanied by a significant antibody titer change. It is
hoped that these differences will be resolved in the future.
We have studied only patients with acute symptomatic respiratory
infections. Currently, there is a growing interest in the possible
existence of persistent infection of C. pneumoniae and its
link to coronary artery disease. Serological markers have been
suggested for such persistent infections based on epidemiological studies. The criteria used in this study to diagnose acute infections were based on a dynamic change of antibody titers. Serological markers
for latent or persistent infection may be validated in patients where
C. pneumoniae DNA from atherosclerotic plaques in arteries
or from mononuclear cells in the blood has been detected.
In conclusion, three new ELISAs based on different chlamydia antigens
are now commercially available. The tests perform well in comparison to
the CF and MIF tests. Diagnostic criteria were assessed, and
adjustments were adopted for several tests in order to minimize
unconfirmed reactions but still preserve high sensitivity. The
validation of diagnostic criteria for serodiagnosis of infections by
C. pneumoniae can be done by judiciously comparing the
results of different serological tests. Using adjusted diagnostic
criteria, only a few positive reactions remained uncorroborated.
Although direct detection methods for C. pneumoniae are
gaining importance, there will be a continuing interest in serological
methods for both C. pneumoniae and C. psittaci.
The new tests assessed in this study all seem to be useful, but
positive findings should preferably be confirmed by an established test
like the MIF test until further experience has been obtained.
| |
ACKNOWLEDGMENTS |
We are indebted to Tamara Tuuminen, Labsystems OY, Helsinki,
Finland, for running all tests with the LOY-EIA and to the Savyon and
Medac companies for providing kits for this study.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Dept.
Clinical Microbiology, Malmö University Hospital, S-205 02 Malmö, Sweden. Phone: 46-40-331365. Fax: 46-40-337312. E-mail: Kenneth.Persson{at}mikrobiol.mas.lu.se.
| |
REFERENCES |
| 1.
|
Aldous, M. B.,
J. T. Grayston,
S. P. Wang, and H. M. Foy.
1992.
Seroepidemiology of Chlamydia pneumoniae TWAR infection in Seattle families, 1966-1979.
J. Infect. Dis.
166:646-649[Medline].
|
| 2.
|
Berdal, B. P.,
O. Scheel,
A. R. Ögaard,
T. Hoel,
T. J. Gutteberg, and G. Ånestad.
1992.
Spread of subclinical Chlamydia pneumoniae infection in a closed community.
Scand. J. Infect. Dis.
24:431-436[Medline].
|
| 3.
|
Black, C. M.,
P. I. Fields,
T. O. Messmer, and B. P. Berdal.
1994.
Detection of Chlamydia pneumoniae in clinical specimens by polymerase chain reaction using nested primers.
Eur. J. Clin. Microbiol. Infect. Dis.
13:752-756[CrossRef][Medline].
|
| 4.
|
Boman, J.,
A. Allard,
K. Persson,
M. Lundborg,
P. Juto, and G. Wadell.
1997.
Rapid diagnosis of respiratory Chlamydia pneumoniae infection by nested touchdown polymerase chain reaction compared with culture and antigen detection by EIA.
J. Infect. Dis.
175:1523-1526[Medline].
|
| 5.
|
Bourke, S. J.,
D. Carrington,
C. E. Frew,
R. D. Stevenson, and S. W. Banham.
1989.
Serological cross-reactivity among chlamydial strains in a family outbreak of psittacosis.
J. Infect.
19:41-45[CrossRef][Medline].
|
| 6.
|
Brade, L.,
H. Brunnemann,
M. Ernst,
Y. Fu,
O. Holst,
P. Kosma,
H. Näher,
K. Persson, and H. Brade.
1994.
Occurrence of antibodies against chlamydial lipopolysaccharide in human sera as measured by Elisa using an artificial glycoconjugate antigen.
FEMS Immunol. Med. Microbiol.
8:27-42[CrossRef][Medline].
|
| 7.
|
Chirgwin, K.,
P. M. Roblin,
M. Gelling,
M. R. Hammerschlag, and J. Schachter.
1991.
Infection with Chlamydia pneumoniae in Brooklyn.
J. Infect. Dis.
163:757-761[Medline].
|
| 8.
|
Ekman, M. R.,
J. T. Grayston,
R. Visakorpi,
M. Kleemola,
C. C. Kuo, and P. Saikku.
1993.
An epidemic of infections due to Chlamydia pneumoniae in military conscripts.
J. Infect. Dis.
17:420-425.
|
| 9.
|
Emre, U.,
P. M. Roblin,
M. Gelling,
W. Dumornay,
M. Rao, and M. R. Hammerschlag.
1994.
The association of Chlamydia pneumoniae infection and reactive airway disease in children.
Arch. Pediatr. Adolesc. Med.
148:727-732[Abstract/Free Full Text].
|
| 10.
|
Gaydos, C. A.,
P. M. Roblin,
M. R. Hammerschlag,
C. L. Hyman,
J. J. Eiden,
J. Schachter, and T. C. Quinn.
1994.
Diagnostic utility of PCR-enzyme immunoassay, culture, and serology for detection of Chlamydia pneumoniae in symptomatic and asymptomatic patients.
J. Clin. Microbiol.
32:903-905[Abstract/Free Full Text].
|
| 11.
|
Gaydos, C. A.,
J. J. Eiden,
D. Oldach,
L. M. Mundy,
P. Auwaerter,
M. L. Warner,
E. Vance,
A. A. Burton, and T. Quinn.
1994.
Diagnosis of Chlamydia pneumoniae infection in patients with community-acquired pneumonia by polymerase chain reaction enzyme immunoassay.
Clin. Infect. Dis.
19:157-160[Medline].
|
| 12.
|
Grayston, J. T.,
C. Mordhorst,
A. L. Bruu,
S. Vene, and S. P. Wang.
1989.
Countrywide epidemics of Chlamydia pneumoniae, strain TWAR, in Scandinavia, 1981-1983.
J. Infect. Dis.
159:1111-1114[Medline].
|
| 13.
|
Grayston, J. T.,
L. A. Campell,
C. C. Kuo,
C. H. Mordhorst,
P. Saikku,
D. H. Thom, and S. P. Wang.
1990.
A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR.
J. Infect. Dis.
161:618-625[Medline].
|
| 14.
|
Hyman, C. L.,
P. M. Roblin,
C. A. Gaydos,
T. C. Quinn,
J. Schachter, and M. R. Hammerschlag.
1995.
Prevalence of asymptomatic nasopharyngeal carriage of Chlamydia pneumoniae in subjectively healthy adults: assessment by polymerase chain reaction-enzyme immunoassay and culture.
Clin. Infect. Dis.
20:1174-1178[Medline].
|
| 15.
|
Kern, D. G.,
M. A. Neill, and J. Schachter.
1993.
A serological study of Chlamydia pneumoniae in Rhode Island: evidence of serological cross-reactivity.
Chest
104:208-213[Abstract/Free Full Text].
|
| 16.
|
Kutlin, A.,
N. Isomura,
U. Emre,
P. M. Roblin, and M. R. Hammerschlag.
1997.
Evaluation of chlamydia immunoglobulin M (IgM), IgG, and IgA rElisas Medac for the diagnosis of Chlamydia pneumoniae infection.
Clin. Diagn. Lab. Immunol.
4:213-216[Abstract].
|
| 17.
|
Ozanne, G., and J. Lefebvre.
1992.
Specificity of the microimmunofluorescence assay for the serodiagnosis of Chlamydia pneumoniae infections.
Can. J. Microbiol.
38:1185-1189[Medline].
|
| 18.
|
Persson, K., and J. Treharne.
1989.
Diagnosis of infection caused by Chlamydia pneumoniae (strain TWAR) in patients with "ornithosis" in Southern Sweden 1981-1987.
Scand. J. Infect. Dis.
21:675-679[Medline].
|
| 19.
|
Persson, K., and S. Haidl.
2000.
Evaluation of a commercial test for the chlamydial lipopolysaccharide (Medac) for the serodiagnosis of acute infections by Chlamydia pneumoniae (TWAR) and Chlamydia psittaci.
APMIS
108:131-138[CrossRef][Medline].
|
| 20.
|
Petitjean, J.,
F. Vincent,
M. Fretigny,
A. Vabret,
J. D. Poveda,
J. Brun, and F. Freymuth.
1998.
Comparison of two serological methods and a polymerase chain reaction-enzyme immunoassay for the diagnosis of acute respiratory infections with Chlamydia pneumoniae in adults.
J. Med. Microbiol.
47:615-621[Abstract/Free Full Text].
|
| 21.
|
Thom, D. H.,
J. T. Grayston,
L. A. Campell,
C. C. Kuo,
V. K. Diwan, and S. P. Wang.
1994.
Respiratory infection with Chlamydia pneumoniae in middle-aged and older adult outpatients.
Eur. J. Microbiol. Infect. Dis.
13:785-792.
|
| 22.
|
Verkooyen, R. P.,
D. Willemse,
C. A. M. Hiep-van Casteren,
S. A. Mousavi Joulandan,
R. J. Snijder,
J. M. M. van den Bosch,
H. P. T. van Helden,
M. F. Peeters, and H. A. Verbrugh.
1998.
Evaluation of PCR, culture, and serology for diagnosis of Chlamydia pneumoniae respiratory infections.
J. Clin. Microbiol.
36:2301-2307[Abstract/Free Full Text].
|
| 23.
|
Wang, S. P., and J. T. Grayston.
1970.
Immunologic relationship between genital TRIC, lymphogranuloma venereum and related organisms in a new microtiter indirect immunofluorescence test.
Am. J. Ophthalmol.
70:367-374[Medline].
|
| 24.
|
Wang, S. P., and J. T. Grayston.
1998.
Chlamydia pneumoniae (TWAR) micro-immunofluorescence antibody studies 1998 update, p. 155-158.
In
R. S. Stephens, G. I. Byrne, G. Christiansen, I. N. Clarke, J. T. Grayston, R. G. Rank, G. L. Ridgway, P. Saikku, J. Schachter, and W. E. Stamm (ed.), Chlamydial infections. International Chlamydia Symposium, San Francisco, Calif.
|
Clinical and Diagnostic Laboratory Immunology, September 2000, p. 739-744, Vol. 7, No. 5
1071-412X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Paldanius, M., Bloigu, A., Alho, M., Leinonen, M., Saikku, P.
(2005). Prevalence and Persistence of Chlamydia pneumoniae Antibodies in Healthy Laboratory Personnel in Finland. CVI
12: 654-659
[Abstract]
[Full Text]
-
Tenenbaum, T., Heusch, A., Henrich, B., MacKenzie, C. R., Schmidt, K. G., Schroten, H.
(2005). Acute Hemorrhagic Pericarditis in a Child with Pneumonia Due to Chlamydophila pneumoniae. J. Clin. Microbiol.
43: 520-522
[Abstract]
[Full Text]
-
Klein, M., Kotz, A., Bernardo, K., Kronke, M.
(2003). Detection of Chlamydia pneumoniae-Specific Antibodies Binding to the VD2 and VD3 Regions of the Major Outer Membrane Protein. J. Clin. Microbiol.
41: 1957-1962
[Abstract]
[Full Text]
-
Paldanius, M., Bloigu, A., Leinonen, M., Saikku, P.
(2003). Measurement of Chlamydia pneumoniae-Specific Immunoglobulin A (IgA) Antibodies by the Microimmunofluorescence (MIF) Method: Comparison of Seven Fluorescein-Labeled Anti-Human IgA Conjugates in an In-House MIF Test Using One Commercial MIF and One Enzyme Immunoassay Kit. CVI
10: 8-12
[Abstract]
[Full Text]
-
Hermann, C., Graf, K., Groh, A., Straube, E., Hartung, T.
(2002). Comparison of Eleven Commercial Tests for Chlamydia pneumoniae-Specific Immunoglobulin G in Asymptomatic Healthy Individuals. J. Clin. Microbiol.
40: 1603-1609
[Abstract]
[Full Text]
-
van der Ven, A. J. A. M., Hommels, M. J., Kroon, A. A., Kessels, A., Flobbe, K., van Engelshoven, J., Bruggeman, C. A., de Leeuw, P. W.
(2002). Chlamydia pneumoniae Seropositivity and Systemic and Renovascular Atherosclerotic Disease. Arch Intern Med
162: 786-790
[Abstract]
[Full Text]
-
Morre, S. A., Munk, C., Persson, K., Kruger-Kjaer, S., van Dijk, R., Meijer, C. J. L. M., van den Brule, A. J. C.
(2002). Comparison of Three Commercially Available Peptide-Based Immunoglobulin G (IgG) and IgA Assays to Microimmunofluorescence Assay for Detection of Chlamydia trachomatis Antibodies. J. Clin. Microbiol.
40: 584-587
[Abstract]
[Full Text]
-
Boman, J., Hammerschlag, M. R.
(2002). Chlamydia pneumoniae and Atherosclerosis: Critical Assessment of Diagnostic Methods and Relevance to Treatment Studies. Clin. Microbiol. Rev.
15: 1-20
[Abstract]
[Full Text]
-
Stralin, K., Fredlund, H., Olcen, P., Bas, S., Vischer, T. L.
(2001). Labsystems Enzyme Immunoassay for Chlamydia pneumoniae Also Detects Chlamydia psittaci Infections. J. Clin. Microbiol.
39: 3425-3426
[Full Text]
-
Derfuss, T., Gurkov, R., Then Bergh, F., Goebels, N., Hartmann, M., Barz, C., Wilske, B., Autenrieth, I., Wick, M., Hohlfeld, R., Meinl, E.
(2001). Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response. Brain
124: 1325-1335
[Abstract]
[Full Text]
-
Tuuminen, T., Varjo, S., Ingman, H., Weber, T., Oksi, J., Viljanen, M.
(2000). Prevalence of Chlamydia pneumoniae and Mycoplasma pneumoniae Immunoglobulin G and A Antibodies in a Healthy Finnish Population as Analyzed by Quantitative Enzyme Immunoassays. CVI
7: 734-738
[Abstract]
[Full Text]
Top
Abstract
Introduction
