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Clinical Microbiology Reviews, January 1998, p. 228-229, Vol. 11, No. 1
0893-8512/98/$00.00+0
LETTERS TO THE EDITOR
Serological Tests for Chlamydia trachomatis
Infections
LETTER
In her review of the current methods of laboratory diagnosis of
Chlamydia trachomatis infections, Black (1)
reported that serologic tests were generally not useful in the
diagnosis of genital tract infection caused by C. trachomatis and that the presence of immunoglobulin M (IgM)
antibodies was an unreliable marker of acute infection in adolescents
and adults.
Chlamydial infections during pregnancy cause a variety of perinatal
complications. Inclusion conjunctivitis, pneumonia, and other
complications develop in neonates born to mothers infected with
C. trachomatis. Delivery of low-birth-weight infants and premature rupture of membranes occurred more frequently in women infected with C. trachomatis. It also has been suggested
that C. trachomatis infection in pregnant women may be
related to premature labor and to perinatal death.
Contrary to Black's assertion, Gencay et al. (2) reported
that the rates of IgM seropositivity for C. trachomatis
during pregnancy were significantly higher in mothers who had given
birth to infants with complications than in matched controls. The
frequency of chorioamnionitis and meconium-stained amniotic fluid was
also higher in the anti-C. trachomatis IgM antibody-positive
pregnant women. However, in serological studies of C. trachomatis infections, the possibility of cross-reactivity with
C. pneumoniae should be considered.
We also reported that some babies born to IgG and IgA antibody-positive
pregnant women had fetal and neonatal distress (3). Although
Black (1) reported that the enzyme immunoassay (EIA) should
be used only for serosurveys of high-risk populations or for the
detection of IgM in infants with chlamydial pneumonitis, a commercially
available EIA kit used in our study detected serum IgG, IgA, and IgM
antibodies against C. trachomatis (3).
Several investigators have reported that 2 to 20% of pregnant women
harbor C. trachomatis in the endocervix. Pregnant women who
carry C. trachomatis in their genital tracts may suffer from a general disturbance of immunoregulation. Although transmission of the
organism from mothers to their infants generally occurs at the time of
delivery with passage of the infant through the infected cervix, the
possibility of intrauterine infection has been reported (5).
Chorioamnionitis is a frequent finding in cases of prematurity and
respiratory insufficiency in premature babies and may be attributable
to intrauterine infection.
Detection of C. trachomatis antigen from endocervical
specimens has been used widely for the purpose of screening for
chlamydial infections during pregnancy. These tests are easily
performed and less costly than culture but have lower sensitivities and low positive predictive values in low-prevalence populations such as in
Japan. However, we reported four infants who developed neonatal C. trachomatis infections and whose mothers had no
detectable chlamydial antigens during pregnancy (4).
The fact that neonates having the symptoms of chronic lung disease also
manifest elevated serum IgM levels to C. trachomatis suggests that these respiratory tract disorders arise from infections during pregnancy (5). Early diagnosis and appropriate
treatment of chlamydial infections may reduce these complications.
Detection of serum antibodies to C. trachomatis during
pregnancy also permits more laboratories to diagnose perinatal
chlamydial infections and is also useful for screening for infection.
REFERENCES
| 1.
|
Black, C. M.
1997.
Current methods of laboratory diagnosis of Chlamydia trachomatis infections.
Clin. Microbiol. Rev.
10:160-184[Abstract].
|
| 2.
|
Gencay, M.,
M. Koskiniemi,
P. Saikku,
M. Puolakkainen,
K. Raivio,
P. Koskela, and A. Vaheri.
1995.
Chlamydia trachomatis seropositivity during pregnancy is associated with perinatal complications.
Clin. Infect. Dis.
211:424-426.
|
| 3.
|
Numazaki, K.,
T. Kusaka, and S. Chiba.
1996.
Perinatal complications are associated with seropositivity for Chlamydia trachomatis during pregnancy.
Clin. Infect. Dis.
23:208[Medline].
|
| 4.
|
Numazaki, K.,
Y. Niida, and S. Chiba.
1997.
Antigen detection of Chlamydia trachomatis from the endocervix is not enough for screening of perinatal complications.
Am. J. Obstet. Gynecol.
174:951-952.
|
| 5.
|
Numazaki, K.,
M. A. Wainberg, and J. McDonald.
1989.
Chlamydia trachomatis infections in infants.
Can. Med. Assoc. J.
140:615-622[Abstract].
|
| | | | |
Kei Numazaki, M.D., Ph.D.
Department of Pediatrics
School of Medicine
Sapporo Medical University
S.1 W.16 Chuo-ku
Sapporo, 060 Japan
|
AUTHOR'S REPLY
I appreciate the interest and comments of Dr. Numazaki with regard to
my recent review of methods for diagnosis of C. trachomatis infection (1). In that review, I stated that serologic tests are generally not useful for diagnosis of acute C. trachomatis genital tract infections due to the fact that
antibodies elicited during infection are long-lived, so that a positive
antibody test will not distinguish a previous from a current infection.
This is particularly true for populations with a high seroprevalence and a high prevalence of infection, e.g., those from a sexually transmitted disease clinic. In addition, I stated that IgM is an
unreliable marker of acute infection since it is often not present,
presumably because the patient had previous chlamydial infections and
is manifesting an anamnestic immune response to subsequent infections.
Serum IgM antibodies against C. trachomatis have been
associated with adverse outcomes of pregnancy in several studies
(2, 3, 8). In contrast, the study by Numazaki that is cited in his letter did not find an association of adverse outcomes in
mothers or babies with the presence of IgM in maternal serum (5). Instead, Numazaki reports an association of adverse
outcomes with IgA. These results strongly suggest that chlamydial
infections during pregnancy cause perinatal complications and indicate
the need for early diagnosis and treatment of infections to prevent adverse outcomes of pregnancy. However, laboratory tests based on
nucleic acid detection, nucleic acid amplification, and antigen detection technologies remain a better choice for diagnosis of chlamydial infections during pregnancy and in other settings than do
serologic tests based on a single serum specimen, due to their higher
positive and negative predictive values. Tests that detect chlamydial
nucleic acid or antigen have the ability to accurately diagnose
infection much earlier than serologic tests, and with treatment,
inflammatory responses are limited sooner, thus reducing the potential
for immunopathologic sequelae. Since antibodies can take up to 4 weeks
or longer to develop, a false-negative serologic test can occur when
patients are tested early during the course of infection. In the
absence of paired specimens, which take a month or more to collect, a
single IgG titer against C. trachomatis proves nothing
except that the patient has been exposed sometime in the past. The
length of time required for collection of paired specimens is not
appropriate for therapy and management of infected patients,
particularly during pregnancy. IgM titers are predictive of infection
only in patients with first-exposure infections, which may not apply to
many pregnant women. Furthermore, IgM antibodies to C. trachomatis may not develop in persons who have been previously
exposed to C. pneumoniae. The commercial enzyme immunoassays
(EIA) used by Numazaki (6) and by others as serologic tests
for C. trachomatis infection are not species specific, and a
positive result cannot distinguish a C. trachomatis infection from an infection caused by any other chlamydial species. The
EIA serologic tests have also been reported to have low predictive values when single serum specimens are used and to be unreliable for
detection of IgM antibodies (7).
Numazaki reported four infants who developed neonatal C. trachomatis infections and whose mothers had negative chlamydial antigen test results during pregnancy (6), but that report does not indicate whether the mothers were also tested for chlamydial antibodies. It is possible that the antigen detection tests were performed prior to the time that the mothers became infected. Since
antigen detection tests have lower sensitivities than culture or
nucleic acid amplification methods, it is possible that these were
false-negative results, highlighting the need for use of highly
sensitive diagnostic tests for chlamydial infection. Nucleic acid
amplification tests are now becoming more widely available and have
been shown to be cost-effective on the basis of preventing the
morbidity associated with undiagnosed and untreated infections, including neonatal infections (4).
REFERENCES
| 1.
|
Black, C. M.
1997.
Current methods for laboratory diagnosis of Chlamydia trachomatis infections.
Clin. Microbiol. Rev.
10:160-184.
|
| 2.
|
Gencay, M.,
M. Koskiniemi,
P. Saikku, et al.
1995.
Chlamydia trachomatis seropositivity during pregnancy is associated with perinatal complications.
Clin. Infect. Dis.
211:424-426.
|
| 3.
|
Harrison, H. R.,
E. R. Alexander,
L. Weinstein, et al.
1983.
Cervical Chlamydia trachomatis and mycoplasmal infections in pregnancy: epidemiology and outcomes.
JAMA
250:1721-1727[Abstract/Free Full Text].
|
| 4.
|
Howell, M. R.,
T. C. Quinn,
W. C. Brathwaite, and C. A. Gaydos.
1996.
Urine-based DNA amplification vs. two non-amplified techniques for identification of C. trachomatis: cost-effectiveness under three screening alternatives in a low prevalence population of women, p. 258.
In
A. Stary (ed.), Proceedings of the European Society for Chlamydia Research. Societa Editrice Esculapio, Bologna, Italy.
|
| 5.
|
Numazaki, K.,
T. Kusaka, and S. Chiba.
1996.
Perinatal complications are associated with seropositivity for Chlamydia trachomatis during pregnancy.
Clin. Infect. Dis.
23:208.
|
| 6.
|
Numazaki, K.,
Y. Niida, and S. Chiba.
1997.
Antigen detection of Chlamydia trachomatis from the endocervix is not enough for screening of perinatal complications.
Am. J. Obstet. Gynecol.
176:951-952[Medline].
|
| 7.
|
Schachter, J., and W. E. Stamm.
1995.
Chlamydia, p. 669-677.
In
P. R. Murray, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (ed.), Manual of clinical microbiology, 6th ed. American Society for Microbiology, Washington, D.C.
|
| 8.
|
Sweet, R. L.,
D. V. Landers,
C. Walker, and J. Schachter.
1987.
Chlamydia trachomatis infection and pregnancy outcome.
Am. J. Obstet. Gynecol.
156:824-833[Medline].
|
| | | | |
Carolyn M. Black
National Center for Infectious Diseases
Centers for Disease Control and Prevention
Atlanta, Georgia
|
Clinical Microbiology Reviews, January 1998, p. 228-229, Vol. 11, No. 1
0893-8512/98/$00.00+0
