Commercial laboratory IgM testing for Toxoplasma gondii in pregnancy: a 20-year experience.

Abstract

This study was performed to review the clinical utility of commercial laboratory Toxoplasmosis-specific IgM testing during pregnancy and outcomes of the gestation at our institution.
A retrospective review of all women referred for suspected acute Toxoplasma gondii infection during pregnancy from 1984 through 2004 was performed. Women were diagnosed with suspected acute toxoplasmosis based on commercial laboratory serologic antibody testing. All women had blood sent to a recognized reference laboratory for antibody testing within 2 weeks of the commercial laboratory results. The study protocol was approved by the Institutional Review Board. Chi-square analysis were used with a significance of P < .05.
A total of 130 women were evaluated during the study period with 116 IgM positive results from the commercial laboratories. The commercial laboratory antibodies were as follows: IgM positive with IgG negative (n = 20), IgM positive with IgG positive (n = 96), and IgM negative with IgG positive (n = 14). There was a significant reduction in the IgM positive results when comparing commercial laboratory (n = 116) with the reference laboratory results (n = 28; p < .001). Acute toxoplasmosis infection was diagnosed in 7 (5%) of the women. All cases of acute toxoplasmosis infection had a positive commercial laboratory IgM result. The false positive rate for the commercial laboratory IgM was 88.6% and the diagnostic indices were sensitivity 100%, specificity 11.4%, positive predictive value 6% and negative predictive value 100%.
Commercial laboratory Toxoplasmosis-specific IgM is associated with a high false positive rate. The commercial and reference laboratory IgM results identified all cases of acute toxoplasmosis infection. Commercial laboratories reflexively obtaining reference laboratory confirmation of positive results could reduce costs associated with testing, referrals, retesting, and invasive procedures.

Full text

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CLINICAL STUDY
Commercial laboratory IgM testing for Toxoplasma gondii in
pregnancy: A 20-year experience
DAVID J. GARRY, ANDREW ELIMIAN, VANDY WIENCEK, & DAVID A. BAKER
Department of Obstetrics, Gynecology and Reproductive Medicine, Stony Brook University, Stony Brook, NY, USA
Abstract
Objective.
testing during pregnancy and outcomes of the gestation at our institution.
Methods.
A retrospective review of all women referred for suspected acute Toxoplasma gondii infection during pregnancy
from 1984 through 2004 was performed. Women were diagnosed with suspected acute toxoplasmosis based on commercial
laboratory serologic antibody testing. All women had blood sent to a recognized reference laboratory for antibody testing
within 2 weeks of the commercial laboratory results. The study protocol was approved by the Institutional Review Board.
Chi-square analysis were used with a significance of P5.05.
Results.
A total of 130 women were evaluated during the study period with 116 IgM positive results from the commercial
laboratories. The commercial laboratory antibodies were as follows: IgM positive with IgG negative (n=20), IgM positive
with IgG positive (n=96), and IgM negative with IgG positive (n=14). There was a significant reduction in the IgM positive
results when comparing commercial laboratory (n=116) with the reference laboratory results (n=28; p5.001). Acute
toxoplasmosis infection was diagnosed in 7 (5%) of the women. All cases of acute toxoplasmosis infection had a positive
commercial laboratory IgM result. The false positive rate for the commercial laboratory IgM was 88.6% and the diagnostic
indices were sensitivity 100%, specificity 11.4%, positive predictive value 6% and negative predictive value 100%.
Conclusion.
Commercial laboratory Toxoplasmosis-specific IgM is associated with a high false positive rate. The commercial
and reference laboratory IgM results identified all cases of acute toxoplasmosis infection. Commercial laboratories reflexively
obtaining reference laboratory confirmation of positive results could reduce costs associated with testing, referrals, retesting,
and invasive procedures.
This study was performed to review the clinical utility of commercial laboratory Toxoplasmosis-specific IgM
Keywords: Perinatal infection, false positive, antibody
Introduction
The seroprevalence of Toxoplasma gondii (toxoplas-
mosis) in women aged 15 to 44 years is approximately
15% [1]. The disease is not nationally reportable in
the United States; however, an estimated 400 to 4000
congenital infections occur annually [2]. Vertical
transmission rates increase from 10 to 15% in the first
trimester to 60% in the third trimester [3,4]. The
severity of disease is inversely related to gestational
age with worsening sequelae occurring earlier in
pregnancy. The annual economic impact of toxo-
plasmosis is millions in US dollars [5].
DetectionoftoxoplasmosisutilizingIgMantibodies
is the most common method used to determine if
infection has occurred. The IgM antibodies rise
quickly in response to infection, but may be persis-
tently elevated for many months [6]. A negative IgM
result during pregnancy is most reassuring that acute
infection has not occurred. Commercial test kits for
Toxoplasmosis-specific IgM have been available for
usage with unacceptably high false positive rates. In
1997 the United States Food and Drug Administra-
tion (FDA) issued an advisory regarding the clinical
limits of the Toxoplasmosis IgM commercial test kits
[7]. A recent survey of obstetrician-gynecologists
demonstrated lack of knowledge to the problems
associated with toxoplasmosis IgM testing [8].
The objective of this study was to review the
clinical utility of Toxoplasmosis-specific IgM testing
during pregnancy and outcomes of the gestation at
our institution.
Materials and methods
The records of all women referred for suspected acute
Toxoplasma gondii infection during pregnancy from
January 1984 through April 2004 were included in
Correspondence: David A. Baker, MD, Department of Obstetrics, Gynecology and Reproductive Medicine, HSC T9, Room 030, Stony Brook University,
Stony Brook, NY 11791, USA. Tel: 6314447650. Fax: 6314443944. E-mail: dbaker@notes.cc.sunysb.edu
Infectious Diseases in Obstetrics and Gynecology, September 2005; 13(3): 151–153
ISSN 1064-7449 print/ISSN 1098-0997 online ª 2005 Taylor & Francis
DOI: 10.1080/10647440500148024

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the study. All women were diagnosed with suspected
acute toxoplasmosis based on commercial laboratory
serologic antibody testing and referred for consulta-
tion. A suspected acute infection was based on
elevated levels of Toxoplasmosis-specific IgM antibody
with or without high levels of Toxoplasmosis-specific
IgG or based on clinical history and a significantly
elevated Toxoplasmosis-specific IgG. All women had
blood sent to a recognized reference laboratory for
toxoplasmosis testing (Toxoplasmosis Serology Lab,
Research Institute, Palo Alto Medical Foundation,
Ames Building, 795 El Camino Real, Palo Alto, CA
94301; http://www.pamf.org/serology/) within two
weeks of the commercial laboratory results. Acute
toxoplasmosis was suggested based on an acute
pattern of additional reference laboratory testing
which included Sabin-Feldman Dye test, IgA ELISA,
IgE ELISA, AC/HS, and IgG avidity testing. Amnio-
tic fluid polymerase chain reaction (PCR) exam-
ination was offered to confirm fetal involvement in all
women diagnosed with acute toxoplasmosis infection
that did not opt to terminate the gestation.
The study protocol was approved by the Institu-
tional Review Board. Student t-test and Mann-
Whitney U test were used for comparison of
continuous variables and w2analysis or Fisher exact
test were used for comparison of dichotomous
variables. Significance was considered when P5.05.
Results
A total of 130 women were evaluated during the
study period with a mean maternal age (+SD) of
30.4 +4.5 years. The mean gestational age (+SD)
was 14.0 +4.9 weeks, 44% (n=57) referred in the
first trimester and 30% (n=39) nulliparous.
There were 116 Toxoplasmosis-specific IgM posi-
tive results from the commercial laboratories. The
commercial laboratory antibodies were as follows:
IgM positive with IgG negative (n=20), IgM positive
with IgG positive (n=96), and IgM negative with
IgG positive (n=14). There was a significant
reduction in the Toxoplasmosis-specific IgM positive
results when comparing
results (n=116) to the reference laboratory Toxo-
plasmosis-specific IgM results (n=28; p5.001).
There was no significant difference in the Toxoplas-
mosis-specific IgG positive results after reference
laboratory testing (commercial
versus reference positive n=99; p=.11). In the
women with significantly elevated commercial la-
boratoryIgG positive
infection, all had IgG positive results in the normal
positive range from the reference laboratory with
negative IgM results.
Acute toxoplasmosis infection was suggested with
the additional reference laboratory testing in 7 (5%)
commercial laboratory
positive
n=110
results that suggested
of the women. Two of the women opted for
termination of pregnancy and further confirmatory
testing was not performed on the aborted products.
The remaining 5 women confirmed the congenital
transmission with amniotic fluid PCR and then
received spiramycin therapy and no congenital
toxoplasmosis infections were found. All cases of
acute toxoplasmosis infection had a positive com-
mercial laboratory IgM result. The false positive rate
for the commercial laboratory Toxoplasmosis-specific
IgM was 88.6% and the diagnostic indices were
sensitivity 100%, specificity 11.4%, positive predic-
tive value 6% and negative predictive value 100%.
The false positive rate for the reference laboratory
Toxoplasmosis-specific IgM was 17.1% and the
diagnostic indices were sensitivity 100%, specificity
82.9%, positive predictive value 25% and negative
predictive value 100% (Table I).
Discussion
Toxoplasma gondii remains an insidious infectious
agent during pregnancy with possible vertical trans-
mission to the fetus. In our population the incidence
of acute maternal disease was 5%, however this
varies by country and location. The serologic testing
for Toxoplasmosis-specific antibodies has changed
little over the 20 year course in our review.
There remains an unacceptably high false positive
rate for Toxoplasmosis-specific IgM testing in preg-
nancy in the diagnosis of acute toxoplasmosis
infection. Serologic testing for toxoplasmosis is not
uniformly consistent in commercial laboratories and
false positive results resulted in the FDA’s advisory 7
years ago [7]. When initial IgM and IgG results
suggest acute infection, repeat testing utilizing a well-
recognized reference laboratory is recommended by
the American College of Obstetrician Gynecologists
[9]. Commercial laboratories do not automatically
utilizeareference laboratory
of suggested acute infection. Recently, a survey
demonstrated only 12% (43/364) of obstetrician-
gynecologists realized that a positive Toxoplamosis-
specific IgM test could be a false positive and only
11% (39/363) were aware of the 1997 FDA advisory
regarding the false positive Toxoplamosis-specific IgM
test [8]. There is great potential for harm when the
obstetrician or other provider confers a false positive
result to the patient without reference laboratory
evaluation [8]. A recent advance has suggested the
use of a single IgG avidity test to more accurately
diagnosis suspected acute infection has been sug-
gested [10].
The finding of a positive commercial laboratory
Toxoplasmosis-specific IgM testing during pregnancy
does have value. First, the negative commercial
laboratory IgM conveys no risk for acute toxoplas-
for confirmation
152
D. J. Garry et al.

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mosis infection. Secondly, all cases of acute tox-
oplasmosis infection had commercial laboratory IgM
results that were positive. Several reports have
related a false immunologic reactivity to the low
molecular weight antigen of Toxoplasma gondii which
is unrelated to acute toxoplasmosis infection and
misleads interpretation of results [11,12]. Commer-
cial laboratories do not currently confirm their
Toxoplasmosis-specific IgM positive results with any
reference laboratory. Utilization of a reference
laboratory is necessary to confirm a positive Tox-
oplasmosis-specific IgM
commercial laboratory. Commercial laboratories
reflexively obtaining a certified reference laboratory
evaluation of all positive Toxoplasmosis-specific IgM
would be cost effective compared to the current
model which includes testing, referral for consulta-
tion, retesting and invasive procedures.
positive resultfroma
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Table I. Diagnostic indices in prediction of acute toxoplasmosis for Toxoplamosis-specific IgM from commercial and reference laboratories.
Sensitivity SpecificityPP+ PP-Accuracy
Commercial laboratory IgM
Reference laboratory IgM
100%
100%
11.4%
82.9%*
6.0%
25%*
100%
100%
13.8%
69.2%
* p5.05; PP+, Positive predictive value, PP-, Negative predictive value.
IgM testing for Toxoplasma gondii153