TABLE 4

Case Definitions of Maternal, Fetal, and Infant T gondii Infection, According to the PAMF-TSL

Patient Group and Infection StatusCase Definition
Maternal infection status
 Not infectedSeronegative mother (negative Toxoplasma IgG and negative Toxoplasma IgMa) (provided that the mother is capable of producing immunoglobulins)
 Chronically infectedSerologic test results suggestive of a maternal T gondii infection acquired in the distant past, before pregnancy (>12 mo before testing).b
 Recently infected (definite/probable acute primary T gondii infection acquired during pregnancy or close to conceptionc)Serologic evidence of a recently acquired T gondii infection, likely to have occurred during pregnancy or very close to conceptionc,d
 Unclear infection status (cannot rule out an acute primary T gondii infection acquired during pregnancy or close to conceptionc)Mother was T gondii infected, but the estimation of the exact time of infection (whether it occurred during pregnancy or before pregnancy) was not possible and complete exclusion of a primary infection acquired during gestation or close to conception also was not possible. For mothers tested very late in pregnancy or at delivery, the characterization of the infection status can occasionally be unclear (unless the maternal serologic test results were either clearly suggestive of an “acute recent infection” or clearly suggestive of a “chronic infection,” acquired >12 months before the time of testing). In such cases, and without having any additional serologic results from early pregnancy, acute maternal primary infections early in pregnancy or close to conceptionc cannot be excluded. (Maternal serologic profiles at the time of testing might have been significantly changed from the early serologic responses, which could have been indicative of an acute primary infection.) Moreover, in cases in which the serologic test results do not exclude a maternal infection acquired within 6 to 12 mo before the date of testing (eg, if the woman was tested for the first time during the late second or third trimester of pregnancy), an accurate estimate of whether the patient acquired the infection before or during pregnancy might not be possible. In those cases, testing of a saved serum sample that might have been obtained during the first 16 weeks of pregnancy would be helpful to determine the timing of infection.
 Additional rare scenarios
  Reactivation of T gondii infection in a chronically infected pregnant woman because of an immunocompromising condition152,c,eLaboratory confirmation of local or systemic reactivation is difficult with testing at a single time point.
  Reinfection with a new, more virulent strain in a previously chronically infected woman149,153The currently available serologic tests cannot differentiate between infections from typical versus atypical or more virulent T gondii strains.
Fetal infection status
 Not infectedSeronegative mother (negative maternal Toxoplasma IgG and Toxoplasma IgM [provided that the mother was able to produce immunoglobulins])
 Unlikely CTMother with evidence of chronic T gondii infection acquired in the distant past and before pregnancy (in the absence of any immunocompromising condition or immunosuppressive medicationsb)
or
AF PCR negative (with acute maternal infections estimated to have occurred in the first or second trimester)
and
normal fetal ultrasonograph.
However, if the acute maternal infection is estimated to have occurred in the third trimester, even a negative AF PCR and a normal fetal ultrasonograph cannot exclude CT. For infections acquired in the third trimester, the NPV of AF PCR has been shown to be lower than the NPV for infections acquired earlier in gestation.
 Infected; definite/probable CTAF PCR positive
and/or
fetal ultrasonographic findings highly suggestive of CT (ventriculomegaly/hydrocephalus, intracranial calcifications, intrauterine growth retardation, etc)
and
serologic evidence of acute maternal T gondii infection acquired during gestation or near the time of conception.c
Infant’s infection status
 Not infectedNegative Toxoplasma IgG dye test
and
negative Toxoplasma IgM ISAGA
and
negative Toxoplasma IgA ELISA (provided that the infant is able to produce immunoglobulins)
and
mother also negative for Toxoplasma IgG dye test antibodies and Toxoplasma IgM and IgA ELISA (provided that the mother is capable of producing immunoglobulins).
 CT could not be completely ruled out (in infant without postnatal treatment)Positive Toxoplasma IgG dye test (with titers equal or lower to the maternal titers)
and
negative Toxoplasma IgM ISAGA
and
negative Toxoplasma IgA ELISA
and
no evidence of CT after complete clinical, radiologic, and laboratory evaluation.
Even with the above scenario, if maternal serology was suggestive of a recently acquired primary infection during gestation and suspicion for CT was high, the initially negative Toxoplasma IgM ISAGA and IgA ELISA results at birth may not completely exclude CT. Repeat testing 2 to 4 weeks after birth and every 4 weeks thereafter until 3 months of age could be considered in such cases to rule out the delayed appearance of IgM or IgA antibodies. In these infants, monthly IgG screening should be continued (until complete disappearance of IgG antibodies) according to the PAMF-TSL. Of note: disappearance of Toxoplasma IgG antibodies in an infant with suspected CT, in the presence of anti-Toxoplasma treatment, does not rule out CT. In postnatally treated infants, repeat serologic testing 1–3 months after neonatal seroconversion from positive Toxoplasma IgG to negative Toxoplasma IgG and after treatment was discontinued, might be needed to rule out CT.f
 CT ruled out (in infant without postnatal treatment)Infants with initially positive Toxoplasma IgG dye test (with titers equal or lower to the maternal titers)
and
negative Toxoplasma IgM ISAGA and Toxoplasma IgA ELISA
and
no evidence of CT after complete clinical, radiologic, and laboratory evaluation
and
in whom monthly serial serologic follow-up (approximately every 4-6 wk after birth; with serial Toxoplasma IgG dye tests tested in parallel with most recent previous test) documented a decrease in the Toxoplasma IgG dye test antibodies by ≥50% every 30 days and eventual disappearance of Toxoplasma IgG antibodies (confirming that previous positive Toxoplasma IgG dye test antibodies were transplacentally transferred maternal antibodies).
 Definite CT; asymptomatic at birthPositive Toxoplasma IgG dye test
and
positive Toxoplasma IgM ISAGA (after 5 d of life) or positive Toxoplasma IgA ELISA (after 10 d of life)
but
without any clinical findings of CT after complete clinical, radiologic, and laboratory evaluation (as described in Table 9). (The role of T gondii DNA PCR in CSF, blood, and urine in the diagnosis is discussed separately in Table 9.)
 Definite CT; symptomatic at birthPositive Toxoplasma IgG dye test
and
positive Toxoplasma IgM ISAGA or Toxoplasma IgA ELISA
and
clinical findings consistent with CT, after a complete clinical, radiologic, and laboratory evaluation (as described in Table 9). (The role of T gondii DNA PCR in CSF, blood, and urine in the diagnosis is discussed separately in Table 9.)
  • a According to the PAMF-TSL, all pregnant women should be screened for both Toxoplasma IgG and IgM. This approach will help capture cases of early seroconversion in which the Toxoplasma IgG might be negative (Toxoplasma IgG did not have the time to increase at the time of testing) and only the Toxoplasma IgM might be positive. In those cases, serial maternal serologic testing within 2–4 weeks from the first testing could help differentiate whether the positive Toxoplasma IgM in the absence of a positive Toxoplasma IgG was attributable to a very early infection (IgG would be expected to increase in the follow-up sample) versus a false-positive Toxoplasma IgM.

  • b Unless the woman is immunocompromised or taking immunosuppressive medications, the risk of reactivation of a chronic infection during pregnancy is close to zero.

  • c Within 2–3 months from conception.154

  • d Serologic testing at the PAMF-TSL with the appropriate panel of tests and interpretation of serologic test results by the medical consultants at PAMF-TSL help in the estimation of the most likely time that the acute primary maternal infection had occurred. Serologic evidence of acute infection: Criteria for the diagnosis of recently acquired T gondii infections, within 6 months from sample collection dates, have been previously published by investigators at PAMF-TSL.73,155158 Those criteria (see following) have been used mainly for research purposes. In routine clinical practice, slightly less strict criteria may be used. (A) Toxoplasma IgG dye test titer ≥1:1024 and Toxoplasma IgM ELISA ≥5.0 and acute pattern in the AC/HS test; (B) Toxoplasma IgG dye test titer ≥1:1024 and Toxoplasma IgM ELISA ≥3.0 and acute pattern in the AC/HS test and either Toxoplasma IgA ELISA ≥5.0 or a low Toxoplasma IgG avidity (<10); (C) Toxoplasma IgG dye test titer ≤1:512 and Toxoplasma IgM ELISA ≥5.0 and acute pattern in the AC/HS test and either Toxoplasma IgA ELISA ≥5.0 or low Toxoplasma IgG avidity (<10).

  • e Recent data from a survey in The Netherlands showed that, contrary to previous beliefs, the incidence rates of recurrent eye disease in pregnant women were not higher than in nonpregnant women (incidence rate ratio: 0.54; 95% CI: 0.22–1.29).159

  • f Postnatal treatment can affect the kinetics of Toxoplasma IgG antibodies. There are reports of infants with CT who seroconverted to Toxoplasma IgG negative during treatment but eventually had a rebound after the discontinuation of the anti-Toxoplasma therapy.96