Early and Accurate Diagnosis of Congenital Toxoplasmosis
Objective: Early diagnosis of congenital toxoplasma infection is difficult to establish using serological methods. We explored specific T cell immunity to Toxoplasma gondii antigens to identify more accurate diagnostic tests for an early diagnosis of toxoplasma infection in newborns at risk for congenital toxoplasmosis.
Study Design: T lymphocyte proliferation, interferon (IFN)-γ production and lymphocyte activation antigens expression were evaluated in 23 infected and 65 uninfected neonates at different times, in the first year of life.
Results: The immunologic tests accurately discriminated when tested ≤90 and >90 days of age, respectively and were significantly lower in uninfected than in infected infants: activation antigen CD25, P <0.001 and P <0.00001; activation antigen histocompatibility leukocyte antigen (HLA)-DR, P <0.01 and P <0.00001; T cell proliferation, P <0.0001 and P <0.00001; IFN-γ production, P <0.001 and P <0.00001. Evaluation of the specific T cell response allowed identification at 3 months of age or younger, 2 of 23 infected neonates, who had negative serologic tests. Moreover specific T lymphocyte activity increased with age even in neonates undergoing therapy, suggesting that medical treatment does not affect lymphocyte response.
Conclusions: Evaluation of T cell immunity is important for an early and accurate diagnosis of congenital toxoplasmosis.
The diagnosis of congenital toxoplasmosis has been based on the detection of specific antibodies. The serologic tests on neonatal serum are complicated by the presence of transplacentally acquired maternal IgG antibodies which can confound results. Moreover, the newborn's production of IgM may vary. For the above reasons, current diagnostic methods frequently fail to establish a diagnosis during the first months of life. Using enzyme-linked immunosorbent assay (ELISA) quantification of specific IgM and IgA antibodies fails to identify 1 case in 4 at birth.
It has been reported that protection against toxoplasmosis is also mediated by cellular immunity. Mononuclear cells isolated from infected adults and infants mount strong proliferative responses in vitro upon stimulation with T. gondii antigens. It has also been shown that the detection of CD25 expression on T cells after T. gondii stimulation is a simple, rapid, sensitive, and specific method for the diagnosis of infection, even in cases in which serologic tests are inaccurate. Wilson et al reported that lymphocyte transformation after exposure to toxoplasma antigen in infants with a suspected congenital toxoplasma infection was superior in sensitivity to the IgM-IFA test. However, a simultaneous comparison of different cellular tests, to define their accuracy in newborns less than 3 months of age, has not been previously attempted. The aim of the present study is to evaluate a method for early and accurate diagnosis of congenital infection by comparing serologic and cellular assays on newborns at risk for congenital toxoplasmosis at different times up to 1 year of age.
Objective: Early diagnosis of congenital toxoplasma infection is difficult to establish using serological methods. We explored specific T cell immunity to Toxoplasma gondii antigens to identify more accurate diagnostic tests for an early diagnosis of toxoplasma infection in newborns at risk for congenital toxoplasmosis.
Study Design: T lymphocyte proliferation, interferon (IFN)-γ production and lymphocyte activation antigens expression were evaluated in 23 infected and 65 uninfected neonates at different times, in the first year of life.
Results: The immunologic tests accurately discriminated when tested ≤90 and >90 days of age, respectively and were significantly lower in uninfected than in infected infants: activation antigen CD25, P <0.001 and P <0.00001; activation antigen histocompatibility leukocyte antigen (HLA)-DR, P <0.01 and P <0.00001; T cell proliferation, P <0.0001 and P <0.00001; IFN-γ production, P <0.001 and P <0.00001. Evaluation of the specific T cell response allowed identification at 3 months of age or younger, 2 of 23 infected neonates, who had negative serologic tests. Moreover specific T lymphocyte activity increased with age even in neonates undergoing therapy, suggesting that medical treatment does not affect lymphocyte response.
Conclusions: Evaluation of T cell immunity is important for an early and accurate diagnosis of congenital toxoplasmosis.
The diagnosis of congenital toxoplasmosis has been based on the detection of specific antibodies. The serologic tests on neonatal serum are complicated by the presence of transplacentally acquired maternal IgG antibodies which can confound results. Moreover, the newborn's production of IgM may vary. For the above reasons, current diagnostic methods frequently fail to establish a diagnosis during the first months of life. Using enzyme-linked immunosorbent assay (ELISA) quantification of specific IgM and IgA antibodies fails to identify 1 case in 4 at birth.
It has been reported that protection against toxoplasmosis is also mediated by cellular immunity. Mononuclear cells isolated from infected adults and infants mount strong proliferative responses in vitro upon stimulation with T. gondii antigens. It has also been shown that the detection of CD25 expression on T cells after T. gondii stimulation is a simple, rapid, sensitive, and specific method for the diagnosis of infection, even in cases in which serologic tests are inaccurate. Wilson et al reported that lymphocyte transformation after exposure to toxoplasma antigen in infants with a suspected congenital toxoplasma infection was superior in sensitivity to the IgM-IFA test. However, a simultaneous comparison of different cellular tests, to define their accuracy in newborns less than 3 months of age, has not been previously attempted. The aim of the present study is to evaluate a method for early and accurate diagnosis of congenital infection by comparing serologic and cellular assays on newborns at risk for congenital toxoplasmosis at different times up to 1 year of age.