Congenital Toxoplasmosis Clinical Trial
Official title:
TOXODIAG: New Diagnostic Approach for Congenital Toxoplasmosis
Caused by Toxoplasma gondii, toxoplasmosis is mostly asymptomatic except in immunocompromised
individuals and infants infected in utero. Congenital toxoplasmosis (CT) results from the
transplacental passage of the parasite, which occurs in 30% of cases of primary infection
during pregnancy. Neonatal biological diagnosis of toxoplasmosis is essential in the case of
(i) suggestive clinical signs in the newborn with no information on the serological status of
the mother, (ii) seroconversion diagnosed during pregnancy, (iii) not or poorly followed
pregnancy, and (iiii) for enhanced effectiveness of treatments administered as soon as
possible to the newborn. Given the limitations of current diagnostic tests, the
characterization of specific immunoglobulin (Ig)G neo-synthesized by the newborn would be of
great help for an early diagnosis of CT.
The main objective of the TOXODIAG project is to validate and evaluate the ELISPOT
(Enzyme-Linked Immunosorbent SPOT assay) method for detecting, in the newborn, B lymphocytes
(LyB) sensitized in utero to produce T. gondii specific immunoglobulins (Ig) following a
primary infection of the mother during the pregnancy. More precisely, the detection and
quantification of LyB secreting IgG and IgM specific for T. gondii using the ELISPOT method
will be applied i) to mononuclear cells of women in seroconversion following a toxoplasmic
primo-infection during pregnancy and ii) to cord blood mononuclear cells of newborns
suspected of CT, in comparison to positive and negative infection controls.
To reach this goal, TOXODIAG is a diagnostic, multicentric, prospective, non-randomized,
comparative and controlled study. It will be performed in 3 parallel groups of pregnant women
performing prenatal follow-up and giving birth in the maternity wards of 3 hospitals of the
AP-HP (Louis MOURIER, Bichat-Claude Bernard and Cochin) which ensure mother/child follow-up
and biological sampling, with great gynecology and obstetrics expertise. Sixty women will be
selected and included into 3 groups according to toxoplasmic seroconversion during pregnancy
(n=30), positive (n=15) or negative (n=15) toxoplasma serology. The necessary biological
material will consist in additional blood tubes which will be taken at the same time as those
performed for the usual pregnancy follow-up examinations and will correspond to maternal
peripheral blood at inclusion, seroconversion and delivery as well as cord blood.
Toxoplasmosis is a cosmopolitan parasitosis that affects one third of the world's population.
This infection, caused by Toxoplasma gondii, is mostly asymptomatic except in
immunocompromised individuals and infants infected in utero. Congenital toxoplasmosis (CT)
results from the transplacental passage of the parasite, which occurs in 30% of cases of
primary infection during pregnancy. The clinical consequences are all the more serious when
fetal contamination is early (death in utero, premature delivery or term childbirth with
perivisceral involvement) and result in mainly neuro-ocular attacks in case of later
contamination. Pregnant women or women of childbearing age therefore constitute a group at
risk and are exposed differently according to their geographical situation and food
consumption. Neonatal biological diagnosis of toxoplasmosis is essential in the case of (i)
suggestive clinical signs in the newborn with no information on the serological status of the
mother, (ii) seroconversion diagnosed during pregnancy, (iii) not or poorly followed
pregnancy, and (iiii) for enhanced effectiveness of treatments administered as soon as
possible to the newborn. This diagnosis is based mainly on parasite research in the neonatal
amniotic fluid or placenta by PCR and / or inoculation in mice, as well as on serological
tests. Immunoglobulins (Ig) A and IgM do not cross the placental barrier and represent good
markers of congenital infection in the newborn. Nevertheless, they are not specific to an
acute infection and are no longer detectable at birth in cases of infections contracted by
the mother before the 3rd trimester of pregnancy. The detection of IgG synthesized by the
child has a diagnostic value only after 6 months of life, once the materno-transmitted IgG
have been eliminated, and the techniques comparing the IgG response profiles of the mother
and the child to a plurality of toxoplasmic antigens remain difficult to interpret (western
blot, ELIFA). It is nevertheless a combination of these different tests that makes up the
decision tree for a neonatal biological diagnosis of CT. The characterization of specific IgG
neo-synthesized by the newborn would be of great help for an early diagnosis of congenital
infection by T. gondii. The present project consists in determining the presence in the
neonate of B lymphocytes (LyB) sensitized in utero to produce specific IgG in case of CT.
This approach can be envisaged because of the maturity acquired by the fetal LyB from the end
of the first trimester of pregnancy, demonstrated by their ability to produce high affinity
Ig in the case of maternal infection or neonatal immunization.
This research is diagnostic, multicentric, prospective, non-randomized, comparative and
controlled. It will be performed in 3 parallel groups of pregnant women performing prenatal
follow-up and giving birth in the maternity wards of 3 hospitals of the AP-HP which ensure
mother/child follow-up and biological sampling, with great gynecology and obstetrics
expertise. Sixty patients will be selected and included according to the following
distribution:
- Positive control group (women with positive toxoplasma serology): 15 patients;
- Negative control group (women with negative toxoplasma serology): 15 patients;
- Group of women diagnosed with toxoplasmic seroconversion during pregnancy: 30 patients.
Non-recruiting centers will be HUPC and HUPNVS biology laboratories for the realization of
serological tests and expertise in biological diagnosis and IRD UMR 216 for coordination,
laboratory experiments and expertise in immunology.
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