impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

Prenatal screening (secondary prevention)
Conversion from seronegative to IgM/ IgG positive
forms a solid basis for indirect diagnosis of primary
toxoplasmosis on gestation. Further testing for high or
rising IgG level, low IgG avidity, positive IgA antibodies,
or combinations of these tests are suggested in
women displaying IgG and IgM positive at their first
prenatal test. None of these tests reliably determine the
timing of parasitaemia; furthermore, sequential use of
highly sensitive IgM assays and methods examining IgG
avidity or stage specificity in the first 12 weeks GA
(gestational age) could reasonably exclude post- conceptional
infection in a mother-to-be (Roberts A et al.,
2001). Once maternal infection is confirmed, secondary
prevention is actuated up to delivery and the
woman referred for amniocentesis (after 14 weeks GA)
for foetal diagnosis. Polymerase Chain Reaction (PCR)
is the gold standard procedure for detection of T.
gondii DNA to avoid more invasive procedures and
unjustified termination, and to inform change in treatment,
such as stoppage of spiramycine and introduction
of pyrimethamine-sulphonamide combination in
the case of positive result, and immediate postnatal
assessment and treatment. A French study of 2000 consecutive
amniotic fluid samples confirmed that a positive
PCR correlates with disease and that PCR is more
sensitive than any other available test (Thalib L et al.,
2005). The test is highly specific but a negative PCR
result does not rule out foetal infection. Sensitivity
varies according to the gene target and GA at infection
(sensitivity 64%, 95% Confidence Interval 53% to
75%). Unfortunately, the last multicentre proficiency
study carried out on 33 EU laboratories displayed the
need for improvement in both sensitivity and specificity,
and for the development of international reference
materials to help laboratories with the development
and validation of their assays (Kaiser K et al., 2007). In
fact, the percentage of data set achieving all panel correct
results was only 42.1% and in 84.2% of data sets
an in- house test had been used. Transmission risk of
mother to child rises steeply with GA at maternal seroconversion;
it is estimated 15% at 13 weeks, 44% at 26
weeks, and 71% at 36 weeks GA, the odds of transmission
increasing by 12% per week of maternal gestation
at seroconversion (SYROCOT, 2007). Overall risk of
clinical signs in infected child is 19%, 14% ocular
lesions, 8% intracranial lesions. The odds of intracranial
lesions shows a marked decreases with older GA at
seroconversion whereas ocular lesions decline less significantly.
Given the relationship between the risk of
infection and clinical signs, the risk of giving birth to a
child with clinical signs is greatest (10%) for women
who seroconvert between 24 and 30 weeks GA
(Gilbert R et al., 2001).
There are nor European nor national guidelines on the
management of seroconverters and there is therefore
great variability between specialised centres in France,
Austria, and Italy with regard to indications for therapeutic
abortion and amniocentesis, treatment protocols
W. Buffolano - Toxoprev
or chemoprophylaxis, as well in the frequency of sonographical
monitoring in the pregnant women as well as
in their infants. As the use of pyrimethamine and
sulphonamides rests on animal studies carried out during
the 1950s, both prenatal and postnatal prophylaxis
are given on the assumption that treatment is beneficial
on either acute symptoms or in preventing later reactivation
by killing the tachyzoites, thus limiting the number
of actively dividing parasites in the lesions.
Although the combination of pyrimethamine and sulphadiazine
(p-s) is considered the treatment of choice,
treatment regimens differs from 3 months continuous
p-s in Denmark, over continuous p-s treatment for 1
year (US) to up to 2 years weekly treatment with
pyrimethamine-sulphadoxine (Reims and Lyon Group,
France).
Newborn Screening
39
Newborn screening is aimed to decrease long-term ocular
sequelae by early treatment of asymptomatic infected
newborn displaying positive IgM (and in some centres
IgA) on Guthrie cards taken on day 3 to 5 post-partum
at a cost about one-tenth as much as antenatal
screening. Although attractive, practical and ethically
acceptable for economic and psychological reasons in
countries with low incidence, the opportunity to treat
the children in utero is not guaranteed. IgM positivity
was considered to detect 78% of infants with CT
(Lebech M et al., 1999). More recently, it has been
demonstrated that only 52-55% of newborn with CT
showed positive IgM, with variations according to
trimester of pregnancy in which the mother seroconverted
(29%, 34% and 71% in the first, the second,
and the third trimester, respectively) (Gilbert RE et al.,
2007). Taking into account pre-test probability of 3, 27
and 59% in the first, second and third trimesters,
respectively, a positive IgM result increases the posttest
probabilities to 20% in the first trimester, 79% in
the second trimester and 90% in the third trimester. A
negative IgM result would reduce post-test probabilities
to 2%, 20% and 32% in the first, second and third
trimester. The largest changes would be a positive IgM
test in the second trimester (change from 27% to 79%)
and a negative test after third trimester seroconversion
(change from 59% to 32%). In term of efficacy/cost of
newborn screening, more than two-thirds of infants
detected by IgM were born to mothers who seroconverted
in the third trimester and, therefore, have a very low
risk of neurological and visual impairment. A promising
improvement in detection rate of newborn with CT
seems possible through new not yet standardised nor
fully marketed technologies, such as Western- Blot and
recombinant antigens (rec-Ag). In 97% of 35 infected
infants IgM were shown positive against at least one of
the following recombinant antigens: MIC2, MIC3,
MIC4, M2AP, AMA1, and SAG1 (Buffolano W et al.,
2005). Interestingly, infected infants recognized a more
diverse repertoire of antigens than sera transferred over
the placenta from the mothers. In fact, in 13 out of 20