impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

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infants with CT newly synthesised anti-MIC2 and SAG1
IgG, mainly of the IgG2 subtype, were demonstrated
within 2 months of age, thus opening the door to an
IgG-based, easy-to-perform, standardisable, marketable
test for early postnatal diagnosis.
Effectiveness of secondary and tertiary prophylaxis
At the end of the second millennium, effectiveness of
prenatal screening has been questioned. A retrospective
European multicentre study found a 70% reduction
in the relative risk of clinical signs in the first year
of life in CT children born to treated mothers (the better
with sulphonamide-pyrimethamine combination)
versus untreated mothers with primary toxoplasmosis
on gestation (Foulon W et al., 1999). Furthermore, a
large prospective European observational study
(EMSCOT) evaluating the effect of treatment delay on
transmission rate failed to confirm prenatal treatment
effectiveness (with either spiramycine or
sulphonamide-pyrimethamine) (Gilbert RE and Gras
L, 2003). Finally, a metanalysis on an individual patient
basis displayed weak evidence for an increased risk of
transmission according to the later prenatal treatment
was started (SYROCOT, 2007). The critically short
time for starting prenatal prophylaxis (within 3 weeks)
could open a new debate on the possibility of applying
early prophylaxis. In fact, the principle on which secondary
prevention was based is that there is a delay
between maternal contamination and actual foetal
transmission. The metanalytic study argued that only a
prospective randomised clinical trial with a placebo
arm can untie the question of secondary prophylaxis
effectiveness. However, several difficulties can be faced
when planning such a trial. First of all, ethical justification
of the trial in countries where prenatal treatment
has been prescribed for decades. Secondly, according to
an estimated incidence of CT, between 1 and
10/10,000 live birth, proper sample size achievement
which must involve several countries and will be
extremely costly (Gilbert RE, 2000). In the US, on a
large sample of 120 infants referred for CT to The
National Collaborative Chicago-Based Congenital
Toxoplasmosis Study and treated with 1 of 2 doses of
p-s within 2 months after birth and continued for 12
months, in the group of infant without substantial neurological
disease at birth the treatment resulted in normal
cognitive, neurological, and auditory outcomes for
all patients. In the group of infant who had moderate to
severe neurological disease at birth it resulted in normal
neurological and/ or cognitive outcomes for >72%
of the patients, and none had sensorineural hearing
loss. Ninety one percent of children without neurological
disease and 64% of those with moderate or severe
neurological disease at birth did not develop new eye
lesions. Although uncontrolled, these outcomes were
considered better than outcomes reported for untreated
or treated for 1 month patients (McLeod R et al.,
2006). In a series of 20 infants with CT identified by
screening one infant showed symptoms of disseminat-
W. Buffolano - Toxoprev
ed infection at birth and 15-20% have healed inflammatory
lesions in the brain and/ or in the eyes, which
can only be detected by imaging or ophtalmoscopy
(Binquet C et al., 2003). In the 23 out of 79 CT cases
new ocular lesions were found by 5 years of age. A parents
filled questionnaire survey on development and
behaviour in 3 years olds children recruited in the
EMSCOT Study showed on average comparable development
and behaviour in infected compared to the
uninfected children and parental anxiety and concerns
(Freeman K et al., 2005). These conclusions have to be
cautiously regarded. First of all, it must be taken into
account the peculiar situation in which they have been
drawn (Salt A, 2005). All the mother-child couples
were enrolled in the setting of prenatal screening care.
Secondly, subtle differences can be addressed only by
clinicians. Thirdly, attrition bias (including lost to follow
up) cannot be excluded. In fact, overall 67% of
parents completed the questionnaire with differences
between parents of infected versus uninfected children
(80% vs. 64%). Fourthly, there were significant differences
of response among centres, according to organisational
attribute of the study centre, with direct
involvement in follow up and access to an address register
as main determinants (Salt A et al., 2005). In the
centre with the highest response rate of 94% and the
highest organizational attribute, more than 75% of the
children were admitted, regular contacts established,
regular address updated and regular connections with
paediatricians established while the most of the other
centres were only central reference laboratories.
Finally, there were not fully investigated outcomes of
the screening, such as compliance with the screening
programme. In the EMSCOT study on the effect of
treatment delay, in which a prospective sequential sampling
has been generated in each study centre, prenatal
screening performed differently in France compared
with Austria and Italy. In France, cases were spread all
over gestational period. In Austria, and even more in
Italy, the most of cases felt in the first half of the gestation,
with very few cases enrolled late on gestation
(Buffolano W, 2003). This distribution by GA found in
the local sample may reflect local screening performance,
thus introducing a selection bias for lower transmission
rate and more severe onset. Additionally, the
preference found in EMSCOT study centres for ultrasonography
(USG), instead of CT-scan, may have introduced
a selection bias causing underestimation of treatment
effect. Poor reliability and accuracy of cerebral
USG in detecting mild abnormalities, such as cerebral
microcalcification are, has recently been demonstrated
(Hintz SR et al., 2007). Another unexplored issue has
been outcomes measurement according to individual
differences in pharmacokinetics, and compliance to
treatment options. Due to bone marrow toxicity, combination
treatment is to be modified or stopped in as
much as 10% to 50% of infant with CT (Guerina NG
et al., 1994). An intriguing field of research could be to
investigate the possibility to adjust treatment according
to host and/or parasite-linked risk. Very recently, differ-