Application to EDL Florence ROBERTGANGNEUX University Hospital of Rennes France Conflict of interest statement None to declare no links with IVD regarding toxoplasmosis ID: 804484
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Slide1
Toxoplasmosis
serology
Application to EDL?
Florence ROBERT-GANGNEUX
University
Hospital of Rennes
France
Slide2Conflict of interest statement
None to declare (no links with IVD regarding toxoplasmosis serology
)
Slide3>60%
40-60%
20-40%
10-20%
<10%
from
Pappas
et al. Int J
Parasitol
, 2009
Role
of
:
Contact
with
felids
Climate
Food habits
Water supply network Urban or rural life Standard of living
Why screening ?High seroprevalence in Latin America, North & Sub-saharan Africa, Midle-East, Malasia, Indonesia
10% South
Africa
(2013)
20% Mali
30% Burkina Faso (2017),
Tanzania
41% Nigeria
46% Mozambique (2013)
50% Benin (2014)
60% Gabon (2013-17),
Egypt
63% Sao Tomé
68% Ivory
Cost
(2016),
75% Ghana (2017)
80% RDC (2014)
70-85%
Ethiopia
(2013-2016)
Slide4Pathogenicity
in Humans
Immunocompetent
Immunocompromised
Fœtus
Low
pathogenicityAsymptomatic infection: 80-90%Low severity infection : 10-20%Mostly reactivation of chronic infectionLife-threatening without treatmentPathogenicity depending on the term of pregnancy at maternal infection (1
st
>2
nd
>3
rd
)
Cerebral
Pulmonary
Disseminated
Ocular
Fetal
lossHydrocephaly, Mental retardationRetinochoroiditis (blindness) Exception: severe
Amazonian toxoplasmosisResponsible for 15% mortality (all causes) in HIV patients (WHO)Unknown incidence in Africa
3/10 000 live
births
(France)
6/10 000 live
births
in Brazil
Slide5Usual
diagnosis of
toxoplasmosis in HIV patients
CT scan with injection
Imaging
Serology
qPCR
Good PCR tests (commercial)
High
Specificity
(>95%)
But
Sensitivity
in
cerebral
toxo
: max 60% in CSF or
blood
(Robert-Gangneux &
Belaz, Curr Op Infect Dis 2016)if positive Confirms that reactivation
is likelyif negative Can rule out diagnosis in HIV patients
+
Slide6Usual
diagnosis of
congenital toxoplasmosis in pregnancy
Imaging
Serology
IgG+IgM
qPCR
Amniocentesis
:
High
Specificity
(100%)
Sensitivity
90%
if IgG+/IgM-
=>
Woman
protected
if IgG+/IgM+
=> Consider IgG avidity to rule out the risk of recent infectionif IgG-/IgM-
Woman at risk Follow-up to detect infection
Slide7Suitability
of serological tests in LIC/MIC
Sensitivity ? To be
evaluated on a HIV population (may be different from other settings)
High NPV needed
Cost Rapid and easy formation of
users Robustness of assays (storage temperature, …)
Slide8Suitability
of serological tests in LIC/MIC
Systematic review:
comparison of assays performances 5 assays have maximal performances =>
1 ELISA 2 automated Immuno-assays
1 ICT assay 1 WB assay
ELISAAutomated immuno-assaysWB (confirmatory test)=>Tertiary
care
labs
(IgG, IgM)
ICT (
cost
~ 5€)
=>
Primary
care
(stable RT 2 mo)
p30
p31
p45
neg
pos
p33
p40
Sensitivity
98%, NPV >98%
Slide9Why
/when performing Toxoplasma
serology?
Advanced HIV
To
improve
diagnosis
:
currently
probably
underestimated
To
exclude
the
hypothesis
of
cerebral
toxoplasmosis => avoid unnecessary treatmentTo prevent the risk of immune reconstitution inflammatory syndrome (IRIS) following ART initiation => start cotrimoxazole beforeTo target prophylaxis intervention ? (side effects, resistance…)
Slide10Toxoplasma
serology
Advanced HIV +Neurological
signs
Negative
Start ARV
Other
screenings
: TB, Crypto Ag…
Positive
Usual
patient management
Bactrim 3-6
weeks
CD4+
counts
<200
Diagnostic
algorythm
No CT scan available
To
target
curative
therapy
Spare
cotrimoxazole use
Improve
tolerance
limit
resistance
development
The
most
frequent
cause of
neurological
symptoms
in patients
without
cotrimoxazole
In the
current
state:
Possibly
misdiagnosed
with
treatment
failure
of
cryptococcosis
Slide11Toxoplasma
serology
Advanced HIV +Neurological
signs
Negative
Start ARV
TB, crypto Ag
Positive
Usual
patient management
Bactrim 3-6
weeks
CD4+
counts
<200
Diagnostic
algorythm
CT scan
available
CT scan
with
enhanced
contrast
lesions
To
target
curative
therapy
Spare
cotrimoxazole use
Improve
tolerance
limit
resistance
development
Non
evocative
CT scan
Usual
patient management
Slide12Toxoplasma
serology
Advanced HIV +No
clinical signsCD4<200
Negative
Bactrim prophylaxis
Positive
No
targeted
prophylaxis
To
target
prophylaxis
use
Spare
cotrimoxazole use
Improve
tolerance
BUT: cotrimoxazole also against PCPProphylaxis guiding
Slide13In 2017:AIDS : 150-200 cas /
yr cerebral toxoplasmosis revealing AIDS
1st cause for neurological signs
Cazein et al.BEH 2011
>1000 cases in 1995-2000
Expectations : the
example
of France
Slide14Why
/when performing Toxoplasma
serology?
Pregnant womanTo identify women
at risk of infection during pregnancyTo target prevention
interventions towards seronegativesTo implement treatment in case of seroconversionTo reduce the
burden of congenital toxoplasmosisImprove management of HIV+ pregnant women at risk for reactivation => congenital toxoplasmosis
Slide15Slide16Toxoplasma
serology
Pregnant
women1st trimester
Negative
Past infection
=>No follow-up
Positive
Serologic
follow-up
To
target
prevention
To guide
treatment
Pregnancy
Frequency ?
If
becomes
+
Treatment
Echographical
surveillance
Referral
to
Ref
Lab
for IgG/IgM+/-
avidity
Recent
infection
=>
Treatment
Slide17Thank
you for your
participation !
University
Hospital of Rennes, France