Evaluation of
toxoplasmosis in neonate
• Shirvani F MD
• Pediatric infectious diseases subspecialist
• Shaheed Beheshti University of Medical
Sciences
Mother infection is asymptomatic
and lymphadenopathy is the most
common manifestation
WHAT Is THE PROSCESS OF
MOTHER INFANT EVALUATION
• IgG POSITIVE low avidity
• IgM True POSITIVE
Mother
screening
Mother
treatment
Fetus
evaluation
• IgG low positive, high
avidity , AC/HS
• IgM Neg
Mother
screening
Mother
NOT
treated
• Except HIV positive mother
PRIMARY evaluation
Prenatal
Sonography in
fetus(every 2 week)
Amnioic fluid
PCR(17th-21th week)
Postnatal
Maternal and
NEONATAL
IgG,IgM,IgA,
IgE
Injection of placenta
specimen,amniotic
fluid,cord blood to
mice
Paired neonate and maternal
serology:IgG
Gold standard= Sabin feldman dye test
IgG immunobloting test
Indirect Immunofluorescent antibody test, more than 1/1000
IgG ELISA
AC acetone fixed/HS formalin fixed direct agglutination
Enzyme linked immunofiltration assay ,discriminates mother and infant IgG
IgG avidity test ,low avidity antibodies dissolve
with urea , high avidity shows more than 3 months OR 16 WEEKS ago
infection, low avidity may remain pos . For a long time
Paired neonate and maternal
serology:IgM
Double sandwich ELISA IgM test is
pos in 50% - 75% of cong inf
- IgM IFA is false neg. in 25% to 75%
-IgM immunosurbant Agglutination assay highly
sensitive(ISAGA)
- IgM immunobloting test
sensitive(ISAGA)
IgM immunoflourescent antibody assay lower sensitivity
than ELISA and immunosurbant test
Paired neonate and maternal
serology:IgA
Specific IgA ELISA
IgA immunofiltration assay
IgA ISAGA
IgA immunobloting test
IgA EIA
Paired neonate and maternal
serology:IgE
IgE ISAGA
IgE ELISA
The IgE-ELISA and IgE-ISAGA are also sometimes useful in
establishing the diagnosis of congenital toxoplasmosis or acute
acquired T. gondii infection
At present, the IgM-ISAGA, the IgA-ISAGA, and the IgA ELISA
are the best tests for diagnosis of congenital infection in the
newborn.
WHAT ARE THE CLINICAL
MANIFESTATION IN NEWBORN:
characteristic triad of chorioretinitis,
hydrocephalus, and cerebral calcifications.
WHAT ARE THE CLINICAL
MANIFESTATION IN NEWBORN:
• OTHER Manifestations of congenital
toxoplasmosis:
• 10% severe congenital toxoplasmosis with CNS
involvement, eye lesions, and general systemic
manifestations;
• 34% mild involvement with normal clinical
examination results other than retinal scars or
isolated intracranial calcifications;
• and 55% no detectable manifestations.
WHAT ARE THE CLINICAL
MANIFESTATION IN NEWBORN:
• From 25% to >50% of infants with clinically
apparent disease at birth are born
prematurely.
Intrauterine growth retardation, low Apgar scores, and
temperature instability are common.
Other manifestations include lymphadenopathy,
hepatosplenomegaly, myocarditis, pneumonitis,
nephrotic syndrome, vomiting, diarrhea, and feeding
problems.
Bands of metaphyseal lucency and irregularity of the
line of provisional calcification at the epiphyseal
plate may occur without periosteal reaction in the
ribs, femurs, and vertebrae.
WHAT ARE THE CLINICAL
MANIFESTATION IN NEWBORN:
Interpretation of neonate Antibodies:
IgM+ IgG+
Rulout FP with RF and ANA of IgM
AC/HS,IgE EIA/ISAGA,IgA EIA,IgM ISAGA in reference LAB, Neonatal evaluation
IgM ± IgG +
Repeat test , do IFA if ELISA and VISEVERSA
IF documented primary infection in mother or neonate= reference LAB
IgM- IgG+
25% false Neg IgMRepeat test , do IFA if ELISA and VISEVERSA
IF documented primary infection in mother or neonate= reference LAB
IgM+ IgG –
NO infection in mother, probable false positive IgM
do IFA if ELISA and VISEVERSA , REPEAT TEST
IgM – IgG -
No infection in neonate
Antibody interpretation:
1-Antibody demonstrated at3rd mo of life if the
infant is untreated.,
2-synthesis may be delayed for as long as the
9th mo of life or, may not occur at all, If the
infant is treated
3-increase in the ratio of specific serum IgG
antibody titer to the total IgG WITH INCREASE
OF ANTIBODY IN ANY SITUATION
Neonatal evaluation:
• ABR
• Ophthalmologic Examination
• CBC
• LFT, Alk Phos., Bil
• CSF microscopic and total IgG
• Csf specific IgG and IgM
• Brain CT and Sonography
• Neonatal serology IgG , IgM , IgA
• PCR of CSF , Urine , blood
• Mouse inoculation of specimen
• Lymphocyte blastogenesis to Toxoplasma antigens
Treatment:
Infected pregnant mother
is treated with spiramycin
If infection in fetus occurs, mother
treatment does not alter the severity
and evolution of disease in fetus
Thus PCR in amniotic fluid
leads us to treat the fetus
Treatment:
Condition medication dosage Lengh of therapy
Congenital infection Pyrimethamin plus 2 mg/kg/day for
2 day then 1
mg/kg/day/for 6
month then 3
times weekly for
6 month
1 year , monitor
weekly complete
blood count and
platelet
Sulfadiazine plus 100 mg / kg/day
divided twice
daily
Folinic acid 5-10 mg three
times weekly
Dose adjusted to
maintain CBC
prednisone 1 mg/kg /divided
twice daily
Until resolution of
CSF protein to <1gr/dl
or sight threatening
Spiramycin can be used
for prophylaxis in
children at risk at first
6 to 9 months of age
• Treatment does not eradicate all cysts bradizoits
• Antibodies rebound 3 to 4 months after treatment
discontinuation
• New retinal lesion occur 3 to 10 years after
treatment stop
Follow up
After one year treatment examine retina
every month till 3 months and every
three months till ability to report their
vision and then every 6 months
prevention
Screening of pregnant
mother s or neonates
with IgM
measurement
Education in
hygiene control
Decision for treatment in neonate
Infection not confirmed
IgG and IgM in cord blood
Infection confirmed
before or after birth
treatment
Follow up
complementary
serologic series and
neonatal evaluation
High risk
neonate
Infection confirmed
treatment
Low risk neonate
complementary
serologic series
Infection confirmed
neonatal evaluation
and treatment
Follow up
Infection not confirmed
Decision for treatment
Follow up
Infection not confirmed
Serial serology
Infection confirmed Infection not confirmed
treatment Follow up
THANK YOU

Cong toxo dr shirvani

  • 2.
    Evaluation of toxoplasmosis inneonate • Shirvani F MD • Pediatric infectious diseases subspecialist • Shaheed Beheshti University of Medical Sciences
  • 7.
    Mother infection isasymptomatic and lymphadenopathy is the most common manifestation
  • 15.
    WHAT Is THEPROSCESS OF MOTHER INFANT EVALUATION
  • 16.
    • IgG POSITIVElow avidity • IgM True POSITIVE Mother screening Mother treatment Fetus evaluation
  • 17.
    • IgG lowpositive, high avidity , AC/HS • IgM Neg Mother screening Mother NOT treated • Except HIV positive mother
  • 18.
    PRIMARY evaluation Prenatal Sonography in fetus(every2 week) Amnioic fluid PCR(17th-21th week) Postnatal Maternal and NEONATAL IgG,IgM,IgA, IgE Injection of placenta specimen,amniotic fluid,cord blood to mice
  • 20.
    Paired neonate andmaternal serology:IgG Gold standard= Sabin feldman dye test IgG immunobloting test Indirect Immunofluorescent antibody test, more than 1/1000 IgG ELISA AC acetone fixed/HS formalin fixed direct agglutination Enzyme linked immunofiltration assay ,discriminates mother and infant IgG IgG avidity test ,low avidity antibodies dissolve with urea , high avidity shows more than 3 months OR 16 WEEKS ago infection, low avidity may remain pos . For a long time
  • 22.
    Paired neonate andmaternal serology:IgM Double sandwich ELISA IgM test is pos in 50% - 75% of cong inf - IgM IFA is false neg. in 25% to 75% -IgM immunosurbant Agglutination assay highly sensitive(ISAGA) - IgM immunobloting test sensitive(ISAGA) IgM immunoflourescent antibody assay lower sensitivity than ELISA and immunosurbant test
  • 23.
    Paired neonate andmaternal serology:IgA Specific IgA ELISA IgA immunofiltration assay IgA ISAGA IgA immunobloting test IgA EIA
  • 24.
    Paired neonate andmaternal serology:IgE IgE ISAGA IgE ELISA The IgE-ELISA and IgE-ISAGA are also sometimes useful in establishing the diagnosis of congenital toxoplasmosis or acute acquired T. gondii infection
  • 26.
    At present, theIgM-ISAGA, the IgA-ISAGA, and the IgA ELISA are the best tests for diagnosis of congenital infection in the newborn.
  • 27.
    WHAT ARE THECLINICAL MANIFESTATION IN NEWBORN: characteristic triad of chorioretinitis, hydrocephalus, and cerebral calcifications.
  • 28.
    WHAT ARE THECLINICAL MANIFESTATION IN NEWBORN: • OTHER Manifestations of congenital toxoplasmosis: • 10% severe congenital toxoplasmosis with CNS involvement, eye lesions, and general systemic manifestations; • 34% mild involvement with normal clinical examination results other than retinal scars or isolated intracranial calcifications; • and 55% no detectable manifestations.
  • 29.
    WHAT ARE THECLINICAL MANIFESTATION IN NEWBORN: • From 25% to >50% of infants with clinically apparent disease at birth are born prematurely.
  • 30.
    Intrauterine growth retardation,low Apgar scores, and temperature instability are common. Other manifestations include lymphadenopathy, hepatosplenomegaly, myocarditis, pneumonitis, nephrotic syndrome, vomiting, diarrhea, and feeding problems. Bands of metaphyseal lucency and irregularity of the line of provisional calcification at the epiphyseal plate may occur without periosteal reaction in the ribs, femurs, and vertebrae. WHAT ARE THE CLINICAL MANIFESTATION IN NEWBORN:
  • 36.
    Interpretation of neonateAntibodies: IgM+ IgG+ Rulout FP with RF and ANA of IgM AC/HS,IgE EIA/ISAGA,IgA EIA,IgM ISAGA in reference LAB, Neonatal evaluation IgM ± IgG + Repeat test , do IFA if ELISA and VISEVERSA IF documented primary infection in mother or neonate= reference LAB IgM- IgG+ 25% false Neg IgMRepeat test , do IFA if ELISA and VISEVERSA IF documented primary infection in mother or neonate= reference LAB IgM+ IgG – NO infection in mother, probable false positive IgM do IFA if ELISA and VISEVERSA , REPEAT TEST IgM – IgG - No infection in neonate
  • 37.
    Antibody interpretation: 1-Antibody demonstratedat3rd mo of life if the infant is untreated., 2-synthesis may be delayed for as long as the 9th mo of life or, may not occur at all, If the infant is treated 3-increase in the ratio of specific serum IgG antibody titer to the total IgG WITH INCREASE OF ANTIBODY IN ANY SITUATION
  • 38.
    Neonatal evaluation: • ABR •Ophthalmologic Examination • CBC • LFT, Alk Phos., Bil • CSF microscopic and total IgG • Csf specific IgG and IgM • Brain CT and Sonography • Neonatal serology IgG , IgM , IgA • PCR of CSF , Urine , blood • Mouse inoculation of specimen • Lymphocyte blastogenesis to Toxoplasma antigens
  • 39.
    Treatment: Infected pregnant mother istreated with spiramycin If infection in fetus occurs, mother treatment does not alter the severity and evolution of disease in fetus Thus PCR in amniotic fluid leads us to treat the fetus
  • 41.
    Treatment: Condition medication dosageLengh of therapy Congenital infection Pyrimethamin plus 2 mg/kg/day for 2 day then 1 mg/kg/day/for 6 month then 3 times weekly for 6 month 1 year , monitor weekly complete blood count and platelet Sulfadiazine plus 100 mg / kg/day divided twice daily Folinic acid 5-10 mg three times weekly Dose adjusted to maintain CBC prednisone 1 mg/kg /divided twice daily Until resolution of CSF protein to <1gr/dl or sight threatening
  • 42.
    Spiramycin can beused for prophylaxis in children at risk at first 6 to 9 months of age
  • 43.
    • Treatment doesnot eradicate all cysts bradizoits • Antibodies rebound 3 to 4 months after treatment discontinuation • New retinal lesion occur 3 to 10 years after treatment stop
  • 44.
    Follow up After oneyear treatment examine retina every month till 3 months and every three months till ability to report their vision and then every 6 months
  • 45.
    prevention Screening of pregnant mothers or neonates with IgM measurement Education in hygiene control
  • 46.
    Decision for treatmentin neonate Infection not confirmed IgG and IgM in cord blood Infection confirmed before or after birth treatment Follow up complementary serologic series and neonatal evaluation High risk neonate Infection confirmed treatment Low risk neonate complementary serologic series Infection confirmed neonatal evaluation and treatment Follow up Infection not confirmed Decision for treatment Follow up Infection not confirmed Serial serology Infection confirmed Infection not confirmed treatment Follow up
  • 47.