IN THE NAME OF GOD

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)

PostnatalMaternal and

NEONATALIgG,IgM,IgA,

IgE

Injection of placenta specimen,amniotic fluid,cord blood to

mice

Paired neonate and maternal serology:IgG

Gold standard= Sabin feldman dye testIgG immunobloting test

Indirect Immunofluorescent antibody test, more than 1/1000IgG ELISA AC acetone fixed/HS formalin fixed direct agglutinationEnzyme 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 testsensitive(ISAGA)

IgM immunoflourescent antibody assay lower sensitivity than ELISA and immunosurbant test

Paired neonate and maternal serology:IgA

Specific IgA ELISA IgA immunofiltration assayIgA ISAGA

IgA immunobloting testIgA 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 LABIgM+ IgG –

NO infection in mother, probable false positive IgMdo 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