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Dr.Anum Zia�FCPS (Paeds)�Fellow Neonatology (FMH)

TORCH INFECTIONS

T	Toxoplasmosis
O	Others …syphilis
R	Rubella
C	CMV
H	HSV

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Congenital Herpes Virus

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Neonatal acquisition

Intrauterine

Rare
maternal primary infection or ascending infection (PROM)

Perinatal –

Commonest
HSV infection present in the genital tract of the pregnant woman at the time of delivery.

Postnatal

Direct contact with active HSV (e.g., herpes labialis).

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Clinical Manifestations

Disseminated Disease (most severe):

Sepsis-like syndrome, affecting multiple organs
Jaundice, respiratory distress, shock, seizures.
High mortality rate.

CNS Disease (with or without SEM)

Encephalitis
EEG shows lateralized periodic discharges (LPDs)
Neuroimaging show brain edema , hemorrhage, or destructive lesions
Long-term neurological sequelae are common.

Skin, Eye, and Mouth (SEM) Disease (least severe):

Vesicular lesions on the skin, eyes (conjunctivitis, keratitis), and mucous membranes of the mouth.
high risk of progression to CNS or disseminated disease if untreated

Asymptomatic Infection

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Diagnosis

Viral Culture:

Surface cultures (skin, conjunctivae, mouth, nasopharynx, rectum) positive in 90%, highest yield.
Culture of other specimens (CSF, blood) less common

PCR (CSF, blood, swabs)

Preferred method for CNS disease.

Direct Fluorescent Antibody (DFA) staining

Rapid but less sensitive than culture or PCR.

Serological Testing (IgM/IgG):

Not recommended

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Evaluation of disease

CBC
LFTs
RFTs and urinalysis
Chest radiograph
CSF cell count, glucose, and protein.

Blood and CSF cultures to evaluate for possible bacterial sepsis
Eye examination
EEG
Neuroimaging
Abdominal ultrasonography

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Treatment�Initial Antiviral Therapy: Acyclovir

Indications:

Virologically proven HSV disease
Clinically suspected HSV disease
Asymptomatic infants with significant perinatal/postnatal exposure + risk factors (PROM/preterm)

Acyclovir Therapy:

IV acyclovir 🡪preferred agent for all categories (SEM, CNS, disseminated).
Dose: 60 mg/kg/day IV divided every 8 hours.

Adverse effects :

Rare 🡪 well tolerated by most neonates
Include: Kidney injury ,neutropenia , seizures

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Duration of Therapy

SEM disease

- Minimum 14 days (if disseminated/CNS excluded).

Disseminated/CNS disease

Minimum 21 days. Repeat LP near end of therapy to ensure CSF HSV PCR is negative.

CSF not obtained:

Individualized. Consider 2 weeks if well-appearing, 3+ weeks if ill-appearing/neurological signs. Consult ID specialist.

Oral suppressive therapy

Following parenteral treatment

oral acyclovir 300 mg/m² per dose q8hours 🡪6 months

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Management of Asymptomatic Exposed Infants

Maternal History of HSV, No Active Lesions:

No evaluation or treatment

Maternal History of HSV, Active Lesions:

Surface cultures/PCR at 24 hours of age.
No routine prophylactic acyclovir unless any risk factors (PROM >4-6 hours, preterm).

No Maternal History of HSV, Active Lesions:

Surface cultures/PCR at 24 hours of age.
Send maternal blood for HSV serology.

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References

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Thankyou

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Outcome�

Disseminated disease —

One-year mortality rate 25%
Normal neurologic development 80%

CNS disease —

-One-year mortality rate 4%

-Normal neurologic development 30%

Skin, eye, and mouth disease —

- Mortality is rare

-Normal neurologic development >90%

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Follow up

Neurological assessments
Ophthalmological evaluations
Audiological testing
Developmental support and early intervention programs

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MCQ

For a neonate diagnosed with localized skin, eye, and mouth (SEM) HSV disease without evidence of central nervous system (CNS) or disseminated involvement, the typical duration of initial intravenous antiviral therapy is:
a) 5 days.
b) 7 days.
c) 10-14 days.
d) 21 days.

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MCQ

For a neonate diagnosed with localized skin, eye, and mouth (SEM) HSV disease without evidence of central nervous system (CNS) or disseminated involvement, the typical duration of initial intravenous antiviral therapy is:

a) 5 days.

b) 7 days.

c) 10-14 days.

d) 21 days.

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Thankyou

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Congenital CMV

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Commonest Congenital Infection

Leading cause of sensorineural hearing loss
Cause of neurodevelopmental disabilities

Double-stranded DNA -- Herpesviridae family (HHV-5).

Can establish latency and reactivate.
Transmission in mother (Close nonsexual contact with saliva or urine, sexual contact, transfusion, organ transplant)

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Relation to Maternal Infection

Primary (First time) Maternal Infection

Highest risk of transmission to the fetus and severe outcomes.
90% mothers asymptomatic ,10% flu-like symptoms

Non-Primary (Reactivation/Reinfection) Maternal Infection

Lower risk of transmission and generally less severe outcomes
Generally asymptomatic in mothers

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Transmission of Congenital CMV�

Transplacental Transmission:
Timing of Infection:

Earlier infection: likely symptomatic disease

frequency of clinical sequlae:

Periconceptional period (4 weeks before to 6 weeks after the last menstrual period) – 28.8 %
First trimester – 19.3 percent
Second trimester – 0.9 percent
Third trimester – 0.4 percent

Infection in late pregnancy: higher transmission rate

Intrapartum Transmission: Less common.

Role of valacyclovir in mother

Breast milk: Asymptomatic in Term but symptomatic infection can occur in preterm infants

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Clinical Manifestations of Congenital CMV

10 % Symptomatic Congenital CMV at Birth

SGA , preterm,
Microcephaly
Jaundice ,Hepatosplenomegaly ,
Petechiae/thrombocytopenia
or any of the late

90 % Asymptomatic Congenital CMV at Birth

At risk for later-onset sequelae

SNLH
Neurodevelopmental delay
Micrcephaly ,seizures, cerebral palsy
Visual impairment

Life Threatening:

-Sepsis like features

-Myocarditis

-HLH , MOF

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�Diagnosis of Congenital CMV - Prenatal�

Maternal Screening During Pregnancy:
Only Targeted screening in high-risk groups.

Diagnosis of Fetal Infection (if maternal primary infection is suspected or confirmed):

Amniocentesis/cordocentesis: Detection of CMV DNA by PCR in amniotic fluid /fetal blood .
Viral load of > 100,000 copies /ml ----severe infection

Fetal Ultrasound/MRI : B/L periventricular intracranial calcifications, ventriculomegaly, fetal growth restriction, hydrops fetalis).
Even if fetal US is normal: 6.5% risk of SNLH, CNS anomaly 4.4% ,neurodevelopmental anomaly 3.1%

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�Diagnosis of Congenital CMV - Postnatal�

Viral Detection:

PCR for CMV DNA /Viral Culture: urine, saliva, or blood

Infant Serology:
CMV-specific IgM
CMV IgG --not diagnostic.

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Screening of Complications:�

Newborn hearing screening
Ophthalmological Examination
Neuroimaging
CBC, LFTS

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Who To treat?

Treatment recommended for infants with virus detection +

Symptomatic congenital CMV infection – (hepatospleenomegaly, jaundice,intracrnial calcifications, SNHL, chorioretinitis )

Infants with primary immunodeficiency –
In asymptomatic infants: No treatment
Isolated hearing loss --? Uncertain role

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Treatment

Antiviral Medications: Ganciclovir (IV):

Start ganciclovir at 6mg/kg/dose IV Q 12 hours

If appropriate response after 6 weeks shift to oral antiviral treatment with valgancyclovir and continue for 6 months
If there is poor response start foscarnet

Valganciclovir (oral prodrug of ganciclovir):

6mg/kg/dose PO q12hours for 6 months

Adverse effects of anti-viral therapy Neutropenia, thrombocytopenia, anemia, hepatitis

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Follow up

Continue breastfeeding

Re-consider in preterm or unwell neonate
Freezing or pasteurization of EBM reduces transmission

Growth monitoring

Complications of treatment (CBC, LFTs, RFTs)

Improvement of symptoms (hearing ,eye evaluation)

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MCQ

what is the typical duration of antiviral therapy with oral valganciclovir suggested for most cases of non-life-threatening congenital cytomegalovirus (cCMV) infection?
a) Three weeks
b) Six weeks
c) Three months
d) Six months

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MCQ

what is the typical duration of antiviral therapy with oral valganciclovir suggested for most cases of non-life-threatening congenital cytomegalovirus (cCMV) infection?

a) Three weeks

b) Six weeks

c) Three months

d) Six months

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REFERENCES

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Thankyou

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Congenital Toxoplasmosis

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Toxoplasma gondii�

The Parasite:

Obligate intracellular protozoan parasite.
Definitive host: Cats (shed oocysts in feces)
Intermediate hosts: Humans and other warm-

blooded animals.

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Transmission

Transmission to Humans:

Ingestion of undercooked or raw meat containing tissue cysts.
Ingestion of food or water contaminated with oocysts from cat feces.

Mother-to-Fetus Transmission:

Mother having a primary T. gondii infection during pregnancy

higher transmission rate but less severe disease later in pregnancy

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The Classic Triad (rare)

Chorioretinitis
Hydrocephalus
Intracranial Calcification

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Clinical manifestations

CNS

Microcephaly , Seizures ,Developmental delay/Intellectual disability

Liver

Jaundice , Hepatosplenomegaly

Blood

Anemia ,Thrombocytopenia

Other

Rash
Lymphadenopathy

Subclinical Infection:

Asymptomatic at birth but may develop sequelae later (e.g., chorioretinitis, learning disabilities).

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Diagnosis of Congenital Toxoplasmosis - Prenatal�

Maternal Screening During Pregnancy:

Serological testing for T. gondii antibodies (IgG and IgM).
Recent primary infection is suggested by:

Seroconversion (negative IgG to positive IgG).
Presence of IgM antibodies (can persist for months).
High or rising IgG titers.

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Fetal Diagnosis (Suspected maternal primary infection)

Amniocentesis:

PCR for T. gondii DNA in amniotic fluid.

Fetal Blood Sampling (Cordocentesis):

T. gondii-specific IgM and IgA antibodies in fetal blood

-PCR for T. gondii DNA

Fetal Ultrasound/MRI brain:

Ventriculomegaly, intracranial calcifications

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Diagnosis of Congenital Toxoplasmosis - Postnatal�

Infant Serology:

positive Toxoplasma IgM (after five days of life) and/or IgA (after 10 days of life) is diagnostic of congenital toxoplasmosis

Persistently elevated T. gondii-specific IgG antibodies beyond the expected clearance of maternal antibodies (typically >1 year).

Detection of T. gondii DNA by PCR - In blood or CSF

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Screening for complications

Cerebrospinal Fluid (CSF) Analysis
Ophthalmological Examination: For chorioretinitis.
Neuroimaging (CT or MRI of the Brain)

For hydrocephalus, intracranial calcifications, and other abnormalities.

Auditory Brainstem Response (ABR)

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TREATMENT:�Who to treat? �

Prenatally diagnosed infants
Symptomatic infection -- Symptoms plus documented infection

positive neonatal serology or PCR

Start treatment even if serology inconclusive

The mother has recent documented T. gondii infection

Asymptomatic but confirmed infection (Serology / PCR )

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Treatment regimen

Pyrimethamine plus sulfadiazine plus folinic acid (leucovorin) For 1 year

Or
Pyrimethamine plus Sulfamerazine (or sulfamethazine) plus folinic acid (leucovorin)

Glucocorticoids if

Chorioretinitis
High CSF protein

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THANKS

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Pyrimethamine

2 mg/kg once daily for two days
then 1 mg/kg once daily for six months and
then 1 mg/kg three times per week (ie, Monday, Wednesday, and Friday) to complete one year of therapy, plus

Sulfadiazine

50 mg/kg every 12 hours, plus

Folinic acid (leucovorin)

10 mg three times per week during and for one week after pyrimethamine therapy�

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Adverse effects of treatment:

Pyrimethamine 🡪Neutropenia (generally resolves when the folinic acid dose is increased)

Sulfadiazine🡪Skin exanthems (hives, allergic dermatitis)

G6PD deficiency should be ruled out

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Follow up

Serologies (IgG and IgM)

Every 3-6 months until 18 months or completion of therapy.

Eye examination

Every 3 months until the age of 18 months
Then every 6-12 months throughout childhood.

Hearing assessments

At diagnosis and then at 9 months

Neurologic examination

Every 3-6 months until 1-2 years of age.

Neurodevelopmental surveillance

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MCQ

For how long is the preferred duration of antiparasitic treatment recommended for most infants with congenital toxoplasmosis?
a) Six months
b) One year.
c) Two years.
d) Until serological tests become negative.

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MCQ

For how long is the preferred duration of antiparasitic treatment recommended for most infants with congenital toxoplasmosis?

a) Six months

b) One year.

c) Two years.

d) Until serological tests become negative.

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REFERENCES

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Thankyou

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Congenital Syphilis

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Congenital Syphilis

Caused By Treponema Pallidum

Thin, motile, fastidious

Survive only briefly outside host
Cannot be cultivated successfully on artificial media

Humans are the only natural host.

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Transmission

Transplacental Transmission:

more frequent at advanced gestation

Direct Contact during Birth:

Occasional transmission through infectious lesions.

Not Transmitted in Breast Milk

(Unless infectious lesion on the breast)

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CS Presentations

Placental Presentation

Large, Oedematous, chorioamnionitis
Dark field microscopy for treponemes.

Fetal Presentation

Hydrops, Stillbirth / Neonatal death
Intrauterine death: 25 % of affected
Perinatal mortality: 25-30 %, if untreated

Early Symptomatic presentation – onset <2 years 🡪 Neonatal (in 1^st 5 weeks of life)
Late Symptomatic – after 2 years of life, as late as 40 years

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Neonatal Presentations

Early Symptomatic

Muco-cutaneous (30-60%)

Snuffles – thick or bloody nasal discharge
Small blister on/around palms, soles, nose and anus which desquamate.

Skeletal (60-70%)

Mostly around large joints especially lower limbs (metaphyseal)
Osteochondritis / Osteitis / periostitis
"Moth-eaten" appearance

Neuro-Syphilis

Asymptomatic with Positive VDRL CSF
Rare as acute meningitis

Hepato-splenomegaly, lymphadenopathy

Late Symptomatic

Muco-Cutaneous

Saddle Nose
copper-coloured, flat or bumpy rash on the face, palms, and soles

Hutchison Triad

Hutchison teeth – notched incisors, wide spaced, peg-shaped

Mulberry Molar – hypertrophied enamel

Sensorineural Deafness
Blindness from Interstitial Keratitis

Skeletal

Swelling of joints – painful / painless
Frontal bossing
Nasal Chondritis – short maxilla, high arched palate, saddle nose
Hard Palate perforation

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Diagnostic Modalities

Direct Detection of T. pallidum (if available):

DFA staining, darkfield microscopy, PCR on skin lesions or nasal discharge.

Placental/Umbilical Cord Pathology (if possible): Fluorescent antitreponemal antibody staining.
Serological tests:

Non-Treponemal Tests

VDRL (Venereal Disease Research Laboratory)
RPR (Rapid plasma reagin)

Treponemal Tests (Not used for neonatal period)

T pallidum immobilization (TPI)
Fluorescent treponemal antibody absorption (FTA-ABS)
Microhemagglutination assay for antibodies to T pallidum (MHA-TP)

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TREATMENT SCENARIOS

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�Unlikely Congenital Syphilus�

Known Maternal Syphilis Before Pregnancy

Was adequately Treated
Mother’s NT titre remained low and stable before, during pregnancy and at delivery .�
Then
Rare - Neonatal NT Titre = < 4x maternal titre
Then

No evaluation required
No treatment required

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�Less likely Congenital Syphilis�

Known Maternal Syphilis During Pregnancy

Adequately Treated
Treatment was administered > 4 weeks before delivery
Mother has no evidence of reinfection or relapse�
Then
Neonatal NT Titre = < 4x maternal titre
Then
No evaluation required
Recommended Regimen –

Benzathine penicillin G 50,000 units/kg/dose IM in a single dose

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Possible Congenital Syphilis

Known Maternal Syphilis during Pregnancy

Inadequately Treated
Mother was treated with erythromycin or other nonpenicillin regimen
Mother received treatment < 4 weeks before delivery
Mother had relapse �
Then
Neonatal NT Titre = < 4x maternal titre
Then

Neonatal workup –

CBC, CRP, LFTs, Long Bone Xray, CSF VDRL, Hearing and Eye assessments

Treat with

Aqueous crystalline penicillin G 50,000 U/kg/dose IV Q 12 hrs. first 7 DOL and Q 8 hrs thereafter for a total of 10 days (If neonatal VDRL/RPR positive)
Single IM benzathine penicillin if evaluation normal and follow-up assured.

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Neonatal Disease (Proven Congenital Syphilis)

Abnormal Physical Examination

And / Or

Serum quantitative NT titre 4x > mother’s titre

+

Proven darkfield microscopy or PCR of a lesion or bodily fluid

Do
Neonatal workup

CBC, CRP, LFTs, Long Bone Xray, CSF VDRL, Hearing and Eye assessments

Treat with

Aqueous crystalline penicillin G 50,000 U/kg/dose IV Q 12 hrs. first 7 DOL and Q 8 hrs thereafter for a total of 10 days

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Evaluation for Extent of Organ Involvement

For Proven or Possible congenital syphilis

CSF Analysis
CBC
LFT RFT
Skeletal Survey
Hearing Evaluation (ABR)
Ophthalmologic Examination
Others

Neuroimaging (if neurologic concerns).
Chest radiograph (if pulmonary findings).
Abdominal imaging (if significant organomegaly).

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Follow-up Evaluations�

Crucial for ALL infants evaluated for congenital syphilis, regardless of initial serology or treatment..
Examination
Developmental surveillance and sensory screening —

Yearly hearing evaluation
Yearly vision screening and eye examination
Serial developmental assessments throughout infancy and childhood.

Follow up serology

Expected response – The infant's VDRL or RPR titers should decline by 2-4 months of age and be nonreactive by 6months of age

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MCQ

A newborn whose birthing parent tested positive for syphilis during pregnancy, received inadequate treatment, and has a normal physical exam with the infant's VDRL titer being less than four-fold the maternal titer, is categorized as having:
a) Proven congenital syphilis
b) Possible congenital syphilis
c) Congenital syphilis less likely
d) Congenital syphilis unlikely

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MCQ

A newborn whose birthing parent tested positive for syphilis during pregnancy, received inadequate treatment, and has a normal physical exam with the infant's VDRL titer being less than four-fold the maternal titer, is categorized as having:

a) Proven congenital syphilis

b) Possible congenital syphilis

c) Congenital syphilis less likely

d) Congenital syphilis unlikely

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REFERENCES

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THANKYOU

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Congenital Rubella

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Rubella Virus and Transmission�

Rubella Virus:

RNA virus belonging to the Rubivirus genus.
Human-only reservoir.
Transmission via respiratory droplets.

Maternal Infection During Pregnancy:

Viremia in the mother leads to placental infection and fetal viremia.
Timing of infection is crucial: highest risk of severe defects in the first trimester.

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The Classic Triad of Congenital Rubella�

Cataracts:

Often bilateral, can lead to blindness.

Congenital Heart Defects:

Commonest PDA
Other pulmonary artery stenosis,

ASD, VSD.

Sensorineural Hearing Loss:

Usually bilateral and permanent.

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Other Common Manifestations of CRS�

Growth Retardation:

IUGR and postnatal growth deficiency.

Microcephaly
Developmental Delay/Intellectual Disability
Neonatal Purpura (Blueberry Muffin Rash):

Due to dermal erythropoiesis.

Hepatosplenomegaly, Jaundice
Meningoencephalitis
Glaucoma, Retinopathy
Thyroid Dysfunction:

Hypothyroidism or hyperthyroidism.

Diabetes Mellitus:

Increased risk later in life.

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Diagnosis of Congenital Rubella - Prenatal�

Maternal Rubella Infection During Pregnancy:

Clinical suspicion based on rash, fever, lymphadenopathy.
Serological testing:

IgM antibodies to rubella indicate recent infection.
Significant rise in IgG titers between acute and convalescent samples.

Amniocentesis:

Rubella-specific IgM in fetal blood (if accessible).
Rubella RNA by PCR in amniotic fluid.

Fetal Ultrasound:

microcephaly, cardiac abnormalities, cataracts.

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Diagnosis of Congenital Rubella - Postnatal�

Infant Serology:

Presence of rubella-specific IgM antibodies in the infant

Persistently elevated rubella-specific IgG antibodies beyond the expected clearance of maternal antibodies (typically >6-12 months).

Viral Culture or PCR

Nasopharyngeal swabs, urine, or CSF.

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THANKS

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�Management of Congenital Rubella - No Specific Antiviral Treatment�

No specific antiviral treatment
Supportive care and addressing individual manifestations.

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Management - Addressing Specific Manifestations�

ECHO for Heart Defects
Red Reflex and Eye Consult

For Cataracts, glaucoma, retinopathy

Hearing Assessment

For Sensori-neural Hearing Loss, need for hearing aids, cochlear implants etc.

Developmental Follow-ups
Free T4, TSH

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MCQ

Which of the following is the most common late manifestation of congenital rubella infection (CRI)?
a) Congenital heart disease
b) Cataracts
c) Sensorineural hearing loss
d) Type 1 diabetes mellitus

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MCQ

Which of the following is the most common late manifestation of congenital rubella infection (CRI)?
a) Congenital heart disease
b) Cataracts
c) Sensorineural hearing loss (80%)
d) Type 1 diabetes mellitus

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REFERENCES

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Thankyou