Congenital Infections:

An Overwiew

By
Junaid Muhib Khan
MD.FAAF.FAAP.CMQ
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Introduction

• TB
• Hep B
• TORCH complex is a medical acronym for a set of perinatal infections .
• The TORCH infections can lead to severe fetal anomalies or even fetal loss.
• They are a group of viral, bacterial, and protozoan infections that gain access to
the fetal blood stream trans-placentally via the chorionic villi.
• Hematogenous transmission may occur at anytime during gestation or
occasionally at the time of delivery via maternal-to-fetal transfusion.

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 Cong. TB

• Congenital tuberculosis Ante-partum (in utero)

• Intrapartum
• Postpartum Exposure to mother or other contact with contagious tuberculosis
• More common than congenital tuberculosis
• Congenital
 Risk of transmission unknown

 ? Higher if mother has primary disease

 Postpartum
 Risk to infants is 60-80% if contact smear positive

 Risk 30-40% if smear negative contact

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 Congenital TB: Pathophysiology
 Ante-partum
 Hematogenous spread through umbilical vein

 Liver, lungs involved

 Aspiration/inhalation of infected amniotic fluid

 Lungs primarily involved

 Intrapartum
 Aspiration/ inhalation of infected amniotic fluid or

infected genital secretions

 Risk of Disease Following Primary Infection

Disseminated TB/
Age TB meningitis Pulmonary TB No Disease
< 1 year 10-20% 30-40% 50%

1-2 years 2-5 % 10-20% 75-80%

2-5 years 0-5% 5% 95%

5-10 years < 0-5% 2% 98%

> 10 years < 0-5% 10-20% 80-90%

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Lancet Infect Dis 2008; 8: 498-510
 Congenital Tuberculosis
 Clinical presentation typically at 2-4 weeks of age
 Nonspecific- mimics bacterial sepsis

 Fever, respiratory distress

 CXR may be abnormal

 Hepatosplenomegaly

 Additional manifestations
 OM/drainage

 Lymphadenopathy

 Cutaneous disease
Congenital TB and Prematurity
 Affected infant often born prematurely
 Multiple reports from neonatal intensive

care units

 Two fold greater risk of prematurity among

Mexican infants born to 35 mothers with
pregnancy complicated by TB

Am J Perinatol 1998; 15: 303-306

 Clinical Features of Congenital Tuberculosis
Sign or Symptom No. of Patients Frequency(%)
Respiratory distress 44 76

Hepatomegaly +/- splenomegaly 38 65

Fever 33 57
Lymphadenopathy 19 33
Poor feeding 18 31
Lethargy, irritability 16 30
Abdominal distention 15 26
Failure to thrive 9 15
Ear discharge 9 15
Rash 5 9

Avery’s Dis of the Newborn,.

 Diagnosis of Congenital TB:
Revised Diagnostic Criteria

 Proved tuberculous lesions AND

 1 of the following
 Lesions in the first week of life

 Primary hepatic complex or caseating hepatic

granulomas
 TB of the placenta or maternal genital tract

 Exclusion or postnatal transmission by thorough

investigation of contacts.

N Engl J Med 1994; 330:1051-1054.

 Evaluation for Congenital TB
 TST- unreliable but helpful to have baseline
 IGRA- very limited data

 Chest radiograph (PA, lateral)

 Mycobacterial confirmation
 Gastric aspirates, tracheal secretions

 Cerebrospinal fluid

 Blood culture

 Otorrhea, tissue

 Yield higher than for older children

Definitions of Positive Tuberculin Skin Test
(TST) Results in Infants, Children, and Adolescents

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 Results of Diagnostic Procedures Performed on 29 Infants With
Congenital Tuberculosis Reported from 1980 to 1994

Type of Specimen Acid-Fast Smear Mycobacterial Culture Smear or Culture

Gastric aspirate 8/9 8/9 9/11

Endotracheal aspirate 7/7 7/7 7/7

Ear discharge 2/2 1/1 2/2

Cerebrospinal fluid 1/2 1/2 1/2

Urine 0/2 0/2 0/2

Peritoneal fluid 1/1 1/1 1/1

Bronchoscopic 1/1 1/1 1/1

specimen
Biopsy specimen 14/19 11/12 16/21

Lymph node 7/8 6/6 7/8

Liver 4/6 1/2 4/6

Skin 1/3 1/1 2/2

Lung 1/1 1/1 2/2

Ear discharge 1/1 1/1 1/1

N Engl J Med 1994; 330: 1051-1054

 Management of the Newborn
Whose Mother has LTBI

 Mother has reactive TST and normal CXR

 If mother is asymptomatic, no separation of

mother and infant is necessary

 Mother should be treated for LTBI

 Newborn needs no further evaluation

 Household members should be evaluated for TB

infection or disease
 Management of the Newborn Whose
Mother has Suspected TB
 Mother has signs/symptoms of TB and/or abnormal CXR
 Evaluation of mother (e.g. PE, sputum, HIV serology)

 Evaluate infant for congenital TB

 If excluded, begin INH

 Separation of mother and infant until evaluation complete and,

if TB suspected, until mother receiving appropriate therapy

 Once INH started for infant, separation no longer necessary

unless mother has DR TB
 Isolation of newborn if intubated or undergoing procedures
involving airway
 Management of Infant with
Postnatal Exposure to Maternal TB
 Determine if age of infant and duration of symptoms in mother
warrant evaluation for congenital tuberculosis
 Evaluation of infant
 PE, TST, chest radiograph

 GA, induced sputum, CSF if warranted

 If mother untreated, separate until isoniazid started for infant

 If evaluation negative
 Start isoniazid

 Repeat TST in 2-3 months

 Consider empiric treatment for LTBI if repeat TST in infant

would not be reliable (< 6 months of age)

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 TORCH
• The capitalization"TORCH”consists of:
• T–TOXOPLASMOSIS
• O- Other infections (Syphilis,Varicella Zoster, ParvovirusB- 19, HEP B)
• R–RUBELLA
• C–CYTOMEGALOVIRUS
• H–HERPES SIMPLEX VIRUS
Frequency of TORCH Infections during Pregnancy in Peshawar, Pakistan
Muhammad Asif Zeb, Shah Faisal Jamal, Awal Mir, Aamir Ali Khan and Aman Ullah
Institute of Paramedical Sciences, Khyber Medical University, Peshawar, Pakistan
Advances in Applied Science Research, 2018, 9(1):22-26

• The present study reveals that the frequency of TORCH infection during pregnancy is 6.99%.
Frequency of anti-Toxoplasma IgM antibodies is 2.5%, Rubella 1.5%, cytomegalovirus 1.8% and
Herpes simplex virus 1.1%

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Effectiveness of interventions to screen and manage infections
during pregnancy on reducing stillbirths:
A review
Sidra Ishaque, Mohammad Yawar Yakoob, Aamer Imdad, Robert L Goldenberg, Thomas P Eisele, and Zulfiqar A Bhutta
BMC Public Health. 2011; 11(Suppl 3): S3.

Conclusions
The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of
syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk
factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH
infections need to be investigated further to help establish the role of prevention/treatment and its
subsequent impact on stillbirth reduction.

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Screening For Torch Infections
• Screening during pregnancy — The practice of screening pregnant women for TORCH
infections varies geographically.
• In the United States, the American College of Obstetricians and Gynecologists (ACOG)
recommends that pregnant women be screened for rubella and syphilis at the first prenatal
visit.
• In UAE we screen for Rubella
• Newborn screening
— Asymptomatic infants generally are not screened for congenital infections
Although identification of immunoglobulin M (IgM) antibodies in the newborn is
suggestive of congenital infection (because IgM antibodies do not cross the placenta),
indiscriminate screening for TORCH infections with a battery of "TORCH titers" is costly
and has a poor diagnostic yield.
Preferred approach involves testing of infants with suspected congenital infections for
specific pathogens based upon their clinical presentation
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Toxoplasmosis
• Toxoplasmosis is a disease caused by an intracellular parasite TOXOPLASMA
GONDII.
• Human acquisition of the infection occurs by:
Oocyst contaminated soil, salads,vegetables.
Ingestion of raw or undercooked meat containing tissue cysts (Sheep, pigs
and rabbits are the most common meat sources)
Unpasteurized goat milk.
Out breaks of toxoplasmosis have also been linked to the consumption of unfiltered
water
• The incubation period of postnatally acquired infection is approximately 7 days,
with a range of 4 to 21 days

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 •Primary maternal
infection in
pregnancy–
Infection rate
higher with
infection in 3rd
trimester.
Fetal death higher
with infection in 1st
trimester

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 Transmission
• Transmission: Vertical transmission can occur in utero
or during vaginal delivery & risk of fetal transmission
is
• 25% in 1st Trimester
• 75% in 3rd Trimester
• 90% during last few weeks prior delivery.
Transmission to fetus from
• Previously seronegative, immunocompetent mother
acute primary infection within 3 months of being
pregnant or during pregnancy
• Reactivation in a previously immune pregnant woman
severely immunocompromised during pregnancy.
• Reinfection of a previously immune pregnant mother
new, more virulent strain

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Signs & Symptoms
• Most infants with congenital toxoplasmosis are asymptomatic or without apparent abnormalities at birth
• Manifestations may include :
Prematurity
• Intrauterine growth restriction IUGR
Fever
Maculopapular rash
Anemia
Jaundice
Seizure
Hepato-spleenomegaly
Thrombocytopenic purpura
Myocarditis
Pneumonitis
Various rashes JMK 2021
The classic triad of findings :
chorioretinitis,
hydrocephalus, and
intracranial calcifications

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Initial Evaluation
• Review of maternal history (evidence of rubella immunity, syphilis serology,
history of herpes simplex virus [HSV], exposure to cats, etc)
• Assessment of physical stigmata consistent with various intrauterine infections
• Complete blood count and platelet count
• Liver function tests (particularly important in HSV infection)
• Radiographs of long bones
• Ophthalmologic evaluation
• Audiologic evaluation
• Neuroimaging
• Lumbar puncture

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Diagnosis

• Serial IgG measurement (for maternal infection)

• Amniotic fluid PCR (for fetal infection)
• Serologic testing, brain imaging, CSF analysis and ophthalmologic evaluation (for
neonatal infection), and PCR testing of various body fluids or tissues

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Confirmed Congenital Toxoplasma Infection

• Any of the following:

• Detection of toxoplasma specific IgM (after 5 days of life) or IgA titres (after 10
days of life) is considered diagnostic of congenital toxoplasmosis in infants with a
positive Toxoplasma IgG titre
• Positive for Toxoplasma IgG beyond 12months of age
• Positive CSF PCR
• Increase in anti-Toxoplasma IgG titer during the first year of life or increasing IgG
titer compared with the mother's

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Management In pregnant women with an established recent infection,
SPIRAMYCIN (3g daily in divided doses) should be given.

• Pyrimethamine at a dose of 1 mg/kg, administered twice daily for 2 days, and then once daily for 6 months,
and then 3 times per week to complete a 12-month total course of therapy (maximum 25 mg/dose); PLUS
• Sulfadiazine at a dose of 50 mg/kg, administered twice daily for a 12-month total course of therapy; PLUS
• Folinic acid (leucovorin) at a dose of 10 mg, administered 3 times per week to complete a 12-month total
course of therapy; folinic acid is used to minimize pyrimethamine toxicity; folic acid may not be substituted
for folinic acid.
• If CSF protein is ≥1 g/dL or patient has severe chorioretinitis: prednisone at a dose of 0.5 mg/kg (maximum
20 mg/dose), administered twice daily until CFS protein <1 g/dL or resolution of severe chorioretinitis; if
steroids are to be used, they should be initiated after 72 hours of anti-Toxoplasma therapy.
• In some centers in Europe, the regimen of pyrimethamine/sulfadoxine every 10 to 15 days is used for
subclinical/mild forms of congenital toxoplasmosis and/or for poor compliance and/or frequent hematologic
adverse effects after the first 2 months of daily therapy with pyrimethamine/sulfadiazine.
• Some centers in Germany have individualized the duration of the postnatal treatment according to the severity
of CT (eg, 3 months’ total treatment for asymptomatic infants; 6 months for mildly symptomatic infants and
12 months for severely symptomatic infants

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 Syphilis
• Treponema pallidum is a spirochaete bacterium with various subspecies that
cause the diseases syphilis, bejel, and yaws. It is transmitted only amongst
humans. It is a helically coiled microorganism usually 6–15 μm long and 0.1–0.2
μm wide
• Route of Infection;
– Direct contact with a spirochete-containing lesion, sexually or
trans-placentally
The incubation period for acquired primary syphilis typically is 3 weeks
but ranges 10 to 90 days

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Transmission
• Humans are the only natural host of T. pallidum
• Congenital syphilis generally is acquired through transplacental transmission of
spirochetes in the maternal bloodstream or, occasionally, through direct contact with an
infectious lesion during birth
• Transplacental transmission of T. pallidum can occur at any time during gestation but
occurs with increasing frequency as gestation advances.
• Women with untreated primary or secondary syphilis are more likely to transmit syphilis
to their fetuses than women with latent disease (60 to 90 versus 40 percent in early latent
and <10 percent in late latent syphilis).
• The risk of transmission decreases with increasing time since primary or secondary
infection and is only 2 percent after four years.
• T. pallidum is not transferred in breast milk, but transmission may occur if the mother
has an infectious lesion (eg, chancre) on her breast
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Syphilis; Clinical Manifestations

Multiple rounded rudimentary enamel

Cusps on permanent 1st molars

The placenta of neonates with congenital syphilis is often large,

thick, and pale. The umbilical cord is edematous and may
resemble a "barber's pole" with spiral stripes of red and light
blue discoloration alternating with streaks of chalky white.

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Diagnosis
• Dark Field Microscopy
– Most specific technique when active disease present.
– Limited by experience of operator, number of live treponemes
– Lesion is cleansed and abraded gently with gauze pad, serous exudate is then
collected on a glass slide.
– T.pallidum has a corkscrew appearance.
– Negative exams on three different days are necessary to consider test negative
• Direct fluorescent antibody in fluid from a lesion, the placenta, or umbilical cord

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Presumptive Diagnosis

• Non treponemal Tests

– Syphilis leads to production of non specific antibodies that react to cardiolipin.
– Quantified by serial serum dilution (four fold change = significance).
– VDRL or rapid plasma regain
Used for screening and monitoring treatment of disease
False positives (pregnancy, autoimmune disorders, infections)
False Negatives (early primary syphilis, late syphilis, prozone effect)
• Treponemal Tests
– Flourescent treponemal antibody absorption test or T pallidum particle agglutination
Confirm diagnosis, more difficult and costly
Remain active for life; not useful in assessing efficacy
False Positives; Lyme disease, SLE, other treponemal infections (YAWS, PINTA)
False Negatives; overwhelming quantity of antibodies (prozone effect)
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 Screening
• Maternal Screening and Treatment
All pregnant woman should be screened
If infected tx = Penicillin G
-f/u with a nontreponemal test and treponemal test q4wks
• Screen infant if;
– Mother has a nontreponemal titer that increased fourfold. OR
Positive treponemal test
without documented treatment
Not treated with penicillin
Tx <4wks prior to delivery
• If signs of congenital syphilis or if infant nontreponemal titer is >4 fold higher than mothers;
Must be treated with Penicillin G
Undergo VDRL test of CSF
CBC, Liver function tests
Long bone radiographs
Opthalmologic Exam
+/- AUS, CXR, neuroimaging
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Management
Inadequate therapy
Treatment with a nonpenicillin antibiotic
Treatment less than four weeks before delivery (including treatment with penicillin)
Inappropriate dose for stage of disease
Inadequate documentation of maternal treatment
Lack of performance of serial non-treponemal* antibody titers after maternal treatment
Maternal therapy was not documented
Inadequate response to therapy
Maternal non-treponemal antibody titers did not decline at least fourfold (two dilutions) after
treatment
Maternal non-treponemal antibody titers suggest reinfection or relapse (ie, fourfold increase)

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 Δ Test for HIV antibody. Infants of HIV-
infected mothers do not require
different evaluation or treatment.
◊ A fourfold change in titer is the same
as a change of 2 dilutions. For example,
a titer of 1:64 is fourfold greater than a
titer of 1:16, and a titer of 1:4 is
fourfold lower than a titer of 1:16.
§ Women who maintain a VDRL titer 1:2
or less or an RPR 1:4 or less beyond 1
year after successful treatment are
considered serofast.
¥ Complete blood cell and platelet
count; CSF examination for cell count,
protein, and quantitative VDRL; other
tests as clinically indicated (eg, chest
radiographs, long-bone radiographs,
eye examination, liver function tests,
neuroimaging, and auditory brainstem
response).
‡ Some experts would consider a single
intramuscular injection of benzathine
penicillin (treatment option 2),
particularly if follow-up is not certain.
† Treatment (option 1 or option 2,
above) with many experts
recommending treatment option 1. If a
single dose of benzathine penicillin G is
used, then the infant must be fully
evaluated, full evaluation must be
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If any part of the infant's evaluation is
Rubella (German Measles)

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Rubella (German Measles)

• Member of Togaviridae family

• Route of Infection;
– Contact with respiratory secretions (direct and droplet)
– Transplacentally
• Occurs 5 – 7 days after maternal inoculation
• Risk of damage due to infection decreases with increased GA

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Transmission
• Intrauterine infection with rubella virus is referred to as congenital rubella
infection (CRI) or syndrome.
• Infection with rubella earlier in pregnancy(1st trimester ) cause worse prognosis
and neonatal complications.
• The virus can be transmitted to the fetus through the placenta and is capable of
causing serious congenital defects, abortions, and stillbirths
• The incubation period for postnatally acquired rubella ranges from 14 to 21 days,
usually 16 to 18 day

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Complications
• Complications;
– Earlier in gestation infection occurs, the more severe the disease
– <12 weeks GA
Often results in congenital defects
Greatest risk is first 10 days of gestation
– >12 weeks GA
May have no clinical manifestations
More likely to result in future hearing loss and visual problems

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Signs & Symptoms
• Transient Clinical Manifestations;
– Lymphadenopathy
– Hepatosplenomegaly
– Thrombocytopenia
– “Blueberry muffin” rash (Dermal erythropoiesis)
– Radiolucent bone disease
– IUGR
– Meningoencephalitis +/- neurological sequelae

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 Manifestations in infancy

Clinical manifestation Frequency Typical time of onset Course

Hearing impairment 60% Early infancy Permanent
Heart defect 45%

Patent ductus arteriosus 20% Early infancy Permanent

Peripheral pulmonic
12% Early infancy Permanent
stenosis*
Microcephaly 27% Neonatal Permanent
Cataracts 25% Early infancy Permanent
Low birth weight (<2500 Poor weight gain may
23% Neonatal
g) persist
Hepatosplenomegaly 19% Neonatal Transient
Purpura 17% Neonatal Transient
Intellectual disability
13% Variable Permanent
(mental retardation)
Meningoencephalitis 10% Neonatal Transient

Radiolucent bone lesions 7% Neonatal Transient

Retinopathy 5% Early infancy Permanent
Late-onset manifestations¶
Hearing loss Permanent
Intellectual disability Permanent
Diabetes mellitus Permanent
Δ
Thyroid dysfunction Permanent
Progressive panencephalitis Permanent
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Diagnosis
• Antenatal detection
• Specific IgM in Fetal blood obtained by percutaneous umbilical cord blood
sampling.
• Rubella antigen and RNA in a Chorionic villous biopsy specimen.
• Postnatal detection of confirmed CRI
• Serology: Detection of Rubella Specific
IgM below 3months (or)
IgG between 6months to 12 months.
• Virus Isolation: pharyngeal secretions/urine sample upto 1 yr

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Management
• Supportive care
• No role for antiviral therapy —
The clinical course of intrauterine rubella infection is not altered by treatment with
antiviral or biologic agents, nor do these agents appear to have any long-term effect
on the duration of viral shedding.
• Multi disciplinary approach
• Hearing loss - hearing aids and referral to an early intervention program
• Structural cardiac defects – Surgical correction
• Ocular abnormalities – Referral to Ophthalmology expert
• CNS abnormalities - special education services, speech, language, occupational, and/or
physical therapy.
• Endocrine abnormalities – Expert Follow-up for Diabetes/Hypothyroidism
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Prevention

• Girls should be vaccinated against rubella before entering the childbearing years.
• Rubella vaccine is a live attenuated vaccine which is available separately or as
triple vaccine (MMR) that contain measles, mumps and rubella.
• Principal goal of Rubella vaccination is Prevention of CRS.
• As per AAP recommendation – two doses of MMR vaccines -1st at 15 months and
the 2nd at 4–6 years
• Special care should be taken in reproductive females to avoid pregnancy for 3
months after MMR vaccination.
• Avoidance of Exposure

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Herpes Simplex Virus
• HSV1 and HSV2 = double stranded DNA viruses from the Herpesviridae family
• Infection is life long as virus lays dormant in dorsal root ganglia
• Route of Infection;
– Contact with infected lesions or mucosa
– Neonates;
passage through vaginal canal during birth or ascending virus after ROM
– Placental transmission;
rare, can cause congenital anomalies or death
– Primary maternal infection during pregnancy (esp third trimester) = greatest risk to fetus
– Postnatal infection;
caregivers kissing or touching the infant

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Transmission
• Transmission typically occurs via direct contact between the neonate and an
infected maternal genital tract
• If the primary HSV infection was acquired during pregnancy, then the risk of
transmission is greater as compared with reactivation of a previous infection
• Incidence of neonatal HSV infection ranges from 1 in 3200 to 1 in 10,000 births
• Enters the host through the inoculation of oral, genital, or conjunctival mucosa.
• Inoculation also can occur through breaks in the skin.
• Dissemination of the virus eventually allows the virus to reach the dorsal root
ganglia, where it remains dormant for the rest of the host’s life.
• Antiviral drugs do not affect latent HSV infection and therefore infection is life-
long

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Signs & Symptoms
• In-utero Infection:
Skin: Scarring, vesicles, hypo/hyperpigmenation Complications
Eyes: Microphthalmia, retinal dysplasia – Untreated
• High morbidity and mortality
CNS: Microcephaly, encephalomalacia, hydranencephaly
– Treated
• Intrapartam/Postpartam Infection: • SEM = best prognosis
SEM disease : Vesicular lesions, Conjunctivitis, excessive tearing, – 50% will have recurrent skin
Ulcerative lesions of the mouth, palate & tongue outbreaks
• Disseminated disease : • CNS Disease
– Good prognosis but significant
Sepsis, Fever, Respiratory distress, DIC,
neurologic sequelae
Skin lesions, CNS involvement(60 to 75%)
• CNS disease+/− Skin :
Seizures, Lethargy, Irritability, Tremors,
Poor feeding, Skin lesions(60 to 70%)
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Lesions Of Neonate With SEM Disease

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Diagnosis
• Diagnosis of neonatal HSV infection can be established through any of the
following methods:
• Isolation of HSV in culture
• Detection of DNA via PCR assays
• Detection of HSV specific antigens using rapid direct immunofluorescence or
enzyme immunoassays.
• EEG and Imaging studies of brain also aids in the diagnosis of HSV encephalitis
• Cytology of vesicular fluid – Presence of Tzanck cells

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 Management
• Acyclovir Therapy- 60 mg/kg/day 3 div doses
• SEM disease : Duration for 14 days
• CNS / Disseminated disease : Duration for at least 21 days,
or longer if the CSF PCR remains positive.
• Infants with ocular involvement : Ophthalmologic
evaluation/ Topical ophthalmic antiviral agents in addition
to parenteral therapy.
• Recent evidence :
• Suggests to start on suppressive therapy following
parenteral treatment with oral acyclovir 300 mg/m2 per
dose three times per day for six months as it reduces
cutaneous recurrences and is associated with improved
neurologic outcomes in infants with CNS disease.
• Prevention :
• C-Section for mothers with genital lesions
• Acyclovir for pregnant mothers with primary HSV
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Management
• Neonates With HSV Infection
Neonates with HSV infection should be hospitalized and managed with contact
precautions if mucocutaneous lesions are present.
• Neonates Exposed to HSV During Delivery.
Infants born to women with active genital HSV lesions should be managed with
contact precautions during the incubation period. Some experts believe that contact
precautions are unnecessary if exposed infants were born by cesarean delivery, provided
membranes were ruptured for less than 4 hours.
The risk of HSV infection in infants born to mothers with a history of recurrent genital
herpes who have no genital lesions at delivery is low, so special precautions are not
necessary.
• Breastfeeding is acceptable if no lesions are present on the breasts and if active lesions
elsewhere on the mother are covered
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VZV

• Route of Infection;
– contact with fluid from vesicles or through airborne contact with respiratory
secretions.
– Congenital varicella is acquired trans-placentally

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Clinical Manifestations

Cutaneous scars, which may be depressed and pigmented in a

dermatomal distribution
●Cataracts, chorioretinitis, microphthalmos, nystagmus
●Hypoplastic limbs
●Cortical atrophy and seizures

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Diagnosis
• Should be suspected in
Mother who has classic varicella S&S
• Prodromal illness with dewdrop lesions developing in crops that form crusts
• Infant who presents with typical vesicular like lesions
• PCR or direct fluorescent antibody of the fluid can be performed.
• IgM titres can diagnose previous disease but will not identify acute infection

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Management
• Acyclovir —
Newborns with severe disseminated VZV infection (eg, pneumonia, encephalitis,
thrombocytopenia, severe hepatitis) are treated with intravenous acyclovir (30 mg/kg per
day in 3 divided doses) for 10 days
Antiviral treatment must be started as soon as possible after the onset of symptoms because most viral
replication has stopped by 72 hours after appearance of the rash.
Evidence supporting use of acyclovir in neonatal varicella is limited to case reports and case series
Indirect evidence is provided from the experience in treating varicella in immunocompromised patients.
Like immunocompromised patients, neonates with disseminated VZV are at increased risk of severe
morbidity and higher mortality compared with older immunocompetent patients.
• Breastfeeding —
Whether VZV is secreted in human milk is uncertain, although VZV DNA has been detected.
Breastfeeding is encouraged in newborns exposed to or infected with varicella because antibody
in breast milk may be protective

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Management Of Exposure
• Management of newborns who are exposed to VZV by maternal infection or
contact with affected individuals includes isolation and postexposure prophylaxis.
• The specific intervention depends upon the timing of exposure, the mother's
serologic status, and gestational age.
• Varicella vaccination, which is used for prevention in older children and adults,
has not been tested for this purpose in newborns.
• Postexposure prophylaxis — Postexposure prophylaxis with varicella-zoster
immune globulin (Varizig) can prevent varicella in exposed neonates or ameliorate
the disease course in patients in whom the infection was not fully prevented
• Varizig is a purified human immune globulin preparation made from plasma
containing high levels of anti-varicella antibodies
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Management Of Exposure
• The American Academy of Pediatrics (AAP), Centers for Disease Control and Prevention (CDC),
and the Advisory Committee on Immunization Practices (ACIP), recommend administration of
Varizig to newborns who have had a significant exposure to VZV plus one or more of the
following :
• Maternal symptoms
– Neonates whose mothers have signs and symptoms of varicella around the time of
delivery (within five days before or two days after) should receive Varizig.
• Preterm infants ≥28 weeks of gestation –
Hospitalized preterm infants born at ≥28 weeks of gestation who have had a significant
exposure to VZV and whose mothers do not have documented immunization, serologic
immunity, or prior documented history of varicella infection should receive Varizig.
• Preterm infants <28 weeks of gestation
– Hospitalized premature infants born at <28 weeks of gestation or who weigh <1000 grams
at birth who have had a significant exposure to VZV should receive Varizig regardless of
maternal history of varicella or vaccination.

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 Management Of Exposure
• Healthy term neonates who are exposed to VZV postnatally (including infants whose mother's rash developed
>48 hours after delivery) generally do not require postexposure prophylaxis.
• This is because postnatally acquired varicella that occurs beyond the immediate newborn period in a term infant
generally is mild.
• However, some experts suggest administering Varizig in this setting (for exposures occurring up to two weeks
after birth) if the mother does not have evidence of immunity to VZV
• Varizig is given intramuscularly at a dose is 125 units (1 vial) for neonates weighing >2.1 kg to 10 kg and 62.5
units (0.5 vial) for children weighing ≤2 kg. Each vial contains lyophilized powder, which must be reconstituted
for intramuscular administration.
• When postexposure prophylaxis is indicated, passive immunization with Varizig should be offered as soon as
possible. The window of passive immunization with Varizig after varicella exposure is up to 10 days
• Its efficacy is inferred from observational data demonstrating considerably lower transmission rates and milder
disease course than would be expected based upon historical data. The supporting evidence is discussed in greater
detail separately.
• If Varizig is unavailable, intravenous immune globulin (IVIG) or prophylaxis with acyclovir can be considered
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 Hep B
Map of hepatitis B prevalence globally

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Etiology
• HBV is a partially double-stranded DNA-containing 42-nm-diameter enveloped
virus in the family Hepad-naviridae. Important components of the viral particle
include an outer lipoprotein envelope containing HBsAg and an inner
nucleocapsid consisting of hepatitis B core antigen (HBcAg).

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Transmission
• Perinatal transmission of HBV is highly efficient and usually occurs from blood
exposures during labor and delivery.
• In utero transmission accounts for less than 2% of all vertically transmitted HBV
infections in most studies.
• Without postexposure prophylaxis, the risk of an infant acquiring HBV from an
infected mother as a result of perinatal exposure is 70% to 90% for infants born to
mothers who are HBsAg and HBeAg positive; the risk is 5% to 20% for infants
born to HBsAg-positive but HBeAg negative mothers.
• Infants born to mothers with very high HBV DNA levels (>200 000IU/mL) are at
high risk of breakthrough infection despite receipt of recommended prophylaxis
• The incubation period for acute HBV infection is 45 to 160 days, with an average
• of 90 days.
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Diagnostic Tests for Hepatitis B Virus (HBV)
Antigens and Antibodies

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 Treatment
• The goal of treatment in chronic HBV infection is to prevent progression to cirrhosis,
hepatic failure, and hepatocellular carcinoma (HCC), with antibody to HBeAg (anti-HBe)
seroconversion as the surrogate endpoint.
• Current indications for treatment of chronic HBV infection include evidence of ongoing
HBV viral replication, as indicated by the presence for longer than 6 months of either
serum HBV DNA greater than 20 000 IU/mL with HBeAg positivity or greater than 2000
IU/mL without HBeAg positivity,
• AND elevated serum ALT concentrations for longer than 6 months or evidence of chronic
hepatitis on liver biopsy. Children without necro-inflammatory liver disease and children in
the immunotolerant phase (ie, normal ALT concentrations despite the presence of HBV
DNA) do not warrant antiviral therapy.
• Treatment response is measured by biochemical, virologic, and histologic response. The
American Association for the Study of Liver Diseases and the Centers for Disease Control
and Prevention (CDC) recommend that women with viral loads >200 000 IU/mL be offered
antiviral therapy to prevent transmission to their child

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 Hepatitis B Immunoprophylaxis
• Two types of products are available for immuno-prophylaxis. Hepatitis B Immune
Globulin.
• HBIG provides short-term protection (3–6 months)
• Hepatitis B Vaccine.
• HepB vaccine is used for preexposure and postexposure prophylaxis and provides
long-term protection.
• Preexposure immunization with HepB vaccine is the most effective means to
prevent HBV transmission.
Breastfeeding of an infant by an HBsAg-positive mother poses no additional risk of
acquisition of HBV infection by the infant with appropriate administration of
HepB vaccine and HBIG

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Administration of Birth Dose of Hepatitis B
Vaccine by Birth Weight and Maternal HBsAg Status.
Follow-up Management of Infants Born to HBsAg-
Positive Mothers
• Infants born to HBsAg positive women should be tested for anti-HBs and HBsAg
at 9 to 12 months of age (generally at the next well-child visit after completion of
the immunization series)
• Testing should not be performed before 9 months of age to maximize likelihood of
detecting late onset of HBV infections
• Immunized infants with anti-HBs concentrations ≥10 mIU/mL and who are
HBsAg negative are considered not to be infected and to have adequate vaccine-
associated immune protection
• Infants with anti-HBs concentrations <10 mIU/mL and who are HBsAg negative
following a 3-dose hepatitis B vaccine series should receive 1 additional dose of
hepatitis B vaccine followed by testing for anti-HBs and HBsAg 1 to 2 months
after the fourth dose

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Follow-up Management of Infants Born to HBsAg-
Positive Mothers
• Infants with anti-HBs concentrations ≥10 mIU/mL and who are HBsAg negative
after the fourth dose are considered not to be infected and to have adequate
vaccine-associated immune protection
• Infants with anti-HBs concentrations <10 mIU/mL and who are HBsAg negative
after the fourth dose should receive 2 additional doses of vaccine, separated by at
least 8 weeks, followed by testing for anti-HBs and HBsAg 1 to 2 months after the
sixth dose
• An alternate approach for children who have completed a 3-dose series of HepB
vaccine but did not achieve anti-HBs titers ≥10 mIU/mL is to give 3 additional
doses of HepB vaccine at the same dosing intervals as the first series and then
retest for anti-HBs titers 1 to 2 months after the third dose of this second series

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