Intrauterine infections:“TORCH”

אופק: קלוטשטיין אריאלה מציגה

' שלזינגר: יחיאל פרופ הנחיה

Hypothetical case

S.A. female neonate Has:

Jaundice

HSM

Ptechiae

PDA

Lymphadenopathy

Hearing loss

What does she have??

Congenital infections :

3 Routs of infection:

Trans placental: TORCH Ascending/intrapartum: HSV, CMV, HBV, HIV Breast milk: HBV, CMV, HIV

Transplacental infection

May occur at any time during gestation Signs and symptoms may be present at birth or be

delayed for months of even years. importance of stage of embryonic life in the

manifestations of the infection: 1st trimester: may alter embryogenesis and result in

malformations (rubella)

3rd trimester: often results in active infection at the time of delivery (toxoplasmosis, syphilis)

Protection

Maternal antibody is effective for protection of the fetus, in some of the cases (rubella)

transplacental transmission of infection to a fetus is variable because the placenta may function as an effective barrier

Clinical signs and symptoms

Maternal- most are asymptomatic

Infant- range from early spontaneous abortion, congenital malformation, intrauterine growth restriction, premature birth, stillbirth, acute or delayed disease in the neonatal period, or asymptomatic persistent infection with sequelae later in life.

In some cases, no apparent effects are seen in the newborn infant.

What is TORCH?

T- Toxoplasmosis

O- others

R- Rubella

C- cytomegalovirus (CMV)

H- Herpes

Toxoplasmosis

Caused by the obligate intra-cellular parasite Toxoplasma Gondii

Route of infection:

Fecal-oral: Cat feces uncooked meet, contaminated water and soil, unpasteurized goat milk.

Usually, the infection causes a mild flu-like illness, or no illness at all.

BUT, in immunocompremised or pregnant women it can be fatal, and cause symtoms such as: encephalitis, myocarditis and pneumonitis.

Toxoplasmosis- continue …

Fetal transmission: in a primary infection, or chronic disease in

immunocopremised mother.

The risk of fetal transmission increases with gestational age

The earlier in pregnancy the transmission occurs- the damage is worse.

Signs and symptoms: 1st trimester: death, opthlmologic and CNS sequalea

2nd trimester: “classic triad”: hydrocephalus, intracranial calcifications, chorioretinitis. Jaundice, HSM, anemia, lymphadenopathy, microcephaly, developemental delay, visual and hearing problems, and seizures.

3rd trimester: usually asymptomatic at birth.

Toxoplasmosis- continue …

Toxoplasmosis- continue …

Treatment: Pyrimethamine- antimalarian medication

Sulfazidime

Leucovorin- folinic acid

Others…

We’ll just come back to it later…

Rubella- “The German Measles”

Member of the Togaviridae family. Route of infection:

Respiratory secretions (both direct contact and droplets)

Transplacentally.

Rubella- continue…

Clinical manifestations: “blueberry muffin” rash

Lymphadenopathy

HSM

Thrmbocytopenia

Interstitial pneumonitis

Radiolucent bone disease

IUGR

Hyperbilirubinenemia

Complications: Eye problems:

micropthalmus, pigmentary retinopathy, cataracts, glaucoma

Cardiac: peripheral pulmonic stenosis, PDA

Endocrine: Diabetes mellitus

Neurologic: developmental delay, encephalitis, sensorineural hearing loss

Rubella- continue…

Diagnosis: Positive infant rubella IgM titer- recent infection

Culture: blood, urine, CSF, oral & nasal secretions

persistently elevated or rising IgG titers over time.

Treatment: Supportive care only.

Cytomegalovirus

Member of the Herpesvirus family Most common congenital infection in the US (0.5-1%

of live births in industrialized nations, approximately 40000 annualy in the US)

Route of infection: Transplacentally

During delivery

Postnatally (breastmilk (causes no clinical sequelae), or direct contact with other body fluids)

Maternal infection before pregnancy significantly reduces the risk of congenital CMV.

CMV- continue… Clinical manifestations:

Most babies are asymptomatic at birth (90%)

Infants to mothers with primary infection- 5-20%: overtly symptomatic.

30% mortality rate

80% of survivors: severe neurologic morbidity

Symptoms include:

IUGR

Microcephaly

Periventricular calcifications

HSM

Petechiae

Hearing loss

Jaundice

Thrombocytopenia

retinitis

Hypotonoia

Lethargy

In preterm infants may present as sepsis

CMV- continue… Complications:

CNS sequelae: retinitis, sensorineural deafness, developmental delay) Will appear in 20% of asymptomatic neonates Will appear in 50% (or more!) of symptomatic neonates

Diagnosis: demonstration of the virus in body fluids (e.g. urine or pharyngeal

secretions). Serology for CMV IgG antibody determination are not useful in this case.

Laboratory abnormalities include: abnormal blood counts (especially thrombocytopenia), hemolytic anemia, elevated transaminases, and elevated direct and indirect serum bilirubin.

Treatment: no approved agent Ganciclovir- improves hearing loss and neurodevelopmental

outcomes

Herpes simplex virus

Double-stranded DNA virus of the herpesviridae family

Route of infection: Primarily: during birth or virus ascending after the rupture

of membranes.

Transplacentally- rare

Postnatally

Greatest risk: primery maternal infection during third trimester.

HSV- continue…

Clinical manifestations: SEM disease: skin, eyes, mucosal involvement

CNS disease- temperature instability, respiratory distress, poor feeding, and lethargy (nonspecific)

Disseminated disease with multiple organ involvement Usually presents in the first 6 weeks.

Most are asymptomatic at birth although many are born prematurely

Complications: Untreated- high morbidity and mortality

Treated: SEM- best prognosis. 50% will suffer from recurrent skin outbreks.

CNS- good survival, significant neurologic sequelae

HSV- continue…

Diagnosis: Serum HSV IgM

HSV PCR of CSF- test of choice, may be false negative in the first 5 days

HSV culture of a lesion/mucosal surface- best for SEM

Treatment: IV acyclovir

improves mortality in all infants

Improves neurologic development in those with SEM and disseminated disease.

And…. Back to Others!

HIV HBV Parvovirus B19 Syphilis

HCV

VZV

TB

HIV Member of the retroviridae family. Route of infection to the fetus:

Transplacentally

During labor and delivery- the highest risk (exposure to maternal blood)

Through breastfeeding

Clinical manifestations: Asymptomatic at birth

T-cell count declines and opportunistic infections take hold: Pneumocystis jiroveci, VZV, CMV, HSV….

HIV- continue… Diagnosis:

The American Academy of Pediatrics and the CDC: HIV screening for all pregnant women in the US.

According to viral load: HIV drug prophylaxis

C-section before rupture of membranes (viral load greater than 1000 copies/mL at full term delivery)

avoidance of breastfeeding

Early detection in the infant

HIV- continue… Diagnosis:

In the infant: HIV-1 DNA/RNA pcr at: 14-21 days after birth

1-2 months

4-6 months

Considered uninfected if: 2 negative tests- one after 1 month, and another at 4 months +2 negative antibody tests from different specimens obtained at 6 months

+

Treatment: Infants suspected: zidovudine until 6 weeks of age Infants confirmed: further antiretroviral treatment

HBV DNA virus of the hepadnavirus family Route of infection:

transplacentally- rare

During delivery with exposure to maternal blood- most cases.

Clinical manifestations: Most asymptomatic at birth

Rarely- signs of hepatitis: jaundice, thrombocytopenia, elevated transaminase conc. , rash.

The risk of morbidity and of progressing to a chronic infection and disease are inversely proportional to gestational age at the initial infection

HBV- continue…

So… why are we worried? Because- 25% of children chronically infected with HBV will

develop hepatocellular carcinoma or cirrhosis!

Diagnosis: In the US- women are screened for HBsAg

If positive- the infant should receive HBV vaccine and Hepatitis B immune globulin within 12 hrs of birth.

They should complete the regular program of vaccinations to HBV+two more+ HBsAg and anti-HBs testing at 9 months of age

HBV- continue…

If the mother’s HBV status is unclear: Immediate test for HBsAg:

If negative- no further treatment

If positive- the infant should receive HBV immunoglobin within 7 days of birth.

Treatment: There is no treatment for acute HBV

For chronic HBV- Lamivudine- approved for 2 years of age and older.

Parvovirus B19

Single-stranded DNA virus Usually causes “fifth disease” (“slapped cheek”), and

other symptoms. Route of infection:

Respiratory tract secretions

Contaminated blood

Transplacentally

Clinical manifestations: Hydrops fetalis (due to severe fetal anemia)

Pleural end pericardial effusions

IUGR

death

Hydrops fetalis:  a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments.

Very high mortality rates

Parvovirus B19- continue…

Diagnosis: IgM titer from the infant serum

PCR of amniotic fluid

Treatment: Supportive care

Hypothetical case

S.A. female neonate Has:

Jaundice

HSM

Ptechiae

PDA

Lymphadenopathy

Hearing loss

What does she have??

Rubella!!

Summary Timely diagnosis of congenital infections is crucial to the

initiation of appropiate therapy High index of suspicion and awareness is required:

Laboratory results obtained from the mother during pregnancy

Clinical manifestations including:

Hydrops fetalis

Microcephaly

Seizures

Cataract

Hearing loss

Congenital heart disease

HSM

Jaundice

Rash

thrombocytopenia

The END…