TORCH

• Congenital infections (sTORCH)
• By professor Dr. Khalid alaaraji, University of Kerbala, College of Medicine, Department of pediatric
• Objectives


  • Why diagnosis of TORCH infection delayed?
  • What are the laboratory evaluations?
  • TORCH infection (Herpes Simplex, Rubella, Toxoplasmosis, Cytomegalovirus infection, Syphilis)
  • Mode of transmission
  • Clinical manifestation
  • Diagnosis
  • Treatment
• Infections in pregnancy are common, but few cause fetal infection
• The fetus may become infected in utero (rubella, cytomegalovirus, toxoplasmosis, HIV) or the newborn may acquire an infection at the time of the birth through contact with the infected blood or vaginal secretion (herpes simplex & HIV)
• Diagnosis of TORCH infection may be delayed


  • Most maternal infections known to cause fetal infection are either asymptomatic or too subtle to recognize clinically
  • Most congenitally infected infants are born without symptoms or signs & it may be weeks, months or even years before adverse effect become apparent
• Occasionally congenitally infected infants may present with IUGR, hepatosplenomegaly, skin rash in neonatal period, jaundice, and purpura (e.g. toxoplasmosis, CMV, or rubella)
• Laboratory evaluation of patients thought to have a congenital infection

  • Isolation by culture for: rubella, CMV, HSV
  • Identify the antigen of the pathogen as for hepatitis B
  • Identify fetal production of antibodies (IgM or increasing titer of IgG) for toxoplasmosis, syphilis, parvovirus, or HIV
• Neonatal Herpes Simplex


  • Transmission: Usually contracted at delivery from contact with genital secretion that contains infectious virus
  • The risk to an infant born vaginally to a mother with a primary genital herpes is about 33% to 50%, while the risk to an infant born to a mother with a reactivated infection is less than 5%
  • Neonatal herpes infection avoided by cesarean section but in most cases, the mother is symptom-less, about 75% of infants are born to mothers with no previous history or no clinical findings consistent with HSV infection
  • The causative agent: 65% HSV-2, and 35% HSV-1
  • Most infants are normal at birth, and symptoms of infection develop at 5-10 days of life
• Patterns of neonatal herpes infection

  • Infection localized to CNS (encephalitis), presents later, mean age of diagnosis 8-17 days
  • Infection localized to the skin, eye, or mouth (SEM disease); most present at 5–11 days of life and typically develop a few small vesicles
  • Disseminated infection, a picture resembling bacterial sepsis, most present at 5-7 days of age
• Diagnosis of neonatal herpes simplex

  • Rapid diagnosis is by direct fluorescence assay (DFA) testing of specimen from skin lesions
  • Gold standard for diagnosis is by Culture (of lesions and/or mucosal sites) but is insensitive in detection of CNS involvement
  • Diagnosing CNS disease is by PCR of CSF detection of HSV nucleic acid and may provide prognostic information -- PCR of blood may also be useful
• Treatment of neonatal herpes simplex virus (HSV) infections


  The treatment of choice is acyclovir
• Congenital rubella


  • Congenital rubella is preventable condition
  • The virus is teratogenic
• Transmission of congenital rubella

  Congenital rubella occurs through transplacental transfer of the organism from the mother to the fetus
• Fetal damage based on timing of maternal rubella infection

  • Weeks 1-8: Damage to about 80-85% of fetuses, most likely to result in severe and multiple defects (microphthalmia, cataract, glaucoma, salt & pepper chorio-retinitis, PDA, PS, deafness, microcephally)
  • Weeks 9-12: Damage to about 50% of fetuses, most likely hearing impairment. Other defect can occur
  • Weeks 13-20: 16% of infants are likely to be affected. Damage other than congenital hearing loss is unusual
  • Infection after 5 months' gestation does not seem to cause disease
• Diagnosis of congenital rubella

  • Virus isolation; Rubella virus can be isolated from blood, urine, CSF, and throat swab specimens
  • Rubella-specific IgM antibody in the newborn indicates congenital rubella infection and may remain up to 3-6 months of age
  • Rubella IgG antibody persisting in the serum beyond about 6-9 months of age (when passively acquired antibodies from the maternal circulation can usually no longer be detected) is another useful method for diagnosis
• Toxoplasmosis


  • The causative agent is the protozoan Toxoplasma gondii
  • Infection is associated with consumption of the raw or under-cooked meat containing cysts or the ingestion of the cysts from the feces of the infected cats, either directly or from contaminated soil
• Transmission of congenital toxoplasmosis


  • Occurs through vertical transmission of Toxoplasma gondii by transplacental transfer of the organism from the mother to the fetus
  • Organism transfer occurs after an acute maternal infection & fetal infection rarely can occur after reactivation of disease in an immunocompromised pregnant mother
• Clinical features of congenital toxoplasmosis

  • 75-90% of the infected neonates is free of symptoms
  • Rarely the classic triad of features may be seen at birth: Hydrocephalus, Chorio-retinitis, Intracranial calcification
  • In addition to a variety of non-specific clinical manifestations may occur e.g. prematurity, IUGR, hypotonia, convulsions, jaundice, hepatosplenomegaly, thrombocytopenia, and CSF lymphocytosis with elevated protein
• Diagnosis of congenital toxoplasmosis

  • IgG-specific antibodies achieve a peak concentration 1 to 2 months after infection and remain positive indefinitely
  • For infants with seroconversion or a fourfold increase in IgG titers, specific IgM antibody determinations should be performed to confirm disease
  • Measurement of IgA and IgE antibodies can be useful to confirm the disease
• Treatment of congenital toxoplasmosis

  • Pyrimethamine + sulfadiazine with a course of folinic acid throughout the first year of life
  • The treatment may decrease the frequency or severity of the adverse sequel
• Cytomegalovirus (CMV) infection


  The most common congenital infection and the leading cause of sensorineural hearing loss, mental retardation, retinal disease, and cerebral palsy
• Transmission of congenital CMV

  • Transplacental: associated with more severe complications
  • Natally: maternal cervical secretions are the likely source of infection (not associated with newborn illness or CNS sequelae)
  • Postnatally: breast milk (not associated with newborn illness or CNS sequelae)
• When primary infection occurs in mothers during a pregnancy, the virus is transmitted to the fetus in approximately 35% of cases
• Prognosis of infants with CMV infection

  Infants with CMV infection have the worst prognosis if: Symptomatic at birth (have microcephaly &/or intracranial calcifications)
• Clinical features of congenital CMV infection

  • > 90% of infants are free of symptoms
  • Approximately 10% of infected infants are SGA and have symptoms at birth (microcephaly, thrombocytopenia, hepatosplenomegaly, hepatitis, intracranial periventricular calcifications, chorioretinitis, and hearing abnormalities and some with blueberry muffin (dermal erythropoiesis))
  • Additional 10% of infected infants may not present until later in infancy or early childhood, when they are found to have sensorineural hearing loss and developmental delays
• Diagnosis of congenital CMV infection

  • Isolation by culture (detection of virus in the urine or saliva)
  • PCR may be useful in diagnosis in selected cases
• Treatment of congenital CMV infection

  Ganciclovir is antiviral agent used in severely symptomatic congenital CMV infection to decrease the progression of hearing loss
• Syphilis


  • The causative agent is Treponema pallidum
  • Transmitted transplacentally from the infected mother to her fetus, and less commonly, at birth
  • Syphilis during pregnancy has transmission rate of 100%
• In untreated pregnant women, syphilis may be transmitted to the fetus at any time, but transmission to the fetus is more common during the first year after the mother has acquired syphilis
• Early congenital syphilis


  • Usually apparent by 3 months of age but can be up to 2 years
  • Presenting signs: Syphilitic rhinitis (snuffles), 'Barber' pole umbilical cord, Cutaneous lesions, Other systemic findings: meningioencephalitis, chorioretinitis, hepatosplenomegaly, lymphadenopathy, low birth weight, prematurity, anemia, thrombocytopenia, respiratory distress and osteochondritis
• Late congenital syphilis


  • Develops >2 years of age
  • Cutaneous findings: rhagades & gummata
  • Extracutaneous findings: Neurosyphilis, Interstitial keratitis, Sensorineural hearing loss, Bony changes (saddle nose, frontal bossing, saber shins, syphilitic arthritis, and Clutton joints)
• In congenital syphilis, congenital malformations are not occurring
• Diagnosis of congenital syphilis

  • Non-treponemal reagin antibody tests: (VDRL, rapid plasma reagin RPR)
  • Specific tests: fluorescent treponemal antibody absorption (FTA-ABS) test & microhemagglutination test for T. pallidum (MHA-TP)
  • Positive CSF VDRL or RPR tests or treponema PCR is diagnostic of CNS involvement
• Treatment of congenital syphilis

  T. pallidum is extremely sensitive to penicillin. Treatment is for at least 10 days-14 days. All babies treated until VDRL –ve