TORCH Infections

Toxoplasmosis

Other (Syphilis)

Rubella

CMV

HSV

Background

TORCH infections are a group of congenitally acquired infections that cause significant morbidity and mortality in neonates. These infections are acquired by the mother and passed either transplacentally or during the birth process. While each infection is distinct, there are many similarities in how these infections present. It is important to consider TORCH infections whenever a neonate presents with intrauterine growth restriction (IUGR), microcephaly, intracranial calcifications, conjunctivitis, hearing loss, rash, hepatosplenomegaly, or thrombocytopenia.

Although the five classic infections are discussed here, the “other” category now also includes HIV, VZV, parvovirus B19, enteroviruses, and others.

There is significant controversy regarding the benefits and cost-effectiveness of universal screening for these diseases and universal antenatal screening is not currently recommended in the United States. Nonetheless, a “TORCH panel” is used by many institutions.

Fun Fact:

In 1971 Andres Nahmias proposed the acronym ToRCH to denote 4 congenital infections that are sometimes difficult to distinguish: TOxoplasmosis, Rubella, Cytomegalovirus, and Herpes Simplex Virus. In 1975 Harold Fuerst proposed that one “particularly disturbing” omission be added to the acronym: syphilis. The new acronym he proposed was STORCH, German for “stork,” which he thought was a particularly suitable name given its association with the perinatal period.

Only a year later Roger Brumback proposed the acronym TORCHES (TOxoplasmosis, Rubella, Cytomegalovirus, HErpes, Syphilis) because it would be better recognized by pediatricians already familiar with the old acronym. As more infections that cause similar sequelae became recognized the “O” in the acronym came to stand for “other.”

Toxoplasmosis:

• Causative Organism – Toxoplasma gondii
• Transmission

1. Transplacental
2. Fecal-oral route
3. Oocysts excreted in cat feces
4. Found in undercooked meat, contaminated water/soil, and unpasteurized goat milk
5. Risk of fetal infection increases with gestational age
6. Severity of fetal infection decreases with gestational age
      

Clinical Manifestations

1. First Trimester – often results in death
2. Second Trimester – classic triad

a.       Hydrocephalus
b.      Intracranial calcifications
c.       Chorioretinitis 

3. Third Trimester – often asymptomatic at birth
4. Symptoms may also include fever, IUGR, microcephaly, seizure, hearing loss, maculopapular rash, jaundice, hepatosplenomegaly, anemia, and lymphadenopathy

Diagnosis

• Definitive – Isolating organism from placenta, serum, or CSF
• Also available – PCR & IgM titer (IgG will be elevated if mother is infected regardless of transmission)

Treatment

• Pyrimethamine 2 mg/kg (maximum 50 mg/dose) once daily for two days; then 1 mg/kg (maximum 25 mg/dose) once daily for six months; then 1 mg/kg (maximum 25 mg/dose) every other day to complete one year of therapy, plus
• Sulfadiazine 100 mg/kg per day divided in two doses every day for one year, plus
• Leucovorin 10 mg three times per week during and once a week after pyrimethamine therapy.
• Infants should be weighed weekly and dosages adjusted accordingly.
• Glucocorticoids (Prednisone 0.5 mg twice per day) are added if CSF protein is > 1 g/dL or when active chorioretinitis threatens vision.

Syphilis

Causative Organism – Treponema pallidum

Transmission

1. Transplacental
2. Sexual activity

Clinical Manifestations

1. Majority are symptomatic at birth
2. Early Congenital Syphilis (symptoms at 1-2 months of age)
3. Maculopapular rash, “snuffles,” maculopapular rash, lymphadenopathy, hepatomegaly, thrombocytopenia, anemia, meningitis, chorioretinitis, osteochondritis
4. Late congenital Syphilis (symptoms after 2 years of age)

• Hutchinson Teeth 
• Mulberry Molars 
• Perforated hard palate 
• Rhagades (cracks or fissures in the skin around the mouth)
• Saber Shins 
• Sensorineural hearing loss (CN VIII)
• Interstitial Keratitis
• Saddle Nose

Diagnosis

• Dark field microscopy
• FTA-Abs, RPR, VDRL

Treatment

• Penicillin
  • For Infants less than one month, either as a single dose of benzathine penicillin G (50,000 units/kg, intramuscularly [IM]) or as a ten day course (aqueous penicillin G 50,000 units/kg intravenously (IV) every 12 hours (for infants ≤7 days of age) and every 8 hours (for infants >7 days of age) for a total of 10 days, or  Procaine penicillin G 50,000 units/kg intramuscularly (IM) as a single daily dose for 10 days
      
  • Single-dose therapy is contraindicated for asymptomatic infants born to women with inadequate/suboptimal treatment unless the infant has undergone appropriate evaluation (CSF quantitative VDRL, cell count, and protein; CBC with differential and platelet count; and long-bone radiographs) and has completely normal results 
       
  • For children diagnosed with congenital syphilis after one month of age (including those with late congenital syphilis) and children with acquired syphilis should be treated with aqueous penicillin G (50,000 units/kg intravenously every four to six hours for 10 days) however some experts suggest that the 10-day course of aqueous penicillin be followed with a single dose of benzathine penicillin (50,000 units/kg intramuscularly).

Rubella

Causative Organism - Togavirus

Transmission

1. Transplacental
2. Respiratory secretions

Clinical Manifestations

• “Blueberry Muffin” rash due to extramedullary hematopoiesis   
• Cataracts

   https://en.wikipedia.org/wiki/Congenital_rubella_syndrome

• “Salt and Pepper” retinopathy 
• Radiolucent bone disease (long bones)
• IUGR, glaucoma, hearing loss, pulmonic stenosis, patent ductus arteriosus, lymphadenopathy, jaundice, hepatosplenomegaly, thrombocytopenia, interstitial pneumonitis, diabetes mellitus

Diagnosis

• Culture from blood, urine, CSF, oral/nasal secretions
• IgM titer

Treatment

• Supportive care

Cytomegalovirus

Causative Organism – Human herpesvirus 5

Transmission

1. Transplacental
2. Perinatal (contact with vagina during delivery or breast milk after delivery)
3. Contact with bodily fluids (urine/saliva)
4. Transmission is possible through reactivation of latent virus (decreased risk of transmission)

Clinical Manifestations

• Majority are asymptomatic at birth
• Periventricular calcifications
• IUGR, developmental delay, microcephaly, sensorineural hearing loss, retinitis, jaundice, hepatosplenomegaly, thrombocytopenia, hypotonia, lethargy, poor suck
• Preterm infants may appear septic – apnea, bradycardia, intestinal distension)
• Postnatal infections are generally asymptomatic

Diagnosis

• Culture (urine or pharyngeal secretions)
• PCR

Treatment

• Studies have shown that gancyclovir can improve hearing loss and neurodevelopmental outcomes.  One report showed 6 mg/kg per dose administered IV for six weeks in newborns with severe congenital CMV disease and neurologic impairment showed protection against hearing loss and head circumference growth in the first 6 to 12 months of life.
• Supportive care

Herpes Simplex Virus

Causative Organism – Human herpesvirus 1 & 2

Transmission

1. Perinatal (contact with vagina during delivery)
2. Contact after rupture of membranes
3. Direct contact with affected areas

Clinical Manifestations

1. SEM disease (Localized to skin, eyes, and mucosal)

• Vesicular lesions on an erythematous base
• Keratoconjunctivitis, cataracts, chorioretinitis 
• Ulcerative lesions of the mouth, palate, and tongue

2. CNS disease

• Seizure, lethargy, irritability, tremor, poor feeding, temperature instability, full anterior fontanelle

3. Disseminated disease

• Multiple organ involvement (CNS, skin, eye, mouth, lung, liver, adrenal glands)
• May appear septic – fever/hypothermia, apnea, irritability, lethargy, respiratory distress
• Hepatitis, ascites, direct hyperbilirubinemia, neutropenia, disseminated intravascular coagulation, pneumonia, hemorrhagic pneumonitis, necrotizing enterocolitis, meningoencephalitis, skin vesicles

Diagnosis

• PCR of CSF, IgM titers, HSV culture of a lesion

Treatment

• Acyclovir IV at a dose of 60 mg/kg per day IV divided every eight hours.  
• Treatment for localized SEM disease should be for a minimum of 14 days if disseminated and CNS disease have been excluded.
• Treated for disseminated and CNS disease should be for a minimum of 21 days and repeat lumbar puncture is recommended to make sure the HSV DNA PCR is negative and all CSF parameters have returned to normal before discontinuing therapy.

References:

1. Brumback RA. TORCHES. Pediatrics. 1976; 58(6):916
2. Epps RE, Pittelkow MR, Su WP. TORCH Syndrome. Seminars in Dermatology. 1995; 14(2):179-86
3. Fuerst HT. Flame or Bird? Pediatrics. 1975; 56(1):107
4. Jeannine Del Pizzo. Focus on Diagnosis: Congenital Infections (TORCH). Pediatrics in Review. 2011; 32:537-542
5. Johnson K. Overview of TORCH Infections. UpToDate, Inc. Ed. Torchia M, Weisman L, Morven S. October 11, 2012. The University of Chicago. October 27, 2012.
6. Naumias AJ, Walls KW, Stewart JA, Flynt WJ. The ToRCH complex-perinatal infections associated with toxoplasma and rubella, ctyomegalo- and herpes simplex viruses. Pediatric Research. 1971; 5:405-406
7. Tian C, Ali SA, Weitkamp J. Congenital Infections, Part I: Cytomegalovirus, Toxoplasma, Rubella, and Herpes Simplex. Neoreviews. 2010; 11(8):e436-46