Lucan · Conditions

Perinatal infections (TORCH)

Australian guidance: ASID Management of Perinatal Infections (3rd ed, 2022)

1. Definition and epidemiology

TORCH is a clinical acronym grouping organisms capable of vertical transmission with potentially severe foetal or neonatal consequences: Toxoplasma gondii, Other (syphilis, hepatitis B, varicella zoster virus, parvovirus B19, and others), Rubella, Cytomegalovirus (CMV), and Herpes simplex virus (HSV). In Australia, CMV is the most prevalent congenital infection with an estimated birth prevalence of 0.64% (approximately 3.85 per 1,000 live births), making it the leading infectious cause of non-genetic sensorineural hearing loss and neurodevelopmental disability in children. Congenital rubella syndrome has become rare following the national MMR immunisation program, but syphilis notifications are rising in Australia, particularly among Aboriginal and Torres Strait Islander women, with incidence of congenital syphilis directly reflecting gaps in antenatal screening coverage.

2. Pathophysiology

The pathophysiology of TORCH infections reflects three distinct mechanisms of vertical transmission and tissue injury, as described in Robbins Ch 8. Transplacental haematogenous spread is the dominant route for CMV, rubella, toxoplasma, syphilis, and parvovirus B19; the trophoblast and placental macrophages (Hofbauer cells) are the principal portals, and the degree of foetal injury relates to both gestational timing and pathogen-specific tropism. First-trimester infection with rubella or toxoplasma causes the highest rates of structural damage because organogenesis is incomplete; the rubella virus is directly cytopathic to endothelial cells of developing vessels, producing ischaemic injury to the lens, cochlea, and cardiac outflow tract. CMV establishes latency in mononuclear cells and reactivates; in primary maternal infection approximately 30% of foetuses are infected, and the virus preferentially infects neural progenitor cells in the periventricular germinal matrix, resulting in periventricular calcifications, polymicrogyria, and sensorineural hearing loss through inner-ear hair-cell destruction. Treponema pallidum crosses the placenta from the second trimester and incites an obliterative endarteritis in foetal organs, particularly the liver, lungs, and long bones. Intrapartum transmission is the dominant mechanism for HSV-2, with the greatest risk in primary maternal genital HSV infection near term. Toxoplasma gondii infection in third-trimester has higher transmission rates (30 to 75%) but causes milder foetal injury, in contrast to first-trimester infection where transmission is low (4 to 15%) but damage is severe (34 to 85% risk of adverse outcome).

3. Clinical presentation and diagnostic criteria

The majority of TORCH infections are asymptomatic at birth, making clinical diagnosis unreliable without targeted investigation. Classic neonatal findings that should prompt TORCH evaluation include: intrauterine growth restriction, microcephaly, hepatosplenomegaly, jaundice, petechiae or purpura, anaemia, and thrombocytopenia. CMV-specific findings include periventricular calcifications, chorioretinitis, and sensorineural hearing loss identifiable on the newborn hearing screen. Congenital rubella syndrome (CRS) presents with the triad of sensorineural deafness (60 to 75%), cardiac defects including patent ductus arteriosus and pulmonary artery stenosis (10 to 20%), and ophthalmological abnormalities including cataracts and retinopathy (10 to 25%). Congenital syphilis may present with rhinitis (snuffles), maculopapular rash involving palms and soles, periostitis with pseudoparalysis, hepatomegaly, and a haemolytic anaemia. Congenital toxoplasmosis classically produces a triad of chorioretinitis, intracranial calcification (typically scattered throughout the cortex rather than periventricular), and hydrocephalus, though most infected infants are asymptomatic at birth with sequelae appearing months to years later.

4. Investigations and AU-specific cutoffs

Investigations are guided by the clinical scenario: maternal screening, foetal assessment, or neonatal evaluation.

Maternal screening (antenatal): All pregnant women should be offered rubella IgG and syphilis serology (Treponema enzyme immunoassay, confirmed with RPR or VDRL titre and TPPA or TPHA) at the first antenatal visit. For women at high risk of syphilis (Aboriginal or Torres Strait Islander background, methamphetamine use, male partner who has sex with men, or late presentation to care), repeat serology is indicated at 26 to 28 weeks and again at 34 to 36 weeks and delivery. Routine CMV and toxoplasma screening is not currently recommended in Australia; testing is indicated by symptoms, suggestive foetal ultrasound findings, or known exposure.

Maternal CMV diagnosis: CMV IgG and IgM serology is the first step. If IgG and IgM are both positive, CMV-specific IgG avidity testing is performed immediately; low avidity indicates recent primary infection, high avidity suggests past infection. Seroconversion (rising IgG titre on serial testing) remains the gold standard for recent primary infection.

Foetal diagnosis of CMV: Amniocentesis for CMV polymerase chain reaction (PCR) is the diagnostic test of choice. When performed at or after 21 weeks gestation and at least 6 weeks after maternal infection, sensitivity is 80 to 95% and specificity approaches 100%. Amniocentesis before 20 weeks has sensitivity of only 45%. Foetal ultrasound features consistent with congenital CMV include microcephaly, cerebral ventriculomegaly, intrauterine growth restriction, hydrops, and hepatomegaly; however, sensitivity is only 30 to 50%.

Toxoplasma foetal diagnosis: Amniocentesis for Toxoplasma gondii PCR at 18 to 20 weeks gestation or 4 weeks after maternal infection, with high sensitivity and specificity.

Neonatal CMV diagnosis: Urine and saliva CMV PCR must be collected within 21 days of birth, ideally before 14 days, to distinguish congenital from postnatal acquisition.

Congenital syphilis workup: Infant RPR titre compared to maternal titre; if infant RPR is more than 4-fold higher than maternal serum, treat as congenital syphilis. Additional investigations include full blood examination, liver function tests, urea electrolytes and creatinine, cerebrospinal fluid (CSF) microscopy and serology (CSF VDRL or CSF FTA-Abs), and long-bone radiographs.

5. Management

CMV in pregnancy: If primary maternal CMV is confirmed, seek specialist advice. Behavioural interventions to reduce acquisition should be offered to all pregnant women, including rigorous hand hygiene after nappy changes and avoiding contact with young children's saliva. CMV hyperimmunoglobulin (HIG) is not routinely recommended for prevention; two randomised controlled trials showed no significant reduction in transmission. High-dose valaciclovir (4 g four times daily) commenced early in primary maternal infection in the first trimester has emerging evidence of transmission reduction from one randomised controlled trial and can be considered in specialist settings.

Congenital CMV in neonates: Symptomatic moderate to severe congenital CMV is treated with 6 months of oral valganciclovir, commenced within 30 days of birth, with monitoring of neutrophil counts and liver function tests every 2 weeks initially. Asymptomatic congenital CMV with isolated sensorineural hearing loss: treatment role is debated and should be managed case by case with specialist input.

Syphilis in pregnancy: Treat according to stage using benzathine penicillin G (1.8 g = 2.4 million units intramuscularly as a single dose for early syphilis; 1.8 g intramuscularly weekly for 3 weeks for late syphilis or syphilis of unknown duration). Desensitise if penicillin hypersensitivity, as no alternatives are reliably effective for prevention of congenital syphilis. Repeat RPR serology at 26 to 28 weeks and 34 to 36 weeks for adequacy of response. The Jarisch-Herxheimer reaction complicates up to 45% of treatment for primary or secondary syphilis and should not delay treatment, but foetal monitoring from 26 weeks is recommended.

Toxoplasmosis in pregnancy: Spiramycin (not routinely available in Australia but importable on request) can be considered from the time of maternal diagnosis to reduce placental transmission, particularly before intrauterine foetal diagnosis is confirmed. Once foetal infection is confirmed by amniotic fluid PCR, or from 18 weeks gestation when maternal infection is certain, treatment is changed to pyrimethamine plus sulfadiazine plus folinic acid.

Rubella: There is no specific antiviral treatment. Non-immune pregnant women exposed to rubella should receive 20 mL of normal human immunoglobulin intramuscularly within 72 hours; this may modify maternal disease but does not reliably prevent foetal infection. Post-delivery MMR vaccination is prioritised for susceptible women.

6. Pharmacology and AU PBS notes

Valganciclovir (Valcyte): oral prodrug of ganciclovir. Neonatal dose: 16 mg/kg twice daily orally for 6 months for symptomatic congenital CMV. Dose adjustment required for renal impairment. PBS listing: streamlined authority for cytomegalovirus retinitis and congenital CMV in immunocompromised patients; specialist initiation required. AU brand: Valcyte (Roche).

Benzathine penicillin G (Bicillin L-A): standard first-line for all stages of maternal syphilis. Not PBS-listed as a standalone Authority item for syphilis in pregnancy; supplied through hospital pharmacy or community dispensing under standard PBS antibiotic provisions. No effective substitute for prevention of congenital syphilis; doxycycline and azithromycin are contraindicated in pregnancy or have demonstrated treatment failures. Procaine penicillin 1.5 g intramuscularly daily for 10 days is an alternative for early syphilis in pregnancy when benzathine preparation is unavailable.

Pyrimethamine plus sulfadiazine plus folinic acid (congenital toxoplasma treatment): pyrimethamine 1 mg/kg every 12 hours for 2 days then 1 mg/kg daily for 6 months then 1 mg/kg three times weekly to complete 12 months; sulfadiazine 50 mg/kg every 12 hours; folinic acid 10 mg three times weekly for 12 months. Pyrimethamine is not PBS-listed for this indication in Australia and requires individual patient access via the TGA Special Access Scheme or importation. Spiramycin (antenatal prophylaxis) similarly requires TGA Special Access Scheme importation.

Valaciclovir (Valtrex): used in primary maternal CMV prevention (investigational, 4 g four times daily). PBS-listed for herpes simplex and varicella-zoster; use for CMV prevention in pregnancy is off-label.

7. Complications and monitoring

CMV: Sensorineural hearing loss is the most clinically significant long-term sequela, occurring in approximately 7 to 10% of asymptomatic congenital CMV infants and 34 to 41% of symptomatic infants; hearing loss may be progressive and late-onset. Neurological sequelae of symptomatic congenital CMV include microcephaly (35 to 50%), seizures (10%), chorioretinitis (10 to 20%), and developmental delay (70%). Early mortality within the first 3 months of life occurs in 5 to 10% of symptomatic infants. Monitoring schedule: audiological assessment every 6 months until age 2, then annually until age 6; ophthalmology annual review until age 6; paediatric review 3 to 6 monthly for first 2 years then annually until age 6.

Congenital rubella syndrome: Late-onset manifestations include progressive sensorineural hearing loss, insulin-dependent diabetes mellitus (up to 50 times the rate in the general population), thyroid dysfunction, and panencephalitis. Infants with CRS remain infectious for at least 12 months and must be isolated from susceptible pregnant contacts. Monitoring: ophthalmology, cardiac, and hearing assessments at birth then 3 to 6 monthly.

Congenital syphilis: Follow-up T. pallidum serology at 1, 2, 4, 6, and 12 months of age, or until non-reactive on 2 occasions. If neurosyphilis was present, repeat CSF examination at 6 months. Re-treat if persistently reactive serology or abnormal CSF.

Congenital toxoplasmosis: High long-term incidence of chorioretinitis in untreated infants (even if asymptomatic at birth); this can be substantially reduced by 12 months of treatment. Monitor hearing, vision, and neurodevelopment throughout infancy and childhood.

Drug monitoring for valganciclovir: Full blood examination every 2 weeks while on treatment; withhold if neutrophil count falls below 0.5 x 10^9/L.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.