Specific Pathogens (TORCHS)

Specific Pathogens (TORCHS)

Toxoplasmosis

• Caused by protozoan, toxoplasma gondii, an intracellular protozoa parasite.
• Domestic cat is the definitive host with infection via:
  • Ingestion of oocysts (uncocked meats, unwashed fruits and vegetables).
  • Contact with oocysts in feces or soil.
• Transmission occurs when a non-immune mother acquires primary infection during pregnancy, and the parasite crosses the placenta.
• Infection of the mother in early pregnancy: low risk of transmission rate (10–15%) but severe disease in the fetus.
• Infection of the mother in late pregnancy: high risk of transmission rate (60–90%) but milder disease.

Pathophysiology

• Parasite invades the placenta → enters fetal circulation.
• Causes tissue cysts and inflammation in brain, eye, and other organs.
• Fetal immune system is immature → severe manifestations.

Clinical Manifestations

• Most (70 – 90%) are asymptomatic at birth.
• Classic triad of symptoms:
  1. Chorioretinitis.
  2. Hydrocephalus.
  3. Intracranial calcification (diffuse, not periventricular like CMV).
• Other symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, thrombocytopenia and lymphadenopathy.
• Initially asymptomatic infants are still at high risk of developing abnormalities especially chorioretinitis.

Visual Evidence - Chorioretinitis of congenital toxoplasmosis

Congenital Toxoplasmosis

Diagnosis

• Maternal IgG test indicates past or chronic infection.
• Fetal diagnosis:
  • Amniotic fluid PCR for T. gondii DNA.
  • Ultrasound: hydrocephalus, intracranial calcifications, HSM growth restriction.
• Neonatal diagnosis:
  • Serology (persistent IgG after 12 months = congenital infection).
  • IgM (produced by infant, not maternal).
  • Neuroimaging (CT/MRI).
  • Ophthalmic exam.

Management

• Prevention: Educate pregnant women: Avoid raw/undercooked meat; Wash fruits/vegetables; Avoid handling cat litter or use gloves. Screening policies.
• Management during pregnancy: Spiramycin (reduces vertical transmission).
• If fetal infection confirmed: pyrimethamine + sulfadiazine + folinic acid (after 18 weeks gestation).
• In neonates: Combination therapy: pyrimethamine + sulfadiazine + folinic acid for 1 year.
• Supportive: Corticosteroids if severe chorioretinitis or very high CSF protein; anticonvulsants, shunt for hydrocephalus.

---

Syphilis

• Congenital syphilis is an infection caused by Treponema pallidum bacteria, transmitted vertically from mother to fetus via the placenta or rarely at birth through contact with maternal genital lesions.
• Risk of transmission is highest in primary and secondary maternal syphilis, decreasing with latent disease.
• Pathogenesis: Treponema pallidum crosses the placenta after ~16 weeks of gestation. Fetal infection leads to inflammation, tissue destruction, and scarring. Can result in miscarriage, stillbirth, or congenital infection.

Clinical Features

• Congenital syphilis is classified into early (<2 years) and late (>2 years).

Early Congenital Syphilis (<2 years)

• At birth may be absent (many infants appear normal).
• Manifestations:
  • Snuffles (syphilitic rhinitis) is the most characteristic early feature of congenital syphilis, highly infectious.
  • Maculopapular or bullous rash with desquamation (palms / soles).
  • Hepatosplenomegaly, Lymphadenopathy.
  • Bone changes: periostitis, osteochondritis → pseudoparalysis.
  • Anemia, jaundice, thrombocytopenia.
  • Failure to thrive.

Visual Evidence (Early) - snuffles in congenital syphilis

Periostitis of long bones seen in neonatal syphilis

Late Congenital Syphilis (>2 years)

• Results from untreated or inadequately treated cases.
• Classic triad:
  1. Interstitial keratitis.
  2. Hutchinson teeth (peg-shaped, notched upper central incisors).
  3. Sensorineural deafness.
• Other stigmata:
  • Frontal bossing, saddle nose deformity.
  • Saber shins, Clutton’s joints (painless knee effusion).
  • Enlarged sternoclavicular joint.

Visual Evidence (Late) - Hutchinson teeth – late result of congenital syphilis

Diagnosis and Treatment

• Maternal testing: VDRL, RPR (Rapid Plasma Reagin test), others – treponemal tests.
• Neonatal testing:
  • Serology: VDRL/RPR (for IgG and IgM); Treponemal tests.
  • PCR or dark-field microscopy of lesions.
  • CSF: for neurosyphilis.
  • Radiology: metaphyseal changes, periostitis.
• Complications: Miscarriage or stillbirth, Neonatal death, Severe physical deformities.
• Treatment: First-line: Penicillin G (the only effective treatment in pregnancy and infants).
  • Infants with proven/highly probable disease → IV crystalline penicillin for 10 days.
  • Asymptomatic infants with uncertain exposure → Benzathine penicillin IM (single dose).
  • Penicillin allergy: Desensitization + penicillin (no alternatives during pregnancy).
• Prevention: Screening of all pregnant women (at first visit, third trimester, and delivery in high-risk areas). Early maternal treatment prevents transmission.

---

Rubella

• Congenital Rubella Syndrome (CRS) results from maternal rubella infection during pregnancy, especially in the first trimester.
• Rubella virus is a togavirus (RNA virus).
• Fetal infection risk and severity, depend on gestational age at maternal infection.
• Epidemiology: Rubella is rare in countries with MMR vaccination.
• Risk of fetal infection:
  • First 12 weeks: up to 90%.
  • 13–16 weeks: ~25%.
  • After 20 weeks: very low risk.

Pathophysiology

• Virus crosses placenta → interferes with organogenesis.
• Causes cell necrosis, vasculitis, and impaired cell division, leading to congenital anomalies.

Clinical Features of CRS

• Classic Triad:
  1. Sensorineural deafness (most common permanent feature).
  2. Congenital heart disease (PDA, pulmonary artery stenosis, VSD).
  3. Eye defects (cataracts, glaucoma, retinopathy, microphthalmia).
• Other Manifestations: Growth restriction, low birth weight, microcephaly, developmental delay, seizures.
• Systemic: HSM, thrombocytopenic purpura (“blueberry muffin rash”).
• Bone: Bone radiolucencies (long bones).

Blueberry muffin spots

Bilateral cataract in congenital rubella

Bilateral glaucoma in congenital rubella

Diagnosis and Management

• Lab tests: Rubella-specific IgM in neonate; Persistence of IgG beyond 6 months; PCR for rubella RNA.
• Management: No specific antiviral treatment. Supportive & multidisciplinary: Cardiology for CHD, Ophthalmology for cataracts/glaucoma, Audiology for deafness, Early developmental support.
• Prevention: MMR vaccination (live attenuated vaccine): Contraindicated in pregnancy. Women of child bearing age should be immune before conception. Pregnant non-immune women exposed to rubella → consider immunoglobulin, but protection is limited.

---

Cytomegalovirus (CMV)

• Cytomegalovirus (CMV) is a member of the Herpesviridae family.
• It is the most common congenital viral infection worldwide.
• Incidence: ~0.2–2% of all live births.
• Major cause of sensorineural hearing loss (SNHL) and neurodevelopmental impairment.
• Transmission: Maternal primary infection during pregnancy → highest risk to fetus.
  • Routes: (a) Transplacental (most significant); (b) Intrapartum (contact with infected genital secretions); (c) Postnatal (through breast milk).
  • Risk of transmission: 30–40% in primary maternal infection, lower in reactivation.

Pathophysiology

• CMV infects multiple organs → especially CNS, liver, and hematopoietic system.
• Leads to: Inflammation, Cellular destruction, Calcification (especially in periventricular areas of the brain).

Clinical Features

• Only 10–15% of infected neonates are symptomatic at birth (> 85 % are asymptomatic at birth).
• Symptomatic congenital CMV at birth:
  • Growth restriction (IUGR).
  • Neurological: Microcephaly, Seizures, Intracranial calcifications (classically periventricular).
  • Hepatic: Hepatosplenomegaly, Jaundice, elevated liver enzymes.
  • Hematologic: Thrombocytopenia → “blueberry muffin” rash.
  • Other: Chorioretinitis, Sensorineural hearing loss (may present later).
• Asymptomatic at birth but at risk of sequelae: - Sensorineural hearing loss (most common long-term complication), - Neurodevelopmental delay, - Vision impairment.

Ventriculomegaly and calcification of congenital CMV

Diagnosis and Management

• Diagnosis: Confirmed by detection of CMV DNA (by PCR) in urine, saliva, or blood collected within the first 3 weeks of life (Gold standard test).
• Imaging: Cranial ultrasound/CT → periventricular calcifications, ventriculomegaly.
• Labs: Thrombocytopenia, elevated transaminases.

Differential Diagnosis Other congenital infections (TORCH):

• Toxoplasmosis → diffuse intracranial calcifications.

• Rubella → cataracts, PDA, deafness.

• Syphilis → snuffles, bone lesions.

• HSV → vesicular lesions, encephalitis.

• Management: Supportive care for complications (platelet transfusion, anti-epileptics, nutritional support).

• Antiviral therapy: Oral valganciclovir (or IV ganciclovir if severe). Indicated for symptomatic infants (especially CNS involvement). Duration: usually 6 months.

• Early intervention (audiology, physiotherapy).

• Prognosis:

  • Symptomatic infants: high risk of mortality (10–30%) and severe disability
  • long-term sequelae eg: sensorineural hearing loss, intellectual disability, cerebral palsy, vision loss.
  • Asymptomatic: ~10–15% may develop hearing loss later.

• Prevention:

  • No vaccine available.
  • Good hygiene in pregnant women (handwashing after handling diapers). Avoiding sharing food/drinks with toddlers.

---

Congenital Herpes Simplex Virus (HSV)

• Congenital HSV infection occurs when a neonate acquires HSV (type 1 or type 2) during the perinatal period, rarely prenatally.
• HSV-2 is more common (70–80%) than HSV-1 in congenital or neonatal infections.
• Epidemiology: Incidence: ~1 in 3,000 to 1 in 20,000 live births.
• Transmission: Intrauterine (rare, <5%): transplacental; Peripartum (majority, ~85%): passage through birth canal; Postnatal (10%): direct contact with caregivers.
• Risk Factors: - Maternal primary genital HSV-2 infection in the third trimester, - Prolonged rupture of membranes, - Instrumental delivery (scalp electrodes, forceps), - Prematurity.

Clinical Presentations (appearing usually between day 5–14 of life)

1. Skin, Eyes, Mouth (SEM disease):
   • Vesicular lesions on skin.
   • conjunctivitis, keratitis.
   • oral ulcers.
   • No CNS/systemic involvement. Accounts for ~45% of cases. Good prognosis with treatment.
2. Central Nervous System (CNS disease):
   • Lethargy, seizures, irritability, bulging fontanelle, poor feeding.
   • Temporal lobe involvement in HSV encephalitis.
   • CSF: pleocytosis, elevated protein, normal glucose. HSV PCR from CSF diagnostic. 30% mortality.
3. Disseminated disease:
   • Multi-organ involvement: liver, lungs, adrenals, CNS.
   • Presents with sepsis-like picture (shock, hepatitis, coagulopathy).
   • Accounts for ~25% of cases.
   • Highest mortality (up to 90% untreated), high morbidity (neurological sequelae).

Diagnosis and Management

• Diagnosis: - PCR for HSV DNA from lesions, blood, CSF (gold standard). - Culture of lesions. - Elevated liver enzymes in disseminated disease. - Neuroimaging: temporal lobe involvement in HSV encephalitis.
• Management: - IV Acyclovir: mainstay of treatment. Dose: 60 mg/kg/day in 3 divided doses for 14–21 days (longer for CNS/disseminated). - Supportive care (anticonvulsants, ventilation, fluids). - Long-term suppressive oral acyclovir for 6 months may reduce recurrence and improve neurodevelopment.
• Prevention:
  • Identify pregnant women with active genital HSV.
  • Cesarean section recommended if lesions present at delivery.
  • Avoid invasive monitoring during labor. Postnatal: avoid kissing/handling neonates with active cold sores.
• Prognosis:
  • SEM disease: excellent if treated.
  • CNS disease: 70% survivors with neurologic impairment.
  • Disseminated disease: high mortality without treatment, ~30% with therapy.

---