What is the pathogenesis of congenital syphilis, congenital rubella, and congenital herpes simplex?

Pathogenesis of Congenital Infections

Congenital Syphilis

Congenital syphilis occurs through transplacental transmission of Treponema pallidum spirochetes from an infected mother to the fetus during pregnancy, with transmission rates approaching 100% during primary and secondary maternal syphilis. 1

Mechanism of Transmission

• T. pallidum crosses the placental barrier via hematogenous spread at any stage of maternal infection 2
• Transmission risk is highest during primary and secondary syphilis when maternal spirochete burden is greatest 1
• The spirochetes can infect fetal tissues throughout gestation, though infection after 18-20 weeks is most common when fetal immunologic competence begins developing 2
• Less commonly, transmission occurs through direct contact with maternal genital lesions during delivery 2

Pathophysiologic Effects

• The spirochetes cause widespread inflammation and tissue destruction in multiple organ systems 3
• Hepatosplenomegaly results from direct hepatic and splenic infiltration with spirochetes causing inflammatory hepatitis 3
• Osteochondritis and periostitis develop from bone invasion, leading to pseudoparalysis of extremities due to pain 3
• Rhinitis ("snuffles") occurs from nasal mucosal inflammation with spirochete-laden discharge 3
• Severe cases manifest with nonimmune hydrops from hepatic dysfunction, anemia, and hypoalbuminemia 4
• Untreated maternal infection can cause spontaneous abortion, stillbirth, or early neonatal death 1

Timing Considerations

• Maternal infection late in pregnancy may result in low or negative infant serologic titers at birth despite active infection 4
• The Jarisch-Herxheimer reaction from maternal treatment in the second half of pregnancy can precipitate premature labor or fetal distress 4

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Congenital Rubella

Congenital rubella results from transplacental transmission of rubella virus during maternal viremia, with the virus directly infecting and damaging developing fetal tissues, particularly during the first trimester when organogenesis is occurring.

Mechanism of Transmission

• Rubella virus crosses the placenta during maternal viremia following respiratory acquisition of the virus
• The virus has tropism for developing fetal tissues and can persist in fetal cells for months
• Transmission risk and severity of fetal damage are inversely related to gestational age at maternal infection

Pathophysiologic Effects

• The virus causes direct cytopathic effects on dividing fetal cells, leading to cell death and inhibition of cellular multiplication
• Vascular endothelial damage results in tissue ischemia and organ hypoplasia
• Persistent viral infection triggers chronic inflammation in affected organs
• Classic triad includes cardiac defects (patent ductus arteriosus, pulmonary stenosis), cataracts, and sensorineural deafness
• Additional manifestations include microcephaly, intellectual disability, hepatosplenomegaly, thrombocytopenia, and "blueberry muffin" skin lesions from dermal erythropoiesis

Critical Period

• First trimester infection (especially first 8-12 weeks) carries the highest risk of severe, multiple congenital defects
• Infection after 20 weeks rarely causes congenital abnormalities
• The virus can be shed from infected infants for months to years after birth, posing transmission risk to susceptible contacts

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Congenital Herpes Simplex

Congenital herpes simplex is predominantly acquired perinatally during passage through an infected birth canal rather than through true transplacental transmission, with the highest transmission risk occurring during primary maternal genital HSV infection at delivery. 4, 5

Mechanism of Transmission

• Intrapartum transmission accounts for 75-85% of neonatal HSV infections, occurring when the infant contacts HSV-infected maternal genital secretions during vaginal delivery 4, 5
• Primary maternal HSV infection at delivery carries 30-50% transmission risk compared to 0-5% risk with recurrent maternal infection 4
• Ascending infection can occur after prolonged rupture of membranes (>6 hours), with HSV ascending from the cervix 4
• Invasive obstetric procedures (fetal scalp monitoring) that disrupt fetal skin integrity increase transmission risk 4
• True congenital (in utero) HSV acquisition is rare but can occur via transplacental transmission, resulting in devastating cutaneous, ocular, and CNS damage present at birth 4, 5

Pathophysiologic Effects

• HSV has cytopathic effects causing direct cellular destruction with characteristic multinucleated giant cells and intranuclear inclusions
• The virus spreads via neural and hematogenous routes from initial mucocutaneous sites
• Three clinical patterns emerge: localized skin/eye/mouth disease (45%), CNS disease (30%), or disseminated disease (25%)
• Disseminated disease involves hepatic necrosis, pneumonitis, DIC, and multiorgan failure
• CNS disease causes necrotizing encephalitis with temporal lobe predilection

Special Considerations in HIV-Coinfected Mothers

• HIV-infected women, particularly those with low CD4+ counts, shed HSV from the vulva and cervix more frequently than HIV-uninfected women 4
• Approximately 10% of HIV/HSV-2 coinfected women have cervical HSV shedding on the day of delivery compared to 2-3% of HIV-uninfected women 4
• The majority of HSV shedding in HIV-infected women is asymptomatic 4
• HSV reactivation frequency increases as HIV-related immunosuppression progresses 4

Key Distinction from Other Congenital Infections

• Unlike CMV, syphilis, rubella, and toxoplasmosis which are transmitted transplacentally during pregnancy, HSV is usually acquired perinatally with shorter time between infection acquisition and potential antiviral therapy initiation 5