The Stealth Threat

Introduction: The Hidden Carrier Conundrum

Pregnant women testing positive for HBsAg are flagged as high-risk, and their newborns receive immediate life-saving interventions. Surprisingly, some women who test negative for HBsAg—specifically those carrying antibodies against the virus's core protein (anti-HBc)—can still transmit HBV to their babies. This stealth transmission route challenges conventional screening protocols and puts infants at risk. Understanding this phenomenon is critical for eliminating mother-to-child HBV transmission globally ^{1 2} .

How Can HBsAg-Negative Moms Transmit HBV?

The Occult Infection Phenomenon

Occult HBV infection (OBI) occurs when individuals test negative for HBsAg but harbor trace amounts of viral DNA in their liver or blood. This state is often seen in people who have "recovered" from a past infection. Their immune systems control—but don't eliminate—the virus. During pregnancy, stressors like immune shifts can reactivate this dormant virus ² .

Routes of Stealth Transmission

Vertical transmission typically occurs through:

1. Intrauterine Exposure: HBV breaches the placental barrier. Studies detect viral DNA in placental layers at increasing rates:
   • 4.2% in the 1st trimester
   • 44.6% by full term
2. During Delivery: Maternal-fetal blood exchange during childbirth.
3. Postnatal Exposure: Breastfeeding (minimal risk if immunoprophylaxis is given) ⁴ .

Hepatitis B virus structure showing core and surface antigens.

The Antibody Paradox

Mothers with isolated anti-HBc (i.e., negative for HBsAg and anti-HBs) lack neutralizing antibodies. Key risk factors include:

• Low anti-HBc IgG: Reduces placental transfer of protective antibodies to the fetus ^{3 6} .
• Anti-HBc IgM: Signals recent infection or viral reactivation, increasing transmission likelihood ⁶ .

The Groundbreaking Discovery: A Key Experiment Unmasking the Risk

Study Design ²

In 2009, researchers investigated whether mothers with isolated anti-HBc could transmit HBV to their infants. The study enrolled:

• Participants: 2,365 HBsAg-negative pregnant women.
• Screening: Tested for anti-HBc at delivery.
• Follow-up: 105 infants born to anti-HBc-positive mothers were tested for HBV markers (HBsAg, HBV DNA) at 3–4 months.

Results

Table 1: Vertical transmission rates in infants of anti-HBc-positive/HBsAg-negative mothers.

Analysis

• None of the infected infants developed chronic infection, suggesting partial immune control.
• The 6.6% transmission rate was alarming, as these infants received no prophylactic treatment at birth.
• Taq PCR's high sensitivity was crucial—standard tests might have missed these cases ² .

Why This Matters: Public Health Implications

Screening Gaps

• Current protocols in most countries test only for HBsAg in pregnancy ⁷ .
• High-risk mothers with isolated anti-HBc are missed, leaving infants unprotected.

Global Vaccination Shortfalls

Despite WHO goals:

• Only 42% of newborns receive the HBV vaccine birth dose (HepB-BD) within 24 hours ⁴ .
• Coverage is lowest in high-endemic regions (e.g., Africa, Asia-Pacific), where OBI is common.

Cost of Inaction

Table 2: Economic impact of screening and prevention strategies ⁷ .

The Scientist's Toolkit

Table 3: Essential reagents for studying stealth HBV transmission ^{2 6} .

Toward Elimination: Solutions and Hope

Policy Shifts Needed

1. Expand Prenatal Screening: Include anti-HBc testing for women with:
   • HBV risk factors (e.g., IV drug use, multiple partners)
   • HIV coinfection (4× higher OBI risk) ⁵ .
2. Universal Birth-Dose Vaccination: Overcome barriers (cost, cold storage) using thermostable vaccines ⁴ .

For Exposed Infants

• Monitor at 3–4 months: Test for HBV DNA and HBsAg.
• Vaccinate if uninfected: Standard 3-dose regimen induces protection in >90% ⁷ .

Future Frontiers