What is the recommended varicella prophylaxis (varicella vaccine, varicella‑zoster immune globulin [VariZIG], oral acyclovir, intravenous acyclovir) for a previously healthy child, adolescent, or adult compared with immunocompromised patients after exposure?

Varicella Post-Exposure Prophylaxis: Recommendations by Patient Population

Previously Healthy Individuals (Children, Adolescents, Adults)

For previously healthy, unvaccinated persons without evidence of immunity, varicella vaccine is the recommended post-exposure prophylaxis and should be administered within 3 days of exposure for optimal protection (>90% efficacy), or up to 5 days post-exposure for continued benefit. 1

Timing and Efficacy of Varicella Vaccine

• Within 3 days of exposure: Varicella vaccine is >90% effective in preventing varicella disease entirely 1
• Within 5 days of exposure: Vaccine is approximately 70% effective in preventing disease and 100% effective in preventing severe disease 1
• The CDC and ACIP recommend this approach for all unvaccinated persons without evidence of immunity, including children, adolescents, and adults 1

Critical Safety Considerations for Vaccine Recipients

• Avoid salicylates for 6 weeks post-vaccination due to Reye syndrome risk 1
• Do not administer varicella vaccine for 3-11 months after receiving blood products or immune globulin, as passively transferred antibodies may inhibit vaccine response 1
• No evidence indicates increased adverse events when vaccine is given during presymptomatic or prodromal stages of infection 1

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Immunocompromised Patients

For immunocompromised patients without evidence of immunity, VariZIG (varicella-zoster immune globulin) is the recommended post-exposure prophylaxis and should be administered as soon as possible after exposure, ideally within 96 hours but up to 10 days post-exposure. 2

Specific High-Risk Groups Requiring VariZIG

The decision to administer VariZIG depends on three factors: (1) lack of evidence of immunity, (2) likelihood of exposure resulting in infection, and (3) increased risk for complications 2

VariZIG is specifically recommended for: 2

• Immunocompromised patients without evidence of immunity
• Newborn infants whose mothers have signs and symptoms of varicella around delivery (5 days before to 2 days after)
• Hospitalized premature infants born at ≥28 weeks gestation whose mothers lack evidence of immunity
• Hospitalized premature infants born at <28 weeks gestation or weighing ≤1,000 g at birth, regardless of maternal immunity status
• Pregnant women without evidence of immunity

VariZIG Dosing and Administration

• Dose: 125 IU/10 kg body weight, up to maximum of 625 IU (five vials) 2
• Minimum dose: 62.5 IU (0.5 vial) for patients weighing ≤2.0 kg; 125 IU (one vial) for patients weighing 2.1-10.0 kg 2
• Route: Intramuscular administration 2
• Timing: Administer as soon as possible after exposure, ideally within 96 hours for greatest effectiveness, but can be given up to 10 days post-exposure 2

Evidence Supporting Extended Window for VariZIG

The FDA approved extension of the administration window from 96 hours to 10 days based on international data showing that administration >4 days (up to 10 days) after exposure resulted in comparable incidence of varicella and attenuation of disease compared to earlier administration 2. A large expanded-access study (n=507) demonstrated similar varicella incidence when comparing VariZIG administration ≤96 hours versus >96 hours (6.2% vs. 9.4%, respectively) 3.

Clinical Outcomes with VariZIG in Immunocompromised Patients

• Varicella incidence after VariZIG was 4.5% in immunocompromised participants overall 3
• In a subgroup analysis of 303 immunocompromised patients (40 adults, 263 children), overall varicella incidence was 6% in adults and 7% in children 4
• Most cases were mild, with only 2 children developing >100 lesions and no cases of varicella-related pneumonia or encephalitis 4
• One serious adverse event (serum sickness) was considered related to VariZIG 3, 4

Important Caveats for VariZIG Use

• VariZIG may prolong the incubation period by ≥1 week; patients should be observed closely for signs and symptoms of varicella for 28 days after exposure 2
• Antiviral therapy should be instituted immediately if signs or symptoms of varicella occur 2
• For patients with repeat exposures ≥3 weeks after initial VariZIG administration, another full dose should be given 2
• Patients receiving monthly high-dose IGIV (>400 mg/kg) are likely protected if the last dose was administered <3 weeks before exposure 2

Special Considerations for Specific Immunocompromised Populations

• Bone marrow transplant recipients should be considered non-immune regardless of previous varicella history or vaccination status in themselves or their donors 2, 5
• Patients who received 2 doses of varicella vaccine before becoming immunocompromised are generally considered protected and do not require VariZIG; they should be monitored closely and treated with acyclovir at earliest signs of disease 2, 5
• Patients on steroid therapy receiving doses >2 mg/kg body weight or total of 20 mg/day prednisone or equivalent require VariZIG 2

Varicella Vaccine Timing After VariZIG

• For patients who become eligible for vaccination, varicella vaccine should be administered ≥5 months after VariZIG administration 2

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Alternative Prophylaxis: Oral Acyclovir

While not formally recommended in current CDC/ACIP guidelines, oral acyclovir or valacyclovir may be considered as post-exposure prophylaxis in high-risk patients when the time window for VariZIG has expired (>10 days post-exposure) 6. However, the evidence for this approach is limited to small studies of mostly healthy children and is not properly designed 6. This represents an off-guideline option for situations where VariZIG is no longer appropriate.

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Key Algorithmic Approach

For Previously Healthy Individuals:

1. Confirm lack of evidence of immunity (no history of varicella, no vaccination, or negative serology)
2. If ≤3 days post-exposure: Administer varicella vaccine (>90% efficacy) 1
3. If 4-5 days post-exposure: Administer varicella vaccine (70% efficacy for prevention, 100% for severe disease) 1
4. Counsel on salicylate avoidance for 6 weeks 1

For Immunocompromised Patients:

1. Confirm lack of evidence of immunity and significant exposure
2. If ≤10 days post-exposure: Administer VariZIG (125 IU/10 kg, max 625 IU) 2
3. Monitor for 28 days for varicella symptoms 2
4. Institute acyclovir immediately if symptoms develop 2
5. If >10 days post-exposure: Consider oral acyclovir/valacyclovir (off-guideline) 6