What are the management and prevention strategies for Herpes Simplex Virus (HSV) 1/2 and varicella infections, particularly in high-risk populations such as neonates, immunocompromised individuals, and the elderly?

Management and Prevention of HSV 1/2 and Varicella-Zoster Virus Infections

Herpes Simplex Virus (HSV) 1/2

Clinical Manifestations and Epidemiology

HSV-1 typically causes orolabial disease while HSV-2 is associated with genital and neonatal infections, though both can cause life-threatening disease in neonates and immunocompromised hosts. 1

• HSV infections are among the most frequently encountered human infections, usually causing mild, self-limited disease of the mouth, lips, or genital sites 1
• In immunocompromised hosts, severe infection is a significant source of morbidity 1
• HSV causes genital ulcerative disease and is associated with increased risk of HIV acquisition 1
• In infants, herpetic whitlow typically results from autoinoculation following primary herpetic stomatitis or gingivostomatitis 2

Antiviral Treatment

For immunocompetent patients with HSV, oral acyclovir 200 mg every 4 hours (5 times daily) for 10 days is indicated for initial genital herpes, while chronic suppressive therapy uses 400 mg twice daily for up to 12 months. 3

Treatment Regimens by Clinical Scenario:

Initial Genital Herpes:

• Acyclovir 200 mg every 4 hours, 5 times daily for 10 days 3
• Treatment initiated more than 72 hours after symptom onset has unestablished efficacy 4

Recurrent Episodes:

• Acyclovir 200 mg every 4 hours, 5 times daily for 5 days 3
• Initiate at earliest prodromal symptoms 3
• Treatment initiated more than 24 hours after symptom onset has unestablished efficacy 4

Chronic Suppressive Therapy:

• Acyclovir 400 mg twice daily for up to 12 months, followed by re-evaluation 3
• Alternative regimens: 200 mg 3-5 times daily 3
• Valacyclovir is effective for suppression beyond 1 year in immunocompetent patients and beyond 6 months in HIV-infected patients 4

Cold Sores (Herpes Labialis):

• Valacyclovir is FDA-approved for treatment in adults and pediatric patients ≥12 years 4
• Efficacy after development of clinical signs (papule, vesicle, ulcer) has not been established 4

High-Risk Populations

HIV-Infected or Immunocompromised Patients:

• IV acyclovir 5-10 mg/kg/dose three times daily for 7-14 days OR oral acyclovir 20 mg/kg/dose three times daily for 7-14 days 2
• Valacyclovir is indicated for chronic suppressive therapy in HIV-1-infected adults with CD4+ count ≥100 cells/mm³ 4

Neonates:

• Efficacy and safety of valacyclovir have not been established for suppressive therapy following neonatal HSV infection 4
• IV acyclovir remains the standard for neonatal HSV infections 2

Transmission Prevention

Caregivers with active cold sores must avoid kissing or direct facial contact with infants until complete crusting of lesions occurs, typically 4-7 days after rash onset. 2

• HSV-1 can transmit even without visible cold sores through asymptomatic viral shedding, making hand hygiene critical for all caregivers 2
• Safer sex practices should be used with suppressive therapy per CDC guidelines 4
• Valacyclovir is indicated for reduction of transmission in immunocompetent adults, though efficacy beyond 8 months in discordant couples and in individuals with multiple partners or non-heterosexual couples has not been established 4

Diagnostic Considerations

• Tzanck preparation shows multinucleated giant cells but does not differentiate HSV from VZV 2
• Diagnostic confirmation using PCR or immunohistochemical staining is crucial in immunocompromised hosts who may have atypical presentations 5

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Varicella-Zoster Virus (VZV)

Clinical Manifestations and Epidemiology

Approximately 95% of U.S. adults born in the United States have had primary VZV infection (varicella), with herpes zoster incidence >15-fold higher in HIV-infected adults than age-matched controls. 6

• Varicella occurs in approximately 85% (range: 65-100%) of susceptible household contacts exposed to VZV 6
• Herpes zoster can occur at any CD4+ count in HIV-infected adults, but frequency is highest with CD4+ <200 cells/µL and is not reduced by ART 6
• Approximately 10-15% of HIV-seropositive patients develop post-herpetic neuralgia following herpes zoster 6
• Most herpes zoster complications, including dissemination, occur in patients with CD4+ <200 cells/µL 6

Transmission Characteristics

Herpes zoster is approximately 20% as contagious as varicella and transmits only through direct contact with fluid from active lesions or rarely through airborne transmission in healthcare settings. 7

• Localized herpes zoster is much less infectious than varicella or disseminated herpes zoster 6
• Airborne transmission is possible but primarily documented in healthcare settings 7
• Household transmission risk from herpes zoster is approximately 20% of the risk from varicella 7
• Transmission requires direct contact with fluid from active vesicles or, rarely in healthcare settings, airborne exposure to viral particles from uncrusted lesions 7

Contagiousness Timeline

The period of contagiousness begins 1-2 days before rash onset and continues until all lesions have dried and crusted, typically 4-7 days after rash onset. 7

• For non-crusting lesions (macules and papules), contagiousness ends when no new lesions appear within 24 hours 7
• Immunocompromised patients may experience slower healing (7-14 days or longer) and prolonged viral shedding 7
• Antiviral therapy reduces time to lesion healing but does not immediately render the patient non-contagious, as viral shedding continues until lesions are fully crusted 7

Antiviral Treatment

For herpes zoster in immunocompetent adults, acyclovir 800 mg every 4 hours (5 times daily) for 7-10 days is the standard treatment, initiated within 72 hours of rash onset. 3

Treatment Regimens:

Herpes Zoster (Immunocompetent Adults):

• Acyclovir 800 mg every 4 hours orally, 5 times daily for 7-10 days 3
• Valacyclovir is FDA-approved for herpes zoster in immunocompetent adults 4
• Efficacy when initiated >72 hours after rash onset is not established 4
• Efficacy and safety for disseminated herpes zoster have not been established 4

Chickenpox:

• Children ≥2 years: Acyclovir 20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days 3
• Children >40 kg and adults: Acyclovir 800 mg 4 times daily for 5 days 3
• Valacyclovir is indicated for chickenpox in immunocompetent pediatric patients aged 2 to <18 years 4
• Treatment should be initiated within 24 hours after rash onset 4, 3
• IV acyclovir is indicated for varicella-zoster infections in immunocompromised patients 3

Immunocompromised Patients:

• Ganciclovir or foscarnet can be considered using treatment schedules and doses similar to CMV disease if HHV-6 disease is determined 6
• Higher doses or longer courses of antiviral therapy may be required 7
• Acyclovir-resistant VZV can be treated with foscarnet 5

Renal Dosing Adjustments

In patients with renal impairment, acyclovir dosing must be modified based on creatinine clearance. 3

• For 800 mg every 4 hours regimen:
  • CrCl >25: 800 mg every 4 hours, 5x daily
  • CrCl 10-25: 800 mg every 8 hours
  • CrCl 0-10: 800 mg every 12 hours 3
• Hemodialysis patients require an additional dose after each dialysis session 3

High-Risk Populations and VZIG Indications

VZIG is indicated for immunocompromised patients without evidence of immunity after direct exposure to varicella or disseminated herpes zoster, neonates whose mothers have varicella from 5 days before to 2 days after delivery, and premature neonates exposed postnatally. 6

Specific VZIG Recommendations:

Immunocompromised Patients:

• VZIG is used for passive immunization after direct exposure to varicella or disseminated herpes zoster 6
• Includes patients with primary/acquired immunodeficiency disorders, neoplastic diseases, and those receiving immunosuppressive treatment 6
• Patients receiving monthly high-dose IGIV (>400 mg/kg) administered <3 weeks before exposure probably do not require VZIG 6
• After household exposure with VZIG, attack rates in immunocompromised children were up to 60%, with severe disease incidence of 27% (vs. 87% predicted without VZIG) 6

Neonates:

• VZIG is indicated for neonates whose mothers have varicella from 5 days before to 2 days after delivery 6
• Not necessary if maternal varicella occurs >5 days before delivery due to transplacental maternal antibody protection 6
• No evidence suggests increased risk if maternal varicella occurs >48 hours after delivery 6
• Attack rate in neonates receiving VZIG was 62%, similar to untreated neonates, but complications and fatal outcomes were substantially lower 6
• Newborns whose mothers develop varicella from 5 days before to 2 days after delivery face severe disease risk with estimated 17-30% developing severe infection and historical mortality estimates of 31% 7

Premature Neonates:

• Premature infants born at ≥28 weeks gestation exposed during neonatal period whose mothers lack evidence of immunity should receive VZIG 6
• Premature infants born at <28 weeks gestation or weighing <1,000 g at birth exposed during neonatal period should receive VZIG regardless of maternal immunity 6
• VZIG is not recommended for healthy, full-term infants exposed postnatally, even if mothers have no varicella history 6

Pregnant Women:

• VZIG should be strongly considered for pregnant women without evidence of immunity who have been exposed 6
• In pregnant women without VZV immunity who received VZIG after exposure, infection rate was 30% (vs. expected >70% without VZIG) 6
• Primary indication is to prevent maternal complications rather than fetal infection 6
• VZIG has not been found to prevent viremia, fetal infection, congenital varicella syndrome, or neonatal varicella 6
• Maternal herpes zoster during pregnancy does not cause congenital varicella syndrome, unlike maternal varicella infection 7

Infection Control in Healthcare Settings

For disseminated herpes zoster or immunocompromised patients with localized herpes zoster, airborne and contact precautions with negative air-flow rooms are mandatory until all lesions are dry and crusted. 7

Precautions by Patient Type:

Immunocompetent Patients with Localized Herpes Zoster:

• Standard and contact precautions are sufficient 7
• Complete lesion coverage is required 7
• Maintain at least 6 feet physical separation from other patients 7
• Patient should wear surgical mask to prevent droplet transmission 7
• Airborne precautions are not required 7
• Continue precautions until all lesions are dried and crusted, typically 4-7 days after rash onset 7

Disseminated Herpes Zoster (Any Immune Status):

• Airborne and contact precautions are mandatory 7
• Negative air-flow room required 7
• Continue precautions until all lesions are dry and crusted 7

Immunocompromised Patients with Any Herpes Zoster:

• Airborne and contact precautions required until disseminated infection is ruled out 7
• Negative air-flow room required 7
• These patients experience prolonged viral shedding and slower healing 7

Healthcare Worker Restrictions

Healthcare workers with localized herpes zoster who are immunocompetent should cover all lesions completely and be restricted from caring for high-risk patients until all lesions have dried and crusted. 7

• Healthcare workers with disseminated zoster or localized zoster in immunocompromised individuals must be excluded from duty until all lesions have dried and crusted 7
• Healthcare workers must be restricted from contact with immunocompromised patients, pregnant women, neonates, and patients in protective environments until all lesions crust 7
• For non-crusting lesions, complete work clearance without restrictions is permitted when no new lesions appear within 24 hours 7
• Standard precautions with complete lesion coverage are mandatory for healthcare workers in high-risk settings, even after return to work 7
• Immunocompromised healthcare workers may require longer periods of isolation due to prolonged viral shedding 7

Vaccination and Prevention

All VZV-susceptible healthcare workers should be strongly encouraged to receive varicella vaccine to minimize transmission risk in healthcare settings. 8

• VZV vaccines are available to prevent varicella and zoster 5
• The recombinant zoster vaccine demonstrates 88.8% efficacy against postherpetic neuralgia by boosting VZV-specific immunity 9
• Pharmaceutical prophylaxis against VZV should be considered in high-risk cancer patients 5

Latency and Reactivation

VZV becomes permanently latent in sensory ganglia after primary infection, and cell-mediated immunity functions as ongoing surveillance rather than an eradicating force. 9

• The virus persists indefinitely in ganglionic neurons and cannot be eliminated by the immune system 9
• Lifetime risk of herpes zoster is 15-30% in the general population, demonstrating that even decades of intact cell-mediated immunity cannot eliminate latent virus 9
• When VZV-specific cell-mediated immunity declines due to aging, immunosuppressive therapy, or conditions like HIV, the virus reactivates and travels along nerve pathways to cause herpes zoster 9
• Vaccination strategies focus on boosting VZV-specific immunity to prevent reactivation rather than clearing established infection 9

Populations at Highest Risk for Severe Disease

Patients with shingles should avoid contact with pregnant women, premature infants and neonates, immunocompromised persons, and anyone without history of chickenpox or varicella vaccination. 7

• These groups are at increased risk for severe disease if exposed and infected 7
• Immunocompromised persons of all ages, premature infants, and neonates are at increased risk for severe disease 7
• Visceral dissemination, especially VZV pneumonitis, is well documented in HIV-seropositive adolescents and adults 6

Common Pitfalls to Avoid

• Do not assume that starting antiviral therapy immediately makes the patient non-contagious—viral shedding continues until lesions are fully crusted 7
• Do not allow healthcare workers with herpes zoster to care for high-risk patients before lesions are fully crusted 7
• Do not fail to recognize that immunocompromised patients may have prolonged periods of viral shedding and contagiousness 7
• Do not provide inadequate covering of lesions, which can lead to transmission even with localized disease 7
• Do not initiate immunomodulator therapy during active shingles infection; reintroduce only after all vesicles have crusted over and fever has resolved 7