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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Diagnosis>Opportunistic Infections>
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Herpes zoster

Emily J. Erbelding, MD, MPH and Khalil G. Ghanem, M.D.
08-03-2009

Zambia Specific Information

  • Zoster is clear indication for HIV testing in Zambia.
  • Zoster is common complication of HIV infection in sub-Saharan Africa; often a sentinel event. no published statistics from Zambia.
  • Dx in Zambia generally clinical, as Tzanck prep, skin Bx, Cx, and PCR rarely performed.
  • Treatment in Zambia is with acyclovir as recommended below; valacyclovir, famciclovir, and foscarnet not generally available.
  • Zoster commonly seen as IRIS reaction after starting ART; peak time of onset is within first 4 months of initiation.
  • Treatment for zoster IRIS is acyclovir; continue ART.

REFERENCES

Zambia Information Author: David Riedel, M.D.

PATHOGENS

  • Varicella zoster virus (VZV), an enveloped double-stranded DNA virus, member of Herpesviridae family; establishes lifelong latency after initial infection
  • Primary infection (varicella) usually acquired by respiratory droplet; acquisition from reactivation zoster less common; contact with vesicle/ulcer (zoster) or disseminated disease (zoster) or pneumonitis (varicella or disseminated zoster).

CLINICAL

  • Primary varicella infection ("chicken pox") usually occurs in early life within community-based outbreaks; significantly less common since widespread adoption of VZV immunization for children
  • Recurrent infection (herpes zoster [HZ] or dermatomal zoster) occurs later; highest risk in elderly or immunocompromised, including HIV/AIDS, where risk is 3.2% per yr
  • Other clinical manifestations: disseminated (non-dermatomal) zoster, acute or chronic encephalitis, transverse myelitis,cerebellar ataxia (especially following acute infection), cerebral angiitis, acute retinal necrosis, pneumonitis.
  • Zoster-associated pain syndromes: major morbidity of HZ; acute neuritis and zoster-associated neuralgia
  • Greater risk of HZ events and HZ complications with lower CD4; case reports and clinical series suggest risk of HZ may increase shortly after HAART initiation as immune restoration occurs
  • Immunocompromise associated with prolonged clinical course, recurrent or chronic lesions, multiple dermatomes, and verrucous or nodular lesions

DIAGNOSIS

  • Characteristic rash (either of primary varicella or HZ) usually leads to clinical Dx without need for additional testing. Lesions may be atypical with advanced immune suppression requiring Tzanck, Bx or Cx for identification
  • "Tzanck prep" of lesion scrapings may demonstrate multinucleated giant cells (60% sensitive for infection with Herpesviridae family)
  • Skin Bx: may be especially useful with atypical lesions; VZV DFA stain diagnostic.
  • PCR from lesion exudate or from CSF (in encephalitis, may be positive with HZ reactivation/meningitis) highly sensitive and specific
  • Cx from lesion also confirmatory; reduced sensitivity if antiviral therapy initiated; rarely useful to support early medical decision-making

TREATMENT

Dermatomal herpes zoster

  • Valacyclovir 1 gm PO three times a day x 7-10 days
  • Famciclovir 500 mg PO three times a day x 7-10 days
  • Acyclovir 800 mg PO 5x/d x 7-10 days
  • Effective in immune competent pts only if initiated within 72h, for immune suppressed, treat unless lesions crusted
  • Use of adjunct corticosteroids for HZ of equivocal benefit in immunocompetent hosts for preventing zoster-associated neuralgia; not recommended in HIV infection.
Severe infection (CNS, ocular, disseminated)

  • Acyclovir 10 mg/kg IV q8h x 14-21 days
  • Consider Tx for severe infection whenever clinical diagnosis of zoster likely + altered mental status or visual Sx while definitive Dx pursued
Suspected ACV resistance

  • Relatively infrequent event, risk of occurrence increases when immunocompromised hosts are on prolonged ACV (or other nucleoside) therapy
  • Foscarnet 40 mg/kg IV q8h or 60 mg/kg IV q12h
  • Consider ACV resistance and viral susceptibility testing when new lesions evolve on high-dose ACV therapy
Pain control and adjunct measures

  • Pain control, in addition to antiviral therapy, is among primary clinical goals in HZ management and is frequently suboptimal, both for acute neuritis and zoster-associated neuralgia. Tricyclic antidepressant (TC) started within 48 hrs reduced occurrence of post-herpetic neuralgia PHN.
  • Narcotics may be most useful for pain of acute episode; for chronic HN, controlled-release oxycodone (up to 60 mg daily) or morphone (up to 240 mg daily)
  • Adjunct for chronic pain: gabapentin: start 100-300 mg qhs or 100 mg three times a day, then titrate by 100 mg three times a day as tolerated to reach 1800-3600 mg daily target; lidocaine patch 5% (lidoderm): use up to 12h daily, up to 3 patches; TCAs: amitriptyline 25 mg qd for 3 mo within 48hr of rash onset
  • Options to try in refractory patients: capsaicin 0.025-0.075% cream four times a day, nerve blocks, spinal cord stimulation, intrathecal methylprednisolone
  • Use of adjunct corticosteroids for HZ of equivocal benefit in immunocompetent hosts for preventing PHN; not recommended in HIV infection.
Prevention and prophylaxis

  • Chronic suppressive antiviral therapy may be warranted in persons with multiple or severe HZ events while at elevated risk (low CD4 or during period of immune restoration with ART)
  • Post-exposure prophylaxis: If exposure to primary or disseminated VZV in person with no history of chickenpox and/or negative anti-varicella IgG, varicella zoster immune globulin (VZIG) indicated, ideally within 48 hrs (up to 96 hrs): 500 units IM (four 125 u vials) for pts 30-40 kg and 625 units IM (one 625 u vial x vial) for pts > 40 kg.
  • Varicella vaccination: Consensus panel recommendations for giving live viral vaccine (Varivax) to HIV+ children if age-specific CD4 15%-24%; 2-dose series starting at 12 mos, at least 3 mos apart. If rash evolves, skin should be covered and contact with immunocompromised adults in household restricted. Adolescents and adults without natural immunity should be vaccinated if CD4 > 200.
  • Period of infectiousness: Primary or disseminated varicella - 48 hrs prior to lesion onset until lesions crusted or dry; for HZ, significant exposure would require direct lesion contact during early eruption (48 hrs)
  • Precautions: airborne and contact isolation in healthcare facility for primary varicella; standard precautions for HZ. Staff who are VZV-susceptible should not care for patients with primary varicella or HZ.
  • Herpes zoster vaccination: Single dose of VZ vaccine approved for use in older non-immunocompromised adults > 60 years to prevent zoster.
  • Per ACIP Recommendations: Zoster vaccine should not be administered to persons with AIDS or other clinical manifestations of HIV, including persons with CD4 counts <200 or CD4 % <15.
Primary Infection: Varicella

  • Normal adult: Rx within 24hr onset of exanthem for efficacy. Acyclovir 800 mg po 5x/d x 5d
  • Varicella pneumonia: acyclovir 10-12 mg/kg q8h, or valacyclovir 1 g po three times a day or famciclovir 500 mg po three times a day, all for 7-10 days.

Drug Comments

DrugRecommendations/Comments
Acyclovir Less convenient oral option due to higher dosing frequency than oral alternatives
Famciclovir More convenient dosing than ACV. Not useful if acyclovir resistant.
Foscarnet Use for suspected ACV resistance;use in combination with acyclovir or ganciclovir IV for acute retinal necrosis
Ganciclovir May be component of combination therapy for acute retinal necrosis; use of intravitreal injections as adjunct to combination IV therapy reported.
Valacyclovir Better absorption, more convenient dosing than acyclovir; not useful if acyclovir resistant

Basis for Recommendations

  • Harpaz R, Ortega-Sanchez IR, Seward JF, et al.; Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP).; MMWR Recomm Rep; 2008; Vol. 57; pp. 1-30; quiz CE2-4;
    ISSN: 1545-8601;
    PUBMED: 18528318
    Rating: Basis for recommendation
    Comments:Comprehensive review of zoster and current vaccine recommendations. Guidelines suggest: zoster vaccine should not be administered to persons with AIDS or other clinical manifestations of HIV, including persons with CD4 <200 or CD4 % <15%.

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