What are the treatment options for pox virus infections?

Treatment of Poxvirus Infections

For severe poxvirus infections requiring antiviral therapy, tecovirimat (TPOXX) is the first-line treatment, with brincidofovir as an alternative option, while most mild cases require only supportive care. 1, 2

Supportive Care for Mild Cases

Most poxvirus infections are self-limited and require only symptomatic management 3:

• Fever, headache, fatigue, myalgia, and chills typically resolve without specific antiviral therapy 3
• Local skin reactions, nonspecific rashes, and lymphadenopathy can be managed with observation and supportive care 3
• Pain management with analgesics is appropriate for skin lesions and systemic discomfort 4
• Skin care focusing on preventing secondary bacterial infections is essential 4

Antiviral Therapy for Severe Disease

Tecovirimat (TPOXX) - First-Line Antiviral

Tecovirimat is FDA-approved for smallpox treatment and is the preferred antiviral for severe poxvirus infections 1:

• Dosing for patients ≥13 kg: Weight-based oral dosing every 12 hours for 14 days 1
• Must be taken within 30 minutes after a full meal containing moderate or high fat to ensure adequate absorption 1
• IV formulation available for patients unable to tolerate oral therapy, administered as a 6-hour infusion 1
• Mechanism: Inhibits viral egress by targeting the F13L gene product 3
• Efficacy: Demonstrated 100% protection in non-human primates challenged with monkeypox virus 3

Brincidofovir (TEMBEXA) - Alternative Antiviral

Brincidofovir is FDA-approved for smallpox and serves as an alternative when tecovirimat is unavailable or contraindicated 2:

• Dosing regimen: 20/5/5 mg/kg administered orally every 48 hours for 3 doses 2
• Demonstrated significant survival benefit in rabbitpox (90% survival vs 29% placebo) and mousepox models (78% survival vs 13% placebo) when initiated after clinical signs appeared 2
• Oral bioavailability advantage over cidofovir with reduced nephrotoxicity 3

Cidofovir - Second-Line Therapy

Cidofovir is available under restricted IND protocol but has significant limitations 3:

• Reserved for cases where VIG is ineffective and other antivirals are unavailable 3
• Major drawbacks: Nephrotoxicity, lack of oral bioavailability, requires IV administration 3
• Should only be used as second-line therapy after VIG failure 3

Vaccinia Immune Globulin (VIG) - Immunotherapy

Indications for VIG

VIG is first-line therapy for specific severe complications of vaccinia virus 3:

Progressive Vaccinia (PV)

• Requires aggressive VIG therapy, intensive monitoring, and tertiary-level supportive care 3
• Characterized by painless progressive necrosis at vaccination site with potential metastases to skin, bones, and viscera 3
• High mortality rate even with treatment; patients with cell-mediated immune deficits have poorer prognosis than those with humoral deficits 3
• Infection control precautions mandatory to prevent secondary transmission 3

Eczema Vaccinatum (EV)

• Patients are often systemically ill and usually require VIG 3
• Occurs in persons with atopic dermatitis history regardless of disease severity or activity 3
• Presents as localized or generalized papular, vesicular, or pustular rash with predilection for areas of previous eczema 3
• Strict infection control required to prevent nosocomial spread 3

Generalized Vaccinia (GV)

• VIG required when patient is systemically ill or has underlying immunocompromising condition 3
• Usually self-limited and benign in immunocompetent patients 3
• Characterized by disseminated maculopapular or vesicular rash on erythematous base, occurring 6-9 days after first-time vaccination 3

Ocular Vaccinia

• Requires ophthalmology evaluation and may need topical antivirals, antibacterial medications, VIG, or topical steroids 3

VIG Administration

• Available in IV and IM preparations under IND protocols through CDC and Department of Defense 3
• Based on worldwide historical experience, making it the established first-line therapy for vaccinia complications 3

Special Populations and Considerations

Immunocompromised Patients

• Tecovirimat efficacy may be reduced based on animal studies showing decreased effectiveness in immunocompromised models 1
• Higher risk for severe disease and death, especially those with advanced HIV (CD4 <200 cells/μL) 4
• Progressive vaccinia risk highest in patients with congenital or acquired immunodeficiencies, HIV/AIDS, cancer, or on immunosuppressive therapies 3

Central Nervous System Disease

• No specific antiviral therapy exists for postvaccinial encephalopathy (PVE) or encephalomyelitis (PVEM) 3
• Supportive care, anticonvulsants, and intensive care are the mainstays of management 3
• Diagnosis of exclusion: PVE and PVEM are not believed to result from replicating vaccinia virus 3

Pregnant Women

• VIG should not be withheld if a pregnant woman develops a condition requiring VIG 3
• No routine prophylactic VIG indicated for unintentionally vaccinated pregnant women 3

Infection Control Measures

Critical to prevent transmission from infected individuals 3:

• Hand hygiene: Wash with warm soapy water or alcohol-based hand rubs (>60% alcohol) immediately after touching lesions or changing bandages 3
• Bandage disposal: Place used bandages in sealed plastic bags before household trash disposal 3
• Contact and respiratory isolation for patients with suspected smallpox or severe complications until diagnosis clarified 3

Access to Investigational Therapies

For civilian patients requiring IND therapies for vaccinia-related adverse reactions 3:

• Contact state health department or CDC Clinician Information Line: 877-554-4625 3
• Clinical evaluation tools available at CDC website 3

Common Pitfalls to Avoid

• Do not delay VIG therapy in progressive vaccinia, eczema vaccinatum, or systemically ill patients with generalized vaccinia—mortality increases with delayed treatment 3
• Do not confuse severe primary reactions with progressive vaccinia—severe primary reactions clear within 1-2 weeks without VIG 3
• Do not use prophylactic VIG for inadvertently vaccinated persons with contraindications; instead, monitor closely for early adverse reactions 3
• Ensure tecovirimat is taken with a high-fat meal—absorption is significantly reduced without adequate fat content 1
• Monitor renal function before and during cidofovir or brincidofovir therapy due to nephrotoxicity risk 3, 2