How should monkeypox be treated, especially in immunocompromised patients?

Treatment of Monkeypox

For immunocompromised patients with monkeypox, tecovirimat is the first-line antiviral therapy, while vaccinia immune globulin (VIG) should be reserved for severe vaccinia-related complications; most immunocompetent patients require only supportive care as the infection is self-limited. 1, 2

Supportive Care for Mild Disease

• Most monkeypox infections are self-limited and require only symptomatic management including treatment of fever, headache, fatigue, myalgia, and chills, which typically resolve within 2-4 weeks without specific antiviral therapy. 1, 3

• Local skin reactions, nonspecific rashes, and lymphadenopathy can be managed with observation and supportive care alone. 1

• Symptoms last from 2 to 4 weeks in typical cases, and the disease has a mortality rate of approximately 0-10%. 4

Antiviral Therapy for Severe Disease

Tecovirimat (First-Line)

• Tecovirimat is FDA-approved as the first-line antiviral for treatment of human smallpox disease in adults and pediatric patients weighing at least 3 kg, and is used off-label for severe monkeypox infections. 2

• The mechanism involves inhibiting viral egress by targeting the orthopoxvirus VP37 envelope wrapping protein (F13L gene product), demonstrating 100% protection in non-human primates challenged with monkeypox virus. 1

• Dosing for oral tecovirimat:

  • 40 kg to <120 kg: 600 mg every 12 hours for 14 days
  • ≥120 kg: 600 mg every 8 hours for 14 days
  • Must be taken within 30 minutes after a full meal containing moderate or high fat. 2

• Dosing for intravenous tecovirimat:

  • 3 kg to <35 kg: 6 mg/kg every 12 hours by IV infusion over 6 hours
  • 35 kg to <120 kg: 200 mg every 12 hours by IV infusion over 6 hours
  • ≥120 kg: 300 mg every 12 hours by IV infusion over 6 hours. 2

Alternative Antivirals

• Brincidofovir is an alternative antiviral option with oral bioavailability advantage over cidofovir and reduced nephrotoxicity, demonstrating significant survival benefit in rabbitpox and mousepox models. 1

• Cidofovir is another alternative but carries significant nephrotoxicity risk requiring renal function monitoring before and during therapy. 1

• Cross-resistance between tecovirimat and brincidofovir is not expected based on their distinct mechanisms of action; orthopoxvirus isolates resistant to cidofovir retain sensitivity to tecovirimat and vice versa. 2

Special Considerations for Immunocompromised Patients

• Tecovirimat efficacy may be reduced in immunocompromised patients based on studies demonstrating reduced efficacy in immunocompromised animal models, though it remains the recommended first-line therapy. 2

• Immunocompromised patients are at higher risk for severe disease and death, especially those with advanced HIV, and require careful consideration of antiviral therapy including tecovirimat and brincidofovir. 1

• The possibility of resistance to tecovirimat should be considered in patients who either fail to respond to therapy or who develop recrudescence of disease after an initial period of responsiveness. 2

Vaccinia Immune Globulin (VIG) - For Vaccinia Complications Only

• VIG is first-line therapy specifically for severe complications of vaccinia virus (from smallpox vaccination), including progressive vaccinia, eczema vaccinatum, and generalized vaccinia, requiring aggressive VIG therapy, intensive monitoring, and tertiary-level supportive care. 5, 1

• VIG is available in IV and IM preparations under IND protocols through CDC and Department of Defense, based on worldwide historical experience as the established first-line therapy for vaccinia complications. 5, 1

• VIG is NOT indicated for routine monkeypox treatment - it is reserved for vaccinia-related adverse reactions from smallpox vaccination. 5

• Pregnant women who develop a condition requiring VIG should not be withheld from treatment, but routine prophylactic VIG is not indicated for unintentionally vaccinated pregnant women. 1

Common Pitfall to Avoid

• Do not confuse severe primary reactions with progressive vaccinia - severe primary reactions clear within 1-2 weeks without VIG, while progressive vaccinia shows painless progressive necrosis at the vaccination site without healing beyond 15 days after vaccination. 5, 1

• Delaying VIG therapy in true progressive vaccinia, eczema vaccinatum, or systemically ill patients with generalized vaccinia can increase mortality. 1

Infection Control Measures

• Hand hygiene with warm soapy water or hand rubs containing >60% alcohol is essential immediately after touching vaccination sites or changing bandages to prevent transmission. 5

• Contact and respiratory isolation should be implemented for patients with suspected smallpox or severe complications until diagnosis is clarified. 5, 1

• Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. 5

• Infection control precautions are mandatory to prevent secondary transmission of poxvirus infections. 1

Access to Investigational Therapies

• For civilian patients requiring IND therapies for vaccinia-related adverse reactions, contact the state health department or CDC Clinician Information Line. 1

• Clinical evaluation tools are available at the CDC website for assessing adverse reactions. 1

Prevention Considerations

• JYNNEOS (modified vaccinia Ankara vaccine) is safe for household contacts of immunocompromised patients and is approved for monkeypox prevention. 5

• ACAM2000 should NOT be used in household members of immunocompromised patients due to risk of unintentional vaccinia transmission (estimated at 5.4 events per 100,000 vaccinations). 5

• Vaccination can provide approximately 85% protection against monkeypox infection when given post-exposure, ideally within 3-4 days of exposure for maximum benefit. 6