What are the treatment options for Orthopoxvirus infections?

Treatment Options for Orthopoxvirus Infections

The primary treatment for Orthopoxvirus infections consists of supportive care, with antiviral medications such as tecovirimat (TPOXX) and brincidofovir as specific therapeutic options for severe cases. 1, 2, 3

Supportive Care

Supportive care remains the cornerstone of treatment for most Orthopoxvirus infections:

• Pain management for lesions and associated symptoms
• Hydration and nutritional support
• Management of fever and other constitutional symptoms
• Isolation measures to prevent transmission

According to CDC guidelines, for most patients with smallpox or related Orthopoxvirus infections, medical care consists primarily of supportive measures 1. For patients with less severe disease, isolation and observation outside a hospital setting may be appropriate to prevent healthcare-associated transmission.

Specific Antiviral Therapy

For severe cases or high-risk patients, specific antiviral therapy should be considered:

First-line Treatment:

• Tecovirimat (TPOXX): FDA-approved for smallpox and effective against multiple orthopoxviruses including variola, monkeypox, rabbitpox, and vaccinia viruses 2
  • Dosing: Oral administration according to FDA-approved regimen
  • Mechanism: Inhibits viral VP37 protein, preventing formation of extracellular virus
  • Indication: Severe disease, immunocompromised patients, complicated lesions, lesions near mouth/eyes/genitals 4

Second-line Treatment:

• Brincidofovir: FDA-approved for smallpox treatment 3
  • Administered orally in a specific dosing regimen
  • Caution: Associated with gastrointestinal toxicity and liver enzyme elevations

Other Treatment Options:

• Vaccinia Immune Globulin (VIG): Available for certain complications of vaccinia vaccination and potentially useful for severe orthopoxvirus infections 1

  • Available in intravenous (IV) and intramuscular (IM) preparations under Investigational New Drug protocols through CDC

• Cidofovir: Considered second-line therapy for vaccinia complications 1

  • Note: Never been used to treat vaccinia infections in humans
  • Available under IND protocols from CDC
  • Significant toxicity concerns (nephrotoxic in humans, carcinogenic in animals)

• Ophthalmic antivirals: For ocular manifestations of orthopoxvirus infections 1

Treatment Considerations for Specific Patient Groups

For patients with severe manifestations or in high-risk groups:

• Immunocompromised patients: Consider early antiviral therapy with tecovirimat 4, 5
• Pregnant/breastfeeding women: Antivirals may be considered based on risk-benefit assessment 4
• Pediatric patients: Require special consideration for antiviral dosing 4
• Patients with complicated lesions: Particularly those near mouth, eyes, or genitals 4

Vaccination as Post-exposure Prophylaxis

Vaccination can be used as post-exposure prophylaxis:

• Vaccinia vaccine can prevent or decrease disease severity when administered within 3-4 days after exposure 1
• Indicated for:
  • Persons exposed to the initial release of virus
  • Close contacts of confirmed or suspected cases
  • Healthcare personnel involved in direct care of confirmed or suspected patients
  • Laboratory personnel handling specimens from infected patients

Important Clinical Considerations

• Report suspected cases immediately: A suspected case of smallpox or other serious orthopoxvirus infection is a public health emergency 1
• Isolation precautions: Implement appropriate isolation facilities and precautions to prevent healthcare-associated transmission 1
• Laboratory confirmation: Coordinate with public health authorities for appropriate specimen collection and testing 1
• Resistance monitoring: Consider the possibility of resistance to tecovirimat in patients who fail to respond to therapy or develop recrudescence of disease 2

Emerging Concerns

The increasing frequency of orthopoxvirus outbreaks in humans and animals suggests a changing ecological and evolutionary pattern among these viruses 6. With most of the world's population now lacking immunity against orthopoxviruses due to cessation of smallpox vaccination, vigilance and preparedness for potential outbreaks are essential.

Human-to-human transmission of orthopoxviruses occurs through direct contact, respiratory droplets, and fomites such as towels and bedding 4. This underscores the importance of infection control measures alongside specific treatments.

Human-to-human transmission of orthopoxviruses occurs through direct contact, respiratory droplets, and fomites such as towels and bedding 4. This underscores the importance of infection control measures alongside specific treatments.