Morphology: Enveloped, double-stranded DNA virus. Family Poxviridae, genus Orthopoxvirus (same genus as Variola/smallpox). Two clades: Clade I (Central African, higher mortality) + Clade II (West African, 2022 global outbreak).
Typical drugs
- #1Tecovirimat— **600 mg PO BID × 14 d** with high-fat meal. Reserved for severe / immunocompromised / high-risk hosts; STOMP trial showed limited benefit in immunocompetent.
Empiric therapy when resistant
Tecovirimat-resistant mpox in immunocompromised → brincidofovir (lipid conjugate of cidofovir, broad DNA virus activity; oral). Limited supply + access.
Resistance mechanisms
altered-target
F13L (VP37 gene) mutations → tecovirimat resistance
Example: Documented in immunocompromised patients on prolonged tecovirimat. Brincidofovir as alternative.
Resistance notes
Resistance emerging with prolonged tecovirimat in advanced HIV. Monitor.
Pearls
2022 outbreak features: predominantly MSM sexual transmission; lesions often genital, perianal, oral; proctitis common + painful; fewer prodromal symptoms than classical mpox. Classical features: prodrome (fever, lymphadenopathy, malaise) → centrifugal vesiculopustular rash (lesions in same stage at one site, unlike chickenpox). Lymphadenopathy is a key distinguishing feature from smallpox. Severe disease + treatment indications (per CDC): extensive lesions, severe pain (proctitis, ocular), immunocompromised (HIV CD4 <200, transplant), pregnancy/lactation, pediatric. JYNNEOS vaccine (replication-deficient vaccinia, 2-dose subQ or ID) for at-risk MSM + post-exposure prophylaxis (give within 4 days for prevention; days 4–14 may modify disease). Reactivation of varicella-zoster precautions + sexual transmission counseling during active lesions until full crusting and re-epithelialization (typically 2–4 weeks).
References
- CDC Mpox Clinical Guidance
- STOMP Trial (NIH 2024) (2024)
- WHO Mpox Public Health Guidance (2024)