Mpox Clinical Presentation, Diagnostic Approaches, and Treatment Strategies

Importance: A global outbreak of clade IIb Monkeypox virus (MPXV) infections spread rapidly across at least 118 countries resulting in a Public Health Emergency of International Concern (PHEIC) from July 2022 to May 2023. This outbreak affected more than 99 000 persons worldwide and caused more than 33 000 infections and 60 deaths in the US. In 2024, there have been approximately 200 new infections per month in the US. On August 14, 2024, the World Health Organization declared mpox a PHEIC for a second time due to a rapid increase in infections with clade I MPXV in Central Africa. Observations: Mpox is primarily acquired through direct skin to skin contact with MPXV. With clade IIb MPXV, infections are most commonly associated with sexual activity among individuals who are gay, bisexual, and other men who have sex with men. After a median incubation period of 7 to 10 days, prodromal symptoms include fever (62%-72%), lymphadenopathy (56%-86%), myalgias (31%-55%), malaise (23%-57%), and headache (25%-55%). Skin lesions progress through 4 well-defined stages (macules, papules, vesicles, and pustules) over 2 to 4 weeks. Clade IIb MPXV is typically a self-limited illness with a low mortality rate (<0.2% in the US); however, severe illness and death may occur in immunocompromised individuals, especially those with advanced HIV (CD4 count <200 cells/μL). Mpox should be suspected in patients with potential exposure to MPXV who have skin lesions, and the diagnosis is confirmed with polymerase chain reaction testing of lesions. Management is supportive and focuses on skin care and symptom relief with analgesics. While no antiviral treatments are currently approved for mpox by the US Food and Drug Administration, several therapeutics, such as tecovirimat, brincidofovir, and vaccinia immune globulin intravenous, are available through expanded access programs or clinical trials. Vaccination with the 2-dose Modified Vaccinia Ankara-Bavarian Nordic vaccine is recommended for high-incidence populations and has an efficacy of 66% to 86%. Conclusions and Relevance: Mpox is a viral infection transmitted primarily through close skin to skin contact that typically causes a self-resolving illness but can result in severe illness and death in immunocompromised individuals. First-line therapy is supportive care, although patients with severe mpox infection may be treated with advanced therapeutics. Mpox vaccination is effective and, if available, should be offered to individuals at risk of exposure to mpox.