Mpox

Mpox is a viral zoonotic infection caused by monkeypox virus, an orthopoxvirus related to variola (smallpox) and vaccinia viruses. It was historically endemic to specific regions of Central and West Africa, with animal to human transmission from infected rodents and other small mammals.

The epidemiology has shifted substantially following the 2022 global outbreak, which demonstrated sustained human to human transmission, particularly through close physical and sexual contact. This extended well beyond the historical endemic regions and prompted a fundamental reassessment of the global public health significance of this infection.

Pathophysiology and transmission

• The virus is transmitted through direct contact with infectious skin or mucosal lesions, body fluids, or respiratory droplets during prolonged close contact. In the historical zoonotic pattern, transmission was through contact with infected animals or contaminated materials.
• The 2022 and subsequent outbreaks showed a particular, though not exclusive, association with transmission during close sexual contact. This contributed to a somewhat different demographic and clinical pattern (including a higher proportion of anogenital lesions) compared with the classical historical presentation.
• Two genetically and clinically distinct clades exist. Clade one (historically associated with Central Africa) is generally associated with greater disease severity and higher case fatality.
• Clade two (historically associated with West Africa) was the predominant clade responsible for the global 2022 outbreak. The distinction is relevant to risk assessment and public health response.

• A prodromal phase of fever, headache, myalgia, lymphadenopathy and malaise typically precedes the onset of the characteristic rash by one to several days. Prominent lymphadenopathy is a notably distinguishing feature from smallpox, which characteristically lacks it.
• This classical prodrome is frequently absent or minimal in the 2022 and subsequent outbreaks. Localised anogenital or oral lesions without a preceding prominent systemic prodrome have been a common presentation.
• The characteristic rash progresses through sequential stages from macules to papules, vesicles, pustules and, finally, crusted scabs. Lesions are classically deeply seated and firm.
• In contrast to varicella, lesions tend to be at a similar stage of development at any given time across the body. Varicella classically shows lesions at multiple different stages simultaneously.
• Lesion distribution in the outbreak associated with sustained human to human and, particularly, sexual transmission has frequently differed from the classical historical pattern. Anogenital, oral and perianal lesions are common, sometimes as the sole or predominant site of involvement.
• The classical historical zoonotic pattern is a more generalised, centrifugal distribution, with greater involvement of the face and extremities.
• Complications occur in a minority, with increased risk in specific populations including significantly immunocompromised individuals (particularly advanced HIV infection), pregnant women and young children.
• Complications include secondary bacterial skin infection, scarring, and proctitis (particularly relevant given the anogenital lesion pattern associated with sexual transmission).
• Rarely, more severe manifestations occur, including encephalitis and pneumonitis. Severe or disseminated disease in significantly immunocompromised patients carries substantial associated mortality.

• Polymerase chain reaction testing of lesion material (swab of vesicle or pustule fluid, or lesion crust) is the diagnostic method of choice, offering rapid and specific confirmation of monkeypox virus infection.
• A thorough sexual health and exposure history is an important component of assessment in patients presenting with a compatible clinical picture, particularly with anogenital lesions. Test for other relevant sexually transmitted infections, given frequent coexposure risk factors in the context of the outbreak associated transmission pattern.
• Any suspected case requires prompt notification to relevant public health authorities, given the significant surveillance and contact tracing implications of this infection. Implement specific isolation and infection control precautions pending and following diagnostic confirmation.

• Management for the majority of cases is supportive, given the generally self limiting nature of clade two associated disease in immunocompetent individuals.
• Supportive care comprises analgesia for pain (which can be significant, particularly with anogenital or oral lesions), appropriate antibiotics for any clinically evident secondary bacterial infection, and wound care of the characteristic skin lesions.
• Tecovirimat, an antiviral agent with specific activity against orthopoxviruses, is available under specific access programmes or emergency use protocols in many jurisdictions.
• Tecovirimat is generally reserved for patients at higher risk of severe disease (significant immunocompromise, extensive or severe disease, involvement of vulnerable sites such as the eye). It is not used routinely for uncomplicated disease in an otherwise healthy individual, given the generally favourable natural history in this broader population.
• Isolation precautions are essential infection control measures given the recognised transmission risk during the symptomatic period. They include avoidance of close physical and sexual contact until lesions have fully crusted and the crusts have separated with new skin formed underneath (reflecting the period of infectivity).
• Healthcare workers providing direct care use appropriate personal protective equipment.
• Vaccination with a modified vaccinia Ankara based smallpox vaccine offers cross protective immunity against monkeypox virus, given the close antigenic relationship between orthopoxviruses.
• It is recommended for pre exposure prophylaxis in individuals at higher ongoing risk of exposure. This is guided by specific local public health risk assessment and eligibility criteria, frequently including men who have sex with men with multiple partners in the context of the outbreak associated transmission pattern.
• It is also recommended for post exposure prophylaxis following a significant, recognised exposure, ideally administered within four days of exposure for optimal effectiveness in preventing disease.
• Administration up to fourteen days post exposure is still considered potentially beneficial in modifying disease severity, even where prevention of infection itself is less certain at this later timepoint.
• Contact tracing and, where indicated according to specific public health protocols and risk assessment, post exposure vaccination of identified close contacts are important components of the public health response to confirmed cases. This reflects the substantial ongoing public health significance of this infection following the sustained human to human transmission established during the 2022 global outbreak.