Most cases are usually mild and self-limiting, and most patients will recover within 2 to 4 weeks without treatment.
More than 90% of survivors have no complications, regardless of smallpox vaccination status. In survivors who do develop long-term complications, the most common sequelae are disfiguring scarring of the skin (including pitted scars) and blindness.
The acute infectious illness results in immunity following recovery. Relapse of disease is rare, but is possible. One UK patient experienced a mild relapse 6 weeks after hospital discharge in 2019. The relapse was short, and was not associated with detectable viraemia.
Severe or complicated disease and death occurs more commonly in younger children and immunocompromised people.
Most reported deaths have occured in younger children and immunocompromised people (e.g., poorly controlled HIV infection).
In the early years of human infection, 100% of deaths were in children <10 years of age. However, between 2000 and 2019, children <10 years of age accounted for only 37.5% of deaths.
Patients with fatal disease had higher viral loads of the virus in their blood, maximum skin lesion count, and elevated transaminases.
Severe complications and sequelae have been found to be more common among unvaccinated patients (74%) compared with vaccinated patients (40%).
Case fatality rates vary according to virus clade, geographical location, and availability of medical facilities, and are vulnerable to case ascertainment bias during outbreaks.
Historically, the case fatality rate (CFR) of the Clade I virus has been estimated to be 1% to 10%, while the CFR of the Clade IIa virus has been estimated to be <3%. More recent data for the Clade IIa virus report a CFR of 1.4%.
The estimated pooled CFR was 8.7% for both clades in one systematic review (10.6% for Clade I and 3.6% for Clade IIa).
The overall CFR was 0% in an outbreak in the US in 2003.
Fatalities in the current ongoing multi-country outbreak due to the Clade IIb variant are rare.
Twenty-three deaths have been reported as of 16 September 2022 (15 in Africa, two in Spain, one in Belgium, one in India, two in Brazil, one in Ecuador, one in Cuba). Therefore, the overall global CFR (based on reported cases only) is approximately 0.04% as of 16 September 2022 (0.013% in countries that have not reported monkeypox previously, and 3% in Africa).
Severe disseminated infection and death due to multi-organ failure has been reported in an immunosuppressed patient in Brazil. The patient was HIV-positive (on treatment with undetectable viral load), and had recently completed chemotherapy for a diffuse large B-cell lymphoma with metastases to the spine, skull, and liver. Other reported causes of death in this outbreak include encephalitis, as well as multi-organ failure in a man with uncontrolled HIV infection and tuberculosis.
Whether mortality in this outbreak is associated with any specific factors is currently unknown.
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