Prognosis
Most cases are usually mild and self-limiting, and most patients will recover within 2 to 4 weeks without treatment.
Typically, 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.[47]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
Persistent symptoms (e.g., anorectal or genital issues, fatigue, loss of physical fitness, pain, scarring, mental health issues) have been reported in up to two-thirds of patients 3-20 weeks after the initial infection in the 2022-23 global outbreak, which may significantly affect the patient's quality of life.[275]Berens-Riha N, Bracke S, Rutgers J, et al. Persistent morbidity in Clade IIb mpox patients: interim results of a long-term follow-up study, Belgium, June to November 2022. Euro Surveill. 2023 Feb;28(7):2300072.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936596
http://www.ncbi.nlm.nih.gov/pubmed/36795501?tool=bestpractice.com
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 viremia.[242]Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022 Aug;22(8):1153-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300470
http://www.ncbi.nlm.nih.gov/pubmed/35623380?tool=bestpractice.com
The occurrence of a second febrile period when the lesions become pustular has been associated with deterioration of the patient’s general condition.[141]McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan;58(2):260-7.
https://academic.oup.com/cid/article/58/2/260/335791
http://www.ncbi.nlm.nih.gov/pubmed/24158414?tool=bestpractice.com
Severe or complicated disease and death occurs more commonly in younger children and immunocompromised people.
Most reported deaths, prior to the 2022-23 global outbreak, occurred in younger children and immunocompromised people (e.g., poorly controlled HIV infection).[47]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
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.[4]Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox – a potential threat? A systematic review. PLoS Negl Trop Dis. 2022 Feb;16(2):e0010141.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870502
http://www.ncbi.nlm.nih.gov/pubmed/35148313?tool=bestpractice.com
Patients with fatal disease had higher viral loads of the virus in their blood, maximum skin lesion count, and elevated transaminases.[47]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
Severe complications and sequelae were more common among unvaccinated patients (74%) compared with vaccinated patients (40%).[141]McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014 Jan;58(2):260-7.
https://academic.oup.com/cid/article/58/2/260/335791
http://www.ncbi.nlm.nih.gov/pubmed/24158414?tool=bestpractice.com
Case fatality rates (CFRs) vary according to virus clade, geographic location, and availability of medical facilities, and are vulnerable to case ascertainment bias during outbreaks.
Historically, the 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 1.4% to 3%.[47]World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance, 10 June 2022. June 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1
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).[4]Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox – a potential threat? A systematic review. PLoS Negl Trop Dis. 2022 Feb;16(2):e0010141.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870502
http://www.ncbi.nlm.nih.gov/pubmed/35148313?tool=bestpractice.com
The overall CFR was 0% in an outbreak in the US in 2003.[36]Huhn GD, Bauer AM, Yorita K, et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005 Dec 15;41(12):1742-51.
https://academic.oup.com/cid/article/41/12/1742/344953
http://www.ncbi.nlm.nih.gov/pubmed/16288398?tool=bestpractice.com
Fatalities due to the Clade IIb virus are rare. Overall mortality has decreased in the 2022-23 global outbreak compared with previous outbreaks.[13]Kumar R, Singh S, Singh SK. A systematic review of 5110 cases of monkeypox: what has changed between 1970 and 2022? Cureus. 2022 Oct;14(10):e30841.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9704117
http://www.ncbi.nlm.nih.gov/pubmed/36451652?tool=bestpractice.com
The overall CFR is 0.16% (as of 9 May 2023).[7]World Health Organization. 2022-23 mpox (monkeypox) outbreak: global trends. May 2023 [internet publication].
https://worldhealthorg.shinyapps.io/mpx_global
Approximately 1.2 deaths per 1000 cases occurred globally during the outbreak, with 1.3 deaths per 1000 cases in the US.[276]Riser AP, Hanley A, Cima M, et al. Epidemiologic and clinical features of mpox-associated deaths - United States, May 10, 2022-March 7, 2023. MMWR Morb Mortal Wkly Rep. 2023 Apr 14;72(15):404-10.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121256
http://www.ncbi.nlm.nih.gov/pubmed/37053126?tool=bestpractice.com
Causes of death have included multi-organ failure and encephalitis.[277]Menezes YR, Miranda AB. Severe disseminated clinical presentation of monkeypox virus infection in an immunosuppressed patient: first death report in Brazil. Rev Soc Bras Med Trop. 2022 Aug 29;55:e0392.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9425919
http://www.ncbi.nlm.nih.gov/pubmed/36037315?tool=bestpractice.com
[278]Sah R, Mohanty A, Abdelaal A, et al. First Monkeypox deaths outside Africa: no room for complacency. Ther Adv Infect Dis. 2022 Jan-Dec;9:20499361221124027.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424878
http://www.ncbi.nlm.nih.gov/pubmed/36051570?tool=bestpractice.com
Whether mortality is associated with any specific factors is currently unknown. However, nearly all deaths in the US were in patients who were immunocompromised at the time of diagnosis.[276]Riser AP, Hanley A, Cima M, et al. Epidemiologic and clinical features of mpox-associated deaths - United States, May 10, 2022-March 7, 2023. MMWR Morb Mortal Wkly Rep. 2023 Apr 14;72(15):404-10.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121256
http://www.ncbi.nlm.nih.gov/pubmed/37053126?tool=bestpractice.com
[279]Filippov E, Duhan S, Lehman L, et al. Treatment failure in patient with severe mpox and untreated HIV, Maryland, USA. Emerg Infect Dis. 2023 May 12;29(6) [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/37172298?tool=bestpractice.com
Cases of suspected reinfection have been reported.
Apparent cases of reinfection have been reported 3-6 months after recovery from initial infection, possibly with different strains of the virus.[280]Golden J, Harryman L, Crofts M, et al. Case of apparent mpox reinfection. Sex Transm Infect. 2023 Jan 27 [Epub ahead of print].
https://sti.bmj.com/content/early/2023/01/26/sextrans-2022-055736.long
http://www.ncbi.nlm.nih.gov/pubmed/36707246?tool=bestpractice.com
[281]Musumeci S, Najjar I, Boffi El Amari E, et al. A case of mpox reinfection. Clin Infect Dis. 2023 Mar 11 [Epub ahead of print].
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad147/7076064?login=true
http://www.ncbi.nlm.nih.gov/pubmed/36905148?tool=bestpractice.com
[282]Zeggagh J, Ferraris O, Salmona M, et al. Second clinical episode of hMPX virus in a man having sex with men. Lancet. 2023 May 13;401(10388):1610.
http://www.ncbi.nlm.nih.gov/pubmed/36972717?tool=bestpractice.com
[283]Álvarez-López P, Borras-Bermejo B, López Pérez L, et al. Suspected case of monkeypox reinfection versus reactivation in a immunocompetent patient, Barcelona, 2022. Int J STD AIDS. 2023 Apr 26 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/37125456?tool=bestpractice.com
[284]Rocha SQ, Fonsi M, Tancredi MV, et al. Mpox in a couple living with HIV: relapse or reinfection? AIDS Res Hum Retroviruses. 2023 May 4 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/37140474?tool=bestpractice.com
Further research is required on immunity after recovering from infection.