Human cases were first identified in 1970 in Zaire (now known as the Democratic Republic of Congo, or DRC). Since then, cases have been increasing in humans, particularly in the DRC, which has reported cases continuously over that time. This increase in cases may be due to cessation of smallpox vaccination (which provided some cross-protection) or waning immunity, environmental factors (e.g., increased population density, human settlements in unknown animal reservoirs, deforestation), and/or genetic evolution of the virus. However, there is no evidence to support these theories.[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
[5]Beer EM, Rao VB. A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl Trop Dis. 2019 Oct;13(10):e0007791.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816577
http://www.ncbi.nlm.nih.gov/pubmed/31618206?tool=bestpractice.com
[6]Nguyen PY, Ajisegiri WS, Costantino V, et al. Reemergence of human monkeypox and declining population immunity in the context of urbanization, Nigeria, 2017-2020. Emerg Infect Dis. 2021 Apr;27(4):1007-14.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007331
http://www.ncbi.nlm.nih.gov/pubmed/33756100?tool=bestpractice.com
The disease was previously known to be endemic in Central and Western Africa.[7]World Health Organization. Epidemiology of human monkeypox (mpox) - worldwide, 2018-2021. Jan 2023 [internet publication].
https://apps.who.int/iris/bitstream/handle/10665/365630/WER9803-29-36.pdf?sequence=1&isAllowed=y
The majority of cases were reported in rural areas (adjacent to or within tropical forests) of the Congo Basin and western Africa, particularly in the DRC where a major outbreak occurred from 1996 to 1997.[5]Beer EM, Rao VB. A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy. PLoS Negl Trop Dis. 2019 Oct;13(10):e0007791.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816577
http://www.ncbi.nlm.nih.gov/pubmed/31618206?tool=bestpractice.com
Between 2000 and 2021, there were 95 suspected and 40 confirmed outbreaks in the Central African Republic, with the number of outbreaks increasing after 2018.[8]Besombes C, Mbrenga F, Schaeffer L, et al. National monkeypox surveillance, Central African Republic, 2001-2021. Emerg Infect Dis. 2022 Nov 3;28(12).
http://www.ncbi.nlm.nih.gov/pubmed/36328951?tool=bestpractice.com
Nigeria experienced a reemergence of cases in 2017 after 39 years without reports of cases. Since then, five outbreaks have occurred between 2017 and 2021.[9]McCollum AM, Shelus V, Hill A, et al. Epidemiology of human mpox: worldwide, 2018-2021. MMWR Morb Mortal Wkly Rep. 2023 Jan 20;72(3):68-72.
https://www.cdc.gov/mmwr/volumes/72/wr/mm7203a4.htm
http://www.ncbi.nlm.nih.gov/pubmed/36656790?tool=bestpractice.com
The largest outbreak of confirmed cases in the Central African Republic occurred in November 2021, with 14 cases and four waves of interhuman transmission.[10]Besombes C, Mbrenga F, Malaka C, et al. Investigation of a mpox outbreak in Central African Republic, 2021-2022. One Health. 2023 Jun;16:100523.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988319
http://www.ncbi.nlm.nih.gov/pubmed/36950196?tool=bestpractice.com
Outbreaks occurred in refugee camps in the Republic of Sudan in 2022, with no zoonotic origin reported.[11]World Health Organization. Mpox (monkeypox): fact sheet. Aug 2024 [internet publication].
https://www.who.int/en/news-room/fact-sheets/detail/monkeypox
Ongoing global clade II mpox outbreak
A global outbreak of clade II mpox was first identified in May 2022 and is ongoing across many countries. Clusters of cases were initially reported across several countries outside of Africa with no direct travel links to an endemic area. This was the first time that chains of transmission were reported in countries without known epidemiologic links to West and Central Africa.
The WHO declared that the outbreak constituted a Public Health Emergency of International Concern (PHEIC) in July 2022. This first PHEIC ended in May 2023 as the frequency of cases had decreased significantly, although cases continue to be reported. The group of viruses largely circulating in the outbreak belong to clade IIb.
Since the beginning of 2022, over 109,000 laboratory-confirmed cases have been reported globally from 123 countries, including 236 deaths, as of 30 September 2024. The most affected countries include the US, Brazil, Spain, the DRC, France, and Colombia.[12]World Health Organization. 2022-24 mpox (monkeypox) outbreak: global trends. Oct 2024 [internet publication].
https://worldhealthorg.shinyapps.io/mpx_global
Sporadic case clusters have been reported in locations where transmission had previously ceased.[13]Centers for Disease Control and Prevention. Notes from the field: emergence of an mpox cluster primarily affecting persons previously vaccinated against mpox - Chicago, Illinois, March 18-June 12, 2023. Jun 2023 [internet publication].
https://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm
Unlike previous outbreaks, cases outside of Africa have predominantly been in younger adult men, most of whom identify as gay, bisexual, or other men who have sex with men.[14]León-Figueroa DA, Barboza JJ, Garcia-Vasquez EA, et al. Epidemiological situation of monkeypox transmission by possible sexual contact: a systematic review. Trop Med Infect Dis. 2022 Sep 27;7(10):267.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607952
http://www.ncbi.nlm.nih.gov/pubmed/36288008?tool=bestpractice.com
[15]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
[16]Liu Q, Fu L, Wang B, et al. Clinical characteristics of human mpox (monkeypox) in 2022: a systematic review and meta-analysis. Pathogens. 2023 Jan 15;12(1):146.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861547
http://www.ncbi.nlm.nih.gov/pubmed/36678494?tool=bestpractice.com
There is no signal suggesting sustained transmission outside of these networks. Males ages between 18 and 44 years have been disproportionately affected.[12]World Health Organization. 2022-24 mpox (monkeypox) outbreak: global trends. Oct 2024 [internet publication].
https://worldhealthorg.shinyapps.io/mpx_global
Cases have also been reported in women (mainly heterosexual, including pregnant women) and children, albeit more rarely.[17]Grothe JH, Cornely OA, Salmanton-García J, et al. Monkeypox in children and adult women in Europe: results from a flash VACCELERATE pilot survey. Enferm Infecc Microbiol Clin. 2022 Sep 19 [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534071
http://www.ncbi.nlm.nih.gov/pubmed/36249472?tool=bestpractice.com
[18]Vallejo-Plaza A, Rodríguez-Cabrera F, Hernando Sebastián V, et al. Mpox (formerly monkeypox) in women: epidemiological features and clinical characteristics of mpox cases in Spain, April to November 2022. Euro Surveill. 2022 Dec;27(48):2200867.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716644
http://www.ncbi.nlm.nih.gov/pubmed/36695461?tool=bestpractice.com
[19]Gaeta F, De Caro F, Franci G, et al. Monkeypox infection 2022: an updated narrative review focusing on the neonatal and pediatric population. Children (Basel). 2022 Nov 26;9(12):1832.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776986
http://www.ncbi.nlm.nih.gov/pubmed/36553276?tool=bestpractice.com
In the US, 2.7% of all reported cases were in women including 3% in pregnant or recently pregnant women (as of November 2022).[20]Oakley LP, Hufstetler K, O'Shea J, et al. Mpox cases among cisgender women and pregnant persons: United States, May 11 - November 7, 2022. MMWR Morb Mortal Wkly Rep. 2023 Jan 6;72(1):9-14.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815154
http://www.ncbi.nlm.nih.gov/pubmed/36602932?tool=bestpractice.com
In Nigeria, there were more cases in children and women, and fewer cases in people without HIV infection and gay, bisexual, or other men who have sex with men, compared to countries outside of Africa. Hospitalization rates were also much higher compared with other countries.[21]Ogoina D, Dalhat MM, Denue BA, et al. Clinical characteristics and predictors of human mpox outcome during the 2022 outbreak in Nigeria: a cohort study. Lancet Infect Dis. 2023 Aug 22:S1473-3099(23)00427-9.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00427-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37625431?tool=bestpractice.com
Transgender and gender-diverse people have been disproportionately affected during the outbreak.[22]Blackburn D, Roth NM, Gold JAW, et al. Epidemiologic and clinical features of mpox in transgender and gender-diverse adults: United States, May - November 2022. MMWR Morb Mortal Wkly Rep. 2022 Dec 30;71(5152):1605-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812441
http://www.ncbi.nlm.nih.gov/pubmed/36580418?tool=bestpractice.com
[23]Wick JM, Pelliccione A, Lee-Rodriguez C, et al. An atypical presentation of mpox transmitted between transgender men through oral sex. Sex Transm Dis. 2023 Oct 1;50(10):685-6.
https://journals.lww.com/stdjournal/fulltext/2023/10000/an_atypical_presentation_of_mpox_transmitted.10.aspx
http://www.ncbi.nlm.nih.gov/pubmed/37195290?tool=bestpractice.com
Racial and ethnic disparities also exist.[24]Kota KK, Hong J, Zelaya C, et al. Racial and ethnic disparities in Mpox cases and vaccination among adult males - United States, May-December 2022. MMWR Morb Mortal Wkly Rep. 2023 Apr 14;72(15):398-403.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121252
http://www.ncbi.nlm.nih.gov/pubmed/37053122?tool=bestpractice.com
Adults ages >50 years appear to have a similar risk of hospitalization and death compared with adults ages <50 years, possibly due to older adults receiving the smallpox vaccine as part of their childhood immunization schedule.[25]Centers for Disease Control and Prevention. Epidemiologic and clinical features of mpox in adults aged >50 years - United States, May 2022-May 2023. Aug 2023 [internet publication].
https://www.cdc.gov/mmwr/volumes/72/wr/mm7233a3.htm
Clade I mpox outbreak originating in Africa
There has been a significant increase in the number of cases and deaths in the DRC throughout 2023 and 2024, with geographic expansion into previously unaffected areas (including neighboring countries such as Burundi, Kenya, Rwanda, and Uganda), and sexual transmission due to the clade Ib virus (a newly identified variant) documented for the first time.[12]World Health Organization. 2022-24 mpox (monkeypox) outbreak: global trends. Oct 2024 [internet publication].
https://worldhealthorg.shinyapps.io/mpx_global
[27]World Health Organization. Disease outbreak news: mpox (monkeypox) - Democratic Republic of the Congo. Nov 2023 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON493
[28]Centers for Disease Control and Prevention. Mpox caused by human-to-human transmission of monkeypox virus in the Democratic Republic of the Congo with spread to neighboring countries. Aug 2024 [internet publication].
https://emergency.cdc.gov/han/2024/han00513.asp
The WHO declared that the outbreak constituted a PHEIC on the 14th August 2024.[29]World Health Organization. WHO Director-General declares mpox outbreak a public health emergency of international concern. Aug 2024 [internet publication].
https://www.who.int/news/item/14-08-2024-who-director-general-declares-mpox-outbreak-a-public-health-emergency-of-international-concern
Approximately 13,126 laboratory-confirmed cases, including 59 confirmed deaths, have been reported in Africa since the beginning of 2022 (as of 27 October 2024). Of these cases, 10,722 were reported in 2024, including 36 deaths, across 19 countries. The three countries with the majority of cases in 2024 are the DRC, Burundi, and Uganda.[12]World Health Organization. 2022-24 mpox (monkeypox) outbreak: global trends. Oct 2024 [internet publication].
https://worldhealthorg.shinyapps.io/mpx_global
The number of suspected cases is much higher; these cases remain untested due to limited diagnostic capacity in some African countries.
The outbreak is ongoing, with sustained community transmission driven by sexual transmission. It is not currently known whether the circulating clade Ib variant is more transmissible or causes more severe disease compared with other clade I variants.[30]World Health Organization. Disease outbreak news: mpox - Democratic Republic of the Congo. Jun 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON522
[31]World Health Organization. Mpox – African region. Aug 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON528
A small number of cases of travel-associated clade Ib infections have been reported outside of Africa (e.g., India, Sweden, Thailand, Germany, the UK).[26]UK Health Security Agency. Latest update on cases of Clade Ib mpox. Nov 2024 [internet publication].
https://www.gov.uk/government/news/ukhsa-detects-first-case-of-clade-ib-mpox
[32]World Health Organization. Mpox – Sweden. Aug 2024 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON531
[33]European Centre for Disease Prevention and Control. Confirmed mpox clade Ib case in Germany, risk remains low for EU/EEA. Oct 2024 [internet publication].
https://www.ecdc.europa.eu/en/news-events/confirmed-mpox-clade-ib-case-germany-risk-remains-low-eueea
Current epidemiologic updates are available from public health authorities.
Previous outbreaks mainly affected children. However, the 2022 global clade II mpox outbreak has primarily affected male adults.[34]Li P, Li J, Ayada I, et al. Clinical features, antiviral treatment and patient outcomes: a systematic review and comparative analysis of the previous and the 2022 mpox outbreaks. J Infect Dis. 2023 Feb 3 [Epub ahead of print].
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad034/7025706?login=false
http://www.ncbi.nlm.nih.gov/pubmed/36735342?tool=bestpractice.com
The median age at presentation has evolved from young children (4 years) in the 1970s to young adults (21 years) between 2010 and 2019.[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
In the 2022 global clade II mpox outbreak, cases have been uncommon in children compared with adults.[15]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
[19]Gaeta F, De Caro F, Franci G, et al. Monkeypox infection 2022: an updated narrative review focusing on the neonatal and pediatric population. Children (Basel). 2022 Nov 26;9(12):1832.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776986
http://www.ncbi.nlm.nih.gov/pubmed/36553276?tool=bestpractice.com
Globally, 1.3% of cases were in children and adolescents ages <18 years of and no deaths were reported.[35]Centers for Disease Control and Prevention. Emerging infectious diseases: mpox in children and adolescents during multicountry outbreak, 2022-2023. Sep 2023 [internet publication].
https://wwwnc.cdc.gov/eid/article/29/10/23-0516_article
In the US, children and adolescents ages <18 years represented <0.01% of all cases and none resulted in critical illness or death. Cases have been reported rarely in neonates.[36]Centers for Disease Control and Prevention. Clinical considerations for mpox in children and adolescents in the U.S. Sep 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/pediatric.html
Available data from the 2022 global clade II mpox outbreak indicated that 28% to 51% of patients have been HIV-positive (in cases where HIV status is known).[37]Centers for Disease Control and Prevention. Clinical considerations for mpox in immunocompromised people. Oct 2024 [internet publication].
https://www.cdc.gov/mpox/hcp/clinical-care/immunocompromised-people.html
[38]O'Shea J, Filardo TD, Morris SB, et al. Interim guidance for prevention and treatment of monkeypox in persons with HIV infection: United States, August 2022. MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1023-8.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7132e4.htm
http://www.ncbi.nlm.nih.gov/pubmed/35951495?tool=bestpractice.com
Although women account for a minority of cases, the proportion of women with HIV has been estimated to be 27% (50% in transgender women).[39]Thornhill JP, Palich R, Ghosn J, et al. Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series. Lancet. 2022 Dec 3;400(10367):1953-65.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02187-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36403584?tool=bestpractice.com
However, in the largest study of women to date, only 4.4% of women had HIV (compared with 40.8% in men).[18]Vallejo-Plaza A, Rodríguez-Cabrera F, Hernando Sebastián V, et al. Mpox (formerly monkeypox) in women: epidemiological features and clinical characteristics of mpox cases in Spain, April to November 2022. Euro Surveill. 2022 Dec;27(48):2200867.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716644
http://www.ncbi.nlm.nih.gov/pubmed/36695461?tool=bestpractice.com
Prior to the 2022 global clade II mpox outbreak, a small number of travel-associated cases had been reported in the UK, the US, Singapore, and Israel.[40]UK Health Security Agency. Monkeypox case in England. December 2018 [internet publication].
https://www.gov.uk/government/news/monkeypox-case-in-england
[41]UK Health Security Agency. Monkeypox case confirmed in England. December 2019 [internet publication].
https://www.gov.uk/government/news/monkeypox-case-confirmed-in-england
[42]World Health Organization. Monkeypox: United Kingdom of Great Britain and Northern Ireland. July 2021 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/monkeypox---united-kingdom-of-great-britain-and-northern-ireland
[43]World Health Organization. Monkeypox: United Kingdom of Great Britain and Northern Ireland. June 2022 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON381
[44]Centers for Disease Control and Prevention. Imported monkeypox case reported in Maryland. Nov 2021 [internet publication].
https://archive.cdc.gov/#/details?url=https://www.cdc.gov/media/releases/2021/s1117-monkeypox.html
[45]Centers for Disease Control and Prevention. CDC and Texas confirm monkeypox in U.S. traveler. Jul 2021 [internet publication].
https://archive.cdc.gov/#/details?url=https://www.cdc.gov/media/releases/2021/s0716-confirm-monkeypox.html
[46]Rao AK, Schulte J, Chen TH, et al. Monkeypox in a traveler returning from Nigeria – Dallas, Texas, July 2021. MMWR Morb Mortal Wkly Rep. 2022 Apr 8;71(14):509-16.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7114a1.htm
http://www.ncbi.nlm.nih.gov/pubmed/35389974?tool=bestpractice.com
[47]World Health Organization. Disease outbreak news. Monkeypox - Singapore. May 2019 [internet publication].
https://www.who.int/emergencies/disease-outbreak-news/item/16-may-2019-monkeypox-singapore-en
[48]Erez N, Achdout H, Milrot E, et al. Diagnosis of imported monkeypox, Israel, 2018. Emerg Infect Dis. 2019 May;25(5):980-3.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478227
http://www.ncbi.nlm.nih.gov/pubmed/30848724?tool=bestpractice.com
An outbreak of over 70 cases occurred in the US Midwest in 2003, and was the first reported occurrence of the disease outside of Africa. The source of this outbreak was exposure to infected prairie dogs that had acquired the infection from Gambian rats imported from West Africa.[49]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