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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Bassel Almarie M.D.[2]

## Overview

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Monkeypox virus was first identified in monkeys shipped from Singapore to Denmark in 1958[1]. First case of monkeypox in humans was reported in a hospitalized child in the Republic of the Congo in 1970[2]. After 1970, monkeypox virus emerged and cases were recorded in 11 African countries. Until the late 1980s, more than 400 cases were recorded[3]. In the early 1990s, the number of reported cases dramatically declined to notably zero cases between 1993 and 1995[4]. In 1996, large number of cases were suspected in an outbreak in Democratic Republic of Congo but only small number of cases were laboratory confirmed[5].

In 2003, 47 cases of monkeypox were confirmed in the United States. In the following years, there has been cases of monkeypox recorded periodically in non-endemic regions, predominately in the United Kingdom and one in Singapore. All of these cases were imported from endemic regions. In May 2022, case clusters of monkeypox were traced around the world over a short period of time. As of May 22, 2022, a total of 109 cases were recorded and 87 suspected around the world. On June 2, 2022, 780 cases of monkeypox were identified or reported to the World Health Organization[6]. As of June 15, 2022, a total of 2103 laboratory confirmed cases, including one death, have been reported to World Health Organization[7]. As of October 19, 2022, a total of 74,785 cases were confirmed globally, including 32 deaths_Monkeypox_|_Poxvirus_|_CDC-8|[8].

## Historical Perspective

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* The clinical expression of monkeypox was first described in 1958. Poxlike disease was observed in cynomolgus (Macaca cynomolgus) monkeys that were shipped from Singapore to a research facility in Copenhagen, Denmark. The virus was isolated and identified as monkeypox virus[1].
* First case of monkeypox in humans was reported on September 1, 1970. A 9-month-old child was suspected of having smallpox and admitted to Basankusu Hospital in Democratic Republic of the Congo. Specimen was collected from patient and sent the World Health Organization Smallpox Reference Center in Moscow, Russia. The specimen revealed a virus similar to, if not identical with, monkeypox virus[2].
* Since 1970, monkeypox virus emerged and cases were recorded in 11 African countries: Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Cote d’Ivoire, Liberia, Nigeria, the Republic of the Congo, Sierra Leone and South Sudan. Until 1990, more than 400 cases were recorded.
* Between 1970 and 1979, the World Health Organization (WHO) confirmed 54 cases[3][9].
* Between 1981 and 1986, the WHO conducted an intensive active surveillance, confirming 338 cases and 33 deaths[10][11].
* Number of reported cases declined after ending the Monkeypox surveillance program. In Cameroon, Gabon and the Democratic Republic of the Congo, 6 cases were reported in 1987, one in 1990, 5 in 1991 and one in 1992.
* Between 1993 and 1995, no cases of monkeypox were reported to the WHO[4].
* Between 1996 and 1997, 511 cases were suspected in an outbreak in Democratic Republic of Congo although only small number were laboratory confirmed[5].

### 2003 U.S. Outbreak

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As of June 7, 2003, cases of suspected monkeypox in the United States had been reported among residents of Wisconsin (18), northern Illinois (10), and northwestern Indiana (1). The disease stemmed from a giant Gambian pouch rat imported by a pet shop in Texas and is believed to have infected domesticated prairie dogs, which were then distributed by other outlets in the Midwest. Electron microscopy and serologic studies were used to confirm that the disease was human monkeypox.

By June 9, CDC officials said the number of suspected or confirmed cases was 22 in Wisconsin, 10 in Indiana, and five in Illinois.

As of June 11, a total of 54 persons with suspected monkeypox had been reported in Wisconsin (20), Illinois (10), Indiana (23), and New Jersey (1). Monkeypox had been confirmed by laboratory tests in nine persons. At least 14 of the people with suspected monkeypox had been hospitalized for their illness; there have been no deaths related to the outbreak. The number of cases and states involved in the outbreak will likely change as the investigation continues.

As of July 8, 2003, a total of 71 cases of monkeypox have been reported to CDC from Wisconsin (39), Indiana (16), Illinois (12), Missouri (two), Kansas (one), and Ohio (one); these include 35 cases laboratory-confirmed at CDC and 36 suspect and probable cases under investigation by state and local health departments[12].

The onset of illness among patients in the United States began in early May 2003. Patients typically experienced a prodrome consisting of fever, headaches, myalgias, chills, and drenching sweats. Roughly one-third of patients had nonproductive cough. This prodromal phase was followed 1-10 days later by the development of a papular rash that typically progressed through stages of vesiculation, pustulation, umbilication, and crusting. In some patients, early lesions have become ulcerated. Rash distribution and lesions have occurred on head, trunk, and extremities; many of the patients had initial and satellite lesions on palms and soles and extremities. Rashes were generalized in some patients. After onset of the rash, patients have generally manifested rash lesions in different stages. All patients reported direct or close contact with prairie dogs, most of which were sick. Illness in prairie dogs was frequently reported as beginning with a blepharoconjunctivitis, progressing to presence of nodular lesions in some cases. Some prairie dogs have died from the illness, while others reportedly recovered.

### 2022 Global Outbreak

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There has been cases of monkeypox recorded periodically over the past few years in non-endemic regions. All of these cases were traced back to travel history to endemic areas or healthcare providers involved in the treatment[13][14][15][16].

In May 2022, case clusters of monkeypox were traced around the world over a short period of time. Unlike previous cases, there was no association to travel history to endemic areas of monkeypox such as Central Africa and West Africa.

Patient zero is believed to be the confirmed case on May 4, 2022 of a British resident returning back to England from Nigeria[17]. Additional cases were identified in the UK that were neither travel-associated nor had a connection to previous cases[18]. On May 18th, 2022, 5 cases were confirmed in Portugal[19], 7 in Spain[20], and 1 in the United States_Monkeypox_|_Poxvirus_|_CDC-21|[21]. As of May 22, 2022, a total of 109 cases were recorded and 87 suspected around the world. On June 2, 2022, 780 cases of monkeypox were identified or reported to the World Health Organization[6]. As of June 15, 2022, a total of 2103 laboratory confirmed cases, including one death, have been reported to World Health Organization[7]. Although monkeypox is not known as a sexually transmitted disease, most of the cases were identified among men who have sex with men[22]. A surge in the number of cases was observed by August 7, 2022, including 11 reported deaths[23]. Undiagnosed cases of monkeypox and lack of testing and quarantining of individuals reporting symptoms may have contributed to this surge.[24]. As of August 17, 2022, a total of 39,434 cases were reported worldwide_Monkeypox_|_Poxvirus_|_CDC-8|[8], including 19,429 reported Europe[25], and 387 in locations that have historically reported monkeypox_Monkeypox_|_Poxvirus_|_CDC-8|[8]. As of October 19, 2022, a total of 74,785 cases were confirmed globally, including 32 deaths_Monkeypox_|_Poxvirus_|_CDC-8|[8].

## References

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1. ↑ 1.0 1.1 Cho CT, Wenner HA (1973). "Monkeypox virus". Bacteriol Rev. 37 (1): 1–18. doi:10.1128/br.37.1.1-18.1973. PMC 413801. PMID 4349404.
2. ↑ 2.0 2.1 Ladnyj ID, Ziegler P, Kima E (1972). "A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo". Bull World Health Organ. 46 (5): 593–7. PMC 2480792. PMID 4340218.CS1 maint: Multiple names: authors list (link)
3. ↑ 3.0 3.1 Sklenovská N, Van Ranst M (2018). "Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans". Front Public Health. 6: 241. doi:10.3389/fpubh.2018.00241. PMC 6131633. PMID 30234087.
4. ↑ 4.0 4.1 Heymann DL, Szczeniowski M, Esteves K (1998). "Re-emergence of monkeypox in Africa: a review of the past six years". Br Med Bull. 54 (3): 693–702. doi:10.1093/oxfordjournals.bmb.a011720. PMID 10326294.CS1 maint: Multiple names: authors list (link)
5. ↑ 5.0 5.1 Hutin YJ, Williams RJ, Malfait P, Pebody R, Loparev VN, Ropp SL; et al. (2001). "Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997". Emerg Infect Dis. 7 (3): 434–8. doi:10.3201/eid0703.010311. PMC 2631782. PMID 11384521.CS1 maint: Multiple names: authors list (link)
6. ↑ 6.0 6.1 "Multi-country monkeypox outbreak: situation update".
7. ↑ 7.0 7.1 Glenn JK, Goldman J, Bonaventura J, Bonaventura C, Sullivan B, Godette G (January 1976). "Task delegation to physician extenders--some comparisons". Am J Public Health. 66 (1): 64–6. doi:10.2105/ajph.66.1.64. PMC 1653348. PMID 2022.
8. ↑ _Monkeypox_|_Poxvirus_|_CDC_8-0|8.0 _Monkeypox_|_Poxvirus_|_CDC_8-1|8.1 _Monkeypox_|_Poxvirus_|_CDC_8-2|8.2 _Monkeypox_|_Poxvirus_|_CDC_8-3|8.3 "2022 Monkeypox Outbreak Global Map | Monkeypox | Poxvirus | CDC". Retrieved 2022-10-20.
9. ↑ "The current status of human monkeypox: memorandum from a WHO meeting". Bull World Health Organ. 62 (5): 703–13. 1984. PMC 2536211. PMID 6096036.
10. ↑ Jezek Z, Marennikova SS, Mutumbo M, Nakano JH, Paluku KM, Szczeniowski M (1986). "Human monkeypox: a study of 2,510 contacts of 214 patients". J Infect Dis. 154 (4): 551–5. doi:10.1093/infdis/154.4.551. PMID 3018091.CS1 maint: Multiple names: authors list (link)
11. ↑ Jezek Z, Khodakevich LN, Wickett JF (1987). "Smallpox and its post-eradication surveillance". Bull World Health Organ. 65 (4): 425–34. PMC 2491031. PMID 3319266.CS1 maint: Multiple names: authors list (link)
12. ↑ Centers for Disease Control and Prevention (CDC) (2003). "Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003". MMWR Morb Mortal Wkly Rep. 52 (27): 642–6. PMID 12855947.
13. ↑ Hobson G, Adamson J, Adler H, Firth R, Gould S, Houlihan C; et al. (2021). "Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021". Euro Surveill. 26 (32). doi:10.2807/1560-7917.ES.2021.26.32.2100745. PMC 8365177 Check `|pmc=` value (help). PMID 34387184 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
14. ↑ Rao AK, Schulte J, Chen TH, Hughes CM, Davidson W, Neff JM; et al. (2022). "Monkeypox in a Traveler Returning from Nigeria - Dallas, Texas, July 2021". MMWR Morb Mortal Wkly Rep. 71 (14): 509–516. doi:10.15585/mmwr.mm7114a1. PMC 8989376 Check `|pmc=` value (help). PMID 35389974 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
15. ↑ Yong SEF, Ng OT, Ho ZJM, Mak TM, Marimuthu K, Vasoo S; et al. (2020). "Imported Monkeypox, Singapore". Emerg Infect Dis. 26 (8): 1826–1830. doi:10.3201/eid2608.191387. PMC 7392406 Check `|pmc=` value (help). PMID 32338590 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
16. ↑ Vaughan A, Aarons E, Astbury J, Balasegaram S, Beadsworth M, Beck CR; et al. (2018). "Two cases of monkeypox imported to the United Kingdom, September 2018". Euro Surveill. 23 (38). doi:10.2807/1560-7917.ES.2018.23.38.1800509. PMC 6157091. PMID 30255836.CS1 maint: Multiple names: authors list (link)
17. ↑ "Monkeypox - United Kingdom of Great Britain and Northern Ireland".
18. ↑ "Monkeypox cases confirmed in England – latest updates - GOV.UK".
19. ↑ "Direção-Geral da Saúde".
20. ↑ "Epidemiological update: Monkeypox outbreak".
21. _Monkeypox_|_Poxvirus_|_CDC_21-0|↑ "Past U.S. Cases and Outbreaks | Monkeypox | Poxvirus | CDC".
22. ↑ Kozlov M (2022). "Monkeypox goes global: why scientists are on alert". Nature. 606 (7912): 15–16. doi:10.1038/d41586-022-01421-8. PMID 35595996 Check `|pmid=` value (help).
23. ↑ "www.google.com". Retrieved 2022-08-18.
24. ↑ De Baetselier I, Van Dijck C, Kenyon C, Coppens J, Michiels J, de Block T; et al. (2022). "Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium". Nat Med. doi:10.1038/s41591-022-02004-w. PMID 35961373 Check `|pmid=` value (help).CS1 maint: Multiple names: authors list (link)
25. ↑ "Joint ECDC-WHO Regional Office for Europe Monkeypox Surveillance Bulletin". Retrieved 2022-08-18.