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Human Monkeypox Virus Infection Part 1: What You Need to Know — Epidemiology

  • Authors: Susan L. Smith, MN, PhD
  • CME / ABIM MOC / CE Released: 8/25/2022
  • Valid for credit through: 8/25/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for clinicians who work in primary care and public health settings.

The goal of this activity is that learners will be better able to differentiate animal-to-human monkeypox virus infection from the current outbreaks of human-to-human monkeypox virus infection.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Ways in which human-to-human monkeypox virus is transmitted
    • People at greatest risk of acquiring and transmitting human monkeypox virus
    • Implications to the healthcare team


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  • Susan L. Smith, MN, PhD


    Owns stock (publicly traded) in: Hepion

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    Director, Accreditation and Compliance, Medscape, LLC


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Human Monkeypox Virus Infection Part 1: What You Need to Know — Epidemiology

Authors: Susan L. Smith, MN, PhDFaculty and Disclosures

CME / ABIM MOC / CE Released: 8/25/2022

Valid for credit through: 8/25/2023, 11:59 PM EST


Note: The information on the monkeypox virus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to monkeypox vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.


Before April 2022, monkeypox virus (MPXV) infection in humans was seldom reported outside of the African regions where it was considered endemic.[1] Thus, few practicing health care professionals in the United States, aside from those who specialized in tropical medicine or global infectious diseases, had heard of MPXV until recently, when the Centers for Disease Control and Prevention (CDC) reported an outbreak (meaning that the number of cases is greater than expected in a geographical area) of MPXV infection in the US.[2] The first case in this outbreak was confirmed on May 17, 2022. As of August 22, 2022, there were 14,115 confirmed cases in the US, with all states except Wyoming affected,[3] and the US government had declared MPXV infection a public health emergency.[4] As of August 2022, outside the US, more than 40,971 cases have been reported in 87 locations that have not historically reported MPXV, and the World Health Organization (WHO) has declared MPXV a public health emergency of international concern.[5]

Information on the outbreak is evolving, and the CDC is continually evaluating new evidence and adapting response strategies as new information and data on changing case demographics, clinical characteristics, transmission, and vaccine effectiveness become available.[6] Thus, health care professionals are encouraged to refer regularly to the CDC websites Information for Healthcare Professionals[7] and Technical Report: Multi-National Monkeypox Outbreak, United States, 2022[8] for up-to-date US and global case counts and epidemiologic parameters associated with the outbreak.

On May 23, 2022, the CDC launched an emergency response for MPXV, which includes educating providers and the public, expanding laboratory testing, outlining prevention strategies, and promoting the use of medical countermeasures for treatment and postexposure prophylaxis.[6] To support that effort, this article is the first in a 3-part series intended to help clinicians understand what MPXV is and its significance for public health. The objective of part 1 is to contrast the historic epidemiology of endemic MPXV with the epidemiology of the outbreak as it unfolds. Part 2 describes the clinical syndrome of MPXV infection, how MPXV is diagnosed, and the associated burden of disease. Part 3 summarizes options for treatment (including postexposure prophylaxis and antiviral treatments available for persons with HIV infection) and prevention of MPXV infection.

The Monkeypox Virus

MPXV, a double-stranded DNA virus (Figure 1), is a member of the Orthopoxvirus genus in the Poxviridae family and is closely related to the variola or smallpox virus. The morphology, genome organization, and morphogenesis of the virus are characterized elsewhere.[9,10]

Figure 1. This electron microscopic image depicts monkeypox virus particles obtained from a skin sample associated with the 2003 prairie dog outbreak in the United States. Mature, oval-shaped virus particles are seen on the left, and crescents and spherical particles of immature virions are seen on the right. [Source: Public Health Image Library.]

MPXV is a large, complex virus (Figure 2). Its DNA genome consists of approximately 190,000 base pairs that encode approximately 200 proteins. An unusual characteristic of poxviruses in general is that they spend their entire life cycle in the cytoplasm of the cells they infect, which requires that they construct all their own DNA-related machinery. They are sequestered within the nucleus of the cells they infect.

Figure 2. Comparison of the size of monkeypox, HIV, SARS CoV-2, and polio viruses. Membranes and membrane-bound proteins are shown in purple, capsids are shown in dark blue, and genomes and nucleoid-associated proteins are shown in turquoise. [Source: RCSB PDB. Poxviruses.]

"Monkeypox" is actually a misnomer. It comes from the discovery of MPXV in monkeys imported from Singapore in a Danish laboratory in 1958.[11,12] However, although the natural host is unknown, MPXV has a wide range of animal reservoirs, consisting primarily of rodents,[13,14] but also monkeys.[9]

Epidemiology of MPXV Infection

There are 3 potential types of transmission of MTXV: animal to human, human to human, and human to animal. The known modes of animal-to-human transmission and human-to-human transmission are described in the Table.

Table. Transmission of MPXV

Type of Transmission

Modes of Transmission

Animal to human (zoonotic)

Direct contact with an infected animal, blood and body fluids of an infected animal, or mucocutaneous lesions of an infected animal[9]

Consumption of an infected animal[9]     

Human to human

Direct contact with contaminated objects and surfaces that have been in contact with a person infected by animal-to-human transmission (nosocomial transmission)[15-17]

Direct contact with large respiratory droplets, bodily fluids except seminal fluid and vaginal fluid,[1] skin lesions, or contaminated objects and surfaces that have been in contact with an infected person (nosocomial transmission)[1,9,13]

Direct contact with genital lesions;[6] despite detection of MPXV DNA in 29 of the 32 persons in whom seminal fluid was analyzed from a case-series report, there is no clear evidence of sexual transmission through seminal or vaginal fluids[1]

Maternal-fetal transmission[18,19]

Human to animal

One case of a dog with confirmed monkeypox virus infection that might have been acquired through human transmission has been described[20]

Animal to Human

Historically, 2 genetic clades (organisms derived from a common ancestor species) of MPXV with unique genomic signatures and epidemiological and clinical differences were characterized: the West African clade and the Central African (Congo basin) clade.[21] The West African clade has a case fatality rate of 3.6% for animal-to-human transmission; human-to-human transmission has not been documented.[22] The Central African clade is more common and more virulent,[13] with a case fatality rate of 10.6%; human-to-human transmission is well documented.[22]

MPXV infection was first diagnosed in 1970 in a human who resided in a remote village in the Democratic Republic of Congo, after which it became endemic in that region and ultimately spread to 11 African countries.[13,21] Convergence of animal reservoirs and factors hypothesized (but not confirmed) to have facilitated animal to human transmission of MPXV include climate change, deforestation of rain forests, armed human conflicts, highly mobile populations, and human-to-animal interactions.[22] In addition, waning herd immunity to MPXV after the eradication of smallpox in 1980 and subsequent discontinuation of smallpox vaccination, which provided 85%[22] cross-protection against MPXV, is thought to have created an opportunity for the resurgence of MPXV.[12]

MPXV was confined to the African continent for more than 3 decades. The first reported animal-to-human cases outside of Africa occurred in 2003 in the United States.[22] There were 47 confirmed and probable cases in people in 6 states who became ill after having contact (ie, touching, receiving a bite or scratch that broke the skin, cleaning the cage, or touching the bedding in the cage) with pet prairie dogs imported from Ghana that had been infected as a result of being house in close proximity to other small mammals that had also been imported from Ghana.[23] Since 2003, cases in the United States related to travel to African countries where MPXV is endemic to import small exotic animals[21] have occurred in the United Kingdom and Israel (2018),[24] Singapore (2019),[25] and the US (2021).[23]

Human-to-Human MPXV Infection: The 2022 Outbreak

The cases in the current outbreak are different in a critically important way: they represent human-to-human transmission. Thus, the current outbreak represents a third clade. A genomic analysis by Isidro and colleagues found that the MPXV responsible for the current outbreak (although the ecology changed significantly) may be related to the MPXV responsible for the cases in the UK, Israel, and Singapore during 2018 and 2019, and are from the West African clade.[26] Isidro and colleagues also found that the current circulating MPXVs are genetically similar to one another, suggesting that the current outbreak most likely arose from a single human case and that the virus continues to evolve as it passes from person to person.[26]

The epidemiologic characteristics of the outbreak in the United States (2891 cases from May 17, 2022 through July 22, 2022) were reported by Philpott and colleagues.[6] Analyses were restricted to cases for which relevant data were available, including case report forms from 1195 (41%) cases. Among these cases:

  • 99% occurred in men, 94% of whom reported male-to-male sexual or close intimate contact during the 3 weeks before onset of symptoms
  • 41% of those infected had HIV infection
  • 41% of cases occurred in non-Hispanic White (White) people, 28% occurred in Hispanic or Latino (Hispanic) people, and 26% occurred in non-Hispanic Black or African American (Black) people.

Human-to-human transmission of MPXV in the US outbreak occurs by close, intimate contact with someone who has monkeypox and was found to be most intense among interconnected networks of sexually active men who have sex with men (MSM), but it is currently not known whether HIV infection affects a person's risk of acquiring monkeypox.[27] However, available data indicate that persons with advanced and uncontrolled HIV infection might be at higher risk for severe or prolonged monkeypox disease after infection.[27] On the basis of these data, the CDC recommends that public health efforts prioritize gay, bisexual, and other MSM.

Clinical Implications

  • A multinational monkeypox outbreak of MPXV infection is ongoing worldwide. Transmission of the virus occurs by direct contact with lesions or infected body fluids.
  • This outbreak is disproportionately affecting men who have sex with men, including persons with HIV infection.
  • Information on the outbreak is evolving, and the CDC is continually evaluating new evidence and adapting response strategies as new information and data on changing case demographics, clinical characteristics, transmission, and vaccine effectiveness become available. Thus, clinicians are encouraged to refer regularly to the CDC websites for up-to-date US and global case counts and epidemiologic parameters associated with the outbreak to be informed of implications for clinical practice.


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