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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 US, 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 22, 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 and Technical Report: Multi-National Monkeypox Outbreak, United States, 2022 for up-to-date US and global case counts and epidemiologic parameters associated with the outbreak.
This article is the second in a 3-part series intended to help health care professionals understand what MPXV is and its public health importance. Part 1 provides an overview of the ecology and epidemiology of MPXV. The objective of part 2 is to describe the clinical syndrome of MPXV infection, how it is diagnosed, and the associated burden of disease, including stigmatization. Part 3 summarizes current and emerging options for and guidance on prevention and treatment of MPXV infection.
MPXV infection is a smallpox-like disease. The illness associated with the current outbreak of human-to-human MPXV (hMPXV) infection has 3 stages: the incubation period, prodromal period, and development of a rash (Table 1) that typically lasts 2 to 4 weeks.[7]
Stages | Signs and Symptoms |
---|---|
Stage 1: Incubation period | Asymptomatic, lasts approximately 1 to 2 weeks |
Stage 2: Prodrome | Fever and lymphadenopathy do not always precede the rash |
Stage 3: Rash (Figure 1) | Deep-seated vesicular or pustular rash that often begins centrally and spreads to the limbs |
Figure 1. Lesions are firm or rubbery, well-circumscribed, deep-seated, and often develop umbilication (resembles a dot on the top of the lesion). The evolution of lesions progresses through 4 stages--macular, papular, vesicular, and pustular--before scabbing over and desquamating. [Source: CDC. https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html.]
Recent surveillance and case-series reports illustrate epidemiologic and clinical characteristics of the current outbreak of hMPXV infection (Table 2). Notably, viremia and shedding of MPXV DNA from the upper respiratory tract have been reported for at least 3 weeks after crusting of cutaneous lesions.[7,8]
Report | Demographics | Signs and Symptoms |
---|---|---|
O'Shea et al[9] Data source: Available summary surveillance data on cases of hMPXV infection in the European Union, England, and the United States |
Not reported |
Symptoms
Rash†/Lesions
|
Philpott et al [6] Data source: 2891 cases of hMPXV infection in the United States, May 17 to July 22, 2022 (analyses restricted to cases with available relevant data available) |
|
Symptoms
Rash†/Lesions
|
Thornhill et al[1] Data source: 528 cases of PCR-confirmed hMPXV infection in 16 countries (43 sites), April 27 to June 24, 2022 |
|
Symptoms
Rash†/Lesions
|
PCR = polymerase chain reaction.
*Prodrome: headache, fever, chills, myalgia, and/or lymphadenopathy preceding rash.
†The rash associated with monkeypox can be confused with other diseases that are encountered in clinical practice, such as secondary syphilis, herpes, chancroid, and varicella zoster.
MPXV infection is diagnosed by a polymerase chain reaction test, the non-variola Orthopoxvirus real-time PCR primer and probe set (nonvariola Orthopoxvirus [NVO]) assay.[10] The CDC recommends that 2 specimens collected by swabs, each from multiple lesions, preferably from different locations on the body, and from lesions with differing appearances be collected for each patient.[10] The swabs should be sent to a Laboratory Response Network laboratory validated to perform the NVO assay in viral transport media. Clinicians who suspect a case of MPXV infection can contact their local or state health department for guidance on handling and submitting specimens. Clinicians can also initiate treatment (described in part 3 of this series) before testing if MPXV infection is suspected on the basis of clinical signs and symptoms and can advise patients to isolate while awaiting test results and take measures to prevent further transmission, such as limiting close contact with others and avoiding the sharing of potential contaminated items.[10]
Although most cases in the current outbreak to date have occurred among gay, bisexual, and other men who have sex with men (MSM), any patient, regardless of sexual or gender identity, with a rash consistent with MPXV infection should be considered for testing. One reason is that the characteristic rash associated with MPXV can be confused with the rashes associated with more common sexually transmitted infections (STIs). Three recent analyses provide evidence of concurrent STIs in patients with PCR test-confirmed hMPXV infection. An observational analysis of demographic and clinical characteristics of 54 patients (all MSM) who attended a sexual health center in the UK from May 14 to May 25, 2022, showed that 25% had a concurrent STI.[11] All patients presented with skin lesions, of which 51 (94%) were anogenital. A multicenter, prospective, observational cohort study of 181 patients with PCR test-confirmed hMPXV infection (92% identified as gay, bisexual, or other MSM) who attended 3 sexual health clinics in Madrid and Barcelona, Spain, showed that 17% had a concurrent STI.[12] A retrospective observational analysis of clinical features among 197 people (196 identified as gay, bisexual, or other MSM) with PCR test-confirmed MPXV infection who were tested and managed in a High Consequence Infectious Diseases center in south London, United Kingdom, showed that 31.5% of those screened for STIs had a concurrent STI.[13] The CDC recommends that patients with a characteristic rash should be considered for testing, even if tests for other infectious diseases are positive.[14]
These analyses also shed some light on the clinical course of hMPXV infection. Although prodromal symptoms do not always occur, fever, lymphadenopathy, and myalgia were common findings.[11-13] In addition, although uncommon, hospitalization occurred for pain from rectal involvement and penile swelling,[13] bacterial cellulitis,[13] and bacterial abscess.[11,12]
Stigma is associated with STIs in general and hinders efforts to test for, disclose, treat, and prevent them, as well as negatively affects the health and quality of life of persons with STIs.[15] "Monkeypox" is actually a misnomer because the virus does not originate in monkeys. The name comes from the discovery of MPXV in monkeys imported from Singapore in a Danish laboratory in 1958.[16,17] On July 26, 2022, the New York City Department of Health and Mental Hygiene sent a letter to the director-general of WHO asking that monkeypox be renamed as soon as possible, expressing serious concern use the stigma the term may engender, and "the painful and racist history within which terminology like this is rooted for communities of color."[18]
For tips on messaging to general and gay and bisexual men audiences, the CDC recommends that MPXV be described as a legitimate public health issue that is relevant to all people.[19] Communication strategies for decreasing stigma include:[15]