Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022 | NEJM – nejm.org
Persons with Infection
Demographic and Clinical Characteristics of the Persons with Monkeypox.
A total of 528 cases of confirmed human monkeypox infection from five continents, 16 countries, and 43 clinical sites are included in this series (Figure 1). Demographic and clinical characteristics of the persons with infection are summarized in Table 1.
Demographic and Clinical Characteristics of Persons with HIV Infection in the Case Series.
Overall, 98% of the persons with infection were gay or bisexual men, and 75% were White. The median age was 38 years. A total of 41% of the persons were living with HIV infection, and in the vast majority of these persons, HIV infection was well controlled; 96% of those with HIV infection were taking ART, and in 95% the HIV viral load was less than 50 copies per milliliter (Table 2). Preexposure prophylaxis had been used in the month before presentation in 57% of the persons who were not known to have HIV infection.
Clinical Findings
Diagnosis and Clinical Characteristics of Monkeypox in the Case Series. 
Lesions in Persons with Confirmed Human Monkeypox Virus Infection.
Panel A shows the evolution of cutaneous lesions in a person with monkeypox; images a1 and a2 show facial lesions, images b1 through b3 show a penile lesion, and images c1 and c2 show a lesion on the forehead. The polymerase-chain-reaction (PCR) status is indicated if available. IM denotes intramuscular, and MSM man who has sex with men. Panel B shows oral and perioral lesions (image a, perioral umbilicated lesions; image b, perioral vesicular lesion on day 8, PCR positive; image c, ulcer on the left corner of the mouth on day 7, PCR positive; image d, tongue ulcer; image e, tongue lesion on day 5, PCR positive; and images f, g, and h, pharyngeal lesions on day 0, 3, and 21, respectively, PCR positive on day 0 and 3 and negative on day 21). Panel C shows perianal, anal, and rectal lesions (image a, anal and perianal lesions on day 6, PCR positive; images b and c, rectal and anal lesions in a single person, PCR positive; image d, perianal ulcers, PCR positive; image e, anal lesions; image f, umbilicated perianal lesion on day 3, PCR positive; image g, umbilicated perianal lesions on day 3, PCR positive; and image h, perianal ulcer on day 2, PCR positive).
The characteristics of monkeypox in this case series are summarized in Table 3. Skin lesions were noted in 95% of the persons (Figure 2). The most common anatomical sites were the anogenital area (73%); the trunk, arms, or legs (55%); the face (25%); and the palms and soles (10%). A wide spectrum of skin lesions was described (see the clinical image Web library), including macular, pustular, vesicular, and crusted lesions, and lesions in multiple phases were present simultaneously. Among persons with skin lesions, 58% had lesions that were described as vesiculopustular. The number of lesions varied widely, with most persons having fewer than 10 lesions. A total of 54 persons presented with only a single genital ulcer, which highlights the potential for misdiagnosis as a different STI. Mucosal lesions were reported in 41% of the persons. Involvement of the anorectal mucosa was reported as the presenting symptom in 61 persons; this involvement was associated with anorectal pain, proctitis, tenesmus, or diarrhea (or a combination of these symptoms). Oropharyngeal symptoms were reported as the initial symptoms in 26 persons; these symptoms included pharyngitis, odynophagia, epiglottitis, and oral or tonsillar lesions. In 3 persons, conjunctival mucosa lesions were among the presenting symptoms. Common systemic features during the course of the illness included fever (in 62%), lethargy (41%), myalgia (31%), and headache (27%), symptoms that frequently preceded a generalized rash; lymphadenopathy was also common (56%).
The initial presenting feature and the sequence of subsequent cutaneous and systemic features (captured as free text) showed considerable variation. The most common presentation was an initial skin lesion or lesions, primarily in the anogenital area, body (trunk or limbs), or face (or a combination of these locations), with the number of lesions increasing over time and with or without systemic features (see the series of timelines in the clinical image Web library). Because of the observational nature of this case series, the variability in the time of presentation, and the reliance on clinical records, a clear chronology of potential exposure and symptoms was available for only 30 persons. Of these 30 persons, 23 had a clearly defined exposure event, with a median time from exposure to the development of symptoms of 7 days (range, 3 to 20). Lesions with prodrome occurred in 17 of the 30 persons; however, isolated anogenital or oral lesions were also observed (13 persons). The median time from the onset of symptoms to the first positive PCR result was 5 days (range, 2 to 20), and the median time from the development of the first skin lesion to the development of additional skin lesions was 5 days (range, 2 to 11) (see the clinical image Web library). In persons for whom data on follow-up PCR testing were available, the latest time point at which a lesion remained positive was 21 days after symptom onset.
The clinical presentation was similar among persons with HIV infection and those without HIV infection. The clinical characteristics of the persons with HIV infection are shown in Table 2. Concomitant STIs were reported in 109 of the 377 persons (29%) who were tested, with gonorrhea, chlamydia, and syphilis found in 8%, 5%, and 9%, respectively, of the those who underwent testing.
Transmission
The suspected means of monkeypox virus transmission as reported by the clinician was sexual close contact in 95% of the persons. It was not possible to confirm sexual transmission. A sexual history was recorded in 406 of 528 persons; among these 406 persons, the median number of sex partners in the previous 3 months was 5 partners, 147 (28%) reported travel abroad in the month before diagnosis, and 103 (20%) had attended large gatherings (>30 persons), such as Pride events. Overall, 169 (32%) were known to have visited sex-on-site venues within the previous month, and 106 (20%) reported engaging in “chemsex” (i.e., sex associated with drugs such as mephedrone and crystal methamphetamine) in the same period.
A total of 70 persons (13%) were admitted to a hospital. The most common reasons for admission were pain management (21 persons), mostly for severe anorectal pain, and treatment of soft-tissue superinfection (18). Other reasons included severe pharyngitis limiting oral intake (5 persons), treatment of eye lesions (2), acute kidney injury (2), myocarditis (2), and infection-control purposes (13). There was no difference in the frequency of admission according to HIV status. Three new cases of HIV infection were identified.
Two types of serious complications were reported: one case of epiglottitis and two cases of myocarditis. The epiglottitis occurred in a person with HIV infection who had a CD4 cell count of less than 200 per cubic millimeter; the person was treated with tecovirimat and recovered completely. The myocarditis cases were self-limiting (<7 days) and resolved without antiviral therapy. One occurred in a person with HIV infection who had a CD4 cell count of 780 per cubic millimeter, and one occurred in a person without HIV infection. No deaths were reported.
In total, 5% of the 528 persons received monkeypox-specific treatment. The drugs administered included intravenous or topical cidofovir (in 2% of persons), tecovirimat (2%), and vaccinia immune globulin (<1%).
Diagnosis
Characteristics of 32 Persons with Monkeypox According to Presence or Absence of Viral DNA in Seminal Fluid on PCR.
The health setting of initial presentation reflected referral patterns and included sexual health or HIV clinics, emergency departments, and dermatology clinics and, less commonly, primary care. A positive PCR result was most commonly obtained from skin or anogenital lesions (97%); other sites were less frequently sampled. The reported percentages of positive PCR results were 26% for nasopharyngeal specimens, 3% for urine specimens, and 7% for blood specimens. Semen was tested in 32 persons from five clinical sites and was PCR positive in 29 persons (4 of these instances have previously been reported19) (Table 4).