A total of 528 confirmed cases of human monkeypox infection from five continents, 16 countries and 43 clinical sites are included in this series (Figure 1). The demographic and clinical characteristics of infected persons are summarized in Table 1.
Overall, 98% of those infected were gay or bisexual men and 75% were white. The median age was 38 years old. A total of 41% of people were living with HIV infection, and in the vast majority of these people, HIV infection was well controlled; 96% of people with HIV infection were on ART, and 95% of them had an HIV viral load below 50 copies per milliliter (Table 2). Pre-exposure prophylaxis was used in the month prior to presentation in 57% of people with unknown HIV infection.
Panel A shows the course of skin lesions in a person with monkeypox; images a1 and a2 show facial lesions, images b1 to b3 show a penile lesion and images c1 and c2 show a lesion on the forehead. Polymerase chain reaction (PCR) status is indicated if available. IM stands for intramuscular and MSM man having sex with men. Panel B shows oral and perioral lesions (image a, perioral umbilical lesions; image b, perioral gallbladder lesion at day 8, PCR positive; image c, ulcer at left corner of mouth at 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 days 0, 3 and 21, respectively, PCR positive on days 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 one person, PCR positive; image d, perianal ulcers, PCR positive; image e, anal lesions; image f, umbilical perianal lesion on D3, PCR positive; image g, umbilical perianal lesions on D3, PCR positive; and image h, perianal ulcer on D2, PCR positive).
The characteristics of monkeypox in this case series are summarized in Table 3. Skin lesions were noted in 95% of people (Figure 2). The most common anatomical sites were the anogenital region (73%); trunk, arms or legs (55%); the face (25%); and palms and soles (10%). A broad spectrum of skin lesions was described (see Clinical Image Web Library), including macular, pustular, vesicular, and crusted lesions, and multi-phase lesions were present simultaneously. Of those with skin lesions, 58% had lesions described as vesiculopustular. The number of lesions varied widely, with most people having less than 10 lesions. A total of 54 people presented with a single genital ulcer, highlighting the possibility of misdiagnosis as a different STI. Mucosal lesions were reported in 41% of people. Anorectal mucosal involvement was reported as a presenting symptom in 61 people; this involvement was associated with anorectal pain, proctitis, tenesmus or diarrhea (or a combination of these symptoms). Oropharyngeal symptoms were reported as initial symptoms in 26 people; these symptoms included pharyngitis, odynophagia, epiglottitis, and oral or tonsillar lesions. In 3 people, lesions of the conjunctival mucosa were among the symptoms presented. Common systemic features during the course of 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 skin and systemic features (captured as free text) showed considerable variation. The most common presentation was initial skin lesion(s), primarily in the anogenital region, 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 Timeline Series in the Clinical Image Web Library). Due to the observational nature of this case series, variability in time of presentation, and reliance on clinical records, a clear timeline of potential exposure and symptoms was only available for 30 people. Of these 30 people, 23 had a clearly defined exposure event, with a median time from exposure to symptom development of 7 days (range, 3 to 20). Prodrome lesions occurred in 17 of 30 people; however, isolated anogenital or oral lesions were also observed (13 people). The median time from onset of symptoms to the first positive PCR result was 5 days (range, 2 to 20), and the median time from development of the first skin lesion to development of additional skin lesions was 5 days (range, 2 to 11) (see the Clinical Image Web Library). In people for whom data on follow-up PCR tests were available, the last time a lesion remained positive was 21 days after symptom onset.
The clinical presentation was similar in HIV-infected and HIV-uninfected people. The clinical characteristics of HIV-infected persons are presented in Table 2. Concomitant STIs were reported in 109 of the 377 people (29%) who were tested, with gonorrhea, chlamydia and syphilis in 8%, 5% and 9%, respectively, of those who were tested.
The suspected means of transmission of monkeypox virus, as reported by the clinician, was close sexual contact in 95% of people. It was not possible to confirm sexual transmission. A sexual history was recorded in 406 of the 528 people; among these 406 people, the median number of sexual partners in the past 3 months was 5 partners, 147 (28%) said they had traveled abroad in the month before diagnosis, and 103 (20%) had attended at large gatherings (>30 people), such as Pride events. Overall, 169 (32%) were known to have visited on-site sex venues in the past month, and 106 (20%) said they had engaged in “chemsex” (i.e. i.e. sex associated with drugs such as mephedrone and crystal meth) in the same period.
A total of 70 people (13%) were hospitalized. The most frequent reasons for admission were the management of pain (21 people), mainly for severe anorectal pain, and the treatment of superinfection of the soft tissues (18). Other reasons included severe pharyngitis limiting oral intake (5 people), treatment for eye damage (2), acute kidney injury (2), myocarditis (2) and infection control goals (13) . There was no difference in frequency of admission by HIV status. Three new cases of HIV infection have been identified.
Two types of serious complications were reported: one case of epiglottitis and two cases of myocarditis. Epiglottitis occurred in an HIV-infected person who had a CD4 cell count of less than 200 per cubic millimeter; the person was treated with tecovirimat and made a full recovery. Cases of myocarditis were self-limiting (<7 days) and resolved without antiviral therapy. One occurred in an HIV-infected person who had a CD4 cell count of 780 per cubic millimeter, and the other occurred in an HIV-uninfected person. No deaths have been reported.
A total of 5% of the 528 people received monkeypox-specific treatment. Drugs given included intravenous or topical cidofovir (in 2% of people), tecovirimat (2%), and anti-vaccine immunoglobulin (<1%).
The health setting of the initial presentation reflected the referral models and included sexual health or HIV clinics, emergency departments and dermatology clinics and, less frequently, primary care. A positive PCR result was most often obtained from skin or anogenital lesions (97%); other sites were sampled less frequently. 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 people from five clinical sites and was PCR positive in 29 people (4 of these cases have been previously reported19) (Table 4).