Monkeypox infection, previously limited to areas where the virus was endemic, was recently declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to the increasing number of cases detected outside endemic zones. The SHARE*-net Clinical Group, comprising an international collaborative of clinicians from countries which have reported monkeypox cases, recently provided vital information on the manifestations and transmission of PCR-confirmed monkeypox.

The present case series consisted of 528 cases of PCR-confirmed monkeypox infection diagnosed at 43 sites in 16 countries between April 27 and June 24, 2022. Of these, 98 percent were reported in gay or bisexual men. Median age of the patients was 38 years, >99 percent were male, and 75 percent were White. Forty-one percent were living with HIV, 96 percent of whom were on antiretroviral therapy (ART) and 95 percent having a HIV viral load <50 copies/mL. Among those without HIV, 57 percent had used pre-exposure prophylaxis in the month preceding presentation for monkeypox infection.

 

Presenting symptoms

The main presenting symptoms were rash/skin lesions (95 percent), anogenital lesions (73 percent), and mucosal lesions (41 percent). Lesions were detected on the trunk, arms, or legs in 55 percent, the face in 25 percent, and the palms and soles in 10 percent. Fifty-eight percent of patients with skin lesions had vesiculopustular lesions. Sixty-four percent had <10 lesions.

Fifty-four patients had a single genital lesion. This could potentially lead to misdiagnosis of monkeypox as a different sexually transmitted infection (STI) and delay monkeypox detection, warned the authors. “[W]e recommend consideration of monkeypox in at-risk persons presenting with traditional STI symptoms,” they said.

Prior to developing skin lesions, 62 percent experienced fever, 56 percent lymphadenopathy, 41 percent lethargy, 31 percent myalgia, and 27 percent headache. Twenty-six patients developed oropharyngeal symptoms as their first symptoms (eg, pharyngitis, odynophagia, epiglottitis, and oral or tonsillar lesions). One case of epiglottitis and two cases of myocarditis were deemed serious.

A total of 377 patients were tested for concomitant STIs which were detected in 29 percent, the most common being syphilis, gonorrhoea, and chlamydia (9, 8, and 5 percent, respectively).

Twenty-three patients had a clear history of exposure to the monkeypox virus, with the incubation period (between exposure and symptom development) ranging between 3 and 20 days (median 7 days). The time between symptom onset and the first positive PCR result ranged between 2 and 20 days (median 5 days).

Five percent of patients received antiretroviral treatment for monkeypox (2 percent received intravenous or topical cidofovir, 2 percent tecovirimat, and <1 percent vaccinia immune globulin).

Thirteen percent of patients (n=70) were hospitalized, primarily due to pain (mainly severe anorectal pain; n=21) or soft-tissue superinfection (n=18). Five patients were hospitalized for pharyngitis limiting oral intake, and two each for eye lesions, acute kidney injury, and myocarditis. Thirteen patients were hospitalized in order to control infection. There were no deaths.

 

Sexual activity as a mode of transmission

Known methods of monkeypox transmission are via large respiratory droplets and close or direct contact with skin lesions, as well as potentially via contaminated fomites, said the authors. [https://www.gov.uk/guidance/monkeypox#transmission, accessed 18 Aug 2022] “There [has been] no clear evidence of sexual transmission through seminal or vaginal fluids,” they added.

In the present case series, suspected mode of transmission was via sexual activity in 95 percent of patients. “[This hypothesis] was supported by the findings of primary genital, anal, and oral mucosal lesions, which may represent the inoculation site,” the authors said. The higher proportion of cases in gay or bisexual men or men who have sex with men (MSM) “suggests amplification of transmission through sexual networks.”

Of the 32 patients who underwent seminal fluid analysis, monkeypox virus DNA was detected in 29, a finding that further supports the sexual transmission hypothesis, they added.

“However, whether semen is capable of transmitting infection remains to be investigated, since it is unknown whether the viral DNA detected in these specimens was replication competent,” the authors said.

 

Current measures, future goals

Most cases of monkeypox in this series were mild and self-limiting. Nonetheless, the potential occurrence of complicated cases warrants further research over a longer period, the authors said. Furthermore, while most cases were detected in gay, bisexual, and other MSM, the detection of monkeypox in nine heterosexual men highlights that anyone could be affected.
 

“The current global outbreak of monkeypox virus infection in humans suggests changes in biologic aspects of the virus, changes in human behaviour, or both,” noted the authors. “Such changes might be driven by waning smallpox immunity, relaxation of COVID-19 prevention measures, resumption of international travel, and sexual interactions associated with large gatherings.”

In order to stem the outbreak, they stressed the importance of education, both of healthcare professionals on recognizing and treating monkeypox, as well as among at-risk populations on the importance of testing. Pertaining to the latter, they highlighted the importance of ensuring interventions were “appropriate and non-stigmatizing.”

Limitations included the observational design, inclusion of only symptomatic patients, and potential exclusion of early symptoms.

 

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