Monkeypox: New clinical symptoms are identified in confirmed cases

The largest study of confirmed monkeypox cases to date has identified new clinical symptoms that are similar to those of syphilis and other sexually transmitted infections and could easily lead to misdiagnosis.1 These symptoms included single genital lesions and sores on the mouth or anal mucosa.

An international collaboration across 16 countries reported 528 infections that were diagnosed between 27 April and 24 June 2022. In the study, published in the New England Journal of Medicine, 95% of these patients presented with a rash, 73% had anogenital lesions, and 41% had mucosal lesions.

A 10th of the patients (54) had only a single genital lesion. Another unexpected finding was that 15% had anal or rectal pain (or both).

The study authors said that the current case definitions for monkeypox should be expanded to help diagnosis and slow the spread of infection. Existing definitions do recommend consideration of monkeypox in the context of any “unusual” rash but do not cover the full range of possible manifestations.

“The current international case definitions need to be expanded to add symptoms that are not currently included, such as sores in the mouth, on the anal mucosa, and single ulcers,” said Chloe Orkin, professor of HIV medicine at Queen Mary University of London and director of the Sexual Health and HIV All East Research (SHARE) collaborative, which is based in east London and investigates the inequalities that lead to poor sexual health and HIV. Orkin added, “These particular symptoms can be severe and have led to hospital admissions, so it is important to make a diagnosis. Expanding the case definition will help doctors more easily recognise the infection and so prevent people from passing it on.”

In the case series, 98% of the people infected were gay or bisexual men, 75% were white, and 41% had HIV. Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), headache (27%), and lymphadenopathy (56%). Among the 23 patients with a clear exposure history the median incubation period was seven days (range 3-20).

Transmission was suspected to have occurred through sexual activity in 95% of the cases. Monkeypox virus DNA was detected in 29 of the 32 people in whom seminal fluid was analysed. However, this may be incidental, as it is not yet known whether it is present at high enough levels to facilitate sexual transmission.

“It is important to stress that monkeypox is not a sexually transmitted infection in the traditional sense; it can be acquired through any kind of close physical contact,” said study author John Thornhill, a consultant physician in sexual health and HIV and clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “However, our work suggests that most transmissions so far have been related to sexual activity—mainly, but not exclusively, among men who have sex with men.”

Most of the cases reported in the series were mild and self-limited, and there were no deaths. The study also found that HIV infection was not linked to monkeypox severity. Although 13% of the patients were admitted to a hospital, no serious complications were reported in the majority of those admitted. Common reasons for admission were pain and bacterial superinfection. However, the study authors pointed out that rare serious complications, including myocarditis and epiglottitis, were observed and that therefore longer term follow-up of cases was needed.

Commenting on the study, Claire Dewsnapp, president of the British Association for Sexual Health, said the UK government must be bold in acting against monkeypox. “These measures must include an effective vaccine procurement and delivery plan, a clearly accountable national response lead, and a national plan for testing, assessment, treatment, and prevention,” she said.

As of 18 July 2022 there were 2137 confirmed cases of monkeypox in the UK, 2050 of them in England. Almost three quarters (73%) of England’s cases were in London.2

In response to the rising number of cases the UK Health Security Agency said that it had procured an additional 100 000 doses of the smallpox vaccine Imvanex. Gay and bisexual men at high risk of exposure to monkeypox will be offered the vaccine.34

On 19 July the UK Health Security Agency also updated its guidance for close contacts of a confirmed monkeypox case.5 This said that close contacts won’t need to isolate at home if they don’t have symptoms, as the latest data showed that a relatively small number of close contacts had gone on to develop monkeypox and there was a lack of evidence of transmission outside close intimate or sexual contact.