In the largest case study series to date, an international collaboration of clinicians has identified new clinical symptoms in people infected with monkeypox.

Their findings will aid in the future diagnosis, slow the spread of infection, and assist the international community in allocating the limited global supply of monkeypox vaccines and treatments to the most vulnerable communities.

The New England Journal of Medicine published a case series on July 21 as the result of an international collaboration involving 16 countries (NEJM). The study, led by Queen Mary University of London researchers, identifies new clinical symptoms of monkeypox infection, which will aid future diagnosis and help to slow infection spread.

It was conducted in response to an emerging global health threat, and it is the largest case series to date, reporting on 528 confirmed infections at 43 sites between April 27 and June 24, 2022.

The virus's current spread disproportionately affects gay and bisexual men, with 98 per cent of infected individuals belonging to this group. Although sexual closeness is the most likely route of transmission in the majority of these cases, researchers emphasise that the virus can be transmitted through large respiratory droplets and potentially through clothing and other surfaces through any close physical contact.

Many of the infected people examined in the study had symptoms that were not recognised by current medical definitions of monkeypox. These symptoms include single genital lesions as well as mouth sores or anus. The clinical symptoms are similar to those of sexually transmitted infections (STIs) and can easily lead to a misdiagnosis.

Anal and oral symptoms in some people have resulted in hospitalisation for pain management and swallowing difficulties. This is why it is critical that these new clinical symptoms be recognised and healthcare professionals are educated on how to identify and manage the disease - misdiagnosis can slow detection and thus hinder efforts to control the virus's spread.

As a result, increased rates of diagnosis will result from the study. As a result of the study, more people from at-risk groups will be diagnosed when they present with traditional STI symptoms. Public health measures, such as increased testing and education, should be developed and implemented in collaboration with at-risk groups to ensure that they are appropriate, non-stigmatizing, and do not send the outbreak underground.

Professor of HIV Medicine at Queen Mary University of London and Director of the SHARE collaborative, Chloe Orkin, said, "Viruses know no borders and monkeypox infections have now been described in 70 countries and in more than 13000 people.

This truly global case series has enabled doctors from 16 countries to share their extensive clinical experience and many clinical photographs to help other doctors in places with fewer cases. We have shown that 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.

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.

Given the global constraints on the vaccine and anti-viral supply for this chronically underfunded, neglected tropical infection, prevention remains a key tool in limiting the global spread of human monkeypox infection."

Dr John Thornhill, Consultant Physician in Sexual Health and HIV at Barts NHS Health Trust and Clinical Senior Lecturer at the Queen Mary University of London, said, "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.

However, our work suggests that most transmissions so far have been related to sexual activity - mainly, but not exclusively, amongst men who have sex with men.

This research study increases our understanding of the ways it is spread and the groups in which it is spreading which will aid rapid identification of new cases and allow us to offer prevention strategies, such as vaccines, to those individuals at higher risk.
In addition, we identified new clinical presentations in people with monkeypox.

While we expected various skin problems and rashes, we also found that one in ten people had only a single skin lesion in the genital area, and 15 per cent had anal and/or rectal pain.

These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes. We, therefore, suggest broadening the current case definitions.

We have also found the monkeypox virus in a large proportion of the semen samples tested from people with monkeypox. However, this may be incidental as we do not know that it is present at a high enough level to facilitate sexual transmission. More work is needed to understand this better."

Harvard University Health and Human Rights Fellow Keletso Makofane, MPH, PhD, said, "Wherever the monkeypox virus has shown up, it has tested the ability of our public health systems to respond decisively and urgently during an emergency. It is gratifying to be part of a collective which has worked furiously to gather and share information with each other and with the global public health community."