Monkeypox Virus Infection in Humans across 16 Countries
- April-June 2022 - New clinical symptoms identified
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We describe a human monkeypox case series that includes 528 infections from four WHO regions (Europe, Americas, Western Pacific, and Eastern Mediterranean) and 16 countries reported over a 2-month period. Sexual activity, largely among gay or bisexual men, was by far the most frequently suspected route of transmission. The strong likelihood of sexual transmission was supported by the findings of primary genital, anal, and oral mucosal lesions, which may represent the inoculation site. Monkeypox virus DNA that was detectable by PCR in seminal fluid in 29 of the 32 cases in which seminal fluid was tested further supports this hypothesis. 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. Reports of clusters associated with sex parties or saunas further underscore the potential role of sexual contact as a promoter of transmission. International travel and attendance at large gatherings linked to sex-on-site activities may explain the global spread of monkeypox infections amplified through sexual networks.
New clinical symptoms identified in largest international case series of confirmed monkeypox cases
An international collaboration of clinicians has identified new clinical symptoms in people infected with monkeypox in the largest case study series to date. Their findings will improve future diagnosis, help to slow the spread of infection and help the international community prioritise the limited global supply of monkeypox vaccines and treatments to communities most at risk.
London, Thursday 21 July 2022: A case series which is the result of an international collaboration across 16 countries is published today (21 July 2022) in New England Journal of Medicine (NEJM). The study identified new clinical symptoms of monkeypox will aid future diagnosis and help to slow the spread of infection were identified in the study. which was carried out in response to the emerging global health threat. The largest case series to date, it reports on 528 confirmed infections at 43 sites between 27 April and 24 June 2022.
The current spread of the virus disproportionately affects gay and bisexual men, with 98% of infected persons from this group. Although sexual closeness is the most likely route of transmission in most of these cases, researchers stress that the virus can be transmitted by any close physical contact through large respiratory droplets and potentially through clothing and other surfaces.
There is a global shortage of both vaccines and treatments for human monkeypox infection. The findings of this study, including the identification of those most at risk of infection, will help to aid the global response to the virus. Public health interventions aimed at this high-risk group could help to detect and slow the spread of the virus. Recognising the disease, contact tracing and advising people to isolate will be key components of the public health response.
Many of the infected individuals reviewed in the study presented with symptoms not recognised in current medical definitions of monkeypox. These symptoms include single genital lesions and sores on the mouth or anus. The clinical symptoms are similar to those of sexually transmitted infections (STIs) and can easily lead to misdiagnosis. In some people, anal and oral symptoms have led to people being admitted to hospital for management of pain and difficulties swallowing. This is why it's so important that these new clinical symptoms be recognised and healthcare professionals be educated on how to identify and manage the disease - misdiagnosis can slow detection and thus hinder efforts to control the spread of the virus. The study will therefore lead to increased rates of diagnosis when persons from at-risk groups present with traditional STI symptoms.
Public health measures - such as enhanced testing and education - should be developed and implemented working with at-risk groups to ensure that they are appropriate, non-stigmatising, and to avoid messaging that could drive the outbreak underground.
Chloe Orkin, Professor of HIV Medicine at Queen Mary University of London and Director of the SHARE collaborative, said:
"Viruses know no borders and monkey pox 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 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 and Clinical Senior Lecturer at Barts NHS Health Trust and 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 percent 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 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 levels to facilitate sexual transmission. More work is needed to understand this better."
Keletso Makofane, MPH, PhD, Health and Human Rights Fellow at Harvard University, 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."
Additional quotes are available in the notes to editors.
NOTES TO EDITORS
Faculty Communications Manager - Medicine and Dentistry
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Details of paper: "Monkeypox Virus Infection in Humans across 16 Countries - April-June
2022." Thornhill JP, Rockstroh J, Palich R, Habibi MS, Boesecke CB, Yakubovsky M, Blanco JL, Maltez FM, Pourcher V, Pintado C, Hansen AE, Lezama JI, Makofane K, Nozza S and Orkin CM. New England Journal of Medicine.
Available at after embargo lifts: https://www.nejm.org/
An embargoed full text PDF of the Original Article will be made available at or around 3 PM ET Thursday 21 July. A draft abstract is available upon request.
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Claire Dewsnapp, President of the British Association for Sexual Health (BASHH), said:
"Since May 2022, the UK Monkeypox outbreak has become a pressing crisis that requires bold action. BASHH welcomes this case series and the international collaboration surrounding this critical public health challenge.
"BASHH is supporting calls to introduce urgent measures to co-ordinate the UK response, developed with experts and community stakeholders, alongside essential additional funding to contain and eliminate 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."
Dr Laura Waters, Chair of the British HIV Association (BHIVA), said:
"BHIVA welcomes the publication of the largest case series describing the global 2022 monkeypox outbreak to date. Whilst people with HIV account for more than 40% of cases so far, it is reassuring that HIV status was not linked with monkeypox severity.
"We must ensure that access to appropriate monkeypox prevention and care is equitable; we must ensure people less able to navigate stretched health services can access vaccine. And we must also strive for equity beyond our own borders. Advocacy in HIV care has achieved excellent outcomes globally so we must also advocate for the outputs of vaccine procurement, funding and research to improve care for all. To not focus progress on the countries long affected by this neglected infection would be an injustice and a failure for global health."
Dr Will Nutland, co-founder The Love Tank CIC/PrEPster, said:"
"This international case series contributes to the growing evidence of how monkeypox is being transmitted, and in which population groups. This evidence, including greater understanding of monkeypox symptoms, further informs international and regional health promotion activity. The research must serve as a further call to properly resource our responses to monkeypox, including upscaling testing, treatment, and vaccination programmes, to the key populations most impacted by the virus".
Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022
J.P. Thornhill, S. Barkati, S. Walmsley, J. Rockstroh, A. Antinori, L.B. Harrison, R. Palich, A. Nori, I. Reeves, M.S. Habibi, V. Apea, C. Boesecke, L. Vandekerckhove, M. Yakubovsky, E. Sendagorta, J.L. Blanco, E. Florence, D. Moschese, F.M. Maltez, A. Goorhuis, V. Pourcher, P. Migaud, S. Noe, C. Pintado, F. Maggi, A.-B.E. Hansen, C. Hoffmann, J.I. Lezama, C. Mussini, A.M. Cattelan, K. Makofane, D. Tan, S. Nozza, J. Nemeth, M.B. Klein, and C.M. Orkin, for the SHARE-net Clinical Group*
Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined.
We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections.
We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having <10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported.
In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.
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%).
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).