NEJMoa2207323.pdf

new england The journal of medicine established in 1812 August 25, 2022 vol. 387 no. 8 Monkeypox Virus Infection in Humans across 16 Countries...

new england The journal of medicine established in 1812 August 25, 2022 vol. 387 no. 8 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*​​ a bs t r ac t BACKGROUND Before April 2022, monkeypox virus infection in humans was seldom reported The authors’ full names, academic de- outside African regions where it is endemic. Currently, cases are occurring world- grees, and affiliations are listed in the Appendix. Prof. Orkin can be contacted at wide. Transmission, risk factors, clinical presentation, and outcomes of infection ­c​.­m​.­orkin@​­qmul​.­ac​.­uk, or at the SHARE are poorly defined. Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University METHODS of London, 4 Newark St., London E1 2AT, We formed an international collaborative group of clinicians who contributed to United Kingdom. an international case series to describe the presentation, clinical course, and out- *The investigators in the SHARE-net clin- comes of polymerase-chain-reaction–confirmed monkeypox virus infections. ical group are listed in the Supplemen- tary Appendix, available at NEJM.org. RESULTS Drs. Thornhill, Barkati, Klein, and Orkin We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites contributed equally to this article. in 16 countries. Overall, 98% of the persons with infection were gay or bisexual This article was published on July 21, men, 75% were White, and 41% had human immunodeficiency virus infection; the 2022, and updated on August 25, 2022, at median age was 38 years. Transmission was suspected to have occurred through NEJM.org. sexual activity in 95% of the persons with infection. In this case series, 95% of the N Engl J Med 2022;387:679-91. persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital DOI: 10.1056/NEJMoa2207323 lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Copyright © 2022 Massachusetts Medical Society. 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 ex- posure history, the median incubation period was 7 days (range, 3 to 20). Monkey- pox 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. CONCLUSIONS 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. n engl j med 387;8 nejm.org August 25, 2022 679 The New England Journal of Medicine Downloaded from nejm.org on August 16, 2024. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved.  The n e w e ng l a n d j o u r na l of m e dic i n e M onkeypox virus, a zoonotic ortho- disproportionately affected men who are gay or pox DNA virus related to the virus that bisexual and other men who have sex with men, causes smallpox, was first described in which suggests amplification of transmission humans in 1970 in the Democratic Republic through sexual networks. A Quick Take of Congo (formerly Zaire).1 Sporadic outbreaks Phylogenetic analyses suggest that the virus is available at of infection have been reported in Africa, typical­ has circulated undetected for some time outside NEJM.org ly originating from contact with wildlife reser- areas where it has been endemic, possibly mas- voirs (particularly rodents).2 Such outbreaks and querading as other sexually transmitted infec- travel-associated cases outside Africa have had tions (STIs).17 The current international case limited secondary spread, and therefore human- definitions (Table S1 and Fig. S1 in the Supple- to-human transmission has been deemed inef- mentary Appendix, available with the full text of ficient.3-9 Despite the fact that monkeypox virus this article at NEJM.org) may not be adequate to has circulated for decades in regions where it reflect the changing spectrum of clinical presen- has traditionally been endemic, research into tations, allow early identification, clarify trans- monkeypox has been neglected and underfunded. mission routes, and inform international public Since early May 2022, more than 3000 monkey- health policies and clinical trials. The case series pox virus infections have been reported in more we report here may help to inform the response. than 50 countries across five regions, prompting the World Health Organization to declare mon- Me thods keypox an “evolving threat of moderate public health concern” on June 23, 2022.10,11 Case Definition and Identification Transmission of monkeypox virus occurs We used the U.K. Health Security Agency (UKHSA) through large respiratory droplets, close or di- definition of a confirmed case: a laboratory- rect contact with skin lesions, and possibly confirmed monkeypox virus infection defined through contaminated fomites.12 There is no by a positive result on monkeypox virus poly- clear evidence of sexual transmission through merase-chain-reaction (PCR) assay in a speci- seminal or vaginal fluids. Vertical transmission men from any anatomical site.18 The type of and fetal deaths have been described.13 clinically qualified PCR assay used for the iden- Endemic monkeypox is generally self-limited, tification of monkeypox virus infections was with clade-dependent case fatality rates of 1 to locally determined on the basis of availability 10%.9 Illness typically begins with fever, fol- and guidelines. lowed by the development of multiple papular, In response to the worldwide outbreaks, aca- vesiculopustular, and ulcerative lesions on the demic researchers within the London-based Sex- face and body and prominent lymphadenopa- ual Health and HIV All East Research (SHARE) thy.9,14 Complications include pneumonitis, en- Collaborative contacted peers in affected coun- cephalitis, keratitis, and secondary bacterial tries through informal clinical and research infections.14 Young children and immunocom- networks and formed a global collaborative promised persons, including persons living with group (SHARE-net). Members of this group con- human immunodeficiency virus (HIV) infection, tributed to a convenience-sample case series in have been reported to be at increased risk for the interests of improving case identification. severe outcomes, but whether effective antiretro- The geographic distribution of SHARE-net con- viral therapy (ART) for HIV infection modifies tributing sites is shown in Figure 1. this risk is unknown.15 The current global outbreak of monkeypox Data Collection virus infection in humans suggests changes in Each contributing center completed a deidenti- biologic aspects of the virus, changes in human fied structured case-report spreadsheet devel- behavior, or both; such changes might be driven oped on May 31, 2022 (Fig. S2). Drop-down by waning smallpox immunity, relaxation of menus and free-text fields were used. The case- coronavirus disease 2019 (Covid-19) prevention report spreadsheet captured clinical data and measures, resumption of international travel, was not part of a research protocol. Variables of and sexual interactions associated with large interest were derived from case definitions that gatherings.16 To date, the current spread has preceded this outbreak and from evolving inter- 680 n engl j med 387;8 nejm.org August 25, 2022 The New England Journal of Medicine Downloaded from nejm.org on August 16, 2024. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved.  Monkeypox Virus Infection across 16 Countries Europe Netherlands 1 Belgium 2 United Kingdom 10 Denmark 2 5 1 Portugal Canada 5 Germany 2 1 2 United States 1 5 France 2 Spain Switzerland Italy 2 Israel Mexico 1 1 Australia Argentina Number of SHARE-net contributing sites per country Figure 1. Global Distribution of SHARE-net Contributing Sites. Among the 528 persons with monkeypox virus infection reported by these sites and included in the case series, 84 (16%) were in the Americas and 444 (84%) were in Europe, Israel, or Australia. national case definitions. The case-report spread- University of London Barts Cancer Institute data sheet was iteratively refined on the basis of safe haven. growing clinical experience within our network. We particularly focused on potential exposures, Statistical Analysis demographic characteristics, early symptoms, Data were analyzed with the use of SPSS soft- clinical findings, and diagnosis. Infections diag- ware, version 28 (IBM). Aggregate or deidenti- nosed since April 27, 2022, were reported be- fied data are presented to avoid deductive disclo- tween June 1 and June 24, 2022. Templates were sure of the identities of the persons with provided for uniform presentation of the clinical infection. image Web library (available in the Supplemen- tary Appendix). R e sult s Ethical Considerations Persons with Infection Persons with PCR-confirmed monkeypox were A total of 528 cases of confirmed human mon- invited to contribute to the case series by their keypox infection from five continents, 16 coun- health care provider. Written informed consent tries, and 43 clinical sites are included in this was obtained in accordance with local standards series (Fig. 1). Demographic and clinical charac- and maintained in the participants’ clinical file, teristics of the persons with infection are sum- along with local institutional review board ap- marized in Table 1. proval when required. Separate image-specific Overall, 98% of the persons with infection consent was obtained for the use of images in- were gay or bisexual men, and 75% were White. cluded in this report. Deidentified data were The median age was 38 years. A total of 41% of securely transferred to the coordinating site and the persons were living with HIV infection, and stored and analyzed within the Queen Mary in the vast majority of these persons, HIV infec- n engl j med 387;8 nejm.org August 25, 2022 681 The New England Journal of Medicine Downloaded from nejm.org on August 16, 2024. For personal use only. No other uses without permission. Copyright © 2022 Massachusetts Medical Society. All rights reserved.  The n e w e ng l a n d j o u r na l of m e dic i n e Table 1. Demographic and Clinical Characteristics of the Persons with Monkeypox.* All Persons Characteristic (N = 528) Median age (range) — yr 38 (18–68) Sex or gender — no. (%) Male 527 (>99) Female 0 Trans or nonbinary   1 (