Monkeypox: disease epidemiology, host immunity and clinical interventions

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Abstract

Monkeypox virus (MPXV), which causes disease in humans, has for many years been restricted to the African continent, with only a handful of sporadic cases in other parts of the world. However, unprecedented outbreaks of monkeypox in non-endemic regions have recently taken the world by surprise. In less than 4 months, the number of detected MPXV infections has soared to more than 48,000 cases, recording a total of 13 deaths. In this Review, we discuss the clinical, epidemiological and immunological features of MPXV infections. We also highlight important research questions and new opportunities to tackle the ongoing monkeypox outbreak.

Abstract

In this Review, Ng and colleagues examine the clinical, epidemiological and immunological aspects of monkeypox virus (MPXV) infections, with a focus on mechanisms of host immunity to MPXV. The authors also consider the unique epidemiological and pathological characteristics of the current non-endemic outbreak of the virus and discuss vaccines, therapeutics and outstanding research questions.

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Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022

John P. Thornhill, Sapha Barkati, Sharon Walmsley … (2022)

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.

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The changing epidemiology of human monkeypox—A potential threat? A systematic review

Eveline M Bunge, Bernard Hoet, Liddy Chen … (2022)

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010–2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades—Central African 10.6% (95% CI: 8.4%– 13.3%) vs. West African 3.6% (95% CI: 1.7%– 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

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Nuclear factor-kappaB (NF-kappaB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappaB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappaB proteins (IkappaBs), which retain inactive NF-kappaB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappaB activation converge on the IkappaB kinase (IKK) complex, which is responsible for IkappaB phosphorylation and is essential for signal transduction to NF-kappaB. Additional regulation of NF-kappaB activity is achieved through various post-translational modifications of the core components of the NF-kappaB signaling pathways. In addition to cytosolic modifications of IKK and IkappaB proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappaB response. This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation.

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Author and article information

Contributors

Lisa F. P. Ng:

ORCID: http://orcid.org/0000-0003-4071-5222

Lisa_Ng@idlabs.a-star.edu.sg

Journal

Journal ID (nlm-ta): Nat Rev Immunol

Journal ID (iso-abbrev): Nat Rev Immunol

Title: Nature Reviews. Immunology

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1474-1733

ISSN (Electronic): 1474-1741

Publication date (Electronic): 5 September 2022

Pages: 1-17

Affiliations

[1 ]GRID grid.185448.4, ISNI 0000 0004 0637 0221, A*STAR Infectious Diseases Labs, Agency for Science, , Technology and Research (A*STAR), ; Singapore, Singapore

[2 ]National Public Health Laboratory, Singapore, Singapore

[3 ]GRID grid.508077.d, National Centre for Infectious Diseases, ; Singapore, Singapore

[4 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore

[5 ]GRID grid.59025.3b, ISNI 0000 0001 2224 0361, Lee Kong Chian School of Medicine, , Nanyang Technological University, ; Singapore, Singapore

[6 ]GRID grid.240988.f, ISNI 0000 0001 0298 8161, Tan Tock Seng Hospital, ; Singapore, Singapore

[7 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore

[8 ]GRID grid.59025.3b, ISNI 0000 0001 2224 0361, School of Biological Sciences, , Nanyang Technological University, ; Singapore, Singapore

[9 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, , University of Liverpool, ; Liverpool, UK

[10 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Institute of Infection, Veterinary and Ecological Sciences, , University of Liverpool, ; Liverpool, UK

Author information

Anthony Torres-Ruesta http://orcid.org/0000-0003-0447-3131

Matthew Z. Tay http://orcid.org/0000-0002-1763-913X

Lisa F. P. Ng http://orcid.org/0000-0003-4071-5222

Article

Publisher ID: 775

DOI: 10.1038/s41577-022-00775-4

PMC ID: 9443635

PubMed ID: 36064780

SO-VID: fde7376a-a3d5-4a51-856b-f35b4425cbdc

Copyright © © Springer Nature Limited 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date accepted : 9 August 2022

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