Mpox (formerly monkeypox): pathogenesis, prevention, and treatment

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Abstract

In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

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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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Clinical features and management of human monkeypox: a retrospective observational study in the UK

Hugh Adler, Susan Gould, Paul Hine … (2022)

Background Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies. Methods In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network. Findings We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22–39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge. Interpretation Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease. Funding None.

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Human monkeypox.

Andrea McCollum, Inger K. Damon (2014)

Human monkeypox is a zoonotic Orthopoxvirus with a presentation similar to smallpox. Clinical differentiation of the disease from smallpox and varicella is difficult. Laboratory diagnostics are principal components to identification and surveillance of disease, and new tests are needed for a more precise and rapid diagnosis. The majority of human infections occur in Central Africa, where surveillance in rural areas with poor infrastructure is difficult but can be accomplished with evidence-guided tools and educational materials to inform public health workers of important principles. Contemporary epidemiological studies are needed now that populations do not receive routine smallpox vaccination. New therapeutics and vaccines offer hope for the treatment and prevention of monkeypox; however, more research must be done before they are ready to be deployed in an endemic setting. There is a need for more research in the epidemiology, ecology, and biology of the virus in endemic areas to better understand and prevent human infections.

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Author and article information

Contributors

Yang Yang: young@mail.sustech.edu.cn

Wenjie Tan:

ORCID: http://orcid.org/0000-0002-5963-1136

tanwj@ivdc.chinacdc.cn

Liang Shen: shenliang.0829@163.com

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 27 December 2023

Publication date PMC-release: 27 December 2023

Publication date Collection: 2023

Volume: 8

Electronic Location Identifier: 458

Affiliations

[1 ]Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, ( https://ror.org/02dx2xm20) Hubei Province Xiangyang, 441021 China

[2 ]GRID grid.198530.6, ISNI 0000 0000 8803 2373, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, , Chinese Center for Disease Control and Prevention, ; Beijing, 102206 China

[3 ]College of Biotechnology, Tianjin University of Science & Technology, ( https://ror.org/018rbtf37) Tianjin, 300457 China

[4 ]Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for infectious disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, ( https://ror.org/04xfsbk97) Shenzhen, 518112 China

Author information

Wenjie Tan http://orcid.org/0000-0002-5963-1136

Article

Publisher ID: 1675

DOI: 10.1038/s41392-023-01675-2

PMC ID: 10751291

PubMed ID: 38148355

SO-VID: 0b9d3bd2-96cd-4ecf-a159-97d015f6c6dc

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 25 July 2023

Date revision received : 14 September 2023

Date accepted : 21 September 2023

Funding

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 82002192

Award Recipient : Liang Shen

Funded by: FundRef https://doi.org/10.13039/501100003819, Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation);

Award ID: 2022CFB539; 2022CFD107

Award Recipient : Liang Shen

Funded by: Young and middle-aged Talents Project of Hubei Provincial Education Department (Q20222605), Scientific Research Ability Cultivation Fund of Hubei University of Arts and Science (2021KPGJ06), Science and Technology Plan (in the field of Medical and health care) of Xiangyang (2022YL05B; 2022YL12A).

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Keywords: drug discovery, infectious diseases

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Mpox (formerly monkeypox): pathogenesis, prevention, and treatment

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Monkeypox

Most cited references 260

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

Clinical features and management of human monkeypox: a retrospective observational study in the UK

Human monkeypox.

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