The Global Health Threat of Monkeypox Virus: Understanding Its Biology, Transmission, and Potential Therapeutic Interventions

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Abstract

Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, shares its genus with Variola virus (VARV), the causative agent of smallpox, and Vaccinia virus (VACV), used for smallpox vaccination. While smallpox has been eradicated, MPXV and related poxviruses continue to pose a global health threat. Monkeypox (Mpox), similar in clinical presentation to smallpox but milder, is endemic in Central and West Africa. Sporadic outbreaks emphasize the potential for wider dissemination. Understanding their biology, transmission, immune evasion, and clinical features informs disease control strategies. The intersection of medical innovation and biotechnology with poxviruses underscores their importance in both disease and scientific advancement. Further research is essential to enhance prevention, management, and therapeutic interventions for these viruses.

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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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The detection of monkeypox in humans in the Western Hemisphere.

Kurt D. Reed, John W. Melski, Mary Beth Graham … (2004)

During May and June 2003, an outbreak of febrile illness with vesiculopustular eruptions occurred among persons in the midwestern United States who had had contact with ill pet prairie dogs obtained through a common distributor. Zoonotic transmission of a bacterial or viral pathogen was suspected. We reviewed medical records, conducted interviews and examinations, and collected blood and tissue samples for analysis from 11 patients and one prairie dog. Histopathological and electron-microscopical examinations, microbiologic cultures, and molecular assays were performed to identify the etiologic agent. The initial Wisconsin cases evaluated in this outbreak occurred in five males and six females ranging in age from 3 to 43 years. All patients reported having direct contact with ill prairie dogs before experiencing a febrile illness with skin eruptions. We found immunohistochemical or ultrastructural evidence of poxvirus infection in skin-lesion tissue from four patients. Monkeypox virus was recovered in cell cultures of seven samples from patients and from the prairie dog. The virus was identified by detection of monkeypox-specific DNA sequences in tissues or isolates from six patients and the prairie dog. Epidemiologic investigation suggested that the prairie dogs had been exposed to at least one species of rodent recently imported into the United States from West Africa. Our investigation documents the isolation and identification of monkeypox virus from humans in the Western Hemisphere. Infection of humans was associated with direct contact with ill prairie dogs that were being kept or sold as pets. Copyright 2004 Massachusetts Medical Society

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Journal

Journal ID (nlm-ta): Infect Drug Resist

Journal ID (iso-abbrev): Infect Drug Resist

Journal ID (publisher-id): idr

Title: Infection and Drug Resistance

Publisher: Dove

ISSN (Electronic): 1178-6973

Publication date (Electronic): 21 December 2023

Publication date Collection: 2023

Volume: 16

Pages: 7759-7766

Affiliations

[1 ]Department of Infection Management, Nanjing Drum Tower Hospital , Nanjing, Jiangsu, People’s Republic of China

[2 ]Department of Ultrasound Diagnostic, Children’s Hospital of Nanjing Medical University , Nanjing, People’s Republic of China

[3 ]Department of Respiratory, Children’s Hospital of Nanjing Medical University , Nanjing, People’s Republic of China

[4 ]Department of Clinical Research, Children’s Hospital of Nanjing Medical University , Nanjing, Jiangsu, People’s Republic of China

Author notes

Correspondence: Wei Li; Man Tian, Email weili126@126.com; tmsweet@163.com

[*]

These authors contributed equally to this work

Author information

Yan He http://orcid.org/0000-0003-0912-3755

Zilie Zhou http://orcid.org/0009-0002-3493-8307

Article

Publisher ID: 438725

DOI: 10.2147/IDR.S438725

PMC ID: 10749784

PubMed ID: 38146310

SO-VID: 10d8c153-e753-479e-9f4a-ce15c21f8414

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This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 08 September 2023

Date accepted : 13 December 2023

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Figures: 0, Tables: 1, References: 49, Pages: 8

Funding

Funded by: China Postdoctoral Science Foundation, open-funder-registry 10.13039/501100002858;

Funded by: the Young Scientists Fund of the National Natural Science Foundation of China;

This work was supported by China Postdoctoral Science Foundation (2022M721682), the Young Scientists Fund of the National Natural Science Foundation of China (82103896) and Nanjing Medical Science and Technology Development Foundation (ZKX20039).

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The Global Health Threat of Monkeypox Virus: Understanding Its Biology, Transmission, and Potential Therapeutic Interventions

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Most cited references 46

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

The detection of monkeypox in humans in the Western Hemisphere.

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