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      Emergence of monkeypox: a worldwide public health crisis

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          Abstract

          The human monkeypox virus (MPV), a zoonotic illness that was hitherto solely prevalent in Central and West Africa, has lately been discovered to infect people all over the world and has become a major threat to global health. Humans unintentionally contract this zoonotic orthopoxvirus, which resembles smallpox, when they come into contact with infected animals. Studies show that the illness can also be transferred through frequent proximity, respiratory droplets, and household linens such as towels and bedding. However, MPV infection does not presently have a specified therapy. Smallpox vaccinations provide cross-protection against MPV because of antigenic similarities. Despite scant knowledge of the genesis, epidemiology, and ecology of the illness, the incidence and geographic distribution of monkeypox outbreaks have grown recently. Polymerase chain reaction technique on lesion specimens can be used to detect MPV. Vaccines like ACAM2000, vaccinia immune globulin intravenous (VIG-IV), and JYNNEOS (brand name: Imvamune or Imvanex) as well as FDA-approved antiviral medications such as brincidofovir (brand name: Tembexa), tecovirimat (brand name: TPOXX or ST-246), and cidofovir (brand name: Vistide) are used as therapeutic medications against MPV. In this overview, we provide an outline of the MPV’s morphology, evolution, mechanism, transmission, diagnosis, preventative measures, and therapeutic approaches. This study offers the fundamental information required to prevent and manage any further spread of this emerging virus.

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

          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

            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.

              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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                Author and article information

                Contributors
                shabaazbegum.ls@geu.ac.in
                leirika100@gmail.com
                semwal.prabhakar@gmail.com
                sakshipainulii@gamil.com
                rohitsharma@bhu.ac.in
                ashim6786@gmail.com
                Journal
                Hum Cell
                Hum Cell
                Human Cell
                Springer Nature Singapore (Singapore )
                0914-7470
                1749-0774
                7 February 2023
                : 1-17
                Affiliations
                [1 ]GRID grid.448909.8, ISNI 0000 0004 1771 8078, Department of Life Sciences, , Graphic Era (Deemed to Be University), ; Dehradun, Uttarakhand 248002 India
                [2 ]Uttarakhand Council for Biotechnology (UCB), Prem Nagar, Dehradun, Uttarakhand 248007 India
                [3 ]GRID grid.411507.6, ISNI 0000 0001 2287 8816, Faculty of Ayurveda, Institute of Medical Sciences, , Banaras Hindu University, ; Varanasi, Uttar Pradesh 221005 India
                [4 ]Future Biologics, Lawrenceville, GA 30043 USA
                [5 ]South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045 USA
                [6 ]BioIntegrate, Lawrenceville, GA 30043 USA
                [7 ]Regenerative Orthopaedics, Uttar Pradesh, Noida, 201301 India
                Author information
                http://orcid.org/0000-0003-4941-5517
                http://orcid.org/0000-0002-8123-994X
                http://orcid.org/0000-0001-5137-5169
                http://orcid.org/0000-0002-8941-2006
                http://orcid.org/0000-0002-3682-3573
                http://orcid.org/0000-0003-1224-2755
                Article
                870
                10.1007/s13577-023-00870-1
                9903284
                36749539
                9fdaac92-328f-46c0-bd51-19337ee3ddfb
                © The Author(s) under exclusive licence to Japan Human Cell Society 2023, Springer Nature or its licensor (e.g. a society or other partner) 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.

                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
                : 20 November 2022
                : 28 January 2023
                Categories
                Review Article

                Cell biology
                monkeypox virus,orthopoxviruses,outbreak,pandemic,antiviral medications,vaccination
                Cell biology
                monkeypox virus, orthopoxviruses, outbreak, pandemic, antiviral medications, vaccination

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