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      The evolving epidemiology of monkeypox virus

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      Author(s): a , 1 , b , 1 , c , c , c , * , a , * , a , *
      Publication date (Electronic):
      Journal: Cytokine & Growth Factor Reviews
      Publisher: Elsevier Ltd.
      Keywords: AIDS, Acquired immunodeficiency syndrome, APOBEC3, Apolipoprotein B mRNA-editing catalytic polypeptide-like 3, CCL5, C-C Motif Chemokine receptor 5, CDC, Center of Disease Control and Prevention, COG4, Conserved oligomeric Golgi 4, COVID-19, Coronavirus disease 2019, C3L, Complement binding protein, dsDNA, double-stranded DNA, dsRNA, double-stranded RNA, EEV, Extracellular enveloped virus, eIF2α, eukaryotic translation initiation factor 2α, ELISA, enzyme linked immunosorbent assay, EMA, European Medicines Agency, EUA, Emergency Use Authorization, FDA, Food and Drug Administration, HA, Haemagglutinin, IEV, Intracellular enveloped virus, IFN, Interferon, IgG, Immunoglobulin G, IL-2, Interleukin 2, IMV, Intracellular mature virus, LAMP, Loop-mediated isothermal amplification, WHO, World Health Organization, MOPICE, Monkeypox inhibitor of complement enzyme, MPXV, Monkeypox virus, MVA, modified vaccinia Ankara, NGS, Next-generation sequencing, NK, Natural killer, PHEIC, Public Health Emergency of International Concern, PKR, Protein kinase R, PRRs, Pattern recognition receptors, RFLP, restriction fragment length polymorphism, RNAPs, RNA polymerases, RPA, Recombinase polymerase amplification, RT-qPCR, Reverse transcription quantitative polymerase chain reaction, SNPs, Single-nucleotide polymorphisms, TNF-α, Tumor necrosis factor alpha, UK, United Kingdom, UKHSA, United Kingdom Health Security Agency, USA, United States of America, VIG, Vaccinia immune globulin, VPS52, Vacuolar protein sorting 52, WGS, Whole genome sequencing, Epidemiology, Evolution, Monkeypox, Public health, Zoonotic disease

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          Abstract

          Monkeypox, caused by the monkeypox virus (MPXV), is a zoonotic disease endemic mainly in West and Central Africa. As of 27 September 2022, human monkeypox has occurred in more than 100 countries (mostly in non-endemic regions) and caused over 66,000 confirmed cases, which differs from previous epidemics that mainly affected African countries. Due to the increasing number of confirmed cases worldwide, the World Health Organization (WHO) has declared the monkeypox outbreak as a Public Health Emergency of International Concern on July 23, 2022. The international outbreak of human monkeypox represents a novel route of transmission for MPXV, with genital lesions as the primary infection, and the emergence of monkeypox in the current outbreak is also new, as novel variants emerge. Clinical physicians and scientists should be aware of this emerging situation, which presents a different scenario from previous outbreaks. In this review, we will discuss the molecular virology, evasion of antiviral immunity, epidemiology, evolution, and detection of MPXV, as well as prophylaxis and treatment strategies for monkeypox. This review also emphasizes the integration of relevant epidemiological data with genomic surveillance data to obtain real-time data, which could formulate prevention and control measures to curb this outbreak.

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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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              Outbreak of human monkeypox in Nigeria in 2017–18: a clinical and epidemiological report

              Adesola Yinka-Ogunleye, Olusola Aruna, Mahmood Hassan Dalhat … (2019)
              Background In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017–18 human monkeypox outbreak in Nigeria. Methods We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus. Findings 122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility. Interpretation This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria. Funding None.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cytokine Growth Factor Rev
                Journal ID (iso-abbrev): Cytokine Growth Factor Rev
                Title: Cytokine & Growth Factor Reviews
                Publisher: Elsevier Ltd.
                ISSN (Print): 1359-6101
                ISSN (Electronic): 1879-0305
                Publication date PMC-release: 8 October 2022
                Publication date (Electronic): 8 October 2022
                Affiliations
                [a ]Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, PR China
                [b ]Department of Clinical Laboratory, The Second Hospital of Shandong University, 250033 Jinan, Shandong, PR China
                [c ]Department of Oncology, Jiangjin Hospital, Chongqing University, Chongqing 402260, PR China
                Author notes
                [* ]Corresponding authors.
                [1]

                These authors contributed equally to this work.

                Article
                Publisher Item ID: S1359-6101(22)00077-6
                DOI: 10.1016/j.cytogfr.2022.10.002
                PMC ID: 9547435
                PubMed ID: 36244878
                SO-VID: bf9d55e6-07e6-4778-bb8a-e1b79e364455
                Copyright © © 2022 Elsevier Ltd. All rights reserved.
                License:

                Elsevier has created a Monkeypox Information Center in response to the declared public health emergency of international concern, with free information in English on the monkeypox virus. The Monkeypox Information Center is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its monkeypox related research that is available on the Monkeypox Information Center - including this research content - immediately available in publicly funded repositories, with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the Monkeypox Information Center remains active.

                History
                Date received : 8 September 2022
                Date revision received : 28 September 2022
                Date accepted : 8 October 2022
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: aids, acquired immunodeficiency syndrome,apobec3, apolipoprotein b mrna-editing catalytic polypeptide-like 3,ccl5, c-c motif chemokine receptor 5,cdc, center of disease control and prevention,cog4, conserved oligomeric golgi 4,covid-19, coronavirus disease 2019,c3l, complement binding protein,dsdna, double-stranded dna,dsrna, double-stranded rna,eev, extracellular enveloped virus,eif2α, eukaryotic translation initiation factor 2α,elisa, enzyme linked immunosorbent assay,ema, european medicines agency,eua, emergency use authorization,fda, food and drug administration,ha, haemagglutinin,iev, intracellular enveloped virus,ifn, interferon,igg, immunoglobulin g,il-2, interleukin 2,imv, intracellular mature virus,lamp, loop-mediated isothermal amplification,who, world health organization,mopice, monkeypox inhibitor of complement enzyme,mpxv, monkeypox virus,mva, modified vaccinia ankara,ngs, next-generation sequencing,nk, natural killer,pheic, public health emergency of international concern,pkr, protein kinase r,prrs, pattern recognition receptors,rflp, restriction fragment length polymorphism,rnaps, rna polymerases,rpa, recombinase polymerase amplification,rt-qpcr, reverse transcription quantitative polymerase chain reaction,snps, single-nucleotide polymorphisms,tnf-α, tumor necrosis factor alpha,uk, united kingdom,ukhsa, united kingdom health security agency,usa, united states of america,vig, vaccinia immune globulin,vps52, vacuolar protein sorting 52,wgs, whole genome sequencing,epidemiology,evolution,monkeypox,public health,zoonotic disease
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: aids, acquired immunodeficiency syndrome, apobec3, apolipoprotein b mrna-editing catalytic polypeptide-like 3, ccl5, c-c motif chemokine receptor 5, cdc, center of disease control and prevention, cog4, conserved oligomeric golgi 4, covid-19, coronavirus disease 2019, c3l, complement binding protein, dsdna, double-stranded dna, dsrna, double-stranded rna, eev, extracellular enveloped virus, eif2α, eukaryotic translation initiation factor 2α, elisa, enzyme linked immunosorbent assay, ema, european medicines agency, eua, emergency use authorization, fda, food and drug administration, ha, haemagglutinin, iev, intracellular enveloped virus, ifn, interferon, igg, immunoglobulin g, il-2, interleukin 2, imv, intracellular mature virus, lamp, loop-mediated isothermal amplification, who, world health organization, mopice, monkeypox inhibitor of complement enzyme, mpxv, monkeypox virus, mva, modified vaccinia ankara, ngs, next-generation sequencing, nk, natural killer, pheic, public health emergency of international concern, pkr, protein kinase r, prrs, pattern recognition receptors, rflp, restriction fragment length polymorphism, rnaps, rna polymerases, rpa, recombinase polymerase amplification, rt-qpcr, reverse transcription quantitative polymerase chain reaction, snps, single-nucleotide polymorphisms, tnf-α, tumor necrosis factor alpha, uk, united kingdom, ukhsa, united kingdom health security agency, usa, united states of america, vig, vaccinia immune globulin, vps52, vacuolar protein sorting 52, wgs, whole genome sequencing, epidemiology, evolution, monkeypox, public health, zoonotic disease

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