Jain, Nityanand

Lansiaux, Edouard

Simanis, Raimonds

New Microbes and New Infections

English

PubMed

Riga Stradins university

EDITORIALThe new face of monkeypox virus: an emerging global emergencyNityanand Jain1, Edouard Lansiaux2 and Raimonds Simanis31) Faculty of Medicine, Riga Stradiņs University, Dzirciema Street 16, LV-1007 Riga, Latvia, 2) Lille University School of Medicine, 2 Avenue Eugène Avinée, 59120Loos, Lille, France and 3) Department of Infectiology, Faculty of Medicine, Riga Stradiņs University, LV-1007 Riga, LatviaKeywords: Global, infections, monkeypox virus, pandemic, sexual transmissionArticle published online: 27 May 2022Corresponding author: Nityanand Jain.Corresponding author: Edouard Lansiaux.E-mails: nityapkl@gmail.com (N. Jain), edouard.lansiaux.etu@univ-lille.fr (E. Lansiaux), raimonds.simanis@rsu.lv(R. Simanis)Nityanand Jain and Edouard Lansiaux contributed equally (co-firstauthors).More than a year ago in March 2021, over 19 senior experts andleaders in various fields from across the globe gathered virtuallyto participate in a tabletop simulative exercise on exploring thegaps in international biosecurity and pandemic response sys-tems. The panel conducted by the non-profit Nuclear ThreatInitiative (NTI; https://www.nti.org/) in association with MunichSecurity Conference (MSC; https://securityconference.org/),explored ways to tackle the effects of high-consequence bio-logical threats like Covid-19 [1]. What makes this panel dis-cussion remarkable was the pathogen that was simulated in thediscussion. The group studied the global uncontrolled spread ofa deadly and unusual strain of monkeypox virus (MPXV) thatemerged in a fictional nation [1]. By the end of the simulatedperiod of 18 months, the virus had infected 3 billion peoplewhilst killing more than 270 million people worldwide [1].Fast forward to today, May 2022, and the simulation seemsto be becoming a reality. On 7th May 2022, the UK HealthSecurity Agency (UKHSA) confirmed the first case of MPXV ina UK traveller who had made a round-trip to Nigeria [2]. In thefollowing two weeks, more than 84 cases have been confirmedwith an additional 61 suspected cases reported in 14 countries(Fig. 1) [3].MPXV is one of the four human pathogenetic speciesbelonging to the Orthopoxvirus genus in the Poxviridae family.Together with Variola virus (causative agent of now eradicatedsmallpox), Cowpox, and Vaccinia virus, these zoonotic virusescan infect a wide range of mammalian species [4,5]. Twoepidemiologically distinct genetic clades of MPXV have beenThis is an odescribed in the literature – West African and Central African(or Congo Basin) clades. The West African clade has a lower-case mortality (3.6%) with no direct human-to-human trans-mission noted in comparison with the Central African cladewith a higher case mortality (10.6%) and known human-to-human transmission [6].MPXV is currently considered a rare zoonotic disease exceptin DRC (Democratic Republic of Congo) where the cases havegrown exponentially. Since 1970, more than 35,000 cases havebeen documented (including confirmed, suspected, and prob-able) worldwide with >95% cases reported in DRC alone, fol-lowed by Nigeria and other neighbouring African countries [6].Until 2003, the MPXV was not reported outside Africa, how-ever, with an increase in trade, business, and travel, sporadicoutbreaks have been reported across the globe, curiously allhaving their contact origins in Nigeria [6].Previous reports have shown that outside Africa, the virustends to predominantly infect adult males (>50% cases) in theage range of 10-21 years (Table 1) [6]. Symptoms develop intwo phases – the invasion period and the skin eruption period.The invasion period (0-5 days post contact) presents with fever,headache, muscle aches, fatigue, backache, and chills. Lymph-adenopathy during this phase is characteristic of MPXV infec-tion [7]. Development of rash starts 1-3 days after the fever andusually affects the face, palms, soles, oral and genital mucousmembranes, and conjunctiva. Rash progresses sequentiallythrough macules, papules, vesicles, pustules, followed by cruststhat dry up and fall off [7]. Though not fatal, the symptoms areself-limiting lasting from 2 to 4 weeks.Based on the mathematical modelling of available literature, ithas been predicted that MPX may exist in a semi-endemicequilibrium, where there is no infection in its animal host, butthe disease persists in humans [8]. Though the authors didn’tfind viral fitness to become endemic solely through humantransmission, mutations in viral proteins could upset the model[8]. Studies have elaborated and highlighted the probable fac-tors that could lead to a rampant spread of the MPX virusacross the globe (Fig. 2) [1,4,6]. Addressing these issues is ofNew Microbe and New Infect 2022; 47: 100989© 2022 The Author(s). Published by Elsevier Ltdpen access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)https://doi.org/10.1016/j.nmni.2022.100989AustraliaDate confirmed: 20-05-22Confirmed: 2Suspected: 0SwedenDate confirmed: 19-05-22Confirmed: 1Suspected: 0United StatesDate confirmed: 18-05-22Confirmed: 2Suspected: 0CanadaDate confirmed: 19-05-22Confirmed: 5Suspected: 17IsraelDate confirmed: 21-05-22Confirmed: 1Suspected: 0PortugalDate confirmed: 17-05-22Confirmed: 14Suspected: 20SpainDate confirmed: 18-05-22Confirmed: 30Suspected: 23England (UK)Date confirmed: 07-05-22Confirmed: 20Suspected: 0FranceDate confirmed: 20-05-22Confirmed: 1Suspected: 0ItalyDate confirmed: 19-05-22Confirmed: 3Suspected: 0GermanyDate confirmed: 19-05-22Confirmed: 3Suspected: 0NetherlandsDate confirmed: 20-05-22Confirmed: 1Suspected: 0BelgiumDate confirmed: 19-05-22Confirmed: 3Suspected: 0SwitzerlandDate confirmed: 21-05-22Confirmed: 1Suspected: 0FIG. 1. Map depicting the geographical spread of the Monkeypox Virus (MPXV) as of 21st May 2022. Date confirmed refers to the date ofconfirmation of the first MPXV case in the country. “Confirmed” refers to the number of confirmed cases whilst “Suspected” refers to the number ofsuspected cases in the respective countries. Note that the map is only for illustrative purposes and the authors remain neutral in regard to territorialdisputes.TABLE 1. Characteristics of confirmed and suspected MPXVcases as of 21st May 2022Characteristics No. of cases Characteristics No. of casesCase Status HospitalizationConfirmed 86 (59%) Yes 21 (14%)Suspected 61 (41%) No 37 (25%)Unknown 89 (61%)Age Groups20-40 56 (38%) Case Isolation40-60 2 (1%) Yes 59 (40%)Unknown 89 (61%) Unknown 88 (60%)Gender Travel HistoryMale 106 (72%) Yes 12Female 1 (1%) No 42Unknown 40 (27%) Unknown 93Reported Symptoms Source of ContactFever 19 Sexual ContactRash (vesicular and/orunspecified)8 Suspected sexualcontact28 (19%)Genital and oral ulcers 22 Man-to-man sex 4 (3%)Lesions (ulcerative, skin) 21 Sauna 15 (10%)Swallowing difficulties 1 Unknown 100 (68%)Perianal papules 1Inguinal adenopathy 1Unknown 942 New Microbes and New Infections, Volume 47 Number C, April-May 2022 NMNIutmost priority to prevent another pandemic, especially sincethe disastrous effects of Covid-19 are still strongly present inthe collective human memory.A group of researchers from Portugal has open-sourced thefirst draft of the genomic sequence of the MPXV, which revealsthe virus belonging to the West African clade with close links tothe viruses which were previously reported in the UK, Israel,and Singapore in 2018-19 [9]. Noticeably, according to theEuropean Centre for Disease Prevention and Control (ECDC),“This is the first time that chains of transmission are reported inEurope without known epidemiological links to West or Cen-tral Africa, where this disease is endemic” [10].What is even more intriguing is that this is also the first timeworldwide whereby cases are being reported amongst the menwho have sex with men (MSM) community [10]. This is evidentalso from the large number of cases reporting genital and oralulcers (Table 1). Close contact has been implicated in thetransmission of the virus however, the identification of theWestern African clade as the causative agent is a puzzlingmystery.Human sexual transmission of Orthopoxvirus has been docu-mented previously [11,12]. However, most cases have beensporadic isolated instances where an unvaccinated partner gotinfected post-coitus from a vaccinated partner (vaccinated against© 2022 The Author(s). Published by Elsevier Ltd, NMNI, 47, 100989This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4Vaccinia virus) having an unhealed vaccination site. In fact, a fewyears ago, a case of secondary and tertiary transmission of theVaccinia virus in a MSM patient was reported by the US Centrefor Disease Control and Prevention (US CDC) [13].Whilst contact tracing and the source of spread are stillunder investigation, Spanish authorities revealed that all 23 men.0/).Diagnosis1. Lack of propersurveillance, case definitions,and reporting programmes2. Expensive testing3. Low funding and manpower4. Fatigue and exhaustion from Covid-19 pandemic5. Inaccurate clinical identificationCessation of Vaccination against Smallpox1. Last vaccination programme in 1980 againstOrthopoxviruses2. Loss of herd immunity and waning immunityIncreased Human-Animal Interactions1. Deforestation and rapid industrialization leading to increasedexposure2. Wars forcing people to flee to forests3. Increase in petting activities including zoos, circuses etc.Increased Travel1. Increased points-of contact and transmission routes2. Non-uniform screening guidelines for travellers3. Lack of education regarding specific endemicdiseasesLack of Biological Research Governance1. Insufficient biotechnology and genetic research oversighttcudnoc-fo-edoc dna senilediug mrofinu fo tnemecrofne fo kcaL.2Lack of International Coordination and Warning1. Insufficient communication and alert warning systemsni-kcik ot serusaem ytiruces rof sreggirt deifitnedi-noN.23. Lack of national and international preparedness plans4. Insufficient training and public education5. Funding and resource inadequacy and disparity amongst different regionsof globe.FIG. 2. Factors promoting the rapid spread of the MPX virus that needs to be addressed to prevent rampant spread of the virus and furtherepidemiological escalation of the situation.NMNI Editorial 3with suspicion of infection had visited the same Paraiso sauna, agay-friendly establishment, that has since been closed (Table 1)[14]. Similarly, Australian authorities have issued an alert forpassengers on the two flights that were taken by the confirmedpatient from London to Melbourne [15]. Interestingly, theAustralian confirmed case was diagnosed by an astute generalpractitioner (GP) [15], which highlights the importance of GPsin early detection, contact tracing, and breaking of transmissionchains.Moving forward, rapid response and action are needed fromall parties including society, healthcare professionals, and poli-cymakers. A detailed interpretation of this topic has beensummarized by Giulio and Eckburg [16]. Vaccination againstsmallpox has shown to have an efficacy of around 85% againstMPXV [17], however, mass vaccination, as with SARS-CoV-2would be counterproductive in this case. A more targeted“ring vaccination” approach can be recommended where high-risk close contacts only are vaccinated [18]. Other newertherapeutical options including the Modified Vaccinia Ankaravaccine against MPXV, and the recently approved antiviralTecovirimat may be used in limited clinical settings with carefulobservation. Vaccinia IVIG (VIVIG) could also be used for themanagement of complications and prevention of the develop-ment of long-term sequelae.Finally, the lessons learned during the Covid-19 pandemicshould not be forgotten, rather should be adjusted, and rapidlyimplemented. As author Donna Maltz summarizes in her book“Conscious Cures: Solutions to 21st Century Pandemics” -“COVID-19 slowed us down, but what have we learned? The virusgave us time to think, but what are we thinking?” In the context ofThis is an oMPXV, these questions are for all of us to consider before it’stoo late.Ethical approvalNot applicable. All data presented in the study has beencollected from open-source platforms with proper citation and/or from media sources.AcknowledgmentsThe support of ECOMSIR (European Collaboration of MedicalStudents in Research) and Riga Stradiņs University is greatlyacknowledged.Conflicts of interestThe authors declare no conflicts of interest in regards with thepresent editorial. The viewpoints presented are personal anddoesn’t necessarily reflect the viewpoints of the affiliatedinstitutions.FundingThe present editorial didn’t receive any external funding andwas self-supported by the authors.© 2022 The Author(s). Published by Elsevier Ltd, NMNI, 47, 100989pen access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).4 New Microbes and New Infections, Volume 47 Number C, April-May 2022 NMNIAuthor contributionsNJ and EL conceptualized the present editorial, whilst all au-thors were involved in data collection and preparation of themanuscript. Supervision was done by RS. Visualizations wasdone by NJ and EL. All authors have read and agreed to the finalversion of the editorial for publication.References[1] Yassif JM, O’Prey KP, Issac CR. Strengthening global systems to pre-vent and respond to high-consequence biological threats: results fromthe 2021 tabletop exercise conducted in partnership with the Munichsecurity conference [online] November 2021. Available from: https://www.nti.org/wp-content/uploads/2021/11/NTI_Paper_BIO-TTX_Final.pdf. [Accessed 20 May 2022]. Accessed.[2] World Health Organization (WHO). 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PLoS Negl Trop Dis 2022 Feb11;16(2):e0010141. https://doi.org/10.1371/journal.pntd.0010141.PMID: 35148313; PMCID: PMC8870502.[7] World Health Organization (WHO). Monkeypox [online] 19th May2022. Available from: https://www.who.int/news-room/fact-sheets/detail/monkeypox. [Accessed 21 May 2022]. Accessed.[8] Bankuru SV, Kossol S, Hou W, Mahmoudi P, Rychtár J, Taylor D.A game-theoretic model of Monkeypox to assess vaccination strate-gies. PeerJ 2020 Jun 22;8:e9272. https://doi.org/10.7717/peerj.9272.PMID: 32607280; PMCID: PMC7316080.© 2022 The Author(s). Published by Elsevier Ltd, NMNI, 47, 100989This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4[9] Isidro J, Borges V, Pinto M, Ferreira R, Sobral D, Nunes A, et al. Firstdraft genome sequence of Monkeypox virus associated with the sus-pected multi-country outbreak (confirmed case in Portugal). [online]20th May 2022. 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The new face of monkeypox virus : an emerging global emergency

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The new face of monkeypox virus: an emerging global emergency

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The new face of monkeypox virus : an emerging global emergency

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