Monitoring Monkeypox: Safeguarding Global Health through Rapid Response and Global Surveillance
Abstract
:1. Introduction
2. Epidemiology of Monkeypox and 2023 Reemergence
3. Challenges in Detecting and Responding to Monkeypox
Diagnostic Assays: Direct and Indirect Methods for the MPXV Screening
- Multiplex real-time PCR techniques have been developed to detect multiple targets at the same time, such as monkeypox and varicella-zoster. For viral detection, these assays use particular gene sections for each virus and distinct dye/quencher combinations. They have a high specificity and sensitivity, detecting the presence of the targeted viruses [23].
- The pan-orthopoxvirus PCR/ESI-MS approach leverages the T5000 platform to identify all orthopoxviruses in a single reaction. This approach provides fast and precise identification without the use of sequencing [23].
- Loop-mediated isothermal amplification (LAMP) is a high-sensitivity and specificity nucleic acid amplification method. LAMP can detect monkeypox and distinguish between virus strains. It is simple to implement and can be used in resource-limited settings [24].
- Recombinase polymerase amplification (RPA) is another isothermal approach that allows for lower-temperature DNA amplification. It has a quick diagnosis, does not require complicated equipment, and is stable in a variety of environmental situations. RPA can be beneficial, particularly in areas with limited access to molecular techniques [25].
- GeneXpert is a portable technology that integrates sample preparation, real-time PCR, and detection into a single closed system. It has advantages, such as requiring fewer samples, being simple to use, and being able to detect several infectious agents, allowing for the effective management and surveillance of monkeypox infections [26].
- Although immunohistochemistry and electron microscopy can provide useful information on virus–host interactions and tissue involvement, they are not commonly used in clinical settings [27].
- Cell culture techniques are appropriate for virus biology and pathobiology research, but they are not suggested for routine diagnostic use [28].
- Serological methods such as ELISA can quantify exposure and vaccine efficacy, although they have limitations in distinguishing orthopoxvirus species [29].
- Although rapid antigen tests and lateral flow assays provide quick and easy diagnosis in minutes, their sensitivity and false–positive rates should be evaluated [30].
- To evaluate the features and diversity of monkeypox viruses, genomic sequencing using either Sanger or next-generation sequencing technologies is advised. The World Health Organization strongly encourages the sharing of genetic data through databases [31].
4. Importance of Rapid Response and Global Surveillance: Enhancing Monkeypox Surveillance and Response
- Early Detention: by detecting and confirming cases as soon as possible, public health authorities can undertake the necessary actions to prevent this virus from spreading further.
- Timely Public Health Interventions: a quick response allows for the adoption of time-sensitive public health interventions, such as case isolation, contact tracing, and vaccination programs.
- Outbreak Containment: the timely sharing of surveillance data and information enables a coordinated response.
- Identifying High-Risk locations: global surveillance initiatives aid in the identification of high-risk locations where monkeypox transmission is more likely to occur or emerge.
- Viral Evolution Monitoring: the continuous surveillance and sequencing of monkeypox virus genomes can provide vital insights into viral evolution and genomic alterations.
- International Collaboration: global surveillance networks enable countries and organizations to collaborate and share information. The coordination of activities can result in a more complete and rapid response, resulting in improved disease control and prevention.
5. Future Directions and Recommendations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Plowright, R.K.; Parrish, C.R.; McCallum, H.; Hudson, P.J.; Ko, A.I.; Graham, A.L.; Lloyd-Smith, J.O. Pathways to zoonotic spillover. Nat. Rev. Microbiol. 2017, 15, 502–510. [Google Scholar] [CrossRef]
- Kreuder Johnson, C.; Hitchens, P.L.; Evans, T.S.; Goldstein, T.; Thomas, K.; Clements, A.; Joly, D.O.; Wolfe, N.D.; Daszak, P.; Karesh, W.B.; et al. Spillover and pandemic properties of zoonotic viruses with high host plasticity. Sci. Rep. 2015, 5, 14830. [Google Scholar] [CrossRef] [PubMed]
- Ellwanger, J.H.; Chies, J.A.B. Zoonotic spillover: Understanding basic aspects for better prevention. Genet. Mol. Biol. 2021, 4, 44–55. [Google Scholar] [CrossRef] [PubMed]
- WHO. Monkeypox Epidemiological Report. Available online: https://www.who.int/news-room/fact-sheets/detail/monkeypox (accessed on 19 July 2023).
- WHO. Monkeypox: Experts Give Virus Variants New Names. Available online: https://www.who.int/news/item/12-08-2022-monkeypox--experts-give-virus-variants-new (accessed on 19 July 2023).
- Isidro, J.; Borges, V.; Pinto, M.; Sobral, D.; Santos, J.D.; Nunes, A.; Mixão, V.; Ferreira, R.; Santos, D.; Duarte, S.; et al. Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus. Nat. Med. 2022, 28, 1569–1572. [Google Scholar] [CrossRef] [PubMed]
- Brown, K.; Leggat, P.A. Human Monkeypox: Current State of Knowledge and Implications for the Future. Trop. Med. Infect. Dis. 2016, 1, 8. [Google Scholar] [CrossRef]
- WHO. World Health Organization. (Monkeypox). Available online: https://www.who.int/news-room/fact-sheets/detail/monk (accessed on 19 July 2023).
- WHO. World Health Organization (18 May 2022). Disease Outbreak News; Monkeypox–United Kingdom of Great Britain and Northern Ireland. Available online: https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON383 (accessed on 19 July 2023).
- Ulaeto, D.; Agafonov, A.; Burchfield, J.; Carter, L.; Happi, C.; Jakob, R.; Krpelanova, E.; Kuppalli, K.; Lefkowitz, E.J.; Mauldin, M.R.; et al. New nomenclature for mpox (monkeypox) and monkeypox virus clades. Lancet Infect. Dis. 2023, 23, 273–275. [Google Scholar] [CrossRef]
- Happi, C.; Adetifa, I.; Mbala, P.; Njouom, R.; Nakoune, E.; Happi, A.; Ndodo, N.; Ayansola, O.; Mboowa, G.; Bedford, T.; et al. Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus. PLoS Biol. 2022, 23, 20–80. [Google Scholar] [CrossRef]
- Endo, A.; Murayama, H.; Abbott, S.; Ratnayake, R.; Pearson, C.A.B.; Edmunds, W.J.; Fearon, E.; Funk, S. Heavy-tailed sexual contact networks and monkeypox epidemiology in the global outbreak, 2022. Science 2022, 378, 90–94. [Google Scholar] [CrossRef]
- Luna, N.; Ramirez, A.L.; Munoz, M.; Ballesteros, N.; Patino, L.H.; Castaneda, S.A.; Bonilla-Aldana, D.K.; Paniz-Mondolfi, A.; Ramirez, J.D. Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: Emergence of a novel viral lineage? Travel. Med. Infect. Dis. 2022, 49, 102–402. [Google Scholar] [CrossRef]
- GISAID. 2023. Available online: https://www.epicov.org/epi3/frontend#56ec7d (accessed on 19 July 2023).
- Guimarães, N.R.; Tomé, L.R.; Lamounier, L.O.; Silva, M.F.; Lima, M.T.; da Costa, A.B.; Luiz, K.C.M.; de Jesus, R.; Trindade, G.d.S.; Oliveira, D.B.; et al. Genomic Surveillance of Monkeypox Virus, Minas Gerais, Brazil, 2022. Emerg. Infect. Dis. 2023, 29, 1270–1273. [Google Scholar] [CrossRef]
- Scarpa, F.; Sanna, D.; Azzena, I.; Cossu, P.; Locci, C.; Angeletti, S.; Maruotti, A.; Ceccarelli, G.; Casu, M.; Fiori, P.L.; et al. Genetic Variability of the Monkeypox Virus Clade IIb B. 1. J. Clin. Med. 2022, 11, 6388. [Google Scholar] [CrossRef]
- Wang, L.; Shang, J.; Weng, S.; Aliyari, S.R.; Ji, C.; Cheng, G.; Wu, A. Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022. J. Med. Virol. 2023, 95, e28036. [Google Scholar] [CrossRef] [PubMed]
- Jolly, B.; Scaria, V. A distinct phylogenetic cluster of Monkeypox genomes suggests an early and cryptic spread of the virus. J. Infect. 2022, 86, e24–e26. [Google Scholar] [CrossRef]
- Forni, D.; Cagliani, R.; Molteni, C.; Clerici, M.; Sironi, M. Monkeypox virus: The changing facets of a zoonotic pathogen. Infect. Genet. Evol. 2022, 105, 105–372. [Google Scholar] [CrossRef] [PubMed]
- Zaeck, L.M.; Lamers, M.M.; Verstrepen, B.E.; Bestebroer, T.M.; van Royen, M.E.; Götz, H.; Shamier, M.C.; van Leeuwen, L.P.M.; Schmitz, K.S.; Alblas, K.; et al. Low levels of monkeypox virus-neutralizing antibodies after MVA-BN vaccination in healthy individuals. Nat. Med. 2023, 29, 270–278. [Google Scholar] [CrossRef] [PubMed]
- Grant, R.J.; Blyn, L.B.; Zoll, S.; Sampath, R.; Baldwin, C.D.; Nalca, A.; Eshoo, M.W.; Whitehouse, C.A.; Matthews, H. Application of the Ibis-T5000 panorthopoxvirus assay to quantitatively detect monkeypox viral loads in clinical specimens from macaques experimentally infected with aerosolized monkeypox virus. Am. J. Trop. Med. Hyg. 2010, 82, 318–323. [Google Scholar] [CrossRef]
- Li, Y.; Olson, V.A.; Laue, T.; Laker, M.T.; Damon, I.K. Detection of monkeypox virus with real-time PCR assays. J. Clin. Virol. 2006, 36, 194–203. [Google Scholar] [CrossRef]
- Lim, C.K.; McKenzie, C.; Deerain, J.; Chow, E.P.F.; Towns, J.; Chen, M.Y.; Fairley, C.K.; Tran, T.; Williamson, D.A. Correlation between monkeypox viral load and infectious virus in clinical specimens. J. Clin. Virol. 2023, 161, 105421. [Google Scholar] [CrossRef]
- Iizuka, I.; Saijo, M.; Shiota, T.; Ami, Y.; Suzaki, Y.; Nagata, N.; Hasegawa, H.; Sakai, K.; Fukushi, S.; Mizutani, T.; et al. Loop-mediated isothermal amplification-based diagnostic assay for monkeypox virus infections. J. Med. Virol. 2009, 81, 1102–1108. [Google Scholar] [CrossRef]
- Davi, S.D.; Kissenkötter, J.; Faye, M.; Böhlken-Fascher, S.; Stahl-Hennig, C.; Faye, O.; Faye, O.; Sall, A.A.; Weidmann, M.; Ademowo, O.G.; et al. Recombinase polymerase amplification assay for rapid detection of Monkeypox virus. Diagn. Microbiol. Infect. Dis. 2019, 95, 41–45. [Google Scholar] [CrossRef]
- Li, D.; Wilkins, K.; McCollum, A.M.; Osadebe, L.; Kabamba, J.; Nguete, B.; Likafi, T.; Balilo, M.P.; Lushima, R.S.; Malekani, J.; et al. Evaluation of the GeneXpert for human monkeypox diagnosis. Am. J. Trop. Med. Hyg. 2017, 96, 405–410. [Google Scholar] [CrossRef]
- Sood, A.; Sui, Y.; McDonough, E.; Santamaría-Pang, A.; Al-Kofahi, Y.; Pang, Z.; Jahrling, P.B.; Kuhn, J.H.; Ginty, F. Comparison of multiplexed immunofluorescence imaging to chromogenic immunohistochemistry of skin biomarkers in response to monkeypox virus infection. Viruses 2020, 12, 787. [Google Scholar] [CrossRef]
- Cho, C.T.; Wenner, H.A. Monkeypox virus. Bacteriol. Rev. 1973, 37, 1–18. [Google Scholar] [CrossRef]
- Karem, K.L.; Reynolds, M.; Braden, Z.; Lou, G.; Bernard, N.; Patton, J.; Damon, I.K. Characterization of acutephase humoral immunity to monkeypox: Use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak. Clin. Vaccine Immunol. 2005, 12, 867–872. [Google Scholar] [CrossRef]
- Sklenovska, N.; Van Ranst, M. Emergence of monkeypox as the most important orthopoxvirus infection in humans. Front. Public Health 2018, 6, 2–41. [Google Scholar] [CrossRef] [PubMed]
- WHO. CDN. Available online: https://cdn.who.int/media/docs/default-source/searo/whe/monkeypox/searo-mp-techbrief_priority-actions_300522.pdf?sfvrsn=ae7be762_1 (accessed on 19 July 2023).
- White House. Available online: https://www.whitehouse.gov/ostp/news-updates/2022/08/11/fact-sheet-ongoing-u-s-monkeypox-research-activities-to-speed-science-for-impact/ (accessed on 19 July 2023).
- Pfaff, F.; Hoffmann, D.; Beer, M. Monkeypox genomic surveillance will challenge lessons learned from SARS-CoV-2. Lancet 2022, 2, 22–23. [Google Scholar] [CrossRef]
- de Jonge, E.F.; Peterse, C.M.; Koelewijn, J.M.; van der Drift, A.R.; van der Beek, R.F.; Nagelkerke, E.; Lodder, W.J. The detection of monkeypox virus DNA in wastewater samples in the Netherlands. Sci. Total Environ. 2022, 15, 852–158265. [Google Scholar]
- Tiwari, A.; Adhikari, S.; Zhang, S.; Solomon, T.B.; Lipponen, A.; Islam, M.A.; Thakali, O.; Sangkham, S.; Shaheen, M.N.F.; Jiang, G.; et al. Tracing COVID-19 Trails in Wastewater: A Systematic Review of SARS-CoV-2 Surveillance with Viral Variants. Water 2023, 15, 1018. [Google Scholar] [CrossRef]
- Ma, Y.; Chen, M.; Bao, Y.; Song, S. MPoxVR: A comprehensive genomic resource for monkeypox virus variant surveillance. Innovation 2022, 3, 5–296. [Google Scholar] [CrossRef]
- Nasri, F.; Kongkitimanon, K.; Wittig, A.; Cortés, J.S.; Brinkmann, A.; Nitsche, A.; Schmachtenberg, A.-J.; Renard, B.Y.; Fuchs, S. MpoxRadar: A worldwide MPXV genomic surveillance dashboard. Nucleic Acids Res. 2023, 5, W331–W337. [Google Scholar] [CrossRef] [PubMed]
- Tosta, S.; Moreno, K.; Schuab, G.; Fonseca, V.; Segovia, F.M.C.; Kashima, S.; Elias, M.C.; Sampaio, S.C.; Ciccozzi, M.; Alcantara, L.C.J.; et al. Global SARS-CoV-2 genomic surveillance: What we have learned (so far). Infect. Genet. Evol. 2023, 108, 105–405. [Google Scholar] [CrossRef] [PubMed]
- Kraemer, M.U.G.; Tegally, H.; Pigott, D.M.; Dasgupta, A.; Sheldon, J.; Wilkinson, E.; Schultheiss, M.; Han, A.; Oglia, M.; Marks, S.; et al. Tracking the 2022 monkeypox outbreak with epidemiological data in real-time. Lancet Infect. Dis. 2022, 22, 941–942. [Google Scholar] [CrossRef] [PubMed]
- WHO. Genomic Surveillance. Available online: https://www.who.int/initiatives/genomic-surveillance-strategy (accessed on 19 July 2023).
STAGE | DURATION | CHARACTERISTICS |
---|---|---|
ENANTHEM | 0–1 day | The first lesions appear on the tongue and in the mouth. |
MACULES | 1−2 days | A macular rash appears after the enanthem and spreads from the face to the arms, legs, hands, and feet, including the palms and soles. Within 24 h, the rash usually disseminates and spreads. |
PAPULES | 1−2 days | On the third day, the rash transforms from macular to papular. |
VESICLES | 1−2 days | By the fourth to fifth day, lesions can progress to vesicular. |
PUSTULES | 5−7 day | By day six or seven, pustules form a central depression. After 5–7 days, pustules crust. |
SCABS | 7−14 days | Pustules crust over by the end of the second week and scabs persist for approximately 7 days before naturally detaching. |
DETECTION METHOD | DETAILS/REQUIREMENTS | ADVANTAGES | DISADVANTAGE | APPLICATION |
---|---|---|---|---|
REAL-TIME PCR |
|
|
|
|
MULTIPLEX REALTIME PCR ASSAY |
|
|
|
|
PAN-ORTHOPOXVIRUS ASSAY |
|
|
|
|
LAMP |
|
|
|
|
RPA |
|
|
|
|
GENEXPERT |
|
|
|
|
IMMUNOHISTOCHEMISTRY |
|
|
|
|
CELL CULTURE |
|
|
|
|
ELISA |
|
|
|
|
RAPID ANTIGENIC ASSAY |
|
|
|
|
GENOME SEQUENCING |
| precise strain identification and outbreak tracking, but it requires specialized laboratory infrastructure, expertise, and time, cost |
|
|
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giovanetti, M.; Cella, E.; Moretti, S.; Scarpa, F.; Ciccozzi, A.; Slavov, S.N.; Benedetti, F.; Zella, D.; Ceccarelli, G.; Ciccozzi, M.; et al. Monitoring Monkeypox: Safeguarding Global Health through Rapid Response and Global Surveillance. Pathogens 2023, 12, 1153. https://doi.org/10.3390/pathogens12091153
Giovanetti M, Cella E, Moretti S, Scarpa F, Ciccozzi A, Slavov SN, Benedetti F, Zella D, Ceccarelli G, Ciccozzi M, et al. Monitoring Monkeypox: Safeguarding Global Health through Rapid Response and Global Surveillance. Pathogens. 2023; 12(9):1153. https://doi.org/10.3390/pathogens12091153
Chicago/Turabian StyleGiovanetti, Marta, Eleonora Cella, Sonia Moretti, Fabio Scarpa, Alessandra Ciccozzi, Svetoslav Nanev Slavov, Francesca Benedetti, Davide Zella, Giancarlo Ceccarelli, Massimo Ciccozzi, and et al. 2023. "Monitoring Monkeypox: Safeguarding Global Health through Rapid Response and Global Surveillance" Pathogens 12, no. 9: 1153. https://doi.org/10.3390/pathogens12091153