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Surveillance Open Access
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Abstract

Background

Mpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.

Aim

To elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.

Methods

Whole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.

Results

Of 242 detected mpox cases, 99% were males (median age: 35 years; range: 15–60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.

Conclusion

We provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.

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/content/10.2807/1560-7917.ES.2024.29.16.2300505
2024-04-18
2024-11-22
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2024.29.16.2300505
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References

  1. Xiang Y, White A. Monkeypox virus emerges from the shadow of its more infamous cousin: family biology matters. Emerg Microbes Infect. 2022;11(1):1768-77.  https://doi.org/10.1080/22221751.2022.2095309  PMID: 35751396 
  2. World Health Organization (WHO). Mpox (monkeypox) - Fact sheet 2023. Geneva: WHO; 2023. [Accessed: 18 Apr 2023]. Available from: https://www.who.int/news-room/fact-sheets/detail/monkeypox
  3. Quarleri J, Delpino MV, Galvan V. Monkeypox: considerations for the understanding and containment of the current outbreak in non-endemic countries. Geroscience. 2022;44(4):2095-103.  https://doi.org/10.1007/s11357-022-00611-6  PMID: 35726117 
  4. Gigante CM, Korber B, Seabolt MH, Wilkins K, Davidson W, Rao AK, et al. Multiple lineages of monkeypox virus detected in the United States, 2021-2022. Science. 2022;378(6619):560-5.  https://doi.org/10.1126/science.add4153  PMID: 36264825 
  5. Bragazzi NL, Kong JD, Mahroum N, Tsigalou C, Khamisy-Farah R, Converti M, et al. Epidemiological trends and clinical features of the ongoing monkeypox epidemic: A preliminary pooled data analysis and literature review. J Med Virol. 2023;95(1):e27931.  https://doi.org/10.1002/jmv.27931  PMID: 35692117 
  6. Saxena SK, Ansari S, Maurya VK, Kumar S, Jain A, Paweska JT, et al. Re-emerging human monkeypox: A major public-health debacle. J Med Virol. 2023;95(1):e27902.  https://doi.org/10.1002/jmv.27902  PMID: 35652133 
  7. Sun YQ, Chen JJ, Liu MC, Zhang YY, Wang T, Che TL, et al. Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study. Global Health. 2023;19(1):58.  https://doi.org/10.1186/s12992-023-00959-0  PMID: 37592305 
  8. Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, et al. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis. 2022;16(2):e0010141.  https://doi.org/10.1371/journal.pntd.0010141  PMID: 35148313 
  9. Americo JL, Earl PL, Moss B. Virulence differences of mpox (monkeypox) virus clades I, IIa, and IIb.1 in a small animal model. Proc Natl Acad Sci USA. 2023;120(8):e2220415120.  https://doi.org/10.1073/pnas.2220415120  PMID: 36787354 
  10. Reda A, Hemmeda L, Brakat AM, Sah R, El-Qushayri AE. The clinical manifestations and severity of the 2022 monkeypox outbreak among 4080 patients. Travel Med Infect Dis. 2022;50:102456.  https://doi.org/10.1016/j.tmaid.2022.102456  PMID: 36116767 
  11. World Health Organization (WHO). Multi-country outbreak of mpox. External Situation Report #31 – 22 December 2023. Geneva: WHO; 2023. Available from: https://www.who.int/publications/m/item/multi-country-outbreak-of-mpox--external-situation-report-31---22-december-2023
  12. Mizushima D, Shintani Y, Takano M, Shiojiri D, Ando N, Aoki T, et al. Prevalence of asymptomatic mpox among men who have sex with men, Japan, January-March 2023. Emerg Infect Dis. 2023;29(9):1872-6.  https://doi.org/10.3201/eid2909.230541  PMID: 37506678 
  13. Dillon C, Igoe D, O'Donnell K, Robinson E. Epi Insight. Epidemiological characteristics of confirmed mpox cases in Ireland; May 2022 to February 2023. Republic of Ireland: HSE Health Protection Surveillance Centre; 2023. Available from: https://ndsc.newsweaver.ie/4otaa688p3/18ojfxozmu1?lang=en&a=1&p=62869572&t=31302978
  14. Li Y, Zhao H, Wilkins K, Hughes C, Damon IK. Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA. J Virol Methods. 2010;169(1):223-7.  https://doi.org/10.1016/j.jviromet.2010.07.012  PMID: 20643162 
  15. Schroeder K, Nitsche A. Multicolour, multiplex real-time PCR assay for the detection of human-pathogenic poxviruses. Mol Cell Probes. 2010;24(2):110-3.  https://doi.org/10.1016/j.mcp.2009.10.008  PMID: 19879351 
  16. Garrigues JM, Hemarajata P, Lucero B, Alarcón J, Ransohoff H, Marutani AN, et al. Identification of human monkeypox virus genome deletions that impact diagnostic assays. J Clin Microbiol. 2022;60(12):e0165522.  https://doi.org/10.1128/jcm.01655-22  PMID: 36445125 
  17. Welkers M, Jonges M, Ouden AVD. Monkeypox virus whole genome sequencing using combination of NextGenPCR and Oxford Nanopore V.1 2022. Available from: https://protocols.io/view/monkeypox-virus-whole-genome-sequencing-using-comb-ccc7sszn
  18. Katoh K, Rozewicki J, Yamada KD. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform. 2019;20(4):1160-6.  https://doi.org/10.1093/bib/bbx108  PMID: 28968734 
  19. Bouckaert R, Vaughan TG, Barido-Sottani J, Duchêne S, Fourment M, Gavryushkina A, et al. BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis. PLOS Comput Biol. 2019;15(4):e1006650.  https://doi.org/10.1371/journal.pcbi.1006650  PMID: 30958812 
  20. Edler D, Klein J, Antonelli A, Silvestro D. raxmlGUI 2.0: A graphical interface and toolkit for phylogenetic analyses using RAxML. Methods Ecol Evol. 2021;12(2):373-7.  https://doi.org/10.1111/2041-210X.13512 
  21. Douglas J, Zhang R, Bouckaert R. Adaptive dating and fast proposals: Revisiting the phylogenetic relaxed clock model. PLOS Comput Biol. 2021;17(2):e1008322.  https://doi.org/10.1371/journal.pcbi.1008322  PMID: 33529184 
  22. Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 2017;22(13):30494.  https://doi.org/10.2807/1560-7917.ES.2017.22.13.30494  PMID: 28382917 
  23. Campbell F, Didelot X, Fitzjohn R, Ferguson N, Cori A, Jombart T. outbreaker2: a modular platform for outbreak reconstruction. BMC Bioinformatics. 2018;19(S11) Suppl 11;363.  https://doi.org/10.1186/s12859-018-2330-z  PMID: 30343663 
  24. Sijmons S, Thys K, Mbong Ngwese M, Van Damme E, Dvorak J, Van Loock M, et al. High-throughput analysis of human cytomegalovirus genome diversity highlights the widespread occurrence of gene-disrupting mutations and pervasive recombination. J Virol. 2015;89(15):7673-95.  https://doi.org/10.1128/JVI.00578-15  PMID: 25972543 
  25. Forni D, Cagliani R, Pozzoli U, Sironi M. An APOBEC3 mutational signature in the genomes of human-infecting orthopoxviruses. MSphere. 2023;8(2):e0006223.  https://doi.org/10.1128/msphere.00062-23  PMID: 36920219 
  26. Smith TG, Gigante CM, Wynn NT, Matheny A, Davidson W, Yang Y, et al. Tecovirimat resistance in mpox patients, United States, 2022-2023. Emerg Infect Dis. 2023;29(12):2426-32.  https://doi.org/10.3201/eid2912.231146  PMID: 37856204 
  27. Bojkova D, Bechtel M, Rothenburger T, Steinhorst K, Zöller N, Kippenberger S, et al. Drug sensitivity of currently circulating mpox viruses. N Engl J Med. 2023;388(3):279-81.  https://doi.org/10.1056/NEJMc2212136  PMID: 36577096 
  28. Babkin IV, Babkina IN, Tikunova NV. An update of orthopoxvirus molecular evolution. Viruses. 2022;14(2):388.  https://doi.org/10.3390/v14020388  PMID: 35215981 
  29. Isidro J, Borges V, Pinto M, Sobral D, Santos JD, Nunes A, et al. Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus. Nat Med. 2022;28(8):1569-72.  https://doi.org/10.1038/s41591-022-01907-y  PMID: 35750157 
  30. Borges V, Duque MP, Martins JV, Vasconcelos P, Ferreira R, Sobral D, et al. Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal. Nat Med. 2023;29(10):2509-17.  https://doi.org/10.1038/s41591-023-02542-x  PMID: 37696933 
  31. Yang S, Guo X, Zhao Z, Abudunaibi B, Zhao Y, Rui J, et al. Possibility of mpox viral transmission and control from high-risk to the general population: a modeling study. BMC Infect Dis. 2023;23(1):119.  https://doi.org/10.1186/s12879-023-08083-5  PMID: 36829116 
  32. Murphy F. Mpox: China’s health authorities fight surge in cases of unknown origin. BMJ. 2023;382:1939.  https://doi.org/10.1136/bmj.p1939  PMID: 37607756 
  33. McQuiston JH, Braden CR, Bowen MD, McCollum AM, McDonald R, Carnes N, et al. The CDC domestic mpox response - United States, 2022-2023. MMWR Morb Mortal Wkly Rep. 2023;72(20):547-52.  https://doi.org/10.15585/mmwr.mm7220a2  PMID: 37200231 
  34. Centers for Disease Control and Prevention. Mpox caused by human-to-human transmission of monkeypox virus with geographic spread in the Democratic Republic of the Congo. Atlanta: CDC; 2023. Available from: https://emergency.cdc.gov/han/2023/han00501.asp
  35. Yadav P, Devasurmutt Y, Tatu U. Phylogenomic and structural analysis of the monkeypox virus shows evolution towards increased stability. Viruses. 2022;15(1):127.  https://doi.org/10.3390/v15010127  PMID: 36680170 
  36. Luna N, Ramírez AL, Muñoz M, Ballesteros N, Patiño LH, Castañeda SA, et al. Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: Emergence of a novel viral lineage? Travel Med Infect Dis. 2022;49:102402.  https://doi.org/10.1016/j.tmaid.2022.102402  PMID: 35840078 
  37. Mourier T, Sadykov M, Carr MJ, Gonzalez G, Hall WW, Pain A. Host-directed editing of the SARS-CoV-2 genome. Biochem Biophys Res Commun. 2021;538:35-9.  https://doi.org/10.1016/j.bbrc.2020.10.092  PMID: 33234239 
  38. Lucey M, Macori G, Mullane N, Sutton-Fitzpatrick U, Gonzalez G, Coughlan S, et al. Whole-genome sequencing to track severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in nosocomial outbreaks. Clin Infect Dis. 2021;72(11):e727-35.  https://doi.org/10.1093/cid/ciaa1433  PMID: 32954414 
  39. Hare D, Gonzalez G, Dean J, McDonnell K, Carr MJ, De Gascun CF. Genomic epidemiological analysis of SARS-CoV-2 household transmission. Access Microbiol. 2021;3(7):000252.  https://doi.org/10.1099/acmi.0.000252  PMID: 34595399 
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