Ann Lab Med.  2023 Mar;43(2):137-144. 10.3343/alm.2023.43.2.137.

Guidelines for the Laboratory Diagnosis of Monkeypox in Korea

• Hong KH
• Kim GJ
• Roh KH
• Lee H
• Park OK
• Kim TS
• Kim JS
• Lee J
• Seong MW
• Kim SY
• Park JS
• Park Y
• Huh HJ
• Ryoo N
• Kim HS
• Sung H
• Yoo CK
• On behalf of the Committee of Management of Laboratory Tests for Infectious Diseases, Korean Society for Laboratory Medicine, and the Bureau of Infectious Disease Diagnosis Control, Korea Disease Control and Prevention Agency

• KMID: 2551690
• DOI: http://doi.org/10.3343/alm.2023.43.2.137

Abstract

While the coronavirus disease 2019 pandemic is ongoing, monkeypox has been rapidly spreading in non-endemic countries since May 2022. Accurate and rapid laboratory tests are essential for identifying and controlling monkeypox. Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have proposed guidelines for diagnosing monkeypox in clinical laboratories in Korea. These guidelines cover the type of tests, selection of specimens, collection of specimens, diagnostic methods, interpretation of test results, and biosafety. Molecular tests are recommended as confirmatory tests. Skin lesion specimens are recommended for testing in the symptomatic stage, and the collection of both blood and oropharyngeal swabs is recommended in the presymptomatic or prodromal stage.

Keyword

Monkeypox; Laboratory diagnosis; PCR; Guidelines; Korea

Reference

1. WHO. Multi-country monkeypox outbreak in non-endemic countries: update. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON388. Updated on May, 2022.

2. Minhaj FS, Ogale YP, Whitehill F, Schultz J, Foote M, Davidson W, et al. 2022; Monkeypox outbreak - nine states, May 2022. MMWR Morb Mortal Wkly Rep. 71:764–9. DOI: 10.15585/mmwr.mm7123e1. PMID: 35679181. PMCID: PMC9181052.

3. Antinori A, Mazzotta V, Vita S, Carletti F, Tacconi D, Lapini LE, et al. 2022; Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022. Euro Surveill. 27:2200421. DOI: 10.2807/1560-7917.ES.2022.27.22.2200421. PMID: 35656836. PMCID: PMC9164671.

4. Hammerschlag Y, MacLeod G, Papadakis G, Adan Sanchez A, Druce J, Taiaroa G, et al. 2022; Monkeypox infection presenting as genital rash, Australia, May 2022. Euro Surveill. 27:2200411. DOI: 10.2807/1560-7917.ES.2022.27.22.2200411. PMID: 35656835. PMCID: PMC9164678.

5. Duque MP, Ribeiro S, Martins JV, Casaca P, Leite PP, Tavares M, et al. 2022; Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022. Euro Surveill. 27:2200424. DOI: 10.2807/1560-7917.ES.2022.27.22.2200424. PMID: 35656830. PMCID: PMC9164676.

6. Vivancos R, Anderson C, Blomquist P, Balasegaram S, Bell A, Bishop L, et al. 2022; Community transmission of monkeypox in the United Kingdom, April to May 2022. Euro Surveill. 27:2200422. DOI: 10.2807/1560-7917.ES.2022.27.22.2200422. PMID: 35656834. PMCID: PMC9164677.

7. Mathieu E, Spooner F, Dattani S, Ritchie H, Roser M. Monkeypox. https://ourworldindata.org/monkeypox. Updated on Jun, 2022.

8. WHO. Surveillance, case investigation and contact tracing for monkeypox: interim guidance, 24 June 2022. https://www.who.int/publications/i/item/WHO-MPX-Surveillance-2022.2. Updated on Jun, 2022.

9. KDCA. Guidelines on response to monkeypox. 1st ed. (for local government). https://www.kdca.go.kr/board/board.es?mid=a20507020000&bid=0019&act=view&list_no=719914. Updated on Jun, 2022.

10. Dubois ME, Slifka MK. 2008; Retrospective analysis of monkeypox infection. Emerg Infect Dis. 14:592–9. DOI: 10.3201/eid1404.071044. PMID: 18394277. PMCID: PMC2570942.

11. Li Y, Meyer H, Zhao H, Damon IK. 2010; GC content-based pan-pox universal PCR assays for poxvirus detection. J Clin Microbiol. 48:268–76. DOI: 10.1128/JCM.01697-09. PMID: 19906902. PMCID: PMC2812294.

12. Kulesh DA, Loveless BM, Norwood D, Garrison J, Whitehouse CA, Hartmann C, et al. 2004; Monkeypox virus detection in rodents using real-time 3 -minor groove binder TaqMan assays on the Roche LightCycler. Lab Invest. 84:1200–8. DOI: 10.1038/labinvest.3700143. PMID: 15208646.

13. McCollum AM, Damon IK. 2014; Human monkeypox. Clin Infect Dis. 58:260–7. DOI: 10.1093/cid/cit703. PMID: 24158414.

14. Bížová B, Veselý D, Trojánek M, Rob F. 2022; Coinfection of syphilis and monkeypox in HIV positive man in Prague, Czech Republic. Travel Med Infect Dis. 49:102368. DOI: 10.1016/j.tmaid.2022.102368. PMID: 35661824. PMCID: PMC9533838.

15. Hughes CM, Liu L, Davidson WB, Radford KW, Wilkins K, Monroe B, et al. 2020; A tale of two viruses: coinfections of monkeypox and varicella zoster virus in the Democratic Republic of Congo. Am J Trop Med Hyg. 104:604–11. DOI: 10.4269/ajtmh.20-0589. PMID: 33289470. PMCID: PMC7866336.

16. Hoff NA, Morier DS, Kisalu NK, Johnston SC, Doshi RH, Hensley LE, et al. 2017; Varicella coinfection in patients with active monkeypox in the Democratic Republic of the Congo. Ecohealth. 14:564–74. DOI: 10.1007/s10393-017-1266-5. PMID: 28894977.

17. Karem KL, Reynolds M, Braden Z, Lou G, Bernard N, Patton J, et al. 2005; Characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak. Clin Diagn Lab Immunol. 12:867–72. DOI: 10.1128/CDLI.12.7.867-872.2005. PMID: 16002637. PMCID: PMC1182207.

18. Sejvar JJ, Chowdary Y, Schomogyi M, Stevens J, Patel J, Karem K, et al. 2004; Human monkeypox infection: a family cluster in the midwestern United States. J Infect Dis. 190:1833–40. DOI: 10.1086/425039. PMID: 15499541.

19. Hammarlund E, Lewis MW, Carter SV, Amanna I, Hansen SG, Strelow LI, et al. 2005; Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat Med. 11:1005–11. DOI: 10.1038/nm1273. PMID: 16086024.

20. WHO. Laboratory testing for the monkeypox virus: interim guidance. https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1. Updated on May, 2022.

21. UK Health Security Agency. De-isolation and discharge of monkeypox-infected patients: interim guidance. https://www.gov.uk/guidance/de-isolation-and-discharge-of-monkeypox-infected-patients-interim-guidance. Updated on May, 2022.

22. Li Y, Olson VA, Laue T, Laker MT, Damon IK. 2006; Detection of monkeypox virus with real-time PCR assays. J Clin Virol. 36:194–203. DOI: 10.1016/j.jcv.2006.03.012. PMID: 16731033.

23. Shchelkunov SN, Gavrilova EV, Babkin IV. 2005; Multiplex PCR detection and species differentiation of orthopoxviruses pathogenic to humans. Mol Cell Probes. 19:1–8. DOI: 10.1016/j.mcp.2004.07.004. PMID: 15652214. PMCID: PMC9533918.

24. Maksyutov RA, Gavrilova EV, Shchelkunov SN. 2016; Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay. J Virol Methods. 236:215–20. DOI: 10.1016/j.jviromet.2016.07.024. PMID: 27477914.

25. Li Y, Zhao H, Wilkins K, Hughes C, Damon IK. 2010; Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA. J Virol Methods. 169:223–7. DOI: 10.1016/j.jviromet.2010.07.012. PMID: 20643162.

26. Sklenovská N. Malik YS, Singh RK, editors. 2020. Monkeypox virus. Animal-origin viral zoonoses. Springer;p. 39–68.

27. Centers for Disease Control and Prevention. Monkeypox. Preparation and collection of specimens. https://www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.html. Updated on Jun, 2022.

28. Hong KH, Lee SW, Kim TS, Huh HJ, Lee J, Kim SY, et al. 2020; Guidelines for laboratory diagnosis of coronavirus disease 2019 (COVID-19) in Korea. Ann Lab Med. 40:351–60. DOI: 10.3343/alm.2020.40.5.351. PMID: 32237288. PMCID: PMC7169629.

29. Adler H, Gould S, Hine P, Snell LB, Wong W, Houlihan CF, et al. 2022; Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 22:1153–62. DOI: 10.1016/S1473-3099(22)00228-6.

30. Peiró-Mestres A, Fuertes I, Camprubí-Ferrer D, Marcos MÁ, Vilella A, Navarro M, et al. Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022. Euro Surveill. 2022; Jul. 27(28):2200503. DOI: 10.2807/1560-7917.ES.2022.27.28.2200503. PMID: 35837964. PMCID: PMC9284919.

31. Tarín-Vicente EJ, Alemany A, Agud-Dios M, Ubals M, Suñer C, Antón A, et al. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022; Aug. 27. 400(10353):661–669. DOI: 10.1016/S0140-6736(22)01436-2.

32. Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. https://www.cdc.gov/poxvirus/monkeypox/clinicians/infection-control-healthcare.html. Updated on May, 2022.

33. Miller JM, Miller SA. A guide to specimen management in clinical microbiology. 3rd ed. Hoboken: John Wiley & Sons;2017. DOI: 10.1128/9781555819620.

34. WHO. Guidance on regulations for the transport of infectious substances 2021-2022. https://www.who.int/publications/i/item/9789240019720. Updated on Feb, 2021.

35. KDCA. Guidance for laboratory biosafety related to monkeypox. 1st ed. (Korean). https://www.kdca.go.kr/board/board.es?mid=a20302111500&bid=0065&act=view&list_no=719904. Updated on Jun, 2022.

36. CLSI. 2015. Molecular diagnostic methods for infectious diseases. 3rd ed. CLSI MM03. Clinical and Laboratory Standards Institute;Wayne, PA:

37. Meechan PJ, Potts J, editors. Biosafety in microbiological and biomedical laboratories (BMBL). 6th ed. United States Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institutes of Health, 2020. https://www.cdc.gov/labs/BMBL.html. Updated on Nov, 2021.

38. Centers for Disease Control and Prevention. Monkeypox. Laboratory procedures and biosafety guidelines. https://www.cdc.gov/poxvirus/monkeypox/lab-personnel/lab-procedures.html. Updated on Nov, 2021.

39. WHO. Vaccines and immunization for monkeypox: interim guidance, 14 June 2022. https://www.who.int/publications/i/item/who-mpx-immunization-2022.1. Updated on Jun, 2022.

40. Rao AK, Petersen BW, Whitehill F, Razeq JH, Isaacs SN, Merchlinsky MJ, et al. 2022; Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 71:734–42. DOI: 10.15585/mmwr.mm7122e1. PMID: 35653347. PMCID: PMC9169520.

41. UK Health Security Agency. Guidance. Monkeypox vaccination recommendations. Recommendations for the use of pre and post-exposure vaccination during a monkeypox incident. https://www.gov.uk/government/publications/monkeypox-vaccination. Updated on Jun, 2022.