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Volume 22, Number 1—January 2016

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Objective Determination of End of MERS Outbreak, South Korea, 2015

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EID Nishiura H, Miyamatsu Y, Mizumoto K. Objective Determination of End of MERS Outbreak, South Korea, 2015. Emerg Infect Dis. 2016;22(1):146-148. https://dx.doi.org/10.3201/eid2201.151383
AMA Nishiura H, Miyamatsu Y, Mizumoto K. Objective Determination of End of MERS Outbreak, South Korea, 2015. Emerging Infectious Diseases. 2016;22(1):146-148. doi:10.3201/eid2201.151383.
APA Nishiura, H., Miyamatsu, Y., & Mizumoto, K. (2016). Objective Determination of End of MERS Outbreak, South Korea, 2015. Emerging Infectious Diseases, 22(1), 146-148. https://dx.doi.org/10.3201/eid2201.151383.

To the Editor: After not finding any additional cases of Middle East respiratory syndrome (MERS) for several weeks in South Korea, in July 2015, the South Korean government and the World Health Organization (WHO) discussed the appropriate time to declare the end of the outbreak in July 2015 (1). This declaration would enable allocation of human resources to healthcare facilities to return to normal and would help restore international travel to the country. A widely acknowledged criteria of WHO to determine the end of an epidemic has been twice the length of the incubation period since the most recently diagnosed case (2). For MERS, the longest incubation period is 14 days. Thus, adopting 28 days as the waiting period, and counting days from diagnosis of the most recent case on July 4, 2015, the earliest date the South Korean government could have declared the end of outbreak was August 2 if it adhered to WHO criteria (1). However, to emphasize safety to the nation and to international travelers at an earlier time, the South Korean government originally decided to announce the end of the MERS outbreak on July 27, the date the last quarantined MERS patient was released from movement restriction. Because we are concerned about the validity of strict adherence to the WHO criteria, we objectively calculated the probability of observing additional cases at a given time and compared that probability with the WHO criteria.

To clearly define the end of the outbreak, we excluded reintroduction of imported cases and cases of MERS coronavirus infection resulting from a zoonotic reservoir. We defined the end of the outbreak as the end of continued chains of transmission. The probability of observing additional cases was derived by using the serial interval; that is, the time from illness onset in the primary case-patient to illness onset in a secondary case-patient, and the transmissibility of MERS (Technical Appendix). Both of these epidemiologic variables were estimated by using case data in South Korea (3,4). As practiced in the determination of the length of quarantine (5), the end of outbreak can be declared if that probability is <5%, a threshold value.

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Thumbnail of Estimated probability of observing additional cases of Middle East respiratory syndrome coronavirus infection, South Korea, 2015. A) Estimated probability of observing additional cases on each calendar date, given that no illness onset has been observed by the specified date. Circles represent posterior median values; whiskers extend to upper and lower 95% credible intervals. Horizontal dashed line represents 5%, a threshold level. Vertical line indicates August 2, 2015, on which th

Figure. Estimated probability of observing additional cases of Middle East respiratory syndrome coronavirus infection, South Korea, 2015. A) Estimated probability of observing additional cases on each calendar date, given that no illness...

Our analysis showed that the first date on which the posterior median probability decreased to <5% was July 21 (Figure, panel A). The first date on which the posterior median decreased to 1% was July 23. Compared with August 2 as calculated from the WHO criteria, the end of the outbreak could have been declared 11 and 9 days earlier, respectively. Because the choice of 5% or 1% as the threshold probability is arbitrary (as practiced in determining the p value in any hypothesis testing) and because of the need to account for parameter uncertainties, we also measured the sensitivity of the first date on which the South Korean government could declare the end of the outbreak to a variety of threshold values (Figure, panel B). Examination of the probability of observing additional cases in the range of 0.5% to 10% indicated the end of the outbreak could have been declared from July 21 to July 24 (i.e., 9–12 days earlier than August 2).

Our proposed method does not account for missing undiagnosed or mild cases, and underdiagnosis would considerably extend the time to declare the end of an outbreak (and thus the proposed method is not directly applicable to, for example, Ebola virus disease in West Africa, for which we are currently developing an alternative method). All possible contact with diagnosed case-patients in the late phase of the MERS outbreak in South Korea were traced (6,7); thus, we believe it was appropriate to ignore ascertainment bias in this specific setting. Although our proposed approach is simplistic, adopting the WHO criteria could have added >1 week to the elevated state of tension, and the use of the incubation period distribution would be fully supported only when the exact times of infection were known for exposed potential contacts. Although it is a posteriori reasoning, the original decision made by the South Korean government at an earlier date was ironically supported by our proposed method. Rather than adopting the use of “twice” and the “incubation period,” which has not been theoretically justified, an objective decision of the end of an outbreak should explicitly rest on the risk of observing at least 1 more case on or after a specified date.

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Acknowledgment

H.N. received funding support from the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) grant nos. 26670308 and 26700028, Japan Agency for Medical Research and Development, the Japan Science and Technology Agency (JST) Core Research for Evolutional Science and Technology (CREST) program and Research Institute of Science and Technology for Society (RISTEX) program for Science of Science, Technology and Innovation Policy.

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Hiroshi NishiuraComments to Author , Yuichiro Miyamatsu, and Kenji Mizumoto

Author affiliations: The University of Tokyo, Tokyo, Japan (H. Nishiura, Y. Miyamatsu, Kenji Mizumoto); Japan Science and Technology Agency, Kawaguchi Saitama, Japan (H. Nishiura, Y. Miyamatsu, K. Mizumoto)

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References

  1. The Chosunilbo. Official end to MERS outbreak expected next month [cited 2015 Jul 18]. http://english.chosun.com/site/data/html_dir/2015/07/13/2015071301669.html
  2. World Health Organization. Criteria for declaring the end of the Ebola outbreak in Guinea, Liberia or Sierra Leone [cited 2015 Jul 18]. http://www.who.int/csr/disease/ebola/declaration-ebola-end/en/
  3. Cowling  BJ, Park  M, Fang  VJ, Wu  P, Leung  GM, Wu  JT. Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015. Euro Surveill. 2015;20:713 . DOIPubMed
  4. Nishiura  H, Miyamatsu  Y, Chowell  G, Saitoh  M. Assessing the risk of observing multiple generations of Middle East respiratory syndrome (MERS) cases given an imported case. Euro Surveill. 2015;20:21181 . DOIPubMed
  5. Nishiura  H. Determination of the appropriate quarantine period following smallpox exposure: an objective approach using the incubation period distribution. Int J Hyg Environ Health. 2009;212:97104. DOIPubMed
  6. Mizumoto  K, Endo  A, Chowell  G, Miyamatsu  Y, Saitoh  M, Nishiura  H. Real-time characterization of risks of death associated with the Middle East respiratory syndrome (MERS) in the Republic of Korea, 2015. BMC Med. 2015;13:228. DOIPubMed
  7. Mizumoto  K, Saitoh  M, Chowell  G, Miyamatsu  Y, Nishiura  H. Estimating the risk of Middle East respiratory syndrome (MERS) death during the course of the outbreak in the Republic of Korea, 2015. Int J Infect Dis. 2015;39:79. DOIPubMed

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DOI: 10.3201/eid2201.151383

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Table of Contents – Volume 22, Number 1—January 2016

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Hiroshi Nishiura, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan


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