DOI QR코드

DOI QR Code

Molecular Detection and Epidemiology of Etiologic Agents among Children with Acute Gastroenteritis at a Secondary Hospital from 2015 to 2018

2015년부터 2018년까지 일개 이차병원에서 동정된 소아 급성 위장염 원인 병원체의 분자진단과 역학의 임상적 연구

  • Kim, Young Sang (Department of Pediatrics, Sanggye Paik Hospital, Inje University School of Medicine) ;
  • Chung, Ju Young (Department of Pediatrics, Sanggye Paik Hospital, Inje University School of Medicine)
  • 김영상 (인제대학교 상계백병원 소아청소년과) ;
  • 정주영 (인제대학교 상계백병원 소아청소년과)
  • Received : 2020.03.09
  • Accepted : 2020.07.05
  • Published : 2020.08.25

Abstract

Purpose: The multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) test developed recently can help detect enteric pathogens of acute gastroenteritis (AGE). This study aimed to investigate the epidemiology of pathogens in children with AGE using the multiplex RT-PCR. Methods: From May 2015 to June 2018, multiplex RT-PCR tests were performed to identify pathogens in the feces of pediatric patients diagnosed with AGE at a secondary hospital in Seoul, Korea. Results: Of the 1,366 stool samples examined for viral pathogens, 483 (35.3%) tested positive for ≥1 pathogen. Group A rotavirus (RV) was detected in 106 cases (7.8%). The positivity rate increased annually from 3.0% (8/263) to 16.7% (48/288) and surged in 2018 (P<0.001). Norovirus (NoV) GII was the most common viral pathogen (263/1,366, 19.3%), and the positivity rate did not increase during the 3 years. Of the 304 stool samples tested for bacterial pathogens, Campylobacter spp. was the most common bacterial pathogen (32/304, 10.5%), followed by Clostridium difficile (22/304, 7.2%) and Salmonella spp. (17/304, 5.6%). The positivity rate of these bacterial pathogens did not change significantly during the study period. Conclusions: NoV GII is the main pathogen in childhood AGE since the introduction of RV vaccine, yet the number of rotavirus-infected patients increased during our study, especially in 2018. Therefore, further research is needed including the possibility of emergence of novel RV strains. Campylobacter spp. is the predominant cause of bacterial AGE in children. For proper treatment, the clinical characteristics of the bacteria should be taken into consideration, and continuous monitoring is necessary.

목적: 급성 위장염의 대부분의 경우 원인 병원체가 확인되지 않는다. 최근 들어 발달한 multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) 검사는 장염 병원체 검출에 도움을 줄 수 있다. 이 연구는 multiplex RT-PCR을 이용해, 소아 장염환자에서 병원체의 역학을 조사하고자 하였다. 방법: 2015년 5월부터 2018년 6월까지 대한민국 서울의 2차병원에서 급성 위장염으로 진단받은 소아 환자의 대변에서 병원체를 확인하기 위해 multiplex RT-PCR 검사를 시행하였다. 결과: 바이러스 병원체에 대한 1,366개의 대변 검체 중, 483개(35.3%)에서 1개 이상의 병원체가 분리되었다. A군 로타바이러스는 106건(7.8%)에서 확인되었으며, 양성률은 3.0% (8/263)에서 16.7% (48/288)까지 매년 증가했다(P<0.001). 노로바이러스 GII는 가장 흔한 바이러스성 병원체였고(263/1366, 19.3%), 3년간 양성률은 증가하지 않았다. 세균성 병원체에 대한 304개의 대변 검체 중 캄필로박터(32/304, 10.5%)는 가장 흔한 세균성 병원체였으며, 그 다음으로 Clostridium difficile (toxin B) (22/304, 7.2%), 살모넬라균(17/304, 5.6%)이었다. 이 균들의 양성률은 연구기간 동안 증가하지 않았다. 결론: 로타바이러스 백신 도입 이후 노로바이러스 GII가 소아 장염에서 주요한 병원체였지만, 연구기간 동안 로타바이러스 감염 환자가 증가했고, 특히 2018년에는 급증했다. 따라서 새로운 로타바이러스 균주의 등장 가능성을 포함한 추가 연구가 필요하다. 캄필로박터는 소아 세균성 장염의 주요 원인이며, 적절한 치료를 위해 이 균의 임상적 특성을 고려하고 지속적 감시가 필요하겠다.

Keywords

References

  1. Parashar UD, Bresee JS, Gentsch JR, Glass RI. Rotavirus. Emerg Infect Dis 1998;4:561-70. https://doi.org/10.3201/eid0404.980406
  2. Ma SH. Acute infectious diarrhea in pediatirc patients. Korean J Pediatr 2005;48:235-50.
  3. Motayo BO, Adeniji JA, Faneye AO. Species A rotavirus (RVA) isolated from Sewage in Nigeria, 2014: close genetic relatedness of partial G, P, and NSP4 gene sequences encoding G1 with cogent genes of other Asian and African rotaviruses. J Pathog 2018;2018:8425621. https://doi.org/10.1155/2018/8425621
  4. Saif LJ. Nongroup A rotaviruses. In: Saif LJ, Theil KW, editors. Viral diarrheas of man and animals. Boca Raton: CRC Press, 1990:73-95.
  5. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD; for the World Health Organization-Coordinated Global Rotavirus Surveillance Network. Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000-2013. Clin Infect Dis 2016;62:S96-105. https://doi.org/10.1093/cid/civ1013
  6. Park SE, Kim KH, Kim JH, Shin SH, Oh SH, Lee HJ, et al. Rotavirus vaccine. Korean J Pediatr 2007;50:803-10.
  7. Glass RI, Parashar UD, Bresee JS, Turcios R, Fischer TK, Widdowson MA, et al. Rotavirus vaccines: current prospects and future challenges. Lancet 2006;368:323-32. https://doi.org/10.1016/S0140-6736(06)68815-6
  8. Leshem E, Tate JE, Steiner CA, Curns AT, Lopman BA, Parashar UD. Acute gastroenteritis hospitalizations among US children following implementation of the rotavirus vaccine. JAMA 2015;313:2282-4. https://doi.org/10.1001/jama.2015.5571
  9. Shah MP, Dahl RM, Parashar UD, Lopman BA. Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States. PLoS One 2018;13:e0191429. https://doi.org/10.1371/journal.pone.0191429
  10. Sohn TY, Lee CJ, Kim YJ, Kang MJ, Kim SH, Lee SY, et al. Clinical and epidemiological study of 1,165 hospitalized cases of rotaviral gastroenteritis before and after the introduction of rotavirus vaccine, 2006-2013. Korean J Pediatr Infect Dis 2014;21:174-80. https://doi.org/10.14776/kjpid.2014.21.3.174
  11. Park DK, Chung JY. The changes in the outbreak of rotavirus gastroenteritis in children after introduction of rotavirus vaccines: a retrospective study at a tertiary hospital. Korean J Pediatr Infect Dis 2014;21:167-73. https://doi.org/10.14776/kjpid.2014.21.3.167
  12. Yoon JM, Han TH, Yoon SW, Kim YJ, Oh SH. Changes in the occurrence of rotavirus gastroenteritis before and after the introduction of rotavirus vaccine among hospitalized pediatric patients and estimates of rotavirus vaccine effectiveness. Pediatr Infect Vaccine 2018;25:26-34. https://doi.org/10.14776/piv.2018.25.1.26
  13. Jin HI, Lee YM, Choi YJ, Jeong SJ. Recent viral pathogen in acute gastroenteritis: a retrospective study at a tertiary hospital for 1 year. Korean J Pediatr 2016;59:120-5. https://doi.org/10.3345/kjp.2016.59.3.120
  14. Barrett J, Fhogartaigh CN. Bacterial gastroenteritis. Medicine 2017;45:683-9. https://doi.org/10.1016/j.mpmed.2017.08.002
  15. Kim NO, Cha I, Kim JS, Chung GT, Kang YH, Hong S. The prevalence and characteristics of bacteria causing acute diarrhea in Korea, 2012. Ann Clin Microbiol 2013;16:174-81. https://doi.org/10.5145/ACM.2013.16.4.174
  16. Pai H. Acute infectious diarrhea. Korean J Med 2007;73:114-8.
  17. Van Lint P, De Witte E, De Henau H, De Muynck A, Verstraeten L, Van Herendael B, et al. Evaluation of a real-time multiplex PCR for the simultaneous detection of Campylobacter jejuni, Salmonella spp., Shigella spp./EIEC, and Yersinia enterocolitica in fecal samples. Eur J Clin Microbiol Infect Dis 2015;34:535-42. https://doi.org/10.1007/s10096-014-2257-x
  18. Ricke SC, Feye KM, Chaney WE, Shi Z, Pavlidis H, Yang Y. Developments in rapid detection methods for the detection of foodborne Campylobacter in the United States. Front Microbiol 2019;9:3280. https://doi.org/10.3389/fmicb.2018.03280
  19. Thongprachum A, Khamrin P, Maneekarn N, Hayakawa S, Ushijima H. Epidemiology of gastroenteritis viruses in Japan: prevalence, seasonality, and outbreak. J Med Virol 2016;88:551-70. https://doi.org/10.1002/jmv.24387
  20. Nicholson MR, Van Horn GT, Tang YW, Vinje J, Payne DC, Edwards KM, et al. Using multiplex molecular testing to determine the etiology of acute gastroenteritis in children. J Pediatr 2016;176:50-56.e2. https://doi.org/10.1016/j.jpeds.2016.05.068
  21. Lu J, Sun L, Fang L, Yang F, Mo Y, Lao J, et al. Gastroenteritis outbreaks caused by norovirus GII.17, Guangdong province, China, 2014-2015. Emerg Infect Dis 2015;21:1240-2. https://doi.org/10.3201/eid2107.150226
  22. Chen CJ, Wu FT, Huang YC, Chang WC, Wu HS, Wu CY, et al. Clinical and epidemiologic features of severe viral gastroenteritis in children: a 3-year surveillance, multicentered study in Taiwan with partial rotavirus immunization. Medicine (Baltimore) 2015;94:e1372. https://doi.org/10.1097/MD.0000000000001372
  23. Rohayem J. Norovirus seasonality and the potential impact of climate change. Clin Microbiol Infect 2009;15:524-7. https://doi.org/10.1111/j.1469-0691.2009.02846.x
  24. Kim YE, Song M, Lee J, Seung HJ, Kwon EY, Yu J, et al. Phylogenetic characterization of norovirus strains detected from sporadic gastroenteritis in Seoul during 2014-2016. Gut Pathog 2018;10:36. https://doi.org/10.1186/s13099-018-0263-8
  25. Chan MC, Hu Y, Chen H, Podkolzin AT, Zaytseva EV, Komano J, et al. Global spread of norovirus GII.17 Kawasaki 308, 2014-2016. Emerg Infect Dis 2017;23:1350-4.
  26. Chan MC, Lee N, Hung TN, Kwok K, Cheung K, Tin EK, et al. Rapid emergence and predominance of a broadly recognizing and fast-evolving norovirus GII.17 variant in late 2014. Nat Commun 2015;6:10061. https://doi.org/10.1038/ncomms10061
  27. de Graaf M, van Beek J, Vennema H, Podkolzin AT, Hewitt J, Bucardo F, et al. Emergence of a novel GII.17 norovirus - end of the GII.4 era? Euro Surveill 2015;20:21178.
  28. Fu J, Ai J, Jin M, Jiang C, Zhang J, Shi C, et al. Emergence of a new GII.17 norovirus variant in patients with acute gastroenteritis in Jiangsu, China, September 2014 to March 2015. Euro Surveill 2015;20:21157.
  29. Gao Z, Liu B, Huo D, Yan H, Jia L, Du Y, et al. Increased norovirus activity was associated with a novel norovirus GII.17 variant in Beijing, China during winter 2014-2015. BMC Infect Dis 2015;15:574. https://doi.org/10.1186/s12879-015-1315-z
  30. Han J, Ji L, Shen Y, Wu X, Xu D, Chen L. Emergence and predominance of norovirus GII.17 in Huzhou, China, 2014-2015. Virol J 2015;12:139. https://doi.org/10.1186/s12985-015-0370-9
  31. Lee CC, Feng Y, Chen SY, Tsai CN, Lai MW, Chiu CH. Emerging norovirus GII.17 in Taiwan. Clin Infect Dis 2015;61:1762-4. https://doi.org/10.1093/cid/civ647
  32. Matsushima Y, Ishikawa M, Shimizu T, Komane A, Kasuo S, Shinohara M, et al. Genetic analyses of GII.17 norovirus strains in diarrheal disease outbreaks from December 2014 to March 2015 in Japan reveal a novel polymerase sequence and amino acid substitutions in the capsid region. Euro Surveill 2015;20:21173.
  33. Parra GI, Green KY. Genome of emerging norovirus GII.17, United States, 2014. Emerg Infect Dis 2015;21:1477-9. https://doi.org/10.3201/eid2108.150652
  34. Han TH, Park SH, Chung JY, Hwang ES. Distribution of human rotavirus genotypes in a tertiary hospital, Seoul, Korea during 2009-2013. Pediatr Infect Vaccine 2015;22:81-90. https://doi.org/10.14776/PIV.2015.22.2.81
  35. Thanh HD, Tran VT, Lim I, Kim W. Emergence of human G2P[4] rotaviruses in the post-vaccination era in South Korea: footprints of multiple interspecies re-assortment events. Sci Rep 2018;8:6011. https://doi.org/10.1038/s41598-018-24511-y
  36. Roczo-Farkas S, Kirkwood CD, Cowley D, Barnes GL, Bishop RF, Bogdanovic-Sakran N, et al. The impact of rotavirus vaccines on genotype diversity: a comprehensive analysis of 2 decades of Australian surveillance data. J Infect Dis 2018;218:546-54. https://doi.org/10.1093/infdis/jiy197
  37. Onori M, Coltella L, Mancinelli L, Argentieri M, Menichella D, Villani A, et al. Evaluation of a multiplex PCR assay for simultaneous detection of bacterial and viral enteropathogens in stool samples of paediatric patients. Diagn Microbiol Infect Dis 2014;79:149-54. https://doi.org/10.1016/j.diagmicrobio.2014.02.004
  38. Kim SY, Kim HJ, Shin EH, Eun BW, Ahn YM, Song MO. Etiology and clinical features of acute bacterial gastroenteritis in children mananged at a secondary hospital. Pediatr Infect Vaccine 2017;24:95-101. https://doi.org/10.14776/piv.2017.24.2.95
  39. Bae JY, Lee DH, Ko KO, Lim JW, Cheon EJ, Song YH, et al. Clinical manifestation of Campylobacter enteritis in children. Korean J Pediatr 2018;61:84-9. https://doi.org/10.3345/kjp.2018.61.3.84
  40. Shim JO, Chang JY, Kim A, Shin S. Different age distribution between campylobacteriosis and nontyphoidal salmonellosis in hospitalized Korean children with acute inflammatory diarrhea. J Korean Med Sci 2017;32:1202-6. https://doi.org/10.3346/jkms.2017.32.7.1202

Cited by

  1. Molecular epidemiologic trends of norovirus and rotavirus infection and relation with climate factors: Cheonan, Korea, 2010-2019 vol.18, pp.12, 2020, https://doi.org/10.14400/jdc.2020.18.12.425
  2. Effects of climatic factors and particulate matter on Rotavirus A infections in Cheonan, Korea, in 2010-2019 vol.28, pp.32, 2020, https://doi.org/10.1007/s11356-021-13852-3