DOI QR코드

DOI QR Code

소아청소년기 중추신경 감염의 주요 원인으로서 Human Parechovirus의 의의

Human Parechovirus as an Important Cause of Central Nervous System Infection in Childhood

  • 정현주 (아주대학교 의과대학 소아청소년과) ;
  • 최은화 (서울대학교 의과대학 소아과학교실) ;
  • 이환종 (서울대학교 의과대학 소아과학교실)
  • Jung, Hyun Joo (Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine) ;
  • Choi, Eun Hwa (Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine) ;
  • Lee, Hoan Jong (Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine)
  • 투고 : 2016.04.20
  • 심사 : 2016.05.14
  • 발행 : 2016.12.25

초록

목적: Human parechovirus (HPeV)는 영아에서 중추신경계 감염 및 패혈증의 주요한 원인의 하나로 최근에 새로이 주목받고 있는 바이러스이다. 그러나, 영아 이후 시기에 발병하는 HPeV 감염에 대한 연구나 보고는 거의 없다. 본 연구는 소아기 전 연령대에 걸친 HPeV의 국내 유병률 및 그 임상적 특징을 알아보고자 하였다. 방법: 2013년 1월부터 2014년 7월까지 발열 혹은 수막염 의심 증상으로 서울대학교병원에 내원하여 뇌척수액 검사를 시행 받은 소아의, 보호자 서면 동의를 얻어 수집한 잉여 뇌척수액 검체를 대상으로 하였다. 뇌척수액 검체에서 HPeV 특이 5' untranslated region을 역전사 중합효소연쇄반응(reverse transcription polymerase chain reaction)으로 증폭하여 HPeV 감염을 진단하고, HPeV의 viral protein 3/1 (VP3/VP1) region의 염기서열을 분석하여 유전자형을 확인했다. 이들의 임상 및 진단검사적 특징을 후향적 의무기록분석을 통해 평가하고, 같은 시기에 뇌척수액 GeneXpert (Cepheid)검사로 진단된 장바이러스(enterovirus [EV]) 수막염 환자군과 비교하였다. 결과: 총 102개의 뇌척수액 검체를 분석하였다. 이 중 HPeV 양성인 검체는 6개(5.9%)였고, 21개의 EV양성 검체 중 2개에서 HPeV가 함께 검출되었다. HPeV는 2013년 6월과 2014년 5월에서 7월 사이에 수집된 검체에서 나타났고, 모두 HPeV3형이었다. HPeV 양성인 환자 중 2명이 3개월 이하의 영아였고, 나머지 4명은 1세 이상이었다(19-180개월). 1세 이하의 HPeV 환자들은 특별한 신경학적 증상 없이 발열과 같은 비특이적 증상을 보였으나, 1세 이상의 HPeV 환자들에서는 발열과 함께 뇌전증, 의식소실과 같은 중증 신경학적 증상이 동반되었다. EV 양성인 뇌척수액 검체의 대다수(73.7%)에서 뇌척수액 내 백혈구 증다증이 관찰된 반면, HPeV의 경우 연령 대비 정상 범위를 보였다. 결론: HPeV에 의한 중추신경 감염증은 주로 3개월 이하의 영아에서 호발하는 것으로 알려져 있으나, 본 연구에 의하면 영아기 이후의 소아청소년에서도 HPeV 감염이 발생할 수 있다. 특히, 영아기 이후의 소아청소년에서 신경학적 증상을 동반한 발열이 있으나 정상 뇌척수액 검사 소견을 보이는 경우 HPeV를 병원체의 하나로 고려할 필요가 있겠다. 국내 소아 전반에 있어서 HPeV 감염의 역학과 임상적 특징을 밝히기 위해 향후 추가 연구가 필요하다.

Purpose: Human parechovirus (HPeV) is an increasingly recognized pathogenic cause of central nervous system (CNS) infection in neonates. However, HPeV infections have not been studied in older children. This study determined the prevalence and clinical features of HPeV CNS infection in children in Korea. Methods: Reverse transcription polymerase chain reaction assays were performed using HPeV-specific, 5' untranslated, region-targeted primers to detect HPeV in cerebrospinal fluid (CSF) samples from children presenting with fever or neurologic symptoms from January 1, 2013, to July 31, 2014. HPeV genotyping was performed by sequencing the viral protein 3/1 region. Clinical and laboratory data were retrospectively abstracted from medical records and compared with those of enterovirus (EV)-positive patients from the same period. Results: Of 102 CSF samples, six (5.9%) were positive for HPeV; two of 21 EV-positive samples were co-infected with HPeV. All samples were genotype HPeV3. Two HPeV-positive patients were <3 months of age and four others were over 1 year old. While HPeV-positive infants under 1 year of age presented with sepsis-like illness without definite neurologic abnormalities, HPeV-positive children over 1 year of age presented with fever and neurologic symptoms such as seizures, loss of consciousness, and gait disturbance. The CSF findings of HPeV-positive patients were mostly within the normal range, whereas most (73.7%) EV-positive patients had pleocytosis. Conclusions: Although HPeV is typically associated with disease in young infants, the results of this study suggest that HPeV is an emerging pathogen of CNS infection with neurologic symptoms in older childhood.

키워드

참고문헌

  1. Wigand R, Sabin AB. Properties of ECHO types 22, 23 and 24 viruses. Arch Gesamte Virusforsch 1961;11:224-47. https://doi.org/10.1007/BF01241688
  2. Oberste MS, Maher K, Pallansch MA. Specific detection of echoviruses 22 and 23 in cell culture supernatants by RTPCR. J Med Virol 1999;58:178-81. https://doi.org/10.1002/(SICI)1096-9071(199906)58:2<178::AID-JMV13>3.0.CO;2-Q
  3. Mayo MA, Pringle CR. Virus taxonomy: 1997. J Gen Virol 1998;79(Pt 4):649-57. https://doi.org/10.1099/0022-1317-79-4-649
  4. Chuchaona W, Khamrin P, Yodmeeklin A, Saikruang W, Kongsricharoern T, Ukarapol N, et al. Detection and characterization of a novel human parechovirus genotype in Thailand. Infect Genet Evol 2015;31:300-4. https://doi.org/10.1016/j.meegid.2015.02.003
  5. van der Linden L, Wolthers KC, van Kuppeveld FJ. Replication and inhibitors of enteroviruses and parechoviruses. Viruses 2015;7:4529-62. https://doi.org/10.3390/v7082832
  6. Levorson RE, Jantausch BA. Human parechoviruses. Pediatr Infect Dis J 2009;28:831-2. https://doi.org/10.1097/INF.0b013e3181badb6a
  7. Harvala H, Robertson I, Chieochansin T, McWilliam Leitch EC, Templeton K, Simmonds P. Specific association of human parechovirus type 3 with sepsis and fever in young infants, as identified by direct typing of cerebrospinal fluid samples. J Infect Dis 2009;199:1753-60. https://doi.org/10.1086/599094
  8. Wolthers KC, Benschop KS, Schinkel J, Molenkamp R, Bergevoet RM, Spijkerman IJ, et al. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis 2008;47:358-63. https://doi.org/10.1086/589752
  9. Selvarangan R, Nzabi M, Selvaraju SB, Ketter P, Carpenter C, Harrison CJ. Human parechovirus 3 causing sepsis-like illness in children from midwestern United States. Pediatr Infect Dis J 2011;30:238-42. https://doi.org/10.1097/INF.0b013e3181fbefc8
  10. Seo JH, Yeom JS, Youn HS, Han TH, Chung JY. Prevalence of human parechovirus and enterovirus in cerebrospinal fluid samples in children in Jinju, Korea. Korean J Pediatr 2015;58:102-7. https://doi.org/10.3345/kjp.2015.58.3.102
  11. Verboon-Maciolek MA, Krediet TG, Gerards LJ, de Vries LS, Groenendaal F, van Loon AM. Severe neonatal parechovirus infection and similarity with enterovirus infection. Pediatr Infect Dis J 2008;27:241-5. https://doi.org/10.1097/INF.0b013e31815c1b07
  12. Mizuta K, Kuroda M, Kurimura M, Yahata Y, Sekizuka T, Aoki Y, et al. Epidemic myalgia in adults associated with human parechovirus type 3 infection, Yamagata, Japan, 2008. Emerg Infect Dis 2012;18:1787-93. https://doi.org/10.3201/eid1811.111570
  13. Mizuta K, Yamakawa T, Kurokawa K, Chikaoka S, Shimizu Y, Itagaki T, et al. Epidemic myalgia and myositis associated with human parechovirus type 3 infections occur not only in adults but also in children: findings in Yamagata, Japan, 2014. Epidemiol Infect 2016;144:1286-90. https://doi.org/10.1017/S0950268815002873
  14. Figueroa JP, Ashley D, King D, Hull B. An outbreak of acute flaccid paralysis in Jamaica associated with echovirus type 22. J Med Virol 1989;29:315-9. https://doi.org/10.1002/jmv.1890290418
  15. Harvala H, Robertson I, McWilliam Leitch EC, Benschop K, Wolthers KC, Templeton K, et al. Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol 2008;46:3446-53. https://doi.org/10.1128/JCM.01207-08
  16. Renaud C, Harrison CJ. Human parechovirus 3: the most common viral cause of meningoencephalitis in young infants. Infect Dis Clin North Am 2015;29:415-28. https://doi.org/10.1016/j.idc.2015.05.005
  17. Esposito S, Rahamat-Langendoen J, Ascolese B, Senatore L, Castellazzi L, Niesters HG. Pediatric parechovirus infections. J Clin Virol 2014;60:84-9. https://doi.org/10.1016/j.jcv.2014.03.003
  18. Han TH, Chung JY, You SJ, Youn JL, Shim GH. Human parechovirus-3 infection in children, South Korea. J Clin Virol 2013;58:194-9. https://doi.org/10.1016/j.jcv.2013.05.023
  19. Zhang DL, Jin Y, Li DD, Cheng WX, Xu ZQ, Yu JM, et al. Prevalence of human parechovirus in Chinese children hospitalized for acute gastroenteritis. Clin Microbiol Infect 2011;17:1563-9. https://doi.org/10.1111/j.1469-0691.2010.03390.x
  20. Pajkrt D, Benschop KS, Westerhuis B, Molenkamp R, Spanjerberg L, Wolthers KC. Clinical characteristics of human parechoviruses 4-6 infections in young children. Pediatr Infect Dis J 2009;28:1008-10. https://doi.org/10.1097/INF.0b013e3181a7ab5f
  21. Felsenstein S, Yang S, Eubanks N, Sobrera E, Grimm JP, Aldrovandi G. Human parechovirus central nervous system infections in southern California children. Pediatr Infect Dis J 2014;33:e87-91. https://doi.org/10.1097/INF.0000000000000112
  22. Sharp J, Harrison CJ, Puckett K, Selvaraju SB, Penaranda S, Nix WA, et al. Characteristics of young infants in whom human parechovirus, enterovirus or neither were detected in cerebrospinal fluid during sepsis evaluations. Pediatr Infect Dis J 2013;32:213-6.
  23. Cabrerizo M, Trallero G, Pena MJ, Cilla A, Megias G, Munoz-Almagro C, et al. Comparison of epidemiology and clinical characteristics of infections by human parechovirus vs. those by enterovirus during the first month of life. Eur J Pediatr 2015;174:1511-6. https://doi.org/10.1007/s00431-015-2566-9
  24. Pineiro L, Vicente D, Montes M, Hernandez-Dorronsoro U, Cilla G. Human parechoviruses in infants with systemic infection. J Med Virol 2010;82:1790-6. https://doi.org/10.1002/jmv.21878

피인용 문헌

  1. BioFire® Meningitis/Encephalitis Panel의 진단적 유용성 평가: 90일 미만 발열영아에서의 예비 연구 vol.28, pp.2, 2016, https://doi.org/10.14776/piv.2021.28.e9