Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Diagnostic Evaluation of the BioFire® Meningitis/Encephalitis Panel: A Pilot Study Including Febrile Infants Younger than 90 Days

BioFire® Meningitis/Encephalitis Panel의 진단적 유용성 평가: 90일 미만 발열영아에서의 예비 연구

  • Kim, Kyung Min (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Park, Ji Young (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Park, Kyoung Un (Department of Laboratory Medicine, Seoul National University Bundang Hospital) ;
  • Sohn, Young Joo (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Choi, Youn Young (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Han, Mi Seon (Department of Pediatrics, Seoul Metropolitan Government-Seoul National University Boramae Medical Center) ;
  • Choi, Eun Hwa (Department of Pediatrics, Seoul National University Children's Hospital)
  • 김경민 (분당서울대학교병원 소아청소년과) ;
  • 박지영 (분당서울대학교병원 소아청소년과) ;
  • 박경운 (분당서울대학교병원 진단검사의학과) ;
  • 손영주 (서울대학교 어린이병원 소아청소년과) ;
  • 최윤영 (서울대학교 어린이병원 소아청소년과) ;
  • 한미선 (서울특별시 보라매병원 소아청소년과) ;
  • 최은화 (서울대학교 어린이병원 소아청소년과)
  • Received : 2021.01.28
  • Accepted : 2021.08.07
  • Published : 2021.08.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Rapid detection of etiologic organisms is crucial for initiating appropriate therapy in patients with central nervous system (CNS) infection. This study aimed to evaluate the diagnostic value of the BioFire® Meningitis/Encephalitis (ME) panel in detecting etiologic organisms in cerebrospinal fluid (CSF) samples from febrile infants. Methods: CSF samples from infants aged <90 days who were evaluated for fever were collected between January 2016 and July 2019 at the Seoul National University Children's Hospital. We performed BioFire® ME panel testing of CSF samples that had been used for CSF analysis and conventional tests (bacterial culture, Xpert® enterovirus assay, and herpes simplex virus-1 and -2 polymerase chain reaction) and stored at -70℃ until further use. Results: In total, 72 (24 pathogen-identified and 48 pathogen-unidentified) CSF samples were included. Using BioFire® ME panel testing, 41 (85.4%) of the 48 pathogen-unidentified CSF samples yielded negative results and 22 (91.7%) of the 24 pathogen-identified CSF samples yielded the same results (enterovirus in 19, Streptococcus agalactiae in 2, and Streptococcus pneumoniae in 1) as those obtained using the conventional tests, thereby resulting in an overall agreement of 87.5% (63/72). Six of the 7 pathogen-unidentified samples were positive for human parechovirus (HPeV) via BioFire® ME panel testing. Conclusions: Compared with the currently available etiologic tests for CNS infection, BioFire® ME panel testing demonstrated a high agreement score for pathogen-identified samples and enabled HPeV detection in young infants. The clinical utility and cost-effectiveness of BioFire® ME panel testing in children must be evaluated for its wider application.

목적: 중추신경계 감염의 적절한 치료를 위해서 신속한 원인 병원체의 확인이 중요하다. 본 연구는 열이 있는 영아의 뇌척수액 검체에서 원인 병원체 검출을 위한 BioFire® Meningitis/Encephalitis (ME) panel 검사 방법의 진단적 가치를 평가하고자 수행되었다. 방법: 2016년 1월부터 2019년 7월까지 발열을 주소로 서울대학교 어린이병원에 내원한 90일 미만의 영아로부터 채취한 뇌척수액으로 기존검사(세균 배양, Xpert® enterovirus assay, herpes simplex virus-1 and -2 중합효소 연쇄반응 검사)를 시행한 후 -70℃ 초저온 냉동고에 보관된 검체를 대상으로 BioFire® ME panel 검사를 시행하였다. 결과: 총 72개 검체(원인 병원체가 검출된 24개와 검출되지 않은 48개)가 포함되었다. BioFire® ME panel 검사 결과, 기존검사로 원인 병원체가 검출되지 않은 48개의 검체 중 41개(85.4%)는 음성이었고 원인 병원체가 검출된 24개 검체 중 22개(91.7%)가 동일한 결과(enterovirus 19개, Streptococcus agalactiae 2개, Streptococcus pneumoniae 1개)를 보여 전체 일치율은 87.5% (63/72)였다. 병원체가 기존검사에서 검출되지 않았으나 BioFire® ME panel에서 검출된 7개의 검체 중 6개에서 human parechovirus (HPeV)가 검출되었다. 결론: 열이 있는 90일 미만 영아에서 BioFire® ME panel 검사법은 원인 병원체가 밝혀진 기존검사 결과와는 비교적 높은 일치도를 보이며, HPeV를 추가적으로 진단할 수 있었다. 향후, 소아청소년 진료 영역에서 BioFire® ME panel 검사법을 적용할 근거를 마련하기 위한 임상적 유용성과 비용 효과에 대한 연구가 필요하다.

Keywords

Acknowledgement

This study was supported by a 2019 grant from the Korean Society of Pediatric Infectious Diseases.

References

  1. Saez-Llorens X, McCracken GH Jr. Bacterial meningitis in neonates and children. Infect Dis Clin North Am 1990;4:623-44. https://doi.org/10.1016/S0891-5520(20)30369-X
  2. Saez-Llorens X, McCracken GH Jr. Bacterial meningitis in children. Lancet 2003;361:2139-48. https://doi.org/10.1016/S0140-6736(03)13693-8
  3. Moreno MT, Vargas S, Poveda R, Saez-Llorens X. Neonatal sepsis and meningitis in a developing Latin American country. Pediatr Infect Dis J 1994;13:516-20.
  4. Kessler SL, Dajani AS. Listeria meningitis in infants and children. Pediatr Infect Dis J 1990;9:61-3. https://doi.org/10.1097/00006454-199001000-00016
  5. Meirovitch J, Kitai-Cohen Y, Keren G, Fiendler G, Rubinstein E. Cerebrospinal fluid shunt infections in children. Pediatr Infect Dis J 1987;6:921-4. https://doi.org/10.1097/00006454-198710000-00013
  6. Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, Hadler JL, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med 2011;364:2016-25. https://doi.org/10.1056/NEJMoa1005384
  7. Tan NW, Lee EY, Khoo GM, Tee NW, Krishnamoorthy S, Choong CT. Cerebrospinal fluid white cell count: discriminatory or otherwise for enteroviral meningitis in infants and young children? J Neurovirol 2016;22:213-7. https://doi.org/10.1007/s13365-015-0387-2
  8. James SH, Kimberlin DW. Neonatal herpes simplex virus infection. Infect Dis Clin North Am 2015;29:391-400. https://doi.org/10.1016/j.idc.2015.05.001
  9. 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
  10. Dorsett M, Liang SY. Diagnosis and treatment of central nervous system infections in the emergency department. Emerg Med Clin North Am 2016;34:917-42. https://doi.org/10.1016/j.emc.2016.06.013
  11. Dagan R, Powell KR, Hall CB, Menegus MA. Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis. J Pediatr 1985;107:855-60. https://doi.org/10.1016/S0022-3476(85)80175-X
  12. Messacar K, Breazeale G, Robinson CC, Dominguez SR. Potential clinical impact of the film array meningitis encephalitis panel in children with suspected central nervous system infections. Diagn Microbiol Infect Dis 2016;86:118-20. https://doi.org/10.1016/j.diagmicrobio.2016.05.020
  13. Oberste MS, Maher K, Pallansch MA. Specific detection of echoviruses 22 and 23 in cell culture supernatants by RT-PCR. 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
  14. Kabuga AI, Nejati A, Soheili P, Yousefipoor S, Yousefi M, Mollaiee Y, et al. Cell culture demonstrates superior sensitivity over one step real time RT PCR and nested VP1 amplification for Enteroviruses. J Virol Methods 2021;287:113994. https://doi.org/10.1016/j.jviromet.2020.113994
  15. Biondi EA, Byington CL. Evaluation and management of febrile, well-appearing young infants. Infect Dis Clin North Am 2015;29:575-85. https://doi.org/10.1016/j.idc.2015.05.008
  16. Shukla B, Aguilera EA, Salazar L, Wootton SH, Kaewpoowat Q, Hasbun R. Aseptic meningitis in adults and children: diagnostic and management challenges. J Clin Virol 2017;94:110-4. https://doi.org/10.1016/j.jcv.2017.07.016
  17. Leber AL, Everhart K, Balada-Llasat JM, Cullison J, Daly J, Holt S, et al. Multicenter evaluation of BioFire FilmArray Meningitis/Encephalitis panel for detection of bacteria, viruses and yeast in cerebrospinal fluid specimens. J Clin Microbiol 2016;54:2251-61. https://doi.org/10.1128/JCM.00730-16
  18. Jung HJ, Choi EH, Lee HJ. Human parechovirus as an important cause of central nervous system infection in childhood. Pediatr Infect Vaccine 2016;23:165-71. https://doi.org/10.14776/piv.2016.23.3.165
  19. 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
  20. 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
  21. Dien Bard J, Alby K. Point-counterpoint: meningitis/encephalitis syndromic testing in the clinical laboratory. J Clin Microbiol 2018;56:e00018-18.
  22. Soucek DK, Dumkow LE, VanLangen KM, Jameson AP. Cost justification of the Biofire FilmArray Meningitis/Encephalitis panel versus standard of care for diagnosing meningitis in a community hospital. J Pharm Pract 2019;32:36-40. https://doi.org/10.1177/0897190017737697