発熱や感染症で抗菌薬を処方される事がありますが、長期にわたり飲み続けると消化管に住んでいる「賢い菌」の住む環境が悪くなり、代わりに毒素を出す「悪い菌」（クロストリジウムディフィシレ）が増え、腸炎や下痢を起こし、その下痢便から排出された病原菌が病院などで拡がる事が問題になっております。（注目の抗菌薬関連下痢症（クロストリジウムディフィシル）について Infection control nurseの部屋）
Commercially available FDA-cleared multiplex nucleic acid-based tests for infectious agents include systems from Luminex, GenMark, and BioFire (now a subsidiary of bioMérieux) (Table 1). At present, all such systems combine the sequential steps of:
Nucleic acid purification from the appropriate human sample matrix (e.g., nasal swab, blood or blood culture, stool)
cDNA synthesis (reverse transcription) to convert viral RNA to DNA, if necessary
Multiplex PCR to amplify molecules of the pathogen nucleic acid
Specific detection of the expected amplicons to confirm that the correct target nucleic acids have been identified
（Multiplex PCR for Detection and Identification of Microbial Pathogens 10 November 2018 Advanced Techniques in Diagnostic Microbiology pp 475-493）
Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis. Clinical Microbiology and Infection Volume 24, Issue 10, October 2018, Pages 1055-1063 diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays—on the detection of viral respiratory infections.
Multiplex PCR for Detection and Identification of Microbial Pathogens 10 November 2018 Advanced Techniques in Diagnostic Microbiology pp 475-493
The FILMARRAY is an FDA-cleared multiplex PCR system that integrates sample preparation, amplification, detection and analysis. It requires just a few minutes of hands-on-time and its turnaround time is just about an hour, giving you faster results which may lead to better patient care. (biomerieux-usa.com)
The Clinical Impact of the BioFire® FilmArray® System 2020/01/17 BioFire Diagnostics
Stop waiting. Start living. The BioFire® FilmArray® System. 2013/10/30 BioFire Diagnostics
BioFire® FilmArray® System Demo 2013/04/06 BioFire Diagnostics
診療科に合わせて検出したい病原体のパネルが用意されているようです。
バイオファイアのフィルムアレイ特許
SALT LAKE CITY, Utah,(March13, 2013) –BioFire Diagnostics,Inc.,today announced that the United States Patent and Trademark Office has issued U.S.Patent No. 8,394,608 covering the company’s FilmArray system. FilmArray’s proprietary technology represents a significant advancement in user-friendliness and multiplex infectious disease testing capability for hospital clinical labs. This is the first U.S. patent issued to cover the FilmArray system, and BioFire has exclusive rights to the patented technology. Specifically, the patent covers methods for sample preparation and two-step multiplex polymerase chain reaction (PCR) in a sealed container. (BioFire Diagnostics)
The FilmArray Blood Culture Identification (BCID) panel, which is able to identify 24 different microorganisms and the resistance genes Klebsiella pneumoniae carbapenemase (KPC), mecA and vanA/B, has the potential to facilitate point-of-care testing and provides results in 1 hour. (Application of BioFire FilmArray Blood Culture Identification panel for rapid identification of the causative agents of ventilator-associated pneumonia. Clinical Microbiology and Infection Volume 24, Issue 11, November 2018, Pages 1213.e1-1213.e4)
BioFire FilmArray Meningitis/Encephalitis panel
The BioFire FA ME addresses such diagnostic underutilization by providing a comprehensive panel testing for 15 CNS pathogens simultaneously using a minimal amount of CSF with rapid turn-around time (1 h). Shown to be an effective alternative for other infections such as gastroenteritis [3], and bacteremia [5–8] BioFire’s FA ME was approved by the Federal Drug Administration on October 8, 2015 with promising results both in the US [9] and internationally [10, 11]. (Enhancing pathogen identification in patients with meningitis and a negative Gram stain using the BioFire FilmArray® Meningitis/Encephalitis panel. Annals of Clinical Microbiology and Antimicrobials volume 15, Article number: 26 (2016))
BioFire FilmArray Pneumonia Panel
The BioFire FilmArray pneumonia panel (BFPP) was recently FDA cleared (November 2018) for detection and identification of multiple respiratory viral and bacterial pathogens in addition to selected antimicrobial resistance genes from sputum or bronchial alveolar lavage (BAL)-like specimens from individuals with suspected lower respiratory tract (LRT) infections. This assay includes targets for 18 bacteria and 8 viruses that commonly cause pneumonia as well as 7 antibiotic resistance genes. (Evaluation of the BioFire FilmArray Pneumonia Panel for Detection of Viral and Bacterial Pathogens in Lower Respiratory Tract Specimens in the Setting of a Tertiary Care Academic Medical Center. Journal of Clinical Microbiology)
The BioFire FilmArray Pneumonia Panel (FA-Pneumo; BioFire Diagnostics, Salt Lake City, UT, USA) was recently cleared by the US Food and Drug Administration (US FDA, Washington, DC, USA). FA-Pneumo is a fully automated multiplex PCR assay for identifying a number of typical and atypical bacterial pathogens, respiratory viruses, and several classes of antimicrobial susceptibility-associated genes directly from sputum, endotracheal aspirate (ETA), and bronchoalveolar lavage-like specimens in approximately 1 h (Table 1). The assay provides semi-quantitative results for 15 typical respiratory bacterial pathogens.
Table 1. FilmArray Pneumonia Panel plus targets.
Typical bacteria
Acinetobacter calcoaceticus–baumannii complex
Enterobacter cloacae complex
Escherichia coli
Haemophilus influenzae
Klebsiella aerogenes
Klebsiella oxytoca
Klebsiella pneumoniae group
Moraxella catarrhalis
Proteus spp
Pseudomonas aeruginosa
Serratia marcescens
Staphylococcus aureus
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Atypical bacteria
Chlamydia pneumoniae
Legionella pneumophila
Mycoplasma pneumoniae
Viruses
Adenovirus
Human metapneumovirus
Human rhinovirus/enterovirus
Influenza A
Influenza B
Parainfluenza virus
Respiratory syncytial virus
Antimicrobial resistance genes
Methicillin resistance
mecA/C and MREJ
Extended-spectrum β-lactamase
CTX-M
Carbapenemases
NDM, IMP, OXA-48-like, KPC, and VIM
(Evaluation of the BioFire FilmArray Pneumonia Panel for rapid detection of respiratory bacterial pathogens and antibiotic resistance genes in sputum and endotracheal aspirate specimens. International Journal of Infectious Diseases Volume 95, June 2020, Pages 326-331)
The BioFire® FilmArray® Gastrointestinal (GI) Panel The FDA-cleared BioFire GI Panel tests for 22 of the most common pathogens associated with gastroenteritis—all from one patient sample and one easy to use reagent, with results available in about one hour.
Impact of the BioFire FilmArray gastrointestinal panel on patient care and infection control. February 6, 2020 PLOS ONE Routine PCR detected one or more pathogens in 52 (28.6%) patients compared to 72 (39.6%) using the FilmArray. Turnaround time (including transport) decreased from median 53 hours for the routine PCR to 16 hours for the FilmArray.
Evaluation of the BioFire FilmArray Gastrointestinal Panel and Real-Time Polymerase Chain Reaction Assays for the Detection of Major Diarrheagenic Pathogens by a Multicenter Diarrheal Disease Surveillance Program in China Foodborne Pathogens and Disease Vol. 16, No. 11
Contribution of the FilmArray® Gastrointestinal Panel in the laboratory diagnosis of gastroenteritis in a cohort of children: a two-year prospective study International Journal of Medical Microbiology Volume 308, Issue 5, July 2018, Pages 514-521
FilmArray™ GI panel performance for the diagnosis of acute gastroenteritis or hemorragic diarrhea 12 May 2017 BMC Microbiology volume 17, Article number: 111 (2017)
Multicenter Evaluation of the BioFire FilmArray Gastrointestinal Panel for Etiologic Diagnosis of Infectious Gastroenteritis. 19 February 2015Journal of Clinical Microbiology Vol. 53, No. 3
New challenges emerge for planned human challenge trials. Warren Cornwall Science04 Dec 2020: Vol. 370, Issue 6521, pp. 1150 DOI: 10.1126/science.370.6521.1150 ”because there are no reliable treatments for severe COVID-19, people who volunteer to test a vaccine could die if they get sick. “
Dozens to be deliberately infected with coronavirus in UK ‘human challenge’ trials Ewen Callaway Nature . 2020 Oct;586(7831):651-652. doi: 10.1038/d41586-020-02821-4.
Human Challengeとは
Exploring human challenge studies with coronavirus to speed up COVID-19 vaccines
The Human Challenge Model is a study during which healthy volunteers are deliberately exposed to a virus, known as the “challenge virus”. This is different to standard vaccine clinical trials where volunteers are exposed to viruses naturally. The Human Challenge Model can provide a more efficient and faster way to develop vaccines as fewer volunteers are required. (About our COVID-19 volunteer trials UK COVID CHALLENGE)
Scientists will expose a small group of unvaccinated volunteers (somewhere between 50 and 90 people) to a very low dose of the virus, gradually increasing it until they find “the Goldilocks dose” — enough to infect most participants, but not enough to make them very ill. (The UK is about to start deliberately infecting volunteers with Covid-19 to test vaccines A “human challenge trial” just received ethics approval. Here’s what data it might provide — and why it’s very controversial. By Sigal Samuel Updated Feb 19, 2021, 1:55pm EST VOX)
Only after this initial phase concludes in the spring would the company actually inject volunteers with candidate vaccines to study their effectiveness. At that point, there would be a control group. “Half the volunteers will get a vaccine, half will get a placebo vaccine, and all of them will be exposed to the virus,” explained Andrew Catchpole, the chief scientific officer at Open Orphan, who’s conducting the study. (The UK is about to start deliberately infecting volunteers with Covid-19 to test vaccines A “human challenge trial” just received ethics approval. Here’s what data it might provide — and why it’s very controversial. By Sigal Samuel Updated Feb 19, 2021, 1:55pm EST VOX)
Covid-19: Human challenge studies will see people purposefully infected with virus BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4101 (Published 22 October 2020) Cite this as: BMJ 2020;371:m4101
University of Oxford researchers have begun testing a COVID-19 vaccine in human volunteers in Oxford today. Around 1,110 people will take part in the trial, half receiving the vaccine and the other half (the control group) receiving a widely available meningitis vaccine. (Oxford COVID-19 vaccine begins human trial stage 23 APR 2020 University of Oxford)
In some COVID-19 vaccine trials, participants in the control group (the group receiving a placebo) are injected with a saline solution. In other trials, they receive an actual treatment. For example, in the COVID-19 vaccine developed by the University of Oxford, the control group receives a meningitis and septicaemiavaccine as a placebo. The benefit of using an actual vaccine as the placebo control is that it will cause a similar reaction at the site of the injection as the COVID-19 vaccine, such as muscle pain and soreness. (Coronavirus vaccine: why it’s important to know what’s in the placebo September 22, 2020 4.14am AEST The Conversation)
Human Challengeという手法自体は、古い歴史があるようですが、新型コロナウイルスのワクチンでやっていいことなのかどうかに関しては、賛否両論ありかなり白熱した議論があるようです。昨年来、賛成派、反対派両者から多数の論文が出版されていました。
Debate arises over human challenge trials in race to develop Covid-19 vaccine 2020/05/22 CNBC Television
Scientists Split Over Safety Of Coronavirus Human Challenge Trials For Vaccine | NBC News NOW 2020/08/19 NBC News
COVID-19 and the ethics of human challenge trials. Gordijn B, Ten Have H. Med Health Care Philos. 2021 Mar;24(1):1-2. doi: 10.1007/s11019-021-10001-y.
Human Challenge Studies With Wild-Type Severe Acute Respiratory Sydrome Coronavirus 2 Violate Longstanding Codes of Human Subjects Research Stanley M Spinola, Camilla Broderick, Gregory D Zimet, Mary A Ott Open Forum Infectious Diseases, Volume 8, Issue 1, January 2021 https://doi.org/10.1093/ofid/ofaa615 Published: 28 December 2020 Open Forum Infectious Diseases
Immunological considerations for SARS-CoV-2 human challenge studies Alexander D Douglas, Adrian V S Hill Nat Rev Immunol . 2020 Dec;20(12):715-716. doi: 10.1038/s41577-020-00472-0.
Coronavirus Human Infection Challenge Studies: Assessing Potential Benefits and Risks Euzebiusz Jamrozik, George S Heriot, Michael J Selgelid J Bioeth Inq . 2020 Dec;17(4):709-715. doi: 10.1007/s11673-020-10030-x. Epub 2020 Aug 25.
Key criteria for the ethical acceptability of COVID-19 human challenge studies: Report of a WHO Working Group. Jamrozik E, Littler K, Bull S, Emerson C, Kang G, Kapulu M, Rey E, Saenz C, Shah S, Smith PG, Upshur R, Weijer C, Selgelid MJ; WHO Working Group for Guidance on Human Challenge Studies in COVID-19. Vaccine. 2021 Jan 22;39(4):633-640. doi: 10.1016/j.vaccine.2020.10.075. Epub 2020 Oct 28.
Human Challenge Studies Are Unlikely to Accelerate Coronavirus Vaccine Licensure Due to Ethical and Practical IssuesJ Infect Dis . 2020 Oct 1;222(9):1572-1574. doi: 10.1093/infdis/jiaa457.
COVID-19 human challenge studies: ethical issues Euzebiusz Jamrozik, Michael J Selgelid Lancet Infect Dis . 2020 Aug;20(8):e198-e203. doi: 10.1016/S1473-3099(20)30438-2. Epub 2020 May 29.
Ethical guidelines for deliberately infecting volunteers with COVID-19 Adair D Richards J Med Ethics . 2020 Aug;46(8):502-504. doi: 10.1136/medethics-2020-106322. Epub 2020 May 27.
COVID-19 vaccine development: Time to consider SARS-CoV-2 challenge studies? G Owen Schaefer, Clarence C Tam, Julian Savulescu, Teck Chuan Voo Vaccine . 2020 Jul 14;38(33):5085-5088. doi: 10.1016/j.vaccine.2020.06.007. Epub 2020 Jun 4.
Severe Acute Respiratory Syndrome Coronavirus 2 Human Challenge Trials: Too Risky, Too Soon Liza Dawson, Jake Earl, Jeffrey Livezey J Infect Dis . 2020 Jul 6;222(3):514-516. doi: 10.1093/infdis/jiaa314.
Why Challenge Trials of SARS-CoV-2 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events Nir Eyal Ethics Hum Res . 2020 Jul;42(4):24-34. doi: 10.1002/eahr.500056. Epub 2020 May 22.
Why we (probably) must deliberately infect Adam J Kolber J Law Biosci. 2020 May 11;7(1):lsaa024. doi: 10.1093/jlb/lsaa024. eCollection Jan-Jun 2020.
Good news for tens of thousands of volunteers in the COVID-19 vaccine trials: Many of those who received a placebo are now being offered a vaccine — in some cases, earlier than they would otherwise have been eligible. (Vaccine trial participants who received placebo now hop the line for the real thing from Pfizer, Moderna By JUDY PERES CHICAGO TRIBUNE | JAN 14, 2021 AT 5:16 PM)
In 2018, Netea’s team published a more direct test. They showed BCG stimulates initial immune defenses enough that it at least partly blocked another virus given experimentally a month later. (Could old vaccines for other germs protect against COVID-19? THE ASSOCIATED PRESS April 14, 2020 at 12:05 JST The Asahi Shimbun)
Impact of Routine Infant BCG Vaccination on COVID-19 Masako Kinoshita Masami Tanaka Published:August 11, 2020DOI:https://doi.org/10.1016/j.jinf.2020.08.013 Journal of Infection VOLUME 81, ISSUE 4, P625-633, OCTOBER 01, 2020
Why does Japan have so few cases of COVID‐19? Akiko Iwasaki Nathan D Grubaugh EMBO Mol Med (2020)12:e12481 2020 May 8 https://doi.org/10.15252/emmm.202012481
They will recruit 1000 health care workers in eight Dutch hospitals who will either receive the vaccine, called bacillus Calmette-Guérin (BCG), or a placebo. BCG contains a live, weakened strain of Mycobacterium bovis,a cousin of M. tuberculosis,the microbe that causes TB. (The vaccine is named after French microbiologists Albert Calmette and Camille Guérin, who developed it in the early 20th century.) （Can a century-old TB vaccine steel the immune system against the new coronavirus? By Jop de VriezeMar. 23, 2020 , 6:25 AM Sciencemag.org news）
