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1
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Lim PP, Morisette K, Keith M, Hines E, Huntington MK. Spinal Phlegmon Secondary to Neisseria meningitidis Meningitis With Possible Herpes Simplex Virus 1 Co-infection in an Immunocompetent Pediatric Patient. Cureus 2025; 17:e80585. [PMID: 40225534 PMCID: PMC11994246 DOI: 10.7759/cureus.80585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2025] [Indexed: 04/15/2025] Open
Abstract
Spinal phlegmon has rarely been reported in meningococcemia. Simultaneous polymicrobial infection has been occasionally reported as the etiology of meningitis. The development of a spinal phlegmon and optic neuritis complicated meningitis in a five-year-old male who presented with clinical sepsis and meningitis. Neisseria meningitidis (N. meningitidis) and herpes simplex virus 1 (HSV-1) were demonstrated in the cerebrospinal fluid. Investigation of potential immunocompromise revealed no identified deficit. Protracted antibiotics and antiviral therapy were completed with a favorable clinical outcome. This is potentially the first reported case of spinal phlegmon associated with meningococcal meningitis in an immunocompetent pediatric patient. It occurred in the clinical context of what appeared to be a simultaneous infection by N. meningitidis and HSV-1.
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Affiliation(s)
- Peter Paul Lim
- Department of Pediatrics, Division of Infectious Diseases, Avera McKennan University Health Center, Sioux Falls, USA
- Department of Pediatrics, Division of Infectious Diseases, University of South Dakota Sanford School of Medicine, Sioux Falls, USA
| | - Kayla Morisette
- Department of Family Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, USA
| | - Meredith Keith
- Department of Family Medicine, Center for Family Medicine, Sioux Falls, USA
- Department of Family Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, USA
| | - Eric Hines
- Department of Family Medicine, Center for Family Medicine, Sioux Falls, USA
- Department of Family Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, USA
| | - Mark K Huntington
- Department of Family Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, USA
- Department of Family Medicine, Center for Family Medicine, Sioux Falls, USA
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2
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Candel FJ, Salavert M, Cantón R, Del Pozo JL, Galán-Sánchez F, Navarro D, Rodríguez A, Rodríguez JC, Rodríguez-Aguirregabiria M, Suberviola B, Zaragoza R. The role of rapid multiplex molecular syndromic panels in the clinical management of infections in critically ill patients: an experts-opinion document. Crit Care 2024; 28:440. [PMID: 39736683 DOI: 10.1186/s13054-024-05224-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 12/19/2024] [Indexed: 01/01/2025] Open
Abstract
Rapid multiplex molecular syndromic panels (RMMSP) (3 or more pathogens and time-to-results < 6 h) allow simultaneous detection of multiple pathogens and genotypic resistance markers. Their implementation has revolutionized the clinical landscape by significantly enhancing diagnostic accuracy and reducing time-to-results in different critical conditions. The current revision is a comprehensive but not systematic review of the literature. We conducted electronic searches of the PubMed, Medline, Embase, and Google Scholar databases to identify studies assessing the clinical performance of RMMSP in critically ill patients until July 30, 2024. A multidisciplinary group of 11 Spanish specialists developed clinical questions pertaining to the indications and limitations of these diagnostic tools in daily practice in different clinical scenarios. The topics covered included pneumonia, sepsis/septic shock, candidemia, meningitis/encephalitis, and off-label uses of these RMMSP. These tools reduced the time-to-diagnosis (and therefore the time-to-appropriate treatment), reduced inappropriate empiric treatment and the length of antibiotic therapy (which has a positive impact on antimicrobial stewardship and might be associated with lower in-hospital mortality), may reduce the length of hospital stay, which could potentially lead to cost savings. Despite their advantages, these RMMSP have limitations that should be known, including limited availability, missed diagnoses if the causative agent or resistance determinants are not included in the panel, false positives, and codetections. Overall, the implementation of RMMSP represents a significant advancement in infectious disease diagnostics, enabling more precise and timely interventions. This document addresses relevant issues related to the use of RMMSP on different critically ill patient profiles, to standardize procedures, assist in making management decisions and help specialists to obtain optimal outcomes.
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Affiliation(s)
- Francisco Javier Candel
- Clinical Microbiology and Infectious Diseases, Hospital Clínico Universitario San Carlos, IdISSC & IML Health Research Institutes, 28040, Madrid, Spain.
| | - Miguel Salavert
- Infectious Diseases Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Rafael Cantón
- Microbiology Department, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, , Madrid, Spain
| | - José Luis Del Pozo
- Infectious Diseases Unit, Microbiology Department, Clínica Universidad de Navarra, Navarra, Spain
- IdiSNA: Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - Fátima Galán-Sánchez
- Microbiology Department, Hospital Universitario Puerta del Mar, Cádiz, Spain
- Instituto de Investigación Biomédica de Cádiz (INIBICA), Cádiz, Spain
| | - David Navarro
- Microbiology Department, INCLIVA Health Research Institute, Clinic University Hospital, Valencia, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
| | - Alejandro Rodríguez
- Intensive Care Medicine Department, Hospital Universitario de Tarragona Joan XXIII, Universitat Rovira I Virgili, CIBER Enfermedades Respiratorias, d'investigacio Sanitaria Pere Virgili, Tarragona, Spain
| | - Juan Carlos Rodríguez
- Microbiology Department, Dr. Balmis University General Hospital, Alicante, Spain
- Department of Microbiology, Institute for Health and Biomedical Research (ISABIAL), Miguel Hernández University, Alicante, Spain
| | | | - Borja Suberviola
- Intensive Care Medicine Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Rafael Zaragoza
- Critical Care Department, Hospital Universitario Dr. Peset, Valencia, Spain
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3
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Pershad J, Crawford L, Preciado D, Harrar D, Molto J, Shapiro C. Status Epilepticus with Fever in a Toddler with Pyogenic Meningitis Due to Complicated Acute Sphenoid Sinusitis. JOURNAL OF PEDIATRICS. CLINICAL PRACTICE 2024; 14:200123. [PMID: 39629202 PMCID: PMC11613199 DOI: 10.1016/j.jpedcp.2024.200123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 08/14/2024] [Accepted: 08/15/2024] [Indexed: 12/07/2024]
Abstract
We present a toddler with acute sphenoid sinusitis presenting as status epilepticus with fever, intracranial abscess and meningitis. Cerebrospinal fluid analysis suggested bacterial meningitis, but polymerase chain reaction test was positive for human herpes virus 6. We highlight diagnosis and treatment of this uncommon condition.
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Affiliation(s)
- Jay Pershad
- Division of Emergency Medicine, Department of Pediatrics, Children's National Hospital, The George Washington School of Medicine and Health Sciences, Washington, DC
| | - Lexi Crawford
- Division of Critical Care, Department of Pediatrics, Children's National Hospital, The George Washington School of Medicine and Health Sciences, Washington, DC
| | - Diego Preciado
- Division of Otolaryngology, Department of Pediatrics, Children's National Hospital, The George Washington School of Medicine and Health Sciences, Washington, DC
| | - Dana Harrar
- Division of Neurology, Department of Pediatrics, Children's National Hospital, The George Washington School of Medicine and Health Sciences, Washington, DC
| | - Jose Molto
- Division of Neuroradiology, Department of Pediatrics, Children's National Hospital, The George Washington School of Medicine and Health Sciences, Washington, DC
| | - Craig Shapiro
- Division of Infectious Disease, Department of Pediatrics, Children's National Hospital, The George Washington School of Medicine and Health Sciences, Washington, DC
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4
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Su LD, Chiu CY, Gaston D, Hogan CA, Miller S, Simon DW, Thakur KT, Yang S, Piantadosi A. Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Central Nervous System Infections: Advances and Challenges. Mol Diagn Ther 2024; 28:513-523. [PMID: 38992308 PMCID: PMC11660858 DOI: 10.1007/s40291-024-00727-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2024] [Indexed: 07/13/2024]
Abstract
Central nervous system (CNS) infections carry a substantial burden of morbidity and mortality worldwide, and accurate and timely diagnosis is required to optimize management. Metagenomic next-generation sequencing (mNGS) has proven to be a valuable tool in detecting pathogens in patients with suspected CNS infection. By sequencing microbial nucleic acids present in a patient's cerebrospinal fluid, brain tissue, or samples collected outside of the CNS, such as plasma, mNGS can detect a wide range of pathogens, including rare, unexpected, and/or fastidious organisms. Furthermore, its target-agnostic approach allows for the identification of both known and novel pathogens. This is particularly useful in cases where conventional diagnostic methods fail to provide an answer. In addition, mNGS can detect multiple microorganisms simultaneously, which is crucial in cases of mixed infections without a clear predominant pathogen. Overall, clinical mNGS testing can help expedite the diagnostic process for CNS infections, guide appropriate management decisions, and ultimately improve clinical outcomes. However, there are key challenges surrounding its use that need to be considered to fully leverage its clinical impact. For example, only a few specialized laboratories offer clinical mNGS due to the complexity of both the laboratory methods and analysis pipelines. Clinicians interpreting mNGS results must be aware of both false negatives-as mNGS is a direct detection modality and requires a sufficient amount of microbial nucleic acid to be present in the sample tested-and false positives-as mNGS detects environmental microbes and their nucleic acids, despite best practices to minimize contamination. Additionally, current costs and turnaround times limit broader implementation of clinical mNGS. Finally, there is uncertainty regarding the best practices for clinical utilization of mNGS, and further work is needed to define the optimal patient population(s), syndrome(s), and time of testing to implement clinical mNGS.
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Affiliation(s)
- LingHui David Su
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
| | - Charles Y Chiu
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Department of Laboratory Medicine and Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA
| | - David Gaston
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Catherine A Hogan
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Steve Miller
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Delve Bio, Inc., San Francisco, CA, USA
- Department of Laboratory Medicine, University of California, San Francisco, CA, USA
| | - Dennis W Simon
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Department of Pediatric Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kiran T Thakur
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Department of Neurology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Shangxin Yang
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Anne Piantadosi
- The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.
- Department of Pathology and Laboratory Medicine, and Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA, USA.
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5
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Ganea OA, Tilișcan C, Streinu-Cercel A, Pițigoi D, Drăgănescu AC, Lazar M, Mihai N, Florea D, Aramă SȘ, Aramă V. Human Herpesvirus 6-A Rare Aetiologic Agent for CNS Infections in Immunocompetent Individuals or an Underestimation? J Clin Med 2024; 13:4660. [PMID: 39200800 PMCID: PMC11355476 DOI: 10.3390/jcm13164660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/04/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Human herpesvirus 6 (HHV-6) is considered a ubiquitous virus, with many countries reporting a seroprevalence of more than 80-90% among the general population. However, this virus is unique among herpesviruses in its ability to integrate into the genetic material of the host's cells. Thus, there are three ways by which HHV-6 can cause an active infection-primary infection, reactivation of a latent acquired infection, or activation of iciHHV-6 (inherited chromosomally integrated HHV-6). Whole blood quantitative polymerase chain reaction (qPCR) is very useful in distinguishing between iciHHV-6 and primary infection/reactivation. Our aim is to assess the role of HHV-6 in the aetiology of central nervous system (CNS) infections in adults and children, to describe all HHV-6-positive cases in an attempt to determine the susceptible population and to identify potential risk factors that can be linked to HHV-6 meningoencephalitis. Methods: We performed a retrospective study involving patients that were admitted to Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, with a diagnosis of meningitis or encephalitis. We only selected the clinical records of patients that had a multiplex PCR Biofire® FilmArray® meningitis/encephalitis panel. Results: We report a 5% HHV-6 positivity in the cerebrospinal fluid (CSF) of patients with CNS infections tested with a commercial multiplex PCR M/E (meningitis/encephalitis) panel. Additionally, 2% to 4% of the total study population (n = 100) had active HHV-6 infections, which denotes 40 to 80% of the HHV-6-positive samples. We did not observe any statistically significant correlation between HHV-6 positivity in the CSF and variables such as age, sex, or comorbidities, including obesity, diabetes, hypertension, immunosuppression, or oncologic disease. Therefore, no risk factors could be linked with HHV-6 positivity in the CSF. Conclusions: although multiplex qualitative PCR is highly useful for providing rapid results and identifying nearly every pathogen that can cause meningitis/encephalitis, we have to be aware of this type of test's limitations. All patients with HHV-6 detectable in their CSF via a multiplex PCR test should also undergo qPCR testing from both CSF and blood to prevent over-diagnosing HHV-6 CNS infections, to avoid unnecessary antiviral treatments, and ensure the accurate identification of the true diagnosis.
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Affiliation(s)
- Oana Alexandra Ganea
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Cătălin Tilișcan
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Anca Streinu-Cercel
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Daniela Pițigoi
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Anca Cristina Drăgănescu
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Mihai Lazar
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Nicoleta Mihai
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Dragoș Florea
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Sorin Ștefan Aramă
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
| | - Victoria Aramă
- Faculty of General Medicine, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, 010458 Bucharest, Romania
- “Matei Bals” National Institute of Infectious Diseases, Dr. Calistrat Grozovici Street No. 1, 021105 Bucharest, Romania
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6
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Al Nuaimi M, Al Khaaldi A, Trad O, Almulla A, Al Rufaye H, Ghatasheh G, Al Dhaheri F. HHV6-Associated Hydrocephalus in a Pediatric Hematopoietic Stem Cell Transplant Recipient: An Unusual Presentation. J Pediatr Hematol Oncol 2024; 46:e426-e429. [PMID: 38832402 DOI: 10.1097/mph.0000000000002892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/25/2024] [Indexed: 06/05/2024]
Abstract
Human herpesvirus 6 (HHV-6) is a widely spread DNA virus that is ubiquitous and persistent with primary infection occurring in early childhood, with reactivation of the infection a common phenomenon in severely immunocompromised hosts, including hematopoietic stem cell transplant (HSCT) patients, influencing morbidity and mortality. A wide spectrum of clinical presentations is reported in the literature with HHV-6 reactivation including post-transplant limbic encephalitis (PALE). We report the unusual case of a 6-year-old female 107 days postallogenic HSCT due to transfusion dependent beta thalassemia major who developed acute cerebellitis with secondary supratentorial hydrocephalus that required invasive surgical intervention. In addition to accompanying imaging findings, the patient tested positive for HHV-6 by PCR from both serum and CSF samples and demonstrated dramatic improvement with the institution of steroid therapy in addition to ganciclovir treatment. The availability of rapid diagnostic measures in addition to a multidisciplinary approach is crucial to manage HHV-6 encephalitis and associated complications in HSCT patients.
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Affiliation(s)
- Mohammed Al Nuaimi
- Division of Pediatric Hematology and Oncology, Tawam Oncology Centre
- Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain
| | - Aisha Al Khaaldi
- Department of Pediatrics, Al Qassimi Women and Children Hospital
- Sharjah University Hospital, Sharjah
| | - Omar Trad
- Division of Pediatric Hematology and Oncology, Tawam Oncology Centre
| | - Asia Almulla
- Division of Pediatric Hematology and Oncology, Tawam Oncology Centre
- Sharjah University Hospital, Sharjah
| | - Haydar Al Rufaye
- Division of Pediatric Hematology and Oncology, Tawam Oncology Centre
| | - Ghassan Ghatasheh
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Tawam Hospital
| | - Fatima Al Dhaheri
- Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain
- Pediatric Infectious Diseases Unit, Department of Pediatrics, Sheikh Khalifa Medical City, Abu-Dhabi, United Arab Emirates
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7
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Ivaska L, Herberg J, Sadarangani M. Distinguishing community-acquired bacterial and viral meningitis: Microbes and biomarkers. J Infect 2024; 88:106111. [PMID: 38307149 DOI: 10.1016/j.jinf.2024.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/16/2024] [Accepted: 01/22/2024] [Indexed: 02/04/2024]
Abstract
Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.
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Affiliation(s)
- Lauri Ivaska
- Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Savitehtaankatu 5, 20521 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Kiinanmyllynkatu 10, 20520 Turku, Finland.
| | - Jethro Herberg
- Section of Paediatric Infectious Disease, Faculty of Medicine, Imperial College London, Norfolk Place, London, United Kingdom.
| | - Manish Sadarangani
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
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8
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Sokolovska L, Cistjakovs M, Matroze A, Murovska M, Sultanova A. From Viral Infection to Autoimmune Reaction: Exploring the Link between Human Herpesvirus 6 and Autoimmune Diseases. Microorganisms 2024; 12:362. [PMID: 38399766 PMCID: PMC10892088 DOI: 10.3390/microorganisms12020362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 01/29/2024] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
The complexity of autoimmunity initiation has been the subject of many studies. Both genetic and environmental factors are essential in autoimmunity development. Among others, environmental factors include infectious agents. HHV-6 is a ubiquitous human pathogen with a high global prevalence. It has several properties suggestive of its contribution to autoimmunity development. HHV-6 has a broad cell tropism, the ability to establish latency with subsequent reactivation and persistence, and a range of immunomodulation capabilities. Studies have implicated HHV-6 in a plethora of autoimmune diseases-endocrine, neurological, connective tissue, and others-with some studies even proposing possible autoimmunity induction mechanisms. HHV-6 can be frequently found in autoimmunity-affected tissues and lesions; it has been found to infect autoimmune-pathology-relevant cells and influence immune responses and signaling. This review highlights some of the most well-known autoimmune conditions to which HHV-6 has been linked, like multiple sclerosis and autoimmune thyroiditis, and summarizes the data on HHV-6 involvement in autoimmunity development.
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Affiliation(s)
- Liba Sokolovska
- Institute of Microbiology and Virology, Riga Stradins University, LV-1067 Riga, Latvia
| | - Maksims Cistjakovs
- Institute of Microbiology and Virology, Riga Stradins University, LV-1067 Riga, Latvia
| | - Asnate Matroze
- Faculty of Residency, Riga Stradins University, LV-1007 Riga, Latvia
| | - Modra Murovska
- Institute of Microbiology and Virology, Riga Stradins University, LV-1067 Riga, Latvia
| | - Alina Sultanova
- Institute of Microbiology and Virology, Riga Stradins University, LV-1067 Riga, Latvia
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9
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Bloch KC, Glaser C, Gaston D, Venkatesan A. State of the Art: Acute Encephalitis. Clin Infect Dis 2023; 77:e14-e33. [PMID: 37485952 DOI: 10.1093/cid/ciad306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Indexed: 07/25/2023] Open
Abstract
Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.
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Affiliation(s)
- Karen C Bloch
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Carol Glaser
- California Department of Public Health, Richmond, California, USA
| | - David Gaston
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Arun Venkatesan
- Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA
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10
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Carneiro VCDS, Moreira ODC, Coelho WLDCNP, Rio BC, Sarmento DJDS, Salvio AL, Alves-Leon SV, de Paula VS, Leon LAA. miRNAs in Neurological Manifestation in Patients Co-Infected with SARS-CoV-2 and Herpesvírus 6 (HHV-6). Int J Mol Sci 2023; 24:11201. [PMID: 37446381 PMCID: PMC10342854 DOI: 10.3390/ijms241311201] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/19/2023] [Accepted: 05/19/2023] [Indexed: 07/15/2023] Open
Abstract
Human herpesviruses (HHVs) can establish latency and be reactivated, also are neurotropic viruses that can trigger neurological disorders. HHV-6 is a herpesvirus that is associated with neurological disorders. Studies have reported the detection of HHV-6 in patients with COVID-19 and neurological manifestations. However, specific diagnoses of the neurological disorders caused by these viruses tend to be invasive or difficult to interpret. This study aimed to establish a relationship between miRNA and neurological manifestations in patients co-infected with COVID-19 and HHV-6 and evaluate miRNAs as potential biomarkers. Serum samples from COVID-19 patients in the three cohorts were analyzed. miRNA analysis by real-time polymerase chain reaction (qPCR) revealed miRNAs associated with neuroinflammation were highly expressed in patients with neurological disorders and HHV-6 detection. When compared with the group of patients without detection of HHVs DNA and without neurological alterations, the group with detection of HHV-6 DNA and neurological alteration, displayed significant differences in the expression of mir-21, mir-146a, miR-155 and miR-let-7b (p < 0.01). Our results reinforce the involvement of miRNAs in neurological disorders and provide insights into their use as biomarkers for neurological disorders triggered by HHV-6. Furthermore, understanding the expression of miRNAs may contribute to therapeutic strategies.
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Affiliation(s)
- Vanessa Cristine de Souza Carneiro
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil
- Laboratory of Technological Development in Virology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil (L.A.A.L.)
| | - Otacilio da Cruz Moreira
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil
- Real Time PCR Platform RPT09A, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | | | - Beatriz Chan Rio
- Laboratory of Technological Development in Virology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil (L.A.A.L.)
| | | | - Andreza Lemos Salvio
- Laboratory of Translacional Neurosciences, Biomedical Institute, Federal University of the State of Rio de Janeiro-UNIRIO, Rio de Janeiro 22290-240, Brazil
| | - Soniza Vieira Alves-Leon
- Laboratory of Translacional Neurosciences, Biomedical Institute, Federal University of the State of Rio de Janeiro-UNIRIO, Rio de Janeiro 22290-240, Brazil
- Department of Neurology, Reference and Research Center for Multiple Sclerosis and Other Central Nervous System Idiopathic Demyelinating Inflammatory Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
| | - Vanessa Salete de Paula
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Luciane Almeida Amado Leon
- Laboratory of Technological Development in Virology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-360, Brazil (L.A.A.L.)
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11
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Everhart J, Henshaw NG. Updates in Molecular Diagnostics in Solid Organ Transplantation Recipients. Infect Dis Clin North Am 2023:S0891-5520(23)00038-7. [PMID: 37244805 DOI: 10.1016/j.idc.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Advances in molecular diagnostics have the potential to improve patient care among solid organ transplant recipients by reducing time to pathogen identification and informing directed therapy. Although cultures remain the cornerstone of traditional microbiology, advanced molecular diagnostics, such as metagenomic next-generation sequencing (mNGS), may increase detection of pathogens. This is particularly true in the settings of prior antibiotic exposure, and when causative organisms are fastidious. mNGS also offers a hypothesis-free diagnostic method of testing. This is useful in situations whereby the differential is broad or when the infectious agent is unlikely to be detected by routine methods.
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Affiliation(s)
- James Everhart
- Duke University Medical Center, 2351 Erwin Road, Wadsworth Building, Room 0170, Durham, NC 27705, USA.
| | - Nancy G Henshaw
- Duke University Medical Center, 2351 Erwin Road, Wadsworth Building, Room 0170, Durham, NC 27705, USA
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12
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García-García A, Pérez de Diego R, Flores C, Rinchai D, Solé-Violán J, Deyà-Martínez À, García-Solis B, Lorenzo-Salazar JM, Hernández-Brito E, Lanz AL, Moens L, Bucciol G, Almuqamam M, Domachowske JB, Colino E, Santos-Perez JL, Marco FM, Pignata C, Bousfiha A, Turvey SE, Bauer S, Haerynck F, Ocejo-Vinyals JG, Lendinez F, Prader S, Naumann-Bartsch N, Pachlopnik Schmid J, Biggs CM, Hildebrand K, Dreesman A, Cárdenes MÁ, Ailal F, Benhsaien I, Giardino G, Molina-Fuentes A, Fortuny C, Madhavarapu S, Conway DH, Prando C, Schidlowski L, Martínez de Saavedra Álvarez MT, Alfaro R, Rodríguez de Castro F, Meyts I, Hauck F, Puel A, Bastard P, Boisson B, Jouanguy E, Abel L, Cobat A, Zhang Q, Casanova JL, Alsina L, Rodríguez-Gallego C. Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia. J Exp Med 2023; 220:e20220170. [PMID: 36880831 PMCID: PMC9998661 DOI: 10.1084/jem.20220170] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 11/11/2022] [Accepted: 01/30/2023] [Indexed: 03/08/2023] Open
Abstract
X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
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Affiliation(s)
- Ana García-García
- Pediatric Allergy and Clinical Immunology Dept., Clinical Immunology and Primary Immunodeficiencies Unit, Hospital Sant Joan de Déu, Barcelona, Barcelona, Spain
- Study Group for Immune Dysfunction Diseases in Children, Institut de Recerca Sant Joan de Déu, Barcelona, Barcelona, Spain
- Clinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic Barcelona, Barcelona, Spain
| | - Rebeca Pérez de Diego
- Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain
| | - Carlos Flores
- Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain
- Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
- Dept. of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
| | - Darawan Rinchai
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Jordi Solé-Violán
- CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
- Dept. of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
- Dept. of Intensive Care Medicine, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
| | - Àngela Deyà-Martínez
- Pediatric Allergy and Clinical Immunology Dept., Clinical Immunology and Primary Immunodeficiencies Unit, Hospital Sant Joan de Déu, Barcelona, Barcelona, Spain
- Study Group for Immune Dysfunction Diseases in Children, Institut de Recerca Sant Joan de Déu, Barcelona, Barcelona, Spain
- Clinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic Barcelona, Barcelona, Spain
| | - Blanca García-Solis
- Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain
| | - José M. Lorenzo-Salazar
- Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain
| | - Elisa Hernández-Brito
- Dept. of Immunology, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
| | - Anna-Lisa Lanz
- Dept. of Pediatrics, Division of Pediatric Immunology and Rheumatology, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Leen Moens
- Laboratory for Inborn Errors of Immunity, Dept. of Microbiology, Immunology and Transplantation KU Leuven, Leuven, Belgium
| | - Giorgia Bucciol
- Laboratory for Inborn Errors of Immunity, Dept. of Microbiology, Immunology and Transplantation KU Leuven, Leuven, Belgium
- Dept. of Pediatrics, Childhood Immunology, UZ Leuven, Leuven, Belgium
| | - Mohamed Almuqamam
- Dept. of Pediatrics, Drexel University College of Medicine, St Christopher’s Hospital for Children, Philadelphia, PA, USA
| | | | - Elena Colino
- Unidad de Enfermedades Infecciosas, Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain
| | - Juan Luis Santos-Perez
- Unidad de Gestión Clínica de Pediatría y Cirugía Pediátrica, Hospital Virgen de las Nieves-IBS, Granada, Spain
| | - Francisco M. Marco
- Dept. of Immunology, Alicante University General Hospital Doctor Balmis, Alicante, Spain
- Alicante Institute for Health and Biomedical Research, Alicante, Spain
| | - Claudio Pignata
- Dept. of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy
| | - Aziz Bousfiha
- Dept. of Pediatric Infectious Diseases and Clinical Immunology, Ibn Rushd University Hospital, Casablanca, Morocco
- Clinical Immunology, Autoimmunity and Inflammation Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Stuart E. Turvey
- Dept. of Paediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | - Stefanie Bauer
- Clinic for Children and Adolescents. Dept. of Hematology and Oncology. University Clinic Erlangen, Erlangen, Germany
| | - Filomeen Haerynck
- Dept. of Pediatric Immunology and Pulmonology, Centre for Primary Immune Deficiency Ghent, Ghent University Hospital, Ghent, Belgium
- Dept. of Internal Medicine and Pediatrics, PID Research Laboratory, Ghent University, Ghent, Belgium
| | | | - Francisco Lendinez
- Dept. of Pediatric Oncohematology, Hospital Materno Infantil Torrecárdenas, Almería, Spain
| | - Seraina Prader
- Division of Immunology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
| | - Nora Naumann-Bartsch
- Clinic for Children and Adolescents. Dept. of Hematology and Oncology. University Clinic Erlangen, Erlangen, Germany
| | - Jana Pachlopnik Schmid
- Division of Immunology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
| | - Catherine M. Biggs
- Dept. of Paediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | - Kyla Hildebrand
- Dept. of Paediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada
| | | | - Miguel Ángel Cárdenes
- Dept. of Internal Medicine, Unit of Infectious Diseases, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
| | - Fatima Ailal
- Dept. of Pediatric Infectious Diseases and Clinical Immunology, Ibn Rushd University Hospital, Casablanca, Morocco
- Clinical Immunology, Autoimmunity and Inflammation Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Ibtihal Benhsaien
- Dept. of Pediatric Infectious Diseases and Clinical Immunology, Ibn Rushd University Hospital, Casablanca, Morocco
- Clinical Immunology, Autoimmunity and Inflammation Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Giuliana Giardino
- Dept. of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy
| | | | - Claudia Fortuny
- Study Group for Immune Dysfunction Diseases in Children, Institut de Recerca Sant Joan de Déu, Barcelona, Barcelona, Spain
- Pediatric Infectious Diseases Unit, Hospital Sant Joan de Déu, Barcelona, Spain
- CIBER of Epidemiology and Public Health, Madrid, Spain; Translational Research Network in Pediatric Infectious Diseases, Madrid, Spain
- Dept. of Surgery and Surgical Specializations, Facultat de Medicina i Ciències de la Salut, University of Barcelona, Barcelona, Spain
| | - Swetha Madhavarapu
- Dept. of Pediatrics, Drexel University College of Medicine, St Christopher’s Hospital for Children, Philadelphia, PA, USA
| | - Daniel H. Conway
- Dept. of Pediatrics, Drexel University College of Medicine, St Christopher’s Hospital for Children, Philadelphia, PA, USA
| | - Carolina Prando
- Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Hospital Pequeno Príncipe, Curitiba, Brazil
| | - Laire Schidlowski
- Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Hospital Pequeno Príncipe, Curitiba, Brazil
| | | | - Rafael Alfaro
- Dept. of Immunology, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
| | - Felipe Rodríguez de Castro
- Dept. of Medical and Surgical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
- Dept. of Respiratory Diseases, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
| | - Isabelle Meyts
- Laboratory for Inborn Errors of Immunity, Dept. of Microbiology, Immunology and Transplantation KU Leuven, Leuven, Belgium
- Dept. of Pediatrics, Childhood Immunology, UZ Leuven, Leuven, Belgium
| | - Fabian Hauck
- Dept. of Pediatrics, Division of Pediatric Immunology and Rheumatology, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Anne Puel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
| | - Paul Bastard
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
- Pediatric Hematology and Immunology Unit, Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France
| | - Bertrand Boisson
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
| | - Emmanuelle Jouanguy
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
| | - Laurent Abel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
| | - Aurélie Cobat
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
| | - Qian Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- University Paris Cité, Imagine Institute, Paris, France
- Department of Pediatrics, Necker Hospital for Sick Children, Paris, France
- Howard Hughes Medical Institute, New York, NY, USA
| | - Laia Alsina
- Pediatric Allergy and Clinical Immunology Dept., Clinical Immunology and Primary Immunodeficiencies Unit, Hospital Sant Joan de Déu, Barcelona, Barcelona, Spain
- Study Group for Immune Dysfunction Diseases in Children, Institut de Recerca Sant Joan de Déu, Barcelona, Barcelona, Spain
- Clinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic Barcelona, Barcelona, Spain
- Dept. of Surgery and Surgical Specializations, Facultat de Medicina i Ciències de la Salut, University of Barcelona, Barcelona, Spain
| | - Carlos Rodríguez-Gallego
- Dept. of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
- Dept. of Immunology, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain
- Dept. of Medical and Surgical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
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13
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Lin GYE, Lin CY, Chi H, Huang DTN, Huang CY, Chiu NC. The experience of using FilmArray Meningitis/Encephalitis Panel for the diagnosis of meningitis and encephalitis in pediatric patients. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2022; 55:1180-1187. [PMID: 35987724 DOI: 10.1016/j.jmii.2022.07.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 07/02/2022] [Accepted: 07/30/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND/PURPOSE Central nervous system infections can cause severe complications and even death in children. Early diagnosis of the causative pathogen can guide appropriate treatment and improve outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) is a multiplex polymerase chain reaction (PCR) assay targeting 14 pathogens. We aimed to examine FA-ME performance compared with conventional assays and its effect on antimicrobial usage. METHODS We prospectively enrolled 55 pediatric patients with suspected meningitis or encephalitis and simultaneously performed FA-ME and conventional assays. Sixty-three hospitalized patients with CNS infection before implementing FA-ME were considered controls. We compared the FA-ME results with conventional assays and the empiric antimicrobial usage and hospital stay between the two study groups. RESULTS Nine patients (16.4%) tested positive by FA-ME, four were bacterial, and five were viral. Three additional pathogens were detected by conventional assays: Enterococcus faecalis, Leptospira, and herpes simplex virus type 2. In the control group, two bacterial pathogens were detected by CSF culture and four viral pathogens by single PCRs. Compared with the control group, the FA-ME group had a shorter time for pathogen detection, but there were no significant differences in pathogen detection rate, duration of empiric antimicrobial therapy, and length of hospital stay. CONCLUSION Although no significant difference was found in empiric antimicrobial duration and length of stay between patients tested with FA-ME and conventional assays, FA-ME had the advantage of a shorter detection time and early exclusion of potential causative pathogens. The FA-ME results should be interpreted carefully based on the clinical presentation.
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Affiliation(s)
- Grace Yong-En Lin
- Department of Pediatric Infectious Diseases, MacKay Children's Hospital, Taipei, Taiwan; Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan.
| | - Chien-Yu Lin
- Department of Medicine, MacKay Medicine College, New Taipei, Taiwan; Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan.
| | - Hsin Chi
- Department of Pediatric Infectious Diseases, MacKay Children's Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medicine College, New Taipei, Taiwan.
| | - Daniel Tsung-Ning Huang
- Department of Pediatric Infectious Diseases, MacKay Children's Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medicine College, New Taipei, Taiwan.
| | - Ching-Ying Huang
- Department of Pediatric Infectious Diseases, MacKay Children's Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medicine College, New Taipei, Taiwan.
| | - Nan-Chang Chiu
- Department of Pediatric Infectious Diseases, MacKay Children's Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medicine College, New Taipei, Taiwan.
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14
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Azar MM, Turbett S, Gaston D, Gitman M, Razonable R, Koo S, Hanson K, Kotton C, Silveira F, Banach DB, Basu SS, Bhaskaran A, Danziger-Isakov L, Bard JD, Gandhi R, Hanisch B, John TM, Odom John AR, Letourneau AR, Luong ML, Maron G, Miller S, Prinzi A, Schwartz I, Simner P, Kumar D. A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients. Am J Transplant 2022; 22:3150-3169. [PMID: 35822346 DOI: 10.1111/ajt.17147] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 06/28/2022] [Accepted: 07/07/2022] [Indexed: 01/25/2023]
Abstract
The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.
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Affiliation(s)
- Marwan M Azar
- Yale University School of Medicine, New Haven, Connecticut, USA
| | - Sarah Turbett
- Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - David Gaston
- John's Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Melissa Gitman
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | - Sophia Koo
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kimberly Hanson
- University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Camille Kotton
- Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Fernanda Silveira
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - David B Banach
- University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Sankha S Basu
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Lara Danziger-Isakov
- Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio, USA
| | - Jennifer Dien Bard
- Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA
| | - Ronak Gandhi
- Department of Pharmacy Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Benjamin Hanisch
- Children's National Hospital, Washington, District of Columbia, USA
| | - Teny M John
- The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Audrey R Odom John
- Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alyssa R Letourneau
- Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Me-Linh Luong
- Department of Microbiology, University of Montreal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada
| | - Gabriela Maron
- St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Steve Miller
- University of California San Francisco School of Medicine, San Francisco, California, USA
| | - Andrea Prinzi
- Infectious Disease Medical Science Liaison, Denver, Colorado, USA
| | - Ilan Schwartz
- Faculty of Medicine and Dentistry, University of Alberta, University of Alberta, Alberta, Canada
| | - Patricia Simner
- John's Hopkins University School of Medicine, Baltimore, Maryland, USA
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Karaaslan A, Çetin C, Köle MT, Çağ Y, Tekol SD, Akın Y. Investigation of the Etiological Causes of Central Nervous System Infection in Children with Multiplex PCR. J PEDIAT INF DIS-GER 2022. [DOI: 10.1055/s-0042-1749647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Objective The aim of this study is to investigate the causative agents of central nervous system (CNS) infection in hospitalized pediatric patients by multiplex polymerase chain reaction.
Methods We retrospectively reviewed the medical records of children who underwent lumbar puncture with suspected CNS infection between September 2019 and September 2021. The cerebrospinal fluid (CSF) samples were evaluated by the BioFire FilmArray Meningitis/Encephalitis (ME) Panel.
Results The etiology of the infection was established in 13,02% (n = 25) cases. Human herpesvirus (HHV) type 6 was the most commonly identified pathogen 60% (n = 15), followed by enterovirus 20% (n = 5), Streptococcus pneumoniae 8% (n = 2), Streptococcus agalactiae 4% (n = 1), HHV type 1 4% (n = 1), and Listeria monocytogenes 4% (n = 1). The statistical analysis showed that the age of the group with enterovirus was younger than the age of the group with other causative microorganisms and the group with HHV-6 (respectively p: 0.032; p: 0.011). The hospitalization periods of the group with enterovirus and HHV-6 were shorter than the hospitalization periods of the other causative microorganisms (respectively p: 0.016; p: 0.000) and the absolute neutrophil count values of the group with HHV-6 were lower than the group of other causative microorganisms (p: 0.015).
Conclusion Our study identified HHV-6 as the main cause of CNS infection in Istanbul during coronavirus disease 2019 pandemic when isolation measures were taken. The duration of hospital stay was found to be shorter in CNS infection caused by viral agents. Revealing the causative agent in the CSF is a fast and effective method that prevents unnecessary antibiotic treatment and shortens the hospitalization period of patients.
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Affiliation(s)
- Ayşe Karaaslan
- Department of Pediatric Infectious Diseases, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Ceren Çetin
- Department of Pediatric Infectious Diseases, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Mehmet Tolga Köle
- Department of Pediatrics, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Yakup Çağ
- Department of Pediatrics, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Serap Demir Tekol
- Department of Microbiology, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
| | - Yasemin Akın
- Department of Pediatrics, University of Health Sciences, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey
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Milburn J, Lechiile K, Siamisang K, Williams CG, Owen L, Gwakuba E, Machiya T, Leeme T, Barton HE, Doyle R, Tenforde MW, Mine M, Goldfarb DM, Mokomane M, Jarvis JN. Human Herpesvirus-6 Detection in Cerebrospinal Fluid on the BioFire FilmArray Meningitis/Encephalitis Panel in a High HIV-prevalence African Setting. Open Forum Infect Dis 2022; 9:ofac229. [PMID: 35854999 PMCID: PMC9280324 DOI: 10.1093/ofid/ofac229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/16/2022] [Indexed: 11/30/2022] Open
Abstract
The prevalence and clinical relevance of human herpesvirus-6 (HHV-6) detection in cerebrospinal fluid (CSF) using multiplex polymerase chain reaction (PCR) testing in patients with suspected meningoencephalitis in high human immunodeficiency virus-prevalence African settings are not known. We describe the clinical and laboratory characteristics of 13 patients with HHV-6 CSF PCR positivity in Botswana.
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Affiliation(s)
- James Milburn
- Botswana Harvard AIDS Institute Partnership, Gaborone, BOTSWANA
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Kwana Lechiile
- Botswana Harvard AIDS Institute Partnership, Gaborone, BOTSWANA
| | | | | | - Leah Owen
- Botswana-UPenn Partnership, Gaborone, BOTSWANA
| | | | - Tichaona Machiya
- Microbiology Department, Princess Marina Hospital, Gaborone, BOTSWANA
| | - Tshepo Leeme
- Botswana Harvard AIDS Institute Partnership, Gaborone, BOTSWANA
| | | | - Ronan Doyle
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | | | - Madisa Mine
- National Health Laboratory, Gaborone, BOTSWANA
| | - David M Goldfarb
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, CANADA
| | | | - Joseph N Jarvis
- Botswana Harvard AIDS Institute Partnership, Gaborone, BOTSWANA
- Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
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17
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Paul SP, Balakumar V, Kirubakaran A, Niharika J, Heaton PA, Turner PC. Turnaround times for molecular testing of pediatric viral cerebrospinal fluid samples in United Kingdom laboratories. World J Clin Pediatr 2022; 11:289-294. [PMID: 35663004 PMCID: PMC9134154 DOI: 10.5409/wjcp.v11.i3.289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/01/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Rapid molecular testing has revolutionized the management of suspected viral meningitis and encephalitis by providing an etiological diagnosis in < 90 min with potential to improve outcomes and shorten inpatient stays. However, use of molecular assays can vary widely.
AIM To evaluate current practice for molecular testing of pediatric cerebrospinal fluid (CSF) samples across the United Kingdom using a structured questionnaire.
METHODS A structured telephone questionnaire survey was conducted between July and August 2020. Data was collected on the availability of viral CSF nucleic acid amplification testing (NAAT), criteria used for testing and turnaround times including the impact of the coronavirus disease 2019 pandemic.
RESULTS Of 196/212 (92%) microbiology laboratories responded; 63/196 (32%) were excluded from final analysis as they had no on-site microbiology laboratory and outsourced their samples. Of 133 Laboratories included in the study, 47/133 (35%) had onsite facilities for viral CSF NAAT. Hospitals currently undertaking onsite NAAT (n = 47) had much faster turnaround times with 39 centers (83%) providing results in ≤ 24 h as compared to those referring samples to neighboring laboratories (5/86; 6%).
CONCLUSION Onsite/near-patient rapid NAAT (including polymerase chain reaction) is recommended wherever possible to optimize patient management in the acute setting.
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Affiliation(s)
- Siba Prosad Paul
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
| | | | - Arangan Kirubakaran
- Department of Paediatrics, Hillingdon Hospital, Uxbridge UB8 3NN, United Kingdom
| | | | - Paul Anthony Heaton
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
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18
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Paul SP, Balakumar V, Kirubakaran A, Niharika J, Heaton PA, Turner PC. Turnaround times for molecular testing of pediatric viral cerebrospinal fluid samples in United Kingdom laboratories. World J Clin Pediatr 2022. [DOI: 10.5409/wjcp.v11.i3.290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Rapid molecular testing has revolutionized the management of suspected viral meningitis and encephalitis by providing an etiological diagnosis in < 90 min with potential to improve outcomes and shorten inpatient stays. However, use of molecular assays can vary widely.
AIM To evaluate current practice for molecular testing of pediatric cerebrospinal fluid (CSF) samples across the United Kingdom using a structured questionnaire.
METHODS A structured telephone questionnaire survey was conducted between July and August 2020. Data was collected on the availability of viral CSF nucleic acid amplification testing (NAAT), criteria used for testing and turnaround times including the impact of the coronavirus disease 2019 pandemic.
RESULTS Of 196/212 (92%) microbiology laboratories responded; 63/196 (32%) were excluded from final analysis as they had no on-site microbiology laboratory and outsourced their samples. Of 133 Laboratories included in the study, 47/133 (35%) had onsite facilities for viral CSF NAAT. Hospitals currently undertaking onsite NAAT (n = 47) had much faster turnaround times with 39 centers (83%) providing results in ≤ 24 h as compared to those referring samples to neighboring laboratories (5/86; 6%).
CONCLUSION Onsite/near-patient rapid NAAT (including polymerase chain reaction) is recommended wherever possible to optimize patient management in the acute setting.
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Affiliation(s)
- Siba Prosad Paul
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
| | | | - Arangan Kirubakaran
- Department of Paediatrics, Hillingdon Hospital, Uxbridge UB8 3NN, United Kingdom
| | | | - Paul Anthony Heaton
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
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19
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Teoh T, Powell J, O’Keeffe J, Donlon E, Dillon L, Lenihan M, Mostyn A, Power L, Boers P, Stapleton PJ, O’Connell NH, Dunne CP. Outcomes of implementation of the FilmArray meningoencephalitis panel in a tertiary hospital between 2017 and 2020. PLoS One 2022; 17:e0265187. [PMID: 35298491 PMCID: PMC8929653 DOI: 10.1371/journal.pone.0265187] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 02/25/2022] [Indexed: 11/23/2022] Open
Abstract
Background Acute meningoencephalitis is encountered commonly in the acute hospital setting and is associated with significant morbidity and mortality, in addition to significant healthcare costs. Multiplex PCR panels now allow syndromic testing for central nervous system infection. The BioFire® FilmArray® Meningoencephalitis (ME) allows testing of 14 target pathogens using only 0.2mls of cerebrospinal fluid (CSF). We conducted a retrospective observational study to assess the performance of the assay and secondarily to observe the clinical utility of negative results by comparing clinical outcomes of aseptic meningitis to bacterial and viral meningoencephalitis. Methods Data for CSF samples tested using the FilmArray ME panel from October 2017 to October 2020 were analysed. Detection of bacterial and viral targets was analysed. Admission to critical care area, 90-day readmission rates, average length of stay and 30-day and 90-day mortality were analysed for three groups with following diagnoses: bacterial meningitis, viral meningoencephalitis, or aseptic meningitis. Results From October 2017 to October 2020, 1926 CSF samples were received in the Clinical Microbiology laboratory. Of those, 543 CSF samples from 512 individual patients were tested using the FilmArray ME panel. Twenty-one bacterial targets and 56 viral targets were detected during the study period. For viral targets, the cumulative specificity was 98.9% (95% confidence interval: 93.1–99.9) when compared to the reference laboratory methods. The outcomes for 30- and 90-day mortality of the aseptic meningitis group were non-inferior relative to the viral meningoencephalitis and bacterial meningitis group. Patients with bacterial meningitis had a longer average length of stay. Aseptic meningitis was associated with a higher 90-day readmission rate than the other 2 groups, but without statistical significance. Conclusion In our hands, implementation of the FilmArray ME panel was relatively straightforward. We experienced a transition in our workflow processes that enabled streamlining of CSF diagnostics and the safe removal of Gram staining in those samples being tested by this molecular assay. Coupled to this improvement, there was a positive clinical impact on patient care due to rapid turnaround time to results.
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Affiliation(s)
- TeeKeat Teoh
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
- Centre for Interventions in Infection, Inflammation & Immunity (4i), Limerick, Ireland
- School of Medicine, University of Limerick, Limerick, Ireland
| | - James Powell
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
| | - Jillian O’Keeffe
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
| | - Eoghan Donlon
- Department of Neurology, University Limerick Hospital Group, Limerick, Ireland
| | - Lisa Dillon
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
| | - Marie Lenihan
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
| | - Amanda Mostyn
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
| | - Lorraine Power
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
| | - Peter Boers
- Department of Neurology, University Limerick Hospital Group, Limerick, Ireland
| | - Patrick J. Stapleton
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
- School of Medicine, University of Limerick, Limerick, Ireland
| | - Nuala H. O’Connell
- Department of Clinical Microbiology, University Limerick Hospital Group, Limerick, Ireland
- Centre for Interventions in Infection, Inflammation & Immunity (4i), Limerick, Ireland
- School of Medicine, University of Limerick, Limerick, Ireland
| | - Colum P. Dunne
- Centre for Interventions in Infection, Inflammation & Immunity (4i), Limerick, Ireland
- School of Medicine, University of Limerick, Limerick, Ireland
- * E-mail:
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20
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Ekambaram M, Nabower A, Rajbhandari P, Eisenberg J, Goodrich N, Ampofo K, Gollehon NS, Martin KC, Lyden E, Snowden J. Evaluation of Discordant Results Between FilmArray Meningitis/Encephalitis Panel and Conventional Testing in Pediatric Patients: A Multisite Retrospective Cohort Study. J Pediatric Infect Dis Soc 2022; 11:134-141. [PMID: 35020927 DOI: 10.1093/jpids/piab126] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/25/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The FilmArray Meningitis/Encephalitis panel (MEP) has an 11% false-positive and 2.2% false-negative rate compared with conventional testing. We describe clinical characteristics, treatment decisions, and outcomes in children with discordant results between MEP and conventional testing. METHODS We conducted a multisite review of patients ≤ 18 years with suspected central nervous system infection and positive results by MEP or conventional testing (cerebrospinal fluid [CSF] culture, herpes simplex virus [HSV] polymerase chain reaction (PCR), and enterovirus [EV] PCR). Descriptive results are provided for patients with discordant results. Comparison between group 1 (MEP and CSF culture positive) and group 2 (MEP positive, CSF culture negative, or showing a different pathogen) was made by Mann-Whitney test for continuous and Fisher's test for categorical variables. RESULTS A total of 355 patients had at least one pathogen identified. More than half of patients with bacterial pathogens identified that are included in the MEP had discordant results (30/52; 58%). There were 28 samples with bacterial pathogen identified on MEP only, 1 with different bacterial pathogens on MEP and culture, and 1 with Escherichia coli identified on CSF culture only. Patients in group 1 were more likely to have CSF pleocytosis, elevated CSF protein, and decreased CSF glucose than group 2 (P < .05). Two patients were HSV positive by MEP while HSV negative by PCR. Ten patients had discordant results between MEP and EV PCR. CONCLUSIONS Discordant results between MEP and conventional testing are common. Treatment decisions based on a positive MEP should be made in the appropriate clinical context.
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Affiliation(s)
- Maheswari Ekambaram
- Department of Pediatrics, Baylor Scott and White Medical Center, Round Rock, Texas, USA
| | - Aleisha Nabower
- Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Prabi Rajbhandari
- Division of Hospital Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio, USA
| | - Jaclyn Eisenberg
- Section of Pediatric Hospital Medicine, Department of Pediatrics, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Nathaniel Goodrich
- Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Krow Ampofo
- Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
| | - Nathan S Gollehon
- Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Kimberly C Martin
- Department of Pediatrics, University of Oklahoma School of Community Medicine, Tulsa, Oklahoma, USA
| | - Elizabeth Lyden
- Department of Biostatistics, University of Nebraska College of Public Health, Omaha, Nebraska, USA
| | - Jessica Snowden
- Department of Pediatrics, University of Arkansas Medical Center, Little Rock, Arkansas, USA
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21
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Differential Performance of the FilmArray Meningitis/Encephalitis Assay To Detect Bacterial and Viral Pathogens in Both Pediatric and Adult Populations. Microbiol Spectr 2022; 10:e0277421. [PMID: 35404096 PMCID: PMC9045182 DOI: 10.1128/spectrum.02774-21] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Meningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients. IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.
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22
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Wenner AM, Weitz L, Ostertag K, Hubmer S, Springer E, Stoiser B, Baumgartner C, Riederer F. Human Herpesvirus 6 in the CSF of a Woman With New-Onset Seizures: Encephalitis or Genomic Integration? Neurol Clin Pract 2021; 11:e753-e756. [PMID: 34840899 DOI: 10.1212/cpj.0000000000001024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 10/21/2020] [Indexed: 11/15/2022]
Affiliation(s)
- Allyson M Wenner
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Lisa Weitz
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Karoline Ostertag
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Stefan Hubmer
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Elisabeth Springer
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Brigitte Stoiser
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Christoph Baumgartner
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
| | - Franz Riederer
- Medical University of Vienna (AMW, LW); Department of Neurology (KO, SH, CB, FR), Hietzing Hospital with Neurological Center Rosenhuegel and Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology (KO, SH, CB, FR); Institute of Radiology (ES), and Department of Microbiology (BS), Hietzing Hospital with Neurological Center Rosenhuegel; Medical Faculty (CB), Sigmund Freund Private University, Vienna, Austria; and Department of Neurology (FR), University Hospital Zurich, University of Zurich, Switzerland
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23
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Ramachandran PS, Wilson MR, Catho G, Blanchard-Rohner G, Schiess N, Cohrs RJ, Boutolleau D, Burrel S, Yoshikawa T, Wapniarski A, Heusel EH, Carpenter JE, Jackson W, Ford BA, Grose C. Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling. Viruses 2021; 13:2286. [PMID: 34835092 PMCID: PMC8620440 DOI: 10.3390/v13112286] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/04/2021] [Accepted: 11/05/2021] [Indexed: 11/21/2022] Open
Abstract
Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3-4 weeks before onset of vaccine meningitis may be a risk factor in some cases.
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Affiliation(s)
- Prashanth S. Ramachandran
- Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USA; (P.S.R.); (M.R.W.); (A.W.)
| | - Michael R. Wilson
- Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USA; (P.S.R.); (M.R.W.); (A.W.)
| | - Gaud Catho
- Division of Pediatric Infectious Diseases, Geneva University Hospitals, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland;
| | - Geraldine Blanchard-Rohner
- Pediatric Immunology and Vaccinology Unit, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland;
| | - Nicoline Schiess
- Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA;
| | - Randall J. Cohrs
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA;
| | - David Boutolleau
- Virology Department, National Reference Center for Herpesviruses, Pitie-Salpetriere Hospital, Sorbonne University, 75013 Paris, France; (D.B.); (S.B.)
| | - Sonia Burrel
- Virology Department, National Reference Center for Herpesviruses, Pitie-Salpetriere Hospital, Sorbonne University, 75013 Paris, France; (D.B.); (S.B.)
| | - Tetsushi Yoshikawa
- Department of Pediatrics, Fujita Health University School of Medicine, Aichi, Toyoake 470-1192, Japan;
| | - Anne Wapniarski
- Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USA; (P.S.R.); (M.R.W.); (A.W.)
| | - Ethan H. Heusel
- Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA; (E.H.H.); (J.E.C.); (W.J.)
| | - John E. Carpenter
- Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA; (E.H.H.); (J.E.C.); (W.J.)
| | - Wallen Jackson
- Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA; (E.H.H.); (J.E.C.); (W.J.)
| | - Bradley A. Ford
- Department of Pathology, University of Iowa, Iowa City, IA 52242, USA;
| | - Charles Grose
- Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA; (E.H.H.); (J.E.C.); (W.J.)
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24
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Abstract
Syndromic panels have allowed clinical microbiology laboratories to rapidly identify bacteria, viruses, fungi, and parasites and are now fully integrated into the standard testing practices of many clinical laboratories. To maximize the benefit of syndromic testing, laboratories must implement strict measures to ensure that syndromic panels are being used responsibly. This article discusses commercially available syndromic panels, the benefits and limitations of testing, and how diagnostic and laboratory stewardship can be used to optimize testing and improve patient care while keeping costs at a minimum.
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Affiliation(s)
- Jennifer Dien Bard
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Boulevard MS#32, Los Angeles, CA 90027, USA; University of Southern California, Keck School of Medicine.
| | - Erin McElvania
- Department of Pathology and Laboratory Medicine, Evanston Hospital, NorthShore University HealthSystem, 2650 Ridge Avenue, Evanston, IL 60201, USA; University of Chicago Pritzker School of Medicine. https://twitter.com/e_mcelvania
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25
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Dou C, Xie X, Peng Z, Tang H, Jiang Z, Zhong Z, Tang J. A case presentation for positive SARS-CoV-2 RNA recurrence in a patient with a history of type 2 diabetes that had recovered from severe COVID-19. Diabetes Res Clin Pract 2020; 166:108300. [PMID: 32663490 PMCID: PMC7354258 DOI: 10.1016/j.diabres.2020.108300] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/07/2020] [Accepted: 06/29/2020] [Indexed: 11/25/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is considered to be spread primarily by people who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss a patient with severe COVID-19 and a history of type 2 diabetes who had a recurrence of positive SARS-CoV-2 ribonucleic acid (RNA) after recovering. The patient was initially discharged after two consecutive negative SARS-CoV-2 RNA tests and partially absorbed bilateral lesions on chest computed tomography (CT). However, at his first follow-up, reverse transcription-polymerase chain reaction (RT-PCR) assay with an oropharyngeal swab sample was positive for SARS-CoV-2. Despite this, he displayed no obvious clinical symptoms and improved chest CT. The patient was prescribed anti-viral medication. Eight consecutive RT-PCR assays on oropharyngeal swab specimens were conducted after he was re-admitted to our hospital. The results tested positive on the 12th, 14th, 19th, 23rd and 26th of March and negative on the 28th of March, and 6th and 12th of April. After his second discharge, he has tested negative for 5 weeks. This case highlights the importance of active surveillance of SARS-CoV-2 RNA during the follow-up period so that an infectivity assessment can be made.
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MESH Headings
- Adult
- Betacoronavirus/genetics
- Betacoronavirus/isolation & purification
- Blood Glucose/metabolism
- COVID-19
- Coronavirus Infections/complications
- Coronavirus Infections/diagnosis
- Coronavirus Infections/transmission
- Coronavirus Infections/virology
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/physiopathology
- Diabetes Mellitus, Type 2/virology
- Humans
- Male
- Pandemics
- Pneumonia, Viral/complications
- Pneumonia, Viral/diagnosis
- Pneumonia, Viral/transmission
- Pneumonia, Viral/virology
- Prognosis
- RNA, Viral/analysis
- RNA, Viral/genetics
- SARS-CoV-2
- Tomography, X-Ray Computed/methods
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Affiliation(s)
- Chengyun Dou
- The First Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China
| | - Xia Xie
- The First Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China
| | - Zhongtian Peng
- The First Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China
| | - Haibo Tang
- The First Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China
| | - Zheng Jiang
- Public Health Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China
| | - Zhefeng Zhong
- Affiliated Nanhua Hospital of University of South China, Hengyang 421000, Hunan, China
| | - Jian Tang
- The First Affiliated Hospital of University of South China, Hengyang 421000, Hunan, China.
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Au CC, Hon KL, Leung AKC, Torres AR. Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents. RECENT PATENTS ON INFLAMMATION & ALLERGY DRUG DISCOVERY 2020; 14:156-165. [PMID: 33238854 DOI: 10.2174/1872213x14999201124195724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 10/14/2020] [Accepted: 10/19/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Infectious encephalitis is a serious and challenging condition to manage. This overview summarizes the current literature regarding the etiology, clinical manifestations, diagnosis, management, and recent patents of acute childhood infectious encephalitis. METHODS We used PubMed Clinical Queries as a search engine and used keywords of "encephalitis" AND "childhood" Patents were searched using the key term "encephalitis" in google.patents.- com and patentsonline.com. RESULTS Viral encephalitis is the most common cause of acute infectious encephalitis in children. In young children, the clinical manifestations can be non-specific. Provision of empiric antimicrobial therapy until a specific infectious organism has been identified, which in most cases includes acyclovir, is the cornerstone of therapy. Advanced investigation tools, including nucleic acid-based test panel and metagenomic next-generation sequencing, improve the diagnostic yield of identifying an infectious organism. Supportive therapy includes adequate airway and oxygenation, fluid and electrolyte balance, cerebral perfusion pressure support, and seizure control. Recent patents are related to the diagnosis, treatment, and prevention of acute infectious encephalitis. CONCLUSION Viral encephalitis is the most common cause of acute infectious encephalitis in children and is associated with significant morbidity. Recent advances in understanding the genetic basis and immunological correlation of infectious encephalitis may improve treatment. Third-tier diagnostic tests may be incorporated into clinical practice. Treatment is targeted at the infectious process but remains mostly supportive. However, specific antimicrobial agents and vaccines development is ongoing.
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Affiliation(s)
- Cheuk C Au
- Department of Paediatrics and Adolescent Medicine, The Hong Kong Children's Hospital, Kowloon Bay, Kowloon, Hong Kong
| | - Kam L Hon
- Department of Paediatrics and Adolescent Medicine, The Hong Kong Children's Hospital, Kowloon Bay, Kowloon, Hong Kong
| | - Alexander K C Leung
- Department of Pediatrics, The University of Calgary and The Alberta Children's Hospital, Calgary, Alberta, Canada
| | - Alcy R Torres
- Department of Pediatrics, Division of Pediatric Neurology, Pediatric Traumatic Brain Injury Program, Associate Professor of Pediatrics and Neurology, Boston University, School of Medicine, Boston, MA, United States
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