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Application of Next Generation Sequencing Technique in Pediatric Bacterial Meningitis

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ClinicalTrials.gov Identifier: NCT03953638
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : May 16, 2019
Sponsor:
Collaborators:
Xingtai People's Hospital
Baoding Children's Hospital
Jinan children's hospital
Liaocheng Children's Hospital
Nanjing Children's Hospital
Shenzhen Baoan Maternal and Child Care Service Centre
Jiangxi Children's Hospital
Kunming Children's Hospital
First Affiliated Hospital of Xinjiang Medical University
Children's Hospital Affiliated to Suzhou University
Information provided by (Responsible Party):
Gang Liu, Beijing Children's Hospital

Brief Summary:
Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. However, cerebrospinal fluid (CSF) culture can be negative in children who receive antibiotic treatment prior to CSF examination.Because of the limitations of clinical laboratory testing, more than half of the central nervous system infection cases cannot be clearly diagnosed. The emergence of powerful next-generation sequencing (NGS) technology have enabled unbiased sequencing of biological samples due to its rapid turnaround time. Previous reports highlight the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) infection. However, the majority of reports are comprised of single case reports and few studies have been reported in the application of NGS for pathogen detection from CSF samples of bacterial meningitis patients, especially in pediatric populations. In this study, we would like to use the NGS technology to detect directly from the CSF samples of children with bacterial meningitis and evaluate the feasibility and significance of the NGS technique on the pathogenic identification of bacterial meningitis.

Condition or disease Intervention/treatment
Next Generation Sequencing Pediatric Bacterial Meningitis Diagnostic Test: Next Generation Sequencing

Detailed Description:

Bacterial meningitis, also known as purulent meningitis, is caused by a variety of bacterial infections. Although the incidence in infants and children has decreased since the use of conjugated vaccines targeting Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitides (N. meningitides), bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children throughout the world. The causative pathogens of bacterial meningitis depend on different age of the patient and predisposing factors.

Pathogen identification is of paramount importance for bacterial meningitis. At present, the pathogen of bacterial meningitis is still mainly based on Gram stain and bacterial culture. However, CSF culture can be negative in children who receive antibiotic treatment prior to CSF examination.Because of the limitations of clinical laboratory testing, more than half of the central nervous system infection cases cannot be clearly diagnosed. Although non-culture methods including multiplex PCR and latex agglutination, etc. have been used in clinical microbiology, only one or several specific pathogens could be targeted by these kinds of technology, let alone rare pathogens.

In recent years, the emergence of powerful NGS technology have enabled unbiased sequencing of biological samples due to its rapid turnaround time. Wilson et al presented a case of neuroleptospirosis, resulting in a dramatic clinical improvement with intravenous penicillin after identifying leptospira infection in the CSF by unbiased NGS technology. Unbiased NGS could facilitate identification of all the potential pathogens in a single assay theoretically. Herpes simplex virus1, herpes simplex virus 2 and human herpes virus type 3 were detected using NGS technology from four cases with clinically suspected viral meningoencephalitis respectively. And the results were further validated using polymerase chain reaction (PCR). Further, Yao et al detected Listeria monocytogenes in CSF from three patients with meningoencephalitis by NGS. These reports highlight the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) infection. However, the majority of reports are comprised of single case reports and few studies have been reported in the application of NGS for pathogen detection from CSF samples of bacterial meningitis patients, especially in pediatric populations. In this study, we would like to use the NGS technology to detect directly from the CSF samples of children with bacterial meningitis and evaluate the feasibility and significance of the NGS technique on the pathogenic identification of bacterial meningitis.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: Application of Next Generation Sequencing Technique in Pediatric Bacterial Meningitis
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Meningitis


Intervention Details:
  • Diagnostic Test: Next Generation Sequencing
    To provide rapid etiological diagnosis of patients by means of next-generation sequencing.


Primary Outcome Measures :
  1. Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of next-generation sequencing in the pathogen detection of Pediatric Bacterial Meningitis [ Time Frame: 2 years ]
    We aim to collect samples cerebrospinal fluid from patients with Pediatric Bacterial Meningitis. Next-generation sequencing will be performed on the collected samples. Our analysis of the sequencing results will focus on the analysis and identification of pathogen genes and will compare the diagnostic performance of next-generation sequencing with conventional etiological diagnostic methods. We anticipate that next-generation sequencing in Pediatric Bacterial Meningitis will show a greater diagnostic value than the traditional methods (including culture, special pathogen antigen, PCR detection of nucleic acids, etc.).


Secondary Outcome Measures :
  1. Diagnostic value (sensitivity and sensibility, positive/negative predictive value) of traditional methods in the pathogen detection of infectious diseases [ Time Frame: 2 years ]
    We aim to collect CSF samples from patients with pediatric bacterial meningitis. Traditional methods including culture, special pathogen serology, PCR detection of nucleic acids, etc, will be performed on the collected samples. Our analysis aims to study the diagnostic power of the traditional diagnostic methods in infectious diseases.


Biospecimen Retention:   Samples With DNA
Cerebrospinal Fluid.


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients that are highly suspected of bacterial meningitis.
Criteria

Inclusion Criteria:

  • Patients highly suspected of bacterial meningitis

Exclusion Criteria:

  • Non-bacterial infectious central nervous system (CNS) confirmed by viral meningitis, tuberculous meningitis cryptococcal meningitis and so on
  • Autoimmune encephalitis cases
  • Central nervous system affected by neoplastic disease
  • Hemorrhagic cerebrospinal fluid
  • Less than 1ml cerebrospinal fluid
  • Refusal to enter the group

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03953638


Contacts
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Contact: Gang Liu 008613370115008 liugang10@hotmail.com

Locations
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China, 北京
Beijing Children's Hospital Recruiting
Beijing, 北京, China, 100045
Contact: Gang Liu    008613370115008    liugang10@hotmail.com   
Sponsors and Collaborators
Beijing Children's Hospital
Xingtai People's Hospital
Baoding Children's Hospital
Jinan children's hospital
Liaocheng Children's Hospital
Nanjing Children's Hospital
Shenzhen Baoan Maternal and Child Care Service Centre
Jiangxi Children's Hospital
Kunming Children's Hospital
First Affiliated Hospital of Xinjiang Medical University
Children's Hospital Affiliated to Suzhou University
Investigators
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Principal Investigator: Gang Liu Beijing Children's Hospital

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Responsible Party: Gang Liu, Professor, Beijing Children's Hospital
ClinicalTrials.gov Identifier: NCT03953638     History of Changes
Other Study ID Numbers: 20190514
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Meningitis
Meningitis, Bacterial
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Bacterial Infections
Bacterial Infections
Central Nervous System Infections