Application of Next Generation Sequencing Technique in Pediatric Bacterial Meningitis

NCT ID: NCT03953638

Last Updated: 2019-05-16

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2020-07-31

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.

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.

Conditions

Next Generation Sequencing; Pediatric Bacterial Meningitis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Next Generation Sequencing

To provide rapid etiological diagnosis of patients by means of next-generation sequencing.

Intervention Type: DIAGNOSTIC_TEST

Eligibility 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

• Minimum Eligible Age: 28 Days
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xingtai People's Hospital

OTHER

Sponsor Role: collaborator

Baoding Children's Hospital

OTHER

Sponsor Role: collaborator

Jinan children's hospital

UNKNOWN

Sponsor Role: collaborator

Liaocheng People's Hospital

OTHER

Sponsor Role: collaborator

Nanjing Children's Hospital

OTHER

Sponsor Role: collaborator

Shenzhen Baoan Maternal and Child Care Service Centre

UNKNOWN

Sponsor Role: collaborator

Jiangxi Children's Hospital

UNKNOWN

Sponsor Role: collaborator

Kunming Children's Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Xinjiang Medical University

OTHER

Sponsor Role: collaborator

Children's Hospital Affiliated to Suzhou University

UNKNOWN

Sponsor Role: collaborator

Beijing Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gang Liu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gang Liu

Role: PRINCIPAL_INVESTIGATOR

Beijing Children's Hospital

Locations

Beijing Children's Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Gang Liu

Role: CONTACT

liugang10@hotmail.com

008613370115008

Facility Contacts

Gang Liu

Role: primary

liugang10@hotmail.com

008613370115008

Other Identifiers

20190514

Identifier Type: -

Identifier Source: org_study_id