Paediatric Infections Point-Of-Care

NCT03900091 | Completed

• 1 other identifier: 2018/1676-31/1
• Study Type: observational
• Target: 351
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to identify the aetiology of childhood meningitis in Southwestern Uganda and develop and evaluate new methods for point-of-care diagnosis of childhood meningitis in a low-income setting. A prospective observational study including 600 children aged 0-12 years will be conducted during 1 year in Mbarara, Uganda. We estimate to recruit about 300 children with suspected meningitis (cases), and 300 with non-severe infection age-matched as controls.

Conditions

Meningitis; Pediatric Infectious Diseases

Keywords

Point of care; Diagnostics; Low-income countries; Meningitis; Pediatrics; MxA; FilmArray; Low-cost diagnostics

Outcome Measures

Primary Outcomes (1)

• Diagnostic accuracy of vertical flow microarray printed on paper for pathogen identification in human cerebrospinal fluid samples

  The newly developed assay will be evaluated with regards to diagnostic accuracy. For this, results will be compared with those from bacterial culture, PCR and FilmArray analyses of the same samples.

  Patient CSF will be analysed with culture, PCR and FilmArray during ongoing patient management in Mbarara, Uganda. Analyses on frozen patient CSF samples with vertical flow paper printed microarray will be done in Stockholm, Sweden within 1 year.

Secondary Outcomes (8)

• Protein profile variance between children with severe and non-severe infection

  Frozen patient blood samples will be analyzed using Luminex Multiplex Assays in Stockholm, Sweden, within 1 year after sample collection in Mbarara, Uganda.

• Variance in concentration of MxA in blood of patients with viral vs. non-viral meningitis and non-severe infection.

  MxA concentration measurements will be conducted on the Luminex platform on frozen patient blood samples in Stockholm, Sweden, within a year from sample collection.

• Diagnostic performance of the FilmArray ME Panel for meningitis diagnostics in children in a low-income setting

  FilmArray analyses on fresh patient CSF samples will be conducted immediately after or within 1 day of sample collection.

• Clinical impact of the FilmArray ME Panel on management of childhood meningits in a low-income setting.

  FilmArray analyses on fresh patient CSF samples will be conducted immediately after or within 1 day of sample collection.

• Usability of the FilmArray ME Panel for meningitis diagnostics in children in a low-income setting.

  Questionnaires will be handed out and collected from participants continuously during the 1 year duration of patient inclusion.

Study Arms (2)

Cases with clinical meningitis

Patients aged 0-12 years with suspected CNS infection, at the pediatric clinics at Mbarara Regional Referral Hospital or Holy Innocents Children's Hospital, Mbarara, Uganda.

Diagnostic Test: Multiplex PCR assay for meningitis; Diagnostic Test: Multiplex vertical flow microarrray assay for meningitis; Diagnostic Test: Profiling of blood proteins by multi-analyte Profiling technology; Other: Typing and whole genome sequencing

Control subjects

Patients aged 0-12 years, visiting the outpatient pediatric clinics at Mbarara Regional Referral Hospital or Holy Innocents Children's Hospital, Mbarara, Uganda, with fever clinically considered non-severe.

Diagnostic Test: Profiling of blood proteins by multi-analyte Profiling technology; Other: Typing and whole genome sequencing

Interventions

Multiplex PCR assay for meningitis DIAGNOSTIC_TEST

CSF from cases to be analysed with a FilmArray ME Panel

Also known as: Biomerieux FilmArray ME Panel

Cases with clinical meningitis

Multiplex vertical flow microarrray assay for meningitis DIAGNOSTIC_TEST

CSF from cases will also undergo analysis with a newly developed prototype for point-of-care diagnostic tool for CNS infections identification. The tool is a DNA-based vertical flow microarray technology printed on paper.

Cases with clinical meningitis

Profiling of blood proteins by multi-analyte Profiling technology DIAGNOSTIC_TEST

Blood from cases and controls to be analysed using Luminex technology to identify protein profiles associated with severe and non-severe infection. Myxovirus protein A (MxA) will also be analysed by the Luminex assay, to associate MxA levels with severe/non-severe infection.

Also known as: Luminex Multi-Analyte Profiling (xMAP)

Cases with clinical meningitis; Control subjects

Typing and whole genome sequencing OTHER

Pathogenic strains isolated from nasopharyngeal swabs from cases and controls will undergo whole genome sequencing (WGS) and typing .

Cases with clinical meningitis; Control subjects

Eligibility Criteria

• Age: 1 Day - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

CASE DEFINITION: Patients aged 0-12 years, with suspected CNS infection understood as, having fever in the past 48 hours (children \<9 months may present with any temp)) AND recent onset of any of the following: * Non-traumatic reduced consciousness; in pre-verbals \<9 months Blantyre coma score \<4; Blantyre coma score \<5 for older pre-verbals. In verbal children Glasgow Coma Scale \<15 * prostration, hypotonia/hypertonia, unexplained irritability * severe headache * photophobia * neck stiffness or bulging fontanel * seizure(s) * focal neurological signs * age \>18 months: positive Kernig or Brudzinski signs * Skin petechiae * Cheyne Stokes CNS infection can be suspected for other reasons CONTROL DEFINITION: Patients aged 0-12 years, visiting the outpatient pediatric clinics with fever and not meeting the case inclusion criteria. For every case, one age-matched control will be sought until included.

You may qualify if:

• Children aged 0 months to 12 years of age, who
• meet the case or control definition criteria, and where
• informed consent is obtained from the parent or guardian

You may not qualify if:

• No, insufficient or inappropriate CSF sample collection

Sponsors & Collaborators

• Karolinska Institutet: lead
• Mbarara University of Science and Technology: collaborator
• Science for Life Laboratory: collaborator
• Epicentre Mbarara Research Center: collaborator
• Stockholm South General Hospital: collaborator

Study Sites (2)

Holy Innocents Children's Hospital

Mbarara, Uganda

Location

Mbarara Regional Referral Hospital

Mbarara, Uganda

Location

Related Publications (2)

• Rasti R, Kumbakumba E, Nanjebe D, Mlotshwa P, Nassejje M, Mzee J, Businge S, Akankwasa G, Nyehangane D, Gantelius J, Boum Y 2nd, Martensson A, Mwanga-Amumpaire J, Alfven T, Gaudenzi G. Clinical utility of the FilmArray(R) meningitis/encephalitis panel in children with suspected central nervous system infection in a low-resource setting - a prospective study in Southwestern Uganda. BMC Infect Dis. 2025 Mar 22;25(1):396. doi: 10.1186/s12879-025-10732-w.

  PMID: 40121439 DERIVED

• Gaudenzi G, Kumbakumba E, Rasti R, Nanjebe D, Reu P, Nyehangane D, Martensson A, Nassejje M, Karlsson J, Mzee J, Nilsson P, Businge S, Loh E, Boum Ii Y, Andersson-Svahn H, Gantelius J, Mwanga-Amumpaire J, Alfven T. Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the "PI-POC" Trial. JMIR Res Protoc. 2020 Nov 4;9(11):e21430. doi: 10.2196/21430.

  PMID: 33146628 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid Nasopharyngeal swabs Whole blood

MeSH Terms

Conditions

Meningitis

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Neuroinflammatory Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Elias Kumbakumba, MD

  Mbarara University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Tobias Alfvén, MD PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: April 2, 2019
• Study Start: April 1, 2019
• Primary Completion: July 24, 2020
• Study Completion: July 24, 2020
• Last Updated: December 16, 2020

Record last verified: 2020-12

Locations

UG (2)