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MeningitisPI-POCNCT03900091

Paediatric Infections Point-Of-Care

An observational study of Meningitis and Pediatric Infectious Diseases, run by Karolinska Institutet at 2 sites in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 day to 12 years
Conditions the study is for
Meningitis, Pediatric Infectious Diseases
What is being tested?
Multiplex PCR assay for meningitis, Multiplex vertical flow microarrray assay for meningitis and Profiling of blood proteins by multi-analyte Profiling technology
How many people
351 participants
Where
2 sitesUganda
Study dates
1 Apr 2019to 24 Jul 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 day to 12 years
  • All sexes
  • No healthy volunteers
  • Child

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.

Who may be able to join

  • 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

Who cannot join

  • all 3 inclusion criteria not met
  • No, insufficient or inappropriate CSF sample collection

Trial locations and contacts

2 sites in 1 country.

Uganda2 sites
  • Holy Innocents Children's Hospital

    Mbarara

  • Mbarara Regional Referral Hospital

    Mbarara

Other trials in Uganda

About this study

Official title: Paediatric Infections Point-Of-Care: Point-of-care Approach for Rapid and Easy Meningitis Diagnosis

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.

Read the detailed description

The current gold standard for laboratory diagnostics of suspected childhood meningitis are microbiology culture of CSF and polymerase chain reaction (PCR). However, these methods are expensive, time-consuming, require dedicated facilities and trained professionals, that are often lacking in low-income health systems. Our team has developed a new vertical flow paper printed microarray method for rapid, inexpensive and multiplexed microbiology analysis of cerebrospinal fluid (CSF), with potential for point-of-care use in low-income settings. This study will evaluate the diagnostic accuracy of this newly developed paper printed microarray method.

The bioMérieux FilmArray® ME Panel is an existing multiplexed PCR based system for rapid microbiology analyses of CSF. Even though previous studies have reported good diagnostic accuracy of the FilmArray® system, the studies have mostly been focused on evaluating the system in high-income settings.

This study will do a field evaluation of the diagnostic performance and clinical usability of the FilmArray® ME Panel in a low-income setting in Mbarara, Uganda.

A study by Page et al, conducted 2009-2012 in Mbarara, Uganda, identified the most frequent pathogen causing childhood bacterial meningitis to be Streptococcus pneumoniae. This is also the case on a global level, with the addition of the bacteria Neisseria meningitidis and Haemophilus influenzae type B. However, the Page study did not find a single case of Neisseria meningitidis, which is in contrast to most other reports from low-, middle- and high-income countries. Furthermore, after the finalisation of the Page study, pneumococcal conjugate vaccines were introduced to the Ugandan childhood immunisation program. This study will identify the current aetiology of childhood meningitis and the impact of the pneumococcal conjugate vaccine, in Mbarara, Uganda, and also study the carriage and characteristics of Neisseria meningitis in children in the area.

Myxovirus resistance protein A (MxA) blood levels have been reported to be elevated in children with respiratory tract infections of viral aetiology, as compared to bacterial aetiology. Previous studies have also shown a higher abundance of MxA in viral encephalitis, however this only through histological analyses of post-mortem brain tissue samples.

This study aims to investigate the correlation of blood MxA levels in children with viral, bacterial and malarial meningitis in Mbarara, Uganda by analysing the protein profile and temporal dynamic in blood of children with severe and non-severe infection.

Being tested
Multiplex PCR assay for meningitis, Multiplex vertical flow microarrray assay for meningitis, Profiling of blood proteins by multi-analyte Profiling technology, Typing and whole genome sequencing
Keywords
Point of care, Diagnostics, Low-income countries, Meningitis, Pediatrics, MxA, FilmArray, Low-cost diagnostics
Medical subject headings
Meningitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Multiplex PCR assay for meningitisDiagnostic test

    Also called Biomerieux FilmArray ME Panel

    CSF from cases to be analysed with a FilmArray ME Panel

  • Multiplex vertical flow microarrray assay for meningitisDiagnostic 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.

  • Profiling of blood proteins by multi-analyte Profiling technologyDiagnostic test

    Also called Luminex Multi-Analyte Profiling (xMAP)

    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.

  • Typing and whole genome sequencingOther

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

Study groups in NCT03900091
Study groupRoleWhat they receive
Cases with clinical meningitisPatients 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.
Receives: 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 subjectsPatients 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.
Receives: Diagnostic Test: Profiling of blood proteins by multi-analyte Profiling technology; Other: Typing and whole genome sequencing

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)
  1. Protein profile variance between children with severe and non-severe infection

    Protein profile (biomarker) concentration (e.g. μg/L) variance in the blood of children with severe infection as compared to those with uncomplicated infection, as well as longitudinal variance in protein profile during the course of severe infection.

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

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

    Difference in MxA concentration (e.g. μg/L) in peripheral blood of patients with viral/non-viral meningitis and non-severe infection will be studied with the Luminex platform, to identify any feasibility of MxA to be used as a blood biomarker to differentiate between aetiologies of meningitis and to differentiate meningitis to non-severe infection. This in order to assist differential diagnostics in the clinical management of childhood fever.

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

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

    Diagnostic accuracy of the FilmArray® (compared to current gold standard methods PCR and culture) for aetiological diagnosis of CNS infections in children. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios will be calculated for the results from FilmArray analyses on patient CSF samples.

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

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

    Parameteres including time to laboratory confirmed diagnosis, time to treatment initiation, duration of hospital stay (all in hours/days) and patient mortality will be measured for suspected cases of meningitis whose CSF has been analyzed using the FilmArray® ME panel.

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

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

    A questionnaire will used to gather experiences from health care personnel in Mbarara involved in clinical management of children with suspected meningitis and laboratory personnel in Mbarara conducting FilmArray analyses, in order to study clinical perspectives on the contribution of FilmArray assays to the management of meningitis, in this low-income setting.

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

  6. Mapping of Neisseria meningitidis carriage and prevalence in children in Mbarara, Uganda

    Whole genome sequencing and serotyping of any strains of N. meningitidis isolated from nasopharyngeal swabs from included children in Mbarara (cases and controls) will be done to understand the local prevalence of N. meningitidis in severe/non-severely ill children in the district.

    Measured: Nasopharyngeal swabs will be collected upon inclusion to the study. Sequencing and serotyping will be done in Stockholm, Sweden, within 1 year after sample collection.

  7. Etiology of childhood meningitis in the Mbarara district, Uganda.

    Current aetiology of childhood meningitis in the Mbarara district, Uganda, will be studied through culture, PCR and FilmArray analyses of CSF samples from children with suspected meningitis.

    Measured: CSF culture, PCR and FilmArray analyses will be conducted during the 1 year duration of the study, in Mbarara, Uganda.

  8. The impact of pneumococcal conjugate vaccines on aetiology of childhood meningits in the Mbarara district.

    Comparison of current (post-vaccination era) to prior (pre-vaccination era) aetiology of childhood meningitis. The pneumococcal vaccine was recently included in the Ugandan childhood immunization program, and just prior to this, the aetiology of childhood meningitis in the Mbarara district was reported by Page et al, finding S. pneumoniae to be the most frequent agent causing bacterial meningitis in the district. Has this changed?

    Measured: CSF culture, PCR and FilmArray analyses will be conducted during the 1 year duration of the study, in Mbarara, Uganda.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2019
  2. Study start1 Apr 2019
  3. Primary completion24 Jul 2020
  4. Study completion24 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
351 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03900091
Sponsor's protocol ID
2018/1676-31/1
Acronym
PI-POC
Status last verified
Dec 2020
First submitted
19 Mar 2019
Last updated
16 Dec 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 40121439
  • 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.

    PubMed 33146628

Questions about this trial

What is this clinical trial studying?

An observational study of Meningitis and Pediatric Infectious Diseases, run by Karolinska Institutet at 2 sites in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diagnostic accuracy of vertical flow microarray printed on paper for pathogen identification in human cerebrospinal fluid samples (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03900091, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2020.

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