Accepted for/Published in: JMIR Research Protocols
Date Submitted: Jun 15, 2020
Date Accepted: Sep 13, 2020
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Point-of-care approaches for meningitis diagnosis in a low-resource setting - The “PI-POC” trial, an observational cohort study protocol from Southwestern Uganda
ABSTRACT
Background:
Timely, differential diagnostics is essential to identify the aetiology of central nervous system (CNS) infections in children, in order to facilitate target treatment, manage patients and improve outcome.
Objective:
The Paediatric Infection – Point of Care (PI-POC) trial is researching novel methods to improve and strengthen the differential diagnosis of suspected childhood CNS infections in low-income health systems such as Southwestern Uganda. This will be achieved by evaluating I) new DNA based assays for CNS infections II) the BIOFIRE® FILMARRAY® Meningitis/Encephalitis (ME) panel for clinical use in a facility-limited laboratory setting III) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever and not severely ill IV) Myxovirus resistance protein A (MxA) as a biomarker in blood as indicative of viral CNS infection. Further changes in aetiology of childhood CNS infection post introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) investigated.
Methods:
The PI-POC trial is a prospective observational study of children including new-borns up to 12-year old with clinical features of CNS infection, and age/sex-matched outpatient controls with fever and not severely ill. l. Participants are recruited at two paediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (cases only), blood and nasopharyngeal swabs (cases and controls), sampled at both clinics are analysed at the Epicentre research laboratory through gold standard methods for CNS infection diagnostic (microscopy, biochemistry and culture) and BIOFIRE® FILMARRAY® for CSF’s multiplex Polymerase Chain Reaction analyses. An additional blood sample from cases is collected at day 3 after admission. After initial clinical analyses in Mbarara, samples will be shipped to Stockholm, Sweden for a) validation analyses of a novel nucleic acid-based point-of-care test, b) biomarker research, and c) serotyping and molecular characteristics of S. pneumoniae and N. meningitidis.
Results:
A pilot study was performed from January to April 2019. The PI-POC trial is and enrolment of patients begun in April 2019 and will continue until June 2020, to include up to 300 cases and controls. Results from the PI-POC study are expected by the end of 2020.
Conclusions:
The findings from the PI-POC study can potentially facilitate rapid aetiological diagnosis of CNS infections in low-resource settings and allow novel methods for determination of the severity of CNS infection adaptation in such environment. Clinical Trial: Registered at clinicaltrials.gov ID: NCT03900091
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