Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial
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Date
2020
Journal Title
Journal ISSN
Volume Title
Publisher
JMIR research protocols
Abstract
A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections
in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome.
Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the
differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern
Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially
available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3)
proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not
severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in
the etiology of childhood CNS infections after the 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) will be investigated.
Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with
clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are
recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs
(for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard
methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial
clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic
acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N.
meningitidis.
Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019
and will continue until September 2020, to include up to 300 cases and controls. Preliminary 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 etiological diagnosis of CNS infections in
low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
Description
Keywords
Global health, Central nervous system infections, Pediatrics, Diagnostics, Low-resource settings, Meningitis, Children
Citation
Gaudenzi, G., Kumbakumba, E., Rasti, R., Nanjebe, D., Réu, P., Nyehangane, D., ... & Alfvén, T. (2020). Point-of-care approaches for meningitis diagnosis in a low-resource setting (Southwestern Uganda): Observational cohort study protocol of the “PI-POC” trial. JMIR research protocols, 9(11), e21430. doi: 10.2196/21430