Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial

Abstract

Background 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. Trial Registration ClinicalTrials.gov NCT03900091; https://clinicaltrials.gov/ct2/show/NCT03900091 International Registered Report Identifier (IRRID) DERR1-10.2196/21430

The emerging role of bacterial regulatory RNAs in disease

“…OPEN ACCESS ncRNAs to be involved in disease, a conventional PCR reaction for that ncRNA could be performed. This has been exemplified by the meningococcal RNAT, where its presence and variants could provide diagnostic information predictive of the disease prognosis [38,62]. Driving down costs by creating quick and robust point-of-care diagnostic methods is beneficial to all healthcare worldwide.…”

Aseptic Meningitis and Its Viral Etiologies, Clinical Characteristics and Management Practices in Children: A Retrospective Hospital-Based Study From Jordan

“…Aetiologies of meningitis may differ according to geographic location and endemicity of pathogens [ 3 , 5 , 6 ]. Several studies on the aetiologies and the clinical characteristics of viral meningitis in children have been reported from different countries, with limited data available from developing/low-resource countries including Jordan [ 7 ]. Polymerase chain reaction (PCR) testing is specific and can help differentiate viral from bacterial meningitis and thus might help adjust the management plan [ 8 , 9 ].…”