Patients must have a clinical diagnosis of meningitis including one or more of the following symptoms: headache, irritability, vomiting, fever and neck stiffness (Table 1). The diagnosis of probable or possible TBM is based on 1) clinical findings 2) CSF results 3) neuroimaging findings 4) evidence for TB outside the central nervous system and 5) additional laboratory criteria. A scoring system then determines whether a patient falls in the probable or possible TBM category. Points are allocated for a positive finding in each of the categories, with a maximum score for each category. A total score of at least 10 is compatible with probable TBM, while a total score of at least 6 equates with a possible TBM diagnosis.

Definite TBM requires demonstration of acid- fast bacilli in the CSF, Mycobacterium tuberculosis culture from CSF, a positive nucleic acid amplification test (PCR) of CSF or histopathological evidence of Mycobacterium tuberculosis from a central nervous system site.

Tuberculous Meningitis

Stellenbosch University Immunology Research Group

Evaluation of New Biomarker-based Approaches for Improving the Diagnosis of Childhood Tuberculous Meningitis

We have identified a total of 51 inflammatory biomarkers in CSF and/or serum samples in children with suspected TBM. 47 of these host markers (including 10 of the 14 that showed potential in serum either as individual markers or as part of 3-marker signatures) were detected in CSF samples, with only four of these proteins (CCL2, IL-4, adipsin and Ab42) showing potential only in serum samples. Using a repository of 100 CSF and serum samples, currently available in our biobank, from children with suspected TBM, n=50 with TBM, we will look for correlated markers that can be substituted to identify the best performing biomarker set for the POC device (Aim 2).

The validated, best performing CSF and serum biomarkers (sub aims 1a and b) will be incorporated into our POC diagnostic platform, at the Engineering Faculty, SU. The first prototype of the biosensor-based assay was shown to quantify antibodies in bodily fluids in the range of 50 ng/ml - 1 µg/ml (22). We will develop a multibiomarker prototype test for 4 biomarkers in CSF or serum. The prototype multi-biomarker test will undergo prospective evaluation in the field (Aim 3), in years 4 and 5. Assay development will be led by Distinguished Professor Willem Perold, a co-investigator on the project, who will be the lead supervisor of one MSc.Engineering student, with Dr. Chegou as co-supervisor.

We will evaluate the newly developed test prospectively in a new cohort of children with suspected TBM.
Clinical study design Recruitment of study participants will follow a longitudinal cohort design. Children suspected of having meningitis will be recruited and assessed for TBM at Tygerberg Academic Hospital, a tertiary level referral hospital and a teaching hospital for SU. It is the second-largest hospital in South Africa. These children will later be classified as having "definite", "probable", "possible" and "no TBM" based on international, standardized criteria (26).

Participant information will be secured using unique participant ID's (PIDs). Participants are minors, and thus published data will use de-identified participant results.

mannose/infarction

Evaluation of New Biomarker-based Approaches for Improving the Diagnosis of Childhood Tuberculous Meningitis

Најкомплетната база на податоци за лековити билки поддржана од науката