# Novel Diagnostic Development for TB Meningitis and Histoplasmosis

> **NIH NIH K23** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $200,705

## Abstract

Project Abstract:
 Dr. Bahr's long-term goal is to become an independent investigator developing novel diagnostic tests for
difficult-to-diagnose infectious diseases affecting low-resource populations. Dr. Bahr's research to date has
emphasized novel molecular technologies and immunodiagnostics to detect TB meningitis. This K23 award will
provide the mentored clinical research experience, didactics, and training in biostatistics, immunology, study
design, regulation, and novel diagnostic test development required for him to establish himself as an
independent researcher.
 Research: Rapid, accurate diagnostic tests are urgently needed for a myriad of infectious diseases that
affect low-income populations and carry high mortality rates. Approximately 1% of TB cases worldwide develop
meningitis. TB meningitis has an unacceptably high mortality rate (>50%), in large part due to slow and
insensitive diagnostics. Dr. Bahr's work with GeneXpert MTB/Rif and the re-engineered GeneXpert MTB/Rif
Ultra has provided evidence to support the use of new, rapid (~2hrs) molecular diagnostic tools with improved
accuracy. Yet, up to one third of TB meningitis cases are missed, even with these improved tests. Adjunctive,
novel, immunologic diagnostics may provide improved diagnostic accuracy for TB meningitis. Histoplasmosis is
common throughout much of the United States and Latin America. In the United States, diagnosis is made by
antigen detection; however, this approach is inadequate and is unavailable in much of the world where only
culture and/or histopathology are available. Diagnosis is particularly difficult for sub-acute/chronic pulmonary
histoplasmosis. The development of an interferon gamma release assay (IGRA) directed at Histoplasma
capsulatum may improve diagnosis of pulmonary histoplasmosis, leading to improved outcomes.
 In both conditions, inadequate diagnostic tests based on pathogen detection lead to delayed diagnosis,
reliance on empiric therapy, and poor outcomes. Alternative diagnostic approaches focused on the host
immune response may provide better results.
 The aims of this proposal are: 1) To determine if GeneXpert MTB/Rif Ultra can improve TB meningitis
diagnosis in comparison to Xpert MTB/Rif, culture, and post-mortem testing, 2) To determine if novel
immunologic biomarkers, when added to standard microbiologic/molecular techniques, can improve TB
meningitis diagnosis, in comparison to conventional techniques alone, and 3) To determine if a novel
Histoplasma capsulatum IGRA can improve diagnosis of pulmonary histoplasmosis, compared to antigen
detection, culture, and histopathology. Together, these aims have the potential to significantly improve the
diagnosis of TB meningitis and pulmonary histoplasmosis. The findings from these proposed studies and the
proposed training in biostatistics, immunology, study design and regulation, and diagnostic test development
will inform an R01 proposal to further evaluate novel diagnostic tests for infe...

## Key facts

- **NIH application ID:** 10220161
- **Project number:** 5K23NS110470-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Nathan Bahr
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $200,705
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220161

## Citation

> US National Institutes of Health, RePORTER application 10220161, Novel Diagnostic Development for TB Meningitis and Histoplasmosis (5K23NS110470-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10220161. Licensed CC0.

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