Fogarty Fellow: Lillian Tugume
Nominated From: University of Minnesota
Research Site: Infectious Disease Institute, Makerere University
Primary Mentor: David Boulware
Utility of Cerebrospinal Fluid C-Reactive Protein as a Diagnostic Biomarker for Tuberculous Meningitis
HIV-associated tuberculous meningitis (TBM) is highly fatal (approximately 50% mortality), yet prompt diagnosis is challenging. Advances in diagnosis with GeneXpert/Rif Ultra (Cepheid) have led to improved case detection, though negative predictive value is imperfect. Thus, a uniform case definition with laboratory and clinical parameters is the international referent standard used in TBM studies. Host biomarkers may have a role in further improving TBM diagnosis. C-reactive protein (CRP) is sensitive to changes in inflammation and has optimal negative predictive value for diagnosis of bacterial meningitis. We hypothesize that cerebrospinal fluid (CSF) CRP will be a cost-effective test for improving diagnostic yield for TBM when added into a stepwise algorithm. We propose to perform a case-control study nested in a cohort of HIV-positive adults with suspected TBM screened for tuberculous meningitis clinical trials in Uganda from January 2019 to date.
In the USA, meningitis accounts for more than 72,000 hospitalizations with a total expenditure of 1.2 billion dollars annually. Many types of infectious meningitis carry high rates of mortality and long-term complications including neurologic deficits and cognitive impairment. Tuberculous meningitis is the most fatal (mortality rate up to 50%) in HIV-positive individuals and 50% of individuals who survive tuberculosis meningitis suffer from neurologic disability. If the proposed diagnostic algorithm for tuberculous meningitis is cost-effective, this could save the country millions of dollars.