651: CELL-FREE DNA TESTING FOR EARLY DIAGNOSIS OF TUBERCULOUS MENINGITIS IN CRITICALLY ILL CHILDREN

Introduction: The majority of currently available diagnostic tests for tuberculosis (TSPOT, TB culture) have low sensitivity and specificity and often have a significant lag time. There is a need for a test with high sensitivity, specificity and shorter time to result in order to facilitate management decisions in critically ill patients. Cell free DNA (cfDNA) test is emerging as an effective tool for early diagnosis of infectious diseases. However, there is a lack of sufficient data on cfDNA testing in critically ill children with tuberculous meningitis (TBm). Here, we present three critically ill children with TBm of whom serum cfDNA testing allowed early diagnosis of TBm and early management. Description: Three critically ill children (two females and one male) ranging in age from 1 to 4 years presented with 2 to 3 weeks history of fever, irritability, and weakness between July 2021 and April 2022. All 3 patients progressed to worsening neurologic status with depressed higher functions and findings of elevated intracranial pressure with or without seizures. In all cases TBm was initially suspected based on clinical presentation, CSF and neuroimaging findings. TSPOT was positive in only one of the three cases. Additionally, cfDNA testing (Karius®) was positive for Mycobacterium tuberculosis complex within three days in all three cases. Based on cfDNA findings, early diagnosis of TBm was possible for all three patients, and the anti-tuberculosis treatment was continued while other antimicrobials were able to be discontinued. Eventually, acid fast cultures resulted positive for Mycobacterium tuberculosis at 4 and 6 weeks for two of the three patients. All three patients survived the hospital discharge. Discussion: Karius® cfDNA testing is a non-invasive test that can detect over a thousand pathogens via microbial cfDNA from one blood sample. Multiple studies have shown evidence of cfDNA from pathogens in the plasma for infections localized to specific organs. However, currently there are no studies evaluating the cfDNA validity of detection of Mycobacterium tuberculosis complex for either pulmonary or extrapulmonary infections. Our cases described here illustrate for the first time, the potential role that cfDNA testing may have in the rapid diagnosis of TBm.