Recent global outbreaks of neurotropic infections highlight our current limitations in predicting the emergence and spread of pathogens, establishing an etiological diagnosis, and preventing poor outcome. Dr. Thakur's K23 proposal will assess the clinical impact of early pathogen identification in acute neurologic infections in adults. Dr. Thakur's goal is to be a clinical researcher with expertise in the distribution, risk factors, and impact of acute neurological infections, including emerging and re-emerging pathogens. Dr. Thakur will define epidemiological, socioeconomic, and clinical factors associated with poor outcome in patients with CNS infections of identified and unknown etiology, which may facilitate diagnostic testing approaches, as well as monitoring and treatment strategies. Dr. Thakur's goal is to define the impact of pathogen identification in patients evaluated by traditional diagnostic methods and an advanced diagnostic platform, the US Food and Drug Administration (FDA) approved multiplex PCR assay (FilmArray Meningitis/Encephalitis Panel (FA ME)). Whether early pathogen identification impacts outcome and whether advanced testing can and should replace traditional diagnostic methods is not known. This study will be one of the fist studies to evaluate the clinical implementation of FA ME testing in adults. Dr. Thakur will test her hypotheses that: 1) Demographic and epidemiologic factors associated with poor outcome will include older age, low education level, and lack of health insurance, as these factors serve as barriers to access to medical care. Clinical factors associated with intensive care unit admission (i.e. need for intubation, status epilepticus), the presence of medical comorbidities and immunocompromised state are associated with poor outcome. 2) In patients evaluated by traditional laboratory methods, CNS infections of unknown etiology will be associated with poor outcome compared to those with an identified etiology. Poor outcome in patients with an unknown etiology will be related to prolonged hospitalizations due to extensive diagnostic testing and empiric treatment; 3) The FA ME panel will significantly reduce time to results and will decrease the duration of inappropriate antimicrobial medications compared to traditional diagnostic methods. Use of FA ME will be cost-effective, associated with decreased hospital length of stay, though will not impact outcome at hospital discharge. This K23 award will provide Dr. Thakur the support needed to develop expertise in 3 major scientific areas: (1) Design and analysis of epidemiologic studies in neuroinfectious diseases; (2) Expertise in comparative effectiveness and outcomes research methodology; (3) Clinical application of advanced diagnostic assays for CNS infections. Dr. Thakur will utilize her clinical-research training in the K23 to lead a population-based multicenter study in New York City to define the burden and impact of CNS infections. The ultimate goal would be that this serves as an early warning system for emerging neurotropic pathogens, with the opportunity to implement and optimize prevention and treatment strategies.
Recent neurotropic infectious outbreaks of public health significance highlight our current limitations in predicting the emergence and spread of pathogens, establishing an etiological diagnosis, and preventing poor outcome. Early pathogen identification is essential for monitoring patterns of distribution, and rapidly implementing prevention and treatment strategies. Defining epidemiological and clinical features associated with poor outcome, and identifying whether early use of advanced diagnostic tools impacts clinical decision making and outcome, are essential as we are faced with the ongoing threats of devastating emerging neuroinfectious diseases.
