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Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda
Joshua Rhein1, Nathan C Bahr2, Andrew C Hemmert3
1Division of Infectious Disease and International Health, Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda.
Abstract:
Meningitis remains a worldwide problem, and rapid diagnosis is essential to optimize survival. We evaluated the utility of a multiplex PCR test in differentiating possible etiologies of meningitis. Cerebrospinal fluid (CSF) from 69 HIV-infected Ugandan adults with meningitis was collected at diagnosis (n=51) and among persons with cryptococcal meningitis during therapeutic lumbar punctures (n=68). Cryopreserved CSF specimens were analyzed with BioFire FilmArray® Meningitis/Encephalitis panel, which targets 17 pathogens. The panel detected Cryptococcus in the CSF of patients diagnosed with a first episode of cryptococcal meningitis by fungal culture with 100% sensitivity and specificity and differentiated between fungal relapse and paradoxical immune reconstitution inflammatory syndrome in recurrent episodes. A negative FilmArray result was predictive of CSF sterility on follow-up lumbar punctures for cryptococcal meningitis. EBV was frequently detected in this immunosuppressed population (n=45). Other pathogens detected included: cytomegalovirus (n=2), varicella zoster virus (n=2), human herpes virus 6 (n=1), and Streptococcus pneumoniae (n=1). The FilmArray Meningitis/Encephalitis panel offers a promising platform for rapid meningitis diagnosis.
Insights
A multiplex PCR test accurately identified meningitis causes in HIV-infected adults. This rapid diagnostic tool, the FilmArray Meningitis/Encephalitis panel, aids in differentiating infections and guiding treatment for better patient outcomes.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Neuroscience
Background:
- Meningitis poses a significant global health challenge, necessitating rapid and accurate etiological diagnosis for improved survival rates.
- HIV-infected individuals are particularly vulnerable to various meningitis pathogens, complicating diagnosis and treatment.
- Current diagnostic methods may lack the speed and comprehensiveness required for timely intervention in meningitis cases.
Purpose of the Study:
- To evaluate the diagnostic utility of a multiplex PCR assay, the BioFire FilmArray Meningitis/Encephalitis (ME) panel, in identifying pathogens causing meningitis in HIV-infected Ugandan adults.
- To assess the panel's ability to differentiate between primary infections, relapses, and immune reconstitution inflammatory syndrome (IRIS) in recurrent meningitis cases.
- To determine the sensitivity and specificity of the FilmArray ME panel for detecting Cryptococcus in cerebrospinal fluid (CSF).
Main Methods:
- Cerebrospinal fluid (CSF) samples were collected from 69 HIV-infected Ugandan adults diagnosed with meningitis.
- Samples were analyzed using the BioFire FilmArray ME panel, targeting 17 common meningitis and encephalitis pathogens.
- Results were compared with conventional diagnostic methods, including fungal culture, for Cryptococcus detection.
Main Results:
- The FilmArray ME panel demonstrated 100% sensitivity and specificity in detecting Cryptococcus compared to fungal culture.
- The panel successfully differentiated between fungal relapse and paradoxical immune reconstitution inflammatory syndrome in recurrent meningitis episodes.
- Epstein-Barr virus (EBV) was frequently detected (n=45) in this immunosuppressed population; other detected pathogens included cytomegalovirus, varicella zoster virus, human herpes virus 6, and Streptococcus pneumoniae.
- A negative FilmArray result was predictive of CSF sterility in follow-up lumbar punctures for cryptococcal meningitis.
Conclusions:
- The BioFire FilmArray ME panel is a valuable tool for the rapid and accurate diagnosis of meningitis in HIV-infected adults.
- This multiplex PCR assay facilitates differentiation of various meningitis etiologies, including fungal infections and viral pathogens.
- The panel's performance suggests its potential to significantly improve meningitis management and patient outcomes in resource-limited settings.
