Structured Abstract
Introduction
Neurological opportunistic infections cause significant morbidity and mortality in people living with HIV (PLHIV) but are difficult to diagnose.
Methods
140 PLHIV with acute neurological symptoms from Iquitos, Peru were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF), cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples were evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses.
Results
27 participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow coma score (p=0.05), unilateral focal motor signs (p=0.01), positive Babinski (p=0.01), and multiple lesions on head computed tomography (CT) (p=0.002) were associated with cerebral toxoplasmosis. Photophobia (p=0.03) and absence of lesions on head CT (p=0.02) were associated with cryptococcal meningitis. mNGS of 42 samples and identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, possible cases of TB meningitis (n=5) and incidental detections of hepatitis B virus (n=1), and pegivirus (n=1). mNGS had a positive percent agreement of 71% and a negative percent agreement of 91% with qPCR for T. gondii. mNGS had a sensitivity of 78% and specificity of 100% for Cryptococcus diagnosis.
Discussion
An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for CNS infections.