Epidemiology of meningitis in an HIV-infected Ugandan cohort

Abstract

There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical.

Figure 1.

Etiologies of meningitis in Uganda among human immunodeficiency virus (HIV)-infected anti-retroviral therapy (ART)-naive persons. Cryptococcal meningitis accounted for the majority (60%) of meningitis among hospitalized patients with suspected meningitis who received a lumbar puncture. Less common etiologies included: bacterial meningitis (1.6%) and tuberculosis (2.5%). Aseptic meningitis accounted for 23% (71 of 314) of etiologies overall. Extensive testing revealed testing positive for tuberculosis by GeneXpert (N = 8), EBV (N = 22), toxoplasmosis (N = 2), John Cunningham (JC) virus (N = 2), VZV (N = 1), and CMV (N = 1). There were 43 specimens (13.7% overall) with no etiology determined despite extensive molecular testing. The population was HIV-infected and not receiving HIV therapy. The percentages of the unknown meningitis sum to > 23% caused by multiple overlapping concurrent identification of viral pathogens. CMV = cytomegalovirus; EBV = Epstein-Barr virus; Toxo = toxoplasmosis; Xpert = GeneXpert MTB/RIF PCR assay. Insufficient samples were missing either cerebrospiral fluid (CSF) white blood cell (WBC) or protein results, most often caused by the CSF being grossly blood stained.