LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.

We conducted a prospective cohort study to determine the prevalence of leukotriene A4 hydrolase (LTA4H) polymorphisms in Zambian adults with tuberculous meningitis (TBM) and its association with mortality. We completed genotype testing on 101 definite cases of TBM and 119 consecutive non-TBM controls. The distribution of genotypes among TBM patients was as follows: C/C (0.83), C/T (0.14), T/T (0.03). There was no significant difference in genotype distribution between TBM and non-TBM patients. We found no relationship between LTA4H polymorphism and survival. Prospective studies are needed to determine the benefit of adjuvant steroids in TBM based upon population LTA4H genotype. ANN NEUROL 2021;90:994-998.

Prospective Cohort Study on Performance of Cerebrospinal Fluid (CSF) Xpert MTB/RIF, CSF Lipoarabinomannan (LAM) Lateral Flow Assay (LFA), and Urine LAM LFA for Diagnosis of Tuberculous Meningitis in Zambia.

Tuberculous meningitis (TBM) is a devastating infection of the central nervous system lacking an adequate point-of-care diagnostic test. We conducted a prospective cohort study of 550 Zambian adults with suspected TBM to determine the diagnostic accuracy of cerebrospinal fluid (CSF) Xpert MTB/RIF, CSF lipoarabinomannan (LAM), urine LAM, CSF total protein, and CSF glucose compared with the gold standard of CSF culture. We categorized patients with a positive CSF tuberculosis (TB) culture as definite TBM. We also assessed inpatient and 1-year mortality on definite TBM patients when CSF Xpert MTB/RIF results were available in real time to treating physicians relative to a historical comparison cohort in whom Xpert results were not available in real time. Of the 550 patients, 474 (86.2%) were HIV-infected and 105/550 (19.1%) had definite TBM based on a positive CSF culture. The sensitivity/specificity of the diagnostic tests were CSF Xpert MTB/RIF, 52.9%/94.2%; CSF LAM, 21.9%/94.2%; urine LAM, 24.1%/76.1%; and CSF glucose <40 mg/dl, and total protein, >100 mg/dl, 66.3%/90%. A model including CSF Xpert MTB/RIF, CSF LAM, CSF glucose, and CSF total protein demonstrated an area under the receiver operating curve of 0.90. The inpatient and 1-year mortality for definite TBM was 43% and 57%, respectively. There was low sensitivity for the diagnosis of TBM across all diagnostics tests. CSF Xpert MTB/RIF and CSF LAM are highly specific for the diagnosis of TBM. Despite the use of Xpert MTB/RIF for diagnostic purpose in real time, TBM was still associated with a high mortality in Zambian patients.

Progressive multifocal leukoencephalopathy in Zambia is caused by JC virus with prototype regulatory region.

There are only few documented cases of progressive multifocal leukoencephalopathy (PML) in Africa. Whether this is caused by a lack of JC virus (JCV) spread or alteration in the JCV genome is unknown. We characterized the clinical presentation, laboratory findings, and JCV regulatory region (RR) pattern of the first documented PML cases in Zambia as well as JCV seroprevalence among HIV+ and HIV- Zambians. We identified PML patients with positive JCV DNA PCR in their cerebrospinal fluid (CSF) among subjects enrolled in an ongoing tuberculous meningitis study from 2014 to 2016 in Lusaka. JCV regulatory region was further characterized by duplex PCR in patients' urine and CSF. Of 440 HIV+ patients, 14 (3%) had detectable JCV DNA in their CSF (age 18-50; CD4+ T cells counts 15-155 × 106/µl) vs 0/60 HIV- patients. The main clinical manifestations included altered mental status and impaired consciousness consistent with advanced PML. While prototype JCV was identified by duplex PCR assay in the CSF samples of all 14 PML patients, only archetype JCV was detected in their urine. All PML Zambian patients tested were seropositive for JCV compared to 46% in a control group of HIV+ and HIV- Zambian patients without PML. PML occurs among HIV-infected individuals in Zambia and is caused by CNS infection with prototype JCV, while archetype JCV strains are present in their urine. JCV seroprevalence is comparable in Zambia and the USA, and PML should be included in the differential diagnosis of immunosuppressed individuals presenting with neurological dysfunction in Zambia.

Clinical presentation and outcomes of syphilitic meningitis among hospitalized adults in lusaka, Zambia.

BACKGROUND: Few studies exist to describe the characteristics of symptomatic syphilitic meningitis, particularly in sub-Saharan Africa, despite a global resurgence. METHODS: We conducted a retrospective analysis of a cohort of adults with meningitis presenting to Zambia's largest referral hospital between April 2014 and December 2017. Individuals with pyogenic bacterial and cryptococcal meningitis were excluded from this cohort. We calculated the prevalence of syphilitic meningitis in the cohort and described the demographic, clinical and laboratory characteristics and outcomes. RESULTS: Of 512 participants, 273 were male, mean age was 37 ± 11 years and 84% were people living with HIV. The prevalence of syphilitic meningitis was 5% with in-hospital and 1-year mortality of 17% and 53%, respectively. Participants with syphilitic meningitis had lower Glasgow Coma Scores than those with other forms of meningitis. Among people living with HIV, those with syphilitic meningitis were less likely to have meningismus and had higher CSF white cell counts. CONCLUSIONS: Syphilitic meningitis was found in 5% of Zambian adults presenting with non-pyogenic bacterial meningitis and non-cryptococcal meningitis, and one-year mortality was high. A high degree of clinical suspicion for syphilitic meningitis in all individuals with meningitis in Zambia is recommended, especially in people living with HIV.