Epidemiology of adult meningitis during antiretroviral therapy scale-up in southern Africa: Results from the Botswana national meningitis survey

Abstract

s u m m a r yObjectives: Data on meningitis epidemiology in high HIV-prevalence African settings following antiretroviral therapy scale-up are lacking. We described epidemiology of adult meningitis in Botswana over a 16-year period. Methods: Laboratory records for adults undergoing lumbar puncture (LP) 20 0 0-2015 were collected, with complete national data 2013-2014. Cerebrospinal fluid (CSF) findings and linked HIV-data were described, and national incidence figures estimated for 2013-2014. Temporal trends in meningitis were evaluated. Results: Of 21,560 adults evaluated, 41% (8759/21,560) had abnormal CSF findings with positive microbiological testing and/or pleocytosis; 43% (3755/8759) of these had no confirmed microbiological diagnosis. Of the 5004 microbiologically-confirmed meningitis cases, 89% (4432/5004) were cryptococcal (CM) and 8% (382/5004) pneumococcal (PM). Seventy-three percent (9525/13,033) of individuals undergoing LP with identifiers for HIV registry linkage had documented HIV-infection. Incidence of LP for meningitis evaluation in Botswana 2013-2014 was 142.6/10 0,0 0 0 person-years (95%CI:138.3-147.1); incidence of CM was 25.0/10 0,0 0 0 (95%CI:23.2-26.9), and incidence of PM was 2.7/10 0,0 0 0 (95%CI:2.4-3.1). In contrast to previously reported declines in CM incidence with ART roll-out, no significant temporal decline in pneumococcal or culture-negative meningitis was observed.Conclusions: CM remained the predominant identified aetiology of meningitis despite ART scale-up. A high proportion of cases had abnormal CSF with negative microbiological evaluation.

Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana

“…We then determined factors associated with CSF viral escape using the following covariates: pleocytosis, CD4+ T-cell count, CSF protein and glucose concentration, duration on ART and the available demographics. Pleocytosis was defined as CSF white cell count (WCC) ≥ 20 cells/mm 3 [ 27 , 28 , 29 ]. The cut-off to identify elevated protein concentration was ≥1 g/L [ 22 ].…”

Optimizing Laboratory Diagnostic Services for Infectious Meningitis in the Meningitis Belt of sub-Saharan Africa

“…The National Institute for Communicable Diseases (NICD) reported that the CM burden remained high among severely immunosuppressed HIV-positive patients in South Africa despite increased antiretroviral therapy coverage . In Botswana, also in Southern Africa, current adult data show 89% (4432/5004) CM and 8% (382/5004) pneumococcal meningitis, whereas pediatric data show 26.9% (175/651) CM, 18.9% (123/651) S. pneumoniaee , 20.3% (132/651) H. influenzae , and 1.1% (7/651) Mycobacterium tuberculosis . , Progress in meningitis assay development and implementation has been very impressive, here accounting for the capacity to identify emerging CNS pathogens. Two in-house multiplex real-time PCR assays were developed for the detection of S. pneumoniaee , N. meningitidis , H. influenzae , enteroviruses, mumps virus, and herpes simplex virus.…”

Laboratory Evaluation of the VISITECT Advanced Disease Semiquantitative Point-of-Care CD4 Test

“…18 The proportions of individuals presenting with advanced HIV disease is still reported to be in the range of 20%-35% in recent studies conducted in the southern and east African region, 12,[15][16][17][18] and the overall number of individuals with very low CD4 counts has remained stable for the past decade. 17,19 A further challenge to effective implementation of the WHO AHD package has been the widespread uptake of rapid or same-day ART initiation. 20 With rapid ART initiation, even if baseline CD4 tests are sent, the current turn-around times with flow-cytometry 21 testing in centralized laboratories, which remains the mainstay of CD4 testing in most LMICs, means that ART initiation occurs in most cases before the availability of CD4 results.…”