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

Abstract

Objectives: 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) 2000-2015 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 142.6/100,000 person-years (95%CI:138.3-147.1); incidence of CM was 25.0/100,000 (95%CI:23.2-26.9), and incidence of PM was 2.7/100,000 (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.

Keywords: Cryptococcal meningitis; HIV; Pneumococcal meningitis; Sub-Saharan Africa; TB meningitis.

Figure 1.. Overall description of 21,560 adult cases. Of 34,505 overall lumbar puncture assessments, 7,238 samples from children, 4,014 with undocumented age, and 1,693 repeat lumbar punctures excluded. Having minor abnormalities was defined as a CSF WCC 6-20 cells/μl; markedly abnormal CSF was defined as a WCC >20 cells/μL.

CSF = cerebrospinal fluid; TB = tuberculosis; WCC = white cell count *>100 percent due to 31 mixed cryptococcal and bacterial meningitis cases and 2 mixed cryptococcal and TB meningitis; 1 additional case of Candida spp and 1 non-tuberculous Mycobacterium without further speciation also found

Figure 2.. Trends in meningitis cases at Botswana national referral hospitals, 2004-2014.

WCC 6-20 cells/μL and >20 cells/μL were used to reflect minor and marked inflammation of the CSF suggesting infection or other central nervous system pathology CSF - cerebrospinal fluid; WCC - cerebrospinal fluid white cell count Classifications for pneumococcal meningitis restricted to culture-positive cases. WCC >20 and WCC 6-20 groups excluded cases of diagnosed cryptococcal meningitis. * Excluded 2006 data for Cryptococcus, WCC>20 and WCC 6-20; a large drop in cryptococcal meningitis cases and concurrent rise in cases with WCC 6-20 and WCC>20 likely represented missed diagnoses of cryptococcal meningitis in this year

Figure 3.. (A) Culture-confirmed pneumococcal meningitis cases, (B) average rainfall (centimetres), and (C) average temperature (Celsius) by month

* Month: 1=January, 2=February, etc.; the number of cases each month represent the total number of cases of pneumococcal meningitis diagnosed during the calendar month over the full observation period; graphed monthly temperature and rainfall also represent mean values observed during a calendar month over the full observation period.