Causes of Pediatric Meningitis in Botswana: Results From a 16-Year National Meningitis Audit

Abstract

Background: Central nervous system (CNS) infections are an important cause of childhood morbidity and mortality in high HIV prevalence settings of Africa. We evaluated the epidemiology of pediatric meningitis in Botswana during the rollout of antiretroviral therapy, pneumococcal conjugate vaccine (PCV13), and Haemophilus influenzae type B (HiB) vaccine. Methods: We performed a cross-sectional study of children (<15 years) evaluated for meningitis by cerebrospinal fluid (CSF) examination from 2000-2015, with complete national records for 2013-2014. Clinical and laboratory characteristics of microbiologically-confirmed and culture-negative meningitis were described and incidence of Streptococcus pneumoniae, Haemophilus influenzae and cryptococcal meningitis estimated for 2013-2014. Results: 6,796 unique cases were identified. Median age was 1 year (IQR 0-3); 10.4% (435/4,186) of children with available HIV-related records were known HIV-infected. Overall, 30.4% (2,067/6,796) had abnormal CSF findings (positive microbiological testing or CSF pleocytosis). Ten-percent (651/6,796) had a confirmed microbiological diagnosis; including 26.9% (175/651) Cryptococcus, 18.9% (123/651) Streptococcus pneumoniae, 20.3% (132/651) Haemophilus influenzae, and 1.1% (7/651) Mycobacterium tuberculosis. During 2013-2014, national cryptococcal meningitis incidence was 1.3 cases/100,000 person-years (PYO)

Global morbidity and mortality of central nervous system tuberculosis: a systematic review and meta-analysis

“…According to the source of data, the prevalence of CNS-TB in the general population was 2.11 per 100,000 inhabitants (95% CI 0.81 to 4.03; I 2 , 99.91%), from 11 studies including 7979 cases and a population of 230 million inhabitants [ 1 , 7 , 13 , 17 , 20 – 22 , 52 , 63 , 68 , 70 ]. For that analysis, values were only available from patients with TB meningitis since no data were found for tuberculoma.…”

“…In hospitalized patients (general hospitalization), the prevalence of CNS-TB was 8.64% (95% CI 5.34–12.55; I 2 , 97.10%) based on 13 studies (14,409 patients and 448 cases) [ 15 , 62 , 64 , 73 , 74 , 77 – 81 , 92 , 95 , 98 ]. On the other hand, the prevalence of CNS-TB was 13.91% of all patients with meningitis (95% CI 10.40–17.81; I 2 , 99.70%; 33 studies, 171,619 patients, and 6460 cases) [ 9 , 11 – 16 , 20 – 22 , 26 , 30 , 31 , 34 – 38 , 41 , 44 , 47 – 52 , 54 , 70 , 79 , 83 , 86 , 88 ], and it represented the 4.55% of patients with TB (95% CI 2.63–6.97; I 2 , 98.81%; 11 studies, 202,265 patients, and 4043 cases) [ 7 , 11 , 17 , 63 , 68 , 69 , 71 , 72 , 90 , 92 , 98 ]. The forest plots for these analyses are presented in Fig.…”

“…The prevalence in general hospitalization was 7.40% (95% CI 4.50–10.91; I 2 , 96.77%), from 12 studies including 419 cases and 14,309 total patients [ 15 , 62 , 64 , 73 , 77 – 81 , 92 , 95 , 97 ]. In patients with meningitis, TB meningitis represented the 14.63% (95% CI 10.95–18.73; I 2 , 99.71%) calculated from 32 studies including 169,538 total patients and 6322 cases [ 9 , 11 – 16 , 20 – 22 , 24 , 26 , 30 , 31 , 34 – 38 , 41 , 44 , 47 – 49 , 51 , 52 , 54 , 70 , 79 , 83 , 86 , 88 ]. Finally, in patients with TB, TB meningitis represented the 3.67% (95% CI 2.16–5.56; I 2 , 99.71%), from 10 studies including 201,223 total patients and 3875 cases [ 7 , 11 , 17 , 63 , 68 , 69 , 71 , 72 , 92 , 98 ].…”

Consensus guidelines for the diagnosis and management of cryptococcosis and rare yeast infections in the haematology/oncology setting, 2021

“…A recent 10-year audit from the Australia paediatric network, described 22 rare paediatric cases of CM; CNS manifestations predominated, and mortality and long-term morbidity were both high. 58 In contrast, CM is the dominant aetiology in paediatric meningitis in Botswana, 59 mirroring adult CM epidemiology in settings with a high burden of HIV. L-AMB has been used safely in immunocompromised children at mg/kg doses comparable to those used in adults.…”

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

“…8,9 Recent reports reveal an increasing surge of laboratory detection of C. neoformans. 10,11 However, the identification of CM is possible only in places with laboratory diagnostics targeting C. neoformans. Mycobacterial meningitis (MM), including those caused by Mycobacterium tuberculosis complex (MTBC) and others caused by nontuberculous mycobacteria (NTM), refractory to therapy, have also been identified in patients with AIDS presenting with prolonged fever and brain symptoms.…”