Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

Mark W Tenforde,Joseph N Jarvis,Brandon L Guthrie,Alida M Gertz,Nicola K Wills,Carey Farquhar,David S Lawrence

doi:10.1002/jia2.25416

Abstract

IntroductionHIV‐associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub‐Saharan Africa (SSA). We performed a systematic review and meta‐analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings.MethodsWe searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized‐controlled trials (RCTs) or investigator‐managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short‐term (in‐hospital or two weeks), medium‐term (up to 10 weeks) and long‐term (up to six months).Results and discussionSeventy‐nine studies met inclusion criteria. In routine care settings, pooled short‐term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole‐based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short‐term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short‐term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized‐controlled trials. Few studies evaluated long‐term outcomes.ConclusionsMortality rates from HIV‐associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV‐associated meningitis in the region.

Highlights

HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in subSaharan Africa (SSA)
Cryptococcal meningitis survival is associated with performance of therapeutic lumbar punctures (LPs) to reduce intracranial pressure (ICP) [11,12], intravenous fluid (IVF) hydration and electrolyte supplementation and monitoring to prevent life-threatening amphotericin-related toxicities [9,10,13], and appropriate follow-up after hospital discharge to initiate antiretroviral therapy (ART) around four to six weeks to reduce the risk of immune-reconstitution inflammatory syndrome [14]
Forty-one observational studies with 10,139 cases of cryptococcal meningitis were included, most in HIV-positive patients treated at district or referral hospitals (Appendix S1)

Summary

Introduction

HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in subSaharan Africa (SSA). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Cryptococcal meningitis survival is associated with performance of therapeutic lumbar punctures (LPs) to reduce intracranial pressure (ICP) [11,12], intravenous fluid (IVF) hydration and electrolyte supplementation and monitoring to prevent life-threatening amphotericin-related toxicities [9,10,13], and appropriate follow-up after hospital discharge to initiate antiretroviral therapy (ART) around four to six weeks to reduce the risk of immune-reconstitution inflammatory syndrome [14]. Effective management of TB meningitis is complicated in resource-constrained settings with challenges in management of common antituberculous drug toxicities, long duration of treatment (of a minimum of six months), poor sensitivity of diagnostic studies and delays for culture results, emergence of drug resistance and lack of integration of TB and HIV services [15,16]. Survival from pneumococcal meningitis can be negatively affected by delayed healthcare access and lack of timely initiation of effective antimicrobial therapy [17]

Results

Discussion

Conclusion