Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis

Abstract

BackgroundCryptococcal meningitis (CM) is a leading cause of adult meningitis in countries with a high burden of HIV. It has remained a significant cause of morbidity and mortality in Africa despite the extensive rollout of HIV antiretroviral therapy (ART). This study aimed to systematically synthesize the evidence on the prevalence of CM among people living with HIV (PLWH) and its predictors of mortality among adults who are on induction antifungal therapy in Africa.MethodsPubMed/MEDLINE, Embase, and Google Scholar were searched for randomized clinical trials or observational studies published in Africa from 1995 to April 2021. Pooled prevalence of CM among PLWH was calculated using R-studio Version 1.4.1717 software and the data extracted from eligible studies were pooled as percentage with a 95% confidence interval (CI). Predictors of mortality among adults on induction antifungal therapy were synthesized narratively.ResultsOut of 364 studies identified, 17 eligible articles were included in the analysis. The prevalence of CM among PLWH in Africa was 5.11% (95% CI 2.71–9.43%; participants = 10,813; studies = 9; I2 = 97%). In the subgroup analysis, the prevalence was 12.9% (95% CI 4.883–30.0; participants = 533; studies = 3; I2 = 63%) in the years 1995–2010 and 3.18% (95% CI 1.54–6.45; participants = 10,280; studies = 6; I2 = 98%) in the years 2011–2021, with the prevalence significantly decreased by 51% (p = 0.02). Predictors of mortality were fluconazole monotherapy, focal neurological signs, low Glasgow coma scale, and delayed diagnosis of CM at varied timepoint.ConclusionPrevalence of CM has significantly decreased from 1996–2010 to 2011–2021 among PLWH on induction therapy in Africa. Fluconazole monotherapy, focal neurological symptoms, diastolic blood pressure < 60 mmHg, and concurrent tuberculosis coinfection were significant predictors of mortality at 2- and 10-weeks timepoints. CM remains a major concern among PLWH despite increases in ART coverage. Improved access to effective antifungal therapies is needed in Africa for timely initiation of combination induction therapy and better treatment outcomes of PLWH.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=254113], identifier [CRD42021254113].

Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda

“…Factors associated with improved long-term survival included adherence to fluconazole and ART, attendance at follow-up return visits after hospital discharge, weight above 50Kgs, and receiving >2 LPs during hospitalization, all of which are consistent with systematic review reports [ 7 , 6 ]. Inadequate follow-up has been reported to be responsible for the sub-optimal long-term outcomes in similar studies in resource-limited settings [ 31 , 32 ].…”

“…Despite decreased CM prevalence globally, high mortality persists [ 6 , 7 ]. In rural, northern Uganda, we reported high mortality, with 90.9% of CM patients being ART-experienced at admission [ 8 ].…”

Opportunistic Pathogens of the Genus Cryptococcus in Louis Pasteur Days and in 200th Anniversary of his Birth

“…Observations performed during the last two to three decades demonstrate that members of the Cryptococcus species complex cause infection in approximately 1 million people per year, with more than 600 thousand mortalities, contributing to death toll in one-third AIDS patients [101,108]. In recent years, thanks to the antiretroviral therapy (ART) implemented in many countries, the number of deaths caused by cryptococcosis in the group of AIDS patients has started to decline [10,87]. For comparison, only in 2014 and 2020 on a global scale 223,100 and 152,000 people suffered from cryptococcosis of the central nervous system (CNS), of which 181,100 and 112,000 died, respectively [61,108].…”

Prevalence, treatment, and factors associated with cryptococcal meningitis post introduction of integrase inhibitors antiretroviral based regimens among People Living with HIV in Tanzania

“…Cryptococcal Meningitis (CM) is one of the leading causes of laboratory-confirmed meningitis among adults living in countries with a high burden of HIV especially in Sub-Saharan Africa (SSA) [ 1 , 2 ]. CM accounts for over 100,000 incident cases of meningitis per year in the SSA [ 3 ]. The burden of CM in PLHIV is high and globally it is estimated to cause 15%-20% of HIV-related deaths.…”