Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950-2017: protocol for a systematic review.

IntroductionCryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223 100, with 73% of them occurring in Africa. Currently available data on the prevalence, incidence, aetiologies and mortality of cryptococcal meningitis across Africa are sparse and of limited quality. We propose to conduct the first systematic review to summarise the epidemiological data available on cryptococcal meningitis and its aetiological causes in Africa.Methods and analysisWe will search PubMed, MEDLINE, Excerpta Medica Database, ISI Web of Science, Africa Index Medicus, Cumulative Index to Nursing and Allied Health for studies on cryptococcal meningitis published between 1st January 1950 and 31st December 2017, involving adults and/or children residing in Africa. After study selection, full text paper acquisition and data extraction, we will use validated tools and checklists to assess the quality of reporting and risk of bias for each study. Heterogeneity across studies will be assessed using the χ2 test on Cochrane's Q statistic and a random effect meta-analysis will be used to estimate the overall prevalence, incidence density and mortality of cryptococcal meningitis across studies with similar characteristics. This protocol is prepared and presented in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Reporting of the results will be compliant with the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines.Ethics and disseminationThere is no requirement for ethical approval since we will be using data from published studies. The final report will be published in a peer-reviewed journal and further presented at conferences. This study is expected to provide useful contextual estimates needed to inform treatment policies on the African continent and assess the impact of diagnostic and prevention strategies on the burden of cryptococcal meningitis in the post antiretroviral therapy era.Prospero registration numberCRD42017081312

A cross-sectional feasibility study of neurovascular ultrasound in Malawian adults with acute stroke-like syndrome.

BACKGROUND:In sub-Saharan Africa, there is a dearth of epidemiologic data on the burden of cerebral atherosclerosis. This is explained by the limited availability and the high cost of standard vascular imaging techniques. Neurovascular ultrasound is portable, cheaper and non-invasive and could, therefore, represent a reasonable alternative to fill this knowledge gap. We explored the feasibility of neurovascular ultrasound in Malawian adults with acute stroke-like syndrome to inform the design of future large stroke studies comparing its diagnostic performance to that of gold standard vascular imaging techniques in sub-Saharan Africa. METHODS:We enrolled consecutive patients diagnosed with acute stroke-like syndrome based on the World Health Organization definition. Clinical and demographic data were recorded, and a comprehensive neurovascular ultrasound was performed. Fisher's exact and Kruskal-Wallis tests were used to study the relationship between atherosclerosis and potential risk factors. RESULTS:Sixty-six patients were enrolled (mean age: 58.7 years). The frequency of extracranial atherosclerosis was 39.4% (n = 26, 95% CI: 28.6-52.2). There were 12 patients with abnormal carotid intima media thickness (18.2%, 95% CI: 9.8-29.6) and 14 patients with a carotid plaque (21.2%, 95% CI: 12.1-33.0). The frequency of intracranial atherosclerosis was 19.2% (95%CI: 6.6-39.4) in 26 patients with successful transcranial insonation. Hypertension (80.8 versus 52.5%, p = 0.03) and hypercholesterolemia (11.5 versus 0.0%, p = 0.05) were more prevalent in patients with extracranial atherosclerosis. CONCLUSIONS:This study demonstrates the feasibility of neurovascular ultrasound to assess cervical arteries in adults with stroke-like syndrome in sub-Saharan Africa. There is a high rate of transcranial insonation failure in this setting, highlighting the need for echocontrast agents

Stroke risk associated with carotid and aortic atherosclerosis in patients with atrial fibrillation: a systematic review

Objective: This review aimed to summarize the evidence on the risk of thromboembolism associated with carotid and aortic atherosclerosis in patients with AF, and the potential impact of their inclusion in current stroke risk stratification scores. Methods: MEDLINE, Web of Science and EMBASE were systematically searched to identify all published studies providing relevant data through 28 February 2021. Results: We identified 10 eligible studies. There was high heterogeneity across studies, precluding a meta-analysis. Carotid stenosis was not associated with incident ischemic stroke in three prospective studies, including the SPAF II trial and the ROCKET-AF trial. An association between carotid stenosis and thromboembolism was found in two studies, with a potential reporting bias due to their retrospective design. The evidence suggesting that carotid plaque predicts stroke or transient ischemic attack in AF patients were more consistent in the four studies evaluating this association. The inclusion of carotid plaque and carotid intima-media thickness (cIMT) into stroke risk stratification tools for AF patients improved their performance. Data on the association of aortic plaque with thromboembolism is scarce in patients with AF. The two studies reporting on this association suggest that aortic plaque alone does not predict incident ischemic stroke. Conclusion: Available data suggest an association of carotid atherosclerosis with the risk of stroke and transient ischemic attack in patients with AF. Future studies should evaluate whether incorporating cIMT and characteristics of carotid and aortic plaques into scoring systems would improve stroke prediction and prevention in patients with AF.Jean Jacques Noubiap, Joseph Kamtchum-Tatuene, John L. Fitzgerald, Prashanthan Sander

Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression.

BACKGROUND IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study). METHODS Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P>0.05 for variable removal. To assess model stability, we computed the E-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples. RESULTS There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β=0.09, P=1.3×10-3), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; P=7.4×10-3, E-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P=9.1×10-6, E-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models. CONCLUSIONS Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention