Low hemoglobin increases risk for cerebrovascular disease, kidney disease, pulmonary vasculopathy, and mortality in sickle cell disease: A systematic literature review and meta-analysis.

Sickle cell disease (SCD) is characterized by deoxygenation-induced polymerization of hemoglobin in red blood cells, leading to hemolytic anemia, vaso-occlusion, and the development of multiple clinical complications. To characterize the clinical burden associated with differences in hemoglobin concentration and hemolysis measures, a systematic literature review of MEDLINE, EMBASE, and related meta-analyses was undertaken. For quantitative analyses related to hemoglobin concentration, pooled results were analyzed using random effects models to control for within-and between-study variability. To derive risk ratios associated with hemoglobin concentration change, we combined ratios of means from select studies, which reported hazard and odds ratios in meta-analyses for hemoglobin concentration-related outcomes and changes between groups. Forty-one studies were identified for inclusion based on relating hemoglobin concentration to clinical outcomes. Meta-analyses demonstrated that mean hemoglobin concentration was significantly lower in patients with cerebrovascular disease (0.4 g/dL), increased transcranial Doppler velocity in cerebral arteries (0.6 g/dL), albuminuria (0.6 g/dL), elevated estimated pulmonary artery systolic pressure (0.9 g/dL), and in patients that subsequently died (0.6 g/dL). In a risk reduction meta-analysis, modeled increased hemoglobin concentrations of 1 g/dL or greater resulted in decreased risk of negative clinical outcomes of 41% to 64%. In conclusion, chronic anemia is associated with worse clinical outcomes in individuals with SCD and even modest increases in hemoglobin concentration may be beneficial in this patient population. This systematic review has been registered on Prospero (Registration number CRD42018096860; https://www.crd.york.ac.uk/prospero/).

Establishing herd immunity against Ebola through vaccination.

OBJECTIVES: In response to recent concern regarding Ebola outbreaks, this study aims to (1) determine the relationship between vaccination coverage and herd immunity, (2) determine the vaccination coverage necessary to establish herd immunity for previous Ebola viruses, and (3) recommend vaccination coverage thresholds for future Ebola viruses. METHODS: Herd immunity thresholds needed to block transmission of Ebola virus were determined using vaccine efficacy and number of secondary cases per infected case during an entire infectious period. RESULTS: In past Ebola outbreaks 42.2-63.0% of the population would need to be vaccinated in order to prevent transmission and outbreaks. Assuming 80% vaccine efficacy as reported by phase I clinical trials, 52.7-78.7% of the population would require vaccination coverage in order to establish herd immunity. In recent ring vaccination trials which considered the vaccine to be 100% effective after 10 days, 42.2-63.0% of the population would need to be vaccinated. CONCLUSION: For future Ebola outbreaks, the spread of the virus can be prevented by vaccinating certain percentages of the population depending on vaccine efficacy and number of secondary cases per infected case.