Summary Background Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. Methods For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine–pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. Findings 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0–78·8), and 54·5% children (95% CI 50·4–58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2–77·3] treated per month and 53·0% [48·5–57·4] treated four times). In 779 individual case safety reports over 2015–16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7–93·4) over 28 days in case-c...
Background and ObjectivesWe aim to explore blood plasma levels of matrix metalloproteinase‐9 (MMP9) in acute mild traumatic brain injury (mTBI), and test if MMP9 levels correlate with quantitative electroencephalography (qEEG) during working memory (WM) testing.MethodsStudy participants were recruited from the emergency department of Huntington Memorial Hospital in Pasadena, CA, consisting of thirteen acute mTBI civilian patients and seven controls who were trauma patients without head injury ranging between 18–50 years of age. Blood samples were collected from three time points: within 1 week, 14 days, and 30 days after the injury. To study blood‐brain‐barrier (BBB) integrity, we quantified three MMP9 peptides (SLGPALLLLQK, QLSLPETGELDSATLK, and LGLGADVAQVTGALR) using liquid chromatography and mass spectrometry with stable isotope standards. We also employed qEEG at each visit to investigate alpha frequency power during N‐back WM processing.Results & DiscussionWe detected the presence of all three MMP9 peptides in blood plasma. We observed that MMP9 peptide levels in both mTBI and controls were decreasing in abundance in the 2–4 weeks after injury compared to the first week. Importantly, the MMP9 levels of the LGLGADVAQVTGALR peptide but not the peptides from the pre‐protein, were significantly higher in the mTBI group 2–4 weeks after the injury, consistent with known “secondary injury” phenomena. MMP9 levels correlated with alpha power during WM testing, at the first visit for the controls but not for the mTBI patients, at specific brain regions during different WM load. Elevated MMP9 levels indicate the BBB integrity is compromised acutely after mTBI. The correlations between MMP9 and alpha power during WM that we only found in the trauma controls need further investigation.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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