The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.

Context.-The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.Objective.-To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, ␤-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).Design.-Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.Setting.-Thirty-seven community hospitals in Minnesota.Patients.-All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.Intervention.-Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.Main Outcome Measures.-Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.Results.-Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of −0.03 at control hospitals (P=.04). For ␤-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.Conclusions.-Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, ␤-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients.