A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination.

BACKGROUND: Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. PURPOSE: The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. METHODS: New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). RESULTS: New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. CONCLUSIONS: Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

Cardiac CT angiography compared with myocardial perfusion stress testing on downstream resource utilization.

BACKGROUND: Nuclear myocardial perfusion stress (MPS) testing and cardiac computed tomographic angiography (CCTA) are commonly used noninvasive tests. Limited studies exist comparing their clinical and cost outcomes. OBJECTIVES: We compared the clinical and cost outcomes of MPS with CCTA in a symptomatic cohort. METHODS: We retrospectively identified 241 symptomatic patients without known coronary artery disease (CAD) who underwent MPS between May 2006 and April 2008. A comparison group of 252 age- and sex-matched symptomatic patients without known CAD underwent 64-slice CCTA during the same period. The primary outcome was the per-patient rate of posttest clinical evaluations and cardiac testing for the presenting symptom. Total direct costs were also compared. RESULTS: The group consisted of 44% women of mean age 53 ± 10 years. There were no differences in risk factors or pretest probability of obstructive CAD (83% intermediate risk) between groups. During mean follow-up of 30 ± 7 months, we found no difference between CCTA and MPS in per-patient rates of any posttest evaluation or testing, 24.6% versus 27.7% (P = 0.44), respectively. CCTA patients had lower utilization of invasive angiography (3.3% vs 8.1%; P = 0.02) and a nonsignificant trend toward reduced downstream cardiac testing (11.5% vs 17.0%; P = 0.08). Including the evaluation of significant incidental findings (7.1% in CCTA), mean direct costs were significantly lower using CCTA ($808; 95% CI, $611-$1005) compared with MPS ($1315; 95% CI, $1105-$1525; P <0.001). CONCLUSIONS: Low-intermediate risk patients without known CAD who underwent CCTA, compared with MPS, had similar rates of posttest evaluations, fewer invasive catheterizations, and lower overall evaluation costs.

A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine made from a strain with deleted lpxL2 and synX and stable expression of opcA.

This phase 1 clinical trial assessed the safety and immunogenicity of a native outer membrane vesicle (NOMV) vaccine prepared from a lpxL2(-) synX(-) mutant of strain 44/76 with opcA expression stabilized. Thirty-four volunteers were assigned to one of the three dose groups (25 mcg, 25 mcg with aluminum hydroxide adjuvant, and 50 mcg) to receive three intramuscular injections at 0, 6 and 24 weeks. Specific local and systemic adverse events (AEs) were solicited by diary and at visits on days 1, 2, 7 and 14 after each vaccination and at the end of the study at 30 weeks. Blood chemistries, complete blood count, and coagulation studies were measured on each vaccination day and again two days later. Blood for antibody measurements and bactericidal assays were drawn 0, 14, and 42 days after each vaccination. The proportion of volunteers who developed a fourfold or greater increase in serum bactericidal activity (SBA) to the wild-type parent of the vaccine strain with high opcA expression at 6 weeks after the third dose was 12/26 (0.46, 95% confidence interval 0.27-0.65). Antibody levels to OpcA were significantly higher in vaccine responders than in non-responders (p=0.008), and there was a trend for higher antibody levels to the lipooligosaccharide (LOS) (p=0.059). Bactericidal depletion assays on sera from volunteers with high-titer responses also indicate a major contribution of anti-OpcA and anti-LOS antibodies to the bactericidal response.These results suggest that genetically modified NOMV vaccines can induce protection against group B meningococcus.

Fatal pulmonary Mycobacterium abscessus infection in a patient using etanercept.

A case of fatal pulmonary Mycobacterium abscessus infection in a 56-year-old man is reported. The patient had a longstanding history of seropositive, nodular rheumatoid arthritis with severe joint manifestations that had been treated with a regimen of prednisone, leflunomide, and etanercept. He presented to our facility with complaint of productive cough, persistent fevers, pleuritic chest discomfort, and dyspnea at rest. The patient was admitted to hospital, placed in isolation, a left-sided chest tube was inserted (left pneumothorax identified), and sputum acid-fast bacteria stains and cultures were obtained. Fluorochrome stains demonstrated numerous acid-fast bacteria, and M. abscessus was recovered from the culture media. He was treated with a regimen of amikacin, cefoxitin, and clarithromycin. He initially responded well, and was discharged home with this regimen. He remained afebrile with decreased cough and sputum production until 15 days after discharge when he was again admitted to hospital, with acute onset dyspnea and right-sided chest discomfort (right pneumothorax identified). He ultimately expired, due to overwhelming pulmonary infection, 20 days after readmission to hospital. Autopsy revealed acid fast bacilli in the setting of numerous, bilateral, necrotic, granulomatous, cavitary pulmonary lesions. Based on its mechanism of action, we propose an association between the use of etanercept, a tumor necrosis factor alpha (TNF-alpha) inhibitor, and this case of fatal pulmonary mycobacterial infection. We recommend that physicians exercise cautious clinical judgment when initiating etanercept therapy in persons with underlying lung disease, especially in communities in which mycobacterial organisms are highly prevalent. We also advise physicians to maintain a high level of vigilance for late onset granulomatous infection in persons using etanercept.

A 22-year-old Army private with chest pain and weight loss.

The objective of this study was to delineate an efficient and effective diagnostic approach in evaluating a patient with weight loss and a posterior mediastinal mass. This case demonstrates the evaluation and management of a 22-year-old Army private with weight loss, chest pain, and a posterior mediastinal mass on chest X-ray. The importance of obtaining a thorough travel history to formulate the differential diagnosis is highlighted.