A Phase 2, Randomized, Active-controlled, Observer-blinded Study to Assess the Immunogenicity, Tolerability and Safety of Bivalent rLP2086, a Meningococcal Serogroup B Vaccine, Coadministered With Tetanus, Diphtheria and Acellular Pertussis Vaccine and Serogroup A, C, Y and W-135 Meningococcal Conjugate Vaccine in Healthy US Adolescents.

BACKGROUND: Bivalent rLP2086, targeting meningococcal serogroup B, will extend prevention of meningococcal disease beyond that provided by quadrivalent serogroup ACWY vaccines; coadministration with recommended vaccines may improve adherence to vaccine schedules. This phase 2, randomized, active-controlled, observer-blinded study assessed whether immune responses induced by coadministration of Menactra (meningococcal A, C, Y and W-135 polysaccharide conjugate vaccine [MCV4]) and Adacel (tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine [Tdap]) with bivalent rLP2086 (Trumenba [meningococcal serogroup B vaccine], approved in the United States) were noninferior to MCV4 + Tdap or bivalent rLP2086 alone. METHODS: Healthy adolescents aged 10 to <13 years received MCV4 + Tdap + bivalent rLP2086, MCV4 + Tdap or bivalent rLP2086. Bivalent rLP2086 response was assessed with serum bactericidal assays using human complement with 2 meningococcal serogroup B test strains expressing vaccine-heterologous factor H-binding protein variants; MCV4 with SBAs using rabbit complement; and Tdap with multiplexed Luminex assays. Safety was evaluated. RESULTS: Two thousand six hundred forty-eight subjects were randomized. Immune responses to MCV4 + Tdap + bivalent rLP2086 were noninferior to MCV4 + Tdap or bivalent rLP2086 alone. Seroprotective serum bactericidal assays using human complement titers were documented for 62.3%-68.0% and 87.5%-90% of MCV4 + Tdap + bivalent rLP2086 recipients after doses 2 and 3, respectively. A ≥4-fold rise in serum bactericidal assays using human complement titers from baseline was achieved by 56.3%-64.3% and 84.0%-85.7% of subjects after doses 2 and 3, respectively. Bivalent rLP2086 alone induced similar responses. Concomitant administration did not substantially increase reactogenicity compared with bivalent rLP2086 alone. CONCLUSIONS: Bivalent rLP2086 given concomitantly with MCV4 + Tdap met all noninferiority immunogenicity criteria without a clinically meaningful increase in reactogenicity. MCV4 and bivalent rLP2086 coadministration would provide coverage against the 5 major disease-causing serogroups.

Intermediate follow-up following intravascular stenting for treatment of coarctation of the aorta.

BACKGROUND: We report a multiinstitutional study on intermediate-term outcome of intravascular stenting for treatment of coarctation of the aorta using integrated arch imaging (IAI) techniques. METHODS AND RESULTS: Medical records of 578 patients from 17 institutions were reviewed. A total of 588 procedures were performed between May 1989 and Aug 2005. About 27% (160/588) procedures were followed up by further IAI of their aorta (MRI/CT/repeat cardiac catheterization) after initial stent procedures. Abnormal imaging studies included: the presence of dissection or aneurysm formation, stent fracture, or the presence of reobstruction within the stent (instent restenosis or significant intimal build-up within the stent). Forty-one abnormal imaging studies were reported in the intermediate follow-up at median 12 months (0.5-92 months). Smaller postintervention of the aorta (CoA) diameter and an increased persistent systolic pressure gradient were associated with encountering abnormal follow-up imaging studies. Aortic wall abnormalities included dissections (n = 5) and aneurysm (n = 13). The risk of encountering aortic wall abnormalities increased with larger percent increase in CoA diameter poststent implant, increasing balloon/coarc ratio, and performing prestent angioplasty. Stent restenosis was observed in 5/6 parts encountering stent fracture and neointimal buildup (n = 16). Small CoA diameter poststent implant and increased poststent residual pressure gradient increased the likelihood of encountering instent restenosis at intermediate follow-up. CONCLUSIONS: Abnormalities were observed at intermediate follow-up following IS placement for treatment of native and recurrent coarctation of the aorta. Not exceeding a balloon:coarctation ratio of 3.5 and avoidance of prestent angioplasty decreased the likelihood of encountering an abnormal follow-up imaging study in patients undergoing intravascular stent placement for the treatment of coarctation of the aorta. We recommend IAI for all patients undergoing IS placement for treatment of CoA.

Procedural results and acute complications in stenting native and recurrent coarctation of the aorta in patients over 4 years of age: a multi-institutional study.

BACKGROUND: We report a multi-institutional experience with intravascular stenting (IS) for treatment of coarctation of the aorta. METHODS AND RESULTS: Data was collected retrospectively by review of medical records from 17 institutions. The data was broken down to prior to 2002 and after 2002 for further analysis. A total of 565 procedures were performed with a median age of 15 years (mean=18.1 years). Successful reduction in the post stent gradient (<20 mm Hg) or increase in post stent coarctation to descending aorta (DAo) ratio of >0.8 was achieved in 97.9% of procedures. There was significant improvement (P<0.01) in pre versus post stent coarctation dimensions (7.4 mm+/-3.0 mm vs. 14.3+/-3.2 mm), systolic gradient (31.6 mm Hg+/-16.0 mm Hg vs. 2.7 mm Hg+/-4.2 mm Hg) and ratio of the coarctation segment to the DAo (0.43+/-0.17 vs. 0.85+/-0.15). Acute complications were encountered in 81/565 (14.3%) procedures. There were two procedure related deaths. Aortic wall complications included: aneurysm formation (n=6), intimal tears (n=8), and dissections (n=9). The risk of aortic dissection increased significantly in patients over the age of 40 years. Technical complications included stent migration (n=28), and balloon rupture (n=13). Peripheral vascular complications included cerebral vascular accidents (CVA) (n=4), peripheral emboli (n=1), and significant access arterial injury (n=13). Older age was significantly associated with occurrence of CVAs. A significant decrease in the technical complication rate from 16.3% to 6.1% (P<0.001) was observed in procedures performed after January 2002. CONCLUSIONS: Stent placement for coarctation of aorta is an effective treatment option, though it remains a technically challenging procedure. Technical and aortic complications have decreased over the past 3 years due to, in part, improvement in balloon and stent design. Improvement in our ability to assess aortic wall compliance is essential prior to placement of ISs in older patients with coarctation of the aorta.

Cough and fear of sleep: early clinical signs of Bordetella pertussis in an adult.

Pertussis is increasing in frequency among adults, but early diagnosis requires special attention to details in the medical history. We describe a 64 year-old male with classic signs and symptoms of pertussis and documented Bordetella pertussis infection that were overlooked because he presented with a chief complaint of cough and fear of falling asleep. Coughing paroxysms and a feeling of suffocation (30-60 seconds) only occurred at night after short periods of deep sleep (30-45 minutes). The physicians did not observe these episodes during daytime examinations, and the basis of the patient's fear of sleep was not explored. We recommend reassessment of how adults describe symptoms of pertussis, including fear of sleep, and we suggest the use of PCR technology to allow early diagnosis and prompt treatment.

Cough and fear of sleep: early clinical signs of Bordetella pertussis in an adult

Pertussis is increasing in frequency among adults, but early diagnosis requires special attention to details in the medical history. We describe a 64 year-old male with classic signs and symptoms of pertussis and documented Bordetella pertussis infection that were overlooked because he presented with a chief complaint of cough and fear of falling asleep. Coughing paroxysms and a feeling of suffocation (30-60 seconds) only occurred at night after short periods of deep sleep (30-45 minutes). The physicians did not observe these episodes during daytime examinations, and the basis of the patient's fear of sleep was not explored. We recommend reassessment of how adults describe symptoms of pertussis, including fear of sleep, and we suggest the use of PCR technology to allow early diagnosis and prompt treatment.

Vaccine adjuvants: A new hope for effective immunization

Two important issue regarding the use of immunization to control infections and malignancies in the futureare: 1) the need to render poorly immunogenic, often highly purified, antigens more effective; and 2) the desire to direct the immune response in specific ways to achieve the most relevant response for each disease. The first issue can be solved by a broad range of vaccine adjuvants. The second requires careful selection among the adjuvants to allow directing of the immune response in the most appropriate manner. For exemple, in different settings expansion of a B cell response, cytotoxic T cell response, or enhancement of either a Th1 or Th2 subset response may be desired. These goals are accomplished by the use of several newly developed non-cytokine adjuvants, or by direct injection of the relevant cytokines. Some non-cytokine molecular adjuvants and cytokines used as adjuvants have already been proven effective in animal models and/or in clinical trials. Here, we review the present state of art in the use of vaccine adjuvants for control of various infections diseases.