Safety and Immunogenicity of Different Immunization Regimens of CVD 103-HgR Live Oral Cholera Vaccine in Soldiers and Civilians in Thailand

Attenuated Vibrio cholerae oral vaccineCVD 103-HgR was well tolerated by 324 Thai soldiers and civilians. Most receiveda single 5 × 108 cfu dose, while 40 each receivedone or two 5 × 109 cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P < .001). Increasing the vaccinedose to 5 × 109 cfu raised the geometric mean titer (P < .001).Asecond 5 × 109 cfu dose one weeklater did not notably increase seroconversions. Likelihood of seroconversionwas inverselycorrelated with baseline vibriocidal titer (P < .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers ⩽1:40, including 100% of civilians after one 5 × 108 cfu dose, 79% of soldiers after one 5 × 109 cfu dose, and 45% of soldiers after one 5 × 108 cfu dose. In persons with elevatedbaseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects,other measurements must be used. Study regimens in endemic areas should use a single 5 × 109 cfu dos

Loss of C-5 Sterol Desaturase Activity Results in Increased Resistance to Azole and Echinocandin Antifungals in a Clinical Isolate of Candida parapsilosis

Among emerging non-albicans Candida species, Candida parapsilosis is of particular concern as a cause of nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole and echinocandins are considered effective treatments for such infections, recent reports of fluconazole and echinocandin resistance in C. parapsilosis indicate a growing problem. The present study describes a novel mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicated differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing revealed that the resistant isolate possessed an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicated a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restored wild-type susceptibility to all azoles and echinocandins tested. Disruption of ERG3 in the susceptible and resistant isolates resulted in a loss of sterol desaturase activity, high-level azole resistance, and an echinocandin-intermediate to -resistant phenotype. While disruption of ERG3 in C. albicans resulted in azole resistance, echinocandin MICs, while elevated, remained within the susceptible range. This work demonstrates that the G111R substitution in Erg3 is wholly responsible for the altered azole and echinocandin susceptibilities observed in this C. parapsilosis isolate and is the first report of an ERG3 mutation influencing susceptibility to the echinocandins

Injuries to Ice Hockey Referees and Linesmen: A Survey of International Ice Hockey Federation Officials

BACKGROUND: Ice hockey referees and linesmen are at risk for musculoskeletal injuries because of the lack of protective equipment and contact with players, sticks, pucks, the ice surface and boards. PURPOSE: To quantify and analyze injuries reported by officials of the International Ice Hockey Federation (IIHF). STUDY DESIGN: Descriptive epidemiology study. METHODS: A 61-question survey tool was designed by an interdisciplinary team to evaluate musculoskeletal injuries experienced by ice hockey officials. This survey was administered to 600 active IIHF referees and linesmen. Only completed survey responses were included in the statistical analysis. Continuous variables were analyzed using unpaired t-tests, while categorical data were assessed utilizing chi-square tests. RESULTS: Of the 600 surveys administered, 264 surveys were completed by officials from 45 countries (44% response rate). Of the respondents, 72% were male, and 28% were female, with a mean age of 31.1 ± 5.8 years. Officiating experience averaged 11.4 ± 6.0 years (6.3 ± 4.5 years with the IIHF). A total of 295 injuries were reported by 55% of the officials. Injuries occurred more frequently during games compared with training, and officials who worked year-round had more total injuries than those who took time off (P = .03). The most common injuries involved the wrist and hand (n = 64 [22%]), head and face (n = 58 [20%]), and the knee (n = 47 [16%]). Wrist and hand trauma included 23 fractures. Knee and shoulder injuries were most likely to require surgery compared with other body areas (P \u3c .001); 30 officials underwent surgery because of an acute knee injury (10%). Injury prevention activities were effective at reducing injuries (P = .04). CONCLUSION: Most ice hockey officials experienced musculoskeletal injuries during their career. The risk of trauma to the wrist and hand can possibly be reduced via equipment modifications including protective gloves. A greater emphasis should be placed on injury prevention programs and time away from officiating competitions

Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus

Objective: Patients with diabetes mellitus are at increased risk for hepatitis B virus (HBV) infection and its complications. HBV vaccination is recommended for adults with diabetes in the United States and other countries. However, few studies have assessed safety and immunogenicity of hepatitis B vaccine in such patients. We assessed the safety and immunogenicity of recombinant hepatitis B vaccine in subjects with and without diabetes mellitus. Methods: Prospective, multi-country controlled study in 21 centers (www.clinicaltrials.gov NCT01627340). Four hundred and sixteen participants with Type-2 diabetes and 258 controls matched for age and body mass index (BMI) (2:1 ratio) received 3-doses of HBV vaccine (Engerix-B™, GSK Vaccines, Belgium) according to a 0, 1, 6\ua0months schedule. Antibodies were measured against HBV surface antigen and expressed as seroprotection rates (anti-HBs ≥10mIU/mL) and geometric mean concentration (GMC). Results: The median age and BMI in patients with diabetes and controls (according-to-protocol cohort) were 54 y and 32.1\ua0kg/m, and 53 y and 30.8\ua0kg/m, respectively. Seroprotection rates (GMCs) one month post-dose-3 were 75.4% (147.6 mIU/mL) and 82.0% (384.2 mIU/mL) in patients with diabetes and controls, respectively. Age-stratified seroprotection rates for patients with diabetes were 88.5% (20–39\ua0years), 81.2% (40–49\ua0years), 83.2% (50–59\ua0years), and 58.2% (≥60\ua0years). The overall safety profile of hepatitis B vaccine was similar between groups. Conclusions: Hepatitis B vaccine is immunogenic in patients with diabetes and has a similar safety profile to vaccination in healthy controls. Because increasing age was generally associated with a reduction in seroprotection rates, hepatitis B vaccine should be administered as soon as possible after the diagnosis of diabetes

Immunogenicity of AS03-adjuvanted and non-adjuvanted trivalent inactivated influenza vaccines in elderly adults: A Phase 3, randomized trial and post-hoc correlate of protection analysis

In this study we describe the immunogenicity results from a subset of older people (N = 5187) who participated in a Phase 3 randomized, observer-blinded trial of AS03-TIV versus TIV (Fluarix™) (ClinicalTrials.gov, NCT00753272). Participants received one dose of AS03-TIV or TIV in each study year and antibody titers against the vaccine strains were assessed using hemagglutination-inhibition (HI) assay at 21 d and 180 d post-vaccination in each vaccine group in the 2008/09 (Year 1) and 2009/10 (Year 2) influenza seasons. Manufacturing consistency of 3 lots of AS03-TIV for HI antibody responses in Year 1 was a co-primary objective. In a post-hoc analysis, a statistical regression model included 4830 subjects in whom immunogenicity and laboratory-confirmed attack rate data were available; the analysis was performed to assess HI antibody titers against A/H3N2 as a correlate of protection for laboratory-confirmed A/H3N2 influenza. AS03-TIV and TIV elicited strong HI antibody responses against each vaccine strain 21 d post-vaccination in both years. The manufacturing consistency of 3 lots of AS03-TIV was demonstrated. In both years and each vaccine group, HI antibody responses were lower for A/H1N1 than the other vaccine strains. Day 180 seroconversion rates (proportion with ≥4-fold increase in titer compared with pre-vaccination titer) in Year 1 in the AS03-TIV and TIV groups, respectively, were 87.7% and 74.1% for A/H3N2, 69.7% and 59.6% for influenza B, and 58.3% and 47.4% for A/H1N1. The post-hoc statistical model based on A/H3N2 attack rates and HI antibody titers estimated that a 4-fold increase in post-vaccination titers against A/H3N2 was associated with a 2-fold decrease in the odds of A/H3N2 infection