Five Antigen Tests for SARS-CoV-2: Virus Viability Matters.

Antigen testing for SARS-CoV-2 (AGT) is generally considered inferior to RT-PCR testing in terms of sensitivity. However, little is known about the infectiousness of RT-PCR positive patients who pass undetected by AGT. In a screening setting for mildly symptomatic or asymptomatic patients with high COVID-19 prevalence (30-40%), 1141 patients were tested using one of five AGTs and RT-PCR. Where the results differed, virus viability in the samples was tested on cell culture (CV-1 cells). The test battery included AGTs by JOYSBIO, Assure Tech, SD Biosensor, VivaChek Biotech and NDFOS. Sensitivities of the ATGs compared to RT-PCR ranged from 42% to 76%. The best test yielded a 76% sensitivity, 97% specificity, 92% positive, and 89% negative predictive values, respectively. However, in the best performing ATG tests, almost 90% of samples with "false negative" AGT results contained no viable virus. Corrected on the virus viability, sensitivities grew to 81-97% and, with one exception, the tests yielded high specificities >96%. Performance characteristics of the best test after adjustment were 96% sensitivity, 97% specificity, 92% positive, and 99% negative predictive values (high prevalence population). We, therefore, believe that virus viability should be considered when assessing the AGT performance. Also, our results indicate that a well-performing antigen test could in a high-prevalence setting serve as an excellent tool for identifying patients shedding viable virus. We also propose that the high proportion of RT-PCR-positive samples containing no viable virus in the group of "false negatives" of the antigen test should be further investigated with the aim of possibly preventing needless isolation of such patients.

Rational Design of a New Class of Toll-Like Receptor 4 (TLR4) Tryptamine Related Agonists by Means of the Structure- and Ligand-Based Virtual Screening for Vaccine Adjuvant Discovery.

In order to identify novel lead structures for human toll-like receptor 4 (hTLR4) modulation virtual high throughput screening by a peta-flops-scale supercomputer has been performed. Based on the in silico studies, a series of 12 compounds related to tryptamine was rationally designed to retain suitable molecular geometry for interaction with the hTLR4 binding site as well as to satisfy general principles of drug-likeness. The proposed compounds were synthesized, and tested by in vitro and ex vivo experiments, which revealed that several of them are capable to stimulate hTLR4 in vitro up to 25% activity of Monophosphoryl lipid A. The specific affinity of the in vitro most potent substance was confirmed by surface plasmon resonance direct-binding experiments. Moreover, two compounds from the series show also significant ability to elicit production of interleukin 6.

Rotavirus vaccination in central Europe.

Each year, rotavirus (RV) infection is the leading cause of acute gastroenteritis requiring hospitalisation and of nosocomially transmitted diseases in children younger than 5 years across Central European Vaccination Awareness Group (CEVAG) countries; however, inadequate surveillance systems and lack of routine RV testing still exist in most CEVAG countries, making it difficult to accurately assess the present burden of acute RV gastroenteritis in the younger population. Furthermore, routine immunisation of infants with RV vaccines has not been implemented, and no official and uniform recommendations exist in most of the countries in these territories. The present study provides CEVAG country-specific estimates of the disease burden of RV gastroenteritis among the youngest population and presents evidence-based advice on the use of RV vaccines in the region, while providing a framework for vaccination at the national level.

Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine: a randomized, controlled trial in adolescent girls.

PURPOSE: Immunization of girls against oncogenic human papillomavirus (HPV) types before sexual debut is important for cervical cancer prevention. This phase III blinded, randomized, controlled trial in adolescent girls assessed safety of the HPV-16/18 AS04-adjuvanted vaccine. METHODS: Girls (mean age 12 years) in 12 countries received the HPV-16/18 L1 virus-like particle AS04-adjuvanted vaccine (N = 1,035) or hepatitis A virus vaccine as control (N = 1,032) at 0, 1, and 6 months. The primary objective was to compare the occurrence of serious adverse events (SAEs) between groups. HPV-16 and HPV-18 antibody titers were assessed by enzyme-linked immunosorbent assay post-vaccination. RESULTS: Up to study month 7, 11 girls in the HPV-16/18 vaccine group reported 14 SAEs and 13 girls in the control group reported 15 SAEs. The difference in SAE incidence between groups was .20% (95% CI, -.78, 1.20). No SAE in the HPV-16/18 vaccine group was considered related to vaccination or led to withdrawal. The incidence of solicited local and general symptoms up to 7 days post-vaccination was moderately higher with the HPV-16/18 vaccine than with control. The incidence of unsolicited symptoms, new onset of chronic diseases, and medically significant conditions was similar between groups. All girls seroconverted for both antigens after three doses of the HPV-16/18 vaccine; geometric mean titers were 19,882.0 and 8,262.0 EU/mL for anti-HPV-16 and -18 antibodies, respectively, in initially seronegative girls. CONCLUSIONS: The HPV-16/18 AS04-adjuvanted vaccine was generally well tolerated and immunogenic when administered to young adolescent females, the primary target of organized vaccination programs.

Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials.

BACKGROUND: Although fever is part of the normal inflammatory process after immunisation, prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion. We assessed the effect of prophylactic administration of paracetamol at vaccination on infant febrile reaction rates and vaccine responses. METHODS: In two consecutive (primary and booster) randomised, controlled, open-label vaccination studies, 459 healthy infants were enrolled from ten centres in the Czech Republic. Infants were randomly assigned with a computer-generated randomisation list to receive three prophylactic paracetamol doses every 6-8 h in the first 24 h (n=226) or no prophylactic paracetamol (n=233) after each vaccination with a ten-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) co-administered with the hexavalent diphtheria-tetanus-3-component acellular pertussis-hepatitis B-inactivated poliovirus types 1, 2, and 3-H influenzae type b (DTPa-HBV-IPV/Hib) and oral human rotavirus vaccines. The primary objective in both studies was the reduction in febrile reactions of 38.0 degrees C or greater in the total vaccinated cohort. The second objective was assessment of immunogenicity in the according-to-protocol cohort. These studies are registered with ClinicalTrials.gov, numbers NCT00370318 and NCT00496015. FINDINGS: Fever greater than 39.5 degrees C was uncommon in both groups (after primary: one of 226 participants [<1%] in prophylactic paracetamol group vs three of 233 [1%] in no prophylactic paracetamol group; after booster: three of 178 [2%] vs two of 172 [1%]). The percentage of children with temperature of 38 degrees C or greater after at least one dose was significantly lower in the prophylactic paracetamol group (94/226 [42%] after primary vaccination and 64/178 [36%] after booster vaccination) than in the no prophylactic paracetamol group (154/233 [66%] after primary vaccination and 100/172 [58%] after booster vaccination). Antibody geometric mean concentrations (GMCs) were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes, protein D, antipolyribosyl-ribitol phosphate, antidiphtheria, antitetanus, and antipertactin. After boosting, lower antibody GMCs persisted in the prophylactic paracetamol group for antitetanus, protein D, and all pneumococcal serotypes apart from 19F. INTERPRETATION: Although febrile reactions significantly decreased, prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced. FUNDING: GlaxoSmithKline Biologicals (Belgium).

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the introduction of HPV vaccines.

Vaccines against human papillomavirus (HPV), the primary causative agent in cervical cancer, are licensed. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on the introduction of HPV vaccines in central Europe. Eight countries currently have medical representatives on CEVAG: the Czech Republic, Estonia, Hungary, Lithuania, Poland, Romania, Slovakia and Turkey. By raising awareness and disseminating information, CEVAG aims to promote the efficient and safe use of vaccines to prevent, control and if possible eliminate infectious diseases. In January 2008, the European Centre for Disease Prevention and Control published a report entitled Guidance for the Introduction of HPV Vaccines in EU Countries. Members of CEVAG have taken the information relevant to their countries from this report and, with consideration of local issues, produced these guidance recommendations for the introduction of HPV vaccines in the CEVAG region, which may be adapted for use in individual countries.

Medialization thyroplasty with a customized silicone implant: clinical experience.

The authors implemented medialization thyroplasty with a customized silicone implant in a total of 43 operations (36 patients) in 1999-2003. In 5 of these patients, the medialization thyroplasty was combined with cricothyroid subluxation (3 cases) or adduction of arytenoid cartilage (3 cases). One patient received medialization thyroplasty, cricothyroid subluxation and adduction of arytenoid cartilage. Postoperatively 36 patients reported substantial reduction of their complaints, 5 patients found their voice improved and only 2 patients (5.6%) stated that their voice had not changed. The subjective evaluation was consistent with the findings of laryngoscopy and the preoperative and postoperative phonation parameters (maximum phonation time, maximum sound pressure level, jitter and shimmer). Average maximum phonation time was 6.5 s before surgery and 12.5 s after surgery. Maximum vocal sound pressure level was, on average, about 4 dB higher after surgery. Jitter was reduced from 5.3 to 3.7% and shimmer from 32.3 to 18.6%. The differences between presurgical and postsurgical parameters in our study were all statistically significant, indicating voice improvement. Medialization thyroplasty with a silicone implant was proven to be a successful and safe surgical method for the treatment of vocal fold paralysis.