We present a method for rapid calculation of coronavirus growth rates and
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-numbers tailored to publicly available UK data. We assume that the case data comprise a smooth, underlying trend which is ...differentiable, plus systematic errors and a non-differentiable noise term, and use bespoke data processing to remove systematic errors and noise. The approach is designed to prioritize up-to-date estimates. Our method is validated against published consensus
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-numbers from the UK government and is shown to produce comparable results two weeks earlier. The case-driven approach is combined with weight–shift–scale methods to monitor trends in the epidemic and for medium-term predictions. Using case-fatality ratios, we create a narrative for trends in the UK epidemic: increased infectiousness of the B1.117 (Alpha) variant, and the effectiveness of vaccination in reducing severity of infection. For longer-term future scenarios, we base future
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on insight from localized spread models, which show
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going asymptotically to 1 after a transient, regardless of how large the
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transient is. This accords with short-lived peaks observed in case data. These cannot be explained by a well-mixed model and are suggestive of spread on a localized network.
This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
Severe diarrhea from rotavirus remains an important cause of illness in infants. In this trial, investigators in Indonesia assessed the potential benefit of a neonatal rotavirus vaccine.
We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 ...(Ad35) vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults.
Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions) or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively) within one of four dosage groups: Ad35-GRIN/ENV 2×10(9) (A), 2×10(10) (B), 2×10(11) (C), or Ad35-GRIN 1×10(10) (D) viral particles.
No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A-D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC) per 10(6) PBMC to any antigen was 78-139 across Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination.
Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second vaccination. T-cell responses were broad and polyfunctional.
ClinicalTrials.gov NCT00851383.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Tillaux fracture is an uncommon injury to the anterolateral distal tibial epiphysis. It occurs during a distinct time period when adolescent patients are transitioning to skeletal maturity. Owing ...to its rarity, the optimal management strategy for this fracture is not well-described. The aim of this review was to assess the outcomes of operatively and nonoperatively managed displaced adolescent Tillaux fractures. We analysed articles from The Cochrane Library, PubMed, MEDLINE, and EMBASE databases that met our predetermined inclusion and exclusion criteria according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. A descriptive data analysis was performed. A total of 461 articles were identified from the data search, of which 13 articles were included for full-text analysis. Five of these studies reported recognised patient outcome measures and the remaining eight reported on radiographic follow-up. The reported studies included a total of 114 patients with Tillaux fractures; 58.8% of patients were female and 34.2% were male. Mean ages ranged from 12.5 to 15 years, with the youngest patient being 12 years old and the oldest 17 years old. Overall mean follow-up was 42.8 months. Of the patients, 40.4% were treated with open reduction internal fixation (ORIF), 14.9% with closed reduction internal fixation (CRIF), and 1.8% arthroscopically. The remainder were treated nonoperatively. Outcome measures were excellent for all patients irrespective of operative management choice. Follow-up radiographic deformity was only evident in Tillaux fractures that were managed nonoperatively; deformity included poor joint congruity, angular deformity, and tibial shortening. These nonoperative patients have a residual fracture displacement of 2 mm. There were no reported instances of premature physeal closure for any patient. This review shows that excellent patient outcomes have been reported for different methods of operative fixation, however, study sizes are small and data is sparse. Further robust comparative studies are required to identify definitive conclusions. The use of established clinical and radiographic outcome measures will help improve the quality of future studies for this relatively rare injury.
A randomized, double-blind, placebo controlled phase I trial.
The trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of prime-boost vaccination ...regimens with either 2 doses of ADVAX, a DNA vaccine containing Chinese HIV-1 subtype C env gp160, gag, pol and nef/tat genes, as a prime and 2 doses of TBC-M4, a recombinant MVA encoding Indian HIV-1 subtype C env gp160, gag, RT, rev, tat, and nef genes, as a boost in Group A or 3 doses of TBC-M4 alone in Group B participants. Out of 16 participants in each group, 12 received vaccine candidates and 4 received placebos.
Both vaccine regimens were found to be generally safe and well tolerated. The breadth of anti-HIV binding antibodies and the titres of anti-HIV neutralizing antibodies were significantly higher (p<0.05) in Group B volunteers at 14 days post last vaccination. Neutralizing antibodies were detected mainly against Tier-1 subtype B and C viruses. HIV-specific IFN-γ ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN-γ ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1(st) and 2(nd) MVA doses as compared to the responses in group B volunteers. However, the priming effect was short lasting leading to no difference in the frequency, breadth and magnitude of IFN-γELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination.
Although DNA priming resulted in enhancement of immune responses after 1(st) MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting.
Clinical Trial Registry CTRI/2009/091/000051.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work surveys over 14,000 respondents in seven countries to assess support for government action to protect the environment, and for different policies at the 2021 UN Climate Change Conference ...(COP26) in Glasgow. Baseline results reveal overwhelming support for action. At least nine out of ten respondents in six countries, and 79% in the USA, agree that all governments should do more. In each country, at least 50% of respondents express support for four policies: protecting wildlife; planting trees; spending more on clean technologies; and reducing the production of greenhouse gases over thirty years. A survey-experiment tests whether support changes when respondents are exposed to short texts framed in different ways. On average, exposure to a patriotism or public health text significantly raises support for action, albeit by only 1.6 and 1.3 percentage points respectively. On policies, exposure to either a public health text or a text based on current UN messaging increases support for tree planting by 2.3 and 2.9 percentage points respectively. These results suggest that international public opinion is overwhelmingly in favour of government action at COP26. They highlight policies that are likely to attract majority support, and suggest that message-framing can have a very small impact.
Abstract
Streptococcus pyogenes (Strep A) infections result in a vastly underestimated burden of acute and chronic disease globally. The Strep A Vaccine Global Consortium’s (SAVAC’s) mission is to ...accelerate the development of safe, effective, and affordable S. pyogenes vaccines. The safety of vaccine recipients is of paramount importance. A single S. pyogenes vaccine clinical trial conducted in the 1960s raised important safety concerns. A SAVAC Safety Working Group was established to review the safety assessment methodology and results of more recent early-phase clinical trials and to consider future challenges for vaccine safety assessments across all phases of vaccine development. No clinical or biological safety signals were detected in any of these early-phase trials in the modern era. Improvements in vaccine safety assessments need further consideration, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance.
Safety assessment methodology and future challenges for the clinical development of Streptococcus pyogenes vaccines are reviewed and discussed. Improvements in vaccine safety assessments, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance, need further consideration.
A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human ...parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers
A prophylactic HIV-1 vaccine is a global health priority.
To assess a novel vaccine platform as a prophylactic HIV-1 regimen.
Randomized, double-blind, placebo-controlled trial. Both participants and ...study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149).
United States, East Africa, and South Africa.
Healthy adults without HIV infection.
2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert Ad26.EnvA and adenovirus serotype 35 with an HIV-1 envelope A insert Ad35.Env, both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.
Safety and immunogenicity and the effect of baseline vector immunity.
217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.
Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.
Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.
International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.
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