The incidence of nontuberculous mycobacterial (NTM) infections is increasing worldwide, particularly NTM lymphadenitis and skin infections (Buruli ulcer). This review summarizes the evidence for the ...protective effectiveness of BCG vaccination against NTM disease.
A systematic search using PRISMA guidelines was done for controlled studies investigating the protective effectiveness of BCG vaccination against NTM disease in immunocompetent individuals. This revealed 10 studies, including almost 12 million participants.
Three cohort studies in industrialized countries suggest that the incidence of NTM lymphadenitis is greatly reduced among BCG-vaccinated children compared with BCG-unvaccinated children, with a risk ratio (RR) of 0.04 (95% confidence interval CI, .01-.21). In two randomized trials in low-income countries, BCG protected against Buruli ulcer for the first 12 months following vaccination (RR, 0.50 95% CI, .37-.69). Four case-control studies had conflicting results. One cohort study found that individuals with Buruli ulcer are less likely to develop osteomyelitis if they have a BCG scar (RR, 0.36 95% CI, .22-.58). No studies have compared different BCG vaccine strains or the effect of revaccination in this setting.
The protective effect of BCG vaccination against NTM should be taken into consideration when deciding on recommendations for discontinuation of universal BCG vaccination programs and in assessing new vaccines designed to replace BCG.
The 1990s saw a questioning of the value of merely satisfying customers and instead focused attention on the importance of customer delight. In a key contribution, Oliver, Rust, and Varki (1997) ...developed a structural model of the antecedents and consequences of customer delight, acting in parallel with satisfaction, that was generally supported for two entertainment services. However, the effect of delight on intention was significant for symphony ticket purchasers but not for theme park patrons. This article first replicates their path analysis for more mundane visits to consumer Web sites. Then it takes advantage of a larger sample and additional measures to address construct measurement issues and to determine whether customer delight is something more than a nonlinear effect of satisfaction on intention.
Controlling COVID-19 transmission in universities poses challenges due to the complex social networks and potential for asymptomatic spread. We developed a stochastic transmission model based on ...realistic mixing patterns and evaluated alternative mitigation strategies. We predict, for plausible model parameters, that if asymptomatic cases are half as infectious as symptomatic cases, then 15% (98% Prediction Interval: 6-35%) of students could be infected during the first term without additional control measures. First year students are the main drivers of transmission with the highest infection rates, largely due to communal residences. In isolation, reducing face-to-face teaching is the most effective intervention considered, however layering multiple interventions could reduce infection rates by 75%. Fortnightly or more frequent mass testing is required to impact transmission and was not the most effective option considered. Our findings suggest that additional outbreak control measures should be considered for university settings.
Tracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing ...every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARS-CoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system, we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020 and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 61.9% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with a marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation.
Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens ...for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for.
Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends ...in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.
University students have unique living, learning and social arrangements which may have implications for infectious disease transmission. To address this data gap, we created CONQUEST (COroNavirus ...QUESTionnaire), a longitudinal online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. Here, we analyse results from 740 students providing 1261 unique records from the start of the 2020/2021 academic year (14/09/2020-01/11/2020), where COVID-19 outbreaks led to the self-isolation of all students in some halls of residences. Although most students reported lower daily contacts than in pre-COVID-19 studies, there was heterogeneity, with some reporting many (median = 2, mean = 6.1, standard deviation = 15.0; 8% had ≥ 20 contacts). Around 40% of students' contacts were with individuals external to the university, indicating potential for transmission to non-students/staff. Only 61% of those reporting cardinal symptoms in the past week self-isolated, although 99% with a positive COVID-19 test during the 2 weeks before survey completion had self-isolated within the last week. Some students who self-isolated had many contacts (mean = 4.3, standard deviation = 10.6). Our results provide context to the COVID-19 outbreaks seen in universities and are available for modelling future outbreaks and informing policy.
An improved understanding of the underlying physicochemical properties of respiratory aerosol that influence viral infectivity may open new avenues to mitigate the transmission of respiratory ...diseases such as COVID-19. Previous studies have shown that an increase in the pH of respiratory aerosols following generation due to changes in the gas-particle partitioning of pH buffering bicarbonate ions and carbon dioxide is a significant factor in reducing SARS-CoV-2 infectivity. We show here that a significant increase in SARS-CoV-2 aerostability results from a moderate increase in the atmospheric carbon dioxide concentration (e.g. 800 ppm), an effect that is more marked than that observed for changes in relative humidity. We model the likelihood of COVID-19 transmission on the ambient concentration of CO
, concluding that even this moderate increase in CO
concentration results in a significant increase in overall risk. These observations confirm the critical importance of ventilation and maintaining low CO
concentrations in indoor environments for mitigating disease transmission. Moreover, the correlation of increased CO
concentration with viral aerostability need to be better understood when considering the consequences of increases in ambient CO
levels in our atmosphere.
The English schools-based human papillomavirus (HPV) vaccination programme has the potential to eliminate HPV-related cancers if high uptake is achieved. However, unmet information needs among some ...parents may contribute to persisting lower uptake among minority ethnic groups. Through this study we aimed to understand the information needs of vaccine-hesitant, ethnically diverse parents during decision-making about the HPV vaccine for their adolescent child, to inform the future development of tailored communication materials.
Recruitment was facilitated thorough healthcare and community organisations within London and the South West of England. Semi-structured interviews took place between April and August 2023. Thematic analysis was undertaken, assisted by NVivo software.
Of the 29 parents interviewed, the majority were mothers (79%), belonged to a minority ethnic group (88%), and had an adolescent child unvaccinated against HPV (72%). Five of the interviews were undertaken in the participants' primary language with translation support. Most parents interviewed had limited knowledge about the HPV vaccine and appeared conflicted as to whether vaccines could offer benefits to health. Misunderstanding around the potential of developing serious side-effects (e.g. fertility issues, developing cancer) were factors that could negatively impact decision-making by parents. Stigma associated with the sexual transmissibility of HPV did not always negatively impact decision-making. However, some parents chose not to vaccinate on the basis of perceptions of low risk and a preference to provide education about sexual behaviours to their adolescent child.
Tailoring communication materials to address misunderstandings could support informed decision-making by vaccine hesitant parents for their adolescent children to be vaccinated against HPV. Future communication materials about the HPV vaccine should highlight the benefits of protection against cancer to increase parents' motivation for protect their adolescent child; provide accurate convincing information in relation to the excellent safety profile; and emphasise the importance of providing HPV vaccine at the recommended age, all alongside communicating the universality and commonality of HPV infection.
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