Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Screening for foot problems in children: is this practice justifiable?

Podiatry screening of children is a common practice, which occurs largely without adequate data to support the need for such activity. Such programs may be either formalised, or more ad hoc in nature, depending upon the use of guidelines or existing models. Although often not used, the well-established criteria for assessing the merits of screening programs can greatly increase the understanding as to whether such practices are actually worthwhile. This review examines the purpose of community health screening in the Australian context, as occurs for tuberculosis, breast, cervical and prostate cancers, and then examines podiatry screening practices for children with reference to the criteria of the World Health Organisation (WHO). Topically, the issue of paediatric foot posture forms the focus of this review, as it presents with great frequency to a range of clinicians. Comparison is made with developmental dysplasia of the hip, in which instance the WHO criteria are well met. Considering that the burden of the condition being screened for must be demonstrable, and that early identification must be found to be beneficial, in order to justify a screening program, there is no sound support for either continuing or establishing podiatry screenings for children

A Transdimensional Bayesian Approach to Ultrasonic Travel-time Tomography for Non-Destructive Testing

Traditional imaging algorithms within the ultrasonic non-destructive testing community typically assume that the material being inspected is primarily homogeneous, with heterogeneities only at sub-wavelength scales. When the medium is of a more generally heterogeneous nature, this assumption can contribute to the poor detection, sizing and characterisation of any defects. Prior knowledge of the varying velocity fields within the component would allow more accurate imaging of defects, leading to better decisions about how to treat the damaged component. This work endeavours to reconstruct the inhomogeneous velocity fields of random media from simulated ultrasonic phased array data. This is achieved via application of the reversible-jump Markov chain Monte Carlo method: a sampling-based approach within a Bayesian framework. The inverted maps are then used in conjunction with an imaging algorithm to correct for deviations in the wave speed, and the reconstructed flaw images are then used to quantitatively measure the success of this methodology. Using full matrix capture data arising from a finite element simulation of a phased array inspection of a heterogeneous component, a six-fold improvement in flaw location is achieved by taking into account the reconstructed velocity map which exploits almost no \textit{a priori} knowledge of the material's internal structure. Receiver operating characteristic curves are then calculated to demonstrate the enhanced probability of detection achieved when the material map is accounted for

Effect of central and non-central frequency components on the quality of damage imaging

Accurate image reconstruction of damage through Lamb wave diffraction tomography (LWDT) requires substantial information of scatter field. This can be achieved using transducer network to collect the scatter field data. However, this requires a large number of transducers that creates logistical constraints for the practical applications of the technique. Various methods have been developed to improve the practicability of LWDT. One of the main approaches is to employ data at multiple frequencies within the bandwidth of the excitation signal. The objective of this study is to investigate the performance of using the data at non-central frequencies to reconstruct the damage image using LWDT. This provides an understanding on the influence of data at each individual frequency in the damage image reconstruction.In this paper, a series of numerical case studies with consideration of different damage sizes and shapes are carried out. Different non-central frequencies data is used to reconstruct the damage image. The results show that using the data at different non-central frequencies leads to different qualities of the reconstructed damage images. The quality of these reconstructed damage images are then compared to investigate the information contained of the data at each individual frequency. The study shows that the non-central frequencies data can provide additional information in the damage image reconstruction. Overall, the results of this study provide insights into the influences of the data at different frequencies, which is essential to advance the developments of the LWDT.Gnana Teja Pudipeddi, Ching-Tai Ng, Andrei Kotouso

BCG vaccination: a role for vitamin D?

BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OH)D concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants

Immunogenicity of Danish-SSI 1331 BCG vaccine in the UK: comparison with Glaxo-Evans 1077 BCG vaccine.

The immunogenicity and reactogenicity, in British schoolchildren, of the newly introduced Danish-SSI 1331 BCG vaccine was compared with that of the previously used Glaxo-Evans 1077 BCG vaccine. Interferon-gamma (IFN-gamma) response to M. tuberculosis purified protein derivative (M.tb PPD) in a 6-day whole blood assay and delayed type hypersensitivity (DTH) to tuberculin PPD were determined before and 1 year after receiving BCG or no vaccination. Scar size was measured 1 year after vaccination. There was no evidence of a difference in immunogenicity (IFN-gamma and DTH conversion rates) but evidence of lower reactogenicity (scar size) with Danish-SSI 1331 compared to Glaxo-Evans 1077 vaccines

An integrative review of systematic reviews related to the management of breathlessness in respiratory illnesses

Background: breathlessness is a debilitating and distressing symptom in a wide variety of diseases and still a difficult symptom to manage. An integrative review of systematic reviews of non-pharmacological and pharmacological interventions for breathlessness in non-malignant disease was undertaken to identify the current state of clinical understanding of the management of breathlessness and highlight promising interventions that merit further investigation.Methods: systematic reviews were identified via electronic databases between July 2007 and September 2009. Reviews were included within the study if they reported research on adult participants using either a measure of breathlessness or some other measure of respiratory symptoms.Results: in total 219 systematic reviews were identified and 153 included within the final review, of these 59 addressed non-pharmacological interventions and 94 addressed pharmacological interventions. The reviews covered in excess of 2000 trials. The majority of systematic reviews were conducted on interventions for asthma and COPD, and mainly focussed upon a small number of pharmacological interventions such as corticosteroids and bronchodilators, including beta-agonists. In contrast, other conditions involving breathlessness have received little or no attention and studies continue to focus upon pharmacological approaches. Moreover, although there are a number of non-pharmacological studies that have shown some promise, particularly for COPD, their conclusions are limited by a lack of good quality evidence from RCTs, small sample sizes and limited replication.Conclusions: more research should focus in the future on the management of breathlessness in respiratory diseases other than asthma and COPD. In addition, pharmacological treatments do not completely manage breathlessness and have an added burden of side effects. It is therefore important to focus more research on promising non-pharmacological intervention

Assessment of Microfinance Interventions and Intimate Partner Violence

ImportanceAn estimated 27% of ever-partnered women aged 15 to 49 years have experienced intimate partner violence (IPV) in their lifetimes, which has been associated with a wide range of both acute and chronic illness. Poverty is thought to be a major driver of IPV, and economic empowerment programs may reduce violence.ObjectiveTo evaluate whether microfinance interventions are associated with reductions in various forms of IPV.Data SourcesOn August 3, 2022, PubMed, CINAHL, Embase, Web of Science, EconLit, and 5 global health databases were searched from inception.Study SelectionIncluded studies were randomized clinical trials evaluating the effect of microfinance interventions vs control on exposure to IPV. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline.Data Extraction and SynthesisAuthors independently assessed study eligibility, extracted prespecified data, and evaluated risk of bias using the Cochrane Risk of Bias tool.Main Outcomes and MeasuresOutcome measures of interest were exposure to overall IPV and 4 World Health Organization–designated IPV domains: physical, psychological and emotional, sexual, and controlling behaviors. Univariate meta-analyses using a random effects model were used to calculate the standardized mean differences (SMDs) and 95% CIs for each IPV outcome. The Grading of Recommendations Assessment, Development, and Evaluation method was used to rate the certainty of findings.ResultsOverall, 10 randomized clinical trials met inclusion criteria, with a total of 16 136 participants, of whom 98% identified as women, with a mean age of 28.9 years. Compared with no intervention, participation in microfinance was associated with lower rates of psychological and emotional violence (SMD, 0.87; 95% CI, 0.80-0.95; I2 = 46%; high certainty), sexual violence (SMD, 0.76; 95% CI, 0.63-0.90; I2 = 44%; low certainty), and controlling behaviors (SMD, 0.82; 95% CI, 0.74-0.92; I2 = 54%; high certainty). There was no significant association with physical violence (SMD, 0.89; 95% CI, 0.76-1.04; very-low certainty).Conclusions and RelevanceThis systematic review and meta-analysis of microfinance interventions found a reduction in exposure to psychological and emotional IPV as well as controlling behaviors among participants receiving microfinance interventions, with high certainty evidence. Further work is needed to evaluate which types of microfinance interventions are most effective at reducing the various forms of IPV.</jats:sec

Polyfunctional CD4 T-cells correlate with in vitro mycobacterial growth inhibition following Mycobacterium bovis BCG-vaccination of infants

AbstractBackgroundVaccination with Bacillus Calmette Guerin (BCG) protects infants against childhood tuberculosis however the immune mechanisms involved are not well understood. Further elucidation of the infant immune response to BCG will aid with the identification of immune correlates of protection against tuberculosis and with the design of new improved vaccines. The purpose of this study was to investigate BCG-induced CD4+ T-cell responses in blood samples from infants for cytokine secretion profiles thought to be important for protection against tuberculosis and compare these to PBMC-mediated in vitro mycobacterial growth inhibition.MethodsBlood from BCG-vaccinated or unvaccinated infants was stimulated overnight with Mycobacterium tuberculosis (M. tb) purified protein derivative (PPD) or controls and intracellular cytokine staining and flow cytometry used to measure CD4+T-cell responses. PBMC cryopreserved at the time of sample collection were thawed and incubated with live BCG for four days following which inhibition of BCG growth was determined.ResultsPPD-specific IFNγ+TNFα+IL-2+CD4+T-cells represented the dominant T-cell response at 4monthsand1yearafter infant BCG. These responses were undetectable in age-matched unvaccinated infants. IL-17+CD4+T-cells were significantly more frequent in vaccinated infants at 4monthsbut not at 1-year post-BCG. PBMC-mediated inhibition of mycobacterial growth was significantly enhanced at 4monthspost-BCG as compared to unvaccinated controls. In an analysis of all samples with both datasets available, mycobacterial growth inhibition correlated significantly with the frequency of polyfunctional (IFNγ+TNFα+IL-2+) CD4+T-cells.ConclusionsThese data suggest that BCG vaccination of infants induces specific polyfunctional T-helper-1 and T-helper-17 responses and the ability, in the PBMC compartment, to inhibit the growth of mycobacteria in vitro. We also demonstrate that polyfunctional T-helper-1 cells may play a role in growth inhibition as evidenced by a significant correlation between the two