Immunogenicity of antigens from the TbD1 region present in M. africanum and missing from "modern" M. tuberculosis: a cross- sectional study

<p>Abstract</p> <p>Background</p> <p>Currently available tools cannot be used to distinguish between sub-species of the <it>M. tuberculosis </it>complex causing latent tuberculosis (TB) infection. <it>M. africanum </it>causes up to half of TB in West- Africa and its relatively lower progression to disease suggests the presence of a large reservoir of latent infection relative to <it>M. tuberculosis</it>.</p> <p>Methods</p> <p>We assessed the immunogenicity of the TbD1 region, present in <it>M. africanum </it>and absent from "modern" <it>M. tuberculosis</it>, in an ELISPOT assay using cells from confirmed <it>M. africanum </it>or <it>M. tuberculosis </it>infected TB patients without HIV infection in the Gambia.</p> <p>Results</p> <p>Antigens from the TbD1 region induced IFNγ responses in only 35% patients and did not discriminate between patients infected with <it>M. africanum </it>vs. <it>M. tuberculosis</it>, while PPD induced universally high responses.</p> <p>Conclusions</p> <p>Further studies will need to assess other antigens unique to <it>M. africanum </it>that may induce discriminatory immune responses.</p

Nasopharyngeal colonization of Gambian infants by Staphylococcus aureus and Streptococcus pneumoniae before the introduction of pneumococcal conjugate vaccines.

Staphylococcus aureus and Streptococcus pneumoniae commonly colonize the upper respiratory tract and can cause invasive disease. Several studies suggest an inverse relationship between these two bacteria in the nasopharynx. This association is of particular concern as the introduction of pneumococcal conjugate vaccines (PCVs) that affect pneumococcal nasopharyngeal carriage become widespread. A cohort of children in rural Gambia were recruited at birth and followed for 1 year, before the introduction of PCV into the routine immunization program. Nasopharyngeal swabs were taken immediately after birth, every 2 weeks for the first 6 months and then every other month. The presence of S. aureus and S. pneumoniae was determined using conventional microbiologic methods. Prevalence of S. aureus carriage was 71.6% at birth, decreasing with age to reach a plateau at approximately 20% between 10 to 20 weeks of age. Carriage with any S. pneumoniae increased during the first 10 weeks of life to peak at approximately 90%, mostly of PCV13 serotypes. Although in the crude analysis S. aureus carriage was inversely associated with carriage of any S. pneumoniae and PCV13 serotypes, after adjusting by age and season, there was a positive association with any carriage (odds ratio 1.32; 95% confidence interval 1.07-1.64; p 0.009) and no association with carriage of PCV13 serotypes (odds ratio 0.99; 95% confidence interval 0.70-1.41; p 0.973). Among Gambian infants, S. aureus and S. pneumoniae are not inversely associated in nasopharyngeal carriage after adjustment for age. Further carriage studies following the introduction of PCV are needed to better understand the relationship between the two bacteria

Safety and immunogenicity of the candidate tuberculosis vaccine MVA85A in West Africa.

BACKGROUND: Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers. METHODS AND FINDINGS: We vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-naïve Gambians than previously studied BCG-naïve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis. CONCLUSIONS: These data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00423839

Effect of age and vaccination with a pneumococcal conjugate vaccine on the density of pneumococcal nasopharyngeal carriage.

BACKGROUND: This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage. METHODS: A cluster-randomized trial was conducted in rural Gambia. In 11 villages (the vaccine group), all residents received 7-valent pneumococcal conjugate vaccine (PCV-7), while in another 10 villages (the control group), only children <30 months old or born during the study period received PCV-7. Cross-sectional surveys (CSSs) were conducted to collect nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after vaccination. Pneumococcal density was defined using a semiquantitative classification (range, 1-4) among colonized individuals. An age-trend analysis of density was conducted using data from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before and after vaccination. RESULTS: Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine-type (VT) and non-vaccine-type (NVT) pneumococci; it decreased with age (P < .001 for VT and NVT). There was a decrease in the density of VT carriage following vaccination in individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from 2.57 to 2.11; P = .070) in the vaccinated villages. Similar decreases in density were observed with NVT within vaccinated and control villages. No significant differences were found between vaccinated and control villages in the postvaccination comparisons for either VT or NVT. CONCLUSIONS: A high density of carriage among young subjects might partly explain why children are more efficient than adults in pneumococcal transmission. PCV-7 vaccination lowered the density of VT and of NVT pneumococcal carriage in the before-after vaccination analysis. CLINICAL TRIALS REGISTRATION: ISRCTN51695599

Measuring attitude towards Buddhism and Sikhism : internal consistency reliability for two new instruments

This paper describes and discusses the development and empirical properties of two new 24-item scales – one measuring attitude toward Buddhism and the other measuring attitude toward Sikhism. The scale is designed to facilitate inter-faith comparisons within the psychology of religion alongside the well-established Francis Scale of Attitude toward Christianity. Data were obtained from a multi-religious sample of 369 school pupils aged between 13 and 15 in London. Application of the two scales demonstrated that adolescents had a more positive attitude to Buddhism than Sikhism. The findings confirm the reliability of the scales and commend them for further use

High-precision polarimetry of nearby stars (d < 50 pc): Mapping the interstellar dust and magnetic field inside the Local Bubble

Context:We investigate the linear polarization produced by interstellar dust aligned by the magnetic field in the solar neighborhood (d Aims: We aim to detect and map dust clouds which give rise to statistically significant amounts of polarization of the starlight passing through the cloud, and to determine the interstellar magnetic field direction from the position angle of the observed polarization.Methods: High-precision broad-band (BV R) polarization observations are made of 361 stars in spectral classes F to G, with detection sensitivity at the level of or better than 10−5 (0.001%). The sample consists of 125 stars in the magnitude range 6–9 observed at the 2.2 m UH88 telescope on Mauna Kea, 205 stars in the magnitude range 3–6 observed at the Japanese (Tohoku) T60 telescope on Haleakala, and 31 stars in the magnitude range 4–7 observed at the 1.27 m H127 telescope of the Greenhill Observatory, Tasmania. Identical copies of the Dipol-2 polarimeter are used on these three sites.Results: Statistically significant (>3σ) polarization is found in 115 stars, and >2σ detection in 178 stars, out of the total sample of 361 stars. Polarization maps based on these data show filament-like patterns of polarization position angles, which are related to both the heliosphere geometry, the kinematics of nearby clouds, and the Interstellar Boundary EXplorer ribbon magnetic field. From long-term multiple observations, a number (~20) of stars show evidence of intrinsic variability at the 10−5 level. This can be attributed to circumstellar effects (e.g., debris disks and chromospheric activity). The star HD 101805 shows a peculiar wavelength dependence, indicating size distribution of scattering particles different from that of a typical interstellar medium. Our high signal-to-noise measurements of nearby stars with very low polarization also provide a useful dataset for calibration purposes

Geo-environmental mapping using physiographic analysis: constraints on the evaluation of land instability and groundwater pollution hazards in the Metropolitan District of Campinas, Brazil

Geo-environmental terrain assessments and territorial zoning are useful tools for the formulation and implementation of environmental management instruments (including policy-making, planning, and enforcement of statutory regulations). They usually involve a set of procedures and techniques for delimitation, characterisation and classification of terrain units. However, terrain assessments and zoning exercises are often costly and time-consuming, particularly when encompassing large areas, which in many cases prevent local agencies in developing countries from properly benefiting from such assessments. In the present paper, a low-cost technique based on the analysis of texture of satellite imagery was used for delimitation of terrain units. The delimited units were further analysed in two test areas situated in Southeast Brazil to provide estimates of land instability and the vulnerability of groundwater to pollution hazards. The implementation incorporated procedures for inferring the influences and potential implications of tectonic fractures and other discontinuities on ground behaviour and local groundwater flow. Terrain attributes such as degree of fracturing, bedrock lithology and weathered materials were explored as indicators of ground properties. The paper also discusses constraints on- and limitations of- the approaches taken

Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases

BACKGROUND: New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. METHODS: We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. RESULTS: We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 × 10(5 )cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. CONCLUSION: Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted

Surprisingly High Specificity of the PPD Skin Test for M. tuberculosis Infection from Recent Exposure in The Gambia

BACKGROUND: Options for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia. METHODOLOGY/PRINCIPAL FINDINGS: Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6–35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p<0.0001). With increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive contacts who were PPD skin test positive increased (p<0.0001), and the proportion of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased (p<0.0001); the converse did not occur. CONCLUSIONS/SIGNIFICANCE: The PPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited