Guest Editorial

A novel blood test for tuberculosis prevention and treatmen

Meeting report: 5th Global Forum on TB Vaccines, 20-23 February 2018, New Delhi India

The 5th Global Forum on TB Vaccines was held in New Delhi, India from 20 to 23 February 2018. This was the largest Global Forum on TB Vaccines to date with nearly 350 participants from more than 30 countries. The program included over 60 speakers in 12 special, plenary and breakout sessions and 72 posters. This Global Forum brought a great sense of momentum and excitement to the field. New vaccines are in clinical trials, new routes of delivery are being tested, novel assays and biomarker signatures are being developed, and the results from the first prevention of infection clinical trial with the H4:IC31 vaccine candidate and BCG revaccination were presented. Speakers and participants acknowledged the significant challenges that the TB vaccine R&D field continues to face - including limited funding, and the need for novel effective vaccine candidates and tools such as improved diagnostics and biomarkers to accurately predict protective efficacy. New solutions and approaches to address these challenges were discussed. The following report presents highlights from talks presented at this Global Forum. A full program, abstract book and presentations (where publicly available) from the Forum may be found at tbvaccinesforum.org

Potential population level impact on tuberculosis incidence of using an mRNA expression signature correlate-of-risk test to target tuberculosis preventive therapy.

Achieving the WHO End-Tuberculosis (TB) targets requires approaches to prevent progression to TB among individuals with Mycobacterium tuberculosis (M.tb) infection. Effective preventive therapy (PT) exists, but current tests have low specificity for identifying who, among those infected, is at risk of developing TB. Using mathematical models, we assessed the potential population-level impact on TB incidence of using a new more specific mRNA expression signature (COR) to target PT among HIV-uninfected adults in South Africa. We compared the results to the use of the existing interferon-γ release assay (IGRA). With annual screening coverage of 30% COR-targeted PT could reduce TB incidence in 2035 by 20% (95% CI 15-27). With the same coverage, IGRA-targeted PT could reduce TB incidence by 39% (31-48) but would require greater use of PT resulting in a higher number needed to treat per TB case averted (COR: 49 (29-77); IGRA: 84 (59-123)). The relative differences between COR and IGRA were not sensitive to screening coverage. COR-targeted PT could contribute to reducing total TB burden in high incidence countries like South Africa by allowing more efficient targeting of treatment. To maximise impact, COR-like tests may be best utilised in the highest burden regions, or sub-populations, within these countries

Framework for the evaluation of new tests for tuberculosis infection

The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. We also briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system patient, and operational characteristics

The Cross-Species Mycobacterial Growth Inhibition Assay (MGIA) Project, 2010-2014.

The development of a functional biomarker assay in the tuberculosis (TB) field would be widely recognized as a major advance in efforts to develop and to test novel TB vaccine candidates efficiently. We present preliminary studies using mycobacterial growth inhibition assays (MGIAs) to detect Mycobacterium bovis BCG vaccine responses across species, and we extend this work to determine whether a standardized MGIA can be applied in characterizing new TB vaccines. The comparative MGIA studies reviewed here aimed to evaluate robustness, reproducibility, and ability to reflect in vivo responses. In doing so, they have laid the foundation for the development of a MGIA that can be standardized and potentially qualified. A major challenge ahead lies in better understanding the relationships between in vivo protection, in vitro growth inhibition, and the immune mechanisms involved. The final outcome would be a MGIA that could be used with confidence in TB vaccine trials. We summarize data arising from this project, present a strategy to meet the goals of developing a functional assay for TB vaccine testing, and describe some of the challenges encountered in performing and transferring such assays

Properties of sunspot umbrae observed in Cycle 24

We analyzed the size, intensity, and magnetic field strength of sunspot umbrae to compare the present cycle 24 with the previous one. We used data of the Helioseismic and Magnetic Imager onboard the Solar Dynamics Observatory and selected all sunspots between May 2010 and October 2012, using one image per day. We created two subsets of this data with a manual tracking algorithm, both without duplication. One is containing each sunspot (910 umbrae within 488 spots) and was used to analyze the distribution of umbral areas, selected with an automated thresholding method. The other one contains 205 fully evolved sunspots. We find nonlinear relations between umbral minimum intensity and size and between maximum magnetic field strength and size. The field strength scales linear with the intensity and the umbral size scales roughly linear with the total magnetic flux, while the size and field strength level off with stronger flux. When separated in hemisphere and averaged temporally, the southern umbrae show a temporal increase in size and the northern umbrae stay constant. There is no temporal variation in the umbral mean intensity detectable. The probability density function of the umbral area in the ascending phase of the current solar cycle is similar to that of the last solar cycle. From our investigation of umbral area, magnetic field, magnetic flux and umbral intensity of the sunspots of the rising phase of cycle 24, we do not find a significant difference to the previous cycle, and hence no indication for a long-term decline of solar activity.Comment: 11 pages, 9 figures, to be published in Astronomy & Astrophysic

Comparison of advanced gravitational-wave detectors

We compare two advanced designs for gravitational-wave antennas in terms of their ability to detect two possible gravitational wave sources. Spherical, resonant mass antennas and interferometers incorporating resonant sideband extraction (RSE) were modeled using experimentally measurable parameters. The signal-to-noise ratio of each detector for a binary neutron star system and a rapidly rotating stellar core were calculated. For a range of plausible parameters we found that the advanced LIGO interferometer incorporating RSE gave higher signal-to-noise ratios than a spherical detector resonant at the same frequency for both sources. Spheres were found to be sensitive to these sources at distances beyond our galaxy. Interferometers were sensitive to these sources at far enough distances that several events per year would be expected