A Population-Based Cohort Study of Mycobacterium tuberculosis Beijing Strains: An Emerging Public Health Threat in an Immigrant-Receiving Country?

Mycobacterium tuberculosis Beijing strains are frequently associated with tuberculosis outbreaks and drug resistance. However, contradictory evidence and limited study generalizability make it difficult to foresee if the emergence of Beijing strains in high-income immigrant-receiving countries poses an increased public health threat. The purpose of this study was to determine if Beijing strains are associated with high risk disease presentations relative to other strains within Canada.This was a retrospective population-based study of culture-confirmed active TB cases in a major immigrant-receiving province of Canada in 1991 through 2007. Of 1,852 eligible cases, 1,826 (99%) were successfully genotyped. Demographic, clinical, and mycobacteriologic surveillance data were combined with molecular diagnostic data. The main outcome measures were site of disease, lung cavitation, sputum smear positivity, bacillary load, and first-line antituberculosis drug resistance.A total of 350 (19%) patients had Beijing strains; 298 (85%) of these were born in the Western Pacific. Compared to non-Beijing strains, Beijing strains were significantly more likely to be associated with polyresistance (aOR 1.8; 95% CI 1.0-3.3; p = 0.046) and multidrug-resistance (aOR 3.4; 1.0-11.3; p = 0.049). Conversely, Beijing strains were no more likely than non-Beijing strains to be associated with respiratory disease (aOR 1.3; 1.0-1.8; p = 0.053), high bacillary load (aOR 1.2; 0.6-2.7), lung cavitation (aOR 1.0; 0.7-1.5), immediately life-threatening forms of tuberculosis (aOR 0.8; 0.5-1.6), and monoresistance (aOR 0.9; 0.6-1.3). In subgroup analyses, Beijing strains only had a significant association with multidrug-resistant tuberculosis (aOR 6.1; 1.2-30.4), and an association of borderline significance with polyresistant tuberculosis (aOR 1.8; 1.0-3.5; p = 0.062), among individuals born in the Western Pacific.Other than an increased risk of polyresistant or multidrug-resistant tuberculosis, Beijing strains appear to pose no more of a public health threat than non-Beijing strains within a high-income immigrant-receiving country

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of Mtb emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults. The protective immunity afforded by BCG is thought to wane with time and considered to last only through adolescent years. Heterologous boosting of BCG-primed immune responses using a subunit vaccine represents a promising vaccination approach to promote strong cellular responses against Mtb. In our earlier studies, we discovered lipopeptides of ESAT-6 antigen with strong potential as a subunit vaccine candidate. Here, we have investigated that potential as a booster to BCG vaccine in both a pre-exposure preventive vaccine and a post-exposure therapeutic vaccine setting. Surprisingly, our results demonstrated that boosting BCG with subunit vaccine shortly before Mtb challenge did not improve the BCG-primed immunity, whereas the subunit vaccine boost after Mtb challenge markedly improved the quantity and quality of effector T cell responses and significantly reduced Mtb load in lungs, liver and spleen in mice. These studies suggest that ESAT-6 lipopeptide-based subunit vaccine was ineffective in overcoming the apparent immunomodulation induced by BCG vaccine in Mtb uninfected mice, but upon infection, the subunit vaccine is effective in re-educating the protective immunity against Mtb infection. These important results have significant implications in the design and investigation of effective vaccine strategies and immunotherapeutic approaches for individuals who have been pre-immunized with BCG vaccine but still get infected with Mtb

Towards the elimination of paediatric tuberculosis in high-income, immigrant-receiving countries: a 25-year conventional and molecular epidemiological case study

The epidemiology of tuberculosis (TB) in high-income countries is increasingly dictated by immigration. The influence of this trend on paediatric TB and TB elimination are not well defined. We undertook a 25-year conventional and molecular epidemiologic study of paediatric TB in Alberta, one of four major immigrant-receiving provinces in Canada. All isolates of Mycobacterium tuberculosis were DNA fingerprinted using standard methodology. Between 1990 and 2014, 176 children aged 0–14 years were diagnosed with TB. Foreign-born children or Canadian-born children of foreign-born parents accounted for an increasingly large proportion of total cases during the study period (from 32.1% to 89.5%). Of the 78 culture-positive cases, 35 (44.9%) had a putative source case identified by conventional epidemiology, with 34 (97.1%) having a concordant molecular profile. Of the remaining 43 culture-positive cases, molecular profiling identified spatially and temporally related sources in six cases (14.0%). These six children, along with four other children whose source cases were discovered through reverse-contact tracing, had a high morbidity and mortality. The increasing burden of paediatric TB in both foreign-born children and Canadian-born children of foreign-born parents calls for more timely diagnosis of source cases and more targeted screening for latent TB infection

The LHS 1678 system : two earth-sized transiting planets and an astrometric companion orbiting an M dwarf near the convective boundary at 20 pc

Funding: The MEarth Team gratefully acknowledges funding from the David and Lucile Packard Fellowship for Science and Engineering (awarded to D.C.). This material is based upon work supported by the National Science Foundation under grants AST-0807690, AST-1109468, AST-1004488 (Alan T. Waterman Award), and AST-1616624, and upon work supported by the National Aeronautics and Space Administration under Grant No. 80NSSC18K0476 issued through the XRP Program. This work is made possible by a grant from the John Templeton Foundation. N. A.-D. acknowledges the support of FONDECYT project 3180063. TD acknowledges support from MIT’s Kavli Institute as a Kavli postdoctoral fellow. KH acknowledges support from STFC grant ST/R000824/1. E.A.G. thanks the LSSTC Data Science Fellowship Program, which is funded by LSSTC, NSF Cybertraining Grant #1829740, the Brinson Foundation, and the Moore Foundation; The material is based upon work supported by NASA under award number 80GSFC21M0002. This work was supported by the lead author’s appointment to the NASA Postdoctoral Program at the Goddard Space Flight Center, administered by Universities Space Research Association under contract with NASAWe present the Transiting Exoplanet Survey Satellite (TESS) discovery of the LHS 1678 (TOI-696) exoplanet system, comprised of two approximately Earth-sized transiting planets and a likely astrometric brown dwarf orbiting a bright (VJ = 12.5, Ks = 8.3) M2 dwarf at 19.9 pc. The two TESS-detected planets are of radius 0.70 ± 0.04 R⊕ and 0.98 ± 0.06 R⊕ in 0.86 day and 3.69 day orbits, respectively. Both planets are validated and characterized via ground-based follow-up observations. High Accuracy Radial Velocity Planet Searcher RV monitoring yields 97.7 percentile mass upper limits of 0.35 M⊕ and 1.4 M⊕ for planets b and c, respectively. The astrometric companion detected by the Cerro Tololo Inter-American Observatory/Small and Moderate Aperture Telescope System 0.9 m has an orbital period on the order of decades and is undetected by other means. Additional ground-based observations constrain the companion to being a high-mass brown dwarf or smaller. Each planet is of unique interest; the inner planet has an ultra-short period, and the outer planet is in the Venus zone. Both are promising targets for atmospheric characterization with the James Webb Space Telescope and mass measurements via extreme-precision radial velocity. A third planet candidate of radius 0.9 ± 0.1 R⊕ in a 4.97 day orbit is also identified in multicycle TESS data for validation in future work. The host star is associated with an observed gap in the lower main sequence of the Hertzsprung–Russell diagram. This gap is tied to the transition from partially to fully convective interiors in M dwarfs, and the effect of the associated stellar astrophysics on exoplanet evolution is currently unknown. The culmination of these system properties makes LHS 1678 a unique, compelling playground for comparative exoplanet science and understanding the formation and evolution of small, short-period exoplanets orbiting low-mass stars.Publisher PDFPeer reviewe

The LHS 1678 System: Two Earth-sized Transiting Planets and an Astrometric Companion Orbiting an M Dwarf Near the Convective Boundary at 20 pc

We present the Transiting Exoplanet Survey Satellite (TESS) discovery of the LHS 1678 (TOI-696) exoplanet system, comprised of two approximately Earth-sized transiting planets and a likely astrometric brown dwarf orbiting a bright (V J = 12.5, K s = 8.3) M2 dwarf at 19.9 pc. The two TESS-detected planets are of radius 0.70 ± 0.04 R ⊕ and 0.98 ± 0.06 R ⊕ in 0.86 day and 3.69 day orbits, respectively. Both planets are validated and characterized via ground-based follow-up observations. High Accuracy Radial Velocity Planet Searcher RV monitoring yields 97.7 percentile mass upper limits of 0.35 M ⊕ and 1.4 M ⊕ for planets b and c, respectively. The astrometric companion detected by the Cerro Tololo Inter-American Observatory/Small and Moderate Aperture Telescope System 0.9 m has an orbital period on the order of decades and is undetected by other means. Additional ground-based observations constrain the companion to being a high-mass brown dwarf or smaller. Each planet is of unique interest; the inner planet has an ultra-short period, and the outer planet is in the Venus zone. Both are promising targets for atmospheric characterization with the James Webb Space Telescope and mass measurements via extreme-precision radial velocity. A third planet candidate of radius 0.9 ± 0.1 R ⊕ in a 4.97 day orbit is also identified in multicycle TESS data for validation in future work. The host star is associated with an observed gap in the lower main sequence of the Hertzsprung-Russell diagram. This gap is tied to the transition from partially to fully convective interiors in M dwarfs, and the effect of the associated stellar astrophysics on exoplanet evolution is currently unknown. The culmination of these system properties makes LHS 1678 a unique, compelling playground for comparative exoplanet science and understanding the formation and evolution of small, short-period exoplanets orbiting low-mass stars

Transit timings variations in the three-planet system : TOI-270

We present ground- and space-based photometric observations of TOI-270 (L231-32), a system of three transiting planets consisting of one super-Earth and two sub-Neptunes discovered by TESS around a bright (K-mag = 8.25) M3V dwarf. The planets orbit near low-order mean-motion resonances (5:3 and 2:1) and are thus expected to exhibit large transit timing variations (TTVs). Following an extensive observing campaign using eight different observatories between 2018 and 2020, we now report a clear detection of TTVs for planets c and d, with amplitudes of ∼10 min and a super-period of ∼3 yr, as well as significantly refined estimates of the radii and mean orbital periods of all three planets. Dynamical modelling of the TTVs alone puts strong constraints on the mass ratio of planets c and d and on their eccentricities. When incorporating recently published constraints from radial velocity observations, we obtain masses of Mb=1.48±0.18M⊕⁠, Mc=6.20±0.31M⊕⁠, and Md=4.20±0.16M⊕ for planets b, c, and d, respectively. We also detect small but significant eccentricities for all three planets : eb = 0.0167 ± 0.0084, ec = 0.0044 ± 0.0006, and ed = 0.0066 ± 0.0020. Our findings imply an Earth-like rocky composition for the inner planet, and Earth-like cores with an additional He/H2O atmosphere for the outer two. TOI-270 is now one of the best constrained systems of small transiting planets, and it remains an excellent target for atmospheric characterization

First case of (imported) babesiosis diagnosed in Canada

This paper describes the first case of babesiosis diagnosed in Canada. This case highlights the need for clinicians to be aware of diseases that may be endemic elsewhere and the importance of a travel history in a patient’s assessment

Improving access to care by allowing self-referral to a hepatitis C clinic

BACKGROUND: Estimates suggest that more than 250,000 Canadians are infected with hepatitis C virus (HCV), but less than 10% have been treated. Access to specialists in Canada is usually via health care professional (HCP) referral and, therefore, may be a barrier to HCV care. However, clinics that operate in conjunction with the Hepatitis Support Program, Edmonton, Alberta, allow self-referral. It is hypothesized that this improves access to care without increasing inappropriate referrals

Multidrug-Resistant Tuberculosis in Alberta and British Columbia, 1989 to 1998

OBJECTIVE: To describe the extent of the problem of multidrug-resistant tuberculosis (MDR-TB) in Alberta and British Columbia from 1989 to 1998.DESIGN: A retrospective, population-based descriptive study of all notified MDR-TB cases in the context of all notified TB cases, all notified culture-positive TB cases and all notified drug-resistant TB cases.SETTING: Provinces of Alberta and British Columbia, and their TB registries.PATIENTS: All people with TB reported to the TB registries of Alberta and British Columbia between January 1, 1989 and June 30, 1998.MAIN OUTCOME MEASURES: Drug susceptibility testing was performed in all cases of culture-positive TB. Demographic, clinical and laboratory data on all cases of MDR-TB were recorded.RESULTS: Of 4606 notified cases of TB, 3553 (77.1%) were culture positive. Of these, 365 (10.3%) were drug resistant; of the drug-resistant cases, 24 (6.6%) were MDR. Most MDR-TB patients were foreign-born; of the four Canadian-born patients, two were infected while travelling abroad. Although foreign-born patients were significantly more likely to harbour drug-resistant strains, 14.3% versus 4.8%, respectively (Pud_less_than0.001), among those who were harbouring a drug-resistant strain, the proportion of Canadian-born versus foreign-born patients with an MDR strain was the same (6.7% versus 6.6%, respectively). From 1994 to 1998 versus 1989 to 1993, the proportion of all drug-resistant strains that were MDR was greater (9.0% versus 4.3%, respectively), but the difference was not statistically significant. Isolates from 16 of the 24 MDR-TB cases had been archived. Each of these was fingerprinted and found to be unique. Most MDR-TB cases (88%) were respiratory. Of those tested for human immunodeficiency virus (n=17), only one was seropositive. MDR-TB was ‘acquired’ in 67% and ‘primary’ in 33% of cases. Eight (33%) of the MDR-TB cases received curative courses of treatment, six (25%) are still being treated, and the remainder have either died (five, 21%), transferred out (four, 17%) or become ‘chronic’ (one, 4%). No secondary case of MDR-TB has been identified in Alberta and British Columbia.CONCLUSIONS: Most MDR-TB in Alberta and British Columbia is imported. The proportion of all drug-resistant cases that are MDR appears to be increasing, but not because of disease acquired from recent contact with MDR-TB in Canada.Peer Reviewe