7 research outputs found
Phylo-epidemiological and pathogenic diversity of Mycobacterium tuberculosis strains in London with implications for vaccine develpoment
No full textPhDApproximately one-third of the global population is infected with tuberculosis causing
approximately 1.7 million deaths. Currently, the BCG vaccine is used to protect
against TB, but it cannot prevent primary infection or reactivation of latent infection.
Ideally a vaccine should protect against a diverse array of Mycobacterium
tuberculosis strains and promote a strong, long-lasting TH1 cell-mediated immune
response. Whilst evaluating the efficiency of novel vaccines using laboratory control
strains (M. tuberculosis H37Rv, H37Ra and M. bovis-BCG), it is important to test
efficacy against a representative panel of wild-type circulating strains. In England
42.2% of TB cases are reported in London and the diversity of nationalities generates
a diverse pool of strains consisting of globally representative TB strains. The aim of
the study was to construct a representative panel of strains for vaccine evaluation
studies and general TB research.
Common M. tuberculosis strains were identified by performing molecular MIRUVNTR
and spoligotyping on 2363 isolates from TB cases reported in London during a
one-year period. Epidemiological analysis demonstrated there were representatives
from 13 global regions, including high TB burden countries. An algorithm was
designed to select strains for a preliminary panel based on associations between
MTBC families in clusters of more common strains, the country of birth and VNTR
sub-clusters. The preliminary panel contained 42 MTBC strains belonging to 10
MTBC families from patients born in 17 countries.
Results of phylogenetic analysis of all 2363 isolates was used to select a smaller panel
of strains from the preliminary panel to represent MTBC lineages to investigate if
wild-type strains were phenotypically similar. The final panel included five strains
from each of the Baker et al., 2004 M. tuberculosis lineages (M. tuberculosis Beijing,
LAM10, two CAS, EAI5 strains representing lineage I, II, III, IV, respectively) and
an M. africanum strain.
In vitro tissue culture experiments demonstrated significantly higher growth of the
Beijing strain compared to the other wild-type and laboratory strains. Higher growth
rates of this strain were also observed in a cell-free culture system. Aerosol challenge
of guinea pigs with wild-type strains showed a quicker dissemination of the EAI5 strain from the lung to the spleen 16 days post-challenge, but significantly higher
c.f.u. count of the Beijing strain in the spleen 56 days post-challenge. Collectively, the
data demonstrated that there are phenotypic differences between wild-type circulating
MTBC strains
Emerg Infect Dis
No full textTo inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >or=5 copies at exact tandem repeat (ETR) A, >or=2 at mycobacterial interspersed repetitive unit 24, and >or=3 at ETR-B associated with the East African-Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity
Emerg Infect Dis
No full textTo address conflicting results about the stability of variable number tandem repeat (VNTR) loci and their value in prospective molecular epidemiology of Mycobacterium tuberculosis, we conducted a large prospective population-based analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and reproducible conditions for reliable PCR and fragment analysis, comprising enzymes, denaturing conditions, and capillary temperature, were identified for a panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of 2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were analyzed by using a standardized 15-loci VNTR panel, then an optimized hypervariable loci panel. The discriminative ability of loci varied substantially; locus VNTR 3232 varied the most, with 19 allelic variants and Hunter-Gaston index value of 0.909. Hypervariable loci should be included in standardized panels because they can provide consistent comparable results at multiple settings, provided the proposed conditions are adhered to
Associations between Mycobacterium tuberculosis strains and phenotypes
No full textTo inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: ≥5 copies at exact tandem repeat (ETR) A, ≥2 at mycobacterial interspersed repetitive unit 24, and ≥3 at ETR-B associated with the East African-Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity
Discriminatory ability of hypervariable variable number tandem repeat loci in population-based analysis of Mycobacterium tuberculosis strains, London, UK
No full textTo address conflicting results about the stability of variable number tandem repeat (VNTR) loci and their value in prospective molecular epidemiology of Mycobacterium tuberculosis, we conducted a large prospective population-based analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and reproducible conditions for reliable PCR and fragment analysis, comprising enzymes, denaturing conditions, and capillary temperature, were identified for a panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of 2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were analyzed by using a standardized 15-loci VNTR panel, then an optimized hypervariable loci panel. The discriminative ability of loci varied substantially; locus VNTR 3232 varied the most, with 19 allelic variants and Hunter-Gaston index value of 0.909 . Hypervariable loci should be included in standardized panels because they can provide consistent comparable results at multiple settings, provided the proposed conditions are adhered to
“Fight like hell”: Projected moral polarisation predicts anticipated conflict and the perceived responsibility to overturn an election loss
No full textLosing an election can be a huge blow. As a result, most elections are associated with a mixture of trepidation and optimism (outgroup vs. ingroup political party winning, respectively). However, we propose that levels of anxiety and future dread in the context of an election are enhanced when society is characterised by deep intergroup divisions and morally charged polarisation. Across two studies spanning two national elections (the 2020 U.S. presidential election and the 2021 Dutch general election; N = 1,079), we examined support for the prediction that projected moral polarisation in the aftermath of an election would be associated with enhanced perceived negative consequences of losing that election (i.e., an outgroup political party winning power). We consistently found that projected moral polarisation when anticipating an election loss predicted enhanced anxiety concerning the future state of society (collective angst), higher perceived likelihood of civil war, and a stronger perceived obligation to fight to overturn the results of the election. Moreover, this association was mediated by the perceived breakdown of leadership in society. The current findings have important implications for understanding the societal and political consequences of moral polarisation, including the potential for enhanced intergroup conflict and threats to democracy.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by an Australian Research Council Laureate Fellowship (FL180100094).Peer-reviewe
Author Correction. A large-scale test of the link between intergroup contact and support for social change
No full textAn amendment to this paper has been published and can be accessed via a link at the top of the paper.ANIDFondecytFondecy
