Article

Mixed-Strain Mycobacterium tuberculosis Infections and the Implications for Tuberculosis Treatment and Control.

Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Clinical microbiology reviews (Impact Factor: 16). 10/2012; 25(4):708-19. DOI: 10.1128/CMR.00021-12
Source: PubMed

ABSTRACT Numerous studies have reported that individuals can simultaneously harbor multiple distinct strains of Mycobacterium tuberculosis. To date, there has been limited discussion of the consequences for the individual or the epidemiological importance of mixed infections. Here, we review studies that documented mixed infections, highlight challenges associated with the detection of mixed infections, and discuss possible implications of mixed infections for the diagnosis and treatment of patients and for the community impact of tuberculosis control strategies. We conclude by highlighting questions that should be resolved in order to improve our understanding of the importance of mixed-strain M. tuberculosis infections.

1 Follower
 · 
99 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We measure dc voltages in a permalloy (Py) single layer and a Py/Pt bilayer under ferromagnetic resonance. The observed voltages can be decomposed into symmetric and antisymmetric components. First, we confirm for Py that the symmetric component results from the planar Hall effect (PHE), whereas the antisymmetric one results from the anomalous Hall effect. Then, we consider the dc voltage induced by the inverse spin Hall effect (ISHE) in Py/Pt superimposing the galvanomagnetic effects, and conclude that the voltage induced by ISHE also contributes to the symmetric component with about 2.5 times smaller magnitude than that by PHE. Our results indicate that one should be careful about the galvanomagnetic effects in the quantitative analyses of dc voltage induced by spin pumping. (C) 2014 The Japan Society of Applied Physics
    Applied Physics Express 01/2014; 7(1):013002. DOI:10.7567/APEX.7.013002 · 2.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High resolution tests for genetic variation reveal that individuals may simultaneously host more than one distinct strain of M. tuberculosis. Previous studies find that this phenomenon, which we will refer to as "mixed infection", may affect the outcomes of treatment for infected individuals and may influence the impact of population-level interventions against tuberculosis. In areas where the incidence of TB is high, mixed infections have been found in nearly 20% of patients; these studies may underestimate the actual prevalence of mixed infection given that tests may not be sufficiently sensitive for detecting minority strains. Specific reasons for failing to detect mixed infections would include low initial numbers of minority strain cells in sputum, stochastic growth in culture and the physical division of initial samples into parts (typically only one of which is genotyped). In this paper, we develop a mathematical framework that models the study designs aimed to detect mixed infections. Using both a deterministic and a stochastic approach, we obtain posterior estimates of the prevalence of mixed infection. We find that the posterior estimate of the prevalence of mixed infection may be substantially higher than the fraction of cases in which it is detected. We characterize this bias in terms of the sensitivity of the genotyping method and the relative growth rates and initial population sizes of the different strains collected in sputum. Copyright © 2014. Published by Elsevier Ltd.
    Journal of Theoretical Biology 12/2014; 368. DOI:10.1016/j.jtbi.2014.12.009 · 2.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific T-cells. In order to objectively gauge Mycobacterium tuberculosis (MTB)-specific CD8+ T-cells at the single-cell level, we developed soluble major histocompatibility complex (MHC) class I multimers/peptide multimers, which allow analysis of antigen-specific T-cells without ex vivo manipulation or functional tests. We constructed 38 MHC class I multimers covering some of the most frequent MHC class I alleles (HLA-A*02:01, A*24:02, A*30:01, A*30:02, A*68:01, B*58:01, and C*07:01) pertinent to a South African or Zambian population, and presenting the following MTB-derived peptides: the early expressed secreted antigens TB10.4 (Rv0288), Ag85B (Rv1886c), and ESAT-6 (Rv3875), as well as intracellular enzymes, i.e., glycosyltransferase 1 (Rv2957), glycosyltransferase 2 (Rv2958c), and cyclopropane fatty acid synthase (Rv0447c). Anti-TB treatment appeared to impact on the frequency of multimer-positive CD8+ T-cells, with a general decrease after 6 months of therapy. Also, a reduction in the total central memory CD8+ T-cell frequencies, as well as the antigen-specific compartment in CD45RA-CCR7+ T-cells was observed. We discuss our findings on the basis of differential dynamics of MTB-specific T-cell frequencies, impact of MTB antigen load on T-cell phenotype, and antigen-specific T-cell responses in tuberculosis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 03/2015; 32:23-9. DOI:10.1016/j.ijid.2015.01.017 · 2.33 Impact Factor