Tuberculosis Disparity between US-born Blacks and Whites, Houston, Texas, USA1

An unusually high proportion of cases in Houston are caused by active transmission of endemic strains among US-born non-Hispanic blacks

Genetic diversity and evidence for acquired antimicrobial resistance in Mycobacterium tuberculosis at a large hospital in South India

AbstractObjectives: To assess genetic diversity and drug resistance of Mycobacterium tuberculosis isolates collected at Christian Medical College Hospital (CMCH), Vellore, India, between July 1995 and May 1996.Materials and Methods: Isolates were subjected to IS6110-based restriction fragment length polymorphism (RFLP) analysis and tested for resistance to isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide, and DNA from selected strains was sequenced in regions associated with drug resistance.Results: One hundred and one M. tuberculosis isolates were collected from 87 patients with pulmonary tuberculosis. Charts of 69 patients were reviewed for history of tuberculosis illness and treatment. DNA from 29 strains was sequenced in katG, rpoB, and gyrA, and sometimes pncA regions. Analysis by RFLP revealed a high degree of genetic diversity, with no identifiable clusters of infection. Of the strains tested, 51 % were resistant to at least one antibiotic, and 43% were resistant to more than one drug. There was a high rate of resistance observed in patients whose charts indicated a history of improperly administered tuberculosis treatment, whereas little drug resistance was observed in patients never previously treated for tuberculosis. Sequencing of genes associated with drug resistance revealed several previously unreported mutations in resistant strains.Conclusions: This analysis suggests that the cases of tuberculosis in the sample are largely reactivation of long-standing infections and that the drug resistance among patients in CMCH is largely acquired or secondary rather than attributable to the spread of drug-resistant strains

Phenotypic Variation in the Group A Streptococcus Due to Natural Mutation of the Accessory Protein-Encoding Gene rocA

Populations of a bacterial pathogen, whether recovered from a single patient or from a worldwide study, are often a heterogeneous mix of genetically and phenotypically divergent strains. Such heterogeneity is of value in changing environments and arises via mechanisms such as gene gain or gene mutation. Here, we identify an isolate of serotype M12 group A Streptococcus (GAS) (Streptococcus pyogenes) that has a natural mutation in rocA, which encodes an accessory protein to the virulence-regulating two-component system CovR/CovS (CovR/S). Disruption of RocA activity results in the differential expression of multiple GAS virulence factors, including the anti-phagocytic hyaluronic acid capsule and the chemokine protease SpyCEP. While some of our data regarding RocA-regulated genes overlaps with previous studies, which were performed with isolates of alternate GAS serotypes, some variability was also observed. Perhaps as a consequence of this alternate regulatory activity, we discovered that the contribution of RocA to the ability of the M12 isolate to survive and proliferate in human blood ex vivo is opposite that previously observed in M1, M3, and M18 GAS strains. Specifically, rocA mutation reduced, rather than enhanced, survival of the isolate. Finally, we also present data from an analysis of rocA transcription and show that rocA is transcribed in both mono- and polycistronic mRNAs. In aggregate, our data provide insight into the important regulatory role of RocA and into the mechanisms and consequences of GAS phenotypic heterogeneity. IMPORTANCE This study investigates the regulatory and phenotypic consequences of a naturally occurring mutation in a strain of the bacterial pathogen the group A Streptococcus (Streptococcus pyogenes). We show that this mutation, which occurs in a regulator-encoding gene, rocA, leads to altered virulence factor expression and reduces the ability of this isolate to survive in human blood. Critically, the blood survival phenotype and the assortment of genes regulated by RocA differ compared to previous studies into RocA activity. The data are consistent with there being strain-or serotype-specific variability in RocA function. Given that phenotypic variants can lead to treatment failures and escape from preventative regimes, our data provide information with regard to a mechanism of phenotypic variation in a prevalent Gram-positive pathogen

Cosmic-Ray Positrons: Are There Primary Sources?

Cosmic rays at the Earth include a secondary component originating in collisions of primary particles with the diffuse interstellar gas. The secondary cosmic rays are relatively rare but carry important information on the Galactic propagation of the primary particles. The secondary component includes a small fraction of antimatter particles, positrons and antiprotons. In addition, positrons and antiprotons may also come from unusual sources and possibly provide insight into new physics. For instance, the annihilation of heavy supersymmetric dark matter particles within the Galactic halo could lead to positrons or antiprotons with distinctive energy signatures. With the High-Energy Antimatter Telescope (HEAT) balloon-borne instrument, we have measured the abundances of positrons and electrons at energies between 1 and 50 GeV. The data suggest that indeed a small additional antimatter component may be present that cannot be explained by a purely secondary production mechanism. Here we describe the signature of the effect and discuss its possible origin.Comment: 15 pages, Latex, epsfig and aasms4 macros required, to appear in Astroparticle Physics (1999

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.Knut and Alice Wallenberg Foundation Swedish Research Council Houston Methodist Hospital Fondren Foundatio

An improved measurement of muon antineutrino disappearance in MINOS

We report an improved measurement of muon anti-neutrino disappearance over a distance of 735km using the MINOS detectors and the Fermilab Main Injector neutrino beam in a muon anti-neutrino enhanced configuration. From a total exposure of 2.95e20 protons on target, of which 42% have not been previously analyzed, we make the most precise measurement of the anti-neutrino "atmospheric" delta-m squared = 2.62 +0.31/-0.28 (stat.) +/- 0.09 (syst.) and constrain the anti-neutrino atmospheric mixing angle >0.75 (90%CL). These values are in agreement with those measured for muon neutrinos, removing the tension reported previously.Comment: 5 pages, 4 figures. In submission to Phys.Rev.Let

Search for Nucleon Decays induced by GUT Magnetic Monopoles with the MACRO Experiment

The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of $\sim 3\cdot 10^{-16} cm^{-2} s^{-1} sr^{-1}$ for $1.1\cdot 10^{-4} \le |\beta| \le 5\cdot 10^{-3}$, based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.Comment: 12 pages, Latex, 10 figures and 2 Table

Improved Search for Muon-Neutrino to Electron-Neutrino Oscillations in MINOS

We report the results of a search for ν_e appearance in a ν_μ beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2×10^(20) protons on the NuMI target at Fermilab, we find 2sin^2(θ_(23))sin^2(2θ_(13))<0.12(0.20) at 90% confidence level for δ=0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin^2(θ_(23))sin^2(2θ_(13))=0.041^(+0.047)_(-0.031)(0.079^(+0.071)_(-0.053). The θ_(13)= 0 hypothesis is disfavored by the MINOS data at the 89% confidence level

Search for the disappearance of muon antineutrinos in the NuMI neutrino beam

We report constraints on antineutrino oscillation parameters that were obtained by using the two MINOS detectors to measure the 7% muon antineutrino component of the NuMI neutrino beam. In the Far Detector, we select 130 events in the charged-current muon antineutrino sample, compared to a prediction of 136.4 ± 11.7(stat)^(+10.2)_(-8.9)(syst) events under the assumption │Δm^2│ = 2.32 X 10^(-3) eV^2, sin^2(2θ) = 1.0

Measurement of the neutrino mass splitting and flavor mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of $7.25 imes 10^{20}$ protons on target. A fit to neutrino oscillations yields values of $|Delta m^2| = (2.32^{+0.12}_{-0.08}) imes10^{-3}$,eV$^2$ for the atmospheric mass splitting and m sin^2!(2 heta) > 0.90 (90%,C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively