The Journal of infectious diseases
-
Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis (TB) are 2 ends of a spectrum of states ranging from asymptomatic infection to overt disease. While progressing from LTBI to TB, patients often undergo asymptomatic states with detectable manifestations indicative of disease. Such asymptomatic disease states frequently remain undiagnosed, and their manifestations and duration are mostly dependent on host immune response. ⋯ We propose using the term "incipient TB" when referring to early, contained disease in asymptomatic, relatively immunocompetent persons. In contrast, we propose using the term "subclinical TB" to refer to disease in asymptomatic, immunocompromised individuals in whom it is largely associated with loss of effective containment. The rationale for this article is to facilitate the discussion of such early disease states, especially in relation to their impact on TB biomarker discovery and assessment of new diagnostics, and with regard to treatment decisions and ultimately outcome.
-
Mice were infected with Mycoplasma pneumoniae and monitored for the synthesis and distribution of the unique adenosine diphosphate-ribosylating and vacuolating Community Acquired Respiratory Distress Syndrome (CARDS) toxin in bronchiolar lavage fluid (BALF) and lung. We noted direct relationships between the concentration of CARDS toxin and numbers of mycoplasma genomes in BALF and the degree of histologic pulmonary inflammation. ⋯ Infected mouse immunoglobulin (Ig) M and IgG titers were positive for CARDS toxin as well as for the major adhesin P1 of M. pneumoniae. These data reinforce the proposed pathogenic role of CARDS toxin in M. pneumoniae-mediated pathologies.
-
Histone deacetylases (HDACs) control gene expression by deacetylating histones and nonhistone proteins. HDAC inhibitors (HDACi) are powerful anticancer drugs that exert anti-inflammatory and immunomodulatory activities. We recently reported a proof-of-concept study demonstrating that HDACi increase susceptibility to bacterial infections in vivo. ⋯ In line with these findings, HDACi decrease the expression of phagocytic receptors and inhibit bacteria-induced production of reactive oxygen and nitrogen species by macrophages. Consistently, HDACi impair the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and inducible nitric oxide synthase. These data indicate that HDACi have a strong impact on critical antimicrobial defense mechanisms in macrophages.
-
Randomized Controlled Trial Multicenter Study Comparative Study
Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults.
LC16m8 is an attenuated cell culture-adapted Lister vaccinia smallpox vaccine missing the B5R protein and licensed for use in Japan. ⋯ LC16m8 generates neutralizing antibody titers to multiple poxviruses, including vaccinia, monkeypox, and variola major, and broad T-cell responses, indicating that LC16m8 may have efficacy in protecting individuals from smallpox. Clinical Trials Registration. NCT00103584.