Background The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults. Methods We investigated SARS-CoV-2 infections among U.S. Marine Corps recruits who underwent a 2-week quarantine at home followed by a second supervised 2-week quarantine at a closed college campus that involved mask wearing, social distancing, and daily temperature and symptom monitoring. Study volunteers were tested for SARS-CoV-2 by means of quantitative polymerase-chain-reaction (qPCR) assay of nares swab specimens obtained between the time of arrival and the second day of supervised quarantine and on days 7 and 14. Recruits who did not volunteer for the study underwent qPCR testing only on day 14, at the end of the quarantine period. We performed phylogenetic analysis of viral genomes obtained from infected study volunteers to identify clusters and to assess the epidemiologic features of infections. Results A total of 1848 recruits volunteered to participate in the study; within 2 days after arrival on campus, 16 (0.9%) tested positive for SARS-CoV-2, 15 of whom were asymptomatic. An additional 35 participants (1.9%) tested positive on day 7 or on day 14. Five of the 51 participants (9.8%) who tested positive at any time had symptoms in the week before a positive qPCR test. Of the recruits who declined to participate in the study, 26 (1.7%) of the 1554 recruits with available qPCR results tested positive on day 14. No SARS-CoV-2 infections were identified through clinical qPCR testing performed as a result of daily symptom monitoring. Analysis of 36 SARS-CoV-2 genomes obtained from 32 participants revealed six transmission clusters among 18 participants. Epidemiologic analysis supported multiple local transmission events, including transmission between roommates and among recruits within the same platoon. Conclusions Among Marine Corps recruits, approximately 2% who had previously had negative results for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits with unknown previous status, tested positive by day 14. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. Transmission clusters occurred within platoons. (Funded by the Defense Health Agency and others.)

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Neisseria gonorrhoeae causes severe exudative urethritis. The exudates from infected individuals contain large numbers of polymorphonuclear leukocytes (PMN) with ingested gonococci. The fate of N. gonorrhoeae within PMN has been a topic of debate for years. In this study, we examined the interactions of N. gonorrhoeae with PMN adherent to surfaces as a system that better models events during clinical disease. Using chemiluminescence to measure reactive oxygen species (ROS), we found that N. gonorrhoeae stimulated PMN to produce a respiratory burst. Different kinetics were seen when PMN were stimulated with opsonized zymosan particles. In addition, ROS were produced predominantly inside the PMN in response to gonococci. Laser scanning confocal microscopy and transmission electron microscopy showed that N. gonorrhoeae rapidly associated with PMN under these experimental conditions and was internalized. Some gonococci were cleared in the first 30 to 60 min after phagocytosis, but a majority of the population persisted for 6 h after phagocytosis. Quantification of viable organisms showed that a significant portion of the population resisted killing. The viability of this subpopulation remained unchanged for 2 h after phagocytosis. A significant increase of viable gonococci from 1 to 6 h was also observed, suggesting intracellular replication. Four different N. gonorrhoeae strains demonstrated the same capacity to resist PMN-mediated killing, whereas Escherichia coli was rapidly killed by PMN under the same conditions. Taken together, these findings suggest that a subpopulation of N. gonorrhoeae resists killing and replicates within PMN phagosomes in spite of NADPH oxidase activation.Neisseria gonorrhoeae (gonococcus) is a gram-negative diplococcus that causes the sexually transmitted disease gonorrhea in humans. Infection with N. gonorrhoeae can result in an acute urethritis. Urethral exudates from infected individuals show predominantly polymorphonuclear leukocytes (PMN), many with large numbers of ingested gonococci (1,10,24,25). Despite the exuberant and rapid PMN recruitment to the site of infection, persistence of disease for weeks to months indicates that the inflammatory response is ineffective in eradicating organisms and suggests that N. gonorrhoeae may possess mechanisms to evade killing by PMN.PMN are professional phagocytes that migrate to sites of infection, where they ingest microorganisms by phagocytosis (11,13,20). PMN kill microorganisms by the combined activity of antimicrobial proteins and reactive oxygen species (ROS). The NADPH oxidase is a multicomponent enzyme responsible for agonist-dependent generation of ROS by PMN (2, 8, 33). The oxidase complex reduces molecular oxygen to form superoxide anion (O 2 Ϫ ), which is converted into hydrogen peroxide (H 2 O 2 ). Hypochlorous acid (HOCl) is then generated through the activity of myeloperoxidase (MPO) (33). PMN ROS generation, referred to as the respiratory burst, is a primary killing component of PMN antimicrobial activity and represents an impo...

SUMMARYBladder cancer accounts for ~13,000 deaths annually, and >60,000 new cases will appear this year, making it the 4 th and 10 th most common cancer among men and women, respectively [1]. The majority of the newly diagnosed cases will be diagnosed prior to muscle invasion, thus potentially completely curable. Unfortunately, >20% of patients initially diagnosed with non-muscle-invasive bladder cancer will eventually die of their disease despite local endoscopic surgery [2]. Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been used for the treatment of bladder cancer since 1976 [3], and continues to be at the forefront of therapeutic options for this malignancy. Despite its success and worldwide acceptance, the antitumor effector mechanisms remain elusive.BCG therapy induces a massive local immune response characterized by cytokine expression of multiple cytokines in the urine and bladder tissue [4] and the influx of granulocytes and mononuclear cells into the bladder wall [5,6]. Findings from our laboratory have demonstrated that TNF-related apoptosis-inducing ligand (TRAIL) is induced by BCG treatment [7] and TRAIL was expressed on polymorphonuclear neutrophils (PMN) in the urine obtained from patients after intravesical BCG instillation. Subsequently, we have determined that BCG and components of the Mycobacterial cell wall can directly stimulate the release of soluble TRAIL from PMN through Toll-Like Receptor-2 (TLR2) recognition that is augmented by interferon (IFN) [8]. Based on our work and that of others implicating the need for T helper type 1 (Th-1) cytokine responses to BCG therapy for therapeutic results, we propose that TRAIL is released by PMN migrating to the bladder in response to BCG treatment. In addition, IFN acts to augment and prolong the amount of TRAIL released by PMN, resulting in an effective therapeutic outcome.

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