Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the ligand-binding domain of TLR5 (TLR5392STOP) is unable to mediate flagellin signaling, acts in a dominant fashion, and is associated with susceptibility to pneumonia caused by Legionella pneumophila, a flagellated bacterium. We also show that flagellin is a principal stimulant of proinflammatory cytokine production in lung epithelial cells. Together, these observations suggest that TLR5392STOP increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR5's essential role as a regulator of the lung epithelial innate immune response.

Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

In 1999, an outbreak of Legionnaires’ disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails.

Long-term prophylactic therapy for PCP may be indicated for RTR with persistent severe lymphocytopaenia.

In 1999 an outbreak involving 188 patients with Legionnaires' disease (LD) occurred among visitors to a flower show in the Netherlands. Two enzyme immunoassays (Binax and Biotest) and one immunochromatographic assay (Binax NOW) were tested, using urine samples from LD patients from the 1999 outbreak. Sensitivity was calculated using positive culture and/or seroconversion as the "gold standard" in outbreakrelated patients with radiographically confirmed pneumonia who fulfilled the epidemiological critera. The Binax EIA, Biotest EIA, and Binax NOW assay showed overall sensitivities of 69, 71, and 72%, respectively. When the tests were performed with concentrated urine samples, the overall sensitivities increased to 79, 74, and 81%, respectively. Using multiple logistic regression analysis with backward elimination, a statistically significant association was found between clinical severity and test sensitivity for all tests. For patients with mild LD, the test sensitivities ranged from 40 to 53%, whereas for patients with severe LD who needed immediate special medical care, the sensitivities reached 88 to 100%. These findings have major implications for the diagnostic process in patients with mild pneumonia and suggest that patients with mild pneumonia may go underdiagnosed if urine antigen tests alone are used. Legionnaires' disease (LD) is an acute pneumonia caused byLegionella, a rod-shaped gram-negative bacillus ubiquitous in (man-made) aquatic reservoirs. Currently 43 Legionella species and 65 serogroups have been described. In the United States, over 90% of Legionnaires' disease cases are caused by Legionella pneumophila, of which 70% of strains belong to serogroup type 1 (16). Legionella spp. are responsible for 1 to 5% of cases of community-acquired pneumonia (CAP) (5). Clinically and radiographically, LD cannot be distinguished from pneumonias caused by other microbial pathogens. Because of the high mortality rate in patients with LD requiring hospitalization, early diagnosis to enable adequate antimicrobial treatment is potentially life-saving. Diagnosis of LD in patients with symptomatic pneumonia is based on culture, serologic testing, or antigen detection in urine. Isolation of Legionella from respiratory secretions is not a very sensitive diagnostic test (25 to 75% sensitivity) (15) and has the disadvantage of delay, because a positive result is not available until at least 3 days of incubation. Seroconversion is a diagnostic test with a high sensitivity and a high (serogroup-dependant) specificity, but it is of limited clinical value since it may take up to 9 weeks for patients to develop detectable antibodies (10, 13).In contrast to the other tests mentioned above, urinary antigen tests combine reasonable sensitivity and high specificity with rapid results. The reported sensitivities of both enzyme immunoassay (EIA) and immunochromatographic test (ICT) show great variation: 50 to 90% (3,7,8,19). These variations may be explained by differences in patient characteristics, the serogroup with which th...