Risk for latent and active tuberculosis in Germany.

PURPOSE: Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. METHODS: Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. RESULTS: From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. CONCLUSIONS: Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.

Sub-Lineage Specific Phenolic Glycolipid Patterns in the Mycobacterium tuberculosis Complex Lineage 1.

"Ancestral" Mycobacterium tuberculosis complex (MTBC) strains of Lineage 1 (L1, East African Indian) are a prominent tuberculosis (TB) cause in countries around the Indian Ocean. However, the pathobiology of L1 strains is insufficiently characterized. Here, we used whole genome sequencing (WGS) of 312 L1 strains from 43 countries to perform a characterization of the global L1 population structure and correlate this to the analysis of the synthesis of phenolic glycolipids (PGL) - known MTBC polyketide-derived virulence factors. Our results reveal the presence of eight major L1 sub-lineages, whose members have specific mutation signatures in PGL biosynthesis genes, e.g., pks15/1 or glycosyltransferases Rv2962c and/or Rv2958c. Sub-lineage specific PGL production was studied by NMR-based lipid profiling and strains with a completely abolished phenolphthiocerol dimycoserosate biosynthesis showed in average a more prominent growth in human macrophages. In conclusion, our results show a diverse population structure of L1 strains that is associated with the presence of specific PGL types. This includes the occurrence of mycoside B in one sub-lineage, representing the first description of a PGL in an M. tuberculosis lineage other than L2. Such differences may be important for the evolution of L1 strains, e.g., allowing adaption to different human populations.

Effects of nitrogen dioxide on human health: systematic review of experimental and epidemiological studies conducted between 2002 and 2006.

In order to assess health effects in humans caused by environmental nitrogen dioxide (NO(2)) a systematic review of studies in humans was conducted. MEDLINE database was searched for epidemiological studies and experiments on adverse effects of NO(2) published between 2002 and 2006. The evidence with regard to NO(2) exposure limits was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) grading system and the modified three star system. Of the 214 articles retrieved 112 fulfilled the inclusion criteria. There was limited evidence that short-term exposure to a 1-h mean value below 200 microg NO(2)/m(3) is associated with adverse health effects provided by only one study on mortality in patients with severe asthma (*2+). The effect remained after adjusting for other air pollutants. There was moderate evidence that short-term exposure below a 24-h mean value of 50 microg NO(2)/m(3) at monitor stations increases hospital admissions and mortality (**2+). Evidence was also moderate when the search was restricted to susceptible populations (children, adolescents, elderly, and asthmatics). There was moderate evidence that long-term exposure to an annual mean below 40 microg NO(2)/m(3) was associated with adverse health effects (respiratory symptoms/diseases, hospital admissions, mortality, and otitis media) provided by generally consistent findings in five well-conducted cohort and case-control studies with some shortcomings in the study quality (**2+). Evidence was also moderate when the search was restricted to studies in susceptible populations (children and adolescents) and for the combination with other air pollutants. The most frequent reasons for decreased study quality were potential misclassification of exposure and selection bias. None of the high-quality observational studies evaluated was informative for the key questions due to the choice of the dose parameter (e.g., 1-week mean) and exposure levels above the limit values. Inclusion of study designs unlisted in the SIGN grading system did not bring additional evidence regarding exposures below the current air quality limit values for NO(2). As several recent studies reported adverse health effects below the current exposure limits for NO(2) particularly among susceptible populations regarding long-term exposure further research is needed. Apart from high-quality epidemiological studies on causality and the interaction of NO(2) with other air pollutants there is a need for double-blinded randomized cross-over studies among susceptible populations for further evaluation of the short-term exposure limits.