Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI.Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls.Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection.Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.

Elevated cTnT level on admission is a strong predictor of short- and long-term mortalities in patients hospitalized with CAP.

BackgroundAdjunctive intravenous corticosteroid treatment has shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent.MethodsIn this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I–III and IV-V). The primary outcome was LOS. This study is registered with ClinicalTrials.gov (NCT01743755).ResultsBetween December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days (95% CI 4.0–5.0)) than in the placebo group (5.0 days (95% CI 4.6–5.4); p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. Secondary ICU admission rate was lower in the dexamethasone arm (5 (3%) versus 14 (7%), p=0.030), 30-day mortality did not differ between groups. In the dexamethasone group rate of hospital readmission tended to be higher (20 (10%) versus 9 (5%); p=0.051) and hyperglycaemia (14 (7%) versus 1 (1%); p=0.001) was more prevalent.ConclusionOral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk-benefit ratio is optimal.

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difference was not significant (Fisher's exact test, p=0•39).In summary, the M1 UK lineage was seen in diverse geographic regions, formed a local disease cluster, and caused severe infection syndromes in the USA from 2015 to 2018. Although this clone did not expand substantially according to data in the ABCs system, continued genomic surveillance is needed to monitor the effects of this and other emerging virulent strains.We declare no competing interests. The findings and conclusions of this Correspondence are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.