Charlotte F. J. Rayner

Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum

Summary Background We investigated the potential of proteomic fingerprinting with mass spectrometric serum profiling, coupled with pattern recognition methods, to identify biomarkers that could improve diagnosis of tuberculosis. Methods We obtained serum proteomic profiles from patients with active tuberculosis and controls by surface-enhanced laser desorption ionisation time of flight mass spectrometry. A supervised machine-learning approach based on the support vector machine (SVM) was used to obtain a classifier that distinguished between the groups in two independent test sets. We used k-fold cross validation and random sampling of the SVM classifier to assess the classifier further. Relevant mass peaks were selected by correlational analysis and assessed with SVM. We tested the diagnostic potential of candidate biomarkers, identified by peptide mass fingerprinting, by conventional immunoassays and SVM classifiers trained on these data. Findings Our SVM classifier discriminated the proteomic profile of patients with active tuberculosis from that of controls with overlapping clinical features. Diagnostic accuracy was 94% (sensitivity 93·5%, specificity 94·9%) for patients with tuberculosis and was unaffected by HIV status. A classifier trained on the 20 most informative peaks achieved diagnostic accuracy of 90%. From these peaks, two peptides (serum amyloid A protein and transthyretin) were identified and quantitated by immunoassay. Because these peptides reflect inflammatory states, we also quantitated neopterin and C reactive protein. Application of an SVM classifier using combinations of these values gave diagnostic accuracies of up to 84% for tuberculosis. Validation on a second, prospectively collected testing set gave similar accuracies using the whole proteomic signature and the 20 selected peaks. Using combinations of the four biomarkers, we achieved diagnostic accuracies of up to 78%. Interpretation The potential biomarkers for tuberculosis that we identified through proteomic fingerprinting and pattern recognition have a plausible biological connection with the disease and could be used to develop new diagnostic tests.

HIV seroprevalence by anonymous testing in patients with Mycobacterium tuberculosis and in tuberculosis contacts

Having witnessed a large increase in Mycobacterium tuberculosis notifications in south London, we wanted to ascertain the prevalence of HIV and tuberculosis co-infection in our patients. All patients with tuberculosis and their contacts were anonymously tested for HIV in blood and saliva, respectively. 11.4% of patients (from various demographic groups) with tuberculosis who attend chest clinics in south London are HIV positive. In addition, 5% of individuals seen in the tuberculosis contact screening clinics and 4% new entrants are HIV positive. All patients with Mycobacterium tuberculosis, irrespective of background, should be urged to have an HIV test.

Management of Chronic Bronchial Sepsis Due to Bronchiectasis

Although saccular bronchiectasis is becoming rare, cylindrical bronchiectasis is increasingly recognized now that thin section computed tomography (CT) scanning is more commonly performed. Patients present with regular sputum production, which may be chronically infected, and frequently with rhinosi

Chest radiographs in pregnancy

Do not hesitate to perform chest radiography in pregnant patients if they fulfil the criteria

Mucus—Bacteria Interactions

Human evolution has necessitated the development of an internal lung for gas exchange, which has developed from an adaptation of the primitive foregut. The surface area required for gas exchange is provided by large numbers of alveoli supplied by repeated branching of the bronchial tree. Through these blind-ending airways pass 1-2 x l04 1 of air per 24 h. The respiratory mucosa is therefore continually exposed to a variety of noxious agents which include bacteria. To prevent infection, the respiratory tract possesses an elaborate array of host defences, whose co-ordinated action ensures sterility of the lung from the first bronchial division [1]. The initial interaction of bacteria with the respiratory mucosa is with mucus, and this influences subsequent events that determine the success or failure of bacterial colonisation.