First-in-Man Open Clinical Trial of a Combined rdESAT-6 and rCFP-10 Tuberculosis Specific Skin Test Reagent

Tuberculin is still the only available skin test reagent for the diagnosis of mycobacterial infection. The product has a remarkable sensitivity, but poor specificity. Previous studies, including two human phase I clinical trials, have indicated that rdESAT-6 has a potential as an improved skin test reagent. Animal studies have shown that the sensitivity may be increased by inclusion of the genetically related CFP-10 antigen in the preparation without loosing specificity.In this study a Lactococcus fermented, recombinant skin test reagent consisting of a 1ratio1 wt/wt of rdESAT-6 and CFP-10 was manufactured according to GMP standards and tested for the first time in 42 healthy adult volunteers. The two doses of 0.01 microg or 0.1 microg were injected intradermally by the Mantoux technique with 6 or 12 weeks interval. No serious adverse events and only mild adverse reactions were reported. The reagent elicited a positive skin test reaction after the first injection in one participant, who most likely was latently infected with M. tuberculosis as indicated by an appreciable IFN gamma response just below the Quantiferon(R) cut-off level at the screening visit. None of the remaining participants in the four groups had any skin test reactions and sensitisation by the reagent could therefore be excluded.The investigational skin test reagent rdESAT-6 and CFP-10 appeared safe and non-sensitising in this first-in-man clinical trial in human volunteers and can now be tested in larger clinical trials involving individuals with latent M. tuberculosis infection or active TB disease.ClinicalTrials.gov NCT00793702

Genetic Influences on Pulmonary Function: A Large Sample Twin Study

Heritability of forced expiratory volume in one second (FE

Incidence and clinical significance of non-tuberculous mycobacteria isolated from clinical specimens during a 2-y nationwide survey

A 2-y nationwide survey of patients in Denmark with non-tuberculous mycobacteria (NTM) cultures was undertaken. Patients were identified by means of records held at the International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Denmark. The objectives were to identify isolated NTM to species level, to describe the incidence of the various species and to evaluate the clinical significance of pulmonary NTM isolates other than M. avium complex (MAC) and M. gordonae. Identification was performed by means of hybridization or sequencing of 16S rDNA. The clinical significance of pulmonary NTM isolates was evaluated by means of questionnaires concerning patients (was sent to the clinicians!) patients who had NTM isolated for the first time using bacteriologic, radiographic and clinical criteria. A total of 1110 specimens (2.1%) from 525 patients grew NTM. After MAC (n = 198) and M. gordonae (n = 168), most patients had M. abscessus (n = 21), M. malmoense (n = 20) and M. xenopi (n = 17) isolated. Of the pulmonary patients, 50.6% met bacteriologic criteria, 75.3% radiographic criteria and 53.4% clinical criteria for significant infection. Almost half of the pulmonary patients met all the criteria for significant NTM infection that could be evaluated. Clinically significant infection was associated with underlying disease in most patients

Relationship between type 1 diabetes and atopic diseases in a twin population

Aim:\ua0To study the association between type 1 diabetes and atopic diseases in a twin population.Methods:\ua0We performed record linkage between questionnaire‐defined atopic dermatitis, asthma and hay fever, and hospital discharge diagnoses of type 1 diabetes in 54 530 Danish twins, 3–71 years of age.Results:\ua0The age‐ and sex‐adjusted risk of atopic dermatitis was decreased in subjects with type 1 diabetes compared with nondiabetic subjects, (2.1%vs\ua09.9%), odds ratio (OR) = 0.23 (0.07–0.71),\ua0P = 0.011, whereas asthma and hay fever were not significantly associated with type 1 diabetes. Within twin pairs discordant for type 1 diabetes, the diabetic twin had a lower risk of atopic dermatitis relative to the nondiabetic co‐twin. Genetic factors for atopic dermatitis and type 1 diabetes were negatively correlated (r = −0.30),\ua0P = 0.0009.Conclusions:\ua0These findings substantiate the Th1\ua0vs\ua0Th2 cell dichotomy for type 1 diabetes and atopic dermatitis, and indicate an inverse association between genetic factors for these disorders