Berit Lange

The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location. Species distribution among nontuberculous mycobacteria isolates from pulmonary specimens is geographically diverse http://ow.ly/npu6r

Risk Assessment of Tuberculosis in Immunocompromised Patients. A TBNET Study

RATIONALE In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. CONCLUSIONS Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Indeterminate results of a tuberculosis-specific interferon-γ release assay in immunocompromised patients

To the Editors: Immunocompromised patients with various causes and degrees of immunodeficiencies, such as stem cell and solid organ transplant recipients, patients with autoimmune diseases, patients with chronic renal failure or HIV-positive patients, are at increased risk of progression from latent Mycobacterium tuberculosis infection to active disease. Therefore, screening for latent tuberculosis and preventive treatment is recommended in this patient population. Tuberculosis-specific interferon (IFN)-γ release assays (TIGRAs) lacking cross-reactivity with Mycobacterium bovis bacille Calmette-Guerin have been introduced into the routine diagnosis of latent tuberculosis infection (LTBI) in the last few years as a more specific alternative to tuberculin skin test (TST). More recent results implicate that QuantiFERON®-TB Gold in tube (QFT-G-IT; Cellestis, Carnegie, Australia) may better predict progression from latent to active disease compared with TST 1, 2. TIGRAs using stimulation of T-cells with phytohemagglutinin (PHA) as a positive control for identification of false negatives and the classification of indeterminate results may be a better alternative for the prediction of LTBI in immunocompromised patients where IFN-γ release may be affected by immunosuppression. The growing list of data existing on reliability of TIGRAs in immunocompromised patients show that the prevalence of indeterminate results may vary depending on the degree of immunosuppression and the TIGRA test used 3. In addition, PHA and recall antigens use different IFN-γ secretion pathways 4, which may be differentially affected by immunosuppressive conditions. Thus, an in-depth analysis of factors influencing PHA-associated IFN-γ secretion is important for the assessment of TIGRAs in immunocompromised patients. Since disease group dependent and independent risk factors of indeterminate results in immunocompromised patients have not been evaluated prospectively using the third generation QFT-G-IT test, we tested QFT-G-IT in patients with diverse conditions of immunosuppression to determine the rate of and identify risk factors for indeterminate results. After approval of …

Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses

BackgroundDried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV.MethodsWe conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias.ResultsFor the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews.ConclusionHCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location. Species distribution among nontuberculous mycobacteria isolates from pulmonary specimens is geographically diverse http://ow.ly/npu6r

Mycobacterium tuberculosis transmission from patients with drug-resistant compared to drug-susceptible TB: a systematic review and meta-analysis.

The extent to which drug-resistant (DR) Mycobacterium tuberculosis strains cause infection and progression to tuberculosis (TB) disease in comparison to drug-susceptible (DS) strains is unknown. Studies in guinea pigs and in vitro experiments have suggested a reduced fitness of organisms that harbour mutations that confer drug resistance [1, 2]; it was therefore believed that transmitted drug resistance was a rare event. However, more recent work using molecular typing has shown transmission events occurring in the context of DR-TB [3]. Understanding the risk of transmission, infection and progression to disease in the context of DR-TB is important to guide control measures and help predict the evolution and magnitude of the multidrug-resistant (MDR)-TB epidemic. Hence, we performed a systematic review and meta-analysis to assess whether M. tuberculosis transmission and progression to TB disease (risk/rate of M. tuberculosis infection in all contacts, risk/rate of TB disease in all contacts and risk/rate of TB disease in infected contacts) differ between DR- and DS-TB. No evidence that drug-resistant TB results in fewer infections or cases in contacts than drug-susceptible TB http://ow.ly/dgez30f87dr

Staphylococcus aureus bloodstream infection in patients with ventricular assist devices - management and outcome in a prospective bicenter cohort

OBJECTIVES Ventricular assist devices (VAD) are increasingly implanted in patients with terminal heart failure. Here we describe the clinical course, management and outcome of VAD patients with S. aureus bloodstream infection (SAB). METHODS We conducted a post hoc analysis of data from 1073 patients who had been prospectively enrolled in two consecutive SAB bicenter cohort studies. Patients with VAD in situ at the onset of SAB were identified. Follow-up of patients was at least 90 days. RESULTS Twelve VAD patients with SAB were identified. Compared to the overall cohort, patients with VAD presented more often with fever (92% vs. 65%) and septic shock (33% vs. 23%) and showed higher C-reactive protein levels (mean 244 vs. 132 g/ml). The median time to onset of SAB after device implantation was 161 days (range 24-790 days). 30-day mortality was comparable to the whole cohort (17% vs. 19%). Infection-related surgical interventions were performed in six patients. Hematogenous dissemination to distant foci was not found in any patient. One out of nine surviving patients required continuous suppressive antibiotic therapy. CONCLUSIONS Mortality rates for VAD patients with SAB were comparable to SAB without VAD. No hematogenous disssemination or persistent infections were recorded, which might be associated with the prompt and aggressive antibiotic and surgical management in VAD patients. SAB per se does not preclude successful transplantation.