Comparative radiological features of disseminated disease due to Mycobacterium tuberculosis vs non-tuberculosis mycobacteria among AIDS patients in Brazil

Background: Disseminated mycobacterial disease is an important cause of morbidity and mortality in patients with HIV-infection. Nonspecific clinical presentation makes the diagnosis difficult and sometimes neglected. Methods: We conducted a retrospective cohort study to compare the presentation of disseminated Mycobacterial tuberculosis (MTB) and non-tuberculous Mycobacterial (NTM) disease in HIV-positive patients from 1996 to 2006 in Brazil. Results: Tuberculosis (TB) was diagnosed in 65 patients (67.7%) and NTM in 31 (32.3%) patients. Patients with NTM had lower CD4 T cells counts (median 13.0 cells/mm3 versus 42.0 cells/mm3, P = 0.002). Patients with tuberculosis had significantly more positive acid-fast smears (48.0% vs 13.6%, P = 0.01). On chest X-ray, miliary infiltrate was only seen in patients with MTB (28.1% vs. 0.0%, P = 0.01). Pleural effusion was more common in patients with MTB (45.6% vs. 13.0%, P = 0.01). Abdominal adenopathy (73.1% vs. 33.3%, P = 0.003) and splenic hypoechoic nodules (38.5% vs. 0.0%, P = 0.002) were more common in patients with TB. Conclusion: Miliary pulmonary pattern on X-ray, pleural effusion, abdominal adenopathy, and splenic hypoechoic nodules were imaging findings associated with the diagnosis of tuberculosis in HIV-infected patients. Recognition of these imaging features will help to distinguish TB from NTM in AIDS patients with fever of unknown origin due to disseminated mycobacterial disease

Ecology and Transmission of Buruli Ulcer Disease: A Systematic Review

Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after tuberculosis. Cases have been reported from at least 32 countries in Africa (mainly west), Australia, Southeast Asia, China, Central and South America, and the Western Pacific. Large lesions often result in scarring, contractual deformities, amputations, and disabilities, and in Africa, most cases of the disease occur in children between the ages of 4–15 years. This environmental mycobacterium, Mycobacterium ulcerans, is found in communities associated with rivers, swamps, wetlands, and human-linked changes in the aquatic environment, particularly those created as a result of environmental disturbance such as deforestation, dam construction, and agriculture. Buruli ulcer disease is often referred to as the “mysterious disease” because the mode of transmission remains unclear, although several hypotheses have been proposed. The above review reveals that various routes of transmission may occur, varying amongst epidemiological setting and geographic region, and that there may be some role for living agents as reservoirs and as vectors of M. ulcerans, in particular aquatic insects, adult mosquitoes or other biting arthropods. We discuss traditional and non-traditional methods for indicting the roles of living agents as biologically significant reservoirs and/or vectors of pathogens, and suggest an intellectual framework for establishing criteria for transmission. The application of these criteria to the transmission of M. ulcerans presents a significant challenge

Genomic characterization of Nontuberculous Mycobacteria

YesMycobacterium tuberculosis and Mycobacterium leprae have remained, for many years, the primary species of the genus Mycobacterium of clinical and microbiological interest. The other members of the genus, referred to as nontuberculous mycobacteria (NTM), have long been underinvestigated. In the last decades, however, the number of reports linking various NTM species with human diseases has steadily increased and treatment difficulties have emerged. Despite the availability of whole genome sequencing technologies, limited effort has been devoted to the genetic characterization of NTM species. As a consequence, the taxonomic and phylogenetic structure of the genus remains unsettled and genomic information is lacking to support the identification of these organisms in a clinical setting. In this work, we widen the knowledge of NTMs by reconstructing and analyzing the genomes of 41 previously uncharacterized NTM species. We provide the first comprehensive characterization of the genomic diversity of NTMs and open new venues for the clinical identification of opportunistic pathogens from this genus

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases