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A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols ([less than or equal to]10 [micro]m) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host-pathogen interactions. Culturable Mycobacterium tuberculosis can be detected in cough aerosol from a high proportion of individuals infected with drug-resistant M. tuberculosis and correlate with a strong cough and low symptom score, indicating the need to focus on targeted interventions., Author(s): Grant Theron [sup.1] [sup.2] , Jason Limberis [sup.1] , Rouxjeane Venter [sup.2] , Liezel Smith [sup.1] [sup.2] , Elize Pietersen [sup.1] , Aliasgar Esmail [sup.1] , Greg Calligaro [sup.1] [...]

Tuberculosis (TB), caused by the human pathogen Mycobacterium tuberculosis, is a recognized disease in human-managed and wild Asian elephants (Elephas maximus) and African elephants (Loxodonta africana) (1-3). Previous findings demonstrate [...]

The African wild dog (Lycaon pictus) is an endangered carnivore occurring in fragmented, small populations (in South Africa, Since 2012, sporadic cases of wild dogs with macroscopic and histological lesions [...]

Tuberculosis (TB) caused by Mycobacterium tuberculosis or M. bovis has been reported in captive rhinoceroses since the early 1800s (1-3). Bovine TB is endemic in many wildlife populations worldwide, including [...]

The mechanisms involved in interactions between Mycobacterium tuberculosis and host innate immune cells determine outcome. Antigen-presenting cells, including macrophages and dendritic cells, express many pattern recognition receptors to identify pathogen-associated molecular patterns, thereby initiating an immune response. A major mycobacterial virulence factor, trehalose-6',6-dimycolate, is recognised by the macrophage-inducible C-type lectin, Mincle, which leads to the activation of the Syk-Card9 signalling pathway in macrophages. Mincle is encoded by CLEC4E, and we investigated polymorphisms in this gene to assess its role in tuberculosis susceptibility. Four tagging single nucleotide polymorphisms (SNPs) (rs10841845, rs10841847, rs10841856 and rs4620776) were genotyped using TaqMan.sup.® SNP assays in 416 tuberculosis cases and 405 healthy controls. Logistic regression models were used for analysis. No association was detected with any of the SNPs analysed. This research highlights tuberculosis disease complexity where recognition proteins which specifically bind mycobacterial glycolipids cannot be conclusively associated with the disease in genetic studies., Author(s): Nicholas Bowker[sup.1] , Muneeb Salie[sup.1] , Haiko Schurz[sup.1] , Paul D. van Helden[sup.1] , Craig J. Kinnear[sup.1] , Eileen G. Hoal[sup.1] , Marlo Moller[sup.1] Author Affiliations: (1) SA MRC [...]

Tuberculosis (TB) is caused by a group of distinct mycobacterial strains that might have evolved as hostadapted ecotypes (1) and that are collectively named the Mycobacterium tuberculosis complex (MTC) (2). [...]

Background South Africa has the highest tuberculosis incidence globally (781/100,000), with an estimated 4.3% of cases being rifampicin resistant (RR). Control and elimination strategies will require detailed spatial information to understand where drug-resistant tuberculosis exists and why it persists in those communities. We demonstrate a method to enable drug-resistant tuberculosis monitoring by identifying high-burden communities in the Western Cape Province using routinely collected laboratory data. Methods and findings We retrospectively identified cases of microbiologically confirmed tuberculosis and RR-tuberculosis from all biological samples submitted for tuberculosis testing (n = 2,219,891) to the Western Cape National Health Laboratory Services (NHLS) between January 1, 2008, and June 30, 2013. Because the NHLS database lacks unique patient identifiers, we performed a series of record-linking processes to match specimen records to individual patients. We counted an individual as having a single disease episode if their positive samples came from within two years of each other. Cases were aggregated by clinic location (n = 302) to estimate the percentage of tuberculosis cases with rifampicin resistance per clinic. We used inverse distance weighting (IDW) to produce heatmaps of the RR-tuberculosis percentage across the province. Regression was used to estimate annual changes in the RR-tuberculosis percentage by clinic, and estimated average size and direction of change was mapped. We identified 799,779 individuals who had specimens submitted from mappable clinics for testing, of whom 222,735 (27.8%) had microbiologically confirmed tuberculosis. The study population was 43% female, the median age was 36 years (IQR 27-44), and 10,255 (4.6%, 95% CI: 4.6-4.7) cases had documented rifampicin resistance. Among individuals with microbiologically confirmed tuberculosis, 8,947 (4.0%) had more than one disease episode during the study period. The percentage of tuberculosis cases with rifampicin resistance documented among these individuals was 11.4% (95% CI: 10.7-12.0). Overall, the percentage of tuberculosis cases that were RR-tuberculosis was spatially heterogeneous, ranging from 0% to 25% across the province. Our maps reveal significant yearly fluctuations in RR-tuberculosis percentages at several locations. Additionally, the directions of change over time in RR-tuberculosis percentage were not uniform. The main limitation of this study is the lack of unique patient identifiers in the NHLS database, rendering findings to be estimates reliant on the accuracy of the person-matching algorithm. Conclusions Our maps reveal striking spatial and temporal heterogeneity in RR-tuberculosis percentages across this province. We demonstrate the potential to monitor RR-tuberculosis spatially and temporally with routinely collected laboratory data, enabling improved resource targeting and more rapid locally appropriate interventions., Author(s): Avery I. McIntosh 1, Helen E. Jenkins 1, Laura F. White 1, Marinus Barnard 2, Dana R. Thomson 3, Tania Dolby 2, John Simpson 2, Elizabeth M. Streicher 4, [...]

Tuberculosis (TB) is among the most devastating human infectious diseases worldwide. An estimated 8.8 million new cases, a global average incidence rate of 128/100,000 population/year, and 1.5 million deaths were [...]

The emergence of drug-resistant tuberculosis (TB) is of major concern to TB control in South Africa. A countrywide survey in 2002 revealed that 1.8% of all new TB patients and [...]

A previously unidentified Mycobacterium tuberculosis complex pathogen has emerged in banded mongooses (Mungos mungo) in Botswana; we named the pathogen mongoose bacillus, or M. mungi sp. nov. This pathogen causes [...]

The emergence of drug-resistant tuberculosis (TB) is often attributed to the failure to implement proper TB control programs and correctly manage TB cases (1,2). Consequently, >450,000 multidrug-resistant (MDR) TB cases [...]

The Beijing strain family has often been associated with tuberculosis (TB) outbreaks and drug resistance worldwide. In this study the authors have compared the protein expression and antigen recognition profiles of a local Beijing strain with a less prevalent clinical isolate belonging to the family 23 strain lineage, and the laboratory strain Mycobacterium tuberculosis H37Rv. Using two-dimensional electrophoresis, liquid chromatography tandem mass spectrometry and Western blot analysis several proteins were identified as quantitatively increased or decreased in both clinical strains compared to H37Rv. Remarkably, the Beijing strain showed increased expression of [alpha]-crystallin and decreased expression of Hsp65, PstS1, and the 47 kDa protein compared to the other clinical strain and H37Rv. One- and two-dimensional Western blot analysis of antigens expressed by the three strains, using plasma from TB patients, confirmed differential antigen expression by strains and patient-to-patient variation in humoral immunity. These observed protein differences could aid the elucidation of mechanisms underlying the success of the Beijing strain family, measured by global dissemination, compared to other M. tuberculosis strains.

When people develop tuberculosis after being successfully treated for the disease, it is not always a reactivation of the previous disease. Researchers used DNA analysis to identify the bacterial strain that was infecting 16 patients who developed tuberculosis for a second time after being successfully treated during the first infection. In 12 of the patients, the DNA analysis revealed that they were infected with a different strain of bacteria than the strain that caused the first infection. This illustrates the importance of strict infection control procedures when people become infected with tuberculosis so the bacterium is not transmitted to other people.

Author(s): Christian Lienhardt 1,*, Knut Lönnroth 1, Dick Menzies 2, Manica Balasegaram 3, Jeremiah Chakaya 4, Frank Cobelens 5, Jennifer Cohn 3, Claudia M. Denkinger 6, Thomas G. Evans 7, [...]

Concerns arise about the threat of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis occurring amid the global economic crisis, due to the increasing costs of treating the disease. It is suggested that financial and political commitment by developed and developing countries are essential to treat tuberculosis effectively.

Black rhinoceros (Diceros bicornis) are under severe threat from poaching and habitat loss. This species has been designated as critically endangered by the International Union for Conservation of Nature Red [...]

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

To the Editor: In a recently published study, van Ingen et al. (1) described the molecular characterization and phylogenetic position of the oryx bacillus, a member of the Mycobacterium tuberculosis [...]