Extensively drug-resistant tuberculosis: epidemiology and management challenges.
ABSTRACT Widespread global use of rifampin for 2 decades preceded the emergence of clinically significant multidrug-resistant tuberculosis (MDR-TB) in the early 1990s. The prevalence of MDR-TB has gradually increased such that it accounts for approximately 5% of the global case burden of disease (approximately half a million cases in 2007). Eclipsing this worrying trend is the widespread emergence of extensively drug-resistant TB (XDR-TB). This article reviews the insights provided by clinical and molecular epidemiology regarding global trends and transmission dynamics of XDR-TB, and the challenges clinicians have to face in diagnosing and managing cases of XDR-TB. The ethical and management dilemmas posed by recurrent defaulters, XDR-TB treatment failures, and isolation of incurable patients are also discussed. Given the past global trends in MDR-TB, if aggressive preventive and management strategies are not implemented, XDR-TB has the potential to severely cripple global control efforts of TB.
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ABSTRACT: Diagnosis represents only one aspect of tuberculosis (TB) control but is perhaps one of the most challenging. The drawbacks of current tools highlight several unmet needs in TB diagnosis i.e. necessity for accuracy, rapidity of diagnosis, affordability, simplicity, and the ability to generate same-day results at point-of-care (POC). When a return visit is required to access test results, time to treatment is prolonged and default rates are significant. However, a good diagnostic tool is also critically dependent on obtaining an adequate biological sample. Here we review the accuracy and potential impact of established and newer potential POC diagnostic tests for TB including smear microscopy, the Xpert MTB/RIF assay (Cepheid) and the Determine TB LAM antigen test (Alere). Novel experimental approaches and detection technologies for POC diagnosis of active TB, including nucleic acid amplification tests, detection of volatile organic compounds or metabolites, mass spectroscopy, microfluidics, SERS, electrochemical approaches, and aptamers amongst others, are discussed. We also discuss future applications, including the potential POC diagnosis of drug-resistant TB and presumed latent TB infection. Challenges to the development and roll-out of POC tests for TB are also reviewed.Respirology 11/2012; · 2.78 Impact Factor
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ABSTRACT: A series of novel S-esters of 2-(4-nitrobenzoyl)hydrazinecarbodithioic acid and S,S′-diesters of (4-nitrobenzoyl)carbonohydrazonodithioic acid were synthesized by reaction of 4-nitrobenzohydrazide and N-methyl-4-nitrobenzohydrazide with carbon disulfide and alkyl halides in the presence of triethylamine. Novel 5-(4-nitrophenyl)-1,3,4-oxadiazoles were also obtained. The structures were confirmed by IR, NMR, and mass spectroscopy, and by elemental analysis. All the compounds obtained were screened in vitro for their tuberculostatic activity. Promising preliminary results were obtained for some of the compounds. The crystal structure of the most active compound was determined. Graphical abstractMonatshefte fuer Chemie/Chemical Monthly 07/2012; 143(4). · 1.63 Impact Factor
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ABSTRACT: Tuberculosis (TB) is an infectious disease that causes more than 1 million deaths worldwide every year. In addition, it is estimated that one third of the world population is infected with M. tuberculosis in a latent state, which involves an eventual risk of progressing to active TB disease. Patients with immunodeficiencies, such as those suffering from haematological malignancies, have a greater risk of progressing to TB disease once infected. It is estimated that the Relative Risk of TB disease in patients with hematologic malignancies is 2-40 times that of the general population. The diagnosis of TB in these patients is often challenging as they often present clinical characteristics that are distinct to those of patients without any other underlying disease. Mortality due to TB is higher. Therefore, it is recommended to diagnose latent TB infection and consider preventive therapy that could avoid the progression from a latent state to active TB disease. There are currently two methods for diagnosing latent TB infection: the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assays (IGRA). Due to the lack of sensitivity in patients with immunodeficient conditions, a combined TST-IGRA testing is probably the best way for latent TB diagnosis in order to gain sensitivity. Treatment of latent TB infection and TB disease should follow the general principles to that in the general population.Mediterranean Journal of Hematology and Infectious Diseases 01/2014; 6(1):e2014026.