Rationale: Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested. Objectives: We sought to quantify the efficacy of surgical face masks when worn by patients with multidrug-resistant TB (MDR-TB). Methods: Over 3 months, 17 patients with pulmonary MDR-TB occupied an MDR-TB ward in South Africa and wore face masks on alternate days. Ward air was exhausted to two identical chambers, each housing 90 pathogen-free guinea pigs that breathed ward air either when patients wore surgical face masks (intervention group) or when patients did not wear masks (control group). Efficacy was based on differences in guinea pig infections in each chamber. Measurements and Main Results: Sixty-nine of 90 control guinea pigs (76.6%; 95% confidence interval [CI], 68-85%) became infected, compared with 36 of 90 intervention guinea pigs (40%; 95% CI, 31-51%), representing a 56% (95% CI, 33-70.5%) decreased risk of TB transmission when patients used masks. Conclusions: Surgical face masks on patients with MDR-TB significantly reduced transmission and offer an adjunct measure for reducing TB transmission from infectious patients.Keywords: infection control; multidrug-resistant tuberculosis; transmission; surgical maskOf an estimated 9 million new cases of tuberculosis (TB) in 2008 globally (1), 440,000 were multidrug-resistant TB (MDR-TB) (2), and more than half of those are believed to have occurred in previously untreated patients, the result of transmission of already drug-resistant strains (2). Recent reports of infection with highly drug-resistant strains of Mycobacterium tuberculosis among patients and health care workers illustrate the dire consequences of nosocomial transmission, especially in areas where HIV is endemic (3, 4). Although once believed to arise primarily from unsupervised or erratic treatment of drug-susceptible TB, MDR-TB and extensively drug-resistant TB (XDR-TB) are now known to be transmissible and have emerged as important threats to patients who enter hospitals for drug-susceptible TB (reinfection) or other illnesses, to the clinical staff caring for them, and to occupants of other congregate settings, such as correctional facilities and shelters. One study in Russia found that hospitalization, rather than treatment nonadherence, conferred a sixfold greater relative risk for the acquisition of MDR-TB by patients (5), whereas another study in Latvia revealed that previous hospitalization was a highly significant risk factor for MDR-TB (odds ratio, 18.33; P , 0.002) (6). In addition, health care workers in diverse settings have been shown to be disproportionately exposed to and infected with drugsusceptible and drug-resistant TB (4, 7). TB among health care workers erodes the already limited supply of hospital personnel in many resource-constrained settings, both directly through illness and indirectly through fear of working in such high-risk envi...

A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant M. tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6mm], only 12% had histopathologic evidence of active disease. Reversions (≥ 6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6 to 13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease.

No abstract

Developing nanoparticulate delivery systems that will allow easy movement and localisation of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(D,L-lactide-coglycolide) (PLGA) nanoparticles containing samarium-153 oxide ([ 153 Sm]Sm 2 O 3 ) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive 153 Sm-loaded -PLGA nanoparticles. The nanoparticles were characterized for size, Zeta potential and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The 153 Sm-loaded -PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The Zeta potential ranged between 5 and 20 mV. The [ 153 Sm]Sm 2 O 3 loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles . While the IV injected [ 153 Sm]Sm 2 O 3 loaded PLGA nanoparticles exhibited the highest localisation of nanoparticles in the spleen (8.63%ID/g) and liver (3.07%ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen, From the biodistribution data obtained it is clear that polymeric nano scale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

A potential anti-TB compound bearing a nitroimidazole moiety from iThemba Pharmaceuticals TB chemical library exhibits promising in vitro activity in the microplate almar blue assay (MABA) with a minimum inhibitory concentration (MIC) value of 3 µg/mL. It is equipotent to the front-line drug Isoniazid, but the compound is less toxic with an IC50 of >100 µg/mL. Therefore, this potential iThemba nitroimidazole, 4-([1,1'-[(14)C6]biphenyl]-4-ylmethyl)-9-nitro-3,4,5,6-tetrahydro-2H-imidazo[2,1-b][1,3,6]oxadiazocine, was radiolabeled with the C-14 isotope. The synthesis of the (14)C-labeled nitroimidazole was accomplished in seven steps from diethanolamine with a final specific radioactivity of 3.552 GBq/mmol, a radiochemical yield of 87%, and a radiochemical purity of ≥96%. The source of the C-14 radiolabel was bromobenzene which was introduced by the Suzuki-Miyaura reaction. Tissue distribution results showed that the radiotracer has a high accumulation in the lungs of TB-infected mice, statistically significantly higher than in healthy mice. However, the clearance (for both TB-infected and non-TB-infected mice) from all organs (except the small intestine) from 1 to 2 h as well as the low percentage of injected dose per gram values achieved indicates breakdown of the compound in vivo and subsequent clearance from the body. The latter suggests that the compound might not be useful as an anti-TB drug in humans.

No abstract

This paper describes a five-step synthesis of a carbon-14-labelled pyrazole compound (11). A total of 2.96 MBq of 11 was obtained with the specific activity of 2242.4 MBq/mmol. The radiochemical purity was >99%, and the overall radiochemical yield was 60% based on the [(14) C6 ] 4-bromoaniline starting material. Biodistribution results showed that the radiotracer (administrated orally) has a high accumulation in the small intestine, large intestine and liver of both non-infected and tuberculosis (TB)-infected mice. Therefore, this suggests that compound 11 undergoes hepatobiliary clearance. The compound under investigation has been found to be slowly released from the liver between 2 and 8 h. The study revealed that 11 has no affinity for TB cells.

No abstract