Levofloxacin combined with cellulase can eradicate bacille Calmette-Guerin biofilm infection / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effects of levofloxacin (LEV) combined with cellulase against bacille CalmetteGuerin (BCG) biofilms in vitro.@*METHODS@#The mature growth cycle of BCG biofilms was determined using the XTT method and crystal violet staining. BCG planktonic bacteria and BCG biofilms were treated with different concentrations of LEV and cellulose alone or jointly, and the changes in biofilm biomass were quantified with crystal violet staining. The mature BCG biofilm was then treated with cellulase alone for 24 h, and after staining with SYTO 9 and Calcofluor White Stain, the number of viable bacteria and the change in cellulose content in the biofilm were observed with confocal laser scanning microscopy. The structural changes of the treated biofilm were observed under scanning electron microscopy.@*RESULTS@#The MIC, MBC and MBEC values of LEV determined by broth microdilution method were 4 μg/mL, 8 μg/mL and 1024 μg/mL, respectively. The combined treatment with 1/4×MIC LEV and 2.56, 5.12 or 10.24 U/mL cellulase resulted in a significant reduction in biofilm biomass (P < 0.001). Cellulase treatments at the concentrations of 10.24, 5.12 and 2.56 U/mL all produced significant dispersion effects on mature BCG biofilms (P < 0.001).@*CONCLUSION@#LEV combined with cellulose can effectively eradicate BCG biofilm infections, suggesting the potential of glycoside hydrolase therapy for improving the efficacy of antibiotics against biofilmassociated infections caused by Mycobacterium tuberculosis.

Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor

The Bacille Calmette-Guérin (BCG) vaccine comprises a family of genetically different strains derived by the loss of genomic regions (RDs) and other mutations. In BCG Moreau, loss of RD16 inactivates rv3405c * , encoding a transcriptional repressor that negatively regulates the expression of Rv3406, an alkyl sulfatase. To evaluate the impact of this loss on the BCG and host cell viability and the cytokine profile, THP-1 cells were infected with BCG Moreau (harbouring the empty vector) and a complemented strain carrying a functional copy of rv3405c. Viability of the host cells and bacteria as well as the pattern of cytokine secretion were evaluated. Our results show that the viability of BCG Moreau is higher than that of the complemented strain in an axenic medium, suggesting a possible functional gain associated with the constitutive expression of Rv3406. Viability of the host cells did not vary significantly between recombinant strains, but differences in the profiles of the cytokine secretion (IL-1β and IL-6) were observed. Our results suggest an example of a functional gain due to gene loss contributing to the elucidation of the impact of RD16 on the physiology of BCG Moreau.

Factors associated with the development of tuberculosis in BCG immunized children.

In this hospital-based case-control study, children attending Siriraj Hospital and Queen Sirikit National Institute of Child Health from 1 December 2002 to 30 June 2003 were studied to define factors associated with TB in BCG immunized children (n = 260). Subjects of the same age and sex were divided into case and control groups by tuberculosis status. Caregivers were interviewed with a structured questionnaire. Data were analyzed by univariate analysis and multivariate analysis for biological factors (birth weight, health status, nutritional status), socioeconomic factors (parental education, education of caregiver, parental occupation, household incomes, and stability of household incomes), and environmental factors (history of contact with a tuberculosis patient, housing ventilation, child's bedroom ventilation, biomass smoke, passive smoking, crowded family and crowded in child's bedroom). Our findings show that children who had contact with TB patients had a very high risk of tuberculosis, even though they were vaccinated at birth. The risks vary according to the closeness level: very close (OR 85.67, 95%CI = 11.33-647.79), close (OR 31.11, 95%CI = 3.93-246.22) and not close (OR 32.70, 95%CI = 4.18-255.94). In order to identify the effect of others variables, the data was reanalyzed only in the group with no history of TB patient contacts (n = 192). Living in a crowded family, which was reflected by an average of 5 or more persons per room, also increased the risk (OR 11.18, 95%CI = 2.35-53.20). The other factor that increased the risk for tuberculosis was passive smoking. Children who were exposed to passive smoking had a 9.31 times increased risk of getting tuberculosis (95%CI = 3.14-27.58). These findings suggest that the public health department must develop a TB surveillance system in high TB prevalence areas, and in high density communities, and encourage smokers in every family to avoid smoking near children. Latent tuberculosis treatment recommendations for TB control cluster, as set by the Bureau of AIDS/TB and STIs, must be implemented in all health centers and an effective TB control program must be reinforced.

Reacción cutánea al BCG en una población de niños vacunados en una unidad de vacunación de un hospital de niños / Skin reaction to BCG in a population of children vaccinated in a vaccination post of a children's hospital

Con el objetivo de determinar la respuesta cutánea al BCG, realizamos un estudio transversal seleccionando 50 niños vacunados en la unidad de vacunación de la Clínica Infantil Dr. Robert Read Cabral, durante el período septiembre-diciembre 1993; de éstos 33 casos (66//) fueron msculinos y 17 casos (34//) fueron femeninos; 27 casos (54//) presentaron reacción cutánea a la vacuna BCG. La reacción fue más frecuente en la tercera semana, 13 casos (48.1//). Los niños eutróficos tuvieron mayor respuesta positiva 25 casos (85.77//), solo 10 casos (20//) presentó complicación

Verificaçäo in vitro da sensibilidade do BCG (estirpe Moreau-Rio de Janeiro) à isoniazida e à rifampicina / \"In vitro\" sensitivity of BCG vaccine Moreau-Rio de Janeiro strain) to isoniazid and rifampicin

Foi realizado um experimento laboratorial para verificaçäo in vitro da sensibilidade da vacina BCG (estirpe Moreau-Rio de Janeiro) á isoniazida e á rifampicina, utilizando-se, para tal, 30 frasco provenientes de trinta diferentes lotes. Os procedimentos laboratoriais foram semelhantes áqueles empregados para realizaçäo dos testes de sensibilidade com o bacilo de Koch. Observou-se crescimento bacilar em todos os tubos, cujos meios de cultrua estavam isentos das duas drogas e em nenhum daqueles que as continham

Role of the mononuclear phagocytic system in the immune and nonspecific clearance of Trypanosoma cruzi bloodstream trypomastigotes

The removal of T. cruzi bloodstream trypomastigotes (BTRYS) from the circulation is mediated mostly by the mononuclear phagocytic system (MPS). In the present study we investigated the the nonspecific and the immune clearance of BTRYS in groups of 4 mice whose MPS activity was either enhanced by BCG treatment or depressed by silica treatment. Treatment with BCG resulted in a significant increase in the nonspecific clearance of both carbon particles (100% after 6 min) and BTRYS (60% after 5 min) 28 days after BCG treatment but there was no change in the immune clearance of the parasites. Pretreatment of the animals with silica induced a significant reduction of the colloidal carbon clearance (80% less than control 15 min later) but did not alter the nonspecific or the immune clearance of BTRYS. We conclude that the removal of the opsonized parasites from the circulation is due to a mechanism different from that of the nonspecific clearance

Microdosis de vacuna BCG en cáncer vesical superficial / Microdose of BCG vaccine in bladder cancer

Se tratan 23 pacientes con cáncer vesical operado, con BCG liofilizado endovesical en microdosis de 1 mgr. De 17 pacientes que terminaron tratamiento, 16 (94 por ciento) están libre de enfermedad con 50 meses de observación. 6 pacientes están actualmente sin recidivas con 6 meses de observación. Durante el tratamiento no se presentaron complicaciones. Los resultados obtenidos demuestran los beneficios de la microdosis de BCG en la profilaxis de recurrencias del cáncer vesical

Diseminación BCG en tratamiento de carcinoma vesical superficial / Disseminations with BCG in treatment of superficial bladder cancer

Se presenta caso clínico de paciente de 76 años con carcinoma vesical de células transicionales II Broders y A de Jewett-Strong que tratado con instilación endovesical de BCG presenta becegeitis. Se relaciona la complicación con maniobra de dilatación uretral

Lymphocyte transformation in lepromatous leprosy: a study of the influence of disease activity and symptom duration.

The lymphocyte hyporesponsiveness to M. leprae of patients with active lepromatous leprosy has been well described. This immune defect is less well understood in terms of its time of origin, possible reversibility and specificity. To further examine the persistence and specificity of this abnormality, lymphocyte transformation tests of 93 leprosy patients to lepromin, BCG and PHA were studied. Among lepromatous patients, a decreased response to M. leprae was seen, whether the disease was active or inactive. Decreased responses to BCG were found in lepromatous patients with active disease, but not in those with inactive disease. The duration of patient symptoms was not associated with differences in LTT responses among the active lepromatous patients.

Anti-leprosy vaccines--field trials and future prospects.

Development of a vaccine for prevention of leprosy is today one of the major challenges for bio-medical sciences. Two vaccines containing (i) M. leprae + BCG and (ii) ICRC, a cultivable mycobacterium, have reached advanced stage with reference to human trials. This article describes comparative features of two vaccines and mechanism of their action. Future possibilities with reference to anti-leprosy vaccine are also discussed.