A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed.
Animals ; Antitubercular Agents/adverse effects/*therapeutic use ; *Drug Discovery ; *Drug Repositioning ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Extensively Drug-Resistant Tuberculosis/drug therapy/microbiology ; Humans ; Lung/*drug effects/microbiology ; Mycobacterium tuberculosis/*drug effects/pathogenicity ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/diagnosis/*drug therapy/microbiology ; Tuberculosis, Pulmonary/diagnosis/*drug therapy/microbiology

OBJECTIVE: To evaluate the multiphase contrast-enhanced magnetic resonance (MR) imaging features of Bacillus Calmette-Guerin (BCG)-induced granulomatous prostatitis (GP). MATERIALS AND METHODS: Magnetic resonance images obtained from five patients with histopathologically proven BCG-induced GP were retrospectively analyzed for tumor location, size, signal intensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI), apparent diffusion coefficient (ADC) value, and appearance on gadolinium-enhanced multiphase images. MR imaging findings were compared with histopathological findings. RESULTS: Bacillus Calmette-Guerin-induced GP (size range, 9-40 mm; mean, 21.2 mm) were identified in the peripheral zone in all patients. The T2WI showed lower signal intensity compared with the normal peripheral zone. The DWIs demonstrated high signal intensity and low ADC values (range, 0.44-0.68 x 10(-3) mm2/sec; mean, 0.56 x 10(-3) mm2/sec), which corresponded to GP. Gadolinium-enhanced multiphase MR imaging performed in five patients showed early and prolonged ring enhancement in all cases of GP. Granulomatous tissues with central caseation necrosis were identified histologically, which corresponded to ring enhancement and a central low intensity area on gadolinium-enhanced MR imaging. The findings on T2WI, DWI, and gadolinium-enhanced images became gradually obscured with time. CONCLUSION: Bacillus Calmette-Guerin-induced GP demonstrates early and prolonged ring enhancement on gadolinium-enhanced MR imaging which might be a key finding to differentiate it from prostate cancer.
Aged ; Gadolinium/*diagnostic use ; Humans ; Image Enhancement ; Immunotherapy/*adverse effects ; Magnetic Resonance Imaging/*methods ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Mycobacterium bovis/*pathogenicity ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/diagnosis ; Prostatitis/*diagnosis ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy

Tuberculosis ranks as the second deadly infectious disease worldwide. The incidence of tuberculosis is high in China. Refractory wound caused by Mycobacterium tuberculosis infection ranks high in misdiagnosis, and it is accompanied by a protracted course, and its pathogenic mechanism is still not so clear. In order to study its pathogenic mechanism, it is necessary to reproduce an appropriate animal model. Up to now the study of the refractory wound caused by Mycobacterium tuberculosis infection is just beginning, and there is still no unimpeachable model for study. This review describes two models which may reproduce a wound similar to the wound caused by Mycobacterium tuberculosis infection, so that they could be used to study the pathogenesis and characteristics of a tuberculosis wound in an animal.
Animals ; Disease Models, Animal ; Mycobacterium tuberculosis ; isolation & purification ; pathogenicity ; Surgical Wound Infection ; diagnosis ; microbiology ; Tuberculosis ; complications ; diagnosis ; microbiology

Adult ; Female ; Heat-Shock Proteins ; genetics ; Humans ; Leprosy ; diagnosis ; genetics ; microbiology ; Male ; Middle Aged ; Mycobacterium leprae ; pathogenicity ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length ; Skin ; metabolism

OBJECTIVEThis study aimed to review the available literatures on control of latent tuberculosis (TB) infection and propose a new control strategy to shorten the course of TB chemotherapy.

DATA SOURCESThe data used in this review were mainly obtained from articles listed in PubMed. The search terms were "therapy (treatment) of tuberculosis," "therapy (treatment) of latent TB infection," and "vaccine of TB."

STUDY SELECTIONArticles regarding treatment and vaccine of TB were selected and reviewed.

RESULTSThe most crucial reason causing the prolonged course of TB chemotherapy is the dormant state of Mycobacterium tuberculosis (M. tuberculosis). Nevertheless, there are, to date, no effective drugs that can directly kill the dormant cells of M. tuberculosis in clinical therapy. In accordance with the growth cycle of dormant M. tuberculosis in the body, the methods for controlling dormant M. tuberculosis include direct killing with drugs, prevention of dormant M. tuberculosis resuscitation with vaccines, and resuscitating dormant M. tuberculosis with preparations or drugs and then thoroughly killing these resuscitated M. tuberculosis by using anti-TB therapy.

CONCLUSIONSThe comprehensive analysis of the above three methods suggests that the drugs directly killing dormant cells are in clinical trials, TMC207 is the most beneficial for controlling TB. Because the side effect of vaccines is less and their action period is long, prevention of dormant cells resuscitation with vaccines is promising. The last control method makes it probable that when a huge number of active cells of M. tuberculosis have been killed and eradicated after 1-month short chemotherapy, only a strong short-term subsequent chemotherapy can completely kill and eradicate the remaining M. tuberculosis. This control strategy is expected to significantly shorten the course of TB chemotherapy and bring a new change and breakthrough in TB treatment.

Antitubercular Agents ; therapeutic use ; Diarylquinolines ; therapeutic use ; Humans ; Latent Tuberculosis ; drug therapy ; Mycobacterium tuberculosis ; pathogenicity ; Tuberculosis ; drug therapy

BACKGROUNDEarly detection of pulmonary tuberculosis (PTB) is a big challenge in smear negative and sputum scarce patients in China. Simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis (MTB) complex (SAT-TB assay) is a novel molecular technique established in our hospital. This method has a high sensitivity and specificity in the lab. In this study, the clinical diagnostic performance of this method in smear-negative or sputum-scarce PTB suspects was investigated and evaluated.

METHODSTwo hundred smear negative and 80 sputum-scarce patients were recruited in this study. Samples that included sputum or bronchial washing fluid were collected and sent for both bacteria culture and SAT-TB assay. Diagnosis for these patients was based on the comprehensive evaluation of chestX- ray/CT study, histology examination, lab results, and treatment response. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each diagnostic test were investigated and calculated using confirmed tuberculosis (TB) and non-TB cases. The time required for detection of MTB was also measured for each method.

RESULTSNinety-two patients (33%) were diagnosed as definitive TB, 112 patients (40%) were probable PTB, and 76 (27%) were non-TB. The sensitivity, specificity, PPV, and NPV of SAT-TB in smear-negative PTB suspects were 93% (95% CI, 84%-98%), 98% (95% CI, 90%-100%), 98% (95% CI, 91%-100%), and 93% (95% CI, 83%-98%). In sputum scarce PTB suspects, the sensitivity, specificity, PPV, and NPV of the SAT-TB assay on bronchial washing fluids were 90% (95% CI, 74%-98%), 100% (95% CI, 85%-100%), 100% (95% CI, 88%-100%), and 88% (95% CI, 69%-97%). The accuracy of the SAT-TB assay is consistent with the bacteria culture assay. The median time required for detecting MTB in the SAT-TB assay was 0.5 day, which was much faster than bacteria culture (28 days).

CONCLUSIONSThe SAT-TB assay is a fast and accurate method for the detection of MTB. It can be widely applied in the clinic and be an asset in early detection and management of PTB suspects, especially in those patients who are smear negative or sputum scarce.

Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; genetics ; pathogenicity ; Nucleic Acid Amplification Techniques ; methods ; Sputum ; microbiology ; Tuberculosis, Pulmonary ; diagnosis ; Young Adult

Along with the rapid spread of HIV / AIDS and TB prevalence, prevention and control of AIDS and tuberculosis has become an urgent problem in the field of public health. Recent studies demonstrate dual infections of HIV and TB are not a simple superposition of two diseases, but a course of mutual promotion. This article has summarized the pathological mechanisms and mutual interactions of HIV/TB dual infections.
Acquired Immunodeficiency Syndrome ; complications ; epidemiology ; prevention & control ; Coinfection ; HIV-1 ; pathogenicity ; Humans ; Mycobacterium tuberculosis ; pathogenicity ; Prevalence ; Public Health ; Tuberculosis ; complications ; epidemiology ; prevention & control

BACKGROUNDDiagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks.

METHODSWe used 12-locus mycobacterial interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects' medical records.

RESULTSAll of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR (DTM-PCR) identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit (MIRU) pattern (232225172531) and the same MIRU pattern (3677235). Strains from family-2 had the same MIRU pattern (2212261553323) and the same MIRU pattern (3685134). Strains from family-3 did not have the same MIRU pattern and they differed at only one locus (223326173533, 223325173533), and did not have the same VNTR pattern with two locus differed (3667233, 3677234).

CONCLUSIONSHousehold transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a family. Household tuberculosis transmission could be prevented with adequate treatment of source patients.

Adult ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Mycobacterium tuberculosis ; classification ; genetics ; pathogenicity ; Radiography ; Tuberculosis, Multidrug-Resistant ; diagnostic imaging ; transmission ; Young Adult

OBJECTIVETo investigate the role of phospholipase C(PLC) in cytoskeleton rearrangement of mouse dendritic cells invaded by Mycobacterium tuberculosis.

METHODSMouse dendritic DC2.4 cells were co-cultured with Mycobacterium tuberculosis H37Rv. F-actin of DC2.4 cells were strained with phalloidin-TRITC, the microtubule was stained with anti-β-tubulin monoclonal antibody and FITC-conjugated AffiniPure anti-mouse IgG. The changes of cytoskeleton in DC2.4 cells induced by Mycobacterium tuberculosis H37Rv were determined by fluorescence microscopy and the rates of F-actin rearrangements were calculated. The expressions of PLC in cytoplasm and cytomembrane of DC2.4 cells were measured by ELISA. DC2.4 cells were pretreated with PLC inhibitor U73122, then F-actin rearrangements induced by invasion of Mycobacterium tuberculosis were observed.

RESULTSBacterial invasion was observed while DC2.4 cells were co-incubated with Mycobacterium tuberculosis H37Rv for 2 h. The rates of invasion were (26.1 ± 4.5)%, (39.9 ± 5.6)%, (51.2 ±5.9)%, (57.9 ± 6.1)% and (63.9 ± 6.8)% at 4, 6, 8, 10 and 12 h of co-culture, respectively; while those were (13.6 ± 3.1)%, (14.2 ± 3.9)%, (15.1 ± 4.3)%, (16.8 ± 4.0)% and (18.3 ± 5.2)% after blocked by PLC, respectively. The rates of the F-actin rearrangements at 2, 4, 6, 8, 10 and 12 h after DC2.4 cells were invaded by H37Rv were (26.9 ± 1.5)%, (59.3 ± 2.8)%, (72.7 ± 4.8)%, (78.2 ± 5.9)%, (63.3 ± 2.9)% and (43.2 ± 2.6)%, respectively; while those were (18.5 ± 1.2)%, (22.3 ± 1.7)%, (3.6 ± 2.5)%, (24.8 ± 2.3)%, (22.3 ± 1.3)% and (23.8 ± 1.8)% after blocked by PLC, respectively. There were no changes of the microtubule observed in DC2.4 cells at the same time points. The rates of the F-actin rearrangements before blocked by PLC were higher than those after PLC blockade at 4, 6, 8 and 10 h (P <0.05). The expressions of PLC in cytomembrane in DC2.4 cells increased after 2 h and reached its highest level at 8 h. The PLC inhibitor U73122 inhibited the expressions of PCL in cytomembrane of DC2.4 cells, but not in cytoplasm.

CONCLUSIONMycobacterium tuberculosis can provoke to F-actin rearrangements through PLC molecule, which would further lead to Mycobacterium tuberculosis invasion of DC2.4 cells.

Actins ; metabolism ; Animals ; Cell Line ; Coculture Techniques ; Cytoskeleton ; metabolism ; Dendritic Cells ; cytology ; microbiology ; Mice ; Microtubules ; metabolism ; Mycobacterium tuberculosis ; pathogenicity ; Type C Phospholipases ; metabolism

PURPOSE: Diagnosis of tuberculosis (TB) in children is more challenging than in adults. This study aimed to describe demographical, clinical and laboratory findings of children diagnosed with tuberculosis in Turkey, including the issues of contact tracing, culture positivity and forms of the disease. MATERIALS AND METHODS: Clinical and laboratory data of 51 children with a mean age of 8.0+/-4.6 years who were diagnosed with TB were retrospectively reviewed. Main diagnostic tools included tuberculin skin test, chest X-ray, sputum/gastric aspirate culture with sensitivity testing, and direct microscopy for acid-fast bacilli on available samples. Clinical characteristics and outcomes of the patients were examined. RESULTS: Thirty-six (70.6%) children were diagnosed with intra-thoracic and 15 (29.4%) with extra-thoracic tuberculosis. Twenty-eight of the patients had a positive Bacillus Calmette-Guerin vaccine scar (28/51, 54.9%) and 23/51 (45.1%) had a positive tuberculin skin test. An adult TB contact was identified in 27 (52.9%) of the cases. On direct microscopy, acid-fast bacilli were found in nine (17.6%) patients and positive culture for Mycobacterium tuberculosis was found in 19 (37.3%). Drug resistance to isoniazid was detected in four (7.8%). One patient with nephrotic syndrome and miliary tuberculosis died during follow-up. All other patients responded well to the treatment. CONCLUSION: Focusing on active contact tracing among all household contacts of tuberculous cases may be helpful in early identification and controlling childhood disease, even in regions with low disease prevalence. Adopting a suspicious and proactive approach in this particular age group is warranted.
Adolescent ; BCG Vaccine/metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Isoniazid/therapeutic use ; Male ; Mycobacterium tuberculosis/pathogenicity ; Retrospective Studies ; Risk Factors ; Tuberculin/metabolism ; Tuberculin Test ; Tuberculosis/*diagnosis/drug therapy/metabolism ; Tuberculosis, Pulmonary/diagnosis/drug therapy/metabolism ; Turkey