A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens. Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost.
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Suspected tuberculosis (TB) patients in Nairobi, Kenya.
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The authors reviewed the literature for side effects of five first-line antituberculous medications (isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin). Incidence of the major side effects were compiled with particular attention to the incidence of isoniazid hepatotoxicity.
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Testing new drugs or drug combinations for activity against tuberculosis is highly problematic: Clinical therapy trials are expensive and time-consuming; animal trial results may not be applicable to humans; and simple in vitro testing on culture medium excludes a vital component of the natural infection, namely the macrophage. Described here is a technique to treat with chemotherapy human macrophages that have been infected ex vivo with tubercle bacilli. Briefly discussed are the results of treating such infected phagocytes with a variety of agents: Streptomycin, ethambutol, pyrazinamide, isoniazid, and ceforanide. Interesting parallels between the macrophage-model results and observed clinical phenomena are noted. This model appears to have considerable potential for evaluating drug activity against tubercle bacilli, nontuberculous mycobacteria, and, perhaps, other intracellular parasites.
To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB.
Management of tuberculosis (TB) is challenging in HIV/TB co-infected children. The World Health Organization (WHO) recommends nucleic acid amplification tests for TB diagnosis, a four-drug regimen including ethambutol during intensive phase of treatment (IP), and initiation of antiretroviral therapy (ART) within eight weeks of TB diagnosis. We investigated TB treatment outcomes by diagnostic modality, IP regimen, and ART status.
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A retrospective chart review was performed on 118 HIV infected patients with pulmonary tuberculosis hospitalized between 1987 and 1996 in a tertiary care center for Infectious Diseases in Rome. The aims of this study were: a) to evaluate global prevalence of and risk factors for drug-resistant Mycobacterium tuberculosis and multidrug resistant tuberculosis; b) to assess trends in prevalence of drug-resistant tuberculosis over the 10-year study period. Prevalence of drug resistance of first Mycobacterium tuberculosis isolates was tested on Lowenstein-Jensen medium with the proportional method. Of the 118 patients studied, 83 had never been treated for tuberculosis and 35 had already been treated for at least 1 month. The overall prevalence of resistance to one or more drugs was 25% (17% in never treated patients vs 46% in already treated patients; p = 0.002). Five percent of isolates were resistant to both isoniazid and rifampin (1% in never treated patients vs 14% in already treated patients; p = 0.008). Resistance rates to individual drugs were: isoniazid 14%, rifampin 8%, ethambutol 0%, streptomycin 13%. During the study period no significant variations in prevalence of drug-resistant tuberculosis were found. In our area, empiric therapy should include 4 drugs: as well as isoniazid, rifampin and pyrazinamide, we recommend ethambutol. Surveillance of drug-resistant tuberculosis is needed. Directly observed therapy should be considered for HIV patients in order to prevent increases in drug resistance, relapses, and treatment failures.
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The mutation at np11778 was identified in 31 cases (39.2%) to establish LHON, which consisted of: all 16 of clinically probable LHON cases, 13 cases (29.5%) of possible LHON, and 2 cases of alcohol amblyopia. The remaining 48 cases were negative for mtDNA mutations at np3460, np11 778, and np14,484.
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Miliary TB is common in Qatar, especially among expatriates. Because the clinical features of the disease are nonspecific, a high index of suspicion is essential for early diagnosis in order avoid delays in therapy and poor outcome.
Tuberculosis remains as a serious infection disease of worldwide distribution, with high morbidity and mortality, mainly in low socio-economic condition countries. The state of emergency of tuberculosis caused by the resistant and multidrug-resistant (MDR) strains, became the main threat to the tuberculosis treatment and control programs. A fast detection method for the resistant strains will allow the implementation of an adequate treatment and contribute for controlling the dissemination of these resistant strains. This study evaluated the performance of the nitrate reductase assay in solid (NRA-LJ) and liquid (NRA-7H9) media, to determine the susceptibility to first line anti-tuberculosis drugs: isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SMR). Both methods NRA-LJ and NRA-7H9 were evaluated among 18 strains with a known susceptibility profile. The resazurin microtiter assay (REMA) was performed as a reference method. One hundred percent of accordance was observed between NRA-7H9 and REMA for the four tested drugs. When the NRA-LJ method was compared to REMA, the sensitivity and the specificity to INH, RMP, EMB and SMR were 100%, 100 %, 85.7%, 76.9% and 80%, 100%, 75% and 80%, respectively. From the 57 clinical isolates of M. tuberculosis evaluated by NRA-7H9 and REMA, 56 (98.2%) were sensitive to all antibiotics tested (INH, RMP, EMB and SMR) by the NRA-7H9 method, while three of these strains were resistant to INH by REMA. One strain showed resistance to INH and RMP for both methods, and MIC of 1.0 μg/ml to INH for both methods, while MIC of 1.0 and 2.0 μg/ml to RMP for REMA and NRA-7H9, respectively. The three assays showed a high level of agreement for rapid detection of rifampicin and isoniazid resistance. Regarding rapidness, the detection of color change in the NRA method is within instants as compared to the overnight incubation required for the REMA test. NRA might represent an inexpensive and alternative assay for rapid detection of resistance in low-income countries.
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Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-γ and IL-12 but positively correlated with IL-10 and TGF-β levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-γ and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206(+) and low CD86(+) macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-β and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-γ, IL-12, IL-10 and TGF-β levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.
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Exfoliative dermatitis to all four first line drugs singly or rarely in combination has been reported. Here we report a rare case of pulmonary tuberculosis with exfoliative dermatitis to all four oral first line antitubercular drugs. (Rifampicin, Isoniazid, Ethambutol, Pyrazinamide). To the best of our knowledge, this is the first such case.
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The summarized sensitivity (95% CI), specificity (95% CI), and AUC (standard error) were 0.869 (0.847-0.890), 0.973 (0.965-0.979) and 0.9690 (0.0188) for fluoroquinolones, 0.868 (0.829-0.900), 0.998 (0.994-0.999) and 0.9944 (0.0050) for amikacin, 0.879 (0.838-0.914), 0.970 (0.958-0.978) and 0.9791 (0.0120) for capreomycin, 0.501 (0.461-0.541), 0.991 (0.983-0.996) and 0.9814 (0.0114) for kanamycin and 0.686 (0.663-0.709), 0.871 (0.852-0.888) and 0.7349 (0.0639) for ethambutol, respectively.