Recombinant M. Tuberculosis Mpt64 Antigen [His]

Background Air pollution and pulmonary tuberculosis (PTB) are still serious worldwide problems, especially in areas of developing countries. Whether there is an association between high ambient air pollutant concentrations and PTB has not been fully explored. Methods Bayesian spatial-temporal models were constructed to analyse the association between ambient air pollutants (particulate matter with aerodynamic diameters of <= 10 mu m (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2)) and PTB incidence, adjusting for socioeconomic covariates. We collected data on pulmonary TB, ambient air pollution (PM10, SO2 and NO2) concentrations and socioeconomic covariates from 17 prefectures in the central Chinese province of Hubei between Jan 1, 2006, and Dec 31, 2015. Results For every annual 10 mu g/m(3) increase in SO2, the relative risk (RR) of PTB incidence was 1.046 (95% credible interval [CI], 1.038-1.054) in the study area. Moreover, we found positive associations with each annual 10 mu g/m(3) increase in ambient air pollutants (PM10, SO2 and NO2) in females but only with SO2 in males. A significant association for each 10 mu g/m(3) increase in SO2 was observed in all the age groups, with a significant association for PM10 only in children under 14 years of age. A significant response relationship was also observed at a 0-1 month moving average lag for each 10 mu g/m(3) increase in SO2. Conclusions High ambient air pollution concentrations in areas of developing countries might increase the risk of regional PTB incidence, especially for women and young people. Precautions and protective measures and efforts to reduce ambient air pollutant concentrations should be strengthened in developing countries.

Background Short-course preventive therapy with 12 doses of once-weekly rifapentine (900 mg) plus isoniazid (900 mg) could greatly improve tuberculosis control, especially in areas with high co-endemicity with HIV. However, a small previous trial of such therapy with dolutegravir in healthy, HIV-negative adults was halted early after two of the four patients developed serious adverse events. Because of the potential use of this therapy, and variable safety outcomes of tuberculosis drugs seen in patients with and without HIV, we aimed to characterise safety, pharmacokinetics, and virological suppression in adults who are HIV positive. Methods DOLPHIN was a phase 1/2, single-arm trial done at The Aurum Institute (Tembisa Clinical Research Site, Tembisa, South Africa), with pharmacokinetic visits done at VxPharma (Pretoria, South Africa). Adults (>= 18 years) with HIV infection and undetectable viral load (<40 copies per mL) after at least 8 weeks of efavirenz-based or dolutegravir-based regimens were recruited in three consecutive groups, subject to approval by the independent safety monitoring committee. Participants received 50 mg of daily dolutegravir in place of efavirenz for 8 weeks, then began once-weekly rifapentine (900 mg)-isoniazid (900 mg) for 12 weeks. Groups 1A (n=12) and 1B (n=18) had intensive dolutegravir pharmacokinetic sampling at week 8 (before rifapentine-isoniazid), at week 11 (after the third dose of rifapentine)-isoniazid and at week 16 after the eighth dose. Group 2 (n=30) were treated with the same schedule and had sparse dolutegravir pharmacokinetic sampling at weeks 8, 11, and 16. Participants were followed 4 weeks after completion of prophylactic tuberculosis treatment. HIV viral loads were measured at baseline and at weeks 11 and 24. Primary endpoints were adverse events (grade 3 or higher) and dolutegravir population pharmacokinetics, assessed in participants who began rifapentine-isoniazid. This trial was registered at ClinicalTrials. gov, NCT03435146. Findings Between Jan 24, 2018, and Nov 25, 2018, 61 participants were enrolled into three groups; one participant withdrew (from group 1A). 43 (70%) of 60 participants were women and all participants were black African. Median age was 40 years (IQR 35-48), CD4 cell count was 683 cells per mu L (447-935), and body-mass index was 28.9 kg/m(2) (24.0-32.9). Three grade 3 adverse events occurred; two elevated creatinine and one hypertension. Rifapentine-isoniazid increased dolutegravir clearance by 36% (relative standard error 13%) resulting in a 26% decrease in dolutegravir area under the curve. Overall geometric mean ratio of trough concentrations with versus without rifapentine-isoniazid was 0.53 (90% CI 0.49-0.56) though this ratio varied by day after rifapentine-isoniazid dose. All but one trough value was above the 90% maximal inhibitory concentration for dolutegravir and HIV viral loads were less than 40 copies per mL in all patients. Interpretation Our results suggest 12 doses of once-weekly rifapentine-isoniazid can be given for tuberculosis prophylaxis to patients with HIV taking dolutegravir-based antiretroviral therapy, without dose adjustments. Further exploration of the pharmacokinetics, safety, and efficacy in children and pharmacodynamics in individuals naive to antiretroviral therapy is needed. Copyright (C) 2020 Elsevier Ltd. All rights reserved.