Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes Higher serum 25-hydroxyvitamin D concentrations are associated with active pulmonary tuberculosis in hospitalised HIV infected patients in a low income tropical setting: a cross sectional study High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. Zinc and vitamin A supplementation fails to reduce sputum conversion time in severely malnourished pulmonary tuberculosis patients in Indonesia Adjunctive micronutrient supplementation for pulmonary tuberculosis. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial Micronutrient supplementation and T cell-mediated immune responses in patients with tuberculosis in Tanzania. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial The effect of multi-vitamin/mineral supplementation on mortality during treatment of pulmonary tuberculosis: a randomised two-by-two factorial trial in Mwanza, Tanzania. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis’ Serum 25-hydroxy-vitamin D3 concentrations increase during tuberculosis treatment in Tanzania. Mobile phone text messaging for promoting adherence to anti-tuberculosis treatment: a systematic review protocol A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis. Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: A phase II trial Forecasting Accuracy of the Hollow Fiber Model of Tuberculosis for Clinical Therapeutic Outcomes. Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment Effect of Short Message Service on Management of Pulmonary Tuberculosis Patients in Anhui Province, China: A Prospective, Randomized, Controlled Study Effect of a Hospital-based Case Management Approach on Treatment Outcome of Patients with Tuberculosis Point-of-care breath test for biomarkers of active pulmonary tuberculosis. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Tuberculosis burden in an urban population: a cross sectional tuberculosis survey from Guinea Bissau
Background The association between pulmonary tuberculosis ( PTB ) and diabetes mellitus ( DM ) has been previously attracted much attention . Diabetes alters immunity to tuberculosis , leading to more frequent treatment failure in TB patients with DM . Moreover , TB and DM often coincide with micronutrients deficiencies , such as retinol and vitamin D , which are especially important to immunity of the body and may influence pancreas β-cell function . However , the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes , immune and nutrition state are still uncertain . We are conducting a r and omized controlled trial of vitamin A and /or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients . Methods / design This is a 2 × 2 factorial trial . We plan to enroll 400 active PTB patients with DM , and r and omize them to VA ( 2000 IU daily retinol ) ; VD ( 400 IU daily cholecalciferol ) ; VAD ( 2000 IU daily retinol plus 400 IU cholecalciferol ) or control ( placebo ) group . Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism , and the secondary outcome measure being immune and nutrition status of the subjects . Of the first 37 subjects enrolled : 8 have been r and omized to VA , 10 to VD , 9 to VAD and 10 to control . To date , the sample is 97.3 % Han Chinese and 91.9 % female . The average fasting plasma glucose level is 12.19 mmol/L. Discussion This paper describes the design and rationale of a r and omized clinical trial comparing VA and /or VD supplementation to active pulmonary TB patients with DM . Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition . This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM.Trial registration Background The inherent risk of developing tuberculosis ( TB ) in HIV- infected individuals is further enhanced by hypovitaminosis D. Interventions that offset HIV-associated immune deterioration potentially arrest disease progression and incidence of opportunistic infections including TB . Despite conflicting reports on association between vitamin D deficiency ( VDD ) and risk of TB , vitamin D ( VD ) supplementation remains a promising intervention . Methods We conducted a comparative cross-sectional study on 145 HIV+/pulmonary TB+ ( PTB ) and 139 HIV+/PTB− hospitalised patients to investigate association of vitamin D status and risk of PTB . Stratified r and om sampling was used to select archived serum specimens from participants enrolled in a r and omised controlled trial ( RCT ) conducted to investigate the impact of using a point-of-care urine lipoarabinomannan strip test for TB diagnosis . PTB status was confirmed using sputum smear microscopy , culture or GeneXpert MTB/RIF .  Serum 25-hydroxyvitamin D [ 25(OH ) D ] concentrations  were assayed by competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment . Effect of VD status on duration of hospital stay and patient outcomes on follow up at 8 weeks were also investigated . Median serum 25(OH ) D concentrations were compared using Mann-Whitney test and covariates of serum VD status were assessed using logistic regression analysis . Results Overall VDD prevalence in the cohort was 40.9 % ( 95 % CI : 35.1–46.8 ) . Median serum 25(OH)D concentrations were significantly higher in HIV+/PTB+ group ( 25.3 ng/ml , IQR:18.0–33.7 ) compared to the HIV+/PTB− group ( 20.4 ng/ml , IQR:14.6–26.9 ) , p = 0.0003 . Patients with serum 25(OH ) D concentration ≥ 30 ng/ml were 1.9 times more likely to be PTB+ compared to those with serum 25(OH ) D concentrations < 30 ng/ml ( odds ratio ( OR ) 1.91 ; 95 % CI 1.1–3.2 ) . PTB-related death was associated with higher odds of having 25(OH ) D levels≥30 ng/ml . Age , gender , CD4 + count , combination antiretroviral therapy ( cART ) status , efavirenz based cART regimen and length of hospital stay were not associated with vitamin D status . Conclusions The finding of an association between higher serum 25(OH ) D concentrations and active PTB and TB-related mortality among hospitalised HIV-infected patients in the present study is at variance with the commonly reported association of hypovitaminosis and susceptibility to TB . Our findings though , are in concordance with a small pool of reports from other setting BACKGROUND Tuberculosis , including multidrug-resistant tuberculosis ( MDR-TB ) , is a major global health problem . Individuals with tuberculosis disease commonly exhibit vitamin D deficiency , which may adversely affect immunity and the response to therapy . OBJECTIVE We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease . DESIGN The study was a double-blind , r and omized , placebo-controlled , intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi , Georgia . Subjects were r and omly assigned to receive oral vitamin D3 [ 50,000 IUs ( 1.25 mg ) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk ] or a placebo concomitant with st and ard first-line antituberculosis drugs . The primary outcome was the time for the conversion of a Mycobacterium tuberculosis ( Mtb ) sputum culture to negative . RESULTS Baseline characteristics between groups were similar . Most subjects ( 74 % ) were vitamin D deficient ( plasma 25-hydroxyvitamin D [ 25(OH)D ] concentration < 50 nmol/L ) . With vitamin D3 , plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16 . Adverse events and plasma calcium concentrations were similar between groups . In 192 subjects with culture-confirmed tuberculosis , an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [ 29 and 27 d , respectively ; HR : 0.86 ; 95 % CI : 0.63 , 1.18 ; P = 0.33 ) . Eight-week culture-conversion rates were also similar ( 84.0 % and 82.1 % for vitamin D3 and placebo , respectively ; P = 0.99 ) . CONCLUSION A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort . This trial was registered at clinical trials.gov at NCT00918086 Background A previous study showed that combination of zinc and vitamin A reduced sputum conversion time in pulmonary tuberculosis ( TB ) patients . Objective We studied the efficacy of which single micronutrient contributed more to the sputum conversion time . Methods In a double-blind r and omized community trial , newly sputum smear positive pulmonary TB patients were assigned r and omly to receive zinc , vitamin A , zinc + vitamin A or placebo on top of TB treatment . Patients were asked to deliver their sputum on weekly basis to measure positivity of the bacteria . Nutritional status , chest x-ray , hemoglobin , C-reactive protein ( CRP ) , retinol and zinc level were examined prior to , after 2 and 6 months of treatment . Results Initially , 300 patients were enrolled , and 255 finished the treatment . Most patients were severely malnourished ( mean BMI 16.5 ± 2.2 Kg/m2 ) . Patients in the zinc + vitamin A group showed earlier sputum conversion time ( mean 1.9 weeks ) compared with that in the other groups ; however the difference was not significant . Also , no benefit could be demonstrated of any of the used supplementations on clinical , nutritional , chest x-ray , or laboratory findings . Conclusions This study among severely malnourished TB patients , did not confirm that single or combined supplementation of zinc and vitamin A significantly reduced sputum conversion time or had other significant benefit OBJECTIVE To assess the effect of micronutrient supplementation on tuberculosis ( TB ) patient outcomes . MATERIAL AND METHODS The r and omized , double-blinded , placebo-controlled study was conducted in pulmonary TB patients undergoing directly observed treatment short course/ tratamiento acortado estrictamente supervisado ( TAES/ DOTS ) at IMSS in Ciudad Juarez , Chihuahua , Mexico , who were recruited during August 2005-July 2006 . Consecutive patients received zinc and vitamin A supplements or matched placebo for four months . Dietary intake , blood zinc and vitamin A , immune response ( IFN-gamma , TNF-alpha , and IL-10 mRNA ) , and sputum smear conversion were measured . RESULTS The proportion of micronutrient compared to placebo group subjects with a negative sputum smear by month 3 was significantly increased ( p= 0.03 ) . This occurred subsequent to increased TNF-alpha and IFN-gamma and decreased IL-10 observed at month 2 . Micronutrient supplementation appeared to accelerate the beneficial therapeutic effect of chemotherapy . CONCLUSIONS The earlier elimination of bacilli from sputum was associated with improved zinc status and Th1 immune response . The therapeutic effect of vitamin A was less evident Background Development of new tuberculosis ( TB ) drugs and alternative treatment strategies are urgently required to control the global spread of TB . Previous results have shown that vitamin D3 ( vitD3 ) and 4-phenyl butyrate ( PBA ) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects . Objective To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to st and ard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients . Methods Adult TB patients ( n = 288 ) were enrolled in a r and omized , double-blind , placebo-controlled  trial conducted in Bangladesh . Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8 . Clinical assessment s and sputum smear microscopy were performed weekly up to week 4 , fortnightly up to week 12 and at week 24 ; TB culture was performed at week 0 , 4 and 8 ; concentrations of LL-37 in cells , 25-hydroxyvitamin D3 ( 25(OH)D3 ) in plasma and ex vivo bactericidal function of monocyte-derived macrophages ( MDM ) were determined at week 0 , 4 , 8 , 12 and additionally at week 24 for plasma 25(OH)D3 . Results At week 4 , 71 % ( 46/65 ) of the patients in the PBA+vitD3-group ( p = 0.001 ) and 61.3 % ( 38/62 ) in the vitD3-group ( p = 0.032 ) were culture negative compared to 42.2 % ( 27/64 ) in the placebo-group . The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group ( p = 0.001 ) and 2.2 times higher in vitD3-group ( p = 0.032 ) compared to placebo . The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 ( p = 0.034 ) . Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo ( log rank 11.38 , p = 0.01 ) . Conclusion Adjunct therapy with PBA+vitD3 or vitD3 or PBA to st and ard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB . Trial Registration clinical trials.gov Limited studies exist regarding whether incorporating micronutrient supplements during tuberculosis ( TB ) treatment may improve cell-mediated immune response . We examined the effect of micronutrient supplementation on lymphocyte proliferation response to mycobacteria or T-cell mitogens in a r and omized trial conducted on 423 patients with pulmonary TB . Eligible participants were r and omly assigned to receive a daily dose of micronutrients ( vitamins A , B-complex , C , E , and selenium ) or placebo at the time of initiation of TB treatment . We found no overall effect of micronutrient supplements on lymphocyte proliferative responses to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV-positive TB patients . Of HIV-negative TB patients , the micronutrient group tended to show higher proliferative responses to concanavalin A than the placebo group , although the clinical relevance of this finding is not readily notable . The role of nutritional intervention in this vulnerable population remains an important area of future research Background Vitamin D ( vitD ) and L-arginine have important antimycobacterial effects in humans . Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis ( TB ) . Methods In a 4-arm r and omised , double-blind , placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis ( PTB ) in Timika , Indonesia , we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo , and L-arginine 6.0 g daily or matching placebo , for 8 weeks , on proportions of participants with negative 4-week sputum culture , and on an 8-week clinical score ( weight , FEV1 , cough , sputum , haemoptysis ) . All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned . Adults with new smear-positive PTB were eligible . The trial was registered at Clinical Trials.gov NCT00677339 . Results 200 participants were enrolled , less than the intended sample size : 50 received L-arginine + active vitD , 49 received L-arginine + placebo vit D , 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model , 99 people received arginine , 101 placebo arginine , 101 vitamin D , 99 placebo vitamin D. Results for the primary endpoints were available in 155 ( 4-week culture ) and 167 ( clinical score ) participants . Sputum culture conversion was achieved by week 4 in 48/76 ( 63 % ) participants in the active L-arginine versus 48/79 ( 61 % ) in placebo L-arginine arms ( risk difference −3 % , 95 % CI −19 to 13 % ) , and in 44/75 ( 59 % ) in the active vitD versus 52/80 ( 65 % ) in the placebo vitD arms ( risk difference 7 % , 95 % CI −9 to 22 % ) . The mean clinical outcome score also did not differ between study arms . There were no effects of the interventions on adverse event rates including hypercalcaemia , or other secondary outcomes . Conclusion Neither vitD nor L-arginine supplementation , at the doses administered and with the power attained , affected TB outcomes . Registry Clinical Trials.gov . Registry number : Malnutrition is common in pulmonary tuberculosis ( TB ) , and may impair survival . The objective of this study was to assess effects of multi-vitamin/mineral ( MVM ) and zinc ( Zn ) supplementation during TB treatment on mortality . Patients diagnosed with sputum-positive pulmonary TB in Mwanza , Tanzania , were r and omised , using a two-by-two factorial design , to Zn ( 45 mg ) or placebo , and MVM ( vitamins A , B , C , D , E , and selenium and copper ) or placebo .  Survival status was ascertained at the end of the 8-month TB treatment and supplementation period . Of 499 TB patients , 213 ( 43 % ) had HIV . The mean weight gain at 7 months was 6.88 kg ( 95 % CI 6.36 , 7.41 ) . Zn and MVM combined , but neither alone ( interaction , P=0.03 ) , increased weight gain by 2.37 kg ( 95 % CI 0.91 , 3.83 ) , irrespective of HIV status . Survival status at 8 months was determined for 422 patients ( 84.6 % ) , of which fifty-two ( 12.3 % ) had died . Among fifty-two deaths , there were no effects of MVM ( relative risk ( RR ) 0.73 ; 95 % CI 0.43 , 1.23 ) and Zn ( RR 0.76 ; 95 % CI 0.46 , 1.28 ) . However , among HIV co-infected patients , marginally significant effects of both MVM ( RR 0.60 ; 95 % CI 0.34 , 1.05 ) and Zn ( RR 0.63 , 95 % CI 0.37 , 1.08 ) were seen , and MVM and Zn combined reduced mortality ( RR 0.29 ; 95 % CI 0.10 , 0.80 ; interaction ratio 0.52 ) . In conclusion , supplementation with MVM , including Zn , during treatment of pulmonary TB may reduce mortality in those co-infected with HIV . A r and omised trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding RATIONALE Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis . OBJECTIVES To test whether vitamin D supplementation of patients with tuberculosis ( TB ) improved clinical outcome and reduced mortality . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau . We included 365 adult patients with TB starting antituberculosis treatment ; 281 completed the 12-month follow-up . The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment . MEASUREMENTS AND MAIN RESULTS The primary outcome was reduction in a clinical severity score ( TBscore ) for all patients with pulmonary TB . The secondary outcome was 12-month mortality . No serious adverse effects were reported ; mild hypercalcemia was rare and present in both arms . Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo .  Overall mortality was 15 % ( 54 of 365 ) at 1 year of follow-up and similar in both arms ( 30 of 187 for vitamin D treated and 24 of 178 for placebo ; relative risk , 1.19 [ 0.58 - 1.95 ] ) . HIV infection was seen in 36 % ( 131 of 359 ) : 21 % ( 76 of 359 ) HIV-1 , 10 % ( 36 of 359 ) HIV-2 , and 5 % ( 19 of 357 ) HIV-1 + 2 . CONCLUSIONS Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB ; it is possible that the dose used was insufficient . Clinical trial registered with www.controlled-trials.com/is rct n ( IS RCT N35212132 ) Background Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma ( IFN-g ) and reducing disease associated inflammation in the host . The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis ( TB ) could influence recovery . Methods Two hundred and fifty nine patients with pulmonary TB were r and omized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses . Assessment s were performed at 4 , 8 and 12 weeks . Early secreted and T cell activated 6 kDa ( ESAT6 ) and Mycobacterium tuberculosis sonicate ( MTBs ) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks . Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student ’s t-test and Chi2 tests . Results After 12 weeks , the vitamin D supplemented arm demonstrated significantly greater mean weight gain ( kg ) + 3.75 , ( 3.16 – 4.34 ) versus + 2.61 ( 95 % CI 1.99 – 3.23 ) p 0.009 and lesser residual disease by chest radiograph ; number of zones involved 1.35 v/s 1.82 p 0.004 ( 95 % CI 0.15 , 0.79 ) and 50 % or greater reduction in cavity size 106 ( 89.8 % ) v/s 111 ( 94.8 % ) , p 0.035 . Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘ Deficient ’ 25-hydroxyvitamin D serum levels ( p 0.021 ) . Conclusions Supplementation with high doses of vitamin D accelerated clinical , radiographic improvement in all TB patients and increased host immune activation in patients with baseline ‘ Deficient ’ serum vitamin D levels . These results suggest a therapeutic role for vitamin D in the treatment of TB.Trial registration Clinical Trials.gov ; No. NCT01130311 ; URL : clinical SETTING Vitamin D deficiency is associated with susceptibility to active tuberculosis ( TB ) in many setting s. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs , isoniazid and rifampicin , reduce 25-hydroxy vitamin D ( 25[OH]D ) concentrations . OBJECTIVE To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB ( PTB ) . DESIGN We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment . RESULTS Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment ( median increase 6.0 nmol/l , IQR -0.7 - 25.0 , P = 0.001 ) . Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l ( median increase 0.46 , IQR -0.2 - 1.1 , P < 0.001 ) . CONCLUSION 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania . Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations Background In 2010 , there were approximately 8.8 million incident cases of tuberculosis ( TB ) worldwide . The treatment of TB is at least six months long and may be complicated by a high pill burden . In addition , TB patients often do not take their medication on schedule simply because they forget . Mobile phone text messaging has the potential to help promote TB treatment adherence . We , therefore , propose to conduct a review of current best evidence for the use of mobile phone text messaging to promote patient adherence to TB treatment . Methods This is a systematic review of the literature . We will preferably include r and omized controlled trials ( RCTs ) . However , non-r and omized studies ( NRS ) will be considered if there is an inadequate number of RCTs .We will search PubMed , EMBASE , CINAHL , CENTRAL , Science Citation Index , Africa-Wide Information , and WHOLIS electronic data bases for eligible studies available by 30 November 2012 regardless of language or publication status . We will also check reference lists for additional studies , identify abstract s from conference proceedings and communicate with authors for any relevant material .At least two authors will independently screen search outputs , select studies , extract data and assess the risk of bias ( using separate criteria for RCTs and NRS ) ; resolving discrepancies by discussion and consensus . We will assess clinical heterogeneity by examining the types of participants , interventions and outcomes in each study and pool studies judged to be clinical ly homogenous . We will also assess statistical heterogeneity using the chi-square test of homogeneity and quantify it using the I-square statistic . If study results are found to be statistically homogeneous ( that is heterogeneity P > 0.1 ) , we will pool them using the fixed-effect meta- analysis . Otherwise , we will use r and om-effects meta- analysis . We will calculate risk ratios and their corresponding 95 % confidence intervals for dichotomous outcomes , and mean differences for continuous outcomes . For other outcomes without quantitative data , a descriptive analysis will be used . Discussion Our results can be used by research ers and policy-makers to help inform them of the efficacy of mobile phone text messaging interventions to promote patient adherence to TB treatment BACKGROUND Tuberculosis ( TB ) often coincides with nutritional deficiencies . The effects of micronutrient supplementation on TB treatment outcomes , clinical complications , and mortality are uncertain . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of micronutrients ( vitamins A , B complex , C , and E , as well as selenium ) in Dar es Salaam , Tanzania . We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months . RESULTS Micronutrients decreased the risk ofTB recurrence by 45 % overall ( 95 % confidence interval [ CI ] , 7 % to 67 % ; P = .02 ) and by 63 % in HIV-infected patients ( 95 % CI , 8 % to 85 % ; P = .02 ) . There were no significant effects on mortality overall ; however , we noted a marginally significant 64 % reduction of deaths in HIV-negative subjects ( 95 % CI , -14 % to 88 % ; P = .08 ) . Supplementation increased CD3 + and CD4 + cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients . Micronutrients reduced the incidence of peripheral neuropathy by 57 % ( 95 % CI , 41 % to 69 % ; P < .001 ) , irrespective of HIV status . There were no significant effects on weight gain , body composition , anemia , or HIV load . CONCLUSIONS Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania Background This study aim ed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis ( TB ) . Material / Methods A phase II trial was performed in 158 patients with pulmonary TB ( 145 initially-treated and 13 re-treated ) and 133 healthy subjects . Skin testing was carried out by injecting purified protein derivative ( PPD ) ( on left forearm ) or recombinant ESAT-6 protein at a dosage of 2 , 5 , or 10 μg/mL ( on the right forearm ) in each subject . Reaction activity and adverse events were monitored at 24 , 48 , and 72 h following the injection . Receiver operating characteristic curves were plotted to determine the areas under the curves ( AUCs ) and the cut-off in duration diameters for the optimal diagnostic performance . Results The reaction activity was significantly increased upon recombinant ESAT-6 injection in pulmonary TB patients compared with healthy subjects . In pulmonary TB patients , the reaction was dose-dependent , and at 48 h , 10 μg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD . The AUCs for a 10 μg/mL dosage were 0.9823 , 0.9552 , and 0.9266 for 24 h , 48 h , and 72 h , respectively , and the in duration diameters of 4.5–5.5 mm were the optimal trade-off values between true positive rates and false positive rates . No serious adverse events occurred in any subjects . Conclusions Recombinant ESAT-6 protein  is efficacious and safe for diagnosing pulmonary TB . Based on the reaction , performance , safety , and practicability , we recommend that 10 μg/mL at 48 h with an in duration cut-off value of 5.0 mm be used BACKGROUND The hollow fiber system model of tuberculosis ( HFS-TB ) , in t and em with Monte Carlo experiments , represents a drug development tool ( DDT ) with the potential for use to develop tuberculosis treatment regimens . However , the predictive accuracy of the HFS-TB , or any other non clinical DDT such as an animal model , has yet to be robustly evaluated . METHODS To avoid hindsight bias , a literature search was performed to identify clinical studies published at least 6 months after HFS-TB experiments ' quantitative predictions . Steps to minimize bias and for reporting systematic review s were applied as outlined in the Preferred Reporting Items for Systematic Review s and Meta-Analyses . Publications were scored for quality of evidence . Accuracy was calculated using the mean absolute percentage error , then summated with weighting assigned by sample size and quality -of- evidence score . Given the lack of a gold-st and ard tuberculosis DDT , the forecasting accuracy of a completely unreliable tool was also calculated from 1000 simulated experiments for a r and om or " total guesswork " model . RESULTS The quantitative forecasting accuracy ( 95 % confidence interval [ CI ] ) for the " total guesswork " model was 15.6 % ( 95 % CI , 8.7%-22.5 % ) ; bias was -0.1 % ( 95 % CI , -2.5 % to 2.2 % ) . Twenty clinical studies were published after HFS-TB experiments predicted optimal drug exposures and doses , susceptibility breakpoints , and optimal combination regimens . Based on these clinical studies , the predictive accuracy of the HFS-TB was 94.4 % ( 95 % CI , 84.3%-99.9 % ) , and bias was 1.8 % ( 95 % CI , -13.7 % to 6.2 % ) . CONCLUSIONS The HFS-TB model is highly accurate at forecasting optimal drug exposures , doses , and dosing schedules for use in the clinic Background Tuberculosis ( TB ) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common . Evidence for tuberculosis treatment in children is largely extrapolated from adult studies . Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months . New paediatric , fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries , making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible . The safety and efficacy of these higher drug doses has not been systematic ally assessed in large studies in children , and the pharmacokinetics across children representing the range of weights and ages should be confirmed . Methods / design SHINE is a multicentre , open-label , parallel-group , non-inferiority , r and omised controlled , two-arm trial comparing a 4-month vs the st and ard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses . We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB , with or without HIV infection . The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post r and omisation and grade 3 or 4 adverse events . Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations , providing model-based predictions for optimal dosing , and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children . Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations . Discussion Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful , the question has never been addressed in children , who have mainly paucibacillary , non-severe smear-negative disease . SHINE should inform whether treatment-shortening of drug-susceptible TB in children , regardless of HIV status , is efficacious and safe . The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in setting s with a high burden of TB . A positive result from this trial could simplify and shorten treatment , improve adherence and be cost-saving for many children with TB.Recruitment to the SHINE trial begun in July 2016 ; results are expected in 2020.Trial registration International St and ard R and omised Controlled Trials Number : IS RCT N63579542 , 14 October 2014.Pan African Clinical Trials Registry Number : PACTR201505001141379 , 14 May 2015 . Clinical Trial Registry-India , registration number : CTRI/2017/07/009119 , 27 July 2017 Calcidiol , the major circulating metabolite of vitamin D , supports induction of pleiotropic antimicrobial responses in vitro . Vitamin D supplementation elevates circulating calcidiol concentrations , and thus has a potential role in the prevention and treatment of infection . The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported . To characterize these effects , we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were r and omized to receive adjunctive high-dose vitamin D or placebo in a clinical trial , and who fulfilled criteria for per- protocol analysis . Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia , monocytosis , hypercytokinaemia , and hyperchemokinaemia . Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses , but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4 , CC chemokine lig and 5 , and IFN-α . We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment . Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality Background To explore the significance of short message service ( SMS ) on the management of pulmonary tuberculosis ( TB ) patients in reinforcing the treatment adherence and health awareness , and provide scientific evidence s for popularizing this model and formulating related polices and measures . Material / Methods Six counties ( districts ) were selected by stratified cluster sampling method , and r and omly divided into control group and intervention group . Pulmonary TB patients eligible to the study criteria were included in the study .  SMS management and regular education of core knowledge about pulmonary TB were carried out in SMS group patients . The conventional directly observed therapy ( DOT ) was carried out in control group . Data was collected by question naire method . Results A total of 350 patients were included in the study , including 160 cases in the SMS group and 190 cases in the control group . There were 270 males ( 77.1 % ) and 80 females ( 22.9 % ) .  The treatment completion rate in SMS group ( 96.25 % ) was significantly higher than that in the control group ( 86.84 % ) ( χ2=9.52 , P=0.002 ) . Both the interrupted treatment rate and the missed dose rate in the SMS group were significantly lower than those in the control group ( χ2=10.41 , P=0.001 ; χ2=28.54 , P<0.001 ) . After a period of treatment , the reexamination rate of SMS group patients was significantly higher than that in control group ( except the reexamination rate after 5 months treatment ) . Conclusions The management of pulmonary TB patients by SMS can effectively reinforce the completed treatment rate of pulmonary TB patients and reduce their missed dose rate and interrupted treatment rate , and further enhance their reexamination awareness . Therefore , SMS on the management of patients may be a new promising therapeutic strategy for pulmonary TB Background / Purpose Tuberculosis ( TB ) continues to pose a heavy public health burden in Taiwan . This prospect i ve study analyzed the factors influencing treatment outcome in patients with TB treated with and without a hospital-based case management ( HBCM ) approach in a referral center in Taipei . Methods A register-based cohort study design was used to enroll all new cases of pulmonary or extra-pulmonary TB from February 2003 to January 2004 . The case manager served as the coordinator among patients , physicians and public health nurses , to facilitate compliance with anti-TB treatment . Treatment outcomes were assessed according to the consensus recommendations of the World Health Organization and the International Union Against Tuberculosis and Lung Disease . Results Suspected or confirmed pulmonary or extrapulmonary TB was diagnosed in 524 patients in our hospital from February 2003 to January 2004 . Fifty-two of these patients were excluded due to duplicate reporting , previous treatment or death before enrollment . Out of 472 patients enrolled , 103 whose original diagnosis was revised were further excluded , leaving 369 cases eligible for analysis . Patients with case management had a significantly higher rate of successful treatment ( cured plus completed treatment ) compared to patients without case management , ( 240/277 , 86.6 % vs. 67/92 , 72.8 % ; p = 0.002 ) . The overall successful treatment rate including both case and non-case management was 83.2 % ( 307/369 ) , which was higher than the nationwide surveillance data of 78.3 % in 2002 and 69.4 % in 2003 . Conclusion Treatment of TB patients by a HBCM approach provides improved treatment outcomes compared to those without case management RATIONALE Volatile organic compounds ( VOCs ) in breath provide biomarkers of tuberculosis ( TB ) because Mycobacterium tuberculosis manufactures VOC metabolites that are detectable in the breath of infected patients . OBJECTIVES We evaluated  breath VOC biomarkers in subjects with active pulmonary TB , using an internet-linked rapid point-of-care breath test . METHODS 279 subjects were studied at four centers in three countries , Philippines , UK , and India , and data was analyzed from 251 ( 130 active pulmonary TB , 121 controls ) . A point-of-care system collected and concentrated breath and air VOCs , and analyzed them with automated thermal desorption , gas chromatography , and surface acoustic wave detection . A breath test was completed in 6 min . Chromatograms were converted to a series of Kovats Index ( KI ) windows , and biomarkers of active pulmonary TB were identified by Monte Carlo analysis of KI window alveolar gradients ( abundance in breath minus abundance in room air ) . MEASUREMENTS AND MAIN RESULTS Multiple Monte Carlo simulations identified eight KI windows as biomarkers with better than r and om performance . Four KI windows corresponded with KI values of VOCs previously identified as biomarkers of pulmonary TB and metabolic products of M. tuberculosis , principally derivatives of naphthalene , benzene and alkanes . A multivariate predictive algorithm identified active pulmonary TB with 80 % accuracy ( area under curve of receiver operating characteristic curve ) , sensitivity=71.2 % , and specificity = 72 % . Accuracy increased to 84 % in age-matched subgroups . In a population with 5 % prevalence , the breath test would identify active pulmonary TB with 98 % negative predictive value and 13 % positive predictive value . CONCLUSIONS A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB AIM to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement , nutritional status , sputum conversion , and radiological improvement . METHODS sixty seven tuberculosis patient visiting the Pulmonary Clinic , of Cipto Mangunkusumo Hospital , Jakarta , from January 1st to August 31st , 2001 were included in this study . The subjects were r and omised to receive vitamin D ( 0.25 mg/day ) or placebo in a double blind method , during the 6th initial week of Tb treatment . The rate of sputum conversion , complete blood counts , blood chemistry as well as radiologic examination were evaluated . RESULTS there were more male patients than females ( 39:28 ) , 78.7 % were in the productive age group , 71.6 % had low nutritional status , 62.4 % with low education level , and 67.2 % with low income . One hundred percent of the vitamin D group and only 76.7 % of the placebo group had sputum conversion . This difference is statistically significant ( p=0.002 ) . CONCLUSION the sputum conversion had no correlation with the hemoglobin level , blood clotting time , calcium level , lymphocyte count , age , sex , and nutritional status . There were more subjects with radiological improvement in the vitamin D group Background Little is known about the prevalence of  pulmonary tuberculosis ( TB ) in low income countries . We conducted a cross sectional survey for pulmonary TB and TB symptoms in Bissau , Guinea-Bissau , in an urban cohort with known HIV prevalence . TB surveillance in the area is routinely based on passive case finding . Methods Two cohorts were selected based on a previous HIV survey , but only 52.5 % of those enrolled in the adult cohort had participated in the HIV survey . One cohort included all adults living in 384 r and omly selected houses ; in this cohort 8 % ( 135/1687 ) were HIV infected . The other included individuals 50 years or older from all other houses in the study area ; of these 11 % ( 62/571 ) were HIV infected . Symptom screening was done through household visits using a st and ardised question naire . TB suspects were investigated with sputum smear microscopy and X-ray . Results In the adult cohort , we found 4 cases among 2989 individuals screened , giving a total TB prevalence of 134/100,000 ( 95 % CI 36 - 342/100,000 ) . In the > 50 years cohort , we found 4 cases among 571 individuals screened , giving a total prevalence of 701/100,000 ( 191 - 1784/100.000 ) . Two of the eight detected TB cases were unknown by the TB program . Of the total TB cases five were HIV uninfected while three had unknown HIV status . The prevalence of TB symptoms was 2.1 % ( 63/2989 ) and 10.3 % ( 59/571 ) in the two cohorts respectively . Conclusions In conclusion we found a moderately high prevalence of pulmonary TB and TB symptoms in the general population , higher among elderly individuals . By active case finding unknown cases were detected . Better awareness of TB and its symptoms needs to be promoted in low income setting
Conclusion Vitamin D supplementation showed no influence on the improvement of sputum smear-negative conversion rates and BMI , as well as the decrease in ESR
Background Vitamin D might be promising to serve as an adjunctive therapy for pulmonary tuberculosis ( TB ) .
However , the results remained controversial .
We conducted a systematic review and meta- analysis to evaluate the efficacy and safety of vitamin D in patients with pulmonary TB .