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The literature review suggested that the audio signal-modified shuttle walk test (SWTSR) was equally reliable and valid when compared to the conventional shuttle walk test. A comparison of SWTSR with the six-minute walk test (6MWT), which is considered the gold standard in walk tests, allowed us to evaluate the SWTSR and determine its validity and reliability as an alternative or supplement to the 6MWT. The objective of this study was to determine the correlation between the distances walked during a SWTSR and the 6MWT in healthy, normal adults. The study recruited 42 healthy normal adults who underwent 6MWT and SWTSR on the same day. The correlation was assessed by Pearson’s correlation coefficient, and agreement between the tests was assessed using a Bland-Altman plot. Additionally, the acceptability of the modified test in comparison to the 6MWT was assessed by the Likert scale. The distances walked (mean ± standard deviation) in the 6MWT and SWTSR were 693.8±58.3 and 951.4±139.7 m, respectively (Pearson’s correlation coefficient of 0.918). The distance covered by the study participants in the 6MWT and SWTSR showed a strong correlation with spirometry results. The SWTSR induced a greater physiological response compared to the 6MWT. The acceptability of the SWTSR was comparable to that of the 6MWT. The distance walked in the SWTSR shows a strong positive correlation with the 6MWT and has comparable acceptability with the 6MWT. The SWTSR may provide a better index of the patient’s ability for his activities of daily living and may be a better measure for studying exercise tolerance than the 6MWT in certain clinical settings.

COVID-19 affected millions of people worldwide, and tuberculosis (TB) continues to affect millions of people each year. The combined pandemic of COVID-19 and TB had a catastrophic effect on healthcare policies and healthcare setups around the globe. The clinical profile and factors affecting the outcome of COVID-19 disease in TB patients on treatment in field conditions have not been studied in detail. The present study attempted to study the occurrence of COVID-19 among patients on TB treatment in terms of severity of COVID-19 disease and outcome of both COVID-19 and TB in patients at National Tuberculosis Elimination Program treatment centers over a period of one year during peak COVID-19 times. Out of 1400 TB patients enrolled, 65 (5%) suffered from COVID-19 disease. Of the 65 TB patients with COVID-19 disease, 37 (57%) were male and under 45 years old, 33 (51%) had a TB diagnosis after first receiving a COVID-19 diagnosis, 29 (45%) had a TB diagnosis first, and received anti-TB treatment before receiving a COVID-19 diagnosis, and only 3 patients (5%) had a COVID-19 and TB diagnosis concurrently. The majority of 59 (91%) patients had mild COVID-19 disease. The outcome of TB treatment was available in 25 patients out of these 65 COVID-19-positive patients, with 21 (84%) patients having a favorable outcome. Out of the 65 COVID-19-positive patients, 4/25 (16%) had unfavorable outcomes, with one patient (4%) failing TB treatment and two patients (8%) dying. This is the first study from India that studied the occurrence and course of COVID-19 among a large number of TB patients taking anti-TB treatment under programmatic conditions. Due to the similarity in symptoms of TB and certain viral respiratory illnesses, a protocol should be established for health care to check patients for both illnesses.

This study was carried out to assess the role of therapeutic drug monitoring of crucial first-line anti-tubercular drugs: rifampicin (R) and isoniazid (H) among 75 non-responding proven drug-sensitive tuberculosis patients on treatment followed by intervention in field conditions. The intervention was done in the form of either an increase in the dosage of R and H in patients with minimally low drug levels or a modification of the regimen in a certain group of patients with significantly low drug levels by augmenting it with three or four second-line drugs in addition to standard first-line drugs. This study also aimed to determine the relationship between the measured plasma concentration of anti-tubercular drugs and various demographic, microbiological, radiological, and malabsorption factors and the presence of co-morbidities affecting them. The study also focused on the clinical impact of the intervention for low plasma levels of anti-TB drugs on TB treatment outcomes. In our study overall, 85.5% of patients had low levels of any drug. In 85.3% of patients, R levels were low, and in 39.1%, H levels were low. On univariate analysis, low body mass index (BMI), hypoalbuminemia, bilateral disease on chest X-rays, and the presence of cavities were found to be significantly associated with low drug levels, while none of the factors were independently significantly associated. Low BMI, pulmonary tuberculosis and disseminated tuberculosis, far-advanced disease and bilateral disease on chest X-ray, presence of cavities, and only low R levels were associated with unfavorable outcomes, with none of the factors found to be significant on multivariate analysis. In our study, it was seen that the treatment outcome was favorable in 59.6% of patients in whom this intervention was done by augmenting the treatment regimen with three/four second-line drugs along with increasing the dose of R and H. To conclude, various factors may be associated with low plasma levels of anti-tubercular drugs. If such patients show clinical non-response after >6 months of treatment and have significantly low drug levels, with an absence of drug resistance, their treatment regimen may need augmentation with three/four second-line drugs along with an increase in the dose of R and H, which may lead to a favorable outcome.

Background The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. Methods This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15–60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. Results A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. Conclusions The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. Trial registration CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) is a significant burden on global tuberculosis (TB) prevention and eradication efforts. MDR-TB can be treated, but it is expensive, takes a long time (typically two years), and contains potentially toxic drugs. Under certain conditions, the WHO recommends standard regimens lasting 9 to 11 months rather than individual regimens lasting at least 18-20 months. The current study sought to identify factors associated with treatment outcome in RR/MDR-TB patients receiving an injection-based regimen for 9-11 months. This ambispective (prospective and retrospective) observational study was conducted at a tertiary tuberculosis institute in New Delhi, India. Between February 2021 and March 2022, patients with RR/MDR-pulmonary TB who received an injection-based shorter regimen were enrolled. Factors related to treatment outcome were investigated and compared in patients who had a successful outcome versus those who did not. A total of 55 patients were enrolled, with 50.91% being successful (cured/treatment completed) and 49.09% failing (including failure, lost to follow up, death, and regimen changed). The following factors were significantly associated with the unsuccessful outcome, according to univariate analysis: BMI (18.5 kg/m2), anaemia, previous anti-TB treatment, bilateral chest X-ray involvement, and far advanced disease on chest X-ray BMI (18.5 kg/m2), anaemia, and far advanced disease on chest X-ray were all significantly associated with mortality. Anaemia was associated with an unsuccessful outcome (p=0.049) and mortality (p=0.048) in the multiple logistic regression analysis. Early treatment initiation, improved nutrition and anaemia, and regular monitoring can all improve RR/MDR-TB patients' outcomes and prognoses.

Introduction Drug-resistant tuberculosis (DR-TB) is a global public health problem. Patients suffer for months if undiagnosed or treated inadequately, transmitting DR-TB in the community before succumbing to the disease. Early diagnosis, prompt treatment initiation and completion play a significant role in treatment success. However, extended regimens with injectable result in poor treatment adherence and outcomes. Our objective is to evaluate the effectiveness, safety and tolerability of various doses and duration of linezolid (LZD) in combination with bedaquiline (BDQ) and pretomanid (Pa) after 26 weeks of treatment in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary TB.Methods and analysis A multicentric, randomised pragmatic clinical trial in India will enrol participants in one of the three arms—control arm (arm 1): BDQ, Pa and LZD 600 mg daily for 26 weeks or intervention arms (arm 2): BDQ, Pa and LZD 600 mg for 9 weeks followed by 300 mg for 17 weeks or arm 3: BDQ, Pa and LZD 600 mg for 13 weeks followed by 300 mg for 13 weeks. The primary endpoint is the proportion of patients with favourable outcomes as sustained cure and treatment completion. The secondary endpoint is unfavourable outcomes, including deaths, treatment failure, toxicity/adverse events and lost to follow-up till 48 weeks post-treatment.Ethics and dissemination The study has been approved by the ethics committees of participating institutes and the National Institute for Research in TB. The trial results will help establish evidence towards a safe and effective dose of LZD that can be used in a fully, all-oral short course regimen for highly DR-TB patients. The results of this study will be shared with the National TB Elimination Programme of the country and the WHO guidelines development group through publications and dissemination meetings.Trial registration number NCT05040126.

Background: Rapidly growing mycobacteria (RGM) comprise nearly half of the validated species of nontuberculous mycobacteria (NTM) and have been reported to have a higher incidence in Asia as compared to Europe and America. There is limited information on RGM infections from South Asia. Hence, the present study aimed to ascertain the incidence of pulmonary infections due to RGM in Delhi and to review the status of available information on the prevalence of RGM in South Asia, a region endemic for tuberculosis. Methods: We analyzed 933 mycobacterial isolates obtained from pulmonary samples in Delhi and performed species identification by polymerase chain reaction (PCR)-restriction analysis (restriction fragment length polymorphism) and line probe assay. Drug susceptibility testing (DST) was performed by broth microdilution method. We also reviewed reports available on pulmonary infections in South Asia, attributed to RGM. Results: Of the 933 mycobacterial isolates studied, NTM were identified in 152 (16.3%). Of these, 65/152 (42.8%) were RGM comprising Mycobacterium fortuitum (34/65; 52.3%), Mycobacterium abscessus (25/65; 38.5%), Mycobacterium chelonae (3/65; 4.61%), Mycobacterium mucogenicum (2/65; 3.1%), and Mycobacterium smegmatis (1/65; 1.5%). On applying the American Thoracic Society/Infectious Diseases Society of America guidelines, 11/25 (44%) M. abscessus, 3/3 (100%) M. chelonae, and both isolates of M. mucogenicum were found to be clinically relevant. DST revealed that maximum susceptibility of the RGM was seen to linezolid, clarithromycin, and amikacin. Conclusions: Of the RGM isolated in the present study, 16/65 (24.6%) were found to be clinically relevant. Hence, it is important to recognize these organisms as potential pathogens to identify patients with RGM disease to initiate appropriate therapy.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

Although a simple and useful pulmonary function test, spirometry remains underutilized in India. The Indian Chest Society and National College of Chest Physicians (India) jointly supported an expert group to provide recommendations for spirometry in India. Based on a scientific grading of available published evidence, as well as other international recommendations, we propose a consensus statement for planning, performing and interpreting spirometry in a systematic manner across all levels of healthcare in India. We stress the use of standard equipment, and the need for quality control, to optimize testing. Important technical requirements for patient selection, and proper conduct of the vital capacity maneuver, are outlined. A brief algorithm to interpret and report spirometric data using minimal and most important variables is presented. The use of statistically valid lower limits of normality during interpretation is emphasized, and a listing of Indian reference equations is provided for this purpose. Other important issues such as peak expiratory flow, bronchodilator reversibility testing, and technician training are also discussed. We hope that this document will improve use of spirometry in a standardized fashion across diverse settings in India.

Background: Treatment of multidrug-resistant (MDR-TB) mainly focuses on bacteriological cure. However, only limited studies have evaluated the sequelae left after the completion of treatment among MDR-TB patients. Objective: To assess the persistent symptoms, radiological sequelae, pulmonary function impairment and quality of life at the completion of treatment among MDR-TB patients. Methods: Forty six MDR-TB patients were enrolled, who completed two years of treatment under programmatic management of Drug Resistant tuberculosis at a tertiary referral institute in Delhi, India. Detailed clinical history was taken. X-ray chest, 6 Minute Walk Test and pulmonary function tests were attempted in all patients. Quality of life was evaluated using Seattle obstructive lung disease questionnaire. Results: At the completion of MDR-TB treatment 95.7% patients had residual symptoms; 100% patients had residual bilateral chest x-ray abnormality with 82.6% patients showing far advanced disease. PFT was abnormal in 97.6% patients with mixed pattern being the commonest abnormality. Quality of Life was impaired with mean physical function of 46%. Conclusion: At the completion of MDR-TB treatment, significant numbers of patients are left with post treatment sequelae. The medical management and social support for these patients should be incorporated in the national programs.

Tuberculosis (TB) does not respect borders, and migration confounds global TB control and elimination. Systematic screening of immigrants from TB high burden settings and—to a lesser degree TB infection (TBI)—is recommended in most countries with a low incidence of TB. The aim of the study was to evaluate the views of a diverse group of international health professionals on TB management among migrants. Participants expressed their level of agreement using a six-point Likert scale with different statements in an online survey available in English, French, Mandarin, Spanish, Portuguese and Russian. The survey consisted of eight sections, covering TB and TBI screening and treatment in migrants. A total of 1055 respondents from 80 countries and territories participated between November 2019 and April 2020. The largest professional groups were pulmonologists (16.8%), other clinicians (30.4%), and nurses (11.8%). Participants generally supported infection control and TB surveillance established practices (administrative interventions, personal protection, etc.), while they disagreed on how to diagnose and manage both TB and TBI, particularly on which TBI regimens to use and when patients should be hospitalised. The results of this first knowledge, attitude and practice study on TB screening and treatment in migrants will inform public health policy and educational resources.

Background: The audio signal in the conventionally accepted protocol of shuttle walk test (SWT) is not well-understood by the patients and modification of the audio signal may improve the performance of the test. Objectives: The aim of this study is to study the validity and reliability of an audio signal modified SWT, called the Singla-Richa modified SWT (SWTSR), in healthy normal adults. Patients and Methods: In SWTSR, the audio signal was modified with the addition of reverse counting to it. A total of 54 healthy normal adults underwent conventional SWT (CSWT) at one instance and two times SWTSRon the same day. The validity was assessed by comparing outcomes of the SWTSRto outcomes of CSWT using the Pearson correlation coefficient and Bland–Altman plot. Test-retest reliability of SWTSRwas assessed using the intraclass correlation coefficient (ICC). The acceptability of the modified test in comparison to the conventional test was assessed using Likert scale. Results: The distance walked (mean ± standard deviation) in the CSWT and SWTSRtest was 853.33 ± 217.33 m and 857.22 ± 219.56 m, respectively (Pearson correlation coefficient - 0.98; P < 0.001) indicating SWTSRto be a valid test. The SWTSRwas found to be a reliable test with ICC of 0.98 (95% confidence interval: 0.97–0.99). The acceptability of SWTSRwas significantly higher than CSWT. Conclusions: The SWTSRwith modified audio signal with reverse counting is a reliable as well as a valid test when compared with CSWT in healthy normal adults. It better understood by subjects compared to CSWT.

One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%–50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%–3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases.

INTRODUCTION:There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE:To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY:Adult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS:Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION:A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

Background and Objectives: Tuberculosis (TB) is an important cause of childhood morbidity and mortality with different clinical presentations and outcomes as compared to TB in adults. The present study was designed to compare these differences and to determine if childhood TB was an important predictor of adverse outcome following treatment under the Revised National Tuberculosis Control Program (RNTCP). Materials and Methods: Retrospective record based study of cases registered between January 2008 and December 2011, at the Amdanga TB Unit (TU), West Bengal. Results: Of the total 1,508 cases notified, 3.4% were childhood TB. Differences with adult TB were noted in the number of cases categorized as cat II and III in children (P = 0.012 and 0.000, respectively). New smear positive pulmonary TB was significantly lower (21.6%, P = 0.000), while new extra-pulmonary TB (39.2%, P = 0.000) was significantly higher in children. Smear negative cases comprised 7.8 and 11.4% of the childhood and adult cases of TB, respectively. Retreatment cases were significantly higher in adults (P = 0.012). Among the registered new smear positive cases, the differences in favourable and adverse outcomes did not have a significant statistical difference (P = .100) . Childhood TB was not a significant risk factor for adverse outcome following treatment (adjusted odds ratio [AOR] = 0.80, 95% confidence interval [CI] = 0.28-2.32). Conclusions: The registration of childhood TB under the RNTCP in the TU was low. There were differences in the clinical presentation and treatment outcomes of TB among children and adults. Childhood TB was not a significant predictor of adverse treatment following treatment.

Background and Objectives: In pulmonary tuberculosis, bacteriological status at two months affects subsequent treatment and prognosis. The effect on treatment outcome and risk factors for sputum conversion at two months treatment in previously untreated pulmonary tuberculosis (PTB) patients was studied in the following report. Methods: A 1:1 case-control study was performed from June 2006 to February 2008 on patients in the Revised National Tuberculosis Control Program in a tertiary level institute in Delhi, India. Patients with previously untreated PTB with sputum smear positive at 2 months of treatment (cases) were compared with those who achieved conversion (controls). Results: In 74 cases and 74 controls, independent risk factors for sputum smear positive at two months were: illness for >2 months, presence of cavity or extensive disease on chest X-ray, and interruption in intensive phase of treatment. Patients with smear positive at 2 or 3 months of treatment were more likely to fail or default from treatment. Aforesaid factors were also associated with sputum culture positive status at 2 months in univariate analysis. Patients who interrupted treatment ≥3 times in the first two months were more likely to be culture positive at two months and had a higher rate of default and failure. Conclusions: Illness for more than 2 months, presence of cavity or extensive disease on chest X-ray, and interruption in intensive phase of treatment are independent risk factors for sputum smear positivity at two months, which in turn is associated with poor treatment outcomes. Patients with these factors merit special attention under the national program.

Lower respiratory tract infection is one of the common causes of morbidity in India which is occasionally undiagnosed. In this regard tracheobronchomegaly is one of those conditions which masquerade as chronic bronchitis and bronchiectasis and are usually undiagnosed. It is a well-defined clinical and radiologic entity characterized by marked dilatation of the trachea and the central bronchi and is frequently associated with recurrent lower respiratory tract infection. Tracheobronchomegaly has been described by a variety of names, including Mounier-Kuhn syndrome, tracheal diverticulosis, tracheobronchiectasis, tracheocele, tracheomalacia, and tracheobronchopathia malacia.

BACKGROUND: India with a major burden of multidrug-resistant tuberculosis (MDR-TB) does not have national level data on this hazardous disease. Since 2006, emergence of extensively drug-resistant TB (XDR-TB) is considered a serious threat to global TB control. This study highlights the demographic and clinical risk factors associated with XDR-TB in Delhi. METHODS: The study was conducted during April 2007 to May 2010. Six hundred eleven MDR-TB suspects were enrolled from four tertiary care hospitals, treating TB patients in Delhi and the demographic details recorded. Sputum samples were cultured using rapid, automated liquid culture system (MGIT 960). Drug susceptibility testing (DST) for Rifampicin (RIF) and Isoniazid (INH) was performed for all positive M. tuberculosis (M.tb) cultures. All MDR-TB isolates were tested for sensitivity to second-line drugs [Amikacin (AMK), Capreomycin (CAP), Ofloxacin (OFX), Ethionamide (ETA)]. RESULTS/FINDINGS: Of 611, 483 patients were infected with MDR M. tuberculosis (M.tb) strains. Eighteen MDR-TB isolates (3.7%) were XDR M.tb strains. Family history of TB (p 0.045), socioeconomic status (p 0.013), concomitant illness (p 0.001) and previous intake of 2(nd) line injectable drugs (p 0.001) were significantly associated with occurrence of XDR-TB. Only two of the patients enrolled were HIV seropositive, but had a negative culture for M. tuberculosis. 56/483 isolates were pre-XDR M. tuberculosis, though the occurrence of pre-XDR-TB did not show any significant demographical associations. CONCLUSIONS: The actual incidence and prevalence rate of XDR-TB in India is not available, although some scattered data is available. This study raises a concern about existence of XDR-TB in India, though small, signaling a need to strengthen the TB control program for early diagnosis of both tuberculosis and drug resistance in order to break the chains of transmission.

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity.