Early efficacy and safety of Bedaquiline and Delamanid given together in a "Salvage Regimen" for treatment of drug-resistant tuberculosis.

BACKGROUND: Drug-Resistant Tuberculosis (DR-TB) patients for whom a WHO recommended regimen along with Bedaquiline (BDQ) cannot be prescribed, Delamanid (DLM) was added along with other drugs to provide a "Salvage Regimen". The experience of the Institute in respect of early efficacy and safety of both drugs given together is presented. OBJECTIVE: To ascertain the early efficacy, safety and tolerability of Bedaquline and Delamanid given together as a part of salvage regimen. METHODS: BDQ and DLM were used together to make regimens along with other drugs where four effective anti TB drugs could not be prescribed as per WHO recommendations. Patients were followed up for sputum smear and culture conversion and adverse events during the treatment. RESULTS: In this cohort study, 53 DR-TB patients (Median age-24) were initiated on regimens containing both BDQ and DLM. Sputum smear conversion was seen in 35% and 94% patients at the end of 1st week and 3rd month respectively. 84% patients had culture conversion at the end of 4th month. 29 adverse events (AE) were reported among 17 patients and there were 11 deaths. QTc prolongation more than 500 MS was seen in only 1 patient. CONCLUSION: BDQ and DLM given together in a salvage regimen is efficacious with low rate of adverse events. The combination provides hope to DR-TB patients with limited treatment options and should be provided as a life saving option.

Initial experience of bedaquiline implementation under the National TB Programme at NITRD, Delhi, India.

BACKGROUND: Bedaquiline (BDQ) was approved for treatment of drug resistant TB (DR-TB) under Conditional Access Programme (CAP) of Revised National Tuberculosis Control Programme (RNTCP) and was also implemented in the National Institute of TB and Respiratory Diseases (NITRD). We present early efficacy and safety of BDQ containing regimens for DR-TB. OBJECTIVE: To ascertain the early efficacy and safety of Bedaquline containing regimens in treatment of DR-TB. METHODS: BDQ containing regimens along with other drugs were designed as per WHO recommendations for DR-TB patients. They were followed up for sputum smear and culture conversion, adverse events during the treatment. RESULTS: A cohort of 290 DR-TB patients (Median age-29.77) were initiated on BDQ containing regimens. Of the available Sputum results, smear conversion was seen in 51% and 91% patients at the end of 1st week and 3rd month respectively. Similarly, 93% and 98% patients had culture conversion at the end of 3rd and 6th month respectively. 201 adverse events (AE) including 47 deaths were reported among 109 patients. QTc prolongation was seen in 29% patients but only 4 required discontinuation of BDQ. Lost to follow up of treatment was about 6%. CONCLUSION: Bedaquiline along with an optimized background regimen has shown early sputum conversion in larger number of difficult to treat patients having additional resistance of second line drugs along with INH and Rifampicin. The regimen is feasible in programmatic conditions and is relatively safe.

Total replacement of a lung by tuberculosis pneumatocele--an unusual post-tuberculosis sequel.

Total replacement of a lung by pneumatocele in pulmonary tuberculosis is rare. The formation of pneumatoceles in adult pulmonary tuberculosis can occur before, during or after anti-tuberculosis treatment. A case of pneumatocele formation in a 19-year young female following pulmonary tuberculosis is reported. The left lung was completely replaced by pneumatocele. Total replacement of a lung by pneumatocele inspite of successful chemotherapy of tuberculosis is rare and should be considered as one of the differential diagnosis for acquired cysts of the lung.

Evaluating the technique of using inhalation device in COPD and bronchial asthma patients.

BACKGROUND: In asthma management, poor handling of inhalation devices and wrong inhalation technique are associated with decreased medication delivery and poor disease control. The key to overcome the drawbacks in inhalation technique is to make patients familiar with issues related to correct use and performance of these medical devices. The objective of this study was to evaluate and analyse technique of use of the inhalation device used by patients of COPD and Bronchial Asthma. METHODS: A total of 300 cases of BA or COPD patients using different types of inhalation devices were included in this observational study. Data were captured using a proforma and were analysed using SPSS version 15.0. RESULT: Out of total 300 enrolled patients, 247 (82.3%) made at least one error. Maximum errors observed in subjects using MDI (94.3%), followed by DPI (82.3%), MDI with Spacer (78%) while Nebulizer users (70%) made least number of errors (p = 0.005). Illiterate patients showed 95.2% error while post-graduate and professionals showed 33.3%. This difference was statistically significant (p < 0.001). Self-educated patients committed 100% error, while those trained by a doctor made 56.3% error. CONCLUSION: Majority of patients using inhalation devices made errors while using the device. Proper education to patients on correct usage may not only improve control of the symptoms of the disease but might also allow dose reduction in long term.

Seizures with single therapeutic dose of isoniazid.

Isoniazid (INH) is an integral component of treatment of tuberculosis. An acute overdose is potentially fatal and is characterised by the clinical triad of repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis with a high anion gap and coma. A case of isoniazid induced seizures after therapeutic dose of 600 mg. as a part of CAT I thrice weekly intermittent anti-tuberculosis regimen for pulmonary tuberculosis is reported. The frequency of the usage of Isoniazid as antituberculosis therapy requires that physicians be aware of such toxicity.

Unilateral and painless development of isoniazid induced gynecomastia during re-treatment of pulmonary tuberculosis.

A case of isoniazid induced gynecomastia is being reported in an 18-year old male, who received a re-treatment regimen for the relapse of pulmonary tuberculosis (TB). At the end of two months of the treatment, the patient developed a painless unilateral gynecomastia, which completely disappeared after a month of the cessation of isoniazid. A review of literature on isoniazid induced gynecomastia is discussed.

Smear microscopy as surrogate for culture during follow up of pulmonary MDR-TB patients on DOTS Plus treatment.

BACKGROUND: DOTS Plus site at LRS Institute, New Delhi, covering 1.8 million population. AIMS: To ascertain if sputum smear could be used as a surrogate for culture during intensive phase of treatment of MDR-TB patients thereby enabling early shift from intensive phase to continuation phase, reducing the need for frequent cultures and saving time and cost in their management. METHODS: The study is a retrospective analysis of 138 MDR-TB patients on DOTS Plus treatment whose sputum samples were simultaneously subjected to smear microscopy and culture, monthly during Intensive Phase and once in two months during Continuation Phase. Sputum results in the treatment card were supplemented from laboratory register, if required, and analyzed. Predictive values, sensitivity and specificity of smear were compared with culture results. RESULTS: The Negative Predictive Value (NPV) of smear was high from the 3rd month onwards (above 91%), at four months 98% or more and approached 100% from eight months onwards. The specificity of smear test gradually increased during treatment and from five months onwards, it was above 90%. CONCLUSIONS: Considerable correlation was observed between sputum smear and culture during follow up of DOTS Plus treatment in the Intensive Phase. Accordingly, sputum smears can be recommended instead of culture.

Tuberculosis pneumonia as a primary cause of respiratory failure--report of two cases.

Tuberculosis (TB) is one of the treatable diseases rarely causing Acute Respiratory Failure (ARF). Hypoxic respiratory failure is often fatal in miliary tuberculosis and acute tuberculous bronchopneumonia. We describe two patients of tuberculous pneumonia with ARF who were successfully treated with early appropriate anti-tuberculosis therapy.

Seven-year DOTS-Plus pilot experience in India: results, constraints and issues.

BACKGROUND: India is initiating the DOTS-Plus strategy at the national level. OBJECTIVES: To highlight the results, constraints and issues of a pilot DOTS-Plus experience in an urban setting in India. METHODS: Records of 126 patients with multidrug-resistant tuberculosis (MDR-TB) enrolled from January 2002 to December 2006, who received a daily fully supervised standardised treatment regimen under a pilot DOTS-Plus study in India, were analysed retrospectively. RESULTS: Of the 126 patients enrolled, 61% were cured, 19% died, 18% defaulted and 3% failed treatment. There was an average delay of 5 months in the diagnosis of MDR-TB and a subsequent delay of approximately 3.3 months in initiating treatment. Of the 24 patients who died, 29% did so within a month of starting treatment. Migration was the most common reason for default. Cycloserine (CYC) had to be stopped in 15 patients and kanamycin (KM) in five due to major adverse effects. CONCLUSIONS: The DOTS-Plus programme in resource-poor settings may provide reasonable results; however, it may confront significant operational difficulties in the timely diagnosis and early initiation of treatment. Early diagnosis and start of treatment may prevent some deaths. Default is commonly due to migration. CYC proved to be the most toxic drug, followed by KM.

A case of Hodgkin's disease presenting as lymphocytic interstitial pneumonitis.

Lymphoproliferative disorders of lung have a broad clinical and pathologic spectrum. The clinical and radiographic features are non-specific. Accurate diagnosis is required to initiate appropriate therapeutic intervention. We report a case of Hodgkin's disease mimicking lymphocytic interstitial pneumonitis in a 21-year-young male.

Role of gallium arsenide laser irradiation at 890 nm as an adjunctive to anti-tuberculosis drugs in the treatment of pulmonary tuberculosis.

BACKGROUND: Tuberculosis is a global emergency with about nine million people developing disease every year. The long duration of treatment has emerged as a major obstacle in the control of tuberculosis. There is a need for development of new drugs and or shortened therapy. METHODS: The present study was carried out to explore whether any benefit could be achieved by the addition of low level energy laser therapy (LLLT) to the conventional anti-tubercular chemotherapy. One-hundred-thirty new sputum smear positive patients of pulmonary tuberculosis were enrolled to evaluate the bio-stimulatory effects of Gallium Arsenide laser irradiation at 890 nm, as an adjuvant therapy. These patients were randomly divided into two groups to receive either LLLT or sham irradiation (control) concomitantly with anti-tuberculosis chemotherpy. RESULTS: The patients treated with semiconductor laser as an adjuvant therapy along with anti-tuberculosis drugs had a faster clearance of tubercle bacilli from the sputum as compared to the control group (P value at :45 days=0.1392, 60 days=0.0117, 75 days=0.00805, 90 days=0.00739). CONCLUSIONS: These findings provide preliminary evidence that low level laser therapy with Gallium Arsenide laser may be a promising adjunctive therapy for patients with tuberculosis. Faster conversion of sputum should prevent the development of resistant mutants.

A case of tuberculosis of the thyroid gland.

We report a case of tuberculosis of the thyroid gland associated with mediastinal lymphadenitis in a 30 years-old male, who presented with dysphagia and a mid line anterior neck swelling. Fine needle aspiration was positive for acid fast bacilli. He made an uneventful recovery with antituberculous drugs. Although seldom observed, tuberculosis should be kept in mind in te differential diagnisis of nodular lesions of the thyroid.

Contralateral pleural effusion during chemotherapy for tuberculous pleural effusion.

A 25 year old woman developed a right pleural effusion 6 weeks after commencement of short course chemotherapy for left sided tuberculous pleural effusion. Since the patient improved following continuation of the same treatment, it is presumed to be a case of paradoxical response to anti-tuberculosis treatment.

Anti-IgG autoantibodies and possible immune regulatory mechanisms in patients with pulmonary tuberculosis.

SETTING: Anti-Ig antibodies are known to have important clinical and biological implications. OBJECTIVES: To determine naturally occurring anti-F(ab')2 gamma and anti-Fc gamma antibodies in patients with pulmonary tuberculosis (PTB) in relation to various clinical manifestations and human leukocyte antigen (HLA). DESIGN: Antibodies to F(ab')2 and Fc portions of IgG were detected in the sera of normal healthy individuals (n = 41), patients with pulmonary tuberculosis (n = 50) and their household family contacts (n = 20) using an enzyme immuno assay (EIA) system. RESULTS: As compared to controls (0.110 +/- 0.01 optical density [OD]), the levels of anti-F(ab')2 gamma were significantly increased in PTB patients (0.998 +/- 0.08 OD, P < 0.0001) and in their contacts (0.486 +/- 0.04 OD, P < 0.001) suggesting that the occurrence of these autoantibodies is related to infection/exposure to Mycobacterium tuberculosis. Anti-F(ab')2 gamma antibodies were significantly increased in both sputum positive and negative patients (P < 0.0001) and no deviation was observed between these two groups. The levels of these antibodies were positively correlated with disease severity assessed by chest X-ray. The drug failure patients had higher activity of anti-F(ab')2 gamma than drug responders and no impact of anti-tuberculosis chemotherapy was observed. A statistically significant increase of anti-F(ab')2 gamma levels (1.25 +/- 0.21 OD) was observed in HLA-DR2 positive patients as compared to the DR2 negative groups (1.02 +/- 0.09 OD), P < 0.01. No deviation was observed in the levels of anti-Fc gamma levels between controls and any group of PTB patients. CONCLUSION: The present data suggests that the elevated levels of anti-F(ab')2 gamma antibodies in PTB patients represent an anti-idiotypic antibody response to anti-M. tuberculosis antibody caused by an immune imbalance following M. tuberculosis infection.