BackgroundWhile the high burden of multidrug-resistant tuberculosis (MDR-TB) itself is a matter of great concern, the emergence and rise of advanced forms of drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug-resistant TB (XXDR-TB) is more troubling. The aim of this study was to investigate the trends over time of patterns of drug resistance in a sample of MDR-TB patients in greater metropolitan Mumbai, India.MethodsThis was a retrospective, observational study of drug susceptibility testing (DST) results among MDR-TB patients from eight health care facilities in greater Mumbai between 2005 and 2013. We classified resistance patterns into four categories: MDR-TB, pre-XDR-TB, XDR-TB and XXDR-TB.ResultsA total of 340 MDR-TB patients were included in the study. Pre-XDR-TB was the most common form of drug-resistant TB observed overall in this Mumbai population at 56.8% compared to 29.4% for MDR-TB. The proportion of patients with MDR-TB was 39.4% in the period 2005–2007 and 27.8% in 2011–2013, while the proportion of those with XDR-TB and XXDR-TB was changed from 6.1% and 0% respectively to 10.6% and 5.6% during the same time period. During the same periods, the proportions of patients with ofloxacin, moxifloxacin and ethionamide resistance significantly increased from 57.6% to 75.3%, from 60.0% to 69.5% and from 24.2% to 52.5% respectively (p<0.05).DiscussionThe observed trends in TB drug-resistance patterns in Mumbai highlight the need for individualized drug regimens, designed on the basis of DST results involving first- and second-line anti-TB drugs and treatment history of the patient. A drug-resistant TB case-finding strategy based on molecular techniques that identify only rifampicin resistance will lead to initiation of suboptimal treatment regimens for a significant number of patients, which may in turn contribute to amplification of resistance and transmission of strains with increasingly advanced resistance within the community.

Air pollution has become the world's single biggest environmental health risk, linked to around 7 million deaths in 2012 according to a recent World Health Organisation (WHO) report. The new data further reveals a stronger link between, indoor and outdoor air pollution exposure and cardiovascular diseases, such as strokes and ischemic heart disease, as well as between air pollution and cancer. The role of air pollution in the development of respiratory diseases, including acute respiratory infections and chronic obstructive pulmonary diseases, is well known. While both indoor and outdoor pollution affect health, recent statistics on the impact of household indoor pollutants (HAP) is alarming. The WHO factsheet on HAP and health states that 3.8 million premature deaths annually - including stroke, ischemic heart disease, chronic obstructive pulmonary disease (COPD) and lung cancer are attributed to exposure to household air pollution. Use of air cleaners and filters are one of the suggested strategies to improve indoor air quality. This review discusses the impact of air pollutants with special focus on indoor air pollutants and the benefits of air filters in improving indoor air quality.

BackgroundAdverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients.MethodsThis was a prospective, observational cohort study, using routine laboratory data in a Médecins Sans Frontières (MSF) clinic in collaboration with Sewri TB Hospital, Mumbai, India. Hypothyroidism was defined as a thyroid stimulating hormone (TSH) result >10 mIU/L at least once during treatment. Patients having a baseline result and one additional result after 3 months were eligible for enrolment.ResultsBetween October 2006 and March 2013, 116 patients were enrolled, 69 of whom were included. The median (IQR) age was 38 years (34-43) and 61% were male. By March 2013, 37/69 (54%) had hypothyroidism after at least 90 days of treatment. Age, gender, CD4 counts and stavudine-based ART were not associated with the occurrence of hypothyroidism in multivariate models. The co-administration of PAS and ethionamide was found to double the risk of hypothyroidism (RR: 1.93, 95% CI: 1.06-3.54).DiscussionHigh rate of hypothyroidism was recorded in a Mumbai cohort of MDR-TB/HIV co-infected patients on treatment. This is a treatable and reversible AE, however, it may go undiagnosed in the absence of regular monitoring. Care providers should not wait for clinical symptoms, as this risks compromising treatment adherence. Simple, affordable and reliable point-of-care tools for measuring TSH are needed, especially in high MDR-TB burden countries. Our findings suggest the need for TSH screening at baseline, three months, six months, and every six months thereafter for HIV-infected patients on MDR-TB treatment regimens containing PAS and/or ethionamide, until newer, safer and more efficacious MDR-TB regimens become available.

Background Médecins Sans Frontières clinic in Mumbai, India has been providing concomitant Bedaquiline (BDQ) and Delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. Methods This was a retrospective cohort study based on routinely collected programme data. In clinic, treatment regimens are designed based on culture-drug sensitivity test patterns, previous drug-exposures and are provided for 20-22 months. The BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February2016-February2018 were included. Result Of the 70 patients included, the median (IQR) age was 25(22-32) years and 56% were females. All except one were fluoroquinolone resistant. The median(IQR) duration of exposure to BDQ and DLM was 77(43-96) weeks. Thirty-nine episodes of serious-adverse-events(SAEs) were reported among 30(43%) patients, including five instances of QTc prolongation-assessed as possibly related to BDQ and/or DLM. Majority(69%) had culture conversion before 24 weeks of treatment. In 61(87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49(70%) patients. Conclusion The successful treatment outcomes of this cohort show that regimens including concomitant bedaquiline and delamanid for longer than 24 weeks are effective and can be safely administered on ambulatory basis. National TB programmes globally should scale up access to life saving DR-TB regimens with new drugs.