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      Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Greater Metropolitan Mumbai: Trends over Time

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          Abstract

          Background

          While 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.

          Methods

          This 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.

          Results

          A 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).

          Discussion

          The 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.

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          Most cited references13

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          Tuberculosis Management by Private Practitioners in Mumbai, India: Has Anything Changed in Two Decades?

          Setting Mumbai, India. A study conducted in Mumbai two decades ago revealed the extent of inappropriate tuberculosis (TB) management practices of private practitioners. Over the years, India's national TB programme has made significant progress in TB control. Efforts to engage private practitioners have also been made with several successful documented public-private mix initiatives in place. Objective To study prescribing practices of private practitioners in the treatment of tuberculosis, two decades after a similar study conducted in the same geographical area revealed dismal results. Methods Survey questionnaire administered to practicing general practitioners attending a continuing medical education programme. Results The participating practitioners had never been approached or oriented by the local TB programme. Only 6 of the 106 respondents wrote a prescription with a correct drug regimen. 106 doctors prescribed 63 different drug regimens. There was tendency to over treat with more drugs for longer durations. Only 3 of the 106 respondents could write an appropriate prescription for treatment of multidrug-resistant TB. Conclusions With a vast majority of private practitioners unable to provide a correct prescription for treating TB and not approached by the national TB programme, little seems to have changed over the years. Strategies to control TB through public sector health services will have little impact if inappropriate management of TB patients in private clinics continues unabated. Large scale implementation of public-private mix approaches should be a top priority for the programme. Ignoring the private sector could worsen the epidemic of multidrug-resistant and extensively drug-resistant forms of TB.
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            Tuberculosis patients and practitioners in private clinics in India.

            Rural and urban areas of Maharashtra, a large state in Western India. To understand tuberculosis (TB) management practices among private medical practitioners (PPs) and the treatment behaviour of the patients they manage. Prospective study of help-seeking patterns and treatment behaviour among 173 pulmonary TB patients diagnosed in private clinics, and the TB management practices of 122 PPs treating these patients. The first source of help for 86% of patients was a PP. The diagnostic and treatment practices of PPs were inadequate; 15% did not consider sputum examination to be necessary, and 79 different treatment regimens were prescribed by 105 reporting PPs. Sixty-seven percent of the patients diagnosed in private clinics remained with the private sector, and the rest shifted to public health services within six months of treatment. The treatment adherence rate among the patients in private clinics was 59%. There were discrepancies between the reported management practices of the PPs and what their patients actually followed. The study identifies and highlights the need to educate PPs and their TB patients, and indicates ways in which PPs could be meaningfully involved in efforts to revitalize the national TB control programme.
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              High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Programme in an urban metropolis (Mumbai) in Western India

              Background India, China and Russia account for more than 62% of multidrug resistant tuberculosis (MDRTB) globally. Within India, locations like urban metropolitan Mumbai with its burgeoning population and high incidence of TB are suspected to be a focus for MDRTB. However apart from sporadic surveys at watched sites in the country, there has been no systematic attempt by the Revised National Tuberculosis Control Programme (RNTCP) of India to determine the extent of MDRTB in Mumbai that could feed into national estimates. Drug susceptibility testing (DST) is not routinely performed as a part of programme policy and public health laboratory infrastructure, is limited and poorly equipped to cope with large scale testing. Methods From April 2004 to January 2007 we determined the extent of drug resistance in 724 {493 newly diagnosed, previously untreated and 231 first line treatment failures (sputum-smear positive at the fifth month after commencement of therapy)} cases of pulmonary tuberculosis drawn from the RNTCP in four suboptimally performing municipal wards of Mumbai. The observations were obtained using a modified radiorespirometric Buddemeyer assay and validated by the Swedish Institute for Infectious Disease Control, Stockholm, a supranational reference laboratory. Data was analyzed utilizing SPSS 10.0 and Epi Info 2002. Results This study undertaken for the first time in RNTCP outpatients in Mumbai reveals a high proportion of MDRTB strains in both previously untreated (24%) and treatment-failure cases (41%). Amongst new cases, resistance to 3 or 4 drug combinations (amplified drug resistance) including isoniazid (H) and rifampicin (R), was greater (20%) than resistance to H and R alone (4%) at any point in time during the study. The trend for monoresistance was similar in both groups remaining highest to H and lowest to R. External quality control revealed good agreement for H and R resistance (k = 0.77 and 0.76 respectively). Conclusion Levels of MDRTB are much higher in both previously untreated and first line treatment-failure cases in the selected wards in Mumbai than those projected by national estimates. The finding of amplified drug resistance suggests the presence of a well entrenched MDRTB scenario. This study suggests that a wider set of surveillance sites are needed to obtain a more realistic view of the true MDRTB rates throughout the country. This would assist in the planning of an adequate response to the diagnosis and care of MDRTB.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 January 2015
                2015
                : 10
                : 1
                : e0116798
                Affiliations
                [1 ]Jupiter Hospital, Thane, India
                [2 ]Vasant Vihar, Thane, India
                [3 ]Médecins Sans Frontières (MSF) / Doctors Without Borders, Mumbai, India
                [4 ]GTB Hospital, Sewri, Mumbai, India
                [5 ]Lilavati Hospital, Mumbai, India
                [6 ]Fortis Hospital, Mumbai, India
                [7 ]Bhatia Hospital, Mumbai, India
                [8 ]Observer Research Foundation, Mumbai, India
                [9 ]L. H. Hiranandani Hospital, Mumbai, India
                [10 ]Dr. D. Y. Patil Hospital, Navi Mumbai, India
                [11 ]P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
                Institute of Pathogen Biology, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AD PI. Performed the experiments: AD RD PP PC SR DR SB JTK CR. Analyzed the data: PI AP MD. Contributed reagents/materials/analysis tools: AD RD PP PC SR DR SB JTK PS CR. Wrote the paper: PI AP MD AD RD PP PC SR DR SB JTK CR PS.

                Article
                PONE-D-14-32719
                10.1371/journal.pone.0116798
                4301863
                25606853
                589c117d-f605-4edf-b05a-60dd6f41014d
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 22 July 2014
                : 14 December 2014
                Page count
                Figures: 1, Tables: 3, Pages: 9
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper.

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