Ajay M. V. Kumar

Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with ‘presumptive TB’ rather than ‘presumptive DR-TB’ and tailor the treatment regimen based on the resistance patterns.

Translational research for tuberculosis elimination: priorities, challenges, and actions

Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035.

How good is compliance with smoke-free legislation in India? Results of 38 subnational surveys

BACKGROUND India has been implementing smoke-free legislation since 2008 prohibiting smoking in public places. This study aimed to assess the level of compliance with smoke-free legislation (defined as the presence of no-smoking signage and the absence of active smoking, smoking aids, cigarette butts/bidi ends and smoking smell) and the role of enforcement systems in Indian jurisdictions. METHODS This was a cross-sectional, retrospective review of reports and primary data sheets of surveys conducted in 38 selected jurisdictions across India in 2012-2013. RESULTS Of 20 455 public places (in 38 jurisdictions), 10 377 (51%) demonstrated full compliance with smoke-free law. Educational institutions and healthcare facilities performed well at 65% and 62%, respectively, while eateries and frequently visited other public places (such as bus stands, railway stations, shopping malls, stadia, cinema halls etc.) performed poorly at 37% and 27%, respectively. Absence of no-smoking signage was the largest contributor to non-compliance across all types of public places. Enforcement systems were present in all jurisdictions, but no associations could be demonstrated between these and smoke-free compliance. CONCLUSION Smoke-free compliance in public places in India was suboptimal and was mainly related to the absence of no-smoking signage. This warrants further pragmatic and innovative ways to improve the situation.

Addressing diabetes mellitus as part of the strategy for ending TB

As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Diseases Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases.

“They Know, They Agree, but They Don’t Do”- The Paradox of Tuberculosis Case Notification by Private Practitioners in Alappuzha District, Kerala, India

Background Despite being a recognized standard of tuberculosis (TB) care internationally, mandatory TB case notification brings forth challenges from the private sector. Only three TB cases were notified in 2013 by private practitioners compared to 2000 TB cases notified yearly from the public sector in Alappuzha district. The study objective was to explore the knowledge, opinion and barriers regarding TB Notification among private practitioners offering TB services in Alappuzha, Kerala state, India. Methods & Findings This was a mixed-methods study with quantitative (survey) and qualitative components conducted between December 2013 and July 2014. The survey, using a structured questionnaire, among 169 private practitioners revealed that 88% were aware of mandatory notification. All patient-related details requested in the notification form (except government-issued identification number) were perceived to be important and easy to provide by more than 80% of practitioners. While more than 95% felt that notification should be mandatory, punitive action in case of failure to notify was considered unnecessary by almost two third. General practitioners (98%) were more likely to be aware of notification than specialists (84 %). (P<0.01). Qualitative purposive personal interviews (n=34) were carried out among private practitioners and public health providers. On thematic framework analysis of the responses, barriers to TB notification were grouped into three themes: ‘private provider misconceptions about notification’, ‘patient confidentiality, and stigma and discrimination ’and ‘lack of cohesion and coordination between public and private sector’. Private practitioners did not consider it necessary to notify TB cases treated with daily regimen. Conclusion Communication strategies like training, timely dissemination of information of policy changes and one-to-one dialogue with private practitioners to dispel misconceptions may enhance TB notification. Trust building strategies like providing feedback about referred cases from private sector, health personnel visit or a liaison private doctor may ensure compliance to public health activities.

Linkage of Presumptive Multidrug Resistant Tuberculosis (MDR-TB) Patients to Diagnostic and Treatment Services in Cambodia

Setting National Tuberculosis Programme, Cambodia. Objective In a cohort of TB patients, to ascertain the proportion of patients who fulfil the criteria for presumptive MDR-TB, assess whether they underwent investigation for MDR-TB, and the results of the culture and drug susceptibility testing (DST). Methods A cross sectional record review of TB patients registered for treatment between July-December 2011. Results Of 19,236 TB patients registered, 409 (2%) fulfilled the criteria of presumptive MDR-TB; of these, 187 (46%) were examined for culture. This proportion was higher among relapse, failure, return after default (RAD) and non-converters at 3 months of new smear positive TB patients (>60%) as compared to non-converters at 2 months of new TB cases (<20%). Nearly two thirds (n = 113) of the samples were culture positive; of these, three-fourth (n = 85) grew Mycobacterium tuberculosis complex (MTBc) and one-fourth (n = 28) grew non-tuberculous Mycobacteria. DST results were available for 96% of the MTBc isolates. Overall, 21 patients were diagnosed as MDR-TB (all diagnosed among retreatment TB cases and none from non-converters) and all of them were initiated on MDR-TB treatment. Conclusion There is a need to strengthen mechanisms for linking patients with presumptive MDR-TB to culture centers. The policy of testing non-converters for culture and DST needs to be reviewed.

Research to policy and practice change: is capacity building in operational research delivering the goods?

Between 2009 and 2012, eight operational research capacity building courses were completed in Paris (3), Luxembourg (1), India (1), Nepal (1), Kenya (1) and Fiji (1). Courses had strict milestones that were subsequently adopted by the Structured Operational Research and Training InitiaTive (SORT IT) of the World Health Organization. We report on the numbers of enrolled participants who successfully completed courses, the number of papers published and their reported effect on policy and/or practice.

Intensive-phase treatment outcomes among hospitalized multidrug-resistant tuberculosis patients: results from a nationwide cohort in Nigeria.

Background Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6–8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them. Methods In this retrospective cohort study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB patients admitted for treatment between July 2010 and October 2012. Results Of 162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV-infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture negative at the end of IP, 24(15%) died and there was no loss-to-follow-up. Mortality was related to low CD4-counts at baseline among HIV-positive patients. The median increase in body mass index among those documented to be underweight was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL among the HIV-infected patients (p<0.01). Conclusions End-IP treatment outcomes were exceptional compared to previously published data from international cohorts, thus confirming the usefulness of a hospitalized model of care. However, less than five percent of all estimated 3600 MDR-TB patients in Nigeria were initiated on treatment during the study period. Given the expected scale-up of MDR-TB care, the hospitalized model is challenging to sustain and the national TB programme is contemplating to move to ambulatory care. Hence, we recommend using both ambulatory and hospitalized approaches, with the latter being reserved for selected high-risk groups.

Feasibility and effectiveness of provider initiated HIV testing and counseling of TB suspects in Vizianagaram district, South India.

Background Though internationally recommended, provider initiated HIV testing and counseling (PITC) of persons suspected of tuberculosis (TB) is not a policy in India; HIV seroprevalence among TB suspects has never been reported. The current policy of PITC for diagnosed TB cases may limit opportunities of early HIV diagnosis and treatment. We determined HIV seroprevalence among persons suspected of TB and assessed feasibility and effectiveness of PITC implementation at this earlier stage in the TB diagnostic pathway. Methods All adults examined for diagnostic sputum microscopy (TB suspects) in Vizianagaram district (population 2.5 million), in November-December 2010, were offered voluntary HIV counseling and testing (VCT) and assessed for TB diagnosis. Results Of 2918 eligible TB suspects, 2465(85%) consented to VCT. Among these, 246(10%) were HIV-positive. Of the 246, 84(34%) were newly diagnosed as HIV (HIV status not known previously). To detect a new case of HIV infection, the number needed to screen (NNS) was 26 among ‘TB suspects’, comparable to that among ‘TB patients’. Among suspects aged 25–54 years, not diagnosed as TB, the NNS was 17. Conclusion The seroprevalence of HIV among ‘TB suspects’ was as high as that among ‘TB patients’. Implementation of PITC among TB suspects was feasible and effective, detecting a large number of new HIV cases with minimal additional workload on staff of HIV testing centre. HIV testing of TB suspects aged 25–54 years demonstrated higher yield for a given effort, and should be considered by policy makers at least in settings with high HIV prevalence.

Patient and Provider Reported Reasons for Lost to Follow Up in MDRTB Treatment: A Qualitative Study from a Drug Resistant TB Centre in India

Introduction Multidrug-resistant Tuberculosis (MDR TB) is emerging public health concern globally. Lost to follow-up (LTFU) is one of the key challenge in MDRTB treatment. In 2013, 18% of MDR TB patients were reported LTFU in India. A qualitative study was conducted to obtain better understanding of both patient and provider related factors for LTFU among MDR TB treatment. Methods Qualitative semi-structured personal interviews were conducted with 20 MDRTB patients reported as LTFU and 10 treatment providers in seven districts linked to Nagpur Drug resistant TB Centre (DRTBC) during August 2012–February 2013. Interviews were transcribed and inductive content analysis was performed to derive emergent themes. Results We found multiple factors influencing MDR TB treatment adherence. Barriers to treatment adherence included drug side effects, a perceived lack of provider support, patient financial constraints, conflicts with the timing of treatment services, alcoholism and social stigma. Conclusions Patient adherence to treatment is multi-factorial and involves individual patient factors, provider factors, and community factors. Addressing issue of LTFU during MDRTB treatment requires enhanced efforts towards resolving medical problems like adverse drug effects, developing short duration treatment regimens, reducing pill burden, motivational counselling, flexible timings for DOT services, social, family support for patients & improving awareness about disease.