Fraser Wares

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Improving tuberculosis control through public-private collaboration in India: literature review

Abstract Objective To review the characteristics of public-private mix projects in India and their effect on case notification and treatment outcomes for tuberculosis. Design Literature review. Data sources Review of surveillance records from Indian tuberculosis programme project, evaluation reports, and medical literature for public-private mix projects in India. Data extraction Project characteristics, tuberculosis case notification of new patients with sputum smear results positive for acid fast bacilli, and treatment outcome. Data synthesis Of 24 identified public-private mix projects, data were available from 14 (58%), involving private practitioners, corporations, and non-governmental organisations. In all reviewed projects, the public sector tuberculosis programme provided training and supervision of private providers. Among the five projects with available data on historical controls, case notification rates were higher after implementation of a public-private mix project. Among seven projects involving private practitioners, 2796 of 12 147 (23%) new patients positive for acid fast bacilli were attributed to private providers. Corporate based and non-governmental organisations served as the main source for tuberculosis programme services in seven project areas, detecting 9967 new patients positive for acid fast bacilli. In nine of 12 projects with data on treatment outcomes, private providers exceeded the programme target of 85% treatment success for new patients positive for acid fast bacilli. Conclusions Public-private mix activities were associated with increased case notification, while maintaining acceptable treatment outcomes. Collaborations between public and private providers of health care hold considerable potential to improve tuberculosis control in India.

Multidrug-resistant tuberculosis around the world: what progress has been made?

Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6–50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40–70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB. A wider adoption of effective diagnostics, treatment and preventive measures is needed to control MDR-TB globally http://ow.ly/zwZWr

Universal access to care for multidrug-resistant tuberculosis: an analysis of surveillance data.

BACKGROUND The prospects for global tuberculosis control in the near future will be determined by the effectiveness of the response of countries to their burden of multidrug-resistant (MDR; resistance to, at least, isoniazid and rifampicin) tuberculosis. During the 2009 World Health Assembly, countries committed to achieve universal access to MDR-tuberculosis care by 2015. We assessed the progress towards the 2015 targets achieved by countries accounting for 90% of the estimated MDR-tuberculosis cases in the world in 2011. METHODS We analysed data reported to WHO by 30 countries expected to have more than 1000 MDR-tuberculosis cases among notified patients with pulmonary tuberculosis in 2011. FINDINGS In the 30 countries, 18% of the estimated MDR-tuberculosis cases were enrolled on treatment in 2011. Belarus, Brazil, Kazakhstan, Peru, South Africa, and Ukraine each detected and enrolled on treatment more than 50% of their estimated cases of MDR-tuberculosis. In Ethiopia, India, Indonesia, the Philippines, and Russia, enrolments increased steadily between 2009 and 2011 with a mean yearly change greater than 50%: however, in these countries enrolment in 2011 was low, ranging from 4% to 43% of the estimated cases. In the remaining countries (Afghanistan, Angola, Azerbaijan, Bangladesh, China, Democratic Republic of the Congo, Kenya, Kyrgyzstan, Moldova, Mozambique, Burma, Nepal, Nigeria, North Korea, Pakistan, South Korea, Thailand, Uzbekistan, and Vietnam) progress in detection and enrolment was slower. In 23 countries, a median of 53% (IQR 41-71) patients with MDR-tuberculosis successfully completed their treatment after starting it in 2008-09. INTERPRETATION Six countries (Belarus, Brazil, Kazakhstan, Peru, South Africa, and Ukraine) can achieve universal access to MDR-tuberculosis care by 2015 should they sustain their current pace of progress. In other countries a radical scale-up will be needed for them to have an effect on their MDR-tuberculosis burden. Unless barriers to diagnosis and successful treatment are urgently overcome, and new technologies in diagnostics and treatment effectively implemented, the global targets for 2015 are unlikely be achieved. FUNDING WHO.

Risk factors for treatment default among re-treatment tuberculosis patients in India, 2006.

Setting Under Indias Revised National Tuberculosis Control Programme (RNTCP), >15% of previously-treated patients in the reported 2006 patient cohort defaulted from anti-tuberculosis treatment. Objective To assess the timing, characteristics, and risk factors for default amongst re-treatment TB patients. Methodology For this case-control study, in 90 randomly-selected programme units treatment records were abstracted from all 2006 defaulters from the RNTCP re-treatment regimen (cases), with one consecutively-selected non-defaulter per case. Patients who interrupted anti-tuberculosis treatment for >2 months were classified as defaulters. Results 1,141 defaulters and 1,189 non-defaulters were included. The median duration of treatment prior to default was 81 days (25%–75% interquartile range 44–117 days) and documented retrieval efforts after treatment interruption were inadequate. Defaulters were more likely to have been male (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI] 1.2–1.7), have previously defaulted anti-tuberculosis treatment (aOR 1.3 95%CI 1.1–1.6], have previous treatment from non-RNTCP providers (AOR 1.3, 95%CI 1.0–1.6], or have public health facility-based treatment observation (aOR 1.3, 95%CI 1.1–1.6). Conclusions Amongst the large number of re-treatment patients in India, default occurs early and often. Improved pre-treatment counseling and community-based treatment provision may reduce default rates. Efforts to retrieve treatment interrupters prior to default require strengthening.

Tuberculosis control in India

We were disappointed and not a little surprised by your news article regarding progress in tuberculosis control in India in 2002. We strongly disagree with the content of the article. Tuberculosis remains a serious public-health problem in India accounting for nearly one-third of the global burden. Despite the introduction of the National Tuberculosis Control Programme in 1962 India has about 2 million new cases every year of which nearly 1 million are infectious smear-positive pulmonary cases. One person dies from tuberculosis in India every minute—more than 1000 every day and 450 000 every year. Indias tuberculosis problem is further compounded by an estimated 3.97 million people infected with HIV tuberculosis being the most common opportunistic disease amongst HIV-infected people. However the news is not all bad. Recognising the devastating socio-economic impact of this airborne disease in 1993 the government of India embarked on an ambitious revised tuberculosis-control programme based on the WHO-recommended directly observed therapy short-course (DOTS) strategy with three pilot sites covering a population of 4.2 million. (excerpt)

Care seeking behavior of chest symptomatics: a community based study done in South India after the implementation of the RNTCP.

Introduction With the creation of the Revised National TB Control Programme (RNTCP), tuberculosis services have become decentralized and more accessible. A 1997 study prior to RNTCP implementation reported that most chest symptomatics accessed first private health care facilities and a general dissatisfaction with government health facilities. The study was repeated post-RNTCP implementation to gain insight into the current care seeking behavior of chest symptomatics. Methodology A cross-sectional community-based study carried out between March-August 2008 in 4 sites (2 rural [R] and 2 urban [U]) from the same two districts of Chennai and Madurai, southern India, as in the 1997 study. Six hundred and forty chest symptomatics were identified (R 314; U 326), and detailed interviews were done for 606 (R311; U295). Results Prevalence of chest symptomatics in the urban and rural areas were 2.7% and 4.9% respectively (p<0.01), and was found to increase with age (Chi-square for trend, p<0.01). Longer delays in seeking care were seen amongst symptomatics above 45 years of age (p 0.01), and those who had taken previous TB treatment (p = 0.05). Overall, 50% (222/444) of the chest symptomatics approached a government health care facility first (R 142 (61%); U 80 (38%), p = <0.001). This was significantly (p<0.001) more than were observed in the 1997 study, where only 38.4% approached a government facility first. Sixty two (28%) of the 222 made a second visit to a government facility (R26%; U31%), while 17% shifted to a private facility (R14%; U21%). Dissatisfaction with the health care facility was one of the major reasons expressed. Conclusions It appears that the RNTCP has had an impact in the community with regard to the availability and accessibility of TB services in government health facilities. However the relatively high levels of subsequent shifting to private health facilities calls for urgent action to make government facilities more patients friendly with quality care facilities in the delivery of RNTCP services.

Prevalence of pulmonary tuberculosis amongst the tribal population of Madhya Pradesh, central India

BACKGROUND This was a prevalence survey of pulmonary tuberculosis (PTB) disease in the tribal population of Madhya Pradesh state, central India. METHODS A community-based cross-sectional tuberculosis (TB) disease prevalence survey was undertaken among adults aged > or = 15 years in the tribal population of Madhya Pradesh. A multistage stratified cluster sampling was adopted. A representative random sample of villages predominated by tribal populations was selected from 11 districts. All eligible individuals were questioned for chest symptoms relating to TB. Sputum samples were collected from all eligible individuals, transported to the laboratory, and examined by Ziehl-Neelsen (ZN) smear microscopy and solid media culture methods. RESULTS Of the 23,411 individuals eligible for screening, 22,270 (95.1%) were screened for symptoms. The overall proportion of symptomatic individuals was 7.9%. Overall prevalence (culture and/or smear positive) of PTB was 387 [95% confidence interval (CI): 273-502] per 100,000 population. The prevalence increased with age and was also significantly higher among males (554/100,000; 95% CI: 415-693) as compared with females (233/100,000; 95% CI: 101-364) (P < 0.001). CONCLUSION The findings suggest that the TB situation amongst the tribal population is not that different from the situation among the non-tribal population in the country. However, TB remains a major public health problem amongst the tribal population and there is a need to maintain and further strengthen TB control measures on a sustained and long-term basis.

Efficacy of a Six-Month versus a 36-Month Regimen for Prevention of Tuberculosis in HIV-Infected Persons in India: A Randomized Clinical Trial

Background The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown. Methods An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared. Findings Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100py (95%CI- 1.4–3.5) and 1.6/100py (95% CI-0.8–3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8–3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6–4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant. Interpretation Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients. The trial is registered at ClinicalTrials.gov, NCT00351702.

Prevalence of Pulmonary Tuberculosis - A Baseline Survey In Central India

Background The present study provides an estimate of the prevalence of bacteriologially positive pulmonary tuberculosis in Jabalpur, a district in central India. Methodology/Principal Findings A community based cross-sectional survey was undertaken in Jabalpur District of the central Indian state of Madhya Pradesh. A stratified cluster sampling design was adopted to select the sample. All eligible individuals were questioned for pulmonary symptoms suggestive of TB disease. Two sputum samples were collected from all eligible individuals and were examined by Ziehl-Neelsen smear microscopy and solid media culture methods. Of the 99,918 individuals eligible for screening, 95,071 (95.1%) individuals were screened. Of these, 7,916 (8.3%) were found to have symptoms and sputum was collected from 7,533 (95.2%) individuals. Overall prevalence of bacteriologically positive PTB was found to be 255.3 per 100,000 population (95% C.I: 195.3–315.4). Prevalence was significantly higher (p<0.001) amongst males (355.8; 95% C.I: 304.4–413.4) compared with females (109.0; 95% C.I: 81.2–143.3). Prevalence was also significantly higher in rural areas (348.9; 95% C.I: 292.6–412.8) as compared to the urban (153.9; 95% C.I: 123.2–190.1). Conclusions/Significance The TB situation in Jabalpur district, central India, is observed to be comparable to the TB situation at the national level (255.3 versus 249). There is however, a need to maintain and further strengthen TB control measures on a sustained and long term basis in the area to have a significant impact on the disease prevalence in the community.