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Nunn A.J.,Medical Research Council Clinical Trials Unit | Jindani A.,St Georges, University of London | Enarson D.A.,International Union Against Tuberculosis and Lung Disease
International Journal of Tuberculosis and Lung Disease | Year: 2011

SETTING: An 8-month isoniazid (INH, H) and ethambutol (EMB, E) based regimen recommended by the World Health Organization (WHO) had never been evaluated in a randomised controlled multicentre trial. OBJECTIVE: To compare, in a non-inferiority study design, two 8-month INH+EMB-based regimens with a standard INH and rifampicin (RMP, R) based regimen. DESIGN: A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly allocated to receive 1) daily EMB, INH, RMP and pyrazinamide (PZA, Z) for 2 months, followed by EMB+INH for 6 months (2EHRZ/6HE); 2) the same drugs in the intensive phase but given three times weekly, followed by the same continuation phase of daily EMB+INH (2(EHRZ)3/6HE); or 3) a control regimen with the same intensive phase as in regimen 1, followed by 4 months of daily RMP+INH (2EHRZ/4HR). All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after randomisation. RESULTS: At 30 months, failure/relapse rates were 11.7% of 281 2EHRZ/6HE, 15.3% of 301 2(EHRZ) 3/ 6HE and 6.0% of 282 2EHRZ/4HR patients (χ 2, 2 degrees of freedom = 12.8, P = 0.002). CONCLUSION: These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the standard 6-month regimen. The WHO has withdrawn its recommendation of these regimens. © 2011 The Union.


Chiang C.-Y.,International Union Against Tuberculosis and Lung Disease | Schaaf H.S.,Stellenbosch University
International Journal of Tuberculosis and Lung Disease | Year: 2010

Drug-resistant tuberculosis (DR-TB) in adults is either acquired due to poor treatment management or transmitted from infectious DR-TB cases, while children mainly have transmitted disease. Diagnosis of DR-TB relies on drug susceptibility testing (DST), which is not routinely performed in high tuberculosis (TB) burden settings. The Category II retreatment regimen is inadequate for Category I failures if multidrug-resistant TB (MDR-TB) is present. Where possible, DST should be performed for Category I failures and other patients with a high risk of DR-TB. Fluoroquinolones (FQs) should be used with caution in the treatment of mono- and polyresistant TB. Modification of regimens for mono- and polyresistance is prone to error if DST results are not reliable or if there is possible additional drug resistance due to further drug exposure. While standardised treatment is feasible for MDR-TB patients never previously treated with second-line drugs, a different strategy is required for those MDRTB patients who have previously been treated with second-line drugs. Sputum conversion, adverse effects and adherence to MDR-TB treatment should be monitored closely. The presence of FQ resistance prior to MDR-TB treatment poses a serious challenge. To prevent the development of extensively drug-resistant TB, strategies to protect the FQs, the most important second-line agents, need to be developed. Clinical trials assessing MDR-TB treatment regimens are urgently needed. © 2010 The Union.


Kapoor S.K.,Harrow Medical Center | Raman A.V.,University of Delhi | Sachdeva K.S.,Directorate General of Health Services | Satyanarayana S.,International Union Against Tuberculosis and Lung Disease
PLoS ONE | Year: 2012

Setting: Revised National Tuberculosis Control Programme (RNTCP), Delhi, India. Objective: To ascertain the number and sequence of providers visited by TB patients before availing treatment services from DOTS; to describe the duration between onset of symptoms to treatment. Study design: A cross sectional, qualitative study. Information was gathered through in-depth interviews of TB patients registered during the month of Oct, 2012 for availing TB treatment under the Revised National TB Control Programme from four tuberculosis diagnosis and treatment centers in Delhi. Results: Out of the 114 patients who registered, 108 participated in the study. The study showed that informal providers and retail chemists were the first point of contact and source of clinical advice for two-third of the patients, while the rest sought medical care from qualified providers directly. Most patients sought medical care from more than two providers, before being diagnosed as TB. Female TB patients and patients with extra-pulmonary TB had long mean duration between onset of symptoms to initiation of treatment (6.3 months and 8.4 months respectively). Conclusion: The pathways followed by TB patients, illustrated in this study, provide valuable lessons on the importance of different types of providers (both formal and informal) in the health system in a society like India and the delays in the diagnosis and treatment of tuberculosis. © 2012 Kapoor et al.


Singh R.J.,International Union Against Tuberculosis and Lung Disease
Indian journal of public health | Year: 2011

Exposure to secondhand smoke (SHS) causes an estimated 5% of the global burden of disease, slightly higher than the burden from direct use of tobacco. This review highlights the urgent need to address this ignored public health issue by presenting the evidence and impact of SHS on those exposed using global studies including those from the South-East Asia Region. The burden of morbidity from SHS exposure is higher in low-income countries in Southeast Asia region compared to the rest of the world. SHS exposure affects those most vulnerable, especially women and children. While several countries in the region have enacted legislation which offer protection to those exposed to SHS, most measures are partial and inadequate. As a result, implementation and compliance at national and sub-national level within the countries of the Southeast Asia region is variable. Governments must ensure that legislation mandates comprehensive smoke-free environments in order to provide public health benefit which offers universal protection to everyone and everywhere. Where comprehensive legislation exists, stringent implementation and enforcement, along with awareness building, education and monitoring through regular compliance studies must be done to sustain smokefree status of public places within jurisdictions.


Chiang C.-Y.,International Union Against Tuberculosis and Lung Disease | Centis R.,Care Network | Migliori G.B.,Care Network
Respirology | Year: 2010

In a population of Mycobacterium tuberculosis, random chromosomal mutation that results in genetic resistance to anti-tuberculosis (TB) drugs occurs at a relatively low frequency. Anti-TB drugs impose selection pressure so that mycobacterial mutants gradually outnumber susceptible bacilli and emerge as the dominant strains. Resistance to two or more anti-TB drugs represents cumulative results of sequential mutation. The fourth report on global anti-TB drug resistance provides the latest data on the extent of such problem in the world. The median prevalence of multi-drug-resistant TB (MDR-TB) in new TB cases was 1.6%, and in previously treated TB cases 11.7%. Of the half a million MDR-TB cases estimated to have emerged in 2006, 50% were in China and India. The optimal duration of any given combination of anti-TB drugs for treatment of MDR- and extensively drug-resistant TB (XDR-TB) has not been defined in controlled clinical trials. Standardized treatment may be feasible for MDR-TB patients not previously treated with second-line drugs, but a different strategy needs to be applied in the treatment of MDR-TB patients who have received second-line drugs before. Unfortunately, the reliability of drug susceptibility testing of most second-line anti-TB drugs is still questionable. Drug-resistant TB is not necessarily less virulent. Findings from modelling exercise warned that if MDR-TB case detection and treatment rates increase to the World Health Organization target of 70%, without simultaneously increasing MDR-TB cure rates, XDR-TB prevalence could increase exponentially. Prevention of development of drug resistance must be accorded the top priority in the era of MDR-/XDR-TB. © 2010 Asian Pacific Society of Respirology.

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