Drug-resistant tuberculosis: time for visionary political leadership

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Abstract

Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans. Copyright © 2013 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.

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National survey of drug-resistant tuberculosis in China.

Yanlin Zhao, Shaofa Xu, Lixia Wang … (2012)

The available information on the epidemic of drug-resistant tuberculosis in China is based on local or regional surveys. In 2007, we carried out a national survey of drug-resistant tuberculosis in China. We estimated the proportion of tuberculosis cases in China that were resistant to drugs by means of cluster-randomized sampling of tuberculosis cases in the public health system and testing for resistance to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and streptomycin and the second-line drugs ofloxacin and kanamycin. We used the results from this survey and published estimates of the incidence of tuberculosis to estimate the incidence of drug-resistant tuberculosis. Information from patient interviews was used to identify factors linked to drug resistance. Among 3037 patients with new cases of tuberculosis and 892 with previously treated cases, 5.7% (95% confidence interval [CI], 4.5 to 7.0) and 25.6% (95% CI, 21.5 to 29.8), respectively, had multidrug-resistant (MDR) tuberculosis (defined as disease that was resistant to at least isoniazid and rifampin). Among all patients with tuberculosis, approximately 1 of 4 had disease that was resistant to isoniazid, rifampin, or both, and 1 of 10 had MDR tuberculosis. Approximately 8% of the patients with MDR tuberculosis had extensively drug-resistant (XDR) tuberculosis (defined as disease that was resistant to at least isoniazid, rifampin, ofloxacin, and kanamycin). In 2007, there were 110,000 incident cases (95% CI, 97,000 to 130,000) of MDR tuberculosis and 8200 incident cases (95% CI, 7200 to 9700) of XDR tuberculosis. Most cases of MDR and XDR tuberculosis resulted from primary transmission. Patients with multiple previous treatments who had received their last treatment in a tuberculosis hospital had the highest risk of MDR tuberculosis (adjusted odds ratio, 13.3; 95% CI, 3.9 to 46.0). Among 226 previously treated patients with MDR tuberculosis, 43.8% had not completed their last treatment; most had been treated in the hospital system. Among those who had completed treatment, tuberculosis developed again in most of the patients after their treatment in the public health system. China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases. (Funded by the Chinese Ministry of Health.).

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Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in iran.

Ali Akbar Velayati, Mohammad- Masjedi, Parissa Farnia … (2009)

The study documented the emergence of new forms of resistant bacilli (totally drug-resistant [TDR] or super extensively drug-resistant [XDR] tuberculosis [TB] strains) among patients with multidrug-resistant TB (MDR-TB). Susceptibility testing against first- and second-line drugs was performed on isolated Mycobacterium tuberculosis strains. Subsequently, the strains identified as XDR or TDR M tuberculosis were subjected to spoligotyping and variable numbers of tandem repeats (VNTR). Of 146 MDR-TB strains, 8 XDR isolates (5.4%) and 15 TDR isolates (10.3%) were identified. The remaining strains were either susceptible (67%) or had other resistant patterns (20%). Overall, the median of treatments and drugs previously received by MDR-TB patients was two courses of therapy of 15 months' duration with five drugs (isoniazid [INH], rifampicin [RF], streptomycin, ethambutol, and pyrazinamide). The median of in vitro drug resistance for all studied cases was INH and RF. The XDR or TDR strains were collected from both immigrants (Afghan, 30.4%; Azerbaijani, 8.6%; Iraqi, 4.3%) and Iranian (56.5%) MDR-TB cases. In such cases, the smear and cultures remained positive after 18 months of medium treatment with second-line drugs (ethionamide, para-aminosalicylic acid, cycloserine, ofloxacin, amikacin, and ciprofloxacin). Spoligotyping revealed Haarlem (39.1%), Beijing (21.7%), EAI (21.7%), and CAS (17.3%) superfamilies of M tuberculosis. These superfamilies had different VNTR profiles, which eliminated the recent transmission among MDR-TB cases. The isolation of TDR strains from MDR-TB patients from different regional countries is alarming and underlines the possible dissemination of such strains in Asian countries. Now the next question is how one should control and treat such cases.

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

D Falzon, E Jaramillo, H. J. Schunemann … (2011)

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.