Epidemiology of antituberculosis drug resistance 2002–07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance

doi:10.1016/S0140-6736(09)60331-7

The Lancet

Volume 373, Issue 9678, 30 May–5 June 2009, Pages 1861-1873

https://doi.org/10.1016/S0140-6736(09)60331-7 Get rights and content

Summary

Background

The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide.

Methods

Data for drug susceptibility were gathered from 90 726 patients in 83 countries and territories between 2002 and 2007. Standardised collection of results enabled comparison both between and within countries. Where possible, data for HIV status and resistance to second-line drugs were also obtained. Laboratory data were quality assured by the Supranational Tuberculosis Reference Laboratory Network.

Findings

The median prevalence of resistance to any drug in new cases of tuberculosis was 11·1% (IQR 7·0–22·3). The prevalence of multidrug resistance in new tuberculosis cases ranged from 0% in eight countries to 7% in two provinces in China, 11·1% in Northern Mariana Islands (although reporting only two cases), and between 6·8% and 22·3% in nine countries of the former Soviet Union, including 19·4% in Moldova and 22·3% in Baku, Azerbaijan (median for countries surveyed 1·6%, IQR 0·6–3·9). Trend analysis showed that between 1994 and 2007, the prevalence of multidrug-resistant (MDR) tuberculosis in new cases increased substantially in South Korea and in Tomsk Oblast and Orel Oblast, Russia, but was stable in Estonia and Latvia. The prevalence of MDR tuberculosis in all tuberculosis cases decreased in Hong Kong and the USA. 37 countries and territories reported representative data on extensively drug-resistant (XDR) tuberculosis. Five countries, all from the former Soviet Union, reported 25 cases or more of XDR tuberculosis each, with prevalence among MDR-tuberculosis cases ranging between 6·6% and 23·7%.

Interpretation

MDR tuberculosis remains a threat to tuberculosis control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for surveillance of resistance in tuberculosis.

Funding

Global Project: United States Agency for International Development and Eli Lilly and Company. Drug resistance surveys: national tuberculosis programmes, the Government of the Netherlands, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Japan International Cooperation Agency, and Kreditanstalt für Wiederaufbau.

Introduction

The Global Project on Anti-Tuberculosis Drug Resistance Surveillance was initiated in 1994 to estimate the burden of drug-resistant tuberculosis worldwide. The project's primary aims are to monitor trends in resistance and estimate the prevalence of multidrug-resistant (MDR) tuberculosis. Countries that participate in the project follow standardised guidelines for data collection to ensure comparability both between and within countries. The report is published approximately every 3 years since most countries need around 18 months to complete a drug resistance survey.

Until 2000, few national tuberculosis programmes were diagnosing and managing drug-resistant tuberculosis cases in the public sector, with the exception of high-income countries and countries of the former Soviet Union. After the successful implementation of pilot projects to manage drug-resistant tuberculosis, the new Stop TB Strategy—which expands on the directly observed treatment, short-course strategy (DOTS)—was launched in 2006. The Stop TB Strategy includes the diagnosis and management of drug-resistant tuberculosis as one of its components and underpins the Second Global Plan to Stop TB 2006–2015, which provides targets and financial estimates for scale-up of the strategy.¹ Nowadays, with the support of the Green Light Committee and other technical and financial partners, many countries are initiating or expanding the diagnosis and management of drug-resistant tuberculosis.

This report provides the latest data on the extent of antituberculosis drug resistance in 83 countries and territories gathered between 2002 and 2007, including the magnitude of extensively drug-resistant (XDR) tuberculosis,² and an analysis of the association between HIV and drug-resistant tuberculosis. Data gathered since 1994, from 115 countries, are used to explore trends in resistance. On the basis of such empirical information, new estimates of the global and regional burden of MDR tuberculosis are presented.

Section snippets

Data collection

A detailed description of the methods of the Global Project can be found in the full report and surveillance guidelines.3, 4, 5, 6 Briefly, the surveys are done on the basis of three main principles: the sample of tuberculosis patients must be representative of all cases of tuberculosis in the geographical setting under assessment; drug resistance must be distinguished according to the treatment history of the patient (ie, never treated or previously treated); and laboratory results must be

Results

The fourth round of the Global Project includes data from 83 countries and territories that provided at least one data point since 2002. Two settings in India completed drug resistance surveys in 2001. We have reported these data in the tables; however, they have been excluded from the analyses. Worldwide, 90 726 tuberculosis cases (consisting of new cases, previously treated cases, and those with an unknown history of previous treatment) were tested for antituberculosis drug resistance. Nine

Discussion

Data from our global survey show regional and national variation in the magnitude and trends in drug-resistant tuberculosis. Countries of the former Soviet Union, followed by some provinces of China, reported the highest prevalence of resistance, while the eastern Mediterranean region and southeast Asia reported prevalence of resistance on par with estimated global averages. The data presented here show that of the half a million MDR-tuberculosis cases estimated to have emerged in 2006, 50%

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Of 709 patients started on a standard regimen, treatment success occurred in 84.7% (587/693), 72.7% (8/11) and 100% (10/10) of patients treated with STR, FQr-mTR and SLIr-mTR as final regimens, respectively. Three (0.6%) patients acquired FQr during treatment. Early mortality occurred in 4.1% (29/709) and was associated with being HIV positive, male sex and being underweight. Overall mortality was associated with missing drug-susceptibility testing results at baseline, being HIV positive, age>40 and male sex.
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MALDI-TOF MS detected 60 copies of Mtb gene mutation, and drug-resistant gene mutation strains accounted for 34.68% (60/173) of positive strains. Rifampicin-related rpoB gene mutations accounted for 86.67% (52/60), isoniazid-related katG + inhA gene mutations accounted for 80.00% (48/60) and inhA-15 gene mutations accounted for 8.33% (5/60), streptomycin-related rpsL gene mutations accounted for 28.33% (17/60), ethambutol-related embB gene mutations accounted for 45.00% (27/60), quinolone-related gyrA basic mutation accounted for 26.67% (16/60), ethyl/propylthiamine-related embB gene mutation accounted for 36.67% (22/60) and inhA-15 gene mutation accounted for 10.00% (6/60), aminoglycoside-related rrs gene mutation accounted for 26.67% (16/60), clofazimine Fazimine, bedaquiline related Rv0678 193 gene mutations accounted for 3.33% (2/60), pyrazinamide, p-aminosalicylate, linezolid were not seen mutated genes. Multi-gene mutant strains accounted for 63.33% (38/60) of drug-resistant strains.
MALDI-TOF MS assay has good agreement with BACTEC960 liquid culture drug sensitivity test, which can be a rapid and effective method to screen for drug resistance of Mycobacterium tuberculosis, and has some clinical application value in patients with relapse tuberculosis.
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The Lancet

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Data collection

Results

Discussion

References (20)

Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis

Lancet

The Global Plan to Stop TB, 2006–2015. Actions for life: towards a world free of tuberculosis

Int J Tuberc Lung Dis

Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000–2004

MMWR Morb Mortal Wkly Rep

Interim recommendations for the surveillance of drug resistance in tuberculosis

Anti-tuberculosis drug resistance in the world: report 4

Quality assurance programme for drug susceptibility testing of Mycobcterium tuberculosis in the WHO/IUATLD supranational laboratory network: first round of proficiency testing

Int J Tuberc Lung Dis

Mycobacteria: laboratory methods for testing drug sensitivity and resistance

Bull World Health Organ

Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes

Bull World Health Organ

Multicenter laboratory evaluation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line drugs and newer antimicrobials

J Clin Microbiol

Cited by (334)

Programmatic management of rifampicin-resistant tuberculosis with standard regimen in Cameroon: a retrospective cohort study

Application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the detection of drug resistance of Mycobacterium tuberculosis in re-treated patients

Mesoporous silica nanoparticles containing silver as novel antimycobacterial agents against Mycobacterium tuberculosis

Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study

Emerging and reemerging infectious diseases

Interleukin-17A Inhibitors in Patients with Psoriasis and Tuberculosis Infection: A 2-Year Prospective Study on Safety Without Preventive Treatment

ArticlesEpidemiology of antituberculosis drug resistance 2002–07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Data collection

Results

Discussion

Lancet

The Global Plan to Stop TB, 2006–2015. Actions for life: towards a world free of tuberculosis

Int J Tuberc Lung Dis

Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000–2004

MMWR Morb Mortal Wkly Rep

Interim recommendations for the surveillance of drug resistance in tuberculosis

Anti-tuberculosis drug resistance in the world: report 4

Quality assurance programme for drug susceptibility testing of Mycobcterium tuberculosis in the WHO/IUATLD supranational laboratory network: first round of proficiency testing

Int J Tuberc Lung Dis

Mycobacteria: laboratory methods for testing drug sensitivity and resistance

Bull World Health Organ

Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes

Bull World Health Organ

Multicenter laboratory evaluation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line drugs and newer antimicrobials

J Clin Microbiol

Articles
Epidemiology of antituberculosis drug resistance 2002–07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance