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An outbreak of a strain of extensive drug-resistant tuberculosis (XDR-TB) was reported recently in 53 patients from a rural district in Kwazulu-Natal, South Africa, where the TB/HIV co-infection rate is over 80% [1]. A World Health Organization-sponsored international meeting was held in South Africa in early September 2006 to address the issue of multidrug-resistant (MDR) tuberculosis in Africa and to further discuss the findings of the XDR-TB outbreak in Kwazulu-Natal. Following the meeting, a global XDR-TB action plan was launched with the objectives of strengthening TB control measures and tackling XDR-TB more effectively [2].

MDR tuberculosis, defined as tuberculosis caused by a strain which is resistant to at least isoniazid and rifampicin (the two main drugs used for TB treatment), emerged as a threat for TB control in the 1990s. MDR-TB cases need to be treated with second line drugs which require prolonged supervised treatment (beyond 18 months), and are less effective, more toxic and more expensive than the standardised short-course regimen. In the European Union (EU), the proportion of TB cases that are multidrug resistant is high in the Baltic countries of Estonia, Latvia and Lithuania (18%-20% of tested cases in 2004) and between 0%-5% in the remaining EU countries.

Extensive drug-resistant TB (XDR-TB) is defined as a multidrug-resistant TB strain which is also resistant to three or more of the six classes of second-line drugs (aminoglycosides, polypeptides, fluoroquinolones, thioamides, cycloserine and para-aminosalicylic acid) [3]. XDR-TB is related to the poor management of MDR-TB cases (which in turn is the consequence of suboptimally managed susceptible TB). Within Europe, countries with high incidence of MDR-TB are at high risk for emergence of XDR-TB.

The recent occurrence of XDR-TB in Kwazulu-Natal does not represent an unprecedented finding. Extensive drug resistant strains have been previously reported in Europe, Asia and the Americas. The media interest in the finding of the XDR-TB strain in South Africa was related to its high mortality, much of which could be attributed to HIV comorbidity. Data from Latvia and the United States show a much lower XDR-TB mortality in HIV negative patients.

Global burden of XDR-TB
A global survey of Supranational Reference Laboratories analysed data on samples collected between 2000 and 2004. Out of 17 690 TB isolates processed (in selected reference laboratories), 20% were MDR and 2% were XDR. In addition, limited population-based data on drug susceptibility of TB isolates were available from the US, Latvia and South Korea where 4%, 19% and 15% of MDR TB cases, respectively, were XDR. The survey clearly showed that XDR-TB is present on every continent and that it has been detected by national laboratories with SLD susceptibility testing capacity for a number of years.

Discussion of European situation
The EU is funding a project which undertakes molecular surveillance of MDR-TB across Europe. This project involves a European network of participants working in national tuberculosis surveillance institutions and laboratories coordinated by EuroTB (http://www.eurotb.org/). Seventeen European countries, including twelve European Union countries, have provided surveillance data. Data collected on cases detected or diagnosed between 1 January 2003 and 31 May 2006 showed that 215 of 1050 MDR reported cases (approx 20%) were extensively drug resistant.

These data should be interpreted with caution in view of the lack of quality assurance and standardisation for second-line drug susceptibility testing. However, reliable data on MDR-TB (resistance to both isoniazid and rifampicin) clearly indicate that the Baltic countries have a high proportion of MDR-TB (ranging from 18% to 20% of tested cases in 2004) [3]. In such settings of high MDR-TB incidence, there is a higher risk of XDR-TB developing in poorly managed cases.

XDR-TB represents a potential risk for public health systems throughout Europe. However, the overall incidence of TB in the 25 EU Member States is relatively low, and the incidence of MDR-TB and XDR-TB is even lower, therefore the risk of being infected by an XDR-TB strain is extremely low for the average citizen in the EU. Nevertheless, even small outbreaks would require special measures for preventing transmission and for treating affected individuals.

Suggested actions at EU level

	Enhance surveillance of MDR and resistance to second line drugs The current EURO-TB project on molecular surveillance of MDR-TB covers 12 out of the 25 member states. This should be expanded and second-line drug surveillance should be established to detect any cases of XDR-TB.
	Strengthen and improve quality of TB control XDR-TB and MDR-TB are healthcare-associated problems, related to poor case management. Emphasis should be placed on strengthening the basics of successful TB control (standardised regimens, treatment support and monitoring, tracing of defaulters). Countries with poor TB control should be identified and technical support provided. Technical support to non-EU countries with extensive MDR-TB problems (i.e. the Russian Federation) should also be considered.
	Improvement of laboratory capacity for susceptibility testing of second line drugs At European level, input and support should be provided for standardising second-line drug susceptibility testing and for ensuring that these services are readily available in countries with high incidence of MDR-TB. External quality assurance (EQA) for these laboratories should be implemented.
	Support international research on new diagnostics and new drugs
	Contact tracing and prophylaxis General guidelines on contact tracing and prophylaxis, based on solid scientific evidence, should be made available at European level. More specifically, evidence gathering and consensus building concerning intensified contact tracing for MDR-TB cases and prophylaxis against MDR strains is needed.

The European Centre for Disease Prevention and Control has made tackling TB a priority and is developing a plan of activities, taking into account the suggested actions above, to assist EU member states in preventing multidrug resistance and the emergence of XDR-TB.

Acknowledgements
Isabelle Devaux and Dennis Falzon from EuroTB provided data from the Molecular surveillance of multi-drug resistant tuberculosis in Europe project (http://www.eurotb.org/mdr_tb_surveillance/index.htm) and made valuable comments on earlier drafts of this article.