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% . 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 .
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) . 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) . 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
Suggested actions at EU level
||Enhance surveillance of MDR and resistance to second line
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
||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
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.
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.