Rise in tuberculosis cases requires action

Brussels, 31 Mar 2006

Drastic rises in the numbers of TB cases in Eastern Europe have caused alarm around the EU. Tuberculosis (TB) infects up to one-third of the world's population, and kills more than two million people worldwide every year. Despite the high rate of infection, only five to ten per cent of cases will go on to develop the disease, but TB remains the second most lethal infectious disease in the world, after HIV/AIDS.

According to statistics published in the journal Eurosurveillance, which has a special edition on TB, 414,163 cases were recorded in 51 of 52 European countries in 2004. 70 per cent of those cases occurred in 12 former Soviet-bloc countries, with average rates of 105 cases per 100,000 people. The EU25 countries by comparison show an average rate of 13 cases per 100,000 people - one-eighth the incidence of the former Soviet-bloc states.

The statistics have prompted the European Centre for Disease Prevention and Control (ECDC) to organise a meeting in October in conjunction with the WHO and the upcoming Finnish Presidency of the EU to address this issue.

Zsuzanna Jakab, director of the ECDC said: 'The continued rise of TB in the former Soviet republics cannot be allowed to continue. We are seeing the emergence there of TB strains that do not respond to antibiotics and a trend towards HIV and TB co-infection. If we want to defend public health in the EU we must address this public health emergency on our doorstep. We must join forces to ensure all countries implement best practice, such as DOTS [Directly Observed Treatment - the WHO and UN-approved regime] and that the emergence of drug resistant TB strains is both monitored and addressed.'

More worrying is that the data on drug resistance in the former Eastern-bloc is at best patchy, but as many as ten per cent of cases are not responding to treatment. A second Eurosurveillance report, written by John Watson from the Health protection Agency in London, suggests that BCG use across the EU is highly inconsistent, and that the use of the BCG vaccine should be re-evaluated.

For drug resistant strains, a third Danish-French study by Falzon and Infuso from EuroTB in Paris, and Scholten from the World Health Organisation (WHO) in Copenhagen, concluded that caution is the best policy and that drug resistant strains identified should be subject to further monitoring. 'Outcome should be reported for all definite pulmonary cases notified, regardless of treatment history. The 12-month maximum period of observation should be applied for the classification of all outcomes. Cases treated beyond 12 months and having MDR [Multiple Drug Resistance] tuberculosis (identified at start or during the current treatment episode) would form the subject of continued monitoring with a longer period of observation (24-36 months).'

While cases of TB in Eastern Europe are indeed high, rates of infection in South-East Asia are double those levels, while levels in South Africa run to four times those levels at 400 cases per 100,000 people - one in every 250 - as a result of the staggering rates of HIV/AIDS infection.

Humans have shared a long history with TB. The disease is thought to have passed from cows to humans around 4,000 BC, which, according to archaeological surveys, is when cows were first domesticated. Digs have unearthed TB bacteria in remains dating back to this time. Characters in classic European novels commonly suffer from 'consumption', bed-ridden, coughing blood and wasting away. Notable Europeans to die of TB include Frédéric Chopin, Franz Kafka and John Keats.

Until relatively recently, TB was considered to have been all but eliminated through the development of modern sanitation and then later, antibiotics and effective vaccinations such as the BCG (Bacillus Calmette-Guerin). By 1950 TB was almost eliminated.

TB's resurgence began in the 1980s, largely through sufferers not completing their courses of medication. This is when the first drug resistant strains emerged. People suffering from AIDS are particularly susceptible to TB infection, and this has exasperated the drug resistance problem. In the days before anti retroviral treatment (ART), those suffering from AIDS would be given more and more antibiotics to combat infections, but as the patients lacked adequate immune responses, they would become re-infected and with a form resistant to the previous form of drug treatment. However, people infected with HIV/AIDS continue to be far more susceptible to TB infection, the two diseases forming a gruesome but successful partnership.

The WHO DOTS programme is a five-step recipe for quick detection, close monitoring and treatment of TB. The first step is simple: sustained political commitment to TB awareness and eradication. The second step is to ensure good access to sputum analysis for quick detection of TB. The third step is standardised short-course drug treatment, which will either cure or reveal any possible drug resistance. The fourth step is to ensure a good supply of drugs to make certain that courses are completed or altered to cope with drug resistant strains. Finally, individual assessment of cases and full follow-ups to give good feedback.

There are several TB research programmes currently underway under FP6 which are intended to reduce these statistics. Most are looking at the effectiveness of new vaccines to replace the long-running BCG vaccine, designed to eradicate TB but recently shown to be effective in children, but less so in adults.

- Vaccines4TB examines CD8 cytotoxic T-cells, a different type to those targeted by HIV/AIDS, to further understanding of these poorly understood pathways and identify possible areas for vaccines.

- The TB-VAC Integrated Project aims to act as an umbrella for FP6 TB vaccine projects, and lead these vaccines to clinical trails with cooperation from 31 EU institutions from nine EU Member States and two African states.

- TB-DRUG OLIGOCOLOR aims to rapidly detect drug resistant TB cultures.

- TB Treatment Marker exploits blood plasma protein suPAR, which is elevated in TB sufferers in the hope that it will yield better methods of monitoring the progression of the disease.

- SENSITIVE TARGETS examines the bacterial mevalonate-independent 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway, which may yield targets for drugs in both TB and Malaria.

- NM4TB is an Integrated Project which aims to create new high potency drugs for TB.

- NEWTBDRUGS aims to develop new drug targets to shorten the treatment time, and so reduce the chances of drug resistance.

The European Commission is also funding the European Developing Countries Clinical Trials Partnership (EDCTP), which brings together the European Union and developing countries to develop clinical trials for drugs and vaccines against HIV/AIDS, Tuberculosis and Malaria.

For further information, please consult the following web addresses:
http:///www.eurosurveillance.org/index-02 .asp
http:///www.ecdc.eu.int/press/press_relea ses/PDF/060323_press_release.pdf
http:///europa.eu.int/comm/research/info/ conferences/edctp/edctp_en.html

CORDIS RTD-NEWS/© European Communities, 2005