Extensively Drug-Resistant Tuberculosis (Xdr-Tb): The Facts

Firstly, some facts about tuberculosis. Tuberculosis (TB) is contagious and spreads through the air; if not treated, each person with active TB infects, on average, 10-15 others every year. One in ten people infected with TB bacilli will become sick with active TB in his or her lifetime. People with HIV are at much greater risk. TB is a disease of poverty, affecting mostly young adults in their most productive years. In the WHO European Region, there were 445 000 new TB cases in 2005 and 66 000 deaths: an estimated 7 deaths every hour. TB is a leading killer among HIV-infected people with weakened immune systems. In 2005, 14 000 new TB cases are estimated to have occurred in HIV-positive adults. TB is a Region-wide pandemic. European Union (EU) countries report 23% of all new cases, and Kazakhstan, Romania, the Russian Federation, Turkey, Ukraine and Uzbekistan account for 73% of the total number of cases in the WHO European Region. Multidrug-resistant TB (MDR-TB) does not respond to the standard treatments, using first-line drugs. MDR-TB is present in virtually all countries recently surveyed by WHO and partners. Every year, 450 000 new MDR-TB cases are estimated to occur worldwide, including 70 000 in the European Region. Extensively drug-resistant TB (XDR-TB) occurs when resistance to second-line drugs develops. It is extremely difficult to treat and cases have been confirmed all over the world.

What is XDR-TB?TB can usually be treated with a course of four standard, or first-line, anti-TB drugs. If these are misused or mismanaged, multidrugresistant TB (MDR-TB) can develop. MDR-TB takes longer to treat with second-line drugs, which are more expensive and have more side-effects. If these drugs are also misused or mismanaged, extensively drug-resistant TB (XDR-TB) can develop. Because XDR-TB is resistant to first- and second-line drugs, treatment options are seriously limited and so are the chances of cure.What is the medical definition of MDR-TB and XDR-TB?MDR-TB is due to bacteria that are resistant to at least isoniazid and rifampicin, the two most powerful first-line anti-TB drugs. XDR-TB is due to bacteria that are resistant to any fluoroquinolone, and at least one of three injectable second-line drugs (capreomycin, kanamycin and amikacin), in addition to isoniazid and rifampicin. This is a revised definition of XDR-TB, on which the WHO GlobalTask Force on XDR-TB agreed in October 2006.How do people develop XDR-TB?People who are ill with pulmonary TB (TB of the lungs, the site most commonly affected) are often infectious and can spread the disease by coughing, sneezing or simply talking, as these acts propel TB bacteria into the air. Another person breathing in these bacteria may become infected with TB but without disease; only the TB skin test becomes positive. If the bacteria overcome the body’s immune system, the person becomes ill with TB. A person ill with TB develops XDR-TB when first- and second-line anti-TB drugs are misused or mismanaged during the course of treatment and become ineffective (that is, when drugs are taken in the wrong combination, are fewer than those prescribed or taken in insufficient doses or insufficient time). People with XDR-TB can be infectious and pass the drug-resistant bacteria to other people.How easily is XDR-TB spread?There is probably no difference between the speed of transmission of XDR-TB and those of any other forms of TB. The spread of TB bacteria depends on factors such as the number and concentration of infectious people in any one place and the time of exposure, along with the presence of people with a higher risk of being infected, such as those with HIV/AIDS.Can XDR-TB be cured or treated?Several countries with good TB control programmes have shown that up to 50-60% of affected people can be cured. Nevertheless, successful treatment also depends greatly on the extent of the drug resistance, the severity of the disease and whether the patient’s immune system is compromised.Can vaccination prevent XDR-TB?The TB vaccine, called the bacille Calmette- Guarin (BCG) vaccine, prevents severe forms of TB in children, such as TB meningitis. BCG would be expected to have the same effect in preventing severe forms of TB in children, even if they were exposed to XDR-TB, but it may be less effective in preventing TB in adults. New vaccines are urgently needed, and WHO and members of the Stop TB Partnership are actively working on them.How do I know if I have TB or XDR-TB?Symptoms of XDR-TB are no different from those of ordinary or drug-susceptible TB:

• a cough with thick, cloudy mucus (or sputum), sometimes with blood, for more than 2 weeks;
• fever, chills and night sweats;
• fatigue and muscle weakness;
• weight loss; and
• in some cases, shortness of breath and chest pain.

If you have these symptoms, you do not necessarily have XDR-TB, but you must see a doctor for a check-up. If you are already being treated for TB and at least some of these symptoms are not improving after a few weeks of treatment, you should inform your clinician or nurse.How quickly can XDR-TB be diagnosed?This depends on the patient’s access to health care services. If TB bacteria are found in the sputum, TB can be diagnosed in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant forms. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Such a final diagnosis for TB, and especially XDR-TB, may take 6-16 weeks. To reduce this period, new tools for rapid TB diagnosis are urgently needed.How can a person with drug-sensitive TB avoid getting XDR-TB?The most important thing is to continue taking all treatment exactly as prescribed. No doses should be missed and treatment should be taken right through to the end. If patients suffer from side-effects – for example, the tablets make them feel sick – they should inform their clinicians or nurses, because simple solutions are often available. If they need to travel for any reason, patients should make sure they have enough tablets with them for the duration of the trip.What is the link between XDR-TB and HIV/AIDS?In places where XDR-TB is most common, people living with HIV are at greater risk of becoming infected with XDR-TB, owing to their weakened immunity. If many HIV-infected people live in these places, there will be a strong link between XDR-TB and HIV. Fortunately, in most places with high HIV rates, XDR-TB is not widespread. For this reason, most people with HIV who develop TB will have drug-susceptible TB, and can be treated with standard first-line anti-TB drugs.How common is XDR-TB?XDR-TB is rare, although numbers of cases are not yet known. WHO estimates that there were almost half a million cases of MDR-TB worldwide in 2004, however, with the highest rates in Europe. Wherever second-line drugs to treat MDR-TB are being misused, the possibility of XDR-TB exists. Recent studies indicate that XDR-TB cases comprise 15% of MDR-TB cases in some areas of Europe and urgent research is under way to find out more.Is it safe to travel to places where XDR-TB has been identified?XDR-TB has been found in every region of the world. The people most at risk if they come into contact with someone with XDR-TB are those with reduced immunity to infectious diseases, such as those with HIV or other medical conditions that can compromise the immune system. Such people should avoid high-risk areas, where no infection control measures are in place. Air travel carries only very minimal risks of infection with TB of any kind. Travellers with concerns about visiting countries with XDR-TB, or other health risks, should seek advice from their doctors, national authorities or trusted travel web sites such as that of WHO(http://www.who.int/topics/travel ). Why have I never heard of XDR-TB before?For some years, isolated cases of very highly resistant TB around the world have been seen that would today be called XDR-TB. These cases have been reported in greater numbers only recently, as regular surveys of drug resistance have been made in more and more countries and laboratory capacities have improved. This has led to the closer examination and naming of the problem.How do countries prevent XDR-TB?Countries can prevent XDR-TB by ensuring that the work of their national TB control programmes, and all practitioners working with people with TB, is carried out according to the International standards for tuberculosis care . These emphasize:

• providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB;
• ensuring regular, timely supplies of all anti-TB drugs;
• properly managing anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; and
• caring for people with XDR-TB in centres with proper ventilation, and minimizing contact with other patients (particularly those with HIV), especially in the early stages before treatment has had a chance to reduce the infectiousness.

Meanwhile, countries should promote the wide dissemination of The patients’ charter for tuberculosis care , which lists the rights and responsibilities of TB patients and their families.What should I do after contact with a person known or suspected to have XDR-TB?You should consult your doctor or a local TB clinic, and be screened for TB. This is most important if you have any symptoms of TB. In case of cough, you will be asked to provide a sample of sputum, which will be tested in the laboratory. Several other tests will be performed in the clinic, including a skin test and a chest radiograph.(Source: World Health Organisation : April 2007.)