Extensively drug-resistant tuberculosis

Extensively drug-resistant tuberculosis (XDR-TB) is defined as tuberculosis that has evolved resistance to rifampicin and isoniazid (resistance to these first line anti-TB drugs defines Multi-drug-resistant tuberculosis, or MDR-TB), as well as to any member of the quinolone family and at least one of the following second-line TB treatments: kanamycin, capreomycin, or amikacin. The old case definition of XDR-TB is MDR-TB that is also resistant to three or more of the six classes of second-line drugs. This definition should no longer be used, but is included here because many older publications refer to it.

The principles of treatment for MDR-TB and for XDR-TB are the same. The main difference is that XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. The epidemiology of XDR-TB is currently not well studied, but it is believed that XDR-TB does not transmit easily in healthy populations, yet is capable of causing epidemics in populations which are already stricken by HIV and therefore more susceptible to TB infection.

Epidemiology of drug-resistant TB
A 1997 survey of 35 countries found mortality rates above 2% in about a third of the countries surveyed. The highest rates were in the former USSR, Argentina, India and China, and was associated with poor or failing national tuberculosis control programs. Likewise, the appearance of high rates of MDR-TB in New York city in the early 1990s was associated with the dismantling of public health programmes.

MDR-TB strains appear to be less fit and less transmissible. It has been known for many years that INH-resistant TB is less virulent in guinea pigs, and the epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in Los Angeles found that only 6% of cases of MDR-TB were clustered. MDR-TB has a mortality rate comparable to lung cancer. People who have weakened immune systems (because of diseases such as HIV or because of drugs) are more susceptible to catching TB.

South African epidemic
Since late 2006, there has been an epidemic of XDR-TB in South Africa. The outbreak was first reported as a cluster of 53 patients in a rural hospital in KwaZulu-Natal of whom 52 died. What was particularly worrisome was that the median survival from sputum specimen collection to death was only 16 days and that the majority of patients had never previously received treatment for tuberculosis. This is the epidemic for which the acronym XDR-TB was first used, and although TB strains that fulfill the current definition have been identified retrospectively, this was the largest group of linked cases ever found. Since the initial report in September 2006, cases have now been reported in most provinces in South Africa. As of 16 March 2007, there were 314 cases reported, with 215 deaths. It is clear that the spread of this strain of TB is closely associated with a high prevalence of Aids and poor infection control; in other countries where XDR-TB strains have arisen, drug resistance has arisen from mismanagement of cases or poor patient compliance with drug treatment instead of being transmitted from person to person. This strain of TB does not respond to any of the drugs currently available in South Africa for first- or second-line treatment. It is now clear that the problem has been around for much longer than health department officials have suggested, and is far more extensive. By 23 November 2006, 303 cases of XDR-TB had been reported, of which 263 were in KwaZulu-Natal. Serious thought has been put to isolation procedures that may deny some patients their mobility. This has been seen as unconstitutional by the government and patients come and go as they see fit. The few that do get quarantined start riots and stone security guards. Quarantining patients is necessary to prevent further spread of this strain of TB.