Extensively drug-resistant tuberculosis (XDR-TB) is as ominous as it sounds. As a second-year resident on the Chest service, you may have treated one or two patients with multi-drug resistant tuberculosis (MDR-TB), which is resistant to at least INH (Isoniazide) and RIF (Rifampin), the two most powerful first-line agents. However, when TB becomes designated as XDR-TB, it implies resistance to any and all Fluoroquinolones and at least one of the three injectable second-line drugs (Amikacin, Capreomycin, and Kanamycin). In short, you have a mycobacterium that Dr. Paul Nunn of the WHO STOP TB Program calls virtually untreatable.
Last year, much media attention was devoted to the problem of XDR-TB in South Africa, where the 11% overall seroprevalence of HIV makes XDR-TB a frightening prospect. Because HIV worsens TB (CD4 cells are required for the control of TB) and TB worsens HIV (TB stimulates the immune system, activating HIV replication), patients with HIV/TB co-infection have three times the risk of death, irrespective of CD4 count. During an outbreak of XDR-TB in the Church of Scotland Hospital in the KwaZulu-Natal hamlet Tugela Ferry in 2005, 52 of the 53 patients (100% HIV positive) died after a median of 25 days. 90% of isolates had the same genetic fingerprint, indicating recent primary infection with XDR-TB, and 56% had previously been admitted to the same hospital, causing concern for nosocomial transmission.
On January 28th, 2007, the New York Times reported that more cases of XDR-TB have been found in South Africa. Since the Church of Scotland Hospital outbreak, 328 cases have been confirmed; and while most have been in KwaZulu-Natal, more cases have been found in 39 hospitals in 8 other South African provinces. On February 3rd, the Independent Online reported the first two cases of XDR-TB to be detected on the Western Cape in South Africa. Further, because of the movement of migrant workers and refugees between South Africa and its neighboring countries of Lesotho, Swaziland, and Mozambique, many experts speculate an impending spread throughout sub-Saharan Africa.
The size of the outbreak may be substantially underestimated because the infrastructure to detect, trace, and treat TB cases is South Africa is very limited. Only one hospital in Durban is capable of isolating and treating actively infected XDR-TB cases to the standards we know here in the US, especially at centers such as Bellevue Hospital. So what has been the response? Prompt TB detection, especially among HIV positive patients, should lead to earlier treatment, less transmission, and less emerging resistance. The WHO STOP-TB program formed a task force in September 2006, and is joining with South African authorities to strengthen TB control with DOT expansion and increasing access to rapid diagnostic and resistance tests (PCR rather than culture-based testing). Unfortunately though, that response has been slow according to clinicians on the front line in South Africa.
While New York City withstood an MDR-TB outbreak in the 1990‚Ń˘s, in part due to the control efforts of our current Department of Health Commissior, Dr. Thomas Freiden, an outbreak of XDR-TB may prove substantially more challenging. So while this current crisis has not hit home here in New York City, it certainly isn‚Ń˘t a bad idea to consider respiratory isolation any time you admit an HIV+ patient with a cough!
Wines M. Virulent TB in South Africa May Imperil Millions Without Quick Action, Experts Warn. New York Times, January 28, 2007.
Lawn SD and Wilkinson R. Extensively drug resistant tuberculosis, BMJ 2006;333:559-560 (16 September).
BBC News ‚Ń˘Virtually untreatable‚Ń˘ TB Found.‚Ń˘Wednesday, 6 September 2006, 07:56 GMT 08:56 UK.
Rich M et al. Guidelines for the programmatic management of drug-resistant tuberculosis. World Health Organization, 2006.
Image courtesy National Library of Medicine, Public Domain