What is XDR TB?
XDR TB is strains of TB that are resistant to rifampicin and isoniazid. They are also resistant to a fluoroquinolone and to at least one of the three injectable TB drugs, capreomycin, kanamycin and amikacin.1“Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control”, Weekly epidemiological record, WHO, Geneva, 2006, 81 www.who.int/
Is a new definition needed?
XDR was defined, and was a helpful definition, when people with drug resistant TB were being treated with injectable drugs. But the injectable drugs are no longer recommended by the World Health Organisation (WHO), and WHO accepts that a new definition is needed.
"the current definition of XDR-TB will probably need to be changed, given the phasing out of injectables, anticipated patterns of resistance that are more relevant to current and future regimens, and advances in diagnostic methods and drug susceptibility testing (DST). Changes to the definition of XDR-TB will be the subject of future expert consultation, and will be included in revised WHO surveillance and reporting guides. Choosing appropriate regimens for patients with strains showing multidrug resistant TB (MDR-TB) plus additional resistance to fluoroquinolones (so called 'pre XDR') are becoming more important and feasable, thanks to rapid advances in molecular DST)."
What is the difference between MDR TB and XDR TB?
MDR TB is strains of TB that are resistant to rifampicin and isoniazid.
What is extensively drug resistant TB?
XDR TB is sometimes referred to as extensively drug resistant TB.2“Global Tuberculosis Report 2015”, WHO, Geneva, 2015
www.who.int/tb/publications/global_report/ There is more about the different types of drug resistant TB.
How many people have XDR TB?
The notified cases of XDR TB, or extensively drug resistant TB, by World Health Organisation (WHO) region for 2019 are given below 3“Global Tuberculosis Report 2020”, WHO, Geneva, 2020
Notified cases of XDR TB in 2019 by WHO region
|Region||Notified Cases of XDR TB|
|Global Total for XDR-TB||12,350|
How many people are treated?
Globally, 8,703 patients with XDR-TB were enrolled in treatment in 70 countries and territories in 2017. This was a small (2%) increase compared with 2016. However in 20 of these countries the number enrolled on treatment was less than the number of cases notified to WHO.
Among 8,399 patients started on treatment in 2015, in 49 countries and territories for which outcomes were reported, 34% completed treatment successfully. Treatment failed for 19%, 26% died and 21% were either lost to follow up or their treatment outcome was not evaluated.
India, the Russian Federation, and Ukraine, accounted for 74% of the 2015 cohort. Cohorts are groups of people who started treatment at a particular time (in this case 2015), and who are then followed for a number of years. Among seven countries with cohorts of more than 100 individuals, mortality was highest (42%) in India and Uzbekistan (41%).
XDR TB in South Africa
In South Africa there were over 1,000 cases of XDR TB diagnosed in the province of KwaZulu-Natal between August 2011 and November 2014. This gives an indication of the level of drug resistant TB in South Africa. It is however believed that many cases are never diagnosed due to a lack of laboratory capacity to test for resistance to second line drugs. Many people may also die from what is thought to be multi drug resistant TB. It may be believed that they were not taking their drugs properly, when they actually had XDR TB and they needed to be given different second line drugs.
A study in KwaZulu-Natal which evaluated the social networks as well as clinical data from people with XDR TB concluded that transmission, in both hospitals and households, had been the primary driver of the XDR TB epidemic in the province.4Auld, S, “South Africa’s XDR-TB epidemic is due to transmission rather then evolution of resistant strains”, CROI, March 2016, www.aidsmap.com This confirms what it is believed happened when the outbreak occurred earlier at Tugela Ferry.
In 2005 South African and US clinicians and researchers identified a large number of cases of extensively drug resistant TB at the Church of Scotland Hospital in Tugela Ferry. Tugela Ferry is a rural and desperately poor part of KwaZulu-Natal province in South Africa.5Tugela Ferry's extensively drug resistant tuberculosis - 10 years on", SAMJ: South African Medical Journal, July 2015 http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742015000700008 It was discovered that of 221 patients with multi drug resistant TB, 53 had XDR TB.6“The tuberculosis X factor”, The Lancet Infectious Diseases, Vol 6, November 2006, 679
www.thelancet.com/journals/ All the patients with XDR-TB had both TB and HIV.
Of the 53 patients with XDR TB diagnosed during the first year of surveillance only one survived. The average survival rate from time of diagnosis was just 16 days among the 42 patients with confirmed dates of death. More than half the patients with XDR TB had never been previously treated for TB. An additional third had either been cured or had completed treatment for previous TB illness.
So it is believed that transmission of XDR-TB strains between individuals had occurred. It was also believed that transmission of TB had occurred in the hospital as two thirds of the patients were recently hospitalised before the onset of XDR TB. At least two health care workers died. These findings were considered to be particularly worrying for resource limited settings where many patients admitted to hospital are HIV positive, and effective TB infection control facilities and practices are extremely limited.7Gandhi, N. “Extensively drug resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa”, The Lancet, Vol 368, 4 November 2006, 1575-1580
By 2009 there had been 820 patients with drug resistant TB at the Tugela Ferry hospital, and 57% had XDR-TB.
It is not just in South Africa that the consequences of what happened at Tugela Ferry are still being seen. Many years later a South African born health care worker died in England of drug resistant TB and he was also infected with HIV. He had worked at the Tugela Ferry hospital during 1996-2002, and it is believed that this is the most likely place that he became infected. It has been said that:
“there were several missed opportunities for diagnosis of TB and HIV that could have prevented this patient’s death.” 8Cooke, G. “International Spread of MDR TB from Tugela Ferry, South Africa”, Emerg Infect Dis, Volume 17, November 2011, 1575-1580
Can XDR TB be cured?
When XDR TB first came to public attention in 2006 it was generally portrayed as a new and virtually incurable disease. The outbreak at Tugela Ferry led many people to believe that being diagnosed with XDR was effectively a death sentence.9“Studies confirm XDR-TB can be cured”, www.pih.org/news/entry/studies-confirm-xdr-tb-can-be-cured/ However a number of studies subsequently published have shown that with intensive and specialised care many people diagnosed with XDR TB can not only be treated but can be cured.
In Peru care was provided to patients with XDR who were not infected with HIV. However they had received numerous previously unsuccessful anti TB treatments. The TB treatment they were provided with was aggressive, with the patients being given many drugs, at the highest doses they could tolerate. In most patients treatment lasted for more than two years.
Drug susceptibility testing was used to decide which regimes were likely to be effective. Some patients were provided with surgery as treatment for their TB. The patients were treated on an outpatient basis and more than half of them were cured of TB.10Mitnick, C. “Comprehensive Treatment of Extensively Drug Resistant Tuberculosis”, N Engl J Med, August 2008, 563-574 www.nejm.org/
This page was last updated in June 2021.
Author Annabel Kanabus
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