The term XDR appears to have been used for the first time in March 2006. A report was published jointly by the US CDC and the World Health Organisation (WHO), describing strains of TB that were resistant not only to isoniazid and rifampicin (that is they were MDR-TB) but they were also resistant to at least three of the six classes of second line anti TB drugs.1“Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs — Worldwide, 2000-2004”, CDC MMWR, March 24 2006
www.cdc.gov/mmwr 2Migliori, G “125 years after Robert Koch’s discovery of the tubercle bacillus: the new XDR-TB threat. Is “science” enough to tackle the epidemic?”, European Respiratory Journal, March 1 2007
This definition was subsequently modified at a meeting of the WHO XDR TB Task Force in October 2006. The revised definition is strains of TB that are resistant to at least rifampicin and isoniazid (which means that it is MDR-TB), and also resistant to a fluoroquinolone and to at least one of the three injectable TB drugs, capreomycin, kanamycin and amikacin.3“Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control”, Weekly epidemiological record, WHO, Geneva, 2006, 81 www.who.int/
XDR is sometimes referred to as extensively drug resistant TB.4“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.
XDR TB Statistics
By the end of 2017 XDR had been reported by 127 Member States of the World Health Organisation. Combining the data, the average proportion of MDR-TB cases with XDR-TB was 8.5%. The best estimate was higher than those based on data available for 2016 (6.2% in 2016, 9.5% in 2015, 9.7% in 2014). Among the 40 countries with a high TB or MDR-TB burden, 22 have data on resistance to second line anti TB drugs.
The proportion of MDR-TB/RR-TB cases with resistance to any fluoroquinolone for which testing was done was 22%.
The notified cases of XDR TB, or extensively drug resistant TB, by World Health Organisation (WHO) region for 2017 are given below 5“Global Tuberculosis Report 2018”, WHO, Geneva, 2018
Notified cases of XDR TB in 2017 by WHO region
|Region||Notified Cases of XDR TB|
|Global Total for XDR-TB||10,800|
If there is a "plus sign" click on it for more columns.
A total of 10,800 cases of XDR-TB were reported by 77 countries (up from 8,014 cases reported by 72 countries in 2016) with 88% of cases being from the WHO European and South-East Asia regions.
The five countries that reported the largest number of cases were Belarus (525), India (2,650), the Russian Federation (3,661), South Africa (747) and Ukraine (1097).
XDR TB Treatment
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.6Auld, 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.
XDR TB 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.7Tugela 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.8“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.9Gandhi, 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.” 10Cooke, G. “International Spread of MDR TB from Tugela Ferry, South Africa”, Emerg Infect Dis, Volume 17, November 2011, 1575-1580
XDR TB is treatable and curable
When XDR 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.11“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.12Mitnick, C. “Comprehensive Treatment of Extensively Drug Resistant Tuberculosis”, N Engl J Med, August 2008, 563-574 www.nejm.org/