Drug Resistant TB

A person with active TB disease has drug resistant TB if the TB bacteria that the person is infected with, will not respond to, and are resistant to, at least one of the main TB drugs.1

Drug susceptible TB is the opposite of drug resistant TB. If someone is infected with TB bacteria that are fully susceptible, it means that all of the TB drugs will be effective so long as they are taken properly. It still means that several drugs need to be taken together to provide effective TB treatment.

Drug resistant TB - how you get it?

There are two ways that people get drug resistant TB.

  • Firstly, people get acquired drug resistant TB when their TB treatment is inadequate. This can be for a number of reasons, including the fact that patients fail to adhere to proper treatment regimes, the wrong drugs are prescribed, or sub standard drugs are used for treatment.
  • Secondly, transmitted or primary drug resistant TB results from the direct transmission of drug resistant TB from one person to another. The occurrence and prevention of primary drug resistant TB has largely been neglected during the development of global TB control programs.

Drug resistant TB - the different types

Some organisations believe that reference should, in most instances, be only made to drug resistant TB generally, as patients can be infected with strains with a wide range of combinations of resistance to different TB drugs. It is also thought by some people that terms as multi drug resistant TB and extensively drug resistant TB can be limiting in terms of treatment regime: as well as their use encouraging patients to be labelled and further stigmatised by their disease.2

However most organisations believe that it is helpful and often necessary to regularly refer to two specific types of drug resistant TB, MDR TB and XDR TB. Another type of drug resistant TB, variously referred to as totally drug resistant TB, XXDR TB or TDR TB has also now been detected.34

Multi drug resistant TB and extensively drug resistant TB

Multi drug resistant TB (MDR TB) is the name given to TB when the bacteria that are causing it are resistant to at least isoniazid and rifampicin, two of the most effective anti TB drugs.

Extensively drug resistant TB (XDR TB) is defined as strains resistant to at least rifampicin and isoniazid in addition to being resistant to one of the fluoroquinolones, as well as resistant to at least one of the second line injectable TB drugs amikacin, kanamycin or capreomycin.5

Multi drug resistant TB and extensively drug resistant TB do not respond to the standard six months of treatment with "first line" anti TB drugs, and treatment for them can take two years or more and requires treatment with other drugs that are less potent, more toxic and much more expensive. Worldwide only a few thousand patients with multi drug resistant TB and extensively drug resistant TB are treated each year.6

In areas of minimal or no multi drug resistant TB, TB cure rates of up to 95 per cent can be achieved. Cure rates for multi drug resistant TB are lower, typically ranging from around 50% to 70%.7

MDR plus TB

Having just two categories for all those people who have MDR or XDR TB, is possibly under representing the extent of resistance to the second line TB drugs, as well as causing confusion as people in an ad hoc way adopt new terms.

A study reported in 2012, showed that of 1,278 patients with MDR TB, some 43.7% had resistance to at least one second line drug. They did not though have the specific resistance to two of the classes of second line drug, necessary for them to be categorised as XDR TB, which in this study was at a level of 6.7%8

It could be useful to have a new category of "MDR plus TB" for people with MDR TB, but who also have some resistance to second line drugs, but not sufficient for them to be categorised as having XDR TB. If monitored by WHO and others, it could enable more information to be available about the extent to which resistance is developing to the second line drugs.

The adoption by WHO of a new category of MDR plus TB, would also reduce the confusion caused by the current use by some people of the term "pre XDR-TB".9

Totally drug resistant TB (XXDR TB)

Totally drug resistant TB is TB which is believed to be resistant to all the first and second line TB drugs. It is sometimes referred to as extremely drug resistant TB, and it is extremely difficult, although not always totally impossible to treat.

XDR plus TB

The World Health Organisation considers all the cases of "totally" drug resistant TB to be XDR TB because they all satisfy the criteria for XDR TB.

As there is currently some considerable confusion being caused by all the different names, one possibility would be to refer to these cases of drug resistant TB as being "XDR plus" TB, meaning cases of XDR TB with additional unspecified resistance. This would be similar to having MDR plus TB for cases of MDR TB where there was additional resistance.

How many cases are there each year of drug resistant TB?

In 2011 the World Health Organisation (WHO) estimated that there were globally 310,000 cases of multi drug resistant TB among those cases of pulmonary TB that were reported to them.10

It was also estimated that in total there were 630,000 cases of multi drug resistant TB among the world’s 12 million prevalent cases of active TB. The number of prevalent cases of MDR-TB is important as it directly influences the active transmission of strains of MDR TB.11 (For more about TB incidence and prevalence see the TB statistics page.)

The WHO is not able to provide an answer as to whether the number of people with multi drug resistant TB is increasing, decreasing or stable, either regionally or globally.12 Some organisations believe that the current statistics for drug resistant TB greatly underestimate the extent of the problem.

“Wherever we're looking for drug resistant TB we're finding it in very alarming numbers. And that suggests to us that the current statistics that are being published about the prevalence of multi drug resistant TB are really just scratching the surface of the problem.”

Dr Leslie Shanks, Medical Director, MSF13

Where does drug resistant TB occur?

Where does multi drug resistant TB occur?

The notified cases of multi drug resistant TB (MDR TB) by WHO region are given below.14

Notified multi drug resistant TB by WHO Region 2011
Region Notified cases of multi drug resistant TB
Africa 12,384
Americas 2,969
Eastern Mediterranean 841
Europe 32,348
South-East Asia 6,615
Western Pacific 4,392
Global Total for multi drug resistant TB 59,549

Globally just under 60,000 cases of MDR TB were notified to WHO in 2011, mostly by European countries and South Africa. This represented just 19% of the 310,000 cases of MDR TB estimated to exist among the patients with pulmonary TB who were notified to WHO in 2011.

The highest prevalence of MDR TB that had been documented by 2012 was in Minsk, Belarus, with a prevalence of 47.8% being reported in 2011. Among patients with infectious (smear positive) pulmonary disease, MDR TB was seen in 35.3% of newly detected cases, and in a massive 76.5% of previously treated patients.15

Where does extensively drug resistant (XDR) TB occur?

By 2012 some 84 countries had reported at least one case of extensively drug resistant TB. These are not just developing countries, but include countries such as England and the United States of America. The proportion of MDR-TB cases with XDR TB was 9.0%.16

High burden drug resistant TB countries

There are 27 "high burden" countries. These are countries where there are at least 4,000 cases of multi drug resistant TB each year and/or at least 10% of newly registered TB cases are of multi drug resistant TB.17

The 27 "high burden" countries are:

Armenia, Azerbaijan, Bangladesh, Belarus, Bulgaria, China, Democratic Republic of the Congo, Estonia, Ethiopia, Georgia, India, Indonesia, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Myanmar, Nigeria, Pakistan, Philippines, Republic of Moldova, Russian Federation, South Africa, Tajikistan, Ukraine, Uzbekistan, Viet Nam.

There is some more about TB in India as well as some more multi drug resistant TB statistics including the number of cases in each high burden country.

WHO estimate that some 5% of people with multi drug resistant TB may actually have extensively drug resistant TB. So if the actual number of multi drug resistant TB cases could be as high as 500,000 people, it means that as many as 25,000 cases of extensively drug resistant TB could already have occurred.18

The cost of treating drug resistant TB

The cost of just the drugs for treating the average multi drug resistant TB patient can be 50 to 200 times higher than the cost of treating a drug susceptible TB patient. The total costs though are much more than just the drug costs, and must include such costs as the equipment for diagnosis as well as all the labor costs.

In addition although the disease may be the same in different countries of the world, the overall costs of treatment can be very different. This is not just because the finances and facilities may be different, but also because the expectations of both patients and health care workers and what is considered to constitute good treatment may be different.

Different countries, different expectations

For example, in many countries discussion about the costs of drug resistant TB may well be about using DOTS Plus and whether it can be afforded, and can the system possibly afford drug susceptibility testing on all initial isolates of TB, as well as the cost of second line drugs for the treatment of drug resistant TB.

a patient with drug resistant TB

A doctor checks for signs of life and finds none, in a patient with drug resistant TB in the Ukraine © Misha Friedman/WHO

By contrast, in many parts of the United States and in some parts of Western Europe, the political and social pressures regarding the financing of drug resistant TB control may well be to locate enough money for negative pressure isolation rooms, so that every single patient coming through the door of a hospital who might possibly have pulmonary TB, can be put in such a room and kept there until it has been proven that they have not got drug resistant TB.19

However, short term decisions about, for example, the affordability of drug susceptibility testing, can and indeed does result in a lack of effective treatment for drug resistant TB in many countries and areas. This not only causes many unnecessary deaths, but also helps to fuel the ongoing spread of drug resistant TB.

Treating drug resistant TB - the problems

There are a number of major problems with providing effective treatment for drug resistant TB. Although many of these also apply to the provision of treatment for drug susceptible TB, they are particularly important in respect of the large scale effective provision of treatment for drug resistant TB.20 21

Diagnosing drug resistant TB

Globally there is very limited capacity to rapidly diagnose drug resistant TB. Although some new TB tests are becoming available such as the Xpert TB test, point of care testing is still practically non existent in the areas with the highest TB burden. To overcome the problems of drug resistant TB there needs to be development of true point of care drug susceptibility tests, and their widespread implementation at affordable cost.

National TB control programs

National TB control programs must include a universal right to treatment for drug resistant TB. It is now accepted that there is a universal right to treatment, for the treatment of HIV/AIDS. Treatment for drug resistant TB should be viewed in the same way

Drug supply

There also needs to be a significant increase in the number of manufacturers of quality assured second line anti TB drugs. Action needs to be taken on this by the Global Drug Fund (GDF) and the Green Light Committee (GLC), as well as by WHO and their international partners, as part of the global TB initiative.

Drug regimes

A major cause of the current drug resistance problems is the complexity and length of even the "basic" treatment regime for drug sensitive TB. There is an urgent need for new drugs with shorter simpler regimes for drug sensitive TB, as well as new drugs for the treatment of TB that is resistant to all the current TB drugs.

Global control of drug resistant TB

Drug susceptible versus drug resistant TB

At the level of global TB control there is a tension between concentrating on either drug susceptible or drug resistant TB. Some people consider that the way forward is to concentrate on drug susceptible TB, and to particularly strengthen national TB control programs, believing that this will limit or even eliminate drug resistant TB. Others consider that drug resistant TB is where the emphasis must be.

“There is a need to directly confront MDR TB and XDR TB, whereas emphasis in the past has been on strengthening TB control programs per se, believing that we could thereby control the problem of MDR and XDR TB.” 22

At local, national and global level, the resources and the commitment need to be found to do both. National TB control programs need to more effectively find and treat people with drug susceptible TB, and they then won't develop and spread drug resistant TB. There is also a need to find and treat those with drug resistant TB, to not only save their lives, but also to prevent them transmitting drug resistant TB to others. There is no reason why this should not be possible.

Doing better with drug resistant TB

“Today MDR TB spreads unchecked in most of the world. It is fuelled by poverty at the individual and family levels, - limiting access to effective treatment - and at the regional and national level, where under resourced governments lack the capacity to tackle this disease.” 23

Where next?

Get some more TB facts, or learn about the prevention of TB and the use of the BCG vaccine.

Major Source

Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global Report on Surveillance and Response, WHO, Geneva, 2010 www.who.int/tb/publications

References

  1. "Drug resistance" National Cancer Institute, http://www.cancer.gov
  2. "A patient centred approach to drug resistant tuberculosis treatment in the community: a pilot project in Khayelitsha, South Africa" MSF South Africa & Lesotho, 2009, www.msf.org.za/publications/reports-and-publications
  3. Velayati, Ali "Emergence of New Forms of Totally Drug Resistant Tuberculosis Bacilli", Chest, Vol 136, August 2009, no. 2 420-425 http://chestjournal.chestpubs.org
  4. Migliori, 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 http://erj.ersjournals.com
  5. "Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control", Weekly epidemiological record, WHO, Geneva, 2006, 81 www.who.int/
  6. "Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global Report on Surveillance and Response", WHO, Geneva, 2010, 4 www.who.int/tb/publications
  7. "The Global Plan to STOP TB 2011-2015", WHO, Geneva, 2010, vi www.stoptb.org/global/plan
  8. Dalton, T. "Prevalence of and risk factors for resistance to second line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study", The Lancet, 30 August 2012 www.thelancet.com/journals/lancet/article/
  9. "A Study to Evaluate the Efficacy and Safety of TMC207 in Patients With Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis", clinicaltrials.gov
  10. "Global Tuberculosis Report 2012", WHO, Geneva, 2012 www.who.int/tb/publications/global_report/
  11. "Global Tuberculosis Report 2012", WHO, Geneva, 2012 www.who.int/tb/publications/global_report/
  12. "Global Tuberculosis Control 2011", WHO, Geneva, 2011, 38 www.who.int/tb/publications/global_report/
  13. DeCapua, J "MSF: Alarming scope of drug resistant TB", Voice of America, March, 2012 www.voanews.com/english/news/
  14. "Global Tuberculosis Report 2012", WHO, Geneva, 2012 www.who.int/tb/publications/global_report/
  15. Hoffner, S. "Unexpected high levels of multidrug-resistant tuberculosis present new challenges for tuberculosis control", The Lancet, 30 August 2012 www.thelancet.com/journals/lancet/article
  16. "Global Tuberculosis Report 2012", WHO, Geneva, 2012 www.who.int/tb/publications/global_report/
  17. "Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global Report on Surveillance and Response", WHO, Geneva, 2010, 15 www.who.int/tb/publications
  18. "Global Tuberculosis Control 2011", WHO, Geneva, 2011, 38 www.who.int/tb/publications/global_report/
  19. Davis, P. "Drug-resistant TB, from Molecules to Macro-economics" Annals of the New York Academy of Sciences, Volume 953, 235
  20. IOM (Institute of Medicine). "Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary" The National Academies Press, 2009, 149
  21. Keshavjee, S., Farmer, P.E. "Time to put boots on the ground: making universal access to MDR-TB treatment a reality", Int J Tuberc Lung Dis, 14(10), October 2010, 1222-1225 http://www.ingentaconnect.com
  22. IOM (Institute of Medicine). "Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary" The National Academies Press, 2009, 12
  23. Keshavjee, S., Farmer, P.E. "Time to put boots on the ground: making universal access to MDR-TB treatment a reality", Int J Tuberc Lung Dis, 14(10), October 2010, 1222-1225 http://www.ingentaconnect.com

Top of the page