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Drug resistant TB – Types, statistics & global control

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 resistance” National Cancer Institute, http://www.cancer.gov

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 susceptibility testing is how you find out which drugs will be effective against certain TB bacteria.

Drug resistant TB – how do 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 keep to proper TB treatment regimes. It can also be that the wrong TB drugs are prescribed, or sub standard TB 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.

What are the main types of drug resistant TB?

There are two main types of drug resistant TB, MDR TB and XDR TB.

MDR TB is the type of drug resistant TB, when the bacteria are resistant to the TB drugs rifampicin and isoniazid

MDR TB is the type of drug resistant TB, when the bacteria are resistant to the TB drugs rifampicin and isoniazid

MDR (multi drug resistant) 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 TB drugs.

XDR TB (extensively drug resistant TB) is defined as strains resistant to at least rifampicin and isoniazid. This is in addition to strains 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.2“Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control”, Weekly epidemiological record, WHO, Geneva, 2006, 81 www.who.int/

MDR TB and XDR TB do not respond to the standard six months of TB treatment with “first line” anti TB drugs. 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 MDR TB and XDR TB are treated each year.3“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 There is more about the treatment of drug resistant TB.

What other types of drug resistant TB are there?

A third type of drug resistant TB, variously referred to as totally drug resistant TB, XXDR TB or TDR TB has also now been detected.4Velayati, Ali “Emergence of New Forms of Totally Drug Resistant Tuberculosis Bacilli”, Chest, Vol 136, August 2009, no. 2 420-425 http://www.ncbi.nlm.nih.gov/pubmed/ 5Migliori, 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 It is sometimes also referred to as extremely drug resistant TB, and it is extremely difficult, although not always totally impossible to treat.

A fourth type of drug resistant TB is RR TB, which is an abbreviation of rifampicin resistant TB. If bacteria are just resistant to rifampicin then this is still called drug resistant TB. However, if the bacteria are also resistant to the drug isoniazid it is known as multi drug resistant TB or MDR TB.  When a person is described as having MDR TB, it is not clear whether they may also be resistant to other drugs as well. So the World Health Organisation has now started to refer to “uncomplicated MRD-TB”. This is TB which is resistant to isoniazid and rifampicin (making it MDR TB) but it is known that the bacteria are not resistant to any of the second line TB drugs.

What are the statistics for 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

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

In 2014 the World Health Organisation (WHO) estimated that 3.3% of new cases and 20% of previously treated cases of TB were of MDR TB.6“Global Tuberculosis Report 2015”, WHO, Geneva, 2015 www.who.int/tb/publications/global_report/

Among patients with pulmonary TB who were notified to WHO in 2014 it is estimated that  300,000 had MDR-TB. Globally in 2014 123,000 patients with MDR-TB or rifampicin resistant TB (RR-TB) were actually notified. This was just 41% of the number of estimated cases of 300,000.

There were also approximately 190,000 deaths from MDR-TB. More than half of these patients were in India, China and the Russian Federation.

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, MSF7DeCapua, J “MSF: Alarming scope of drug resistant TB”, Voice of America, March, 2012 www.voanews.com

XDR TB has been reported by 105 countries. On average an estimated 9.7% of people with MDR TB have XDR TB.

Very few statistics are available for totally drug resistant TB.8Velayati, Ali “Emergence of New Forms of Totally Drug Resistant Tuberculosis Bacilli”, Chest, Vol 136, August 2009, no. 2 420-425 http://www.ncbi.nlm.nih.gov/pubmed/ 9Migliori, 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

Where does MDR TB occur?

The estimated cases of MDR TB, among notified cases of MDR TB, by World Health Organisation (WHO) region are given below.10“Global Tuberculosis Report 2015”, WHO, Geneva, 2015 www.who.int/tb/publications/global_report/

Notified MDR TB by WHO Region 2014
Region Estimated cases of multi drug resistant TB
Africa 32,000
Americas 7,000
Eastern Mediterranean 15,000
Europe 72,000
South-East Asia 99,000
Western Pacific 71,000
Global Total for multi drug resistant TB 300,000

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.11Hoffner, 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

High burden drug resistant TB countries

There are 27 TB drug resistant “high burden” countries. These are the 27 countries with the highest incidence of TB. They are also countries where there are at least 4,000 cases of MDR TB each year and/or at least 10% of newly registered TB cases are of MDR TB.12“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

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 more about  “high burden” drug resistant TB countries and the list is now being revised.

There is also some more about drug resistant TB in India and drug resistant TB in South Africa.

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 Genexpert 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.

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. They believe 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.” 13IOM (Institute of Medicine). “Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary” The National Academies Press, 2009, 12

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. They then won’t develop and spread drug resistant TB. There is also a need to find people and provide treatment for their drug resistant TB. This is 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.

There is also a need for higher income countries which are not so directly affected, to play their part at a global level in combating drug resistant TB. In 2015 a plan was published by the United States to combat drug resistant TB, both within the United States and in other countries.

Doing better with drug resistant TB

 “Today MDR TB spreads unchecked in most of the world. It is fueled 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.” 14Keshavjee, 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

Major sources for drug resistant TB

Drug resistant TB 2014 Supplement Global Tuberculosis Report, WHO, Geneva, 2014 www.who.int/tb/publications/global_report/en

Global Tuberculosis Control 2015, WHO, Geneva, 2015 www.who.int/tb/publications/global_report/

References

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1. “Drug resistance” National Cancer Institute, http://www.cancer.gov
2. “Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control”, Weekly epidemiological record, WHO, Geneva, 2006, 81 www.who.int/
3. “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
4. Velayati, Ali “Emergence of New Forms of Totally Drug Resistant Tuberculosis Bacilli”, Chest, Vol 136, August 2009, no. 2 420-425 http://www.ncbi.nlm.nih.gov/pubmed/
5. 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
6. “Global Tuberculosis Report 2015”, WHO, Geneva, 2015 www.who.int/tb/publications/global_report/
7. DeCapua, J “MSF: Alarming scope of drug resistant TB”, Voice of America, March, 2012 www.voanews.com
8. Velayati, Ali “Emergence of New Forms of Totally Drug Resistant Tuberculosis Bacilli”, Chest, Vol 136, August 2009, no. 2 420-425 http://www.ncbi.nlm.nih.gov/pubmed/
9. 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
10. “Global Tuberculosis Report 2015”, WHO, Geneva, 2015 www.who.int/tb/publications/global_report/
11. 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
12. “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
13. 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
14. 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