1. Multidrug-/ rifampicin-resistant TB
(MDR/RR-TB):
Update 2017

2. Estimated number of deaths, 2016
The global TB situation (1)
Estimated incidence, 2016
Estimated number of deaths, 2016
1.3 million*
(1.2–1.4 million)
10.4 million
(8.8–12.2 million)
600,000 (540,000–660,000)
All forms of TB
Multidrug- / rifampicin-resistant TB (MDR/RR-TB)
HIV-associated TB
1.0 million
(0.9–1.2 million)
374,000
(325,000–427,000)
Source: WHO Global Tuberculosis Report 2017
In 2016, it was estimated that the global incidence of TB was 140 cases per 100,000 population, with most cases occurring in Asia (62%) and Africa (25%). With 1.67 million deaths in 2016, TB is the ninth leading cause of death worldwide and, since 2012, the top killer among the infectious conditions, topping HIV. An estimated 490,000 new MDR-TB cases and 110,000 rifampicin-resistant TB (RR-TB) cases emerged in MDR/RR-TB was responsible for an estimated 240,000 deaths in the same year.
240,000 (140,000–340,000)
* Excluding deaths attributed to HIV/TB

3. The global TB situation (2)
TB incidence and mortality,
Global TB incidence and mortality rates have been falling for the last decade in all six WHO regions (estimates of TB deaths among HIV-positive people are also on the decline). The rate of decrease in incidence rate (at 1.4% per year between 2000 and 2016) remains far too low to achieve the TB elimination threshold by 2050.

4. The Global Project on
Anti-TB Drug Resistance Surveillance,
Global Project launched
SRL network launched
1st global DRS report
2nd global DRS report
3rd global DRS report
4th global DRS report
M/XDR-TB report
Global TB reports
1994
1997
2000
2003
2004
2008
2009
2010
2017
1st ed. DRS guidelines
2nd ed. DRS guidelines
3rd ed. DRS guidelines
4th ed. DRS guidelines
5th ed. DRS guidelines
The Global Project on Anti-TB Drug Resistance Surveillance is the oldest and most elaborate global initiative of its kind. Established in 1994 and supported by a global network of supranational laboratories, the project has established a standardised methodology for drug-resistance surveillance which is serving as a model for the monitoring of other forms of antimicrobial resistance in the world. The results and methods have been published in several publications over the last two decades.
Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

5. The WHO Network of TB Supranational Reference Laboratories comprises 37 laboratories that provide a benchmark for proficiency testing, and can also provide long-term technical assistance to partner countries under a framework of collaborative agreements. The network was developed in 1994, initially to ensure the quality of drug resistance surveys. The Centre for Tuberculosis at the National Institute for Communicable Diseases in Johannesburg, South Africa became the third SRL in the WHO African Region in 2016 and in October 2017 the laboratory in Cotonou, Benin became a full SRL. Over 150 countries and territories have a formal link with a partner SRL.
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO All rights reserved
Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

6. World Health Organization
Measuring TB drug resistance
Periodic surveys vs. continuous surveillance
13 October, October, 2018
Data on drug resistance have now been collected and analyzed from 160 countries worldwide (82% of the 194 WHO Member States), which collectively have more than 97% of the world’s population and TB cases. This includes 90 countries with continuous surveillance systems based on routine diagnostic DST of TB patients, and 70 countries that rely on representative patient. Surveys conducted about every 5 years represent the most common approach to investigating the burden of drug resistance in resource-limited settings where routine DST is not accessible to all TB patients. Among the 40 countries with high burden of TB or MDR-TB, 37 now have had at least one direct measurement of resistance to rifampicin and other anti-TB drugs (Angola, Congo and Liberia have yet to undertake such surveys).

7. Measuring TB drug resistance
Year of most recent data

8. Percentage of new and previously treated TB cases with MDR/RR-TB, 2016
The proportion of MDR/RR-TB among TB patients averages to 4.1% in the new and 19% among the retreatment cases on a global level. This is similar to the levels reported in previous years. Risk of drug resistance however differs markedly between countries and regions, with very high levels in the eastern part of the WHO European Region.
a Best estimates are for the latest available year
Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

9. % MDR/RR-TB in new TB cases
Figures are based on the most recent year for which data have been reported, which varies among countries. Data reported before 2002 are not shown

10. % MDR/RR-TB in previously treated TB cases
Figures are based on the most recent year for which data have been reported, which varies among countries. Data reported before 2002 are not shown. The high percentages of previously treated TB cases with MDR-TB in Bahamas, Belize, French Polynesia, Puerto Rico and Sao Tomé and Principe refer to only a small number of notified cases (range: 1–8 notified previously treated TB cases).

11. 30 high MDR-TB burden countries
30 countries concentrate about 90% of the global disease burden of MDR/RR-TB. These countries are defined as the top 20 countries in terms of estimated numbers of incident MDR-TB and the top 10 by estimated MDR-TB incidence rate per population in 2014 (above a threshold of 1,000 estimated incident MDR-TB cases that year)
Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

12. Estimated incidence of MDR/RR-TB, 2016 for countries with at least 1000 incident cases
Most of the burden of MDR/RR-TB in the world is concentrated in populous countries with a large burden of TB. India, China, the Russian Federation, Indonesia, Nigeria and Pakistan together account for about 60% of the global burden.

13. Trends in new TB (blue) and new MDR-TB (red) case rates selected high MDR-TB burden countries
Time trends can be analysed in countries with stable surveillance system or else which undertake regular representative surveys (9 examples from high MDR-TB burden countries shown in this slide). These measurements can indicate whether drug-resistance is advancing or regressing among TB patients, and can be compared with trends in overall TB notifications. At times these trends reflect the differential impact that TB efforts can have on treating and controlling TB, MDR-TB or both.
Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

14. Isoniazid-resistant TB cases (Hr-TB) Relative burden of Hr-TB among all new and all retreatment TB cases notified globally in 2016 (compared with RR-TB)
New guidelines on the treatment of isoniazid-resistant TB are being released in 2017, in an effort to improve treatment effectiveness in such patients. The 2017 Global tuberculosis report included estimates for the resistance to isoniazid (additional to MDR-TB). Levels of resistance to isoniazid without concurrent rifampicin resistance are available for 158 countries over the period 2002–2016. Among all TB cases, the global average of isoniazid resistance without concurrent rifampicin resistance was 8.5% (95% CI: 7.4–9.7). In new and previously treated TB cases, the global averages were 7.3% (95% CI: 6.1–8.6) and 14% (95% CI: 12–17), respectively. Close to 80% of the Hr-TB cases burden is in new TB cases (in contrast to about 60% for RR-TB cases). Previous reviews had shown higher % of Hr among TB cases in the WHO European Region and Asia than elsewhere.
Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

15. Pyrazinamide resistance
Pyrazinamide is an important component of first-line and second-line TB treatment. It is also one of three drugs in an experimental regimen under trial. Recent surveillance coordinated by WHO has shown high levels of resistance to pyrazinamide even in new patients. Among patients with rifampicin-resistant strains in 5 countries, resistance to pyrazinamide ranged from 37% to 81%.
Source: Zignol M et al. Lancet Infect Dis Jul 7. pii: S (16)

16. Countries ever notifying an XDR−TB case
By the end of October 2017, extensively drug-resistant TB (XDR-TB) had been reported by 121 WHO Member States. The proportion of MDR-TB/RR-TB cases with resistance to any fluoroquinolone for which testing was done – including ofloxacin, levofloxacin and moxifloxacin – was 20% (95% CI: 14–26%. Overall, 6.2% (95% CI: 3.6–9.5%) of MDR-TB cases had XDR-TB, a value lower than past estimates (e.g. 9.5% in 2016), although within the uncertainty limits: it is based on a larger quantity of routine surveillance data and more precise country-specific measures of 2nd line drug resistance among MDR-TB cases. In some countries the frequency of MDR-TB strains resistant to second-line drugs is much higher than the global average.
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO 2017 All rights reserved

17. Moxifloxacin resistance
Later-generation fluoroquinolones are central to second-line regimens for MDR-TB and XDR-TB. Moxifloxacin is one of a handful of members of this class of drugs which is being used, and which is also being tested in experimental regimens for both drug-resistant and susceptible TB. Recent surveys have shown levels of resistance which vary between 8% and 27% among rifampicin-resistant cases in 6 different settings (when tested at 2.0μg/mL frequencies of resistance were lower than those shown in this slide but reached 9% in RR-TB patients in Belarus)
Source: Zignol M et al. Lancet Infect Dis Jul 7. pii: S (16)

18. DR-TB RESPONSE

19. % of bacteriologically confirmed TB cases tested for RR-TB
Diagnostic DST (1)
% of bacteriologically confirmed TB cases tested for RR-TB
Coverage of drug-susceptibility testing for MDR/RR-TB among TB patients increased since 2009 in all WHO Regions and reached 41% of bacteriologically confirmed TB cases notified in 2016, with highest levels achieved in the European Region. The low score is partly due to insufficient access of TB patients to DST. Another reason in some countries is the poor capture of results from laboratories owing to inadequate TB information systems.

20. Diagnostic DST (2)
% of MDR/RR-TB cases with DST results for fluoroquinolones and 2nd line injectable agents
In MDR/RR-TB patients, the detection of resistance to fluoroquinolones and second-line injectable drugs has important implications for the selection of patients eligible for the shorter treatment regimen and for the customization of longer regimens. About one third of MDR-TB patients have resistance to one of these drug classes, or to both (extensive drug resistance; XDR-TB). Many of these patients would be eligible for treatment with new medicines, which are approved for inclusion in MDR-TB regimens and available through donations and/or concessional pricing for most low and middle-income countries. In 2016, close to 40% of MDR/RR-TB patients had DST results reported for these two classes of drugs, although the levels varied substantially by region and country. Poor recovery of laboratory test results accounts to a certain extent for the low coverage observed. Capacity to test more patients is facilitated by the WHO endorsement of line-probe assays (LPA) to fluoroquinolone and 2nd line injectable agents in 2016; LPA technology is already employed in TB diagnostics in over 500 sites in 70 low- and middle-income countries.

21. MDR/RR-TB detection and treatment
MDR/RR-TB cases detected (violet) and number enrolled on MDR-TB treatment (green) , compared with incident MDR/RR-TB cases in 2016 (uncertainty interval shown in blue)
MDR/RR-TB detection and enrolment on treatment increased steadily but slowly between 2009 and In 2016, 153,000 MDR/RR-TB cases were detected and 130,000 TB cases were reported to have started MDR-TB treatment. This falls well below the number of TB patients needing MDR-TB regimens globally; an estimated 600,000 of these cases emerged afresh in 2016 alone. The shortfall reflects combined weaknesses in patient access to diagnostics and medicines and challenges for national programmes to collect data on patients in both the public and private sectors.

22. MDR/RR-TB treatment coverage
Enrolments on MDR-TB treatment as a % of the incident MDR/RR-TB cases, 30 high MDR−TB burden countries, regions and globally, 2016
When the 130,000 TB cases starting MDR-TB treatment worldwide in 2016 are analysed by country burden, very disparate levels of coverage can be discerned among the 30 high MDR-TB burden countries which together concentrate 90% of global MDR/RR-TB burden. In some countries the confidence limits are wide reflecting uncertainties about the underlying burden as a result of incomplete surveillance data.

23.  WHO 2017. All rights reserved
Countries that had used shorter MDR-TB treatment regimens by the end of 2016
By 2016, 36 countries, mostly in Africa and Asia, reported having used shorter MDR-TB regimens. These regimens have been reported to achieve high treatment success rates (87–90%) in selected MDR/RR-TB patients and a standardized shorter MDR-TB regimen is recommended by WHO subject to eligibility criteria. By June 2017, 89 countries were known to have imported or started using bedaquiline and 54 countries had used delamanid. Most (75%) of the patients treated with bedaquiline were reported by two countries: the Russian Federation and South Africa
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO All rights reserved

24. Number of patients with laboratory-confirmed
XDR-TB started on treatment in 2016
In 2016, 70 countries and territories reported treating people with XDR-TB. Globally, 8,500 patients with XDR-TB were enrolled on treatment (higher than in 2015, with 7,256). 80% of the cases were enrolled in India, the Russian Federation, Ukraine, South Africa, and Belarus.
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO All rights reserved

25. Outcomes of MDR/RR-TB treatment
Annual cohorts, by WHO region and global,
The number of MDR/RR-TB cases monitored for outcomes has increased progressively in all WHO Regions. Likewise, the completeness of the outcome reports has improved in several regions and also globally. Nonetheless, treatment success has remained static, reaching only 54% in the cohort of patients starting treatment in 2014, with 16% deaths, 8% with treatment failed, 15% losses to follow-up and 7% unevaluated. However, 8 countries with cohorts >400 patients reported 70% success rate or more.

26. Outcomes of XDR-TB treatment
2014 cohort, by WHO region and global
Among 6,777 XDR-TB patients in 54 countries for whom outcomes were reported in the 2014 cohort, 30% overall completed treatment successfully and 28% died (in 21% treatment failed and 21% were lost to follow up or unevaluated). The biggest numbers reported were in Europe (Russian Fed and Ukraine); nearly all of the African reports were from South Africa and India dominated the figures for the SE Asian Region.
*number of cases observed shown next to the bars

27.  WHO 2017. All rights reserved
Use of SMS, video−supported treatment or electronic medication monitors to improve TB treatment adherence and delivery, 2016
Digital technologies are being used in a variety of ways in TB care, amongst which to support medication adherence in patients on MDR-TB treatment. Some interventions are pilot projects
whereas others are implemented at a much larger scale. Among high TB burden countries, adoption in the public sector has been reported by Cambodia, China, Papua New Guinea, the Russian Federation and Viet Nam. Many countries in the WHO African Region report no use. Although data on the impact of these interventions on improving treatment outcomes of TB
patients and reducing costs to health services remain limited, several studies that are expected to improve the quality of the evidence and provide more information on their performance in different settings are now underway
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO All rights reserved

28. MDR/RR-TB and financing (1)
Funding for prevention, diagnosis and treatment
by intervention area, 2006—2017
(constant 2017 US$ billions)
118 countries with 97% of reported cases reported the data shown. Funding for MDR-TB was estimated at US$ 1.7 billion in 2017, and this amount has decreased since 2014, following a marked increase in 2009–2014. The shortfall between the funding available in 2017 and the requirement of US$ 2.0 billion in 2017 estimated in the Global Plan is comparatively small (US$ 0.3 billion). However, funding for diagnosis and treatment of MDR-TB needs to increase substantially. This is evident from large and persistent gaps in detection and treatment of MDR-TB, both globally and in most countries with a high burden of MDR-TB. It is also evident from the Global Plan, in which the annual funding required for MDR-TB reaches US$ 3.6 billion in 2020, more than double the amount of US$ 1.7 billion available in Domestic funding accounts for a larger share of the funding for MDR-TB than for drug-susceptible TB (many of the high MDR-TB burden countries are in the middle-income bracket). Given the large gaps in detection that remain for MDR-TB, and the gaps between the numbers of cases detected and started on treatment, more funding is required for MDR-TB globally and in most of the high MDR-TB burden countries.

29. MDR/RR-TB and financing (2)
Estimated funding needed for TB control in low- and middle-income countries, 2016—2020
Funding required for a full response to the global TB epidemic, to achieve the End TB Strategy milestones for 2020, have been set out in the Stop TB Partnership’s Global Plan to End TB, 2016–2020. Annual funding required for MDR-TB reaches US$3.6 billion in 2020, more than double the US$ 1.7 billion available in An additional US$ 9 billion was estimated to be needed for TB research and development over the 5-year period

30. MDR/RR-TB and financing (3)
Funding for drug-susceptible TB (green) and MDR-TB (brown), 2006–2017, by country group (constant 2017 US$ millions)
Trends in funding for MDR-TB have been driven by the BRICS (Brazil, Russian Federation, India, China and South Africa) group of countries. The downturn after 2014 is explained by decreasing funding in the Russian Federation (2014–2017) and South Africa (2013–2016). Funding in other countries has meanwhile increased.

31. MDR/RR-TB and financing (4)
Estimated cost per patient treated for MDR-TB, 2016*
* Limited to 80 countries with at least 20 patients on MDR-TB treatment in 2016
The cost per MDR-TB treatment increases by GDP per capita, although there is remarkable variation in cost between countries with similar GDP and caseload. This estimate does not take into account the effectiveness of the treatment programmes, which very often remains unsatisfactory

32. Conclusions
Although only 4.1% of new and 19% of retreatment TB cases have MDR/RR-TB, globally they amount to ~600,000 incident cases each year, challenging the prospect of ending TB by 2035
Coverage of DST for first and second-line TB medicines is improving but only a minority of MDR/RR-TB and XDR-TB patients are being detected and placed on adequate treatment
Surveillance and monitoring continue to improve. Digital technologies offer an opportunity to help bridge some of the weaknesses in data management as well as for patient care (e.g. adherence support)
New policy issued by WHO in promotes novel treatment regimens. Scale-up of such treatment options is needed to impact global success rates for drug-resistant TB patients, especially in countries with large burdens.

33. 5 priority actions
In summary

34. © World Health Organization 2017
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Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis