ECDC/WHO: World TB Day - Focus On MDR & XDR Treatment Outcomes

 

Map Credit - Tuberculosis surveillance and monitoring in Europe 2014

 

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Next Monday (March 24th) is World TB Day, and so for the next couple of weeks we can expect to see a flurry of reports and assessments released on the global battle against this insidious disease.  The ECDC describes this year’s campaign:

 

2014 theme: MDR TB and MDR TB treatment outcomes

For World TB Day 2014, ECDC is focusing on multidrug-resistant tuberculosis (MDR TB), particularly on MDR TB treatment and treatment outcomes.

In the EU/EEA, the treatment success rates of MDR TB patients have remained stable but at a very low level: only one in every three (34%) patients in the reporting EU/EEA countries finishes MDR TB treatment successfully. More than half die, fail treatment or default (stop taking treatment).

MDR and XDR TB patients face much longer treatment, take more drugs, suffer from more side effects and treatment costs are five times higher compared to drug-susceptible TB. Only complete and successful tuberculosis treatment helps to prevent disease transmission and development of resistant strains that lead to the development of extensively drug-resistant TB (XDR TB), which is almost impossible to treat.

Merely 7 of the 21 countries reporting have maintained a mean five-year decline in MDR notification rates and the overall MDR TB treatment success rate remains far below the 70% target defined by the Framework Action Plan to Fight Tuberculosis in the European Union.

Why is MDR TB still a public health concern?

• TB is slowly declining but MDR and XDR TB pose a serious challenge in the attempt to eliminate TB across Europe, even though the number of reported MDR TB cases seem to decline slowly.
  
• In EU, only 1 in every 3 MDR TB patients has a successful treatment outcome; more than half either die, fail treatment or default (stop taking treatment). XDR TB has even worse treatment outcomes: only 1 in 4 patients finishes treatment successfully
  
• By not diagnosing and not treating patients with MDR TB early and successfully, we put their live at risk and pave the way for XDR TB
  
• Only complete and successful tuberculosis treatment helps to prevent disease transmission and development of resistant strains

 

Today the ECDC and the World Health Organization released an extensive (15mb, 218 pg) PDF report on the TB situation in Europe entitled:

 

Tuberculosis surveillance and monitoring in Europe 2014

18 Mar 2014

Available as PDF in the following languages

ENGLISH

Abstract

​The sixth report launched jointly by the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe (WHO/Europe) indicates that, despite notable progress in the past decade, tuberculosis (TB) is still a public health concern in many countries across Europe. Of particular concern are the high rates of multidrug resistant (MDR) TB outside the European Union (EU)/European Economic Area (EEA). Meanwhile EU/EEA countries themselves have a significant number of TB cases among vulnerable population groups, such as people of foreign origin and prisoners.

An assessment of progress towards TB elimination for the four epidemiological indicators and eight core indicators defined in the report ‘Progressing towards TB elimination: A follow-up to the Framework Action Plan to Fight Tuberculosis in the European Union’ showed that none of the core indicators was achieved at EU/EEA level.

 

While progress has been made in reducing the overall incidence of Tuberculosis in Europe over the past decade, as the following press release indicates, the rise in MDR and XDR TB – and their dismal treatment outcomes -  has tempered any celebrations:

 

Tuberculosis cases down by 6% but only 1 in 3 MDR TB patients finishes treatment successfully

18 Mar 2014

​In 2012, 68 423 cases of tuberculosis (TB)  were reported in 29 EU/EEA countries according to new data published by the European Centre for Disease Prevention and Control and the WHO Regional Office for Europe ahead of World Tuberculosis Day. This results in a notification rate of 13.5 per 100 000 population and constitutes a 6% decrease compared to 2011 (72 000 cases reported), confirming the average annual decline of 5% since 2008.

The surveillance data show that the majority of EU/EEA countries report sustained low levels of TB, which means fewer than 20 TB cases per 100 000 population. In 19 of them, the number of tuberculosis patients decreased. Rates were below 10 per 100 000 population in 18 countries and below 20 in 23 countries.

Overall, the EU/EEA countries have been – and still are – successful in the fight against TB and met the target of an average five-year decline. However, they have not yet met the set targets for successful treatment of the multidrug-resistant form of tuberculosis, MDR TB.

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The Lancet : TB 2013

(From the 2011 TB Progress Report)

 

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To coincide with World TB Day, The Lancet Infectious Diseases  today has published a series of six papers (and comments) on the ongoing battle against tuberculosis, and the rising tide of of multidrug resistant (MDR) and extensively drug-resistant (XDR) TB infections around the globe.

 

Roughly 1/3rd of all new TB cases fall into the MDR-TB or XDR-TB category. Just over a year ago new alarm bells began ringing when an ahead-of-print letter to the journal Clinical Infectious Diseases announced that four cases of TDR (totally drug resistant) tuberculosis had been identified in India.

 

The term TDR-TB was quickly labeled as controversial, and poorly-defined. From the January 2012 ECDC report New drug resistant form of tuberculosis reported in India.

 

Total drug resistant TB is a relative notion and depends on the local drugs available and tested on. This term/expression should either be avoided or should be defined worldwide. The World Health Organization (WHO) has internationally-endorsed treatment recommendations for the treatment of drug-susceptible, MDR-TB and XDR-TB.

 

During this time, Maryn McKenna – Flublogia’s favorite scary disease girl – wrote extensively about these developments on her Superbug Blog:

 

Totally Resistant TB: Earliest Cases in Italy

• By Maryn McKenna January 12, 2012

India Reports Completely Drug-Resistant TB

• By Maryn McKenna January 9, 2012 

Totally Drug-Resistant TB: A Patient Is Missing

• By Maryn McKenna January 14, 2012 

 

A couple of my efforts included Resistant TB: The Limits Of Surveillance & Reporting & EID Journal: Challenges To Defining TDR-TB.

 

Recently the World Health Organization released their 2012 Global Tuberculosis Report, with the following statement regarding reports of TDR-TB.

 

“Totally drug-resistant TB” and developments in India in 2012

In December 2011, clinicians in Mumbai, India reported TB patients with what was termed “total drug resistance”.1 As a result of the intense public interest generated by this episode, in March 2012 WHO convened 40 experts to discuss its implications, whether current evidence makes it possible to define patterns of drug resistance beyond extensively drug resistance TB (XDR-TB) and if better guidance on appropriate treatment options for these patients was possible. While the group acknowledged that patients such as those described in Mumbai pose a formidable challenge to clinicians and public health authorities, no reliable definition beyond XDR-TB could be proposed.

 

Without having a better evidence base, no changes to the current guidelines on how to design treatment regimens for patients with broad patterns of resistance could be recommended. Improvements in the accuracy of drug susceptibility testing to certain drugs and the release of innovative new drugs will, however, change this position in future.

Since December 2011, several important measures have been taken by the Indian government. In Mumbai, laboratory and hospital facilities were improved, contact-tracing stepped up and efforts made to train staff on drug-resistant TB and infection control. Medical staff and funding were increased substantially. Access to second-line drugs was provided to eligible patients. National regulations governing private sales of anti-TB medication were strengthened. By the end of 2012, all 35 states in the country are expected to provide
programmatic management of drug-resistant TB. In May 2012, India made TB a notifiable disease and data collection on TB using a webbased system was initiated.2

 

 

Despite the academic debate over the definition (and existence) of TDR-TB, in January of this year - in  EID Journal: The Emergence Of `Totally Resistant TB’ - more evidence was presented suggesting that TDR-TB is either already here, or on its way.

 

In a similar vein, one of the articles appearing in the Lancet today called Drug-resistant tuberculosis: time for visionary political leadership, warns that:

 

WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis.

 

While a free registration is required, these articles are available online in their entirety. Follow the links to read:

 

Tuberculosis 2013

Published March 24, 2013

Executive summary

To commemorate World TB Day 2013, The Lancet Infectious Diseases publishes a Series of papers on tuberculosis, a disease that has long plagued human beings and was declared a global emergency in 1993 by WHO. Without concerted action from political leaders, health policy makers, funders, and others, health systems worldwide are at risk of being overwhelmed by increasing numbers of patients with treatment-resistant tuberculosis.

 

As new diagnostic tests, drugs, and drug regimens become available that have the potential to radically improve the detection and management of tuberculosis, the papers in the Series explore the challenges for successful implementation of these interventions.

Comments

Tuberculosis 2013 Series

John McConnell, Sally Hargreaves

Full Text | PDF

Zero deaths from tuberculosis: progress, reality, and hope

Alimuddin Zumla, Peter Kim, Markus Maeurer,Marco Schito

Full Text | PDF

Progress and challenges in childhood tuberculosis

Ben J Marais, Stephen M Graham, Markus Maeurer,Alimuddin Zumla

Full Text | PDF

Series Papers

Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test

Stephen D Lawn, Peter Mwaba, Matthew Bates, Amy Piatek, Heather Alexander, Ben J Marais, Luis E Cuevas, Timothy D Mchugh, Lynn Zijenah,Nathan Kapata, Ibrahim Abubakar, Ruth McNerney, Michael Hoelscher, Ziad A Memish, Giovanni Battista Migliori, Peter Kim, Markus Maeurer,Marco Schito, Alimuddin Zumla

Full Text | PDF

Tuberculosis biomarkers discovery: developments, needs,and challenges

Robert S Wallis, Peter S Kim, Stewart Cole, Debra Hanna, Bruno B Andrade, Markus Maeurer, Marco Schito, Alimuddin Zumla

Full Text | PDF

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts

Ben Marais, Knut Lönnroth, Stephen D Lawn, Giovanni B Migliori, Peter Mwaba, Philippe Glaziou, Matthew Bates, Ruth Colagiuri, Lynn Zijenah,Soumya Swaminathan, Ziad Memish, Michel Pletschette, Michael Hoelscher, Ibrahim Abubakar, Rumina Hasan, Afia Zafar, Guiseppe Pantaleo,Gill Craig, Peter Kim, Markus Maeurer, Marco Schito, Alimuddin Zumla

Full Text | PDF

Alignment of new tuberculosis drug regimens and drug susceptibility testing: a framework for action

William A Wells, Catharina C Boehme, Frank G J Cobelens, Colleen Daniels, David Dowdy, Elizabeth Gardiner, Jan Gheuens, Peter Kim, Michael E Kimerling, Barry Kreiswirth, Christian Lienhardt, Khisi Mdluli, Madhukar Pai, Mark D Perkins, Trevor Peter, Matteo Zignol,Alimuddin Zumla, Marco Schito

Full Text | PDF

Drug-resistant tuberculosis: time for visionary political leadership

Ibrahim Abubakar, Matteo Zignol, Dennis Falzon, Mario Raviglione, Lucica Ditiu, Baroness Susan Masham, Ifedayo Adetifa, Nathan Ford,Helen Cox, Stephen D Lawn, Ben Marais, Timothy D McHugh, Peter Mwaba, Matthew Bates, Marc Lipman, Lynn Zijenah, Simon Logan,Ruth McNerney, Adam Zumla, Krishna Sarda, Payam Nahid, Michael Hoelscher, Michel Pletschette, Ziad Memish, Peter Kim, Richard Hafner,Stewart Cole, Giovanni-Battista Migliori, Markus Maeurer, Marco Schito, Alimuddin Zumla

Full Text | PDF

Engaging communities in tuberculosis research

Renaud F Boulanger, Stephanie Seidel, Erica Lessem, Lee Pyne-Mercier, Sharon D Williams, Laia Ruiz Mingote, Cherise Scott, Alicia Y Chou, James V Lavery, on behalf of the Critical Path to TB Drug Regimens' Stakeholder and Community Engagement Workgroup

Full Text | PDF

WHO/ECDC: 1 In 5 TB Patients With Extrapulmonary TB

Credit ECDC

 

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While many are unaware of it, tuberculosis infections can spread far beyond the lungs. When that happens it most often involves the lymph nodes (Tuberculous lymphadenitis), or  pleural, and skeletal/joint areas, although any organ can be involved.

When the TB bacillus infects areas outside of the lungs it is considered an extrapulmonary infection. Diagnosis of extrapulmonary TB can be difficult, and is easily missed.

 

Today, in advance of next Sunday’s World TB Day, the ECDC and the World Health Organization have released a joint report on the treatment of TB. While reductions in pulmonary TB were reported in EU/EEA countries in 2011, the same cannot be said for extrapulmonary TB infections.

 

New ECDC/WHO Euro report: One in five TB patients has extrapulmonary tuberculosis

19 Mar 2013

Every day, around 200 people fall sick with tuberculosis (TB) across the EU/EEA, signalling that there is no room for complacency when it comes to TB prevention and control even in times of financial austerity. To mark World TB Day on the 24 March, ECDC and the WHO Regional Office for Europe release new surveillance data today.

 

The data show that the EU/EEA countries reported over 72 000 cases of TB in 2011, which is a 4% decrease compared to 2010. The average notification rate - 14.2 per 100 000 population - also represents a decline of pulmonary TB notifications. Notification rates vary significantly across Europe, from 2.8 in Iceland to 89.7 in Romania.

 

ECDC contributes to TB control by raising awareness and supporting  EU countries, as director Marc Sprenger points out: “Our primary aim is to further reduce TB transmission by timely diagnosis and adequate treatment of pulmonary TB. This is essential for TB elimination. But we should not forget about the patients with extrapulmonary TB: this group is often neglected in TB control strategies. In 2011, 22% of all notified patients in the EU/EEA had extrapulmonary TB, which can affect any organ of the body making the diagnosis particularly difficult for both physicians and patients”.

Extrapulmonary TB: a challenging diagnosis

A case with TB outside the lungs is considered an extrapulmonary TB case. Symptoms may be diffuse and mimic other pathologies, delaying the diagnosis or making it particularly difficult. In 2011, globally 6.2 million TB cases were notified, 0.8 million with extrapulmonary TB. In the European Union, one in five tuberculosis patients has extrapulmonary TB and unlike pulmonary TB, this form of the disease does not show a downward trend. Extrapulmonary TB is rarely infectious but contributes significantly to TB-related morbidity and can cause complications, lifelong sequelae and disabilities.

 

For World TB Day 2013, ECDC is launching a video documentary that focuses on extrapulmonary tuberculosis (TB). Two patient stories illustrate how difficult the diagnosis of extrapulmonary TB can be before proper treatment and care can start:

Winnie, 39 years old, living in Stockholm (Sweden)

After the first symptoms of abdominal pain started, Winnie visited her family doctor. With increasing swelling of the abdomen, the 39 year-old mother of two was later referred to Stockholm’s Karolinska Hospital gynaecological clinic. The suspected diagnosis of ovarian cancer made Winnie fear for her life and the future of her family.
Seven months after the first symptoms, Winnie was finally told she had extrapulmonary tuberculosis. Treatment started almost immediately: it was just the beginning of Winnie’s battle against the disease.

Italian patient, 54 years old, living in Brescia (Italy)

Nothing indicated that it could be tuberculosis causing the painful swelling in the chest of one Italian patient. For months, her family doctor and several speciality doctors struggled to find a diagnosis that matched her elusive symptoms.
Only after a full clinical investigation did the 54 year-old housewife learn that she had tuberculosis, not in her lungs, but in her chest. For her, the word “tuberculosis” still carries stigma and discrimination. That’s why she decided to share her story but not her identity.

TB treatment

Adequate treatment is essential to prevent the development of the drug-resistant forms of the disease, the multidrug-resistant TB (MDR TB) and the extensively drug-resistant TB (XDR TB). In 2011, cases of MDR TB have decreased but continue to be prevalent especially in the Baltic countries.

 

The ECDC/WHO surveillance report highlights that for the patients with known treatment outcome, only 74% were treated successfully. For 17%, treatment outcome is unknown. This is especially serious given that one untreated TB or MDR TB patient can infect 10-15 other individuals per year.

Press Release “Adequate treatment essential to stop TB across Europe - ECDC/WHO new report”

Watch

Extrapulmonary Tuberculosis: a challenging diagnosis - video documentary

Download

ECDC/WHO TB Surveillance and Monitoring Report 2013
ECDC/WHO TB Surveillance and Monitoring Report 2013 Slide presentation - main findings

Join
Joint twitter chat on Tuberculosis - 22 March 11:00 CET
Use #TBchat
Follow us on @ECDC_EU

 

A few recent blogs on the spread of TB, and particularly the threat posed by MDR-TB, you may wish to revisit:

 

Study: Substandard & Falsified TB Drugs

Lancet: TB Vaccine Trial Disappoints

EID Journal: The Emergence Of `Totally Resistant TB’

EID Journal: XDR-TB/HIV Treatment Outcomes

World TB Day Roundup

 

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Tomorrow - March 24th - is World TB Day, which commemorates the date 130 years ago (1882) when Dr. Robert Koch announced his discovery of the bacillus that causes tuberculosis; Mycobacterium tuberculosis.

 

Despite great advances made against this disease that began with the antibiotic era of the 1940s, in recent years we’ve seen the rise of new drug resistant strains of this killer disease.

 

Although the numbers continue to drop, in 2010 1.4 million deaths were attributed to this disease, and TB remains one of the three greatest causes of death of women (ages 14-44) in the world.

 

WHO Fact Sheet on TB

 

In the days leading up to this annual event we see a number of activities, publications, and conferences - and so today a roundup of just a few of them.

 

First stop, excerpts from an MMWR report issued yesterday by the CDC, called:

 

Trends in Tuberculosis — United States, 2011

Weekly

March 23, 2012 / 61(11);181-185

What is already known on this topic?

Although tuberculosis (TB) has been on the decline in the United States since 1993, an increasing proportion of cases has been observed among the foreign-born. Racial and ethnic minorities have represented a higher proportion of cases among the U.S.-born.

What is added by this report?

Provisional 2011 surveillance data indicate a TB case rate of 3.4 cases per 100,000 persons, which is the lowest rate since 1993. For the first time since current reporting began in 1993, Asians have become the most widely represented racial/ethnic group among TB cases, even though case rates also have declined in this group. Reporting of human immunodeficiency (HIV) status at diagnosis has improved in the most recent reporting year, and HIV infection among TB cases is at an all-time low.

What are the implications for public health practice?

Continued awareness and surveillance of TB is needed despite the decline. Initiatives to improve awareness, testing, and treatment of latent infection and TB disease in minorities and foreign-born populations should facilitate progress toward the elimination of TB in the United States.

FIGURE 1. Rate* of tuberculosis cases — United States, 2011†

* Per 100,000 population.

 

For a listing of events and activities that the CDC and its domestic and international partners will be conducting, you can visit their World TB Day 2012 webpage.

 

Next stop, from the Health Protection Agency, which has released a report indicating that the number of new TB cases in the UK increased by 5% in 2011.

 

 

More than 9,000 TB cases reported in 2011

23 March 2012

Provisional figures released today by the Health Protection Agency (HPA) show there were 9,042 new cases of tuberculosis (TB) in the UK in 2011. Compared to provisional numbers reported in 2010 (8,587), this is a five per cent increase.

 

The figures, released in the HPA’s annual TB newsletter ahead of World TB Day on Saturday 24 March, show the main burden of this infection is still in London with 3,588 cases reported in 2011, accounting for 40 per cent of the UK total. According to the provisional data, country of origin was recorded in 8,453 new cases, and almost three quarters (6,270) were in non-UK born people.

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Earlier this week (see link) the ECDC released a New ECDC-WHO report: tuberculosis on the retreat in Europe but concerns about drug-resistant TB and treatment failure remain.

 

And from the World Health Organization today, as one would expect, a number of items, including this media release on the need for better diagnostics and research on drug resistant TB.

 

More evidence and better diagnostics needed before redefining severe forms of drug-resistant TB says WHO

Note for the media

23 March 2012 | Geneva - Reports of tuberculosis (TB) cases with severe patterns of drug resistance are increasing, said experts who attended a WHO meeting in Geneva on 21-22 March. Participants stressed that the emergence of drug resistance should be a wake-up call for Ministries of Health. The group urged the global TB community to make greater efforts to prevent drug resistance and scale up provision of appropriate care and management to avoid a scenario where TB becomes incurable.

Insufficient evidence

The meeting concluded that there is currently insufficient evidence to adopt new case definitions for drug-resistant TB. Drug susceptibility testing (DST), which is key to defining new levels of drug resistance, lacks accuracy for several of the drugs that are used to treat multi drug-resistant (MDR) and extensively drug resistant (XDR)-TB. Secondly, there is insufficient correlation of DST results with clinical response to treatment for several drugs currently used to treat XDR-TB. Thirdly, new drugs are currently undergoing clinical trials, and could prove effective against drug resistant strains. The meeting urged diagnostics companies and TB laboratories to develop better diagnostic tests and also agreed that WHO and technical partners should develop more detailed guidance on XDR-TB treatment.

 

Prior to results from randomized controlled trials, which are not expected for at least four years, participants called on WHO to lead a process with partners to improve the quality and quantity of observational data on the management of cases of severe forms of drug resistance. These data should be collected in a standardized manner which is essential for stronger future policy decisions on the management of drug resistant TB.

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And to finish off, some World TB Day links from the WHO:

World TB Day site

WHO programme on TB

Stop TB Partnership

More about tuberculosis

WHO-ECDC: Joint Report On Tuberculosis In Europe

 

 

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World TB day is March 24nd, and the ECDC, the World Health Organization, the CDC, along with many other partners (including the National TB Controllers Assoc., Stop TB USA, and the global Stop TB Partnership) have joined together around the globe to raise awareness and promote strategies to reduce TB around the world.

 

 

Today, the ECDC and WHO released a 172 page Tuberculosis Surveillance And Monitoring In Europe report for 2012, that finds some encouraging signs, but also cautions on the increased incidence of extensively drug resistant (XDR) TB in parts of the EU.

 

Here is the announcement from the ECDC.

 

New ECDC-WHO report: tuberculosis on the retreat in Europe but concerns about drug-resistant TB and treatment failure remain

19 Mar 2012

ECDC

In 2010, the EU/EEA countries reported nearly 74 000 tuberculosis cases – around 7% less than 2009. While the notifications for multidrug- and extensively drug-resistant tuberculosis (M/XDR TB) have been stable over the past 5 years, the proportion of extensively drug-resistant patients among this group rose from 8.2% in 2009 to 13.2% in 2010 in the EU/EEA, possibly due to increased reporting.

These rising numbers pose a serious threat in the attempt to eliminate TB, highlighting the importance of early detection and adequate treatment of tuberculosis patients in the region.

 

ECDC Director Marc Sprenger, stresses that “Countries with low incidence of TB – which means less than 20 patients per 100 000 population – face a particular challenge in taking the final step towards elimination of the disease as TB often concentrates in big cities. In this setting, key populations like people who inject drugs, homeless people and migrants are disproportionally affected by TB. That is why we have to exchange best practices from across Europe: if TB services are not tailored towards the needs of urban risk groups there is a continuing risk of higher rates of TB in general and drug-resistant TB in particular.”

On the occasion of World TB Day 2012, ECDC supports simultaneous Urban TB Control events in Barcelona, Milan, London and Rotterdam on 22 and 23 March.

 

Join us on Tuesday, 20 March, when ECDC and WHO/Euro host a joint Twitter chat on the current TB situation in Europe. Use the hashtag #TBchat.

Read more:

Read the full press release

 

The full ECDC-WHO report Tuberculosis surveillance and monitoring in Europe 2012

ECDC report Towards TB elimination A follow-up to the Framework Action Plan to fight TB in the EU

ECDC Spotlight Tackling Tuberculosis in Children 2011