EID Journal: Challenges To Defining TDR-TB

 

(From the 2011 TB Progress Report)

 

# 6600

 

In January of this year reports began to emerge out of India regarding what was being called Totally Drug Resistant (TDR) tuberculosis (see Crof’s report India: New TB strain is "totally drug-resistant" (updated)).

 

While not an officially recognized term, TDR-TB was portrayed by the media as a frightening escalation of the existing classifications of Multi-drug resistant (MDR-TB) and Extensively-drug resistant (XDR-TB).

 

Resistant forms of Tuberculosis have come about primarily as the result of incomplete, irregular, or inappropriate treatment and management of infected patients.

 

A few days later (January 14th), the World Health Organization updated their Drug-resistant tuberculosis FAQ where they take exception to the term TDR-TB.

 

Why are these terms not yet recognised by WHO?

Terms such as “totally drug resistant” have not been clearly defined for tuberculosis. While the concept of “total drug resistance” is easily understood in general terms, in practice, in vitro drug susceptibility testing (DST) is technically challenging and limitations on the use of results remain: conventional DST for the drugs that define MDR and XDR-TB has been thoroughly studied and consensus reached on appropriate methods, critical drug concentrations that define resistance, and reliability and reproducibility of testing

Around the same time we saw an ECDC Comment On Drug Resistant TB In India. One of the points being made in the comments section (excerpted below) is that the term TDR-TB is as yet not well defined, and may be misleading.

 

 

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.

 

In March, as part of my World TB Day Roundup, the World Health Organization released this statement on the supposed TDR-TB, cautioning:

 

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.

(Continue . . . )

 

 

All of which brings us to a new article appearing ahead of print in the CDC’s EID Journal that looks at the:

 

Challenges and Controversies in Defining Totally Drug-Resistant Tuberculosis

Peter Cegielski , Paul Nunn, Ekaterina V. Kurbatova, Karin Weyer, Tracy L. Dalton, Douglas F. Wares, Michael F. Iademarco, Kenneth G. Castro, and Mario Raviglione

Abstract

In March 2012, in response to reports of tuberculosis (TB) resistant to all anti-TB drugs, the World Health Organization convened an expert consultation that identified issues to be resolved before defining a new category of highly drug-resistant TB.

 

Proposed definitions are ambiguous, and extensive drug resistance is encompassed by the already defined extensively drug-resistant (XDR) TB. There is no evidence that proposed totally resistant TB differs from strains encompassed by XDR TB.

 

Susceptibility tests for several drugs are poorly reproducible. Few laboratories can test all drugs, and there is no consensus list of all anti-TB drugs. Many drugs are used off-label for highly drug resistant TB, and new drugs formulated to combat resistant strains would render the proposed category obsolete. Labeling TB strains as totally drug resistant might lead providers to think infected patients are untreatable. These challenges must be addressed before defining a new category for highly drug-resistant TB.

(Continue . . . )

 

Given the complexities of evaluating for total drug resistance, attaching the label TDR-TB to these strains may well be both premature and inaccurate.

  

But the sobering fact remains, if you are infected with one of these XDR-TB strains - and no drug is available to you that can treat it – for you, it may as well be totally resistant.

 

Of course, this disparity of available medical treatment exists for a great many diseases around the world, and is not just limited to TB.

 

 

The authors of the EID study conclude with this warning:

 

As countries increase treatment of MDR and XDR TB, it is inevitable that resistance to second-line drugs will increase. New drugs and better diagnostic tools are needed urgently for patients with highly drug-resistant TB.

 

For more on the global spread of TB, you may wish to revisit:

 

WHO-ECDC: Joint Report On Tuberculosis In Europe

Resistant TB: The Limits Of Surveillance & Reporting

WHO: Blood Tests To Detect Active TB Unreliable

»» Read More

WHO: Drug Resistant TB At Record Levels

 

# 4446

 

The World Health Organization has released a sobering new report on the global spread of Multidrug and Extensively Drug-Resistant  Tuberculosis  (M/XDR-TB), and has posted a press release on their website summarizing the problem.

 

77 Page PDF File

 

Drug-resistant tuberculosis now at record levels

 

18 MARCH 2010 | GENEVA | WASHINGTON DC -- In some areas of the world, one in four people with tuberculosis (TB) becomes ill with a form of the disease that can no longer be treated with standard drugs regimens, a World Health Organization (WHO) report says.

 

For example, 28% of all people newly diagnosed with TB in one region of north western Russia had the multidrug-resistant form of the disease (MDR-TB) in 2008. This is the highest level ever reported to WHO. Previously, the highest recorded level was 22% in Baku City, Azerbaijan, in 2007.

 

In the new WHO's Multidrug and Extensively Drug-Resistant Tuberculosis: 2010 Global Report on Surveillance and Response, it is estimated that 440 000 people had MDR-TB worldwide in 2008 and that a third of them died. In sheer numbers, Asia bears the brunt of the epidemic. Almost 50% of MDR-TB cases worldwide are estimated to occur in China and India. In Africa, estimates show 69 000 cases emerged, the vast majority of which went undiagnosed.

 

Encouraging signs

Tuberculosis programmes face tremendous challenges in reducing MDR-TB rates. But there are encouraging signs that even in the presence of severe epidemics, governments and partners can turn around MDR-TB by strengthening efforts to control the disease and implementing WHO recommendations.

 

Two regions in the Russian Federation, Orel and Tomsk, have achieved a remarkable decline in MDR-TB in about five years. These regions join two countries, Estonia and Latvia, which have reversed rising high rates of MDR-TB, ultimately achieving a decline. The United States of America and China, Hong Kong Special Administrative Region (SAR), have achieved sustained successes in controlling MDR-TB.

Slow progress

Progress remains slow in most other countries. Worldwide, of those patients receiving treatment, 60% were reported as cured. However, only an estimated 7% of all MDR-TB patients are diagnosed. This points to the urgent need for improvements in laboratory facilities, access to rapid diagnosis and treatment with more effective drugs and regimens shorter than the current two years.

 

WHO is engaged in a five year project to strengthen TB laboratories with rapid tests in nearly 30 countries. This will ensure more people benefit early from life-saving treatments. It is also working closely with the Global Fund to Fight AIDS, Tuberculosis and Malaria and the international community on increasing access to treatment.

Additional information

Multidrug-resistant TB (MDR-TB) is caused by bacteria that are resistant to at least isoniazid and rifampicin, the most effective anti-TB drugs. MDR-TB results from either primary infection with resistant bacteria or may develop in the course of a patient’s treatment.

 

Extensively drug-resistant TB (XDR-TB) is a form of TB caused by bacteria that are resistant to isoniazid and rifampicin (i.e. MDR-TB) as well as any fluoroquinolone and any of the second-line anti-TB injectable drugs (amikacin, kanamycin or capreomycin).

 

These forms of TB do not respond to the standard six-month treatment with first-line anti-TB drugs and can take up to two years or more to treat with drugs that are less potent, more toxic and much more expensive, from 50 to 200 times higher. While a course of standard TB drugs cost approximately US$ 20, MDR-TB drugs can cost up to US$ 5 000, and XDR-TB treatment is far more expensive.

 

In 2008, there were an estimated 9.4 million new TB cases, and 1.8 million TB deaths. 440 000 MDR-TB cases are estimated to have emerged in the same year with 150 000 MDR-TB deaths. No official estimates have been made on the number of XDR-TB cases, but there may be around 25 000 a year with most cases fatal. Since XDR-TB was first defined in 2006, a total of 58 countries have reported at least one case of XDR-TB.

 

(Continue. . . )

 

For more information contact:

Glenn Thomas - Communication Officer
Stop TB, WHO
Mobile phone: +41 79 509 0677
E-mail: thomasg@who.int

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