08 September 2010

Multidrug-resistant forms of TB

The second paper in The Lancet series of tuberculosis. This paper focuses on the affects of multidrug-resistant TB, how they are identified and treated.


An estimated 440 000 cases of multidrug-resistant tuberculosis (MDR TB) occurred worldwide in 2008 (3,6% of all TB cases that year), but only 7% of these cases were identified and treated.

Extensively drug-resistant TB (XDR TB) has also been reported in most countries and is even more difficult to treat than MDR TB. Without significant investment in technology and capacity for prevention, diagnosis and treatment, MDR TB threatens to become the dominant strain of TB over the next few decades.

The issues are discussed in the second paper in The Lancet serieson Tuberculosis, written by Dr Neel R Gandhi, Albert Einstein College of Medicine and Montefiore Medical Centre, Yeshiva University, New York, USA, and Dr Paul Nunn, Stop TB Department of the World Health Organisation, Geneva, Switzerland, and colleagues.

Drug-resistant TB a major threat

Drug-resistant TB poses a major threat to existing TB control programs since it is associated with substantially lower cure rates and higher mortality rates than drug-susceptible TB disease.

Additionally, MDR TB treatment is less effective, requiring 24 months of treatment rather than the usual six months, and far more costly. Thus, even though there are fewer cases of drug-resistant TB, the cost and complexity of their management place a significantly greater burden on the health system than do drug-susceptible TB cases.

MDR TB was traditionally believed to develop as a result of improper treatment in patients with drug-susceptible TB, allowing for selection of drug-resistant TB strains.

TB drug resistance, however, can also be transmitted from people with MDR or XDR TB, giving rise to drug-resistant TB disease in people with no previous exposure to TB drugs.

Estimates suggest transmission of drug resistance now accounts for more than half of global MDR TB cases; although improper treatment of drug-susceptible TB also continues to play a major role in the development of new cases of drug resistance.

MDR TB prevention limited by failure

Efforts to prevent MDR TB cases have been severely limited by a failure to implement infection control program in most low- and middle-income countries, together with insufficient financial and human resources, laboratory capacity and access to second-line TB drugs.

Although MDR and XDR TB exist on every continent, the true extent of the epidemic remains unknown. Drug resistance surveys have been carried out in only 59% of countries, and of these data, 20% were collected before 2003 and are outdated. India and China together carry nearly 50% of the global MDR TB burden, followed by Russia (9%).

The trend of whether drug resistance is increasing or decreasing worldwide is also unknown, since more than one drug-resistance survey has been completed in only 59 (31%) countries.

MDR TB reversible in some countries

Some countries have shown that epidemics of MDR TB can be reversed by use of technologies which already available.  

In these countries (Estonia, Hong Kong [Special Administrative Region], Latvia, Lithuania, Russia [Orel and Tomsk regions], Singapore, and the USA) the incidence of MDR TB is known to be decreasing.

But in Botswana, Peru, South Korea, the incidence of MDR TB has been rising, leading to concerns that the same may be true in other developing countries where trend data are not available. Alarmingly, in Botswana, all cases of tuberculosis are increasing in incidence, and MDR TB is increasing even faster.

Treatment success rates in MDR TB can be as high as 83%,and 60% in patients with XDR TB, in treatment programs that function optimally and have low rates of HIV co-infection. MDR TB and XDR TB patients should be treated with four to six drugs to which their strains are known or likely to be susceptible. 

Trained health workers needed

In order to achieve these high levels of treatment success on a broad scale, however, health systems and national TB programmes will need to recruit and train sufficient health workersand ensure that drug-resistant TB treatment is provided by accredited physicians with experience in managing MDR and XDR TB cases.

Additionally, major improvements in laboratory capacity, infection control, and treatment regimens for both drug-susceptible and drug-resistant disease will be needed, together with a massive scale-up in diagnosis and treatment of MDR and XDR TB, to prevent drug-resistant strains becoming the dominant form of tuberculosis.

Next decade holds hope for diagnostics and drugs

New diagnostic tests and drugs may become available during the next decade and would help control of MDR and XDR TB. However, they must be made available in resource-limited settings which are hit hardest by this epidemic. 

Moreover, the authors say, we must “ensure that these new drugs are not exposed to the weak health systems and irrational drug practices that are currently giving rise to resistance.”

They conclude: “Unless countries invest substantially in management of MDR TB, the possibility remains that MDR strains could become the dominant form of TB. Moreover, the future possibility of strains that are totally resistant to all anti-tuberculosis drugs is not inconceivable...

“Equally important, especially in the highest-burden countries of India, China, and Russia, will be a commitment to tuberculosis control including improvements in national policies and health systems that remove financial barriers to treatment, encourage rational drug use, and create the settings necessary to manage MDR TB on a national scale.” (The Lancet, September 2010)

Information provided from

Dr Neel R Gandhi, Albert Einstein College of Medicine and Montefiore Medical Center, Yeshiva University, New York, USA. T) +1 718-944-3865 E)

Dr Paul Nunn, Stop TB Department, WHO, Geneva, Switzerland. T) +41 22 791 2963 E)

Glenn Thomas, Senior Communications Adviser, WHO Stop TB Department. T) +41 79 509 0677 E)

For full Series paper 2, see:


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