In 2011, World Health Organization (WHO) data indicated the global presence of 12 million cases of tuberculosis (TB), with 630,000 (approximately 5%) cases of multi-drug resistant TB (MDR-TB). MDR-TB is caused by TB organisms that are resistant to the first-line drugs, isoniazid and rifampin, used to treat individuals with TB. At least 9% of MDR-TB patients go on to suffer extensively drug resistant TB (XDR-TB), which demonstrates resistance to first-line drugs and any second-line drugs. However, the prevalence of MDR-TB is estimated at much higher levels because of a deficiency in diagnostic methods and reporting problems in countries, such as India, China, Russia, and South Africa, where more than 60% of these cases flourish. With 84 countries reporting cases of XDR-TB, the fear of an approaching untreatable disease is elevated.
The term "totally drug resistant TB (TDR-TB)" has not been accepted by the WHO or the Centers for Disease Control and Prevention (CDC) because of incomplete reporting from the countries where TB predominates. However, in 2011, India reported cases that were totally resistant to all the available anti-tuberculosis drugs. The patient isolates are phenotypically resistant to the available first- and second-line anti-TB drugs, defined by their susceptibility tests (12 drugs tested). Inconsistencies in methods of diagnosis and susceptibility testing added to patient problems of co-infection with HIV. Drug addiction also contributed to the deficiency of data from these countries.
After the 1992 outbreak of MDR-TB in New York City was under control, the overall incidence of the disease began to subside in the United States (US). The CDC data show a consistent decline in both drug-susceptible and drug-resistant strains to 2011. However, reports for the US indicated a gradual increase in cases of MDR-TB in foreign-born patients; in 2010 there were 1.2% (89 cases) and in 2011, 1.3% (98 cases). Also in 2010, there were four cases of XDR-TB, showing resistance to first-line drugs and any of the second-line drugs (fluoroquinolones, capreomycin, amikacin, and kanamycin).
The maps, presented with the permission of the WHO, show the countries with MDR-TB (upper image) and XDR-TB (lower image) by the end of 2011.
The US Food and Drug Administration (FDA) has granted approval for bedaquiline to be used to treat drug resistant TB. This is the first new medicine for TB in more than 40 years. Additional anti-TB medications are currently under development or awaiting FDA approval, including delaminid (OPC7683), SQ109, PA824, AZD5847. Good news in diagnostic technology confirms that the Xpert
® MTB/RIF test (Cepheid) received United States market approval by the Food and Drug Administration (FDA) in July 2013. It is designed to provide rapid molecular detection of
Mycobacterium tuberculosis DNA in specimens and, when positive, it also detects rifampin resistance.
In this course, the presentation of a brief history of tuberculosis and its developing resistance to anti-tuberculosis drugs is followed by case histories from India, Italy, and the US-Mexican border. The pathogenesis of TB disease in humans is diagrammed and a review of diagnostic laboratory methods, susceptibility testing, and methods of control are explored.
