Tuberculosis

Imagine having to take 14,000+ pills and daily injections for 6 months (a regimen that can last up to 2 years) to treat an under-diagnosed disease (second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent). This prospect is faced by a significant portion of at least 8.6 million people (2012 estimates) who contracted the multi-drug resistant form of tuberculosis (MDR-TB). Pulmonary and extra-pulmonary TB are caused by Mycobacterium tuberculosis and affect the lungs and other organ systems respectively. Although TB is treatable and curable, MDR-TB can occur due to improper disease management. MDR-TB strains are resistant to at least the first-line therapies, isoniazid and rifampin. Globally, the number of people with MDR-TB nearly doubled between 2011 and 2012, and in most high-burden countries less than one in four people estimated to have MDR-TB were detected. In addition, treatment gaps may have contributed to the reports of extensively drug-resistant TB (XDR-TB) by 92 countries (2012 estimates). Direct treatment costs averaged $134,000 per MDR-TB and $430,000 per XDR-TB patient in the United States alone (for the period: 2005-2007) (1).

Some of the pre-clinical and clinical studies

M. tuberculosis resides asymptomatically in the body of one-third of the world’s population, but only 5% develop the disease. Swedish researchers have found that the organism can lurk inside macrophages, ready to destroy them and spread the infection to other cells. Other researchers have attributed the latency and persistence of the bacterium to cell-wall-deficient variants (L-forms) that arise as an adaptive strategy in order to survive under unfavorable circumstances (2). Latency and bacterial persistence are subjects of ongoing investigation.

The search for simpler, cost-effective therapies of shorter duration for all TB patients is also a work in progress. Based on successes from smaller trials, the TB alliance has just announced that they will be moving forward with a regimen that shows promise to significantly shorten therapy, especially for some forms of MDR-TB. This affordable regimen will involve 360 or fewer pills (no injections) taken for up to 6 months.

Priorities to accelerate progress (World Health Organization)

·         Reach the missed cases

·         Address MDR-TB as a public health crisis

·         Accelerate the response to TB/HIV

·         Increase financial aid to close resource gaps

·         Ensure rapid uptake of innovations

Sources

1.            Marks SM, Flood J, Seaworth B, et al. Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007. Emerg Infect Dis. 2014;20(5):812-821.

2.            Markova N, Slavchev G, Michailova L. Unique biological properties of Mycobacterium tuberculosis L-form variants: impact for survival under stress. Int Microbiol. 2012;15(2):61-68.

3.            Ginsberg AM, Spigelman M. Challenges in tuberculosis drug research and development. Nat Med. 2007;13(3):290-294.