Shorter TB Therapy Could Reduce Cases and Deaths

BOSTON, Aug. 1 -- Decreasing tuberculosis treatment to two months from six months and improving case detection would theoretically double or triple the expected decline in TB incidence and mortality, according to a mathematical model.

Exploring a number of different future scenarios that might become possible with new drugs, the researchers calibrated their model to reflect South-East Asia, where about one-third of global cases and deaths occur. Potential benefits for shorter treatment were dramatic, according to a report in the August online edition of the Public Library of Science Medicine.

Compared with continuing treatment at current levels with existing drug regimens, the two-month protocol if introduced by 2012 could prevent around 20% (range 13%-28%) of new Mycobacterium tuberculosis cases and 25% (range 19%-29%) of deaths between 2012 and 2030, said Joshua Salomon, Ph.D., of the Harvard School of Public Health here and colleagues.

This shortened regimen, according to the model, would double, even triple the rates of decline in new cases and deaths, which would amount to total reductions between 2012 and 2030 of up to 40% of the expected numbers.

If, as expected, effective treatment with existing drugs were to expand rapidly, overall incremental benefits of shorter regimens would be lower, the researchers said. However, benefits would still be considerable (for reductions in both incidence (13% [range 8%-19%]) and mortality (19% [range 15%-23%]) between 2012 and 2030.

The sooner the shorter regimens are introduced, the greater the benefits would be, the researchers said. However, they cautioned that a 10-year delay in the introduction of new drugs would erase nearly three-fourths of the total expected benefits in this region through 2030.

The dramatic benefit from curtailed treatment would result from a reduction in the opportunity for patients to default on their therapy and a reduction in the period during which they might infect others, Dr. Salomon said.

Every year, some eight or nine million people develop active TB, and about two million people die. The World Health Organization's treatment strategy relies on at least six-months of chemotherapy with four or more drugs given while observed by health care workers.

No new first-line TB drugs have been developed in the past 30 years. However, promising new drug candidates have been identified recently, some of which are expected to have a faster cure rate. New, faster-acting drugs suggest that shorter regimens may enter the TB arsenal in the coming years, the researchers said.

Thus far, they reported, considering the potential benefits of a two-month regimen available by the year 2012, the total benefits through the year 2030 could be as high as 11 million cases and 5 million deaths averted in the South-East Asia region alone.

The researchers also suggested that shorter treatment regimens, perhaps in combination with new diagnostic technologies, could enhance case detection by reducing resource demands per treated patient and by simplifying infrastructure, monitoring, and administrative requirements, as well as by lowering patient-related barriers to starting treatment.

Inevitably, the mathematical required a series of simplifying assumptions, the researchers said, including the fact that they may not have accounted for the possible development of resistance to the new drugs. Furthermore, Dr. Salomon said, certain elements defined here, such as the potential impact of new drugs on case detection, should be interpreted as "what-if" assessments rather than as firm predictions.

Long-term strategies for reducing the global TB burden require a balanced approach to pursuing new treatment and detection technologies while promoting wider implementation of proven strategies," Dr. Salomon concluded.