TOMSK, RUSSIA—After a half century of neglect, a search for better drugs and diagnostics to treat tuberculosis (TB) is underway. But progress is slow, and the breakthroughs that will help reduce the global burden of TB remain years away.

The modern diagnostics lab under construction in this Siberian capital is a good example. It will shorten the time it takes to identify a case of multidrug resistant (MDR) tuberculosis from two to three months to two or three weeks by using liquid media instead of solid media to grow individuals' samples of M. tuberculosis and test them for resistance to first-line treatments. MDR-TB accounts for a shockingly high 15 percent of cases here, and its misdiagnosis almost always leads to treatment failure.

When the $1.5-million lab opens in December (built with funding from international aid groups), it will have at best an incremental impact on public health. Because all patients initially diagnosed with TB here are hospitalized in crowded wards, a lab that can quickly diagnose which of those patients have MDR-TB should reduce the amount of time the other patients will be exposed to a harder-to-treat form of the disease.

It should also improve the MDR-TB patients' survival chances, because it will get them on the proper drug regimen more quickly. "There will be more MDR-TB because of better diagnosis, but that's good because...they will be better treated with the latest technology," says Albert Adamyan, the region's minister of health.

Eventually, however, the health authorities here would like to install DNA-amplification techniques for identifying resistant TB strains, such as those used in a test recently unveiled by the Geneva-based Foundation for Innovative New Diagnostics (FIND). That could shorten the analysis time to two or three days.

But even that method will not meet the needs of the globe's poorest precincts, which account for the vast majority of the nine million new cases of TB each year, a growing share of which are resistant to some first-line drugs. In sub-Saharan Africa and south Asia, for instance, TB treatment is usually offered in rural health clinics without access to sophisticated labs. "What we really need is point-of-care testing for resistance," says Michael Rich, a physician with the nonprofit Partners in Health who splits his time between Russia and Rwanda.

And that is the number one priority for FIND. "Where we're investing the most is in riskier research to develop a dipstick test that can be used in the lowest technology settings," says Richard O'Brien, a former U.S. Centers for Disease Control and Prevention (CDC) official who now runs product development at FIND. "It would be a rapid assay that you could use with blood or sputum or even urine." But such a test is still far off.

The drug regimens for treating both "susceptible" and resistant forms of TB are also badly in need of an overhaul. The World Health Organization (WHO)–approved DOTS regimen (directly observed therapy, short course) isn't very short. It involves taking four first-line antibiotics—isoniazid, rifampin, pyrazinamide and ethambutol—for two months, and continuation therapy with isoniazid and rifampin for another four months. Rifampin, in particular, is problematic because it induces liver enzymes that break down the protease inhibitors used to combat HIV/AIDS, which co-infects many TB patients.

The MDR-TB regimen, meanwhile, is simply brutal. It can last up to two years, and involves taking drugs like capreomycin, which must be injected every day; cycloserine, which patients have dubbed "psycho-serine" because of its mind-bending side effects; or one or more fluoroquinolones. The last are among the most expensive antibiotics on the market, even when acquired through the multilateral purchasing consortium organized by the WHO and CDC known as the Green Light Committee. They also can cause liver problems and tendon ruptures.

1 Comments

1. 1. jfulkerson 04:15 PM 8/29/08

   Merrill Goozners piece, In Pursuit of Better Weapons to Combat TB, does clearly highlight efforts to develop better drugs and diagnostics to identify and treat tuberculosis. Yet TB vaccines offer a promising avenue of hope. In fact, epidemiologic modeling has shown that a new effective vaccine will be required to eliminate TB as a global health problem by 2050. While confined existing epidemics like that in Siberia require new treatment methods, a safe and effective TB vaccine could help prevent people at risk from getting sick in the first place.
   
   
   
   A TB vaccine known as BCG is available today, but it offers only limited protection against the small percentage of severe childhood cases. For this reason, organizations across the globe are working to ensure rapid development of new TB vaccine candidates.
   
   
   
   With partners in Africa, Asia, Europe, and the United States, the Aeras Global TB Vaccine Foundation has assembled the largest and broadest TB vaccine product pipeline in the world. Four TB vaccine candidates are in Phase I human trials and two are scheduled enter Phase I trials in 2009. Aeras goal is to develop, test, license, manufacture and distribute at least one new TB vaccine regimen by 2016 and to ensure availability to all who need it.
   
   
   
   It is obvious that current tools are not enough to control a global TB pandemic that is increasingly severe and complex due to increased drug resistance and the deadly relationship between TB, HIV and poverty. Together with new drugs and new diagnostics, new TB vaccines could one day help eliminate this threat.
   
   
   
   John Fulkerson, PhD
   
   Director of Vaccine Discovery
   
   Aeras Global TB Vaccine Foundation
   
   

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