Patient Friendly Research To Fight Tuberculosis (TB)
The present diagnosis and treatment regimen for tuberculosis is almost 40 years old. According to the WHO, with the currently available diagnostic tools, we are able to diagnose just 61% of TB cases globally. This means that 40% of the cases go undetected and inadvertently help in further transmission of the disease in healthy people.
Dr Christian Lienhardt, who heads the Research Movement of the Stop TB Partnership, gave exclusive interview to CNS during the recently concluded “Open Forum 4: Critical Path to TB Regimen: New Hope of Life for TB Patients” in Addis Ababa, Ethiopia (18-19 August 2010).
The current drug regimen comprises 4 different drugs/tablets which have to be taken daily for a period of 6 months. It has a fairly good success rate of 80%. But the treatment is very cumbersome. The patient has to take the drugs, which are available at the Directly Observed Treatment Shortcourse (DOTS)/ health centres, usually every day. This is easier said than done. It has been seen that many patients discontinue treatment before the stipulated 6 months period. They may have to trudge long distances to reach the clinic, and/or have to take leave from work, or might just be unable to bear the severe side effects. This discontinuation of the treatment midway could result in a relapse or drug resistant TB, which is still more difficult to cure. Even the existing TB vaccine (Bacillus Calmette Guerin - BCG) has a variable efficacy which is waning with time. According to the WHO, "BCG vaccine has a documented protective effect against meningitis and disseminated TB in children. It does not prevent primary infection and, more importantly, does not prevent reactivation of latent pulmonary infection, the principal source of bacillary spread in the community. The impact of BCG vaccination on transmission of Mtb is therefore limited."
It is true that after reaching a peak in 2004, the incidence of the disease has shown a decline. But this is very slight—a mere 1% per year. With this slow pace it would be almost impossible to reach either the Millennium Development Goal (MDG) of halting and reversing the incidence of TB by 2015. So we need better tools for early detection and efficient treatment to cure 100% of the patients and also control the spread of the disease.
All this requires extensive basic research in all allied fields. Researchers have to come up with new vaccines for prevention, better diagnostic equipment/tests, and shorter treatment regimens which are more patient friendly. Research in all these fields is of utmost importance. Researchers from various facilities –be they bio chemical labs, or pharmaceutical companies or PDPs (product development partnerships) -- will have to join hands for the discovery of better drugs.
It is very important that there is enough funding to put all this basic research in place for new discoveries to happen as soon as possible. The next phase involves a long drawn out period of clinical trials to test the efficacy of the new tools in real life situations.
Then comes the implementation part of research which ensures that the new vaccines/ drugs/ diagnostics are adopted where needed most. This is very important, especially at the diagnostic stage, as the diagnosis of TB will vary according to the level where it can be applied. If the patient has access to a modern hospital with trained personnel, then he/she can undergo more sophisticated and reliable tests. In peripheral labs we need simpler tests which allow one to identify TB cases with the help of easily available instruments which do not require professionals to operate them.
Dr Christian Lienhardt mentioned some existing modern diagnostic tools, some of which can shorten the time of diagnosis to as less as 2 hours. One of them is LED Microscopy which gives far better and quicker results than the normal sputum testing done by an ordinary microscope. Another method is the culture base method. This method allows the bacteria, in a culture of sputum, to grow for better identification. Then the effect of the drugs on these germs is tested. If a drug kills them they are sensitive to it; if not then it is established that they are drug-resistant. The latest in this line is the Interferon Gamma Release Assay (IGRA) test which involves taking a blood sample to test for dormant as well as active TB. But these are not cost effective, and currently not being used commercially on a general basis, and are available only in a few select hospitals. The WHO recommends the use of these tools as they can dramatically shorten the time taken for TB diagnosis, which is a crucial factor in TB treatment.
As for the availability of new drug regimens which will make the TB treatment simpler and shorter, Dr Lienhardt feared that we may have to wait for a couple of years. Despite best efforts of like minded partners like TB Alliance, the proverbial magic cure will not come about over night. However, there is greater excitement on the front of new drugs for MDR-TB (multi drug resistant TB). There are two new drugs for MDR-TB which have shown very encouraging results and are in the second phase of clinical trials. They show the promise of better efficacy and shorter treatment duration, and hope to be used in the foreseeable future.
The first step forward has been taken with active support from the TB Alliance which has been working to spearhead the testing of new TB drug candidates in combination with one another. This has lead to a revolutionary cross-sector initiative called the Critical Path to TB Regimens (CPTR), which is a collaboration of pharmaceutical companies; government/ regulatory agencies; donors; academia; advocates— all having the common aim to accelerate the development of new, safe, and highly effective tuberculosis (TB) treatment regimens with shorter therapy durations. This is an urgent public need for saving millions of lives. (CNS)
Shobha Shukla - CNS