Fusing journalism and TB – telling the stories as they are

Tuberculosis diagnosis – its importance for eradicating the white plague

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Journalists against TB is honoured to feature guest writer, Jasmine Grenier, a medical student from Mc Gill University, Montreal, Canada.

As medical students, we have all heard about the white plague, consumption, phthisis, the wasting disease, Tuberculosis: the disease commonly known as TB. We have heard our peers in the medical field and elsewhere discuss the causes, the prognosis, the ravaging course of the disease and the hopeless statistics of infection and mortality. We have heard people say it is a disease of the poor, and we have strongly defended that it is a disease of the world. We know that tuberculosis has been successfully controlled in some areas but remains an imminent threat in others. Not so long ago students in Montreal were given a PPD test in schools as routine testing to screen for M. Tuberculosis infection and although there are still some areas and population groups which are more at risk (such as the Inuit and Cri populations in the north of Quebec as well as children who recently immigrated to Canada from high TB burden countries), there is no longer a significant threat in the city. However, there are countries where the infection and disease burden is enormous. Countries such as India see almost 2 million new TB cases per year, which all require proper diagnosis, treatment plan and completion of treatment to ensure cure.

It is often believed that the main hindrance in reducing the rate of infection and mortality in developing countries, which generally hold the highest burden of disease, is the lack of appropriate medication for the type of tuberculosis (latent, active, pulmonary, extra-pulmonary) and for the length required (6 months in most cases, and up to 2 years, in cases of significant multi-drug resistant TB). That is of course a problem which is continuously encountered and has been greatly tackled by the WHO and the Stop TB Partnership. Most of us have heard of DOTS – Directly Observed Treatment, Short-course; which has been endorsed by the WHO and implemented as widely as possible. This program strives to ensure availability of diagnosis and ‘directly observed’ drug therapy so as to optimize adherence, which is often difficult to maintain for complicated drug regiments that last months at a time and often imply significant side-effects. It is true then, that the administration of and adherence to TB treatment represents an ongoing challenge. However, there is another aspect of TB management that causes significant drawbacks: the diagnostic process.

Over the years, the causes and manifestations of TB have been eluded: starting off as mythical causes, we now not only know the infectious agent but also its complete infectious mechanism. The treatment has also evolved, from sanatorium care to a complex multi-drug regimen. The only thing that has not changed substantially is the diagnostic process, at least until recently. The most reliable diagnostic method for tuberculosis remains Robert Koch’s sputum smear microscopy and sputum culture, discovered in 1882. Although when used in conjunction both these tests are reliable, a culture takes weeks to grow which is much longer than one would hope to wait for the diagnosis of active TB disease. This is without mentioning the difficulty in diagnosing TB in HIV co-infected patients, whose sputum usually shows up as smear negative even when active TB disease is present. If TB is not diagnosed early, patients continue to spread the infection to those around them. In many developing countries, TB is diagnosed as many as 2 – 3 months after the patient becomes symptomatic. Thus, undiagnosed TB and delays in diagnosis continues to fuel the epidemic of TB.

In the search for new diagnostics, there have been many that have been attempted, such as the interferon-gamma release assay (IGRA), for one. This has proven to be a very specific diagnostic test, endorsed by the WHO, for the diagnosis of latent TB only. In fact, these tests cannot distinguish between latent and active TB infection and so remain mostly irrelevant for high burden areas where active TB is the biggest priority. However, some practitioners use IGRAs for the diagnosis of active TB as well, for which it is not specific at all. What the WHO encourages and what researchers are investigating is an ideal point-of-care test (one that can be conducted on the spot and which results can be obtained at that time) for the diagnosis of active TB disease. In the midst of this search a new type of test was developed and is now commonly found: serological rapid test kits. These tests measure the presence of antibodies against M. Tuberculosis. They are sold, imported and used in many high burden countries, especially in the private sector. Although most of these test kits claim 100% accuracy, serological tests for the detection of active TB have been proven to be inaccurate and inconsistent. For the first time in its history, the WHO has issued a negative policy advising against the use of TB serological tests. However, these inaccurate tests are widely sold and administered by practitioners and are often used to determine initiation of anti-TB therapy. The damage that a TB misdiagnosis can inflict is immense, as nicely illustrated by a recent story, entitled “A deadly misdiagnosis” in the New Yorker magazine by Michael Specter (published in November 2010). Whether a person receives antibiotics when none are needed or whether a person does not receive treatment for an active disease has tremendous consequences on the level of drug resistance, mortality and transmission of the infection in the community.

In our fight against Tuberculosis, it is important to remember that the challenges we face are manifold but that by recognizing the different problems, we can address them and move forward. The negative policy by the WHO is a grand step toward eradicating inaccurate diagnostic tests. In conjunction with this effort, the Stop TB Partnership’s New Diagnostics Working Group, co-chaired by Dr. Madhukar Pai a leading TB researcher affiliated with McGill University, is pioneering research and innovation in TB diagnostics. Moreover, the development of new and accurate point of care tests seems to be promising. Cepheid, a molecular diagnostics company, has recently manufactured the Xpert MTB/RIF (using the GeneXpert platform), a point of care test for the diagnosis of TB. The test is a completely automated PCR assay that is highly sensitive and specific and detects presence of M. Tb in the sputum as well as resistance to Rifampin in only two hours. This test can be done on table top, does not require a sophisticated lab or a highly trained personnel to operate it. The WHO recently endorsed this assay, and although its cost is still too great to allow for mass distribution throughout the developing world, price negotiations have been put in place and the test shows promise, especially if it can be used at the point of treatment in high TB burden settings to achieve early diagnosis.

Advancements like DOTS and the Xpert assay address core issues in the management of TB but there are many more factors that play a significant role in the development of the disease such as the overall health status of the patients and even more fundamentally, their nutritional status. As healthcare professionals-to-be these are issues that we must keep in mind and work to overcome. Although global control of tuberculosis remains difficult, the progress being made must encourage us to share our knowledge with our peers, to advocate and to work toward better solutions.

The views expressed in this post are entirely of the author.

Written by JournalistsAgainstTB

February 2, 2011 at 4:27 pm

Posted in TB and Media

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