Empirical use of antituberculosis drugs should not be equated to their inappropriate and indiscriminate use

Sir,

Tuberculosis is endemic in India accounting for about 20% of the global burden of tuberculosis. About 1.8 million new cases of tuberculosis are reported in India every year.[1] Although effective drugs as well as appropriate guidelines for treatment are available, irrational practices on anti-tuberculosis treatment (ATT) are still widespread in India.[2,3] Many patients are erroneously diagnosed and treated for tuberculosis. Even quacks (unqualified doctors) with a limited understanding of disease prescribe anti-tubercular drugs in India. The availability of anti-tubercular drugs “over the counter” facilitate their indiscriminate use. The erroneous diagnosis of tuberculosis deprives patients from getting necessary treatment as the actual underlying condition remains undetected. Therefore, it tends to increase the disease burden as well as the cost of healthcare. Moreover, a wide of range of ATT regimens are being used in India by different practitioners[2] and many of them are grossly inadequate, poorly combined, and improperly instituted. Incomplete treatment or incorrect drugs, especially in the initial phase of ATT are a major cause of acquired multi-drug resistance (MDR) tuberculosis, the rising incidence of which India has seen during recent years. According to a latest estimate, India ranks as number one amongst the high burden MDR tuberculosis countries.[1]

Overdiagnosis of tuberculosis is frequently made in patients with prolonged febrile illness, unexplained lymphadenopathy or weight loss, ascites, intestinal obstruction, and pleural effusion etc, without subjecting them to proper diagnostic tests to rule out diseases simulating tuberculosis like other infective illnesses, inflammatory and malignant diseases. Several physicians in India often give over importance to certain diagnostic tests like erythrocyte sedimentation rate, tuberculin skin test, and serological tests, which have a low sensitivity, specificity, and positive predictive value for tuberculosis. As of now, with appropriate clinical evaluation and investigations including microbiological, imaging, and histopathological tests, it is possible to make a correct diagnosis of tuberculosis in majority of infected patients. However, in some cases diagnosing tuberculosis may be a real challenge. This is especially true for extrapulmonary tuberculosis, which is usually paucibacillary and manifestations are often non-specific. A typical example of this is differentiating intestinal tuberculosis from Crohn's disease. In a recent study from India, 43% of 166 patients with definite or probable diagnosis of Crohn's disease had to be given ATT initially because of diagnostic uncertainty even after appropriate evaluation.[4] Since tuberculosis is a treatable condition and is associated with poor outcome if untreated, empirical use of ATT can be justified in cases where index of suspicion is high. However, a close monitoring and follow-up is needed to confirm an appropriate clinical response, to validate its further continuation and to detect drug toxicity at the earliest. In a country with hyperendemicity of tuberculosis, empirical ATT can also be justified in severely ill patients with manifestations consistent with tuberculosis when investigations are non-contributory.

The empirical use of ATT should not be equated to their inappropriate and indiscriminate use. The unwanted prescription of ATT is not safe because of its propensity to cause severe hepatotoxicity and even death by causing acute liver failure (ALF). The reported rates of ATT induced hepatotoxicity vary from 2.3% to 28% and are higher among the Indian population (11.5%) than the Western population (4.3%).[5] The presence of malnutrition, co-infection with hepatotrophic viruses, HIV infection, and alcoholism in India leave such patients at a higher risk of ATT hepatototoxicity. The mortality rates from ATT-induced hepatitis after development of jaundice vary from 4% to 12%. A recent large study from India has identified 63% of patients who developed ATT-induced ALF received ATT with presumptive diagnosis of tuberculosis and the mortality rates among them was very high (67%).[3] Thus, ATT, not only can save lives, but its inappropriate use can also take lives.

The intermittent ATT (thrice weekly) has been found to be equally effective and safer in terms of adverse events in comparison to daily treatment. Even though India has adopted directly observed treatment short course (DOTS), which delivers intermittent treatment, under the Revised National Tuberculosis Control Programme (RNTCP) decades ago, its success has largely been suboptimal to date. In a country where as high as 65% of households seek healthcare from private sector, only 0.3% of private practitioners are implementing RNTCP.[6] The situation deserves a serious note and warrants awareness programs in order to prevent irrational practices on tuberculosis in India. Since private practitioners treat a substantial proportion of these patients, there should be strategies to provide DOTS training to them in order to improve their knowledge, attitude and practice on tuberculosis. All health providers should be encouraged to adopt RNTCP, which is the best way to practice tuberculosis as per international standard. The success, feasibility, and cost-effectiveness of integrated public private collaboration have already been proved.[7,8] Like in several developed countries, there should be a drug and therapeutics committee to look after proper use of medicines at all levels of healthcare. The quacks should be prohibited from using anti-tubercular drugs. Moreover, appropriate laboratory support and frequent referral to higher centers, in case of diagnostic uncertainty, can avoid over or under diagnosis of tuberculosis.