|Year : 2005 | Volume
| Issue : 4 | Page : 105-106
Treatment of Latent Tuberculous Infection in India: is it worth the salt?
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research,Chandigarh., India
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research,Chandigarh.
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Agarwal R. Treatment of Latent Tuberculous Infection in India: is it worth the salt?. Lung India 2005;22:105-6
According to an estimate performed in 1999, as many as 1.86 billion, or almost one third of the world's population is infected with tuberculosis (TB).  Latent TB infection (LTBI) is a clinical condition defined by a positive tuberculin skin test in patients who have no clinical or radiological evidence of active disease. On an average, 10% of immunocompetent hosts with LTBI will develop active disease, and this risk increases in the immune deficient host e.g, persons with HIV infection may develop active TB at a rate as high as 10% per annum.  Although Mycobacterium tuberculosis is known to attain a dormant or latent state in human tissues, many fundamental questions about the mechanisms of so called latency remain unanswered.  For instance, isoniazid is poorly effective against persisters, but remains the most commonly used drug for chemoprophylaxis. Whatever be the mechanism by which M tuberculosis becomes latent, studies have shown that treatment of LTBI definitely prevents active disease. 
In developed countries where incidence of TB has fallen to low levels, most new cases of TB occur in persons who were infected in the remote past, contained their infection, and subsequently developed active disease. In low-prevalence countries, therefore, the treatment of persons with LTBI is a major component of TB control as they represent an enormous reservoir of potential cases.  Treatment of LTBI can achieve up to 8090% reduction in active TB in a community where all cases of active TB result from reactivation of LTBI provided all these persons with LTBI are identified and complete treatment.  But the situation is different in high prevalence TB areas such as India where efficient detection and treatment of persons with active TB remains the highest priority for all TB control programs. It is therefore important to answer whether there is any role of treatment of LTBI in India ?
The priority of any TB control program is treatment of active TB, and inclusion of treatment of LTBI in the national program will only increase the logistic and financial burden on the health system. Secondly, there is a constant exposure of the host to M tuberculosis, and considerable number of cases could theoretically result from re-infection with TB bacilli. One might therefore need to give recurrent courses of chemoprophylaxis since a single course may not be sufficient to prevent the disease occurrence. This does not mean that there is no role for treating LTBI in India. The epidemiological impact of the treatment of LTBI on the community is likely to be minimal in high TB prevalence countries, but may be significant for an individual patient.
Treatment of LTBI is likely to be beneficial in persons with reversible risk factors that increase the chance of developing active TB [Table 1]. For instance, it has been shown that prolonged systemic steroid therapy causes a significant increase in the incidence of TB (5% vs. 0.1% risk in the community),  and one can use chemoprophylaxis for TB in such situations. The policy is primarily good only for patients with reversible factors. If a person has got a persistent risk factor (e.g. type 2 diabetes mellitus or rheumatoid arthritis), therefore there remains a high chance of re-infection in a high TB prevalence country, and therefore, the individual would have the same risk after, as that prior to receiving treatment for LTBI. Unfortunately, there is also the potential risk of creating drug resistant strains because of the wise of
[Table 1]: Possible indications for treatment of latent tuberculosis (TB) infection in India
Children less than two years who are household contacts of patients with smear-positive pulmonary TB (Between two to five years of age, if associated with protein energy malnutrition)
Reversible risk factors like glucocorticoid therapy, immunosuppressive therapy which is likely to be stopped after a definite period of time.
HIV-infected individuals who are likely to receive highly active antiretroviral therapy (till reversal of immune suppression).
Once one decides to treat, what should be the choice of drugs? Isoniazid administered for a period of 9-12 months is the most commonly used regime. But, its use is limited by its hepatotoxicity, poor compliance because of long duration, and in India, by the presence of high primary resistance to the drug (10%).  On the other hand, the incidence of liver injury is higher among people receiving short-course (two-month) rifampin and pyrazinamide therapy for LTBI than among those receiving isoniazid (odds ratio 8.5, 95% confidence interval 1.9-76.5).  Recently, a meta-analysis showed that a three-month therapy with isoniazid plus rifampin was equivalent to standard therapy with isoniazid in terms of its efficacy, the proportion of severe side effects and the mortality.  This may be the preferred regime for treating LTBI in India.
Many of the above recommendations are based on logical conclusions. The need of the hour is to properly conduct randomized controlled trials to define the role of treatment of LTBI in the community and in specific clinical situations, in high-prevalence countries, including India.
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