Should Latent Tuberculosis Be Treated?

Question no. 1:
Should latent tuberculosis be treated in a high prevalence country like India?
Latent TB infection (LTBI) is a condition defined by a positive tuberculin skin test in patients who have no clinical or radiological evidence of active disease. Persons with latent TB infection do not have TB disease and and cannot spread TB infection to others. In these cases TB bacteria lie dormant in the body but have produced antibodies against them which we detect by most of our screening tests. Even the BCG vaccination given soon after birth to all our children born in our country aims to produce an army of antibodies againt the TB baceria, which act as first line of defence to fight any fresh inhalation of TB bacteria from the environment. BCG is not given in the west as the environment is almost free from these bacteria.

The prevalence rate of latent tuberculosis in India is very high and ranges from 40- 50% in various populations, which means at any given time >500 million population would have latent tuberculosis in our country. However, only 5 to 10% of these cases may convert into active TB disease in ones lifetime, that also mainly when ones immunity is low. Our environment has a very heavy load of mycobacterium tuberculosis and is the biggest souce of tuberculosis for us in India. This environmental load comes from open cases of lung tuberculosis which therefore is our main target for anti tuberculous treatment. Therefore, even with the high prevalence of latent TB in a heavily populated country like ours, the “Revised National TB control program” (RNTCP) only recommends treatment of active tuberculosis in our country. As per RNTCP treating latent tuberculosis would only result in financial burden which may not be logistic as the treatment of active disease is of utmost importance.

On the contrary, in western countries the prevalence of latent tuberculosis is as low as 0.5%. These cases of latent tuberculosis represent the majority of reservoir of potential cases of tuberculosis disease in low prevalence zones such as in the United States and Europe, as their environment is practically free of this bacteria.Therefore their major prevention of the disease is by treating cases of latent TB as there is very little chance of re-infection from the environment which practically has no TB bacteria.

Treatment of latent tuberculosis is not recommended unless the person develops a condition where general immunity is lowered and the chance of latent TB converting to active disease becomes higher or the person leaves the country to live in a low prevalence zone. The reservoir of LTBI is therefore a major barrier to the ultimate control and elimination of tuberculosis. The concern with latent tuberculosis is that it (LTBI) can itself progress to active disease in approximately 5 to 10% of infected persons in a life time. The progression of latent tuberculosis to active disease occurs mostly in immunologically compromised individuals.

Question no 2.
Why it is difficult to treat latent tuberculosis in India? How is the situation different from the west?
In developed countries where incidence of TB has fallen to low levels (0.5%) are recognized as low prevalent areas. In such areas most new cases of TB occur in persons who were infected in the remote past, contained their infection as latent TB, and subsequently developed active disease as a result of lowered immunity. In low-prevalence countries, therefore, the treatment of persons with LTBI is a major component of TB control as they represent the main reservoir of potential cases and 90% of active TB cases occur from activation of latent TB as environment has very scanty prevalence of tuberculosis bacteria. Treatment of LTBI can achieve up to 80 times reduction in active TB in a community where most cases of active TB result from reactivation of LTBI provided all these persons with LTBI are identified and complete the treatment.

On the reverse, in high prevalent areas the environment has very high concentration of tuberculosis bacteria and latent tuberculosis is seen in 40 to 50% of population vs 0.5% incidence which is seen in low prevalent areas. Therefore, the situation in high prevalence TB areas such as India is different because here 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 answer is probably an emphatic no.

The reasons are:
Firstly, the inclusion of treatment of LTBI in the national program will only increase the logistic and financial burden on the health system as long as people with active TB are not treated completely we shall not be able to change the prevalence of the disease in the country
Secondly, there is a constant exposure of the population to tuberculosis as they live in high prevalent areas, and considerable number of cases could 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 latent disease occurrence lifelong. However, this population will have a very low chance of developing active TB as they have good immunity

Treatment of LTBI is likely to be beneficial in persons with reversible risk factors that increase the chance of developing active TB. For instance, it has been shown that prolonged systemic steroid therapy causes a significant increase in the incidence of TB and one can use chemoprophylaxis for TB in such situations. The policy is primarily good only for patients with reversible factors.
On the other hand 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.

Question no. 3:
What are the dangers of treating latent tuberculosis in a high prevalence country like India?

1. There is a constant risk of exposure to the omnipresent bacilli and re-infection.
2. The social stigma attached with the tuberculosis especially genital tuberculosis label: leads to marital discord, social ostracization and depression.
3. The deluge of fatal side-effects related to the chemotherapeutic medicines.
4. The risk of causing drug resistance where one may need many more antibiotic combinations in higher doses and their antecedant side effects.
5. India’s urban population has developed the strains for multi drug resistance (MDR) tuberculosis in more than 40% of active TB disease versus 5% in the rural population. The reason for this difference in development of MDR is that all these fancy tests to detect latent tuberculosis are not available in rural India, nor can this population afford this prolonged treatment, in absence of any symptoms or disease. There are cases which have even developed total drug resistance (TDR) in cities and in want of sanitoriums have to be sent away from their families and from cities to suffer in seclusion till their end, least they would infect other contacts with the same drug resistant strain of TB.
6. The picture is scary and may be by treating latent TB we are moving toward an India which will need sanitoriums again and to the era 100 years behind, when no antibiotics were available to treat this disease.

Remember these are individuals with no symptoms or signs of active disease and do not need the treatment anyways.

Question no. 4:
Can latent tuberculosis cause infertility?
This a bacilli that has been contained by the immune system already and hence is prevented from actively dividing or acting up through its incitement of immunological reaction.

There is no evidence to suggest that latent infection with the tuberculosis bacilli anywhere in the body leads to an alteration of the ovarian, tubal or endometrial function, if there has been no prior active infection involving the reproductive tract. Women with active pulmonary tuberculosis are seen toilling the ante natal out- patient department of hospitals in great numbers.

References
*Mayurnath S, Vallishayee RS, Radhamani MP, et al, Prevalence study of tuberculosis infection over fifteen years, in a rural population in Chingleput district (south India). Indian J Med Res 1991;93:74-80.
*Horsburgh CR. Priorities for the treatment of Latent Tuberculosis Infection in the United States. N Engl J Med 2004; 350: 2060-2064.
*Taylor Z. What is the epidemiological impact of treatment of latent tuberculosis infection? In: Toman’s Tuberculosis Case detection, tratement and monitoring: questions and answers. Freiden TR (Editor).2nd edition. Geneva, World Health Organization 2004: 226-229. (WHO/TB/2004;334