Spotting latent infection: the path to better tuberculosis control

Tuberculosis (TB) control is based on prevention as well as prompt diagnosis and treatment of active TB. Since the latter is usually accomplished quite effectively in developed countries, and since BCG vaccination is of limited effectiveness, better TB control will require improved diagnosis and preventative treatment of latent tuberculosis infection (LTBI).^1–3 The reservoir of latently infected individuals is much larger than the number of active TB cases, and includes recently infected contacts of pulmonary TB cases and immigrants from high prevalence regions who acquired infection in their country of origin. This latter group is becoming increasingly important because over half the burden of TB in many low prevalence countries is carried by immigrants,^3–5 and because several higher prevalence countries will soon join the European Union.

Prophylactic treatment of LTBI is highly effective in preventing the subsequent development of active TB;¹ the difficulty lies in identifying who is harbouring latent bacilli. TB control programmes rely exclusively on the century old tuberculin skin test (TST) for diagnosing LTBI in asymptomatic individuals with known or suspected TB exposure.^1,3 The success or otherwise of TB control and elimination in the developed world thus hinges on the oldest diagnostic test in medicine, and the multiple limitations of the TST constitute a major roadblock to better TB control.

The main drawback of the TST is its poor specificity because of false positive results in BCG vaccinated individuals caused by antigenic cross reactivity of purified protein derivative (PPD) with BCG;⁶ this confounding effect persists for as long as 15 years after vaccination.⁷ This is a widespread problem as most of the world’s population is BCG vaccinated and, even in low prevalence countries that have ceased BCG vaccination, most TB cases …