Describe the tuberculin (Mantoux) test with its principle, interpretation and limitations.

Principle and Technique

0.1 mL of PPD (purified protein derivative) containing 5 tuberculin units is injected intradermally into the flexor surface of the forearm → A correct injection raises a pale wheal of 6 to 10 mm; if no wheal forms the injection was subcutaneous and must be repeated elsewhere → Sensitised T lymphocytes recognise the antigen and release cytokines → Macrophages and lymphocytes accumulate over the following hours → Read at 48 to 72 hours → Measure the transverse diameter of induration, not of erythema, by palpation or the ballpoint pen method

Causes of False Results

• False positive — previous BCG vaccination (though the effect wanes over years); infection with non-tuberculous mycobacteria; incorrect reading of erythema instead of induration; and the booster phenomenon, in which a first test restimulates waning immunity so that a second test weeks later appears larger and is misread as recent conversion
• False negative (anergy) — overwhelming tuberculosis itself, particularly miliary disease and tuberculous meningitis; HIV and other immunosuppression; corticosteroids and cytotoxic drugs; malnutrition; measles, chickenpox and other viral infections and live viral vaccination within 6 weeks; sarcoidosis, lymphoma; extremes of age; and the window period of 4 to 6 weeks after infection before hypersensitivity develops
• Technical errors — subcutaneous injection, deteriorated or improperly stored PPD, and reading at the wrong time

Uses and Limitations

• Uses — supporting a diagnosis of tuberculosis in children (where it carries more weight than in adults); detecting latent infection before immunosuppressive or anti-TNF therapy, before transplantation and in contacts; epidemiological surveys of infection prevalence; and assessing cell-mediated immunity
• Limitations — it cannot distinguish latent infection from active disease, nor recent from remote infection; it is confounded by BCG and environmental mycobacteria; it requires two visits; and reading is subjective
• Interferon-gamma release assays use ESAT-6 and CFP-10, antigens absent from BCG, so they are not confounded by vaccination, require only one visit and are objective — but they are expensive and equally unable to separate latent from active disease
• A strongly positive test in a young child is more meaningful, since it suggests recent infection and a real risk of progression, which is why contact tracing in children is worthwhile

Applied Aspects

• Never diagnose or exclude tuberculosis on this test alone — it supports a clinical diagnosis and nothing more
• Measure induration by palpation, not erythema; reading redness is the commonest technical error and consistently overcalls the result
• A negative test in a very ill patient may indicate anergy rather than absence of infection, and this is exactly the situation in which the disease is most dangerous
• Its value is limited in India by universal BCG and a high prevalence of infection, which is why the national programme relies on bacteriological confirmation rather than on tuberculin testing
• Use it to screen for latent infection before anti-TNF therapy, transplantation or prolonged steroids, where identifying and treating latent tuberculosis prevents a potentially fatal reactivation
• Store PPD correctly and use it promptly; it is light-sensitive and adsorbs to glass and plastic, and deteriorated antigen gives false negatives
• A single test result cannot be compared with one done elsewhere unless the same antigen strength and reading method were used; conversion should be judged on tests performed under comparable conditions
• Treat latent infection where it is identified before immunosuppression, usually with isoniazid or a rifamycin-based regimen; identifying it and doing nothing wastes the test