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Relationship between IFN-gamma and skin test responsiveness to Mycobacterium tuberculosis PPD in healthy, non-BCG-vaccinated young adults in Northern Malawi.

SETTING
Rural northern Malawi, where vaccination with BCG Glaxo (1077) provides protection against leprosy but not against pulmonary tuberculosis.


OBJECTIVE
To evaluate the patterns of responsiveness to purified protein derivative of Mycobacterium tuberculosis (PPD) in terms of delayed type hypersensitivity (DTH) and interferon-gamma (IFN-gamma) production.


DESIGN
IFN-gamma was measured in 6 day whole blood cultures diluted 1 in 10, stimulated with PPD RT48, and the results compared to the DTH response to PPD RT23. A total of 633 individuals aged 12 to 28 years, without prior BCG vaccination, were recruited.


RESULTS
Overall, 63% of subjects made a positive IFN-gamma response (defined as >62 pg/ml), and 37% gave a DTH induration of >5 mm. A strong correlation between skin test and IFN-gamma responses was observed, although with interesting exceptions: 13/270 individuals with zero DTH showed IFN-gamma responses >500 pg/ml, and 7/53 individuals with >10 mm induration showed IFN-gamma responses < or = 62 pg/ml. The prevalence of skin test responsiveness increased with age, and was higher among older males than females; age-sex patterns were less clear for IFN-gamma production.


CONCLUSION
The 6 day IFN-gamma response to PPD correlates well with Mantoux skin test induration. The discordant individuals may represent important subsets in terms of protective immunity and risk of clinical tuberculosis.