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

SETTING: Rural northern Malawi, where vaccination with BCG Glare (1077) pro vides protection against leprosy but not against pulmonary tuberculosis. OBJECTIVE: To evaluate the patterns of responsiveness to purified protein d erivative of Mycobacterium tuberculosis (PPD) in terms of delayed type hype rsensitivity (DTH) and interferon-gamma (IFN-gamma) production. DESIGN: IFN-gamma was measured in G day whole blood cultures diluted 1 in 1 0, stimulated with PPD RT48, and the results compared to the DTH response t o PPD RT23. A total of 633 individuals aged 12 to 28 years, without prior B CG vaccination, were recruited. RESULTS: Overall, 63% of subjects made a positive IFN-gamma response (defin ed as > 62 pg/ml), and 37% gave a DTH induration of >5 mm. A strong correla tion between skin test and LFN-gamma responses was observed, although with interesting exceptions: 13/270 individuals with zero DTH showed IFN-gamma r esponses > 500 pg/ml, and 7/53 individuals with > 10 mm induration showed I FN-gamma responses less than or equal to 62 pg/ml. The prevalence of skin t est responsiveness increased with age, and was higher among older males tha n females; age-sex patterns were less clear for IFN-gamma production. CONCLUSION: The 6 day IFN-gamma response to PPD correlates well with Mantou x skin test induration. The discordant individuals may represent important subsets in terms of protective immunity and risk of clinical tuberculosis.