02842nas a2200457   4500000000100000008004100001260001600042653001500058653001000073653000900083653002400092653001600116653001000132653002100142653001100163653002200174653001100196653003000207653002300237653001400260653001100274653001200285653001100297653000900308653001600317653002500333653003100358653001500389653003200404653001500436653001700451100001200468700001500480700001900495700001300514245008300527300001100610490000800621520174100629022001402370       1994                            d  c1994 Nov 0510aAdolescent10aAdult10aAged10aAntigens, Bacterial10aBCG Vaccine10aChild10aChild, Preschool10aFemale10aFollow-Up Studies10aHumans10aHypersensitivity, Delayed10aImmunity, Cellular10aIncidence10aInfant10aleprosy10aMalawi10aMale10aMiddle Aged10aMycobacterium leprae10aMycobacterium tuberculosis10aPrevalence10aSensitivity and Specificity10aSkin Tests10aTuberculosis1 aFine PE1 aSterne J A1 aPonnighaus J M1 aRees R J00aDelayed-type hypersensitivity, mycobacterial vaccines and protective immunity.  a1245-90 v3443 a<p>There is a longstanding debate over the implications of natural and vaccine-induced delayed type hypertensivity for protective immunity to mycobacterial infections. The identification of correlates of vaccine-induced protective immunity should help explain the inconsistent behaviour of BCG vaccines in different populations and assist in efforts to devise improved vaccines. More than 70,000 subjects in Karonga District, northern Malawi were skin tested with soluble antigens of the tubercle and leprosy bacilli, and then followed up for five years for tuberculosis and leprosy incidence. Incidence rate ratios were calculated to compare subjects with different levels of prior skin test sensitivity, after controlling for the effects of age, sex and previous BCG vaccination. BCG vaccination protected against leprosy without persistent delayed-type hypersensitivity to tuberculin or to soluble antigens of the leprosy bacillus. In subjects who had not received BCG, hypersensitivity to tuberculin or to antigens of the leprosy bacillus was associated with strong protection against leprosy. In BCG-vaccinated and unvaccinated subjects, there was a J-shaped relation between hypersensitivity to tuberculin and subsequent rates of tuberculosis, with lowest rates associated with low grade sensitivity (induration 1-10 mm). This study shows that delayed-type hypersensitivity to mycobacterial antigens has different implications for tuberculosis and leprosy: low-level hypersensitivity (probably attributable to environmental mycobacteria) is associated with protection, but persistent vaccine-associated hypersensitivity to mycobacterial antigens is not a correlate of vaccine-derived protection against mycobacterial diseases.</p>  a0140-6736