Does the protective effect of neonatal BCG correlate with vaccine-induced tuberculin reaction?

A case-control study was conducted in Saudi Arabia, where the same strain of BCG has been used and surveys had shown that up to 88% of vaccinated children remain tuberculin negative. Active cases were obtained by surveying the seven tuberculosis centers in 1 yr. Control subjects were obtained from a nationwide survey of normal individuals. Vaccination in both groups was ascertained by history and BCG scar. Relative risk of contracting active tuberculosis in the vaccinated versus unvaccinated and protection was calculated. Protection was as follows: age group 5 to 14 yr, 82% (55 to 93%); age group 15 to 24 yr, 67% (55 to 77%); and age group 25 to 34 yr, 20% (-6 to 37%). We document the uninterrupted record of protection by BCG administered in the neonatal period and discuss the significance of vaccination timing. We concur with other studies that protection lapsed after about 20 yr. More importantly, this is the first large study that documents a lack of tuberculin sensitivity despite protection. This challenges the view that sensitization is essential for protection and supports the "two-pathway" theory that BCG vaccination could trigger either protective (Lister type) or antagonistic (tuberculin or Koch type) reactions and that the most protective vaccines would have little tuberculin-sensitizing effect because the two pathways are competitive.