Tuberculin conversion and leukocyte migration inhibition test after BCG vaccination in newborn infants

There are reports that BCG vaccine take-up may be delayed or poor among preterm and low birth weight babies

The present study was conducted with the objective of (a) studying BCG take-up through tuberculin conversion by Mantoux test at 12 weeks and 6 months of age in babies vaccinated with BCG at birth and (b) evaluating the Leukocyte Migration Inhibition Test (LMIT) in BCG vaccinated babies who did not react to Mantoux test.

Prospective observational study.

BCG vaccine was administered to 143 neonates of 31-41 weeks gestation within 7 days of birth. At 12 weeks of age, Purified Protein Derivative (1 TU PPD-RT 23 with Tween 80) was injected to all the babies and induration was measured at the injection site after 48 hours. Mantoux negative babies were subjected to the LMIT. All the Mantoux test and LMIT negative babies were followed up and given another Mantoux test at 6 months. Those babies who showed a negative Mantoux test at 6 months and negative LMIT at 12 weeks were subjected to another LMIT at 6 months.

Local BCG reaction was exhibited by 95.5% babies at 8 weeks and scar formed in 47.2% of them by 12(+1) weeks. The tuberculin conversion rate after 12 weeks of BCG vaccination was 42.7%. The rate of tuberculin conversion was significantly more in babies with birth weight>2500 g as compared to low birth weight babies. Also, the rate of tuberculin conversion was significantly more in term infants as compared to preterm babies. Six months after BCG vaccination, 41.5% of previously Mantoux negative babies showed tuberculin conversion. Overall, 66.4% babies reacted to PPD after 6 months. LMIT was positive in 84.1% babies who had a negative Mantoux test at 12 weeks. Six months after BCG vaccination, 53.8% of babies who had LMIT negative at 3 months became LMIT positive. Thus out of 143 babies, 95.8% had either a reactive Mantoux test or positive LMIT 6 months after BCG vaccination. There were only 6 babies (4.2%) who did not show adequate responses to BCG vaccination.

Preterm babies of 31 to 36 weeks of gestation and low birth weight babies weighing <2,500 gram at birth can be effectively vaccinated with BCG vaccine in the early neonatal period. However, tuberculin conversion is not a reliable indicator to assess responses induced by BCG vaccination either 12 weeks or 6 months after vaccination because inspite of negative Mantoux test, the vaccinated infant may still be having an adequate response to BCG vaccine. The local BCG reaction at 8 weeks corresponds to cell mediated immunity conferred by BCG vaccination.