Skin test of tuberculin purified protein derivatives with a dissolving microneedle-array patch

摘要

BackgroundThe tuberculin skin test (TST) is a long-established screening method for tuberculosis. However, the Mantoux technique is often difficult to reliably perform, which affects testing results and safety, which causes local skin pain and pruritus.MethodsIn this study, dissolving microneedle-array patches (MNP) were used to deliver purified protein derivative (PPD) tuberculin into the skin. The skin reaction was compared between MNP delivery and conventional injection.ResultsThe MNP penetrated the skin easily with a thumb press, and the microneedle dissolved into the skin completely after 1h. The storage life of MNP loaded with PPD (MNP-PPD) was 7weeks at atmospheric pressure and room temperature. Only 1/50 dosage of PPD (approximately 0.04IU) was needed in MNP compared with conventional injection (2IU) in terms of skin reactivity to TST. When TST was tested in volunteers, the redness and induration of the skin were 19.75.6mm in TB patients, 12.6 +/- 4.4mm in LTBI (latent TB infection) patients, and 5.8 +/- 2.7mm in BCG vaccination healthy volunteers and lasted approximately 26 +/- 5.4days. When applied with MNP-PPD, the redness and induration on the skin decreased significantly to 3.1 +/- 0.7mm in TB patients and 2.0 +/- 0.5mm in LTBI, and the duration time was only 8.5 +/- 1.5days. Moreover, despite the relatively mild skin reactivity in BCG vaccination healthy volunteers with conventional injection, there was no skin reactivity in BCG vaccination healthy volunteers with MNP-PPD.ConclusionIn addition to being minimally invasive, needle-free, and painless, no adverse effects were attributed to the new diagnostic method, which may be of value for the safe and effective clinical administration of TB screening. When applied with MNP-PPD, an area of redness and induration greater than 2.5mm can identify a TB-positive patient.