Wei Wang1, Hou Ming Liu2, Jing Zhou3, Yu Guang Wang4, Xi Feng5, Hao Tang5, Qinying Yan6, Rong Sheng Zhu7, Yu Wei Wu7, Xing Guo Wang7, Dan He7, Fan Chen8. 1. Department of Laboratory Medicine, Health Science Center; Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, Guangdong, China. 2. Clinical Laboratory of Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China. 3. Clinical Laboratory of Wuhan Pulmonary Hospital, Wuhan, 430030, Hubei, China. 4. Center of Digital Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. 5. The Department of Pathology, Hubei Cancer Hospital, Wuhan, 430079, China. 6. College of Pharmaceutical Sciences, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310032, China. 7. State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, 368 Youyi Road, Wuhan, 430062, China. 8. State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, 368 Youyi Road, Wuhan, 430062, China. chenfan1688cn@aliyun.com.
Abstract
BACKGROUND: The 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. METHODS: In 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. RESULTS: The MNP penetrated the skin easily with a thumb press, and the microneedle dissolved into the skin completely after 1 h. The storage life of MNP loaded with PPD (MNP-PPD) was 7 weeks at atmospheric pressure and room temperature. Only 1/50 dosage of PPD (approximately 0.04 IU) was needed in MNP compared with conventional injection (2 IU) in terms of skin reactivity to TST. When TST was tested in volunteers, the redness and induration of the skin were 19.7 ± 5.6 mm in TB patients, 12.6 ± 4.4 mm in LTBI (latent TB infection) patients, and 5.8 ± 2.7 mm in BCG vaccination healthy volunteers and lasted approximately 26 ± 5.4 days. When applied with MNP-PPD, the redness and induration on the skin decreased significantly to 3.1 ± 0.7 mm in TB patients and 2.0 ± 0.5 mm in LTBI, and the duration time was only 8.5 ± 1.5 days. 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. CONCLUSION: In 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 2.5 mm can identify a TB-positive patient.
BACKGROUND: The 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. METHODS: In 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. RESULTS: The MNP penetrated the skin easily with a thumb press, and the microneedle dissolved into the skin completely after 1 h. The storage life of MNP loaded with PPD (MNP-PPD) was 7 weeks at atmospheric pressure and room temperature. Only 1/50 dosage of PPD (approximately 0.04 IU) was needed in MNP compared with conventional injection (2 IU) in terms of skin reactivity to TST. When TST was tested in volunteers, the redness and induration of the skin were 19.7 ± 5.6 mm in TBpatients, 12.6 ± 4.4 mm in LTBI (latent TBinfection) patients, and 5.8 ± 2.7 mm in BCG vaccination healthy volunteers and lasted approximately 26 ± 5.4 days. When applied with MNP-PPD, the redness and induration on the skin decreased significantly to 3.1 ± 0.7 mm in TBpatients and 2.0 ± 0.5 mm in LTBI, and the duration time was only 8.5 ± 1.5 days. 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. CONCLUSION: In 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 2.5 mm can identify a TB-positive patient.
Authors: Kristi M Guinn; Mark J Hickey; Sanjeev K Mathur; Kelly L Zakel; Jeff E Grotzke; David M Lewinsohn; Sherilyn Smith; David R Sherman Journal: Mol Microbiol Date: 2004-01 Impact factor: 3.501