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1. Patient-related factors drive high rates of reported antibiotic allergies: A qualitative study

Author

Renee Berry, Susan Herrmann, and Michaela Lucas

Subjects
Antibiotic allergy, Patient perspective, Qualitative, Medicine
Abstract

Background: Unnecessary antibiotic avoidance due to allergy fears has adverse cost and health implications however, the problem is difficult to resolve because patient and provider-related factors leading to avoidance are multifactorial. We use qualitative research methods to explore patient perspectives of antibiotic allergy and testing to reach the heart of the problem. Objective: To reveal factors leading patients to report antibiotic allergy, and determine what education is required to prevent the cycle of erroneous allergy reporting. Methods: The 29 patients were a sample of convenience recruited from a tertiary public hospital in Western Australia between March 2020 until August 2020; 18 were inpatients and 11 outpatients, with a median age of 64.2 years, and 15 (55%) were female. Semi-structured interviews assessed patients’ understanding and knowledge of three topics: (1) antibiotic allergy, (2) antibiotic allergy testing, and (3) outcomes of testing. Interview transcripts underwent thematic analysis by two researchers, independently. Results: Three main, overlapping themes emerged as influential across topics: (1) Severity of the Index Reaction, (2) Trust in family and health care providers, and (3) Health literacy. Patients were largely unaware of the benefits of confirmatory testing, and the detrimental health consequences of unnecessary avoidance. Patients displayed trust in health care providers’ expertise and assumed that medical records were accurate to prevent prescribing errors. Conclusions: The findings provide evidence for an effective patient education strategy and highlight failures among hospital and primary health providers to recognise the potential harm of unverified antibiotic allergy. Healthcare professionals are influential at multiple steps of a patient's healthcare journey and addressing unconfirmed antibiotic allergy should be taken at each opportunity.

Published
2024
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2. Distinguishing DRESS syndrome from drug rash and eosinophilia: Beyond RegiSCAR criteria

Author

Grace Thompson, MBBS, Syed Ali, MBBS, Michelle Trevenen, PhD, Philip Vlaskovsky, PhD, Kevin Murray, PhD, and Michaela Lucas, MD

Subjects
Drug reaction, eosinophilia, systemic symptoms, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) can be challenging. Objectives: We sought to identify clinical and laboratory features outside of the Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria that distinguish patients with probable DRESS (RegiSCAR ≥ 4) from those with drug rash and eosinophilia (DRE). Methods: Using international coding classifications of drug-induced fever, generalized skin eruption due to medications, and eosinophilia, a retrospective audit from 2008 to 2023 of hospitalized patients was performed. Results: Forty-four cases of DRESS were compared to 80 cases of DRE. In addition to the RegiSCAR distinguishing factors for DRESS were longer drug latency before symptom onset (median 21 vs 5 days, P < .001) and higher alanine transaminase levels (increase by a factor of 2.49 [95% confidence interval, 1.56, 4.00; P = .009]). Follow-up (mean 5.67 years) revealed a low rate of statewide drug alert reporting (29.6%) and drug allergy testing in DRESS (20.5%). Inadvertent reexposure to a culprit or structurally related drug resulted in recurrent DRESS in 3 patients (7.5%), and tolerance of structurally related drugs occurred in 8 patients (17.5%). Conclusion: In this large study evaluating DRE patients whose disease does not meet the RegiSCAR criteria for DRESS, we found that additional factors outside the RegiSCAR criteria may help clinicians differentiate DRESS, which is critical for optimal and timely patient management. Our study also highlights the need for development of local protocols to ensure appropriate allergy labeling and testing are performed to prevent recurrent DRESS.

Published
2024
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3. Patient-related factors impact the implementation of inpatient antibiotic allergy delabeling

Author

Susan Herrmann, PhD, Rishabh Kulkarni, MBChB, Michelle Trevenen, PhD, Hana Karuppasamy, CN, Catherine Willis, MBBS, Renee Berry, MBBS, Britta Von Ungern-Sternberg, MD, Niklesh Warrier, BMedSci, Ian Li, PhD, Kevin Murray, PhD, and Michaela Lucas, MD

Subjects
Antibiotic allergy, delabeling, adult inpatients, drug allergy, Immunologic diseases. Allergy, RC581-607
Abstract

Background: The clinical consequences of an antibiotic allergy label are detrimental, impacting health care delivery and patient outcomes. We assessed hospital inpatients with intent to offer free antibiotic allergy labeling (AAL) assessment within a randomized controlled trial. Objective: We sought to determine the feasibility of establishing an adult antibiotic allergy delabeling service in a Western Australian tertiary public hospital. Methods: Inpatients (N = 1503) with AAL were identified through medical records and screened for eligibility to participate in a randomized controlled trial. Those recruited were randomized to undergo assessment by skin testing ± oral challenge, or direct oral challenge. A control group received usual care. Results: Of the 1503 inpatients with an AAL, 429 (28.5%) were eligible for AAL assessment. The primary excluding factor (1074 [71.5%]) was contraindicated medication use (387 [36.0%]), followed by cognitive impairment (298 [27.9%]). Thirty-nine patients were randomized, of which 20 received allergy testing and 19 usual care; all patients were followed up for 5 years. Older patients were less likely to be eligible (10-year increase: odds ratio, 0.82; 95% CI, 0.77-0.88; P < .0001), whereas surgical patients were more likely to be eligible than medical patients (odds ratio, 2.49; 95% CI, 1.97-3.16; P < .0001). Conclusions: Antibiotic allergy delabeling in the acute care context is not straightforward. Competing clinical concerns and patient acceptance are some barriers to an inpatient service. Nor is it apparent that inpatient versus outpatient testing is cost saving although select patient groups may benefit. Testing younger people and those with predicted high antibiotic usage will derive maximal individual and health system benefits.

Published
2024
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4. Plastics in human diets: development and evaluation of the 24-h Dietary Recall — Plastic Exposure and the Dietary Plastics Score

Author

Amelia Harray, Susan Herrmann, Hannah Papendorf, Claire Miller, Andrea Vermeersch, Tony Smith, and Michaela Lucas

Subjects
plastic-associated chemicals, dietary intake, dietary assessment, bisphenols, phthalates, 24-h Dietary Recall, Nutrition. Foods and food supply, TX341-641
Abstract

BackgroundHumans are commonly exposed to plastic through their dietary intake and food consumption patterns. Plastic-associated chemicals (PAC), such as bisphenols and phthalates, are recognized as endocrine-disrupting and are associated with increased risk of cardiovascular disease and metabolic syndrome. However, accurate methods to assess dietary exposure to plastic products and PAC are inadequate, limiting interrogation of health impacts.AimTo develop a tool that captures complete dietary exposure to plastics and establish a diet quality score to measure adherence to a low plastic dietary pattern.MethodsWe developed the 24-h Dietary Recall – Plastic Exposure (24DR-PE) and administered it to healthy adults (n = 422). This computer-assisted, interviewer-administered tool systematically collects data on food volumes and types, packaging materials, storage, processing, cooking, and consumption methods to assess a food’s exposure to plastic. Specifically, the 24DR-PE incorporates predefined criteria for identifying high-risk practices and food characteristics, such as individually packaged items or those microwaved in plastic, enabling the assignment of scores based on a theoretically derived Dietary Plastics Scoring Matrix.ConclusionThe 24DR-PE is the first tool specifically designed to capture detailed data on dietary exposures to plastic products. The next step is to validate the score using laboratory results of urine samples we collected contemporaneous to the dietary information. Once validated, the tool has potential for widespread distribution making it valuable for population monitoring, intervention guidance, and future research investigating the interplay between plastics, diet, and human health.

Published
2024
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5. Promoting patient-centred care in the management of allergic rhinitis in Asia-Pacific countries

Author

Hiroshi Chantaphakul, MD, De Yun Wang, MD, PhD, Tran Thi Thuy Hang, ThS, BS, CKII, Khizuan Abdul Kadir, MD, MS, Hoang Thi Lam, MD, PhD, Cecilia Gretchen Navarro-Locsin, MD, MS, Sira Nanthapisal, MD, PhD, Danilo Poblete, MD, Pongsakorn Tantilipikorn, MD, PhD, Wong Hui Tong, MBBS, MS, MCRS, Dinesh Nagrale, MD, and Michaela Lucas, MD

Subjects
Rhinitis, Allergic, Allergy and immunology, Asia, Patient-centred care, Decision-making, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Allergic rhinitis (AR) has a high burden of disease in the Asia-Pacific region (APAC). Although guidelines provide recommendations regarding the diagnosis and treatment of AR, it is increasingly being recognised that there are gaps in their implementation. Patient-centred care involves accounting for the specific needs and desires of patients as well as including the patient in the decision-making process, and this may provide a means to reduce these gaps and consequently the burden of AR. Methods: A group of 11 experts in immunology and otorhinolaryngology from APAC provided information regarding their practices and experiences in the management of AR through an online survey. The group then discussed the barriers and solutions for the implementation of patient-centred care across the patient journey in a face-to-face meeting. Results: Key barriers to the implementation of patient-centred care for AR in APAC included a lack of patient awareness of the condition and treatment options, low adherence to treatments, financial constraints for patients, and time constraints for physicians. The solutions proposed include improving the knowledge of the patients about their conditions, the use of shared decision-making, the consideration of patient characteristics when choosing treatments, and the use of outcome measures to aid the optimisation of patient care. We provide specific recommendations for clinical practice. Conclusion: A greater focus on patient-centred approaches has the potential to improve the management of AR in APAC. More emphasis should be placed on each patient's specific health needs and desired outcomes.

Published
2024
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6. Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trialResearch in context

Author

Laure F. Pittet, Nicole L. Messina, Ellie McDonald, Francesca Orsini, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Mariana G. Croda, Margareth Dalcolmo, Kaya Gardiner, Amanda Gwee, Bruno Jardim, Marcus V.G. Lacerda, Michaela Lucas, David J. Lynn, Laurens Manning, Kirsten P. Perrett, Jeffrey J. Post, Cristina Prat-Aymerich, Peter C. Richmond, Jorge L. Rocha, Jesus Rodriguez-Baño, Adilia Warris, Nicholas J. Wood, Andrew Davidson, Nigel Curtis, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Susan Herrmann, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Bruna Tayara LEOPOLDINA MEIRELES, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, P.M.G. Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, R.C. Pon, Lieke Preijers, J.H. van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, Neil Gow, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Bacille Calmette-Guérin (BCG) vaccine, Immunity, Heterologous, Health personnel, Randomised controlled trial, Primary prevention, Medicine (General), R5-920
Abstract

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Published
2024
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7. Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines—an exploratory sub-study of the BRACE trialResearch in context

Author

Nicole L. Messina, Susie Germano, Rebecca McElroy, Rhian Bonnici, Branka Grubor-Bauk, David J. Lynn, Ellie McDonald, Suellen Nicholson, Kirsten P. Perrett, Laure F. Pittet, Rajeev Rudraraju, Natalie E. Stevens, Kanta Subbarao, Nigel Curtis, Andrew Davidson, Kaya Gardiner, Amanda Gwee, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Thanh Dang, Jenny Hua, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O’Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O’Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O’Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Simone Barry, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O’Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Laurens Manning, Susan Herrmann, Michaela Lucas, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Bruno Jardim, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Julio Croda, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Marc Bonten, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Cristina Prat-Aymerich, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, Margreet Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, Roos Pon, Lieke Preijers, Joke van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, John Campbell, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O’Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Adilia Warris, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Vaccine, Off-target, Immunoregulation, Cytokine, SARS-CoV-2, Heterologous immunity, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Published
2024
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8. Perspectives and gaps in the management of food allergy and anaphylaxis in the Asia-Pacific Region

Author

Agnes Sze Yin Leung, MRCPCH, Ruby Pawankar, MD, Punchama Pacharn, MD, Lydia Su Yin Wong, MRCPCH, Duy Le Pham, MD, Grace Chan, MD, Iris Rengganis, MD, Jing Zhao, MD, Jiu Yao Wang, MD, Kent Chee-Keen Woo, MD, Komei Ito, MD, Kyunguk Jeong, MD, Marysia Recto, MD, Michaela Lucas, MD, Mizuho Nagao, MD, Rommel Crisenio M. Lobo, MD, Sonomjamts Munkhbayarlakh, MD, Sumadiono Sumadiono, MD, Syed Rezaul Huq, MD, Thushali Ranasinghe, MBBS, and Mimi Tang, MBBS, PhD

Subjects
Food allergy, anaphylaxis, allergy service, allergist, adrenaline autoinjector, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region. Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia. Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey. Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories. Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.

Published
2024
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9. Bacillus Calmette-Guérin vaccination for protection against recurrent herpes labialis: a nested randomised controlled trialResearch in context

Author

Laure F. Pittet, Cecilia L. Moore, Ellie McDonald, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Margareth Dalcolmo, Andrew Davidson, Mark W. Douglas, Kaya Gardiner, Amanda Gwee, Bruno Jardim, Marcus V.G. Lacerda, Michaela Lucas, David J. Lynn, Laurens Manning, Roberto D. de Oliveira, Kirsten P. Perrett, Cristina Prat-Aymerich, Peter C. Richmond, Jorge L. Rocha, Jesus Rodriguez-Baño, Adilia Warris, Nicholas J. Wood, Nicole L. Messina, Nigel Curtis, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Susan Herrmann, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, P.M.G. Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, R.C. Pon, Lieke Preijers, J.H. van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Herpes simplex virus, Cold sore, Herpes labialis, Bacille Calmette-Guérin, Mycobacterium bovis, Prevention, Medicine (General), R5-920
Abstract

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Published
2023
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11. Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

Author

Paola Villanueva, Nigel W. Crawford, Mariana Garcia Croda, Simone Collopy, Bruno Araújo Jardim, Tyane de Almeida Pinto Jardim, Laurens Manning, Michaela Lucas, Helen Marshall, Cristina Prat-Aymerich, Alice Sawka, Ketaki Sharma, Darren Troeman, Ushma Wadia, Adilia Warris, Nicholas Wood, Nicole L. Messina, Nigel Curtis, and Laure F. Pittet

Subjects
BCG vaccine, BCG scar, Vaccination technique, Vaccine safety, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial (‘BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers’; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2–0.9), BCG revaccination (OR 1.7, 95%CI 1.3–2.0), female sex (OR 2.0, 95%CI 1.7–2.4), older age (OR 0.4, 95%CI 0.4–0.5) and study country (Brazil OR 1.6, 95%CI 1.3–2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine.Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Published
2023
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12. Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

Author

Paola Villanueva, Ushma Wadia, Nigel Crawford, Nicole L. Messina, Tobias R. Kollmann, Michaela Lucas, Laurens Manning, Peter Richmond, Laure F. Pittet, and Nigel Curtis

Subjects
Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

Published
2022
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13. Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19

Author

Lyn R. Frumkin, Michaela Lucas, Curtis L. Scribner, Nastassja Ortega-Heinly, Jayden Rogers, Gang Yin, Trevor J. Hallam, Alice Yam, Kristin Bedard, Rebecca Begley, Courtney A. Cohen, Catherine V. Badger, Shawn A. Abbasi, John M. Dye, Brian McMillan, Michael Wallach, Traci L. Bricker, Astha Joshi, Adrianus C. M. Boon, Suman Pokhrel, Benjamin R. Kraemer, Lucia Lee, Stephen Kargotich, Mahima Agochiya, Tom St. John, and Daria Mochly-Rosen

Subjects
immunoglobulin Y, IgY, chicken immunoglobulin, infectious diseases, SARS-CoV-2, COVID-19, Immunologic diseases. Allergy, RC581-607
Abstract

COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is different from sera of immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT04567810, identifier NCT04567810.

Published
2022
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14. Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease

Author

Katie Meehan, Connull Leslie, Michaela Lucas, Angela Jacques, Bob Mirzai, James Lim, Max Bulsara, Yasir Khan, Nicholas C. Wong, Benjamin Solomon, Chady Sader, Peter Friedland, Gisela Mir Arnau, Timothy Semple, and Annette M. Lim

Subjects
FOXP3, Immune signature, oral tongue squamous cell carcinoma, PD‐L1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P

Published
2020
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15. The safety of co-administration of Bacille Calmette-Guérin (BCG) and influenza vaccines

Author

Paola Villanueva, Ushma Wadia, Nigel W. Crawford, Nicole L. Messina, Tobias R. Kollmann, Michaela Lucas, Laurens Manning, Peter Richmond, Laure F. Pittet, and Nigel Curtis

Subjects
Medicine, Science
Abstract

Background With the emergence of novel vaccines and new applications for older vaccines, co-administration is increasingly likely. The immunomodulatory effects of BCG could theoretically alter the reactogenicity of co-administered vaccines. Using active surveillance in a randomised controlled trial, we aimed to determine whether co-administration of BCG vaccination changes the safety profile of influenza vaccination. Methods Participants who received influenza vaccine alone (Influenza group) were compared with those who also received BCG-Denmark vaccine in the contralateral arm (Influenza+BCG group). Data on the influenza vaccination site were collected using serial questionnaires and active follow-up for 3 months post vaccination. Results Of 1351 participants in the Influenza+BCG group and 1418 participants in the Influenza group, 2615 (94%) provided influenza vaccine safety data. There was no significant difference in the proportion of participants with any local adverse reaction between the Influenza+BCG group and the Influenza group (918/1293 [71.0%] versus (906/1322 [68.5%], p = 0.17). The proportion of participants reporting any pain, erythema and tenderness at the influenza vaccination site were similar in both groups. Swelling was less frequent (81/1293 [6.3%] versus 119/1322 (9.0%), p = 0.01) and the maximal diameter of erythema was smaller (mean 1.8 cm [SD 2.0] versus 3.0 cm [SD 2.5], pConclusions Adverse events following influenza vaccination are not increased when BCG is co-administered.

Published
2022

16. Flow cytometric characterization of tissue-resident lymphocytes after murine liver and heart transplantation

Author

Amy Prosser, Sarah Dart, Irma Larma-Cornwall, and Michaela Lucas

Subjects
Cell isolation, Flow Cytometry/Mass Cytometry, Immunology, Science (General), Q1-390
Abstract

Summary: Alterations to organ biology caused by transplantation can have major impacts on the outcome. Tissue-resident lymphocytes normally maintain an organ’s immunity and function and are transferred during transplantation. Here, we provide a detailed protocol for the isolation of leukocytes, including tissue-resident lymphocytes, from transplanted livers and hearts in mice. Phenotypic and functional analysis of conventional and unconventional T cells by flow cytometry is included. This protocol can also be used for the effective isolation of leukocytes from non-transplanted livers and hearts.For complete details on the use and execution of this protocol, please refer to Prosser et al. (2021).

Published
2021
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17. BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)

Author

Donna Legge, Katherine J Lee, Rachel Dixon, Amanda Gwee, Nigel Curtis, Helen Marshall, Fiona McDonald, Nick Evans, Adam Finn, Mark McMillan, Peter Richmond, Joyce Chan, John Carlin, Anthony Byrne, Helen Thomson, Richard Hall, Jesús Rodríguez-Baño, Robert Harrison, Kirsten P Perrett, Michaela Lucas, Sue Evans, Melissa O’Donnell, Justin Waring, Andrew Davidson, Heidi Hutton, Laure F Pittet, Jan Kluytmans, Ana Maria Barriocanal, Emily Fletcher, James Moore, John Campbell, Kate Sidaway-Lee, Alex Harding, Katherine Lee, David Paterson, Juliana Silva, Michael Gibbons, Denise Faustman, Nicole L Messina, Kaya Gardiner, Frank Shann, Veronica Abruzzo, Susie Germano, Laurens Manning, Justin Beardsley, Jason Bell, Francesca Orsini, Jeremy Anderson, Kim Mulholland, Andrew Dunn, Jeffrey Post, Catherine Flynn, Clare Seamark, Andrew Steer, Sigrid Pitkin, Emma Watts, Carlos Garcia, Kristen Overton, Daniel Santos, Christina Guo, Antoni Rosell, Sarah Fowler, Richard Malley, Nicholas J Wood, Wim Boersma, Kanta Subbarao, Karen Jones, Chris Richards, Nigel Crawford, Adilia Warris, Mary Corbett, Pamela Palasanthiran, Cristina Pérez, Esther Calbo, Shelley Rhodes, Brendan McMullan, Jane Jones, Wendy Norton, Luke Stevens, Craig F Munns, Louise Goodchild, Mary Walker, Bridget Knight, Thilanka Morawakage, Josune Goikoetxea, Teresa Rodrigues, Nienke Roescher, David Seamark, Jorge Rocha, Stephanie Reynolds, Lynne Quinn, Harry Tripp, Tobias R Kollmann, Marc Bonten, Steve Wesselingh, Irene Latorre, Maria Esteve, Kate Hamilton, Angela Young, Cristina Prat-Aymerich, NICK WOOD, RAMÓN CASTRO, Ruth Warren, Christopher Martin, Diane Dawson, Lorrie Symons, Ann Krastev, Ellie McDonald, Claudia González Rico, Ester Valls, Julio Croda, Tobias Kollmann, Victoria Gordon, Marcus Vinícius Guimarães Lacerda, Jennifer Kent, Samantha Bannister, Margareth Dalcolmo, Sonja Elia, Casey Goodall, Tenaya Jamieson, Bruno Jardim, David J Lynn, Cristina Prat Aymerich, Eva Sudbury, Paola Villanueva, Katherine Lieschke, Carolinne Abreu, Lynne Addlem, Sophie Agius, Adelita Agripina Barbosa, Ahmed Alamrousi, Ayla Alcoforado Santos, Yasmeen Al-Hindawi, Samyra Almeida Da Silveira, Lais Alves Cruz, Christina Anthony, Andrea Antonia Pereira, Francisco Arnaiz Almajano, Annabelle Arnold, Beth Arrowsmith, Kristy Azzopardi, Cristina Badia Marti, Twinkle Bahaduri, Sarah Barney, Lydia Barrera, Anabel Barriocanal, Dayanne Barros, Adam Bartlett, Lilian Muranaka, Therese Baulman, Morgan Bealing, Ana Belen Gutierrez, Vicki Bennett-Wood, Nikki Bergant, Fabiane Bianca Barbosa, Wouter Bijllaardt, Patricia Bimboese, Camila Bitencourt Andrade, Kitty Blauwendraat, Pilar Bohedo Garcia, Rhian Bonnici, Anne Boon, Anna Bourke, Kirsty Bowes, Larissa Brasil, Clare Brophy, Sandy Buchanan, Jess Bucholc, Alison Burns, Emma Burrell, Natalia Bustos, Bridie Byrne, Jorge Calvo Montes, Beatriz Camesella, Atsegiñe Cangas, Maria Carmen Roque, Roberta Carolina Diogo, Estela Carvalho, Irma Casas, Erika Castro, Helen Catterick, Rodrigo Cezar Escobar, Jo Cheah, Thilakavathi Chengodu, Marianna Ciaverella, Sharon Clark, Marie-Alix Clement Espindola, Annie Cobbledick, Clinton Colaco, Simone Collopy, Patricia Comella, Gabriela Correa Castro, Erlane Costa, Raquel Coya, Alda Cruz, Jac Cushnahan, Anna Czajko, Renato da Silva, Bouchra Daitiri, Karen Dalton, Aiken Dao, Phoebe Dawe, Miriam Jesus Costa, Karina De La Cruz, Almudena de Serna, Fabiani de Morais Batista, Adriely de Oliveira, Rocio del Rey Morillo, Maria Desylva, Helga Dijkstra, Maria Dolores Lopez, Jose Dominguez, Angel Dominguez Castellano, Glauce Dos Santos, Joyce Santos Lencina, Débora Santos Silva, Mark Douglas, Ross Dunn, Jemma Dunnill, Harriet Edmund, Nat Eiffler, Hannah Elborough, Olivia Elkington, Michelle England, Wellyngthon Espindola Ayala, Krist Ewe, María Carmen Álvarez, Kieran Fahey, Jill Fairweather, Erica Fernandes Silva, Monique Fernandez, Galina Fidler, P.M.G. Filius, Carolyn Finucane, Stephanie Firth, Lorraine Flynn, Liam Fouracre, Thamires Freitas, Ana Carolina Furtado, Maria Gabriela Oliveira, Anna Gabriela Santos, Leandro Galdino Gonçalves, Laura Galletta, Larissa Gama, Dinusha Gamage, Radhika Ganpat, Mariana Garcia Croda, Evangeline Gardiner, Grace Gell, Aline Gerhardt Oliveira, Camille Gibson, Alison Gifford, Teresa Giménez Poderos, Ann Ginsberg, Jet Gisolf, Bojana Gladanac, Penny Glenn, Vanessa Godinho, Mayara Góes Santos, Telma Goldenberg, Adriano Gomes, Susana Gonzalez Marcos, Frances Greven, Ana Greyce Capella, David Gutierrez Campos, Manuel Gutierrez Cuadra, Lydia Hall, Matthew Hannan, Houda Harbech, Neil Haker, Robert Jan Hassing, Thaynara Haynara Rosa, Zaheerah Haywood, Nadine Henare, Paulo Henrique Andrade, Susan Herrmann, Erin Hill, Sam Hilton, Danique Huijbens, Axel Janssen, Tyane Jardim, Lance Jarvis, Narelle Jenkins, Jan Jones, Leticia Jorge, Maria Jose Vilegas, Sri Joshi, Rosemary Joyce, Joel Junior, Rama Kandasamy, Anushka Karunanayake, Hana Karuppasamy, Tom Keeble, Paul Kloeg, Tony Korman, Nathan La, Marcus Lacerda, Alicia Lacoma, Renier Lagunday, Debbie Lalich, Erin Latkovic, Paulo Leandro Junior, Toos Lemmers, Titia Leurink, Kee Lim, Gemma Lockhart, Cíntia Lopes Bogéa, Karla Lopes Santos, Reyes Lopez Marques, Maria Luciana Freitas, Norine Ma, Sam Macalister, Cristiane Machado, Matheus Machado Ramos, Francesca Machingaifa, Ivan Maia, Bernardo Maia, Sarah Manton, Jose Manuel Carrerero, Cíntia Maria Alves, Rosa Maria Pereira, Bianca Maria Arruda, Adriana Marins, Katya Martinez Almeida, Wayne Mather, Megan Mathers, Fábio Mauricio Gomes, Mariana Mayumi Tadokoro, Nadia Mazarakis, Kelry Mazurega, Sonia McAlister, Amy McAndrews, Rebecca McElroy, Nick McPhate, Lee Mead, Andrea Meehan, Bob Meek, Rosangela Melo, Guillermo Mena, Daniella Mesquita, Nicole Messina, Isabella Mezzetti, Hugo Miguel Vieira, Skye Miller, Kirsten Mitchell, Marcus Mitchell, Jesutofunmi Mojeed, Kitty Molenaar, Gemma Molina, Barbara Molina, Lisa Montgomery, Cecilia Moore, Simone Moorlag, Julie Moss, Will Moyle, Craig Munns, Elizandra Nascimento, Nicolas Navarrette, Mihai Netea, Juliana Neves, Georgina Newman, Belle Ngien, Jill Nguyen, Khanh Nguyen, Fran Noonan, Jess O’Bryan, Abby O’Connell, Sasha Odoi, Liz O’Donnell, Roberto Oliveira, Marilena Oliveira, Thais Oliveira, Ingrid Oliveira, Nadia Olivier, Ligia Olivio, Benjamin Ong, Jaslyn Ong, Joanne Ong, Jakob Onysk, Isabelle Ooi, Frances Oppedisano, Belinda Ortika, Orygen Group, Arthur Otsuka, Rosie Owens, Rayssa Paes, Virginia Palomo Jiménez, Girlene Pandine, Kimberley Parkin, Alvaro Pascual Hernandez, Nienke Paternotte, Ana Paula Souza, Lisa Pelayo, Casey Pell, Sille Pelser, Handerson Pereira, Gabrielle Pereira, Glady Perez, Tomás Perez Porcuna, Susan Perlen, Kirsten Perrett, Amandine Philippart Floy, Laure Pittet, R.C. Pon, Ines Portillo Calderón, Catherine Power, Christiane Prado, Endriaen Prajitno, Lieke Preijers, Marco Puga, Evelyn Queiroz, Ashleigh Rak, Leticia Ramires Figueiredo, Encarnacion Ramirez de Arellano, Pedro Ramos, Karla Regina Oliveira, Jack Ren, Claudinalva Ribeiro Santos, Holly Richmond, Ana Rita Souza, Laleyska Rodrigues, Bebeto Rodrigues, Iara Rodrigues Fernandes, Sally Rogers, Anke Rol, Jannie Romme, Maria Roser Font, Sonia Sallent, Vanderson Sampaio, Nuria Sanchez, Blanca Sanchez, Tilza Santos, Ariandra Sartim, Amber Sastry, Alice Sawka, Nikki Schultz, Engelien Septer-Bijleveld, Raquel Serrano, Ketaki Sharma, Margaret Shave, Lisa Shen, Adrian Siles Baena, Rafaela Silva, Emanuelle Silva, Mariana Simão, Ronita Singh, Marilda Siqueira, Marciléia Soares Chaves, Thijs Sondag, Enoshini Sooriyarachchi, Antonny Sousa, Leena Spry, Sarah Statton, Dyenyffer Stéffany Santos, Katrina Sterling, Leah Steve, Carolyn Stewart, Lisa Stiglmayer, Lida Stooper, Josephine Studham, Astrid Suiker, Esther Taks, Niki Tan, Bruna Tayara Meireles, Menno te Riele, Jaap ten Oever, Guilherme Teodoro Lima, Jhenyfer Thalyta Angelo, Ryan Toh, Alexandre Trindade, Enriqueta Tristán, Darren Troeman, Alexandra Truelove, Daniel Tsuha, Marlot Uffing, Fernando Val, Olga Valero, Chantal van Ven, Leo Van Heuvel, Sigrid van Veen, Marije van Waal, J.H. van Leusen, Linda van Mook, H. van Onzenoort, Marjoleine van Opdorp, Miranda van Rijen, Nicolette van Sluis, Adria Vasconcelos, Noelia Vega, Sunitha Velagapudi, Louise Vennells, Tamsin Venton, Harald Verheij, P.M. Verhoeven, Caroliny Veron Ramos, Paulo Victor Silva, Sandra Vidal, Patricia Vieira, Matheus Vieira Oliveira, Rosario Vigo Ortega, Raquel Villar, Amanda Vlahos, Ushma Wadia, Kate Wall, Rachael Wallace, Michelle Wearing-Smith, Daniel Webber-Rookes, Jamie Wedderburn, Ashleigh Wee-Hee, Jia Wei Teo, Bethany Whale, Phoebe Williams, Beatrijs Wolters, Ivy Xie, Angela Younes, Felipe Zampieri Batista, Carmen Zhou, Vivian Zwart, Simone Barry, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Catriona Doran, Georgina Eden, Liddy Griffith, Christine Heath, Jane James, Meredith Krieg, David Lynn, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, and Rob ter Heine

Subjects
Medicine
Abstract

Introduction BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysis This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and dissemination Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registration ClinicalTrials.gov NCT04327206

Published
2021
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18. Dynamic changes to tissue-resident immunity after MHC-matched and MHC-mismatched solid organ transplantation

Author

Amy Prosser, Wen Hua Huang, Liu Liu, Sarah Dart, Monalyssa Watson, Bastiaan de Boer, Philip Kendrew, Andrew Lucas, Irma Larma-Cornwall, Silvana Gaudieri, Gary P. Jeffrey, Luc Delriviere, Axel Kallies, and Michaela Lucas

Subjects
liver transplantation, heart transplantation, tissue-resident lymphocyte, innate lymphoid cell, unconventional T cell, Biology (General), QH301-705.5
Abstract

Summary: The heterogeneous pool of tissue-resident lymphocytes in solid organs mediates infection responses and supports tissue integrity and repair. Their vital functions in normal physiology suggest an important role in solid organ transplantation; however, their detailed examination in this context has not been performed. Here, we report the fate of multiple lymphocyte subsets, including T, B, and innate lymphoid cells, after murine liver and heart transplantation. In major histocompatibility complex (MHC)-matched transplantation, donor lymphocytes are retained in liver grafts and peripheral lymphoid organs of heart and liver transplant recipients. In MHC-mismatched transplantation, increased infiltration of the graft by recipient cells and depletion of donor lymphocytes occur, which can be prevented by removal of recipient T and B cells. Recipient lymphocytes fail to recreate the native organs’ phenotypically diverse tissue-resident lymphocyte composition, even in MHC-matched models. These post-transplant changes may leave grafts vulnerable to infection and impair long-term graft function.

Published
2021
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19. Cross With Caution: Antibiotic Cross-Reactivity and Co-Reactivity Patterns in Severe Cutaneous Adverse Reactions

Author

Grace Thompson, Andrew McLean-Tooke, and Michaela Lucas

Subjects
severe cutaneous adverse drug reactions, antibiotic cross-reactivity, antibiotic co-reactivity, beta-lactam, antibiotics, Immunologic diseases. Allergy, RC581-607
Abstract

Current understanding of cross-reactivity in severe cutaneous adverse reactions to beta-lactam antibiotics is limited, thereby making recommendations for future prescribing difficult. The underlying immunopathogenesis of these reactions is not completely understood but involves interactions between small molecule drugs, T cells and HLA molecules. Historically, these reactions were considered to be specific to the inciting antibiotic and therefore likely to have minimal cross-reactivity. We assessed patients presenting with non-SJS/TEN severe cutaneous adverse reactions to a tertiary hospital drug allergy clinic. In our case series cross-reactivity or co-reactivity commonly occurred among the beta-lactam antibiotic class, however further research is required to investigate and understand patterns of cross-reactivity. Based on our experience we provide clinicians with a practical algorithm for testing for cross-reactivity in non-SJS/TEN severe cutaneous adverse reactions.

Published
2021
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22. Regeneration and repair in the healing lung

Author

Andrew Lucas, Joe Yasa, and Michaela Lucas

Subjects
inflammation, lung, regeneration, repair, therapeutics, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract The lung achieves an efficient gas exchange between a complex non‐sterile atmosphere and the body via a delicate and extensive epithelial surface, with high efficiency because of elastic deformation allowing for an increase and decrease in volume during the process of breathing and because of an extensive vasculature which aids rapid gas diffusion. The lungs’ large surface area exposes the organ to a continual risk of damage from pathogens, toxins or irritants; however, lung damage can be rapidly healed via regenerative processes that restore its structure and function. In response to sustained and extensive damage, the lung is healed via a non‐regenerative process resulting in scar tissue which locally stiffens its structure, which over time leads to a serious loss of lung function and to increasing morbidities. This review discusses what is known about the factors which influence whether a lung is healed by regeneration or repair and what potential new therapeutic approaches may positively influence lung healing.

Published
2020
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23. Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome

Author

Michaela Lucas, Pooja Deshpande, Ian James, Andri Rauch, Katja Pfafferott, Elouise Gaylard, Shahzma Merani, Anne Plauzolles, Andrew Lucas, Wyatt McDonnell, Spyros Kalams, Mark Pilkinton, Cody Chastain, Louise Barnett, Amy Prosser, Simon Mallal, Karen Fitzmaurice, Heidi Drummer, M. Azim Ansari, Vincent Pedergnana, Ellie Barnes, Mina John, Dermot Kelleher, Paul Klenerman, and Silvana Gaudieri

Subjects
Medicine, Science
Abstract

Abstract Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher’s exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes.

Published
2018
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24. Deep sequence analysis of HIV adaptation following vertical transmission reveals the impact of immune pressure on the evolution of HIV.

Author

Jennifer Currenti, Abha Chopra, Mina John, Shay Leary, Elizabeth McKinnon, Eric Alves, Mark Pilkinton, Rita Smith, Louise Barnett, Wyatt J McDonnell, Michaela Lucas, Francine Noel, Simon Mallal, Joseph A Conrad, Spyros A Kalams, and Silvana Gaudieri

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Human immunodeficiency virus (HIV) can adapt to an individual's T cell immune response via genomic mutations that affect antigen recognition and impact disease outcome. These viral adaptations are specific to the host's human leucocyte antigen (HLA) alleles, as these molecules determine which peptides are presented to T cells. As HLA molecules are highly polymorphic at the population level, horizontal transmission events are most commonly between HLA-mismatched donor/recipient pairs, representing new immune selection environments for the transmitted virus. In this study, we utilised a deep sequencing approach to determine the HIV quasispecies in 26 mother-to-child transmission pairs where the potential for founder viruses to be pre-adapted is high due to the pairs being haplo-identical at HLA loci. This scenario allowed the assessment of specific HIV adaptations following transmission in either a non-selective immune environment, due to recipient HLA mismatched to original selecting HLA, or a selective immune environment, mediated by matched donor/recipient HLA. We show that the pattern of reversion or fixation of HIV adaptations following transmission provides insight into the replicative cost, and likely compensatory networks, associated with specific adaptations in vivo. Furthermore, although transmitted viruses were commonly heavily pre-adapted to the child's HLA genotype, we found evidence of de novo post-transmission adaptation, representing new epitopes targeted by the child's T cell response. High-resolution analysis of HIV adaptation is relevant when considering vaccine and cure strategies for individuals exposed to adapted viruses via transmission or reactivated from reservoirs.

Published
2019
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25. Successful treatment of idiopathic mast cell activation syndrome with low‐dose Omalizumab

Author

Renee Berry, Peter Hollingsworth, and Michaela Lucas

Subjects
bee venom immunotherapy, idiopathic non‐clonal mast cell disorder, mast cell activation syndrome, omalizumab, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives Idiopathic mast cell disorders, a recently defined and recognised syndrome in clinical practice, are similar to the previously termed non‐clonal mast cell disorder. Patients with idiopathic mast cell activation syndrome (MCAS) suffer all the classical signs of mast cell activation but do not have evidence of mast cell clonality. Furthermore, treatment of these patients can be limited and burdensome in those with refractory symptoms. Methods Here, we describe treatment of a patient with idiopathic MCAS utilising a single monthly subcutaneous injection of omalizumab and review the current classification and therapeutic options for clonal and non‐clonal MCAS. Results Low‐dose omalizumab treatment has successfully led to a 5‐year, sustained clinical response, controlled debilitating symptoms of mast cell activation and allowed for reintroduction and long‐term maintenance of bee venom subcutaneous immunotherapy. Conclusion Low‐dose omalizumab of 150 mg monthly should be considered for maintenance management of patients with idiopathic MCAS for its cost and quality‐of‐life benefits.

Published
2019
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26. Anti-hepatitis C virus T-cell immunity in the context of multiple exposures to the virus.

Author

Katja Pfafferott, Pooja Deshpande, Elizabeth McKinnon, Shahzma Merani, Andrew Lucas, David Heckerman, Simon Mallal, Mina John, Silvana Gaudieri, and Michaela Lucas

Subjects
Medicine, Science
Abstract

Characterisation of Hepatitis C virus (HCV)-specific CD8+ T-cell responses in the context of multiple HCV exposures is critical to identify broadly protective immune responses necessary for an effective HCV vaccine against the different HCV genotypes. However, host and viral genetic diversity complicates vaccine development. To compensate for the observed variation in circulating autologous viruses and host molecules that restrict antigen presentation (human leucocyte antigens; HLA), this study used a reverse genomics approach that identified sites of viral adaptation to HLA-restricted T-cell immune pressure to predict genotype-specific HCV CD8+ T-cell targets. Peptides representing these putative HCV CD8+ T-cell targets, and their adapted form, were used in individualised IFN-γ ELISpot assays to screen for HCV-specific T-cell responses in 133 HCV-seropositive subjects with high-risk of multiple HCV exposures. The data obtained from this study i) confirmed that genetic studies of viral evolution is an effective approach to detect novel in vivo HCV T-cell targets, ii) showed that HCV-specific T-cell epitopes can be recognised in their adapted form and would not have been detected using wild-type peptides and iii) showed that HCV-specific T-cell (but not antibody) responses against alternate genotypes in chronic HCV-infected subjects are readily found, implying clearance of previous alternate genotype infection. In summary, HCV adaptation to HLA Class I-restricted T-cell responses plays a central role in anti-HCV immunity and multiple HCV genotype exposure is highly prevalent in at-risk exposure populations, which are important considerations for future vaccine design.

Published
2015
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27. Abacavir-reactive memory T cells are present in drug naïve individuals.

Author

Andrew Lucas, Michaela Lucas, Anette Strhyn, Niamh M Keane, Elizabeth McKinnon, Rebecca Pavlos, Ellen M Moran, Viola Meyer-Pannwitt, Silvana Gaudieri, Lloyd D'Orsogna, Spyros Kalams, David A Ostrov, Søren Buus, Bjoern Peters, Simon Mallal, and Elizabeth Phillips

Subjects
Medicine, Science
Abstract

BACKGROUND:Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. METHODS:To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. RESULTS:Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. CONCLUSIONS:We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.

Published
2015
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28. Genetic variations in IL28B and allergic disease in children.

Author

Silvana Gaudieri, Michaela Lucas, Andrew Lucas, Elizabeth McKinnon, Hiba Albloushi, Andri Rauch, Julia di Iulio, David Martino, Susan L Prescott, and Meri K Tulic

Subjects
Medicine, Science
Abstract

Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences.

Published
2012
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29. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

Author

Katja Pfafferott, Silvana Gaudieri, Axel Ulsenheimer, Ian James, Malte Heeg, David Nolan, Mina John, Andri Rauch, Simon Mallal, Andrew Lucas, Paul Klenerman, Helmut M Diepolder, and Michaela Lucas

Subjects
Medicine, Science
Abstract

Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

Published
2011
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30. Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.

Author

Michaela Lucas, Axel Ulsenheimer, Katja Pfafferot, Malte H J Heeg, Silvana Gaudieri, Norbert Grüner, Andri Rauch, J Tilman Gerlach, Maria-Christina Jung, Reinhart Zachoval, Gerd R Pape, Winfried Schraut, Teresa Santantonio, Hans Nitschko, Martin Obermeier, Rodney Phillips, Thomas J Scriba, Nasser Semmo, Cheryl Day, Jonathan N Weber, Sarah Fidler, Robert Thimme, Anita Haberstroh, Thomas F Baumert, Paul Klenerman, and Helmut M Diepolder

Subjects
Medicine, Science
Abstract

CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays.Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C.During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

Published
2007
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31. Patient-related factors drive high rates of reported antibiotic allergies: a qualitative study

Author

Renee Berry, Susan Herrmann, and Michaela Lucas

Abstract

Background Unnecessary antibiotic avoidance due to allergy fears has adverse cost and health implications however, the problem is difficult to resolve because patient and provider-related factors leading to avoidance are multifactorial. The perspectives of patients can be explored using qualitative research methods to reach the heart of the problem. Objective To reveal factors leading patients to report antibiotic allergy, and determine what education is required to prevent the cycle of erroneous allergy reporting. Methods The 29 patients were a sample of convenience recruited from a tertiary public hospital in Western Australia; 18 were inpatients and 11 outpatients, with a median age of 64.2 years, and 15 (55%) were female. Semi-structured interviews assessed patients’ understanding and knowledge of three topics: (1) antibiotic allergy, (2) antibiotic allergy testing, and (3) outcomes of testing. Interview transcripts underwent thematic analysis by two researchers, independently. Results Three overlapping themes emerged as influential across topics: (1) Severity of the Index Reaction, (2) Trust in family and health care providers, and (3) Health literacy. Patients were largely unaware of the benefits of confirmatory testing, and the detrimental health consequences of unnecessary avoidance. Patients displayed trust in health care providers’ expertise, and assumed that medical records were accurate to prevent prescribing errors. Conclusions The findings provide evidence for an effective patient education strategy, and highlight failures among hospital and primary health providers to recognise the potential harm of unverified antibiotic allergy. Healthcare professionals are influential at multiple steps of a patient’s healthcare journey and addressing unconfirmed antibiotic allergy should be taken at each opportunity.

Published
2023
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32. Antibiotic allergy labels and optimal antimicrobial stewardship

Author

John Dyer, Anna McKeogh, Arindam Chakravorty, Michaela Lucas, Paul R. Ingram, Kevin Murray, Matthew Rawlins, Michelle Trevenen, and Elene Binder

Subjects
Adult, medicine.medical_specialty, Referral, business.industry, medicine.drug_class, Incidence (epidemiology), Antibiotics, Retrospective cohort study, Antimicrobial, Anti-Bacterial Agents, Drug Hypersensitivity, Antimicrobial Stewardship, Anti-Infective Agents, Cohort, Internal Medicine, medicine, Humans, Antimicrobial stewardship, Observational study, Intensive care medicine, business, Retrospective Studies
Abstract

Background Although common, antimicrobial allergy labels (AAL) rarely reflect immunologically-mediated hypersensitivity and can lead to poorer outcomes from alternative antimicrobial agents. Antimicrobial stewardship programs are ideally placed to assess AAL early as a means of improving antimicrobial use. Objectives To quantify the prevalence of AAL in patients referred for antimicrobial stewardship review and assess their impact on antibiotic prescribing, patient mortality, hospital length of stay, readmission, and rates of multidrug-resistant infections. Methods We conducted a retrospective analysis of adult patients referred for inpatient antimicrobial prospective audit and feedback rounds (PAFR) via an electronic referral system (eReferrals) over a 12-month period in 2015. Outcome data was collected for a period of 36 months following the initial review. Results Of the 639 patient records reviewed, 630 met inclusion criteria; 103 (16%) had an AAL, of which 82 (13%) had reported allergies to β-lactam antibiotics. Those with AAL were significantly less likely to be receiving guideline-recommended antimicrobial therapy (50% versus 64%, p=0.0311), however there were no significant difference in mortality, hospital length of stay, readmission or increased incidence of multidrug-resistant infections. Conclusions Our cohort demonstrated that AAL was associated with reduced adherence to antibiotic guidelines. The lack of association with adverse outcomes may reflect limitations within the study including retrospective cohort study numbers and observational nature, further skewed by high rates of poor documentation. A clear opportunity exists for antimicrobial stewardship programs to incorporate allergy assessment, delabelling, challenge and referral into these rounds. This article is protected by copyright. All rights reserved.

Published
2022
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33. The role of endocrine-disrupting phthalates and bisphenols in cardiometabolic disease: the evidence is mounting

Author

Andrew Lucas, Susan Herrmann, and Michaela Lucas

Subjects
Nutrition and Dietetics, Endocrinology, Metabolic Diseases, Cardiovascular Diseases, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Environmental Exposure, Obesity, Endocrine Disruptors
Abstract

There is substantive and accumulating evidence that endemic exposure to plastic-associated chemicals (PACs) contribute to the pathophysiology of metabolic conditions, like obesity, diabetes, and heart disease. The consequences of this endemic exposure in inducing a pro-inflammatory state in adipose tissues as a critical link between exposure and disease is reviewed.In general, PACs are classified as nonpersistent in vivo because of their rapid metabolism to easily excreted forms. The parental chemicals, however, are typically lipophilic, with the potential to bioaccumulate. Recent data from selected association studies suggest exposure to PACs drive predisease states like obesity and inflammation of the adipose tissues. A range of experimental studies are discussed with a focus on biological mechanisms that are susceptible to the influence of PACs and which may promote metabolic disease, the detection of PACs within susceptible tissues and biological effects that are detectable at doses that correspond to real-life exposures to these chemicals.If we hypothesize the toxic pressure from chronic exposure to PACs will progress disease processes, then individuals with comprehensively characterized indicators of premetabolic disease could undergo trials of quantifiable interventions to reduce exposure to PACs to test if the trajectory of disease-associated analytes, is altered.

Published
2022
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34. Disparities and inequalities of penicillin allergy in the Asia‐Pacific region

Author

Philip H. Li, Ruby Pawankar, Bernard Y. H. Thong, Hugo W. F. Mak, Grace Chan, Wen‐Hung Chung, Meng Juan, Hye‐Ryun Kang, Byung‐Keun Kim, Rommel Crisenio M. Lobo, Michaela Lucas, Duy Le Pham, Thushali Ranasinghe, Iris Rengganis, Ticha Rerkpattanapipat, Munkhbayarlakh Sonomjamts, Yi‐Giien Tsai, Jiu‐Yao Wang, Masao Yamaguchi, and James Yun

Subjects
Immunology, Immunology and Allergy
Published
2023
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35. Subset-specific Retention of Donor Myeloid Cells After Major Histocompatibility Complex-matched and Mismatched Liver Transplantation

Author

Sarah J. Dart, Amy C. Prosser, Wen Hua Huang, Liu Liu, Andrew D. Lucas, Luc Delriviere, Silvana Gaudieri, Gary P. Jeffrey, and Michaela Lucas

Subjects
Transplantation
Abstract

During solid organ transplantation, donor leukocytes, including myeloid cells, are transferred within the organ to the recipient. Both tolerogenic and alloreactive roles have been attributed to donor myeloid cells; however, their subset-specific retention posttransplantation has not been investigated in detail.Major histocompatibility complex (MHC)-matched and mismatched liver transplants were performed in mice, and the fate of donor and recipient myeloid cells was assessed.Following MHC-matched transplantation, a proportion of donor myeloid cells was retained in the graft, whereas others egressed and persisted in the blood, spleen, and bone marrow but not the lymph nodes. In contrast, after MHC-mismatched transplantation, all donor myeloid cells, except Kupffer cells, were depleted. This depletion was caused by recipient T and B cells because all donor myeloid subsets were retained in MHC-mismatched grafts when recipients lacked T and B cells. Recipient myeloid cells rapidly infiltrated MHC-matched and, to a greater extent, MHC-mismatched liver grafts. MHC-mismatched grafts underwent a transient rejection episode on day 7, coinciding with a transition in macrophages to a regulatory phenotype, after which rejection resolved.Phenotypic and kinetic differences in the myeloid cell responses between MHC-matched and mismatched grafts were identified. A detailed understanding of the dynamics of immune responses to transplantation is critical to improving graft outcomes.

Published
2022

38. Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity

Author

Axel Kallies, William R. Heath, Dane M. Newman, Nicholas D. Huntington, Thomas N. Burn, Andrew Lucas, Francis R. Carbone, Luke C. Gandolfo, Simone L Park, Terence P. Speed, Michaela Lucas, Natasha Zamudio, Fernando Souza-Fonseca-Guimaraes, Laura K. Mackay, Gabrielle T. Belz, Maximilien Evrard, Nicholas Collins, Laurent Bartholin, Wei Shi, Daniel G. Pellicci, Yannick O. Alexandre, Raissa Fonseca, Scott N. Mueller, David Chisanga, Florent Ginhoux, and Susan N Christo

Subjects
Cell growth, Cellular differentiation, Immunology, Cell, Transdifferentiation, Biology, Phenotype, Cell biology, medicine.anatomical_structure, Cell Plasticity, medicine, Immunology and Allergy, Signal transduction, Memory T cell
Abstract

Tissue-resident memory T (TRM) cells are non-recirculating cells that exist throughout the body. Although TRM cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze TRM cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRM cell function, durability and malleability. We find that unequal responsiveness to TGFβ is a major driver of this diversity. Notably, dampened TGFβ signaling results in CD103- TRM cells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFβ-responsive CD103+ TRM counterparts. Furthermore, whereas CD103- TRM cells readily modified their phenotype upon relocation, CD103+ TRM cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for TRM cell development, tissue adaptation of these cells confers discrete functional properties such that TRM cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.

Published
2021
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39. A Modified Murine Heterotopic Heart Transplant Protocol Matching Contemporary Standards of Aseptic Technique, Anesthesia, and Analgesia

Author

Andrew Lucas, Michaela Lucas, Amy Prosser, Monalyssa Watson, Jaskirat Kaur, Liu Liu, Wen Hua Huang, Gabrielle C. Musk, and David A. Singer

Subjects
Graft Rejection, Mice, Infection Control, Transplantation, Heterotopic, General Immunology and Microbiology, General Chemical Engineering, General Neuroscience, Animals, Heart Transplantation, Anesthesia, Mice, Inbred Strains, Analgesia, General Biochemistry, Genetics and Molecular Biology
Abstract

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.

Published
2022
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41. Asia-Pacific survey of physicians' perceptions and managements of chronic rhinosinusitis

Author

Shan, Shao, Ming, Zheng, Xiangdong, Wang, Amir Ha, Latiff, Dong Young, Kim, Jiu Yao, Wang, Marysia, Recto, Michaela, Lucas, Munkhbayarlakh, Sonomjamts, Narantsetseg, Logi, Niken, Lestari, Nina, Irawati, Pongsakorn, Tantilipikorn, Samir, Bhargava, Soumya, Ms, Takeshi, Shimizu, Ting Fan, Leung, Wasu, Kamchaisatian, Ruby, Pawankar, and Luo, Zhang

Abstract

The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions.Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS 2020 guidelines.A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS 2020 guidelines.Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.5% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment.This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

Published
2022

42. Penicillin allergy SHACK: Survey of hospital and community knowledge

Author

Katherine Collins, Kristina Rueter, Michaela Lucas, David Sommerfield, Aine Sommerfield, Nazim Khan, and Britta S von Ungern‐Sternberg

Subjects
Adult, Drug Hypersensitivity, Surveys and Questionnaires, Pediatrics, Perinatology and Child Health, Australia, Humans, Penicillins, Child, Anaphylaxis, Hospitals, Anti-Bacterial Agents
Abstract

Penicillin allergy accounts for the majority of all reported adverse drug reactions in adults and children. Foregoing first-line antibiotic therapy due to penicillin allergy label is associated with an increased prevalence of infections by resistant organisms and longer hospitalisation. Clinician awareness of allergy assessment, referral indications, management of allergy and anaphylaxis is therefore vital but globally lacking. We aim to assess the knowledge of penicillin allergy, assessment and management in Western Australian health professionals.An anonymous survey was distributed to pharmacists, nurses and physicians within Western Australian paediatric and adult Hospitals, Community and General Practice.In total, 487/611 were completed and included in the statistical analysis. Only 62% (301/487) of respondents routinely assessed for patient medication allergies. Of those who assessed allergy, 9% (28/301) of respondents met the Australian standards for allergy assessment. Only 22% (106/487) of participants correctly cited all indications for management with adrenaline in anaphylaxis to antibiotics and 67% (197/292) of physicians rarely or never referred to an allergy service. Paediatric clinicians had an increased understanding of allergy assessment and anaphylaxis management. Recent penicillin allergy education within a 5-year period led to significant improvements in allergy knowledge.Overall, knowledge, assessment and management of penicillin allergies among practitioners in Western Australia are currently inadequate in adults and paediatric clinicians to provide safe and effective clinical care. The implementation of a targeted education program for WA health professionals is urgently required and is expected to improve clinician knowledge and aid standardised penicillin assessment (de-labelling) practices.

Published
2022

43. Frequent occurrence of low-level positive autoantibodies in chronic hepatitis C

Author

Elizabeth McKinnon, Silvana Gaudieri, Pooja Deshpande, Michaela Lucas, Rosemary A. Ffrench, Margaret Hellard, Anna L. Wilkinson, Christine Bundell, and Heidi E. Drummer

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Anti-nuclear antibody, Hepatitis C virus, Autoimmunity, medicine.disease_cause, Gastroenterology, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Clinical significance, Aged, Autoantibodies, Autoimmune disease, business.industry, Autoantibody, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 030104 developmental biology, Antibodies, Antinuclear, 030220 oncology & carcinogenesis, Cohort, Female, business
Abstract

Evidence of autoimmune disease associated with hepatitis C virus (HCV)-infection has important clinical implications. A systematic profile of these autoantibodies in relevant clinical cohorts relative to healthy controls is needed to better inform current standard of care for chronic hepatitis C. Samples from an Australian cohort of chronic HCV-infected subjects (n=127) were tested for the presence of 19 diagnostic autoantibodies and compared with data available from a control cohort representing a general Caucasian population (n=198). Chronic HCV-infected individuals had a greater number of autoantibodies than controls (p

Published
2020
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44. Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease

Author

Nicholas C. Wong, Benjamin Solomon, Max Bulsara, Peter L. Friedland, James Lim, Michaela Lucas, Bob Mirzai, Katie Meehan, Yasir Khan, Chady Sader, Gisela Mir Arnau, Connull Leslie, Angela Jacques, Annette M. Lim, and Timothy Semple

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Gene Expression, Pembrolizumab, medicine.disease_cause, B7-H1 Antigen, 0302 clinical medicine, Melanoma, Original Research, Cancer Biology, Immune signature, biology, FOXP3, Forkhead Transcription Factors, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Tongue Neoplasms, 030220 oncology & carcinogenesis, CD4 Antigens, Female, medicine.medical_specialty, CD8 Antigens, lcsh:RC254-282, 03 medical and health sciences, Tongue, Internal medicine, PD-L1, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, business.industry, Squamous Cell Carcinoma of Head and Neck, Gene Expression Profiling, Immunotherapy, Immune dysregulation, Gene signature, medicine.disease, Gene expression profiling, 030104 developmental biology, oral tongue squamous cell carcinoma, PD‐L1, biology.protein, Lymph Nodes, business
Abstract

We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P, Oral tongue squamous cell carcinomas (OTSCC) exhibit primary immune failure to control carcinogenesis demonstrated by the absence of an immune response to the development of nodal metastases or recurrent disease. Proinflammatory immune gene expression is counteracted by immunosuppressive signaling mediated by FOXP3 and PD‐L1 expression. A gene signature was identified that was not prognostic in HNSCC but was significantly associated with survival in other cancers, demonstrating histotype‐dependent prognostic effects of immune regulation.

Published
2020

45. The safety of co-administration of Bacille Calmette-Guérin (BCG) and influenza vaccines

Author

Paola Villanueva, Ushma Wadia, Nigel W. Crawford, Nicole L. Messina, Tobias R. Kollmann, Michaela Lucas, Laurens Manning, Peter Richmond, Laure F. Pittet, and Nigel Curtis

Subjects
Multidisciplinary, Influenza Vaccines, Influenza, Human, Vaccination, BCG Vaccine, Humans
Abstract

Background With the emergence of novel vaccines and new applications for older vaccines, co-administration is increasingly likely. The immunomodulatory effects of BCG could theoretically alter the reactogenicity of co-administered vaccines. Using active surveillance in a randomised controlled trial, we aimed to determine whether co-administration of BCG vaccination changes the safety profile of influenza vaccination. Methods Participants who received influenza vaccine alone (Influenza group) were compared with those who also received BCG-Denmark vaccine in the contralateral arm (Influenza+BCG group). Data on the influenza vaccination site were collected using serial questionnaires and active follow-up for 3 months post vaccination. Results Of 1351 participants in the Influenza+BCG group and 1418 participants in the Influenza group, 2615 (94%) provided influenza vaccine safety data. There was no significant difference in the proportion of participants with any local adverse reaction between the Influenza+BCG group and the Influenza group (918/1293 [71.0%] versus (906/1322 [68.5%], p = 0.17). The proportion of participants reporting any pain, erythema and tenderness at the influenza vaccination site were similar in both groups. Swelling was less frequent (81/1293 [6.3%] versus 119/1322 (9.0%), p = 0.01) and the maximal diameter of erythema was smaller (mean 1.8 cm [SD 2.0] versus 3.0 cm [SD 2.5], p Conclusions Adverse events following influenza vaccination are not increased when BCG is co-administered.

Published
2021

47. Autoimmunity elicited by the chemokine response to adenovirus vector vaccines may underlie vaccine-induced immune thrombotic thrombocytopaenia: a hypothesis

Author

Michaela Lucas, Andrew McLean-Tooke, and Martyn A. French

Subjects
2019-20 coronavirus outbreak, Chemokine, Coronavirus disease 2019 (COVID-19), biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, News and Commentary, RC581-607, medicine.disease_cause, Autoimmunity, Viral vector, Immune system, biology.protein, Immunology and Allergy, Medicine, Immunologic diseases. Allergy, business, General Nursing
Published
2021

49. An update on allergy and anaphylaxis in pediatric anesthesia

Author

Michaela Lucas, David Sommerfield, Bojana Stepanovic, and Britta S. von Ungern-Sternberg

Subjects
Allergy, medicine.medical_specialty, business.industry, Perioperative, medicine.disease, Atopy, Anesthesiology and Pain Medicine, Food allergy, Child, Preschool, Pediatrics, Perinatology and Child Health, Epidemiology, Hypersensitivity, Humans, Medicine, Anesthesia, Family history, Child, business, Intensive care medicine, Pediatric anesthesia, Anaphylaxis
Abstract

Childhood allergy is common, and increasing. Many children are incorrectly labeled as having allergy or adverse drug reactions. This can pose a dilemma for anesthetists and lead to a change in practice or drug selection. We review the pathophysiology of hypersensitivity reactions and the implications for anesthesia of food allergy, atopy, and family history of allergy in children. The epidemiology of anaphylaxis is discussed. We discuss the common triggers of perioperative anaphylaxis in children and explore emerging triggers including chlorhexidine and sugammadex. Accurate data on pediatric perioperative anaphylaxis is limited worldwide, with marked geographic variation. This highlights the need for accurate local, district and/or nationwide incident reporting. The clinical features, diagnosis, and management of anaphylaxis under anesthesia are discussed. We review the process of expert allergy testing following a suspected case of anaphylaxis to guide future safe anesthesia administration. The preoperative consultation is an opportunity for referral for allergy testing to allow de-labeling. This has the potential for improved antibiotic stewardship and more effective treatment with first-line therapeutic agents.

Published
2019
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50. Screening and Prophylaxis to Prevent Hepatitis B Reactivation

Author

Marion G. Peters, Joe Sasadeusz, Seng Lee Lim, Andrew Grigg, Peter Hughes, Monica A. Slavin, Geoff McColl, Joseph Doyle, James A Rickard, Kumar Visvanathan, Sue-Anne McLachlan, Peter De Cruz, Michaela Lucas, Vijaya Sundararajan, Nicholas A. Shackel, Robert G. Gish, and Alexander J. Thompson

Subjects
Oncology, medicine.medical_specialty, Cost effectiveness, Hepatitis C virus, medicine.medical_treatment, medicine.disease_cause, Organ transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Immunity, Internal medicine, Medicine, In patient, Mass screening, Hepatitis B virus, Hepatitis, Hepatology, business.industry, Immunosuppression, Immunotherapy, Entecavir, Hepatitis C, Hepatitis B, Acquired immune system, medicine.disease, Transplantation, 030220 oncology & carcinogenesis, Immunology, Rituximab, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.

Published
2019
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