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1. Factors influencing adverse events following COVID-19 vaccination

Author

Paola Villanueva, Ellie McDonald, Julio Croda, Mariana Garcia Croda, Margareth Dalcolmo, Glauce dos Santos, Bruno Jardim, Marcus Lacerda, David J. Lynn, Helen Marshall, Roberto D. Oliveira, Jorge Rocha, Alice Sawka, Fernando Val, Laure F. Pittet, Nicole L. Messina, and Nigel Curtis

Subjects
COVID-19 vaccine, adverse events, antibody responses, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

ABSTRACTVarious novel platform technologies have been used for the development of COVID-19 vaccines. In this nested cohort study among healthcare workers in Australia and Brazil who received three different COVID-19-specific vaccines, we (a) evaluated the incidence of adverse events following immunization (AEFI); (b) compared AEFI by vaccine type, dose and country; (c) identified factors influencing the incidence of AEFI; and (d) assessed the association between reactogenicity and vaccine anti-spike IgG antibody responses. Of 1302 participants who received homologous 2-dose regimens of ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech) or CoronaVac (Sinovac), 1219 (94%) completed vaccine reaction questionnaires. Following the first vaccine dose, the incidence of any systemic reaction was higher in ChAdOx1-S recipients (374/806, 46%) compared with BNT162b2 (55/151, 36%; p = 0.02) or CoronaVac (26/262, 10%; p

Published
2024
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2. 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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3. 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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5. 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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6. HIV infection increases the risk of acquiring Plasmodium vivax malaria: a 4-year cohort study in the Brazilian Amazon HIV and risk of vivax malaria

Author

Cecilia Victoria Caraballo Guerra, Bernardo Maia da Silva, Pia Müller, Djane Clarys Baia-da-Silva, Marco Antônio Saboia Moura, José Deney Alves Araújo, Juan Carlo Santos e Silva, Alexandre Vilhena Silva-Neto, Antonio Alcirley da Silva Balieiro, André Guilherme da Costa-Martins, Gisely Cardoso Melo, Fernando Val, Quique Bassat, Helder I. Nakaya, Flor Ernestina Martinez-Espinosa, Marcus Lacerda, Vanderson Souza Sampaio, and Wuelton Monteiro

Subjects
Medicine, Science
Abstract

Abstract Globally, malaria and human immunodeficiency virus (HIV) are both independently associated with a massive burden of disease and death. While their co-infection has been well studied for Plasmodium falciparum, scarce data exist regarding the association of P. vivax and HIV. In this cohort study, we assessed the effect of HIV on the risk of vivax malaria infection and recurrence during a 4-year follow-up period in an endemic area of the Brazilian Amazon. For the purpose of this study, we obtained clinical information from January 2012 to December 2016 from two databases. HIV screening data were acquired from the clinical information system at the tropical hospital Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD). The National Malaria Surveillance database (SIVEP malaria) was utilized to identify malaria infections during a 4-year follow-up period after diagnosis of HIV. Both datasets were combined via data linkage. Between 2012 and 2016, a total of 42,121 people were screened for HIV, with 1569 testing positive (3.7%). Out of all the patients diagnosed with HIV, 198 had at least one episode of P. vivax malaria in the follow-up. In the HIV-negative group, 711 participants had at least one P. vivax malaria episode. When comparing both groups, HIV patients had a 6.48 [(5.37–7.83); P

Published
2022
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7. Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil

Author

Karla Cristina Silva Petruccelli, Djane Clarys Baía-da-Silva, Fernando Val, Monica Santos Valões, Nadia Cubas-Vega, Alexandre Vilhena Silva-Neto, Vanderson Sampaio, Aline Alencar, Roberto Pecoits-Filho, Rodrigo Carvalho Moreira, Sandra Wagner Cardoso, Ronaldo I. Moreira, Iuri Costa Leite, José Valdez Madruga, Esper G. Kallas, Paulo R. Alencastro, Brenda Hoagland, Beatriz Grinsztejn, Valdiléa Gonçalves Veloso Santos, and Marcus Vinícius Guimarães Lacerda

Subjects
PrEP, Kidney function, HIV, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. Methods Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. Results Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = − 0.005; p

Published
2022
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8. Intensive care management of patients with COVID-19: a practical approach

Author

Ludhmila Abrahão Hajjar, Isabela Bispo Santos da Silva Costa, Stephanie Itala Rizk, Bruno Biselli, Brenno Rizerio Gomes, Cristina Salvadori Bittar, Gisele Queiroz de Oliveira, Juliano Pinheiro de Almeida, Mariana Vieira de Oliveira Bello, Cibele Garzillo, Alcino Costa Leme, Moizo Elena, Fernando Val, Marcela de Almeida Lopes, Marcus Vinícius Guimarães Lacerda, José Antonio Franchini Ramires, Roberto Kalil Filho, Jean-Louis Teboul, and Giovanni Landoni

Subjects
COVID-19, Intensive care unit, Circulatory support and invasive ventilation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient’s survival.

Published
2021
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9. Should we care about Plasmodium vivax and HIV co-infection? A systematic review and a cases series from the Brazilian Amazon

Author

Paola López Del-Tejo, Nadia Cubas-Vega, Cecilia Caraballo-Guerra, Bernardo Maia da Silva, Jefferson da Silva Valente, Vanderson Souza Sampaio, Djane Clarys Baia-da-Silva, Daniel Barros Castro, Flor Ernestina Martinez-Espinosa, André Machado Siqueira, Marcus Vinícius Guimarães Lacerda, Wuelton Marcelo Monteiro, and Fernando Val

Subjects
Plasmodium vivax, HIV, Co-infection, Systematic review, Epidemiology, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available information related to Plasmodium falciparum on the African continent. It is unclear whether HIV can change the clinical course of vivax malaria and increase the risk of complications. In this study, a systematic review of HIV/PvCo studies was performed, and recent cases from the Brazilian Amazon were included. Methods Medical records from a tertiary care centre in the Western Brazilian Amazon (2009–2018) were reviewed to identify HIV/PvCo hospitalized patients. Demographic, clinical and laboratory characteristics and outcomes are reported. Also, a systematic review of published studies on HIV/PvCo was conducted. Metadata, number of HIV/PvCo cases, demographic, clinical, and outcome data were extracted. Results A total of 1,048 vivax malaria patients were hospitalized in the 10-year period; 21 (2.0%) were HIV/PvCo cases, of which 9 (42.9%) had AIDS-defining illnesses. This was the first malaria episode in 11 (52.4%) patients. Seven (33.3%) patients were unaware of their HIV status and were diagnosed on hospitalization. Severe malaria was diagnosed in 5 (23.8%) patients. One patient died. The systematic review search provided 17 articles (12 cross-sectional or longitudinal studies and 5 case report studies). A higher prevalence of studies involved cases in African and Asian countries (35.3 and 29.4%, respectively), and the prevalence of reported co-infections ranged from 0.1 to 60%. Conclusion Reports of HIV/PvCo are scarce in the literature, with only a few studies describing clinical and laboratory outcomes. Systematic screening for both co-infections is not routinely performed, and therefore the real prevalence of HIV/PvCo is unknown. This study showed a low prevalence of HIV/PvCo despite the high prevalence of malaria and HIV locally. Even though relatively small, this is the largest case series to describe HIV/PvCo.

Published
2021
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10. Early Antiretroviral Therapy in AIDS Patients Presenting With Toxoplasma gondii Encephalitis Is Associated With More Sequelae but Not Increased Mortality

Author

Nadia Cubas-Vega, Paola López Del-Tejo, Djane C. Baia-da-Silva, Vanderson Souza Sampaio, Bruno Araújo Jardim, Monique Freire Santana, Luiz Carlos Lima Ferreira, Izabella Picinin Safe, Márcia A. Araújo Alexandre, Marcus Vinícius Guimarães Lacerda, Wuelton Marcelo Monteiro, and Fernando Val

Subjects
Toxoplasma gondii, toxoplasmic encephalitis, HIV/AIDS, therapy, antiretroviral, complications, Medicine (General), R5-920
Abstract

BackgroundEvidence on the optimal time to initiate antiretroviral therapy (ART) in the presence of toxoplasmic encephalitis (TE) is scarce. We compared the impact of early vs. delayed ART initiation on mortality and neurologic complications at discharge in a Brazilian population co-infected with HIV and TE.MethodsWe retrospectively evaluated data from 9 years of hospitalizations at a referral center in Manaus, Amazonas. All ART-naïve hospitalized patients were divided into early initiation treatment (EIT) (0-4 weeks) and delayed initiation treatment (DIT) (>4 weeks). The groups were compared using chi-square test and mortality at 16 weeks.ResultsFour hundred sixty nine patients were included, of whom 357 (76.1%) belonged to the EIT group. The median CD4+ lymphocyte count and CD4+/CD8+ ratio were 53 cells/mm3 and 0.09, respectively. Mortality rate and presence of sequelae were 4.9% (n = 23) and 41.6% (n = 195), respectively. Mortality was similar between groups (p = 0.18), although the EIT group had the highest prevalence of sequelae at discharge (p = 0.04). The hazard ratio for death at 16 weeks with DIT was 2.3 (p = 0.18). The necessity for intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation were similar between groups.ConclusionIn patients with AIDS and TE, early ART initiation might have a detrimental influence on the occurrence of sequelae.

Published
2022
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11. 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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12. Snakebites in 'Invisible Populations': A cross-sectional survey in riverine populations in the remote western Brazilian Amazon.

Author

Guilherme Kemeron Maciel Salazar, Joseir Saturnino Cristino, Alexandre Vilhena Silva-Neto, Altair Seabra Farias, João Arthur Alcântara, Vinícius Azevedo Machado, Felipe Murta, Vanderson Souza Sampaio, Fernando Val, André Sachett, Paulo Sérgio Bernarde, Marcus Lacerda, Fan Hui Wen, Wuelton Monteiro, and Jacqueline Sachett

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

In the Brazilian Amazon, long distances, low healthcare coverage, common use of ineffective or deleterious self-care practices, and resistance to seeking medical assistance have an impact on access to antivenom treatment. This study aimed to estimate snakebite underreporting, and analyze barriers that prevent victims from obtaining healthcare in communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Information on the participants' demographics, previous snakebites, access to healthcare, time taken to reach medical assistance, use of self-care practices, and the reason for not accessing healthcare were collected through semi-structured interviews. In the case of deaths, information was collected by interviewing parents, relatives or acquaintances. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed. A total of 73 different treatment procedures was reported by 65.1% of the participants. Participants living in different river basins share few self-care procedures that use traditional medicine, and 91 (52.9%) participants reported that they had access to healthcare. Living in communities along the Juruá River [OR = 12.6 (95% CI = 3.2-49.7; p

Published
2021
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13. Non-lactational Infectious Mastitis in the Americas: A Systematic Review

Author

Victor Costa Morais Oliveira, Nadia Cubas-Vega, Paola López Del-Tejo, Djane C. Baía-da-Silva, Michel Araújo Tavares, Izabella Picinin Safe, Marcelo Cordeiro-Santos, Marcus Vinícius Guimarães Lacerda, and Fernando Val

Subjects
non-lactational mastitis, clinical mastitis, granulomatous mastitis, Mycobacterium tuberculosis, epidemiology, Medicine (General), R5-920
Abstract

Background: Non-lactational infectious mastitis (NLIM) is an inflammatory breast disease with broad clinical presentation. Inadequate treatment can lead to chronic infections that cause breast deformities. NLIM information is limited, especially in the Americas. A systematic review and meta-analysis have been conducted here.Methods: Literature search was conducted in three databases (Lilacs, PubMed, and Scielo) on NLIM cases in the Americas. Demographic, epidemiological, clinical, radiological, and laboratory data were extracted. The main characteristics and results were also compared according to the country's gross national income.Results: A total of 47 articles were included, resulting in 93 cases. The etiological agent was described in 86 (92.5%) patients. Bacteria were the most prevalent etiology (73; 84.8%). Amongst bacterial diagnoses, more frequent cases were Mycobacterium tuberculosis (28; 38.4%); Corynebacterium spp. (15; 20.5%); non-tuberculous mycobacteria (13; 17.8%). The cases were reported in eight different countries, with the USA being the country with the highest number of cases (35; 37.6%). Patients from high-income countries group presented a shorter diagnostic time when compared to low, low-middle, and upper-middle-income countries. A greater number of radiographic studies with pathological findings were described in high-income countries.Conclusion: Non-lactational infectious mastitis is a complex public health problem with diagnostic and treatment challenges. Hence, multi-professional approach-based additional studies are recommended on its epidemiology, diagnosis, treatment, and control.

Published
2021
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14. Increased prevalence of hypertension among people living with HIV: where to begin?

Author

Aldrey Nascimento Costa, Fernando Val, Álvaro Elias Macedo, Nadia Cubas-Vega, Paola López Del Tejo, Marly M. Marques, Aristóteles Comte de Alencar Filho, and Marcus Vinicius Guimarães de Lacerda

Subjects
HIV, Non-communicable diseases, Cardiovascular diseases, hypertension, Arctic medicine. Tropical medicine, RC955-962
Abstract

Abstract INTRODUCTION: Cardiovascular diseases (CDVs) have become increasingly important for progressively older people living with HIV (PLHIV). Identification of gaps requiring improvement in the care cascade for hypertension, a primary risk factor for CVDs, is of utmost importance. This study analyzed the prevalence of hypertensive status and described the care cascade for hypertension screening, diagnosis, treatment, treatment adherence, and management in PLHIV. METHODS: This cross-sectional study included 298 PLHIV (age >40 years) who visited a referral center in the western Brazilian Amazon. Data were collected through a structured questionnaire interview and medical examinations. Thus, information regarding sociodemographic and clinical aspects, blood pressure, weight, height, body mass index, and laboratory profile was obtained. Descriptive and analytical statistics were performed, and results were considered significant ifp

Published
2020
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15. Bothrops atrox, the most important snake involved in human envenomings in the amazon: How venomics contributes to the knowledge of snake biology and clinical toxinology

Author

Wuelton Marcelo Monteiro, Jorge Carlos Contreras-Bernal, Pedro Ferreira Bisneto, Jacqueline Sachett, Iran Mendonça da Silva, Marcus Lacerda, Allyson Guimarães da Costa, Fernando Val, Lisele Brasileiro, Marco Aurélio Sartim, Sâmella Silva-de-Oliveira, Paulo Sérgio Bernarde, Igor L. Kaefer, Felipe Gobbi Grazziotin, Fan Hui Wen, and Ana Maria Moura-da-Silva

Subjects
Common lancehead, Envenoming, Venomics, Antivenomics, Antivenom, Viperidae, Toxicology. Poisons, RA1190-1270
Abstract

Bothrops atrox snakes are mostly endemic of the Amazon rainforest and is certainly the South American pit viper responsible for most of the snakebites in the region. The composition of B. atrox venom is significantly known and has been used to trace the relevance of the venom phenotype for snake biology and for the impacts in the clinics of human patients involved in accidents by B. atrox. However, in spite of the wide distribution and the great medical relevance of B. atrox snakes, B. atrox taxonomy is not fully resolved and the impacts of the lack of taxonomic resolution on the studies focused on venom or envenoming are currently unknown. B. atrox venom presents different degrees of compositional variability and is generally coagulotoxic, inducing systemic hematological disturbances and local tissue damage in snakebite patients. Antivenoms are the effective therapy for attenuating the clinical signs. This review brings a comprehensive discussion of the literature concerning B. atrox snakes encompassing from snake taxonomy, diet and venom composition, towards clinical aspects of snakebite patients and efficacy of the antivenoms. This discussion is highly supported by the contributions that venomics and antivenomics added for the advancement of knowledge of B. atrox snakes, their venoms and the treatment of accidents they evoke.

Published
2020
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17. Validation of a Culturally Relevant Snakebite Envenomation Clinical Practice Guideline in Brazil

Author

Gisele dos Santos Rocha, Altair Seabra Farias, João Arthur Alcântara, Vinícius Azevedo Machado, Felipe Murta, Fernando Val, Joseir Saturnino Cristino, Alícia Cacau Santos, Mena Bianca Ferreira, Leonardo Marques, Yasmim Vieira Rocha, André Sachett, Mailma Costa Almeida, Aline Alencar, Lisele Brasileiro, Érica da Silva Carvalho, Pedro Ferreira Bisneto, Marcus Lacerda, Anna Tupetz, Catherine A. Staton, João R.N. Vissoci, Elizabeth Teixeira, Charles J. Gerardo, Fan Hui Wen, Jacqueline Sachett, and Wuelton Monteiro

Subjects
snakebite, antivenom, health education, clinical practice guideline, validation, Medicine
Abstract

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.

Published
2022
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18. Sudden spleen rupture in a Plasmodium vivax-infected patient undergoing malaria treatment

Author

Aleix Elizalde-Torrent, Fernando Val, Ingrid Cardoso C. Azevedo, Wuelton M. Monteiro, Luiz C. L. Ferreira, Carmen Fernández-Becerra, Hernando A. del Portillo, and Marcus V. G. Lacerda

Subjects
Plasmodium vivax, Malaria, Spleen rupture, Portable ultrasound, Recurrent parasitemia, Splenectomy, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Splenomegaly is one of the most common features of malaria. However, spontaneous splenic rupture, although unusual, represents a severe complication often leading to death. It is mostly seen in acute infection and primary attack, and it is most commonly associated with Plasmodium vivax. Here, a case of spontaneous splenic rupture diagnosed with a portable ultrasound apparatus shortly after starting treatment and with recurrent parasitaemia after splenectomy, is reported. Case description In November 2015, a 45-year-old Brazilian man presented to the hospital in Manaus with fever, headache and myalgia. He was diagnosed with P. vivax malaria and, after a normal G6PD test, he started treatment with chloroquine and primaquine and was discharged. Two days later, he went back to the hospital with abdominal pain, dyspnea, dry cough, pallor, oliguria and fever. Using a portable ultrasound, he was diagnosed of rupture of the spleen, which was removed by emergency surgery. After this episode, he suffered two more malaria episodes with high parasitaemia at approximately 2-month intervals. DNA from different portions of the spleen was extracted and a qualitative PCR was performed to detect P. vivax. Conclusions The splenic rupture suffered by this patient occurred 2 days after starting the treatment. Having a portable ultrasound apparatus may have saved the patient’s life, as it revealed a haemorrhage needing an urgent surgery. Parasites were detected by PCR in the extracted spleen. This patient suffered two more vivax malaria diagnosed episodes in spite of receiving and completing treatment with chloroquine and primaquine for each clinical attack. Splenic rupture during acute malaria is uncommon, but it is likely underdiagnosed and underreported, because the lack of means and equipment hinders diagnostic confirmation, especially in endemic areas.

Published
2018
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19. Are respiratory complications of Plasmodium vivax malaria an underestimated problem?

Author

Fernando Val, Sara Avalos, André Alexandre Gomes, José Evelio Albornoz Zerpa, Gustavo Fontecha, André Machado Siqueira, Quique Bassat, Maria Graças Costa Alecrim, Wuelton Marcelo Monteiro, and Marcus Vinícius Guimarães Lacerda

Subjects
Plasmodium vivax, Severe malaria, Respiratory distress, Lung, Case fatality, Prevalence, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Respiratory complications are uncommon, but often life-threatening features of Plasmodium vivax malaria. This study aimed to estimate the prevalence and lethality associated with such complications among P. vivax malaria patients in a tertiary hospital in the Western Brazilian Amazon, and to identify variables associated with severe respiratory complications, intensive care need and death. Medical records from 2009 to 2016 were reviewed aiming to identify all patients diagnosed with P. vivax malaria and respiratory complications. Prevalence, lethality and risk factors associated with WHO defined respiratory complications, intensive care need and death were assessed. Results A total of 587 vivax malaria patients were hospitalized during the study period. Thirty (5.1%) developed respiratory complications. Thirteen (43.3%) developed severe respiratory complications, intensive care was required for 12 (40%) patients and 5 (16.6%) died. On admission, anaemia and thrombocytopaenia were common findings, whereas fever was unusual. Patients presented different classes of parasitaemia and six were aparasitaemic on admission. Time to respiratory complications occurred after anti-malarials administration in 18 (60%) patients and progressed very rapidly. Seventeen patients (56.7%) had comorbidities and/or concomitant conditions, which were significantly associated to higher odds of developing severe respiratory complications, need for intensive care and death (p

Published
2017
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20. Providing Antivenom Treatment Access to All Brazilian Amazon Indigenous Areas: ‘Every Life has Equal Value’

Author

Wuelton Marcelo Monteiro, Altair Seabra de Farias, Fernando Val, Alexandre Vilhena Silva Neto, André Sachett, Marcus Lacerda, Vanderson Sampaio, Deugles Cardoso, Luiza Garnelo, João Ricardo Nickenig Vissoci, Jacqueline Sachett, and Fan Hui Wen

Subjects
snakebite, antivenom, indigenous groups, health service, health decentralization, Medicine
Abstract

Snakebites are more frequent in the Brazilian Amazon than in other parts of Brazil, representing a high cost for the health system since antivenoms are only available through medical prescription from central municipal hospitals in most cases. The need for a cold chain and physicians usually restricts access to the only effective treatment of a snakebite, the antivenom. The complex topography of the rivers contributes to delays in treatment, and consequently increases the risk of severe complications, chronic sequelae and death. Thus, decentralization of antivenom treatment to primary healthcare facilities in the interior would increase access by indigenous population groups to proper healthcare. To standardize and evaluate the decentralization to low complexity indigenous healthcare units, we suggest the (i) development and validation of standardized operational procedures, (ii) training of professionals in the validated protocol in a referral health unit, (iii) implementation of the protocol in an indigenous healthcare unit, (iv) assessment of perceptions towards and acceptability of the protocol, and (v) estimation of the impact of the protocol’s implementation. We expect that antivenom decentralization would shorten the time between diagnosis and treatment and, as such, improve the prognosis of snakebites. As health cosmology among indigenous populations has an important role in maintaining their way of life, the introduction of a new therapeutic strategy to their customs must take into account the beliefs of these peoples. Thus, antivenom administration would be inserted as a crucial therapeutic tool in a world of diverse social, natural and supernatural representations. The information presented here also serves as a basis to advocate for support and promotion of health policy initiatives focused on evidence-based care in snakebite management.

Published
2020
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22. Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile.

Author

Barbara Baro, Katrien Deroost, Tainá Raiol, Marcelo Brito, Anne C G Almeida, Armando de Menezes-Neto, Erick F G Figueiredo, Aline Alencar, Rodrigo Leitão, Fernando Val, Wuelton Monteiro, Anna Oliveira, Maria Del Pilar Armengol, Carmen Fernández-Becerra, Marcus V Lacerda, and Hernando A Del Portillo

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Published
2017
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23. Plasma metabolomics reveals membrane lipids, aspartate/asparagine and nucleotide metabolism pathway differences associated with chloroquine resistance in Plasmodium vivax malaria.

Author

Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, and Dean P Jones

Subjects
Medicine, Science
Abstract

BACKGROUND:Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance. METHODS:An untargeted high-resolution metabolomics analysis was performed on plasma samples collected in a malaria clinic in Manaus, Brazil. Male and female patients with Plasmodium vivax were included (n = 46); samples were collected before CQ treatment and followed for 28 days to determine PvCR, defined as the recurrence of parasitemia with detectable plasma concentrations of CQ ≥100 ng/dL. Differentially expressed metabolic features between CQ-Resistant (CQ-R) and CQ-Sensitive (CQ-S) patients were identified using partial least squares discriminant analysis and linear regression after adjusting for covariates and multiple testing correction. Pathway enrichment analysis was performed using Mummichog. RESULTS:Linear regression and PLS-DA methods yielded 69 discriminatory features between CQ-R and CQ-S groups, with 10-fold cross-validation classification accuracy of 89.6% using a SVM classifier. Pathway enrichment analysis showed significant enrichment (p

Published
2017
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26. Sequelae and mortality in patients with HIV/AIDS and Progressive Multifocal Leukoencephalopathy: Systematic review and case series in the Brazilian Amazon

Author

Jefferson Valente, Paola López Del-Tejo, Nadia Carolina Cubas-Vega, Maria Gabriela de Almeida Rodrigues, Francisco Railson Bispo de Barros, Márcia Araújo Alexandre, Guilherme Peixoto Tinoco Arêas, Michele Bastos, Sérgio Damasceno Pinto, Camila Miriam S. S. Barros, Eveny Perlize Marinho, Sabrina Mello, Ewerton Ferreira, Valderjane Aprigio, Rossiclea Lins Monte, Vanderson Sampaio, Marcus Lacerda, Djane Clarys Baia-da-Silva, and Fernando Val

Subjects
Fuel Technology, Process Chemistry and Technology, Economic Geology, General Medicine
Abstract

BackgroundProgressive Multifocal Leukoencephalopathy (PML) is an opportunistic neurological disease that mainly affects individuals with HIV/AIDS and has high morbidity and mortality, due to its demyelinating characteristic. This co-infection has been reported since the begging of HIV/Aids epidemic with increasing unfavorable outcomes, however, factors associated to sequelae and death are greatly unknown. In this study we aimed to understand factors associated with the main outcomes of individuals diagnosed with PML and HIV/AIDS, in addition to reporting the characteristics of patients presenting to a referral center in infectious diseases in the Brazilian Amazon.MethodsA systematic review was performed until July 2022, following the PRISMA guidelines, at Medline/Pubmed, Web of Science, Lilacs and Scielo databases using combinations of HIV, Aids, JC Virus and Progressive Multifocal Leukoencephalopathy, with no restriction to publication date. Additional cases, meeting the eligibility criteria, were added from our hospital database, which consisted of patients presenting PML/HIV between 2010 and 2022. A meta-analysis aiming to explore factors associated to sequelae and death was performed. Baseline characteristics were described using mean and standard deviation, or median and interquartile range when appropriate; multivariate analysis was performed to study factors associated to death and sequelae outcomes.ResultsEighteen patients were diagnosed between 2010 and 2022, of these, 10 had positive PCR for JC virus. In the Systematic Review, 216 studies yielded 235 confirmed cases of co-infection. A total of 245 were included for analysis. The rates of death and sequelae were, respectively, 47.1% (114/242) and 41.2% (54/131). The use of antiretroviral therapy was more associated with a lower chance of death (OR 0.30, 95% CI: 0.11-0.83), while muscle weakness (OR 4.82, 95% CI: 2.07-11.21) and muscle spasms (OR 6.12, 95% CI: 1.05-35.76) were associated with greater chances of sequelae.ConclusionThose on antiretroviral therapy appear to be less likely to die, and among those who survive, those who have muscle weakness as a symptom on admission are more likely to develop sequelae. Adherence to ART, as well as a comprehensive clinical evaluation and follow-up may help to improve clinical outcomes and awareness of morbidities.

Published
2023
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27. Subgemmal neurogenous plaques of the tongue: a systematic autopsy study

Author

José Fernando, Val-Bernal, María Francisca, Garijo, and Natalia, Fontanil

Abstract

Subgemmal neurogenous plaque (SNP) is a subepithelial nerve plexus associated with taste buds, occasionally observed in tongue biopsies. There is no evaluation of the prevalence of this structure in the general population. We present a systematic study of samples obtained at random from the dorsal portion of the oral tongue in 205 consecutive complete autopsies. Each sample was about 15 mm long and 10 mm thick. Four hundred fifty-eight samples were routinely obtained and an average of 2.23±0.88 samples per case (range 1-7) was collected. The total number of SNPs observed was 556, with a mean of 2.71±2.68 per case (range 0-16). This means that for every 15 linear mm of the oral tongue, approximately 2.7 SNPs can be present. SNPs display several ages, and they do not show sex differences. The mean size of these structures was 2.1±0.94 mm (range 0.6-3.6 mm). SNP is characterized by its unique neural, zonal pattern with a superficial neurofibroma-like area and a deeper neuroma-like area. Special features of the SNPs include the presence of taste buds (49.1%), ganglion cells (26.3%), dilated thin-walled vessels (11.3%), salivary gland excretory ducts emptying on the surface of the papillae (6.1%), moderate-severe inflammatory infiltrate (6.8%), presence of lymphoid tissue in the vicinity (7.0%), and hyperplasia of the epithelial cover with pseudoepitheliomatous appearance (7.0%). The differential diagnoses include schwannoma, neurofibroma, ganglioneuroma, traumatic neuroma, mucosal neuroma, and squamous cell carcinoma. SNPs are small, normal structures that may undergo hyperplasia and are usually seen incidentally.

Published
2023

28. Colonic tubular adenoma with incidental oxyntic gastric heterotopia

Author

José Fernando Val-Bernal, María Luisa Cagigal, Marta Cuadrado, Carlos Rodriguez-Escaja, and Marta Mayorga

Subjects
Adenoma, heterotopia, Embryology, Pathology, medicine.medical_specialty, heterotopic oxyntic mucosa, Colonic Polyps, Colonoscopy, Case Report, Pathology and Forensic Medicine, tubular adenoma, Tubular adenoma, Humans, Medicine, Colon Tubular Adenoma, Aged, gastric heterotopia, colon, medicine.diagnostic_test, business.industry, Cell Biology, General Medicine, medicine.disease, digestive system diseases, Epithelium, Gastric chief cell, medicine.anatomical_structure, Dysplasia, Colonic Neoplasms, Adenocarcinoma, Immunohistochemistry, Female, business, Developmental Biology
Abstract

Oxyntic gastric heterotopia (GH) in the colon is not common. Its presence in a colon tubular adenoma is even rare. A 73-year-old woman with a history of resected colon carcinoma underwent periodical colonoscopies for the removal of tubular adenomas for 12 years. In the last colonoscopy, a sessile, non-ulcerated polyp, centrally depressed, with a smooth surface, measuring 20 mm, located at 50 cm from the anal verge was excised. A histological study identified a tubular adenoma with focal low-grade dysplasia and ectopic gastric oxyntic epithelium. The GH, composed of parietal and chief cells, and was found incidentally. Oxyntic GH in a tubular adenoma is extraordinarily rare. To the best of our knowledge, there is only one previously published case. The main possible difficulties and/or errors in the diagnosis include a tissue floater or a cross-contaminant. Precise diagnosis of oxyntic GH is basic for appropriate management. Diagnosis relies on histopathological examination. The immunohistochemical study for mucin 6 (MUC6) can confirm the nature of the epithelium. Oxyntic GH has the potential to produce serious complications including tumor development. However, GH is considered a benign disease and adenocarcinoma rarely occurs in the heterotopic mucosa. The optimal treatment of oxyntic GH associated with a tubular adenoma is endoscopic complete polypectomy.

Published
2021
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29. Acquired Elastotic Hemangioma-like Change of the Vulva Associated With Lichen Sclerosus

Author

José-Fernando Val-Bernal, Sandra Hermana, and Laura Aller

Subjects
Adult, medicine.medical_specialty, Pathology, Ultraviolet Rays, Lichen sclerosus, Vulvar Lichen Sclerosus, Vulva, Pathology and Forensic Medicine, Lesion, Hemangioma, medicine, Humans, Angiosarcoma, Hyperplasia, integumentary system, business.industry, Obstetrics and Gynecology, medicine.disease, Lichen Sclerosus et Atrophicus, medicine.anatomical_structure, Female, Histopathology, Sarcoma, medicine.symptom, business, Reticular Dermis
Abstract

Acquired elastotic hemangioma (AEH) is a rare variant of hemangioma that usually presents as an asymptomatic, solitary, slow-growing red plaque on a sun-exposed site of an adult. Ultraviolet radiation can contribute to the pathogenesis of this hemangioma. Lichen sclerosus (LS), a scarring disease, may present a prominent accumulation of elastic fibers in the reticular dermis reflecting a reparative process. Vulvar elastosis, a novel diagnostic entity with fibers similar to solar elastosis, is more common in women 45 yr and older and is related to aging and/or hormonal changes. We herein report for the first time a case of AEH-like change located in the vulva, a sun-protected area, associated with genital LS. An 81-yr-old woman presented with a painful vulvar lesion of 1-yr duration. Clinical examination revealed vulvar LS and 1 cm-flat, erythematous, well-defined plaque with increased consistency located on the left labium minus. Histopathology showed a non-neoplastic proliferation of WT1-positive, small vascular channels surrounded and intertwined by intense elastosis in the reticular dermis. Alpha-smooth muscle actin positive pericytes encircled the vascular channels. The lesion can be understood as a reparative process within an LS with the appearance of epidermal hyperplasia, proliferation of small vascular channels, and hyperplastic elastosis. There is a close link between epidermal hyperplasia and angiogenesis in the formation of this reparative lesion. Recognition of this lesion is crucial to avoid confusion with other significant processes especially Kaposi sarcoma and well-differentiated angiosarcoma.

Published
2021
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31. Basaloid squamous cell carcinoma with prominent shadow (ghost) cell differentiation. An unreported neoplasm of the parotid gland

Author

José Fernando, Val-Bernal, Gonzalo, Herrera, Alejandro, Fernández-Flórez, and María, Martino

Subjects
Aged, 80 and over, Male, Carcinoma, Squamous Cell, Humans, Parotid Gland, Cell Differentiation, Adenocarcinoma, Salivary Gland Neoplasms
Abstract

Basaloid squamous cell carcinoma (BSCC) is an aggressive type of squamous cell carcinoma (SCC) predominant in the upper aerodigestive tract. To our knowledge, only one case of that tumor has been previously described in the parotid gland. Shadow (ghost) cell differentiation (SCD) is a specialized form of keratinization characteristic of pilomatricoma, and other skin tumors with follicular differentiation. SCD has also been described infrequently in some visceral carcinomas and rarely in the minor salivary glands. Recently, an SCC with prominent SCD has been reported in the parotid. We report for the first time the case of parotid BSCC with prominent SCD in an 87-year-old man. He was admitted due to the appearance in the last few months of a mass, painful on palpation, in the left parotid region. Imaging studies and tru-cut biopsies indicated the need for surgical removal. A left superficial parotidectomy, including the branch of the cervicofacial nerve, was performed. The BSCC showed predominance (62%) of SCD. Immunohistochemically, the basaloid cells were positive for β-catenin, pan-cytokeratin (pan-CK) AE1∕AE3, CK19, high-molecular-weight CK (HMWCK), p63, p40, and cluster of differentiation 10 (CD10) in a diffuse pattern. No signs of recurrence or metastasis were observed four months after surgery. The main differential diagnoses include nuclear protein in testis (NUT) carcinoma, adamantinoma-like Ewing sarcoma, embryonal carcinoma, and basal cell adenocarcinoma of the solid type. SCD in BSCC of the parotid should be recognized to avoid misdiagnosis, especially in small samples. Although rare, BSCC with SCD should be added to the list of tumors that may originate in the parotid gland.

Published
2022

32. Mitigating the risks of post-acute sequelae of SARS-CoV-2 infection (PASC) with intranasal chlorpheniramine: perspectives from the ACCROS studies

Author

Fernando Valerio-Pascua, Fernando Baires, Anupamjeet Kaur Sekhon, Mari L. Tesch, Estela Jackeline Pineda, Syed A. A. Rizvi, Jarmanjeet Singh, David Abraham Cortes-Bandy, Amy C. Madril, Jana Radwanski, Anita S. Lewis, Miguel Sierra-Hoffman, Mark L. Stevens, and Franck F. Rahaghi

Subjects
COVID-19, SARS-CoV-2, Intranasal chlorpheniramine, Efficacy, Randomized clinical trial, Double-blind, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The World Health Organization (WHO) declared the end of the COVID-19 (SARS-CoV-2) global public health emergency on May 5, 2023, but its long-term consequences have still been haunting the global population. Post-acute sequelae of COVID-19 (PASC) and long-term COVID-19 are serious concerns and present with various symptoms. Intranasal chlorpheniramine (iCPM) has been shown to decrease the viral burden of SARS-COV-2. iCPM uses decreased COVID-19 disease progression and severity in Accelerating COVID-19 Clinical Recovery in an Outpatient Setting (ACROSS)-I & III randomized control trials (RCT). Methods This prospective survey study included 259 participants in ACROSS I and III RCTs. We compared the effect of iCPM versus placebo on the reduction of PASC symptoms. A PASC questionnaire containing 17 questions regarding the most common PASC symptoms was used in this study. T-test and Pearson chi-square statistics were performed according to continuous and categorical data using STATA 17.0 Basic Edition software. Findings The iCPM cohort had a lower proportion of patients with fatigue or tiredness vs. placebo (0 Vs 17, 21, p

Published
2024
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34. COVID-19-Associated Pulmonary Aspergillosis in a Series of Complete Autopsies from the Brazilian Amazon

Author

Maria Eduarda Farias, Monique Freire Santana, Luiz Ferreira, Mayla Borba, João Silva-Neto, José Diego Brito-Sousa, Djane Clarys Baía-da-Silva, Guilherme Pivoto João, Fernando Val, Mariana Simão, João Vicente Souza, Felipe Naveca, Gisely Melo, Wuelton Monteiro, and Marcus Lacerda

Subjects
Adult, Male, SARS-CoV-2, Incidence, COVID-19, Infectious Diseases, Virology, Confidence Intervals, Humans, Parasitology, Autopsy, Pulmonary Aspergillosis, Brazil, Aged
Abstract

Between April and July 2020, and, therefore, prior to the broad recommendation of corticosteroids for severe COVID-19, a total of 50 full autopsies were performed in Manaus. We confirmed two invasive cases of aspergillosis through histopathology and gene sequencing (4%) in our autopsy series. The confirmed invasive aspergillosis incidence seems much lower than expected based on the “probable and possible” definitions, and an individualized approach should be considered for each country scenario. Interestingly, a prolonged length of stay in the intensive care unit was not observed in any of the cases. Timely diagnosis and treatment of fungal infection can reduce mortality rates.

Published
2022
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35. Esophageal spindle cell lipoma

Author

José Fernando, Val-Bernal, Marta María, Mayorga, Natalia, Fontanil, and Álvaro, Terán

Subjects
Diagnosis, Differential, Polyps, Esophageal Neoplasms, Humans, Female, Lipoma, Liposarcoma, Middle Aged
Abstract

Symptomatic ordinary esophageal lipomas are rare tumors. Spindle cell lipomas (SCLs) of this location are even more infrequent. To our knowledge, only a previous esophageal SCL case has been reported. We describe herein the case of a 62-year-old woman with a long history of heartburn and feeling of abdominal distension. Preoperative investigations, including a Barium meal, gastroscopy, and echoendoscopy revealed a lipomatous polypoid mass attached to the middle esophageal segment. The lesion (3.5×2×1 cm) was excised endoscopically under deep sedation. The final histopathology diagnosis was pedunculated SCL. An accurate diagnosis of esophageal SCL is crucial to rule out malignant lesions, relieve symptoms, and undertake suitable treatment. The main differential diagnosis includes well-differentiated sclerosing liposarcoma, atypical spindle cell∕pleomorphic lipomatous tumor, giant fibrovascular polyp, and fat-forming solitary fibrous tumor. Although rare, SCL should be added to the list of lipomatous tumors that can affect the esophagus. Complete excision is the appropriate treatment.

Published
2022

36. «He sido como he querido ser»: Carmen Martín Gaite entre el artículo y el ensayo

Author

Fernando Valls

Subjects
Romanic languages, PC1-5498
Abstract

Analizamos un aspecto de la obra de la autora que ha sido menos tenido en cuenta, su cultivo del artículo y del ensayo, sobre todo en dos libros de 1973 y 2002, ahora reeditados, significativamente ampliados, imprescindible para com prender sus ideas literarias, y cómo la creación siempre estuvo acompañada a lo largo de toda su trayectoria como escritora de un análisis y una reflexión crítica, pero también de las especulaciones propias del ensayo.

Published
2024
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37. Unity is strength: creation and future actions for a consortium for HIV cure research in Latin America and the Caribbean ‘Lac-Cura’

Author

Gabriela Turk, Gastón Devisich, Fernando Valiente-Echeverria, María Inés Figueroa, Isabel Cassetti, Pedro Cahn, Claudia P. Cortes, Brenda Crabtree-Ramírez, Omar Sued, and Natalia Laufer

Subjects
hiv, cure research, consortium, latin america and the caribbean, Infectious and parasitic diseases, RC109-216
Abstract

The development of effective HIV cure strategies is crucial. However, most research in this area has been concentrated in high-income countries, underscoring the need to expand efforts to regions like Latin America and the Caribbean (LAC), which face distinct biomedical, social, political, and economic challenges. Data on LAC’s participation in HIV cure research, along with stakeholder perceptions, reveal that the work being done in the region is scarce, fragmented, scattered, and characterized by limited resources and infrastructure. Establishing a regional consortium of basic researchers, clinicians, social scientists, and community members in LAC could be a key step in integrating the region into the global HIV cure landscape. We have already begun laying the groundwork for its creation and propose to name it ‘LAC-Cura’—short for ‘Latin America and the Caribbean HIV Cure Consortium’.

Published
2024
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38. Fine-needle aspiration cytology in the diagnosis of salivary gland lesions. The role of the Milan system for reporting cytopathology

Author

José-Fernando Val-Bernal, María Martino, Belén García-Montesinos, Sara Marcos, and Elena Yllera

Subjects
medicine.medical_specialty, Suspicious for Malignancy, Salivary gland, business.industry, Risk of malignancy, 030209 endocrinology & metabolism, General Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Otorhinolaryngology, Fine needle aspiration cytology, Cytopathology, 030220 oncology & carcinogenesis, medicine, Atypia, In patient, Radiology, Salivary gland neoplasm, business
Abstract

Background Fine needle aspiration cytology (FNAC) is an established technique in the management of salivary gland lesions. The Milan System for reporting salivary gland cytopathology (MSRSGC) intents to standardize diagnostic categories. Current studies are trying to evaluate the diagnostic approach of this system. Methods FNAC of salivary gland lesions were retrieved over an 11-year period. 185 FNAC specimens from 182 patients were reviewed blindly and classified according to the criteria established by the MSRSGC. 136 (74.7%) patients had follow-up of their processes. Results The total number of diagnostic categories and risk of malignancy (ROM) in 185 specimens were the following: non-diagnostic 39 (21.1%; ROM 12%), non-neoplastic 35 (18.9%; ROM 0%), atypia of undetermined significance (AUS) 17 (9.2%; ROM 46.1%), benign neoplasm 75 (40.5%; ROM 4.9%), salivary gland neoplasm of uncertain malignant potential 4 (2.2%; ROM 100%), suspicious for malignancy 7 (3.8%; ROM 100%), malignant 8 (4.3%; ROM 100%). No false positives were observed in groups IVb, V, and VI in this series. The overall sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy were 88%, 91.8%, 96.3%, 76.7%, and 91% respectively. Conclusion The ROM reported in our study was in keeping with ROM published by the MSRSGC. This system provides standardized information for risk stratification. The category AUS encompassed cases causing uncertainty representing a challenge in management. Defining criteria for AUS category need to be refined. The system facilitates communication between pathologists and clinicians favoring improvement in patient care.

Published
2020
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39. Case Report: Adrenal Pathology Findings in Severe COVID-19: An Autopsy Study

Author

Jaume Ordi, Marcos Vinícius Oliveira Queiroga, Luiz Carlos de Lima Ferreira, Djane Clarys Baia-da-Silva, Gisely Cardoso de Melo, Maria Eduarda Leão de Farias, Márcia A. A. Alexandre, Marcus V. G. Lacerda, Ludhmila Abrahão Hajjar, Fernando Val, Mariana Simão Xavier, Wuelton Marcelo Monteiro, Monique Freire Santana, Jose Diego Brito-Sousa, Cecília Cunha Camilo, Guilherme Augusto Pivoto João, Felipe Gomes Naveca, and Mayla Gabriela Silva Borba

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Necrosis, Adrenalitis, Hydrocortisone, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, 030231 tropical medicine, Autopsy, Degeneration (medical), Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Virology, Adrenal Glands, medicine, Adrenal insufficiency, Humans, Pandemics, Aged, SARS-CoV-2, business.industry, COVID-19, Articles, Middle Aged, medicine.disease, Pneumonia, Infectious Diseases, Female, Parasitology, medicine.symptom, Coronavirus Infections, business, medicine.drug
Abstract

Although high mortality has been reported in many COVID-19 studies, very limited postmortem information from complete autopsies is available. We report the findings in the adrenal glands in 28 autopsies with confirmed SARS-CoV-2 infection. Microscopic lesions were identified in the adrenal glands in 12/28 patients (46%). Seven cases showed necrosis, generally ischemic; four showed cortical lipid degeneration; two showed hemorrhage; and one unspecific focal adrenalitis. Vascular thrombosis in one patient and focal inflammation in association with other findings in three patients were observed. No case presented adrenal insufficiency. In conclusion, adrenal lesions are frequent in patients with severe COVID-19. The lesions are mild but could contribute to the lethal outcome.

Published
2020
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40. Bothrops atrox Snakebite: How a Bad Decision May Lead to a Chronic Disability: A Case Report

Author

João Arthur Alcântara, Christielle da Silva Montenegro, Jacqueline de Almeida Gonçalves Sachett, Nadia Cubas-Vega, Thiago G. de Souza, Wuelton Marcelo Monteiro, Monique Freire Santana, Luiz Carlos de Lima Ferreira, Fernando Val, and Iran Mendonça da Silva

Subjects
medicine.medical_specialty, biology, business.industry, medicine.medical_treatment, Public Health, Environmental and Occupational Health, Compartment Syndromes, 030208 emergency & critical care medicine, 030229 sport sciences, biology.organism_classification, Fasciotomy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Respiratory failure, Emergency Medicine, Global health, Bothrops, Medicine, Chronic disability, business, Intensive care medicine, Envenomation
Abstract

Snakebites are a neglected and underestimated global health hazard. In the Brazilian Amazon, Bothrops snakebites are the most prevalent and may lead to severe complications. Here we describe a severe case of Bothrops atrox snakebite that, owing to delayed medical assistance, presented with renal and respiratory failure, compartment syndrome, and tissue necrosis. After several fasciotomy surgeries, the patient survived; however, he showed significant functional disability. Prompt management of snake envenomation would aid in the early diagnosis of local and systemic complications and, consequently, would result in a better functional outcome with improved quality of life.

Published
2020
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41. Endoscopic ultrasound‐guided fine‐needle aspiration cytology in the diagnosis of the gastrointestinal stromal tumor of the stomach

Author

Angel Vázquez‐Boquete, Ihab Abdulkader Nallib, Elena Yllera, María Moris, María Martino, and José-Fernando Val-Bernal

Subjects
Adult, Male, Endoscopic ultrasound, medicine.medical_specialty, Histology, Gastrointestinal Stromal Tumors, 030209 endocrinology & metabolism, Endosonography, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Gastrectomy, Stomach Neoplasms, Humans, Medicine, Gastric Gastrointestinal Stromal Tumor, Stromal tumor, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Pathological, Antrum, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, GiST, business.industry, Stomach, General Medicine, Middle Aged, Immunohistochemistry, digestive system diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Radiology, business
Abstract

Background This study aims to evaluate the usefulness of endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) in the diagnosis of the gastric gastrointestinal stromal tumor (GIST). Methods We retrospectively investigated the efficacy and accuracy of EUS-FNAC in the diagnosis of gastric GIST. Cytological smears and cytoblock sections including immunohistochemistry and mutational studies from patients diagnosed as gastric GISTs were retrieved. Results Thirty patients (mean age 68.8 years, range 32-88 years, Male:Female 1:1.7) were diagnosed by cytological and cytoblock study to have GIST. The size of tumors ranged from 1.6 to 25 cm (mean 6.0 cm). 7 (23%) cases were incidentally discovered. Location was: gastric body 13 (43.3%), fundus 8 (26.7%), antrum 7 (23.3%), cardia 2 (6.7%). The study of removed tumors was correlated with the cytological findings. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 75%, 100%, 100%, 46%, and 96%. There were no false-positive cases. The preoperative risk assessment of 27 cases with cytoblock were: none 3 (11.1%), very low 8 (29.6%), low 12 (44.4%), high 3 (11.1%), insufficient clinical data 1 (3.7%). The follow-up varied from 2 to 120 months (mean 46.7 months). Only 1 patient of the high-risk group died. The most frequent mutations found were those of c-KIT in exon 11. Conclusions Pathological diagnosis was based on a combination of cytological, histopathological, and immunohistochemical features. EUS-FNAC is a reliable, accurate, and safe method for the diagnosis of GIST. The cytoblock allows tumor risk classification and mutational study of the cases.

Published
2020
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42. Renal oncocytoma with prominent xanthomatous reaction. A rare histopathological variant of oncocytoma

Author

José Fernando, Val-Bernal, María Francisca, Garijo, and José Javier, Gómez-Román

Subjects
Diagnosis, Differential, Biomarkers, Tumor, Adenoma, Oxyphilic, Humans, Carcinoma, Renal Cell, Kidney Neoplasms
Abstract

Renal oncocytoma (RO) is a distinctive neoplasm with a well-recognized gross and cytoarchitectural appearance. However, on some occasions, it may show uncommon, atypical, or worrisome gross and microscopic features potentially generating diagnostic difficulties. We herein review the oncocytoma variant characterized by a significant intraneoplastic xanthomatous reaction that produces a variegated macroscopic appearance. This feature may pose a genuine diagnostic problem with conventional (clear cell) renal cell carcinoma (RCC) because this reaction creates a departure from the typical uniform, tan-brown appearance of oncocytoma. The microscopic presence of foamy macrophages in RO may potentially lead to diagnostic difficulties with tumors exhibiting eosinophilic cells and significant infiltration for lipid-laden foamy macrophages such as cystic RCC, unclassified RCC rich in foamy macrophages, the solid variant of papillary RCC with oncocytic features, post-neuroblastoma RCC, succinate dehydrogenase-deficient RCC, mucinous-poor tubular and spindle cell carcinoma, and the oncocytic variant of the epithelioid angiomyolipoma. In conflictive cases, an immunohistochemical panel should help to solve the diagnostic problem. Therefore, the presence of abundant foamy macrophages should not dissuade the pathologist from establishing a diagnosis of RO. Prominent xanthomatous reaction despite its low frequency (4.3%) can be considered an additional feature of RO. Thus, RO should be added to the list of renal tumors that can show a significant reaction of lipid-laden foamy macrophages. Besides, Gamna-Gandy bodies can be present in this tumor.

Published
2022

43. Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil

Author

A Magalhaes, Edson Delatorre, Paola Cristina Resende, Vanderson de Souza Sampaio, Roberto D. Lins, Marilda M. Siqueira, Karina Pessoa, Gisely Cardoso de Melo, Fernanda Nascimento, Ligia Fernandes Abdalla, Alex Martins, Valdinete Alves do Nascimento, Maria Júlia Brandão, Ágatha Costa, Michele Silva de Jesus, Victor Costa de Souza, Nathânia Dábilla, Mariana Xavier Simão, Danilo F. Coêlho, Felipe Gomes Naveca, Maria Paula Gomes Mourão, Luciana Márcia Gonçalves, André de Lima Guerra Corado, Cristiano Fernandes, Gabriel Luz Wallau, Fabio Miyajima, Tirza Mattos, Eduardo Ruback dos Santos, Tiago Gräf, João Hugo Abdalla Santos, erika Lopes Rocha Batista, George Silva, Matheus V. F. Ferraz, Débora Duarte, Lucas Carlos Gomes Pereira, Matilde Mejía, Gonzalo Bello, Fabiola Mendonça Chui, Fernando Vinhal, Fernando Val, Marcus V. G. Lacerda, and Fernando Braga Stehling Dias

Subjects
Microbiology (medical), Lineage (genetic), COVID-19 Vaccines, Physiology, Population, Amino Acid Motifs, Cleavage (embryo), law.invention, Immunity, law, Genetics, Humans, education, Furin, Phylogeny, Infectivity, education.field_of_study, biology, General Immunology and Microbiology, Ecology, SARS-CoV-2, COVID-19, Genomics, Cell Biology, Virology, Transmission (mechanics), Infectious Diseases, Mutation, Spike Glycoprotein, Coronavirus, biology.protein, Antibody, Brazil
Abstract

SummaryThe Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated as Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we found no overrepresentation of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sub-lineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting new variants with higher infectivity are expected to increase.

Published
2022
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45. On-demand transposition across light-matter interaction regimes in bosonic cQED

Author

Fernando Valadares, Ni-Ni Huang, Kyle Timothy Ng Chu, Aleksandr Dorogov, Weipin Chua, Lingda Kong, Pengtao Song, and Yvonne Y. Gao

Subjects
Science
Abstract

Abstract The diverse applications of light-matter interactions in science and technology stem from the qualitatively distinct ways these interactions manifest, prompting the development of physical platforms that can interchange between regimes on demand. Bosonic cQED employs the light field of high-Q superconducting cavities coupled to nonlinear circuit elements, harnessing the rich dynamics of their interaction for quantum information processing. However, implementing fast switching of the interaction regime without deteriorating the cavity coherence is a significant challenge. We present an experiment that achieves this feat, combining nanosecond-scale frequency tunability of a transmon coupled to a cavity with lifetime of hundreds of microseconds. Our implementation affords a range of useful capabilities for quantum information processing; from fast creation of cavity Fock states using resonant interaction and interchanging tomography techniques at qualitatively distinct interaction regimes on the fly, to the suppression of unwanted cavity-transmon dynamics during idle evolution. By bringing flux tunability into the bosonic cQED toolkit, our work opens up the possibility to probe the full range of light-matter interaction dynamics within a single platform and provides valuable pathways towards robust and versatile quantum information processing.

Published
2024
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46. HIV infection increases the risk of acquiring Plasmodium vivax malaria: a 4-year cohort study in the Brazilian Amazon HIV and risk of vivax malaria

Author

Cecilia Victoria Caraballo Guerra, Bernardo Maia da Silva, Pia Müller, Djane Clarys Baia-da-Silva, Marco Antônio Saboia Moura, José Deney Alves Araújo, Juan Carlo Santos e Silva, Alexandre Vilhena Silva-Neto, Antonio Alcirley da Silva Balieiro, André Guilherme da Costa-Martins, Gisely Cardoso Melo, Fernando Val, Quique Bassat, Helder I. Nakaya, Flor Ernestina Martinez-Espinosa, Marcus Lacerda, Vanderson Souza Sampaio, and Wuelton Monteiro

Subjects
Cohort Studies, Male, Multidisciplinary, Recurrence, HIV Seropositivity, Malaria, Vivax, Humans, PLASMODIUM, HIV Infections, Brazil
Abstract

Globally, malaria and human immunodeficiency virus (HIV) are both independently associated with a massive burden of disease and death. While their co-infection has been well studied for Plasmodium falciparum, scarce data exist regarding the association of P. vivax and HIV. In this cohort study, we assessed the effect of HIV on the risk of vivax malaria infection and recurrence during a 4-year follow-up period in an endemic area of the Brazilian Amazon. For the purpose of this study, we obtained clinical information from January 2012 to December 2016 from two databases. HIV screening data were acquired from the clinical information system at the tropical hospital Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD). The National Malaria Surveillance database (SIVEP malaria) was utilized to identify malaria infections during a 4-year follow-up period after diagnosis of HIV. Both datasets were combined via data linkage. Between 2012 and 2016, a total of 42,121 people were screened for HIV, with 1569 testing positive (3.7%). Out of all the patients diagnosed with HIV, 198 had at least one episode of P. vivax malaria in the follow-up. In the HIV-negative group, 711 participants had at least one P. vivax malaria episode. When comparing both groups, HIV patients had a 6.48 [(5.37–7.83); P P. vivax malaria. Moreover, being of the male gender [ARR = 1.41 (1.17–1.71); P P P = 0.038] were independent risk factors associated with an increased risk of clinical malaria. Education ≥ 8 years [ARR = 0.41 (0.26–0.64); P P = 0.007] were associated to a lower risk of P. vivax malaria. A total of 28 (14.1%) and 180 (25.3%) recurrences (at least a second clinical malaria episode) were reported in the HIV-positive and HIV-negative groups, respectively. After adjusting for sex and education, HIV-positive status was associated with a tendency towards protection from P. vivax malaria recurrences [ARR = 0.55 (0.27–1.10); P = 0.090]. HIV status was not associated with hospitalizations due to P. vivax malaria. CD4 + counts and viral load were not associated with recurrences of P. vivax malaria. No significant differences were found in the distribution of parasitemia between HIV-negative and HIV-positive P. vivax malaria patients. Our results suggest that HIV-positive status is a risk factor for vivax malaria infection, which represents an additional challenge that should be addressed during elimination efforts.

Published
2021

47. Snakebites in 'Invisible Populations': A cross-sectional survey in riverine populations in the remote western Brazilian Amazon

Author

Felipe Leão Gomes Murta, André Sachett, João Arthur Alcântara, Paulo Sérgio Bernarde, Jacqueline de Almeida Gonçalves Sachett, Alexandre Vilhena Silva-Neto, Marcus V. G. Lacerda, Joseir Saturnino Cristino, Guilherme Kemeron Maciel Salazar, Fan Hui Wen, Wuelton Marcelo Monteiro, Vanderson de Souza Sampaio, Fernando Val, Altair Seabra Farias, and Vinícius Azevedo Machado

Subjects
Rural Population, Cross-sectional study, Economics, RC955-962, Distribution (economics), Marine and Aquatic Sciences, Social Sciences, Snake Bites, Geographical locations, Health Services Accessibility, Medical Conditions, Arctic medicine. Tropical medicine, Health care, Medicine and Health Sciences, Medicine, Snakebite, Community Health Services, Geographic Areas, Geography, Amazon rainforest, Antivenins, Infectious Diseases, Public aspects of medicine, RA1-1270, Brazil, Research Article, Neglected Tropical Diseases, Freshwater Environments, Urban Areas, Demographics, Interview, MEDLINE, Pain, Human Geography, Urban Geography, Signs and Symptoms, Rivers, Complementary and Alternative Medicine, Environmental health, Intervention (counseling), Animals, Humans, Demography, business.industry, Ecology and Environmental Sciences, Public Health, Environmental and Occupational Health, Aquatic Environments, Bodies of Water, South America, Tropical Diseases, Traditional Medicine, Self Care, Cross-Sectional Studies, Earth Sciences, Medicine, Traditional, People and places, Clinical Medicine, business, Finance
Abstract

In the Brazilian Amazon, long distances, low healthcare coverage, common use of ineffective or deleterious self-care practices, and resistance to seeking medical assistance have an impact on access to antivenom treatment. This study aimed to estimate snakebite underreporting, and analyze barriers that prevent victims from obtaining healthcare in communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Information on the participants’ demographics, previous snakebites, access to healthcare, time taken to reach medical assistance, use of self-care practices, and the reason for not accessing healthcare were collected through semi-structured interviews. In the case of deaths, information was collected by interviewing parents, relatives or acquaintances. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed. A total of 73 different treatment procedures was reported by 65.1% of the participants. Participants living in different river basins share few self-care procedures that use traditional medicine, and 91 (52.9%) participants reported that they had access to healthcare. Living in communities along the Juruá River [OR = 12.6 (95% CI = 3.2–49.7; p, Author summary Many patients bitten by snakes in the Brazilian Amazon do not seek medical care since they live great distinces from health facilities and often do not have the financial resources to travel in search of assistance. In this situation of vulnerability, a wide variety of traditional methods, without proven efficacy, and some known to be harmful, are used by individuals. As a result, many cases of snakebites that are not treated in the official health network are consequently not reported to the epidemiological surveillance system, thus generating underreporting. Knowing the proportion of underreported cases and their hostspots is very important for planning interventions that will improve the coverage of the healthcare network and the logistics of delivery of antivenoms. In a pioneering way in Brazil, this study was carried out to estimate snakebite underreporting and analyze obstacles that prevent victims from obtaining healthcare in the communities located in 15 municipalities on the banks of the Solimões, Juruá and Purus Rivers, in the remote Western Brazilian Amazon. Cases of deaths due to snakebites were also investigated. A total of 172 participants who reported having suffered snakebites during their lifetime were interviewed, as well as the circumstances of 4 deaths. Most patients recalled using some traditional medicine in the form of self-care to treat snakebite. In total, there were 73 different treatment procedures, which were quite different between the different regions studied. Almost half of the participants did not seek medical advice, claiming as reason for that the prioritization for traditional treatments and the non-regognition of the situation as potentially severe. In the Juruá River communities, this frequency was around 70%. The preference of traditional medicine was also associated with the lack of access to healthcare. We believe that this situation will only be mitigated if the antivenoms are made available closer to snakebite victims, i.e., in riverside and rural health units.

Published
2021

48. Reply to Nguyen and Frost

Author

Quique Bassat, Gisely Cardoso de Melo, Márcia A. A. Alexandre, Mayla Gabriela Silva Borba, Fernando Val, Djane Clarys Baia-da-Silva, Christiane Maria Prado Jeronimo, Ludhmila Abrahão Hajjar, Jose Diego Brito-Sousa, Vanderson de Souza Sampaio, Mariana Simão Xavier, Wuelton Marcelo Monteiro, Gustavo Adolfo Sierra Romero, and Marcus V. G. Lacerda

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, Infectious Diseases, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Frost, Medicine, business, Virology
Published
2020
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49. Perspectives and recommendations towards evidence-based health care for scorpion sting envenoming in the Brazilian Amazon: A comprehensive review

Author

Hui Wen Fan, Altair Seabra Farias, Iran Mendonça da Silva, Marcus V. G. Lacerda, Paulo Sérgio Bernarde, Jacqueline de Almeida Gonçalves Sachett, Jacimara Vasques Gomes, José María Gutiérrez, Luiz Carlos de Lima Ferreira, Vanderson de Souza Sampaio, Fernando Val, Aristóteles Alencar, Ageane Mota da Silva, Gisely Cardoso de Melo, Nelson Ferreira Fé, Wuelton Marcelo Monteiro, and Pedro Pereira de Oliveira Pardal

Subjects
0106 biological sciences, medicine.medical_specialty, Antivenom, Scorpion stings, Toxicology, complex mixtures, 01 natural sciences, Health Services Accessibility, Indigenous, Scorpions, 03 medical and health sciences, Environmental health, Epidemiology, medicine, Animals, Humans, 0303 health sciences, Scorpion Stings, Antivenins, business.industry, Amazon rainforest, Incidence, 010604 marine biology & hydrobiology, Public health, 030302 biochemistry & molecular biology, Evidence-based medicine, medicine.disease, Sting, business
Abstract

Although underreported across the Amazon region, scorpion stings are very prevalent in some areas and can be potentially life-threatening, especially in children. The most vulnerable populations are those living in locations far from the capitals, hence having limited access to the health system where the appropriate structure for the treatment of severe cases is found. An abundant and diverse fauna of scorpions is found in the region, but few studies have been conducted to decipher the clinical characteristics and therapeutic response of the available antivenoms in envenomings caused by the various species. Antivenom underdosage as well as delayed medical assistance are common among indigenous populations, resulting in poor outcome rates. An in depth understanding of the epidemiological, clinical and therapeutic aspects of scorpion sting envenomings in the Amazon is necessary to improve the outcome of these cases.

Published
2019
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50. Tafenoquine for the prophylaxis, treatment and elimination of malaria: eagerness must meet prudence

Author

Marcus Vg Lacerda, Fernando Val, Jose Diego Brito-Sousa, André Siqueira, Fabio T. M. Costa, Quique Bassat, Wuelton Marcelo Monteiro, Liam B. King, and Lucio Luzzatto

Subjects
Microbiology (medical), medicine.medical_specialty, Primaquine, Tafenoquine, 030231 tropical medicine, Plasmodium vivax, medicine.disease_cause, Microbiology, Antimalarials, 03 medical and health sciences, High morbidity, chemistry.chemical_compound, 0302 clinical medicine, Malaria elimination, parasitic diseases, Animals, Humans, Medicine, 030212 general & internal medicine, Intensive care medicine, Randomized Controlled Trials as Topic, biology, business.industry, biology.organism_classification, medicine.disease, Malaria, chemistry, Superinfection, Aminoquinolines, Drug Evaluation, Disease prevention, business, medicine.drug
Abstract

Malaria puts more than 3 billion people at risk of infection and causes high morbidity and mortality. Plasmodium vivax forms hypnozoites, which may initiate recurrences, even in the absence of reinfection or superinfection. Until recently, the only drug available for eliminating hypnozoites was primaquine (PQ), which, given its short half-life, requires a relatively long course of treatment. Tafenoquine (TQ) is a PQ analog with a longer half-life. This enables radical cure of malaria with a single dose and overcomes adherence issues associated with PQ, thereby increasing effectiveness in real-life settings. Clinical studies have provided sound evidence for TQ's safety and efficacy against malaria, which recently led to its approval by the US FDA. Here, we review aspects of TQ, including how to avoid hemolytic anemia in G6PD deficient patients. We believe that TQ promises to be a major advance toward malaria elimination.

Published
2019
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