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1. Editorial special edition: Addressing antimicrobial resistance in Southeast Asia

Author: Harish Kumar Tiwari, Justin Beardsley, Ruth Zadoks, Daniel KY Tan, Sothavireak Bory, Phuc Pham Duc, Thi Thu Hoai Nguyen, and Watthana Theppangna
Subjects: Medicine (General), R5-920
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. Exploring fungal diversity in Vietnam: A citizen science initiative

Author: Tra-My N. Duong, Minh-Hang Le, Thanh-Van Le, Thuy T. Ha, Maryam Roudbary, and Justin Beardsley
Subjects: Mycology, Surveillance, AMR, Diversity, Citizen science, Methodology, Medicine (General), R5-920
Abstract: Invasive fungal diseases are increasing globally, causing a large burden of disease in vulnerable populations. At the same time, antifungal resistance is rapidly emerging. Affordable nationwide and regional surveillance of fungal pathogens is needed.We have adapted a citizen-science methodology developed by a United Kingdom research group to study six key fungi in Vietnam, where there is no existing formal surveillance. These pathogens were ranked as high or critical in the World Health Organization fungal priority pathogens list and recognized as major disease-causing agents in Vietnam. Secondary school students (n = 90) in Hanoi were our citizen scientists, collecting soil (n = 90) and air (n = 90) samples for fungal identification and characterisation of drug-susceptibility in the laboratory.Pilot studies confirmed the effectiveness of our revised isolation procedure, which used selective culture media to improve the isolation of target fungi. Through active school and student involvement, optimized protocols, and our cost-effective sampling, the study could be scaled across Vietnam.We demonstrate an approach to fungal surveillance which also enhances science education, and awareness of fungal diseases. It addresses critical healthcare and education challenges in Vietnam while combating the growing issues of invasive fungal diseases and antifungal resistance.
Published: 2024
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4. 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. Hospitalized COVID-19 Patients with Urinary Tract Infection in Iran: Candida Species Distribution and Antifungal Susceptibility Patterns

Author: Zeinab Soleimani Shiyadeh, Shirin Farahyar, Laleh Vahedi Larijani, Justin Beardsley, Noura Nouri, Shahram Mahmoudi, Shahla Roudbar Mohammadi, Célia Fortuna Rodrigues, and Maryam Roudbary
Subjects: Candida species, candiduria, COVID-19, antifungal susceptibility, Therapeutics. Pharmacology, RM1-950
Abstract: Candida species, typically part of the human skin and mucous membrane flora, can cause opportunistic fungal infections, notably urinary tract infections (UTIs), which are on the rise among hospitalized COVID-19 patients. The lack of understanding of UTIs in this population, coupled with the emergence of multidrug-resistant strains, poses significant challenges for effective treatment and further investigations. In this study, urine samples were collected from 70 COVID-19 patients with UTIs in sterile containers for microbiology examination. After microscopic observation, the isolates were identified both by phenotypic and molecular techniques such as multiplex PCR. Antifungal susceptibility testing (AFST) against fluconazole (Flu), itraconazole (Itr), and amphotericin B (AMB) was performed according to CLSI M27/S4 standard methods, with the frequency of isolates including Candida albicans (n = 20, 51.3%), Candida tropicalis (n = 15, 38.4%), Nakaseomyces glabrata (previously Candida glabrata) (n = 2, 5.1%), Pichia kudriavzevii (previously Candida krusei), and Candida parapsilosis (n = 1, 2.5%). All isolates of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis were sensitive to amphotericin B, while C. kruzei was resistant to AMB. Around 70% of C. albicans isolates were sensitive to Flu; 20% of C. tropicalis were resistant to itraconazole, while 33% were resistant to fluconazole. C. albicans and C. tropicalis were the main causes of candiduria in infected cases and both Flu and AMB showed good results in AFST in these species. Performing drug susceptibility testing for clinical isolates of Candida spp. provided guidance for appropriate management and control, and timely antifungal treatment.
Published: 2024
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6. Invasive aspergillosis in adult patients in Australia and New Zealand: 2017–2020Research in context

Author: Shio Yen Tio, Sharon C.-A. Chen, Kate Hamilton, Christopher H. Heath, Alyssa Pradhan, Arthur J. Morris, Tony M. Korman, Orla Morrissey, Catriona L. Halliday, Sarah Kidd, Timothy Spelman, Nadiya Brell, Brendan McMullan, Julia E. Clark, Katerina Mitsakos, Robyn P. Hardiman, Phoebe Williams, Anita J. Campbell, Justin Beardsley, Sebastiaan Van Hal, Michelle K. Yong, Leon J. Worth, and Monica A. Slavin
Subjects: Invasive aspergillosis, Epidemiology, Outcome, Australasia, Public aspects of medicine, RA1-1270
Abstract: Summary: Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice. Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017–December 2020). Descriptive analyses were used to report patients’ demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM). Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria – 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51–69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04–3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93–8.17, p
Published: 2023
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7. 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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8. Retrospective Cohort Study of Effects of the COVID-19 Pandemic on Tuberculosis Notifications, Vietnam, 2020

Author: Tasnim Hasan, Viet Nhung Nguyen, Hoa Binh Nguyen, Thu Anh Nguyen, Hien T.T. Le, Cuong D. Pham, Nam Hoang, Phuong T.M. Nguyen, Justin Beardsley, Guy B. Marks, and Greg J. Fox
Subjects: COVID-19, respiratory infections, tuberculosis and other mycobacteria, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, SARS, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We evaluated the effects of the coronavirus disease pandemic on diagnosis of and treatment for tuberculosis (TB) in Vietnam. We obtained quarterly notifications for TB and multidrug-resistant/rifampin-resistant (MDR/RR) TB from 2015–2020 and evaluated changes in monthly TB case notifications. We used an interrupted time series to assess the change in notifications and treatment outcomes. Overall, TB case notifications were 8% lower in 2020 than in 2019; MDR/RR TB notifications were 1% lower. TB case notifications decreased by 364 (95% CI −1,236 to 508) notifications per quarter and MDR/RR TB by 1 (95% CI −129 to 132) notification per quarter. The proportion of successful TB treatment outcomes decreased by 0.1% per quarter (95% CI −1.1% to 0.8%) in 2020 compared with previous years. Our study suggests that Vietnam was able to maintain its TB response in 2020, despite the pandemic.
Published: 2022
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9. The impact of climate change and biodiversity loss on the health of children: An ethical perspective

Author: Phoebe C. M. Williams, Justin Beardsley, David Isaacs, Anne Preisz, and Ben J. Marais
Subjects: climate change, child health, global health, medical ethics, biodiversity loss, health inequity, Public aspects of medicine, RA1-1270
Abstract: The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, biodiversity collapse is increasingly driving the emergence and spread of infectious diseases, the consequences of which are inequitable globally. Climate change is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences. Over half a billion of the world's children live in areas vulnerable to extreme weather events. Without immediate action, the health of today's children and future generations will be compromised. We consider the impact of biodiversity collapse on the spread of infectious diseases and outline a duty of care along a continuum of three dimensions of medical ethics. From a medical perspective, the first dimension requires doctors to serve the best interests of their individual patients. The second dimension considers the public health dimension with a focus on disease control and cost-effectiveness. The neglected third dimension considers our mutual obligation to the future health and wellbeing of children and generations to come. Given the adverse impact of our ecological footprint on current and future human health, we have a collective moral obligation to act.
Published: 2023
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10. Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections

Author: David Pham, Annaleise R. Howard-Jones, Rebecca Sparks, Maurizio Stefani, Varsha Sivalingam, Catriona L. Halliday, Justin Beardsley, and Sharon C.-A. Chen
Subjects: mucormycosis, Mucorales, epidemiology, DNA sequencing, diagnostics, antifungal agents, Biology (General), QH301-705.5
Abstract: Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.
Published: 2023
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11. Inappropriate supply of antibiotics for common viral infections by community pharmacies in Vietnam: A standardised patient survey

Author: Shukry Zawahir, Hien Thi Thu Le, Thu-Anh Nguyen, Justin Beardsley, Anh Duc Dang, Sarah Bernays, Kerri Viney, Thai Hung Cao, Dorothy Drabarek, Hoang Huy Tran, Son Tu Nguyen, Van Thi Thuy Pham, Tan Minh Luong, Hung Thi Mai Tran, Nhung Viet Nguyen, Stephen Jan, Ben J Marais, Joel Negin, Guy B Marks, and Greg J Fox
Subjects: Antibiotics, Standardised patients, Vietnam, Viral infections, Pharmacy, Antimicrobial resistance, Public aspects of medicine, RA1-1270
Abstract: Summary: Background: This study aimed to evaluate the appropriateness of antibiotic dispensing of private pharmacies in Vietnam. Methods: Standardised patient surveys were conducted in randomly selected community pharmacies across 40 districts in Vietnam. Four clinical scenarios were represented by patient actors: (a) an adult requesting treatment for a sibling with a viral upper respiratory tract infection (URTI), (b) a parent requesting treatment for a child with acute diarrhoea, (c) an adult making a direct antibiotic request, and (d) an adult presenting with an antibiotic prescription. We calculated the proportion of interactions that resulted in inappropriate supply of antibiotics and patient advice. Predictors of inappropriate antibiotic supply were assessed. Findings: Patient actors attended 949 pharmacies, resulting in 1266 clinical interactions. Antibiotics were inappropriately supplied to 92% (291/316) of adults requesting treatment for URTI symptoms, 43% (135/316) for children with acute diarrhoea symptoms and to 84% (267/317) of direct request for antibiotics. Only 49% of pharmacies advised patients regarding their antibiotic use. Female actors were more likely to be given antibiotics than male actors for URTI (aOR 2·71, 1·12–6·60) but not for diarrhoeal disease. Pharmacies in northern Vietnam were more likely than those in southern Vietnam to supply antibiotics without a prescription: for adult URTI (aOR=5·8, 95% CI: 2·2–14·9) and childhood diarrhoea (aOR=3·5, 95% CI: 2·0–6·0) symptoms, but less likely to dispense for direct antibiotics request. Interpretation: Inappropriate antibiotic supply was common in Vietnamese private pharmacies. Multifaceted measures are urgently needed to achieve WHO's global action plan for the optimal use of antimicrobials. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.
Published: 2022
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12. Harnessing new mHealth technologies to Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART trial): a protocol for a randomised controlled trial

Author: Ben J Marais, Joel Negin, James Johnston, Virginia Wiseman, Greg J Fox, Thu Anh Nguyen, Binh Hoa Nguyen, Viet Nhung Nguyen, Justin Beardsley, Guy Barrington Marks, Kavindhran Velen, Tho Dang, Hoang Anh Nguyen, Dinh Hoa Vu, Thu Thuong Do, Cuong Pham Duc, Huu Lan Nguyen, Huu Thuong Pham, and Warwick Britton
Subjects: Medicine
Abstract: Introduction Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem globally. Long, complex treatment regimens coupled with frequent adverse events have resulted in poor treatment adherence and patient outcomes. Smartphone-based mobile health (mHealth) technologies offer national TB programmes an appealing platform to improve patient care and management; however, clinical trial evidence to support their use is lacking. This trial will test the hypothesis that an mHealth intervention can improve treatment success among patients with MDR-TB and is cost-effective compared with standard practice.Methods and analysis A community-based, open-label, parallel-group randomised controlled trial will be conducted among patients treated for MDR-TB in seven provinces of Vietnam. Patients commencing therapy for microbiologically confirmed rifampicin-resistant or multidrug-resistant tuberculosis within the past 30 days will be recruited to the study. Participants will be individually randomised to an intervention arm, comprising use of an mHealth application for treatment support, or a ‘standard care’ arm. In both arms, patients will be managed by the national TB programme according to current national treatment guidelines. The primary outcome measure of effectiveness will be the proportion of patients with treatment success (defined as treatment completion and/or bacteriological cure) after 24 months. A marginal Poisson regression model estimated via a generalised estimating equation will be used to test the effect of the intervention on treatment success. A prospective microcosting of the intervention and within-trial cost-effectiveness analysis will also be undertaken from a societal perspective. Cost-effectiveness will be presented as an incremental cost per patient successfully treated and an incremental cost per quality-adjusted life-year gained.Ethics Ethical approval for the study was granted by The University of Sydney Human Research Ethics Committee (2019/676).Dissemination Study findings will be disseminated to participants and published in peer-reviewed journals and conference proceedings.Trial registration number ACTRN12620000681954.
Published: 2022
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13. Thymoquinone Antifungal Activity against Candida glabrata Oral Isolates from Patients in Intensive Care Units—An In Vitro Study

Author: Noura Nouri, Shahla Roudbar Mohammadi, Justin Beardsley, Peyman Aslani, Fatemeh Ghaffarifar, Maryam Roudbary, and Célia Fortuna Rodrigues
Subjects: thymoquinone, Candida glabrata, EPA6 and EPA7, antifungal susceptibility, oral candidiasis, Microbiology, QR1-502
Abstract: The number of Candida spp. infections and drug resistance are dramatically increasing worldwide, particularly among immunosuppressed patients, and it is urgent to find novel compounds with antifungal activity. In this work, the antifungal and antibiofilm activity of thymoquinone (TQ), a key bioactive constituent of black cumin seed Nigella sativa L., was evaluated against Candida glabrata, a WHO ‘high-priority’ pathogen. Then, its effect on the expression of C. glabrata EPA6 and EPA7 genes (related to biofilm adhesion and development, respectively) were analyzed. Swab samples were taken from the oral cavity of 90 hospitalized patients in ICU wards, transferred to sterile falcon tubes, and cultured on Sabouraud Dextrose Agar (SDA) and Chromagar Candida for presumptive identification. Next, a 21-plex PCR was carried out for the confirmation of species level. C. glabrata isolates underwent antifungal drug susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), amphotericin B (AMB), and TQ according to the CLSI microdilution method (M27, A3/S4). Biofilm formation was measured by an MTT assay. EPA6 and EPA7 gene expression was assessed by real-time PCR. From the 90 swab samples, 40 isolates were identified as C. glabrata with the 21-plex PCR. Most isolates were resistant to FLZ (n = 29, 72.5%), whereas 12.5% and 5% were ITZ and AMB resistant, respectively. The minimum inhibitory concentration (MIC50) of TQ against C. glabrata was 50 µg/mL. Importantly, TQ significantly inhibited the biofilm formation of C. glabrata isolates, and EPA6 gene expression was reduced significantly at MIC50 concentration of TQ. TQ seems to have some antifungal, antibiofilm (adhesion) effect on C. glabrata isolates, showing that this plant secondary metabolite is a promising agent to overcome Candida infections, especially oral candidiasis.
Published: 2023
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14. What’s New in Cryptococcus gattii: From Bench to Bedside and Beyond

Author: Justin Beardsley, Aiken Dao, Caitlin Keighley, Katherine Garnham, Catriona Halliday, Sharon C.-A. Chen, and Tania C. Sorrell
Subjects: Cryptococcus gattii, cryptococcosis, fungal infection, medical mycology, diagnostic tools, epidemiology, Biology (General), QH301-705.5
Abstract: Cryptococcus species are a major cause of life-threatening infections in immunocompromised and immunocompetent hosts. While most disease is caused by Cryptococcus neoformans, Cryptococcus gattii, a genotypically and phenotypically distinct species, is responsible for 11–33% of global cases of cryptococcosis. Despite best treatment, C. gattii infections are associated with early mortality rates of 10–25%. The World Health Organization’s recently released Fungal Priority Pathogen List classified C. gattii as a medium-priority pathogen due to the lack of effective therapies and robust clinical and epidemiological data. This narrative review summarizes the latest research on the taxonomy, epidemiology, pathogenesis, laboratory testing, and management of C. gattii infections.
Published: 2022
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15. Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam

Author: Ben J Marais, Stephen Jan, Joel Negin, Shannon McKinn, Sarah Bernays, Kerri Viney, Thu Anh Nguyen, Guy B Marks, Justin Beardsley, Hien Le, Kavindhran Velen, Hoang Huy Tran, Gregory Fox, Shukry Zawahir, Anh Dang Duc, Thai Cao Hung, Son Nguyen Tu, Tan Luong Minh, Hung Tran Thi Mai, Nhung Nguyen Viet, Ha Nguyen Viet, Van Nguyen Thi Cam, and Thanh Nguyen Trung
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Background Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB.Methods A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs’ referral.Results In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan.Conclusions Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.
Published: 2021
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16. 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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17. An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

Author: Nguyen Thi Thuy Ngan, Nhat Thanh Hoang Le, Nguyen Ngo Vi Vi, Ninh Thi Thanh Van, Nguyen Thi Hoang Mai, Duong Van Anh, Phan Hai Trieu, Nguyen Phu Huong Lan, Nguyen Hoan Phu, Nguyen Van Vinh Chau, David G Lalloo, William Hope, Justin Beardsley, Nicholas J White, Ronald Geskus, Guy E Thwaites, Damian Krysan, Luong Thi Hue Tai, Evelyne Kestelyn, Tran Quang Binh, Le Quoc Hung, Nguyen Le Nhu Tung, and Jeremy N Day
Subjects: cryptococcus neoformans, cryptococcus gattii, HIV, randomised controlled trial, cryptococcal meningitis, Viet Nam, Medicine, Science, Biology (General), QH301-705.5
Abstract: Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential. Methods: Open label randomized controlled trial. Participants received standard care – amphotericin combined with fluconazole for the first 2 weeks – or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) – the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031. Results: Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (−0.48log10 colony-forming units/mL/CSF control arm versus −0.49 tamoxifen arm, difference −0.005log10CFU/ml/day, 95% CI: −0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation. Conclusions: High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed. Funding: The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.
Published: 2021
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18. Pulmonary Cryptococcosis

Author: Annaleise R. Howard-Jones, Rebecca Sparks, David Pham, Catriona Halliday, Justin Beardsley, and Sharon C.-A. Chen
Subjects: cryptococcosis, diagnosis, antifungal agents, immunosuppression, Biology (General), QH301-705.5
Abstract: Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus-derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high.
Published: 2022
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19. A case of percutaneous tricuspid valve infective endocarditis vegetation debulking using the AngioJet rheolytic catheter system—A novel therapeutic use

Author: Liam Marsden Back, Siobhan Hurley, Justin Beardsley, and Virag Kushwaha
Subjects: AngioJet rheolytic catheter, debulking, tricuspid valve endocarditis, Medicine, Medicine (General), R5-920
Abstract: Abstract In patients with fulminant tricuspid valve infective endocarditis precluded from cardiothoracic intervention based on comorbidities or clinical status, percutaneous vegetation debulking utilizing the AngioJet rheolytic catheter system appears a viable rescue option to achieve source control.
Published: 2021
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20. Quality of life and associated factors among HIV positive patients after completion of treatment for Cryptococcal meningitis.

Author: Jonathan Kitonsa, Julius Kiwanuka, Zacchaeus Anywaine, Sheila Kansiime, Kenneth Katumba, Namirembe Aeron, Justin Beardsley, Freddie Kibengo, Alastair Gray, Pontiano Kaleebu, and Jeremy Day
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: BackgroundCryptococcal meningitis (CCM) remains one of the leading causes of mortality among HIV infected patients. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine QOL and associated factors at week 10 and six months from treatment initiation.MethodologyCryptoDex was a double-blind placebo-controlled trial of adjunctive dexamethasone in HIV infected adults with CCM, conducted between 2013 and 2015 in six countries in Asia and Africa. QOL was determined using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We derived index scores, and described these and the VAS scores at 10 weeks and 6 months; and used linear regression to determine the relationship between various characteristics and VAS scores at both time points. VAS scores were interpreted as very good (81-100), good (51-80), normal (31-50) and bad/very bad (0-30).ResultsOf 451 patients enrolled in the trial, 238 had QOL evaluations at week 10. At baseline, their mean age (SD) was 35.2(8.5) years. The mean index scores (SD) were 0.785(0.2) and 0.619(0.4) among African and Asian patients respectively at week 10, and 0.879(0.2) and 0.731(0.4) among African and Asian patients respectively at month six. The overall mean VAS score (SD) at 10 weeks was 57.2 (29.7), increasing significantly to 72(27.4) at month six (pConclusionQOL was good among patients that had completed therapy for CCM, but below perfect. Strategies to improve QOL among CCM survivors are required.
Published: 2021
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21. Applying one health methods to improve cocoa production in Bougainville: A case study

Author: Merrilyn Walton, Jessica Hall, David Guest, James Butubu, Grant Vinning, Kirsten Black, and Justin Beardsley
Subjects: One health, Livelihood, Bougainville, Cocoa, Productivity, Poverty, Medicine (General), R5-920
Abstract: Cocoa production is the major contributor to livelihoods for farming families that constitute nearly two-thirds of the population of the Autonomous Region of Bougainville, a Province in Papua New Guinea (PNG). These families, living mostly in subsistence poverty as a result of the Bougainville Civil War (1988–98), have significantly reduced cocoa production. Efforts to rebuild the industry have not been realised, due to known agricultural factors such as labour shortages, pests and diseases, poor support for farmers from trained agricultural extension officers and inefficient cocoa supply chains. But cocoa production involves factors other than agricultural ones. This article describes how we applied One Health methods to design and undertake a 6-year research project in Bougainville to improve cocoa productivity. Maximising the health and wellbeing of farming families and increasing agricultural productivity we argue, requires an in-depth understanding of the non-linear interactions between health, labour, household decision-making, yields and incomes.
Published: 2020
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22. The extent to which the domestic conditions of cocoa farmers in Bougainville impede livelihoods

Author: Merrilyn Walton, Jessica Hall, Floris Van Ogtrop, David Guest, Kirsten Black, Justin Beardsley, Clement Totavun, and Grant Hill-Cawthorne
Subjects: Livelihood, Health, Water, Sanitation, Bougainville, Cocoa, Medicine (General), R5-920
Abstract: Background: Bougainville, an autonomous region of Papua New Guinea (PNG) is slowly improving services and infrastructure destroyed 20 years ago during the ten year civil war. However, the region still faces significant constraints to economic growth and human development and remains under-developed compared to PNG and close Pacific neighbours. PNG's 2017 Human Development Category (HDC) was one of the lowest at 0.544. The Bougainville Strategic Development Plan 2018–2022 noted significant gaps in health services and infrastructure, had inadequate water and waste disposal and experienced weak markets and cocoa quality. This research examines domestic conditions and the extent to which they impact on livelihoods. Method: A cross-sectional livelihood survey was administered to cocoa growing households in 33 Village Assemblies (VAs) with 11 VAs in each of the three regions. Results: Data was collected from 5172 individuals. A significant majority of households reported multiple health issues, rudimentary housing, unimproved sanitation and unimproved water. Over two-thirds of cocoa growers did not sell any cocoa bags in 2014–2016 resulting in low incomes and greater food insecurity compared to families selling cocoa. Families that produced no saleable cocoa were more likely to have rudimentary housing, unimproved toilet facilities and unsafe water, factors that increase the likelihood of chronic disease and exacerbate malnutrition and poor labour productivity. Conclusion: This study provides key information about the health and livelihood status of cocoa growers in Bougainville. If productivity is to increase, farmer health needs to improve including improving water and sanitation practices and diets. Building a responsive health system for the community is a challenge when a majority of the population live in small villages with difficult access to health centres. Establishing and integrating outreach village health clinics will enable health care to be more accessible to these remote communities.
Published: 2020
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23. Factors influencing undernutrition among children under 5 years from cocoa-growing communities in Bougainville

Author: Kirsten Black, Justin Beardsley, Jessica Hall, Merrilyn Walton, Floris Van Ogtrop, and David Guest
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Half the children under the age of 5 years in Papua New Guinea (PNG) are undernourished, more than double the global average with rural areas disproportionately affected. This study examines factors associated with stunting, wasting and underweight in cocoa growers’ children (
Published: 2020
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24. Chronic Pulmonary Aspergillosis: Burden, Clinical Characteristics and Treatment Outcomes at a Large Australian Tertiary Hospital

Author: Olivier Despois, Sharon C-A. Chen, Nicole Gilroy, Michael Jones, Peter Wu, and Justin Beardsley
Subjects: chronic pulmonary aspergillosis, chronic obstructive pulmonary disease, tuberculosis, mycoses, antifungal, Aspergillus, Biology (General), QH301-705.5
Abstract: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection associated with high morbidity and mortality. Yet, it remains under-recognized worldwide, with few Australian clinical data available. This retrospective study aimed to investigate CPA at a major tertiary referral hospital in Sydney. We identified patients having International Classification of Diseases (ICD-10) codes for “aspergillosis” and/or positive respiratory microbiology samples for Aspergillus species from January 2012–December 2018 at Westmead Hospital. Eligible cases were classified using European Respiratory Society 2016 CPA guidelines. We diagnosed 28 CPA patients: median age 60 years (IQR: 57–66), with 17 (60.7%) being males. Most had chronic cavitary pulmonary aspergillosis phenotype (n = 17, 60.7%). Twenty-three patients had outcomes data returned. Nineteen (82.6%) received antifungal therapy (median duration: 10.5 months (IQR: 6.5–20.7)). Eight (34.7%) patients received
Published: 2022
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25. The Implementation of Mass-Vaccination against SARS-CoV-2: A Systematic Review of Existing Strategies and Guidelines

Author: Tasnim Hasan, Justin Beardsley, Ben J. Marais, Thu Anh Nguyen, and Greg J. Fox
Subjects: covid, vaccination, national policy data, implementation, Medicine
Abstract: The global drive to vaccinate against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2020 with countries in Europe, Middle East, and North America leading the roll out of a mass-vaccination program. This systematic review synthesised all available English-language guidelines and research regarding mass-vaccination for COVID-19 until 1 March 2021—the first three months of the global mass-vaccination effort. Data were extracted from national websites, PubMed, Embase, Medline and medRxiv, including peer and non-peer review research findings. A total of 15 national policy documents were included. Policies were summarised according to the World Health Organisation (WHO) framework for mass vaccination. All included policies prioritised front-line health care workers and the elderly. Limited information was available regarding staffing, cold chain, communication strategies and infrastructure requirements for effective vaccine delivery. A total of 26 research studies were identified, reporting roll-out strategies, vaccine uptake and reasons for refusal, adverse effects, and real-life estimates of efficacy. Early data showed a reduction in SARS-CoV-2 cases, hospitalisation and deaths in settings with good coverage. Very low rates of vaccine-related serious adverse events were observed. These findings provide an overview of current practice and early outcomes of COVID-19 mass-vaccination, guiding countries where roll-out is yet to commence.
Published: 2021
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26. Immunomodulatory effects of pharmaceutical opioids and antipyretic analgesics: Mechanisms and relevance to infection

Author: Justin Beardsley, Christina Abdel Shaheed, Richard Day, and Andrew McLachlan
Subjects: Pharmacology, Analgesics, Antipyretics, Morphine, Anti-Inflammatory Agents, Non-Steroidal, COVID-19, Communicable Diseases, COVID-19 Drug Treatment, Analgesics, Opioid, Coronavirus, Pharmaceutical Preparations, Animals, Humans, Pharmacology (medical)
Abstract: Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its clinical benefit in humans needs to be resolved in large clinical trials. Certain opioid analgesics are associated with immunosuppressive effects, with a developing understanding that fentanyl, morphine, methadone and buprenorphine suppress innate immunity, whilst having diverse effects on adaptive immunity. Morphine suppresses key cells of the innate immunity and is associated with greater risk of infection in the postsurgical setting. Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery.
Published: 2022
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27. Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?

Author: Tra My N. Duong, Phuong Tuyen Nguyen, Thanh Van Le, Huong Lan P. Nguyen, Bich Ngoc T. Nguyen, Bich Phuong T. Nguyen, Thu Anh Nguyen, Sharon C.-A. Chen, Vanessa R. Barrs, Catriona L. Halliday, Tania C. Sorrell, Jeremy N. Day, and Justin Beardsley
Subjects: Aspergillus flavus, azole resistance, environmental, Biology (General), QH301-705.5
Abstract: The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account.
Published: 2020
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28. A randomized open label trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis. [version 1; referees: 2 approved]

Author: Nguyen Thi Thuy Ngan, Nguyen Thi Hoang Mai, Nguyen Le Nhu Tung, Nguyen Phu Huong Lan, Luong Thi Hue Tai, Nguyen Hoan Phu, Nguyen Van Vinh Chau, Tran Quang Binh, Le Quoc Hung, Justin Beardsley, Nicholas White, David Lalloo, Damian Krysan, William Hope, Ronald Geskus, Marcel Wolbers, Le Thanh Hoang Nhat, Guy Thwaites, Evelyne Kestelyn, and Jeremy Day
Subjects: Medicine, Science
Abstract: Background: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combined in vitro with amphotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with amphotericin and fluconazole. Method: A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with amphotericin (1mg/kg/day) and fluconazole (800mg/day) for the first 2 weeks therapy for HIV infected or uninfected adults with cryptococcal meningitis. The study recruits at Cho Ray Hospital and the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The primary end point is Early Fungicidal Activity (EFA-the rate of yeast clearance from CSF), over the first two weeks of treatment. 50 patients will be recruited providing ≈80% and 90% power to detect a difference in the EFA of -0.11 or -0.13 log10CFU/ml/day, respectively. Discussion: The results of the study will inform the decision to proceed to a larger trial powered to mortality. The size of effect detectable has previously been associated with reduced mortality from this devastating disease. Particular side effects of interest include QT prolongation. Trial registration: Clinicaltrials.gov NCT03112031 (11/04/2017)
Published: 2019
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29. Updated Estimation of the Burden of Fungal Disease in Vietnam

Author: Tra‐My N. Duong, Minh‐Hang Le, Justin Beardsley, David W. Denning, Ngoc‐Huy Le, and Bich‐Ngoc T. Nguyen
Subjects: Infectious Diseases, Dermatology, General Medicine
Abstract: Anecdotally, the burden of fungal diseases in Vietnam is rapidly rising, but there has been no updated estimate on this issue since a previous report in 2015.In this study, we aimed to estimate the incidence and prevalence of serious fungal infections for the year 2020.We made estimates with a previously described methodology, using reports on the incidence and prevalence of various established risk factors for fungal infections from local, regional, or global sources.We estimated 2,389,661 cases of serious fungal infection occurred in Vietnam in 2020. The most common condition was recurrent vaginal candidiasis (4,047/100,000 women annually). Among people living with HIV, we estimated 451 cases of cryptococcal meningitis, 1,030 of pneumocystis pneumonia, 166 of histoplasmosis and 1,612 of talaromycosis annually. Candidaemia incidence was estimated at 12/100,000 population each year. Owing to its high burden of tuberculosis and respiratory diseases, Vietnam had high rates of severe infections caused by Aspergillus species. Incidence of invasive aspergillosis is 24/100,000 population, allergic bronchopulmonary aspergillosis 78/100,000, and severe asthma with fungal sensitisation 102/100,000. Five-year period prevalence of chronic pulmonary aspergillosis is 120/100,000 population /5-year period. Mucormycosis, fungal keratitis, and tinea capitis were estimated at 192, 14,431 and 201 episodes each year, respectively.The number of patients with mycoses in Vietnam is likely underestimated due to lack of local data and limited diagnostic capacity, but at least 2.5% of the population might have some form of serious fungal disease.
Published: 2022

30. Consensus guidelines for the diagnosis and management of cryptococcosis and rare yeast infections in the haematology/oncology setting, 2021

Author: Christina C, Chang, Victoria, Hall, Celia, Cooper, George, Grigoriadis, Justin, Beardsley, Tania C, Sorrell, Christopher H, Heath, and Anna, Khanina
Subjects: Australia, Cryptococcus neoformans, Internal Medicine, Humans, Cryptococcus gattii, Cryptococcosis, Hematology, Saccharomyces cerevisiae
Abstract: Cryptococcosis caused by the Cryptococcus neoformans-Cryptococcus gattii complex is an important opportunistic infection in people with immunodeficiency, including in the haematology/oncology setting. This may manifest clinically as cryptococcal meningitis or pulmonary cryptococcosis, or be detected incidentally by cryptococcal antigenemia, a positive sputum culture or radiological imaging. Non-Candida, non-Cryptococcus spp. rare yeast fungaemia are increasingly common in this population. These consensus guidelines aim to provide clinicians working in the Australian and New Zealand haematology/oncology setting with clear guiding principles and practical recommendations for the management of cryptococcosis, while also highlighting important and emerging rare yeast infections and their recommended management.
Published: 2021
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31. Azole‐resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type

Author: Matthew C. Fisher, Tra-My N. Duong, Sharon C.-A. Chen, Catriona Halliday, Khanh-Linh H. Tran, Tania C. Sorrell, Justin Beardsley, Huong-Lan P. Nguyen, Jeremy N. Day, Greg J. Fox, Thu Anh Nguyen, Guy B. Marks, Jessica J. Talbot, Phuong-Tuyen Nguyen, Michael Walsh, Thanh-Van Le, Bich-Ngoc T. Nguyen, Bich-Phuong T. Nguyen, Vanessa R. Barrs, Johanna Rhodes, Medical Research Council (MRC), and Wellcome Trust
Subjects: Azoles, Antifungal, Posaconazole, Veterinary medicine, Antifungal Agents, Itraconazole, medicine.drug_class, Azole resistance, Microbial Sensitivity Tests, SUSCEPTIBILITY, Microbiology, MECHANISMS, Aspergillus fumigatus, Southeast asia, Fungal Proteins, 0603 Evolutionary Biology, Drug Resistance, Fungal, SURVEILLANCE, parasitic diseases, medicine, CYP51A GENE, TR34/L98H MUTATIONS, Ecology, Evolution, Behavior and Systematics, chemistry.chemical_classification, Voriconazole, Science & Technology, CYSTIC-FIBROSIS, biology, bacterial infections and mycoses, biology.organism_classification, Vietnam, chemistry, Azole, SECTION FUMIGATI, BURDEN, Life Sciences & Biomedicine, 0605 Microbiology, medicine.drug
Abstract: Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).
Published: 2021
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32. Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients

Author: Justin Beardsley, Tania C. Sorrell, and Sharon C.-A. Chen
Subjects: Cryptococcosis, Cryptococcus neoformans, Cryptococcus gattii, central nervous system, meningo-encephalitis, cerebral infection, HIV-negative patients, epidemiology, antifungal therapy, Biology (General), QH301-705.5
Abstract: Central nervous system (CNS) cryptococcosis in non-HIV infected patients affects solid organ transplant (SOT) recipients, patients with malignancy, rheumatic disorders, other immunosuppressive conditions and immunocompetent hosts. More recently described risks include the use of newer biologicals and recreational intravenous drug use. Disease is caused by Cryptococcus neoformans and Cryptococcus gattii species complex; C. gattii is endemic in several geographic regions and has caused outbreaks in North America. Major virulence determinants are the polysaccharide capsule, melanin and several ‘invasins’. Cryptococcal plb1, laccase and urease are essential for dissemination from lung to CNS and crossing the blood–brain barrier. Meningo-encephalitis is common but intracerebral infection or hydrocephalus also occur, and are relatively frequent in C. gattii infection. Complications include neurologic deficits, raised intracranial pressure (ICP) and disseminated disease. Diagnosis relies on culture, phenotypic identification methods, and cryptococcal antigen detection. Molecular methods can assist. Preferred induction antifungal therapy is a lipid amphotericin B formulation (amphotericin B deoxycholate may be used in non-transplant patients) plus 5-flucytosine for 2–6 weeks depending on host type followed by consolidation/maintenance therapy with fluconazole for 12 months or longer. Control of raised ICP is essential. Clinicians should be vigilant for immune reconstitution inflammatory syndrome.
Published: 2019
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33. Mapping access to drug outlets in Vietnam: distribution of drug outlets and the sociodemographic characteristics of the communities they serve

Author: Justin Beardsley, Joshua Mark Chambers, Thanh Tuan Lam, Shukry Zawahir, Hien Le, Thu Anh Nguyen, Michael Walsh, Pham Thi Thuy Van, Nguyen Thi Cam Van, Tran Huy Hoang, Tran Thi Mai Hung, Cao Hung Thai, Dang Duc Anh, and Greg J. Fox
Subjects: Psychiatry and Mental health, Infectious Diseases, Health Policy, Pediatrics, Perinatology and Child Health, Public Health, Environmental and Occupational Health, Internal Medicine, Obstetrics and Gynecology, Geriatrics and Gerontology
Published: 2023
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34. Author response: An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

Author: David G. Lalloo, Nguyen Thi Thuy Ngan, Nguyen Phu Huong Lan, Jeremy N. Day, Ninh Thi Thanh Van, Luong Thi Hue Tai, Nguyen Van Vinh Chau, Nguyen Hoan Phu, Nguyen Thi Hoang Mai, Ronald B. Geskus, Le Quoc Hung, Damian J. Krysan, Tran Quang Binh, Guy E. Thwaites, Nhat Thanh Hoang Le, Phan Hai Trieu, Justin Beardsley, Nguyen Le Nhu Tung, Evelyne Kestelyn, William Hope, Nguyen Ngo Vi Vi, Nicholas J. White, and Duong Van Anh
Subjects: medicine.medical_specialty, business.industry, law.invention, Randomized controlled trial, law, Internal medicine, Amphotericin B, medicine, Open label, business, Cryptococcal meningitis, Fluconazole, Tamoxifen, medicine.drug
Published: 2021
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35. An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

Author: Ninh Thi Thanh Van, Nhat Thanh Hoang Le, Le Quoc Hung, Tran Quang Binh, Nguyen Van Vinh Chau, Nguyen Phu Huong Lan, Phan Hai Trieu, Luong Thi Hue Tai, Justin Beardsley, Nicholas J. White, Guy E. Thwaites, Nguyen Thi Thuy Ngan, Nguyen Hoan Phu, William Hope, Damian J. Krysan, Jeremy N. Day, Duong Van Anh, Nguyen Thi Hoang Mai, Ronald B. Geskus, David G. Lalloo, Nguyen Ngo Vi Vi, Evelyne Kestelyn, and Nguyen Le Nhu Tung
Subjects: Male, Antifungal Agents, Cryptococcus, Meningitis, Cryptococcal, law.invention, Flucytosine, Randomized controlled trial, cryptococcal meningitis, law, Amphotericin B, Clinical endpoint, Biology (General), Fluconazole, 0303 health sciences, Microbiology and Infectious Disease, cryptococcus neoformans, biology, General Neuroscience, General Medicine, qv_252, 3. Good health, Long QT Syndrome, Viet Nam, Medicine, Drug Therapy, Combination, Female, medicine.drug, Research Article, Adult, medicine.medical_specialty, QH301-705.5, Science, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, wl_200, Internal medicine, medicine, Humans, cryptococcus gattii, 030304 developmental biology, Cryptococcus neoformans, General Immunology and Microbiology, 030306 microbiology, business.industry, HIV, biology.organism_classification, wc_475, Tamoxifen, Other, business, randomised controlled trial
Abstract: Background:Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential.Methods:Open label randomized controlled trial. Participants received standard care – amphotericin combined with fluconazole for the first 2 weeks – or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) – the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031.Results:Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (−0.48log10 colony-forming units/mL/CSF control arm versus −0.49 tamoxifen arm, difference −0.005log10CFU/ml/day, 95% CI: −0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation.Conclusions:High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed.Funding:The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.
Published: 2021

36. Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam

Author: Nhung Nguyen Viet, Shannon McKinn, Ben J. Marais, Hoang Huy Tran, Stephen Jan, Thu Anh Nguyen, Tan Luong Minh, Shukry Zawahir, Justin Beardsley, Thanh Nguyen Trung, Son Nguyen Tu, Ha Nguyen Viet, Guy B. Marks, Thai Cao Hung, Van Nguyen Thi Cam, Anh Dang Duc, Kerri Viney, Gregory J. Fox, Sarah Bernays, Joel Negin, Kavindhran Velen, Hien Thi Thu Le, and Hung Tran Thi Mai
Subjects: pharmacy, medicine.medical_specialty, Tuberculosis, Referral, Cross-sectional study, case detection, standardised patient survey, Pharmacy, other study design, 1117 Public Health and Health Services, Tuberculosis diagnosis, Medicine, Humans, Medical prescription, 11 Medical and Health Sciences, Original Research, Pharmacies, business.industry, Health Policy, public health, Public Health, Environmental and Occupational Health, Health services research, medicine.disease, health services research, Cross-Sectional Studies, Vietnam, tuberculosis, Family medicine, Private healthcare, business
Abstract: BackgroundOf the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB.MethodsA cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs’ referral.ResultsIn total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan.ConclusionsFew SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.
Published: 2021

37. The Implementation of Mass-Vaccination against SARS-CoV-2: A Systematic Review of Existing Strategies and Guidelines

Author: Thu Anh Nguyen, Tasnim Hasan, Ben J. Marais, Justin Beardsley, and Greg J. Fox
Subjects: medicine.medical_specialty, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, MEDLINE, Staffing, lcsh:Medicine, Review, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, Health care, Medicine, National Policy, Pharmacology (medical), 030212 general & internal medicine, 0101 mathematics, Cold chain, implementation, Adverse effect, Pharmacology, business.industry, lcsh:R, 010102 general mathematics, COVID-19, covid, vaccination, national policy data, Vaccination, Coronavirus, Infectious Diseases, Family medicine, business
Abstract: The global drive to vaccinate against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2020 with countries in Europe, Middle East, and North America leading the roll out of a mass-vaccination program. This systematic review synthesised all available English-language guidelines and research regarding mass-vaccination for COVID-19 until 1 March 2021—the first three months of the global mass-vaccination effort. Data were extracted from national websites, PubMed, Embase, Medline and medRxiv, including peer and non-peer review research findings. A total of 15 national policy documents were included. Policies were summarised according to the World Health Organisation (WHO) framework for mass vaccination. All included policies prioritised front-line health care workers and the elderly. Limited information was available regarding staffing, cold chain, communication strategies and infrastructure requirements for effective vaccine delivery. A total of 26 research studies were identified, reporting roll-out strategies, vaccine uptake and reasons for refusal, adverse effects, and real-life estimates of efficacy. Early data showed a reduction in SARS-CoV-2 cases, hospitalisation and deaths in settings with good coverage. Very low rates of vaccine-related serious adverse events were observed. These findings provide an overview of current practice and early outcomes of COVID-19 mass-vaccination, guiding countries where roll-out is yet to commence.
Published: 2021

38. Assessing the virulence of Cryptococcus neoformans causing meningitis in HIV infected and uninfected patients in Vietnam

Author: Charles Giamberardino, Jennifer L. Tenor, Lan Phu Huong Nguyen, Stephen Baker, Jeremy N. Day, Chau Van Vinh Nguyen, John R. Perfect, Trinh Mai Nguyen, Justin Beardsley, Trieu Hai Phan, Chau Thi Hong Tran, Yohannes G. Asfaw, Dena L. Toffaletti, Anh Van Duong, Thanh Tuan Lam, Guy E. Thwaites, Philip Ashton, Greg Sempowski, Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository
Subjects: Male, Lineage (genetic), Genotype, Colony Count, Microbial, Virulence, Biology, Meningitis, Cryptococcal, Microbiology, 03 medical and health sciences, Mice, Fungal Capsules, In vivo, Hiv infected, medicine, Animals, Humans, Typing, Lung, 030304 developmental biology, Cryptococcus neoformans, 0303 health sciences, AIDS-Related Opportunistic Infections, 030306 microbiology, HIV, General Medicine, biology.organism_classification, medicine.disease, Phenotype, In vitro, immunocompetent, 3. Good health, Infectious Diseases, Vietnam, AcademicSubjects/SCI00960, Cytokines, Original Article, Amplified fragment length polymorphism, Female, Immunocompetence, AcademicSubjects/MED00010, Meningitis, Cryptococcal meningitis
Abstract: We previously observed a substantial burden of cryptococcal meningitis in Vietnam atypically arising in HIV-uninfected individuals. This disease was associated with a single genotype ofCryptococcus neoformans(Sequence Type (ST)5), which was significantly less common in HIV-infected individuals. Aiming to compare the phenotypic characteristics of ST5 and non-ST5 C. neoformans we selected 30 representative Vietnamese isolates, compared theirin vitropathogenic potential andin vivovirulence. ST5 and non-ST5 organisms exhibited comparable characteristics with respect toin vitrovirulence markers including melanin production, replication at 37°C, and growth in cerebrospinal fluid. However, the ST5 isolates had significantly increased variability in cellular and capsular sizing compared with non-ST5 organisms (pp
Published: 2020

39. Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?

Author: Bich Ngoc T. Nguyen, Phuong Tuyen Nguyen, Vanessa R. Barrs, Tania C. Sorrell, Tra My N. Duong, Sharon C.-A. Chen, Bich Phuong T. Nguyen, Justin Beardsley, Thanh Van Le, Catriona Halliday, Huong Lan P. Nguyen, Jeremy N. Day, and Thu Anh Nguyen
Subjects: Microbiology (medical), Itraconazole, Aspergillus flavus, Plant Science, Drug resistance, Aspergillosis, environmental, Microbiology, Aspergillus fumigatus, 03 medical and health sciences, azole resistance, Amphotericin B, medicine, skin and connective tissue diseases, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, 030306 microbiology, Communication, Chronic pulmonary aspergillosis, medicine.disease, biology.organism_classification, chemistry, lcsh:Biology (General), Azole, medicine.drug
Abstract: The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account.
Published: 2020

40. Factors influencing undernutrition among children under 5 years from cocoa-growing communities in Bougainville

Author: Floris van Ogtrop, Justin Beardsley, David Guest, Merrilyn Walton, Jessica Caudwell Hall, and Kirsten I. Black
Subjects: medicine.medical_specialty, 030309 nutrition & dietetics, Cross-sectional study, cross-sectional survey, Child health, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Thinness, Environmental health, Prevalence, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, Child, Wasting, Growth Disorders, Original Research, 0303 health sciences, lcsh:R5-920, Health Policy, Public health, public health, Malnutrition, stunting, Public Health, Environmental and Occupational Health, New guinea, medicine.disease, nutrition, Cross-Sectional Studies, Geography, Child, Preschool, child health, Female, Rural area, Underweight, medicine.symptom, lcsh:Medicine (General)
Abstract: Half the children under the age of 5 years in Papua New Guinea (PNG) are undernourished, more than double the global average with rural areas disproportionately affected. This study examines factors associated with stunting, wasting and underweight in cocoa growers’ children (
Published: 2020

41. Do Intracerebral Cytokine Responses Explain the Harmful Effects of Dexamethasone in Human Immunodeficiency Virus–associated Cryptococcal Meningitis?

Author: Nguyen Van Vinh Chau, Freddie Kibengo, Jeremy N. Day, Wirongrong Chierakul, Guy E. Thwaites, Ronald B. Geskus, Tran Quang Binh, Nguyen Le Nhu Tung, Nhat Le Thanh Hoang, Thuong Thuy Thuong Nguyen, Justin Beardsley, and Le Q. Hung
Subjects: 0301 basic medicine, medicine.medical_treatment, Gene Expression, HIV Infections, Meningitis, Cryptococcal, corticosteroids, 0302 clinical medicine, Uganda, 030212 general & internal medicine, Articles and Commentaries, Macrophage inflammatory protein, Chemokine CCL2, Epoxide Hydrolases, biology, Thailand, 3. Good health, Treatment Outcome, Infectious Diseases, Cytokine, medicine.anatomical_structure, Vietnam, Tumor necrosis factor alpha, medicine.drug, Microbiology (medical), Genotype, 030106 microbiology, dexamethasone, Tuberculous meningitis, Proinflammatory cytokine, Interferon-gamma, 03 medical and health sciences, medicine, Humans, cryptococcal, Interleukin 6, Glucocorticoids, Dexamethasone, Adaptor Proteins, Signal Transducing, LTA4H, Tumor Necrosis Factor-alpha, business.industry, Interleukins, Monocyte, Granulocyte-Macrophage Colony-Stimulating Factor, HIV, medicine.disease, Survival Analysis, cytokines, Cryptococcus, Immunology, biology.protein, business
Abstract: Background The CryptoDex trial showed that dexamethasone caused poorer clinical outcomes and slowed fungal clearance in human immunodeficiency virus–associated cryptococcal meningitis. We analyzed cerebrospinal fluid (CSF) cytokine concentrations from participants over the first week of treatment to investigate mechanisms of harm and test 2 hypotheses: (1) dexamethasone reduced proinflammatory cytokine concentrations, leading to poorer outcomes and (2) leukotriene A4 hydrolase (LTA4H) genotype influenced the clinical impact of dexamethasone, as observed in tuberculous meningitis. Methods We included participants from Vietnam, Thailand, and Uganda. Using the Luminex system, we measured CSF concentrations of the following: interferon γ, tumor necrosis factor (TNF) α, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant 1, macrophage inflammatory protein 1α, and interleukin 6, 12p70, 8, 4, 10, and 17. We determined the LTA4H genotype based on the promoter region single-nucleotide polymorphism rs17525495. We assessed the impact of dexamethasone on cytokine concentration dynamics and the association between cytokine concentration dynamics and fungal clearance with mixed effect models. We measured the influence of LTA4H genotype on outcomes with Cox regression models. Results Dexamethasone increased the rate TNF-α concentration’s decline in (−0.13 log2pg/mL/d (95% confidence interval, −.22 to −.06 log2pg/mL/d; P = .03), which was associated with slower fungal clearance (correlation, −0.62; 95% confidence interval, −.83 to −.26). LTA4H genotype had no statistically significant impact on outcome or response to dexamethasone therapy. Better clinical outcomes were associated with higher baseline concentrations of interferon γ. Conclusions Dexamethasone may slow fungal clearance and worsen outcomes by increasing TNF-α concentration’s rate of decline., We investigated clinical and microbiological impacts of longitudinal cerebrospinal fluid cytokine concentrations in human immunodeficiency virus–associated cryptococcal meningitis, and interactions with dexamethasone therapy or leukotriene A4 hydrolase genotype. We found that faster declines in tumor necrosis factor α were associated with reduced fungal clearance.
Published: 2018
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42. Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside

Author: Justin Beardsley, Catriona Halliday, Tania C. Sorrell, and Sharon C.-A. Chen
Subjects: Azoles, Microbiological Techniques, 0301 basic medicine, Microbiology (medical), Antifungal, medicine.medical_specialty, Antifungal Agents, medicine.drug_class, 030106 microbiology, Antifungal drug, Review, Drug resistance, Models, Biological, Microbiology, Echinocandins, 03 medical and health sciences, Drug Resistance, Fungal, medicine, Humans, Available drugs, Intensive care medicine, Candida, Resistance (ecology), business.industry, Fungal genetics, Aspergillus, Mycoses, Candida spp, business
Abstract: The incidence of serious fungal infections is increasing rapidly, and yet the rate of new drugs becoming available to treat them is slow. The limited therapeutic armamentarium is a challenge for clinicians, because the available drugs are often toxic, expensive, difficult to administer, ineffective or a combination of all four. Given this setting, the emergence of resistance is especially concerning, and a review of the topic is timely. Here we discuss antifungal drug resistance in Candida spp. and Aspergillus spp. with reference to the most commonly used first-line antifungal agents – azoles and echinocandins. We review the resistance mechanisms of the leading pathogens, how resistance can be identified in the diagnostic lab and the clinical implications of resistance once detected.
Published: 2018
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43. Unprecedented Prevalence of Azole-Resistant Aspergillus fumigatus Identified in the Environment of Vietnam, with Marked Variability by Land Use Type

Author: Guy B. Marks, Nguyen Phu Huong Lan, Nguyen Phuong Tuyen, Le Thanh Van, Johanna Rhodes, Nguyen Thi Phuong, Greg J. Fox, Vanessa R. Barrs, Jeremy N. Day, Nguyen Thu Anh, Michael Walsh, Duong Nu Tra My, Justin Beardsley, Matthew C. Fisher, Tania C. Sorrell, Catriona Halliday, Jessica J. Talbot, N. B. Ngoc, Tran Hoang Khanh Linh, and Sharon C.-A. Chen
Subjects: Aspergillus, Veterinary medicine, Posaconazole, Tuberculosis, biology, Itraconazole, National park, Chronic pulmonary aspergillosis, Drug resistance, biology.organism_classification, medicine.disease, Aspergillus fumigatus, medicine, medicine.drug
Abstract: Background: Azole-resistant Aspergillus fumigatus (ARAF) presents a threat to global public health, particularly where prior tuberculosis or underlying lung disease is prevalent. Southeast Asia is estimated to have a large burden of Aspergillus disease yet mycology diagnostic laboratory capacity is limited and systematic surveillance for drug resistance is absent. ARAF’s threat is thus poorly understood in this populous region. Methods: We conducted environmental surveillance in southern Vietnam, collecting air and ground samples across land-use types including cultivated land, urban residential land, and national park. We determined susceptibilities of A. fumigatus and non-fumigatus Aspergillus section Fumigati (ASF) isolates using EUCAST methodology, and measured residual agricultural azole concentrations in soil using liquid chromatography / tandem mass spectrometry. Findings: 95·2% of A. fumigatus isolates (59/62) were azole-resistant (31·6% for non- fumigatus ASF isolates (18/57)). Of all 119 ASF isolates, 55% were resistant or non-wild type to itraconazole, 65% to posaconazole and 50% to voriconazole. Both resistant isolates and agricultural azole residues were over-represented in cultivated land. The odds ratio for azole-resistance being detected, compared to national park sites, was ranged from 3·15-7·16 in cultivated lands types, and was highest in urban residential sites (9·31, p=0.0002). cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus isolates carried known resistance mutations, with TR34/L98H most frequent (34/38). Interpretation: Our data demonstrate alarmingly high levels of azole-resistant A. fumigatus in this region, which challenge the reliance of existing treatment guidelines on empiric azole therapy. Funding Statement: This project received internal funding from the University of Sydney. Declaration of Interests: None of the authors have any financial and personal potential conflicts of interest. Ethics Approval Statement: National Lung Hospital, Hanoi, Vietnam provided ethical approval for the study.
Published: 2020
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44. Burden of injuries in Vietnam: emerging trends from a decade of economic achievement

Author: Nicholas L S Roberts, Thanh Huong Nguyen, Sonia Lewycka, Justin Beardsley, Quynh Anh P. Nguyen, Zichen Liu, Nhung T Nguyen, Bach Xuan Tran, Chi Linh Hoang, Thu Ha Nguyen, Spencer L. James, Zachary V Dingels, Khanh Bao Tran, Chris D Castle, Jack T Fox, Dillon O Sylte, Anh Kim Dang, Giang Thu Vu, Hai Quang Pham, Ali H. Mokdad, and Son Hoang Nguyen
Subjects: Poison control, burden of disease, Global Health, Suicide prevention, Occupational safety and health, Global Burden of Disease, 03 medical and health sciences, 0302 clinical medicine, Injury prevention, Humans, Medicine, Disabled Persons, 030212 general & internal medicine, Original Research, business.industry, Incidence, Incidence (epidemiology), Mortality rate, Public Health, Environmental and Occupational Health, Human factors and ergonomics, 030208 emergency & critical care medicine, global, economic development, Years of potential life lost, Vietnam, Wounds and Injuries, Quality-Adjusted Life Years, business, Demography
Abstract: BackgroundVietnam has been one of the fastest-growing world economies in the past decade. The burden of injuries can be affected by economic growth given the increased exposure to causes of injury as well as decreased morbidity and mortality of those that experience injury. It is of interest to evaluate the trends in injury burden that occurred alongside Vietnam’s economic growth in the past decade.MethodsResults from Global Burden of Disease 2017 were obtained and reviewed. Estimates of incidence, cause-specific mortality, years lived with disability, years of life lost, disability-adjusted life years were analysed and reported for 30 causes of injury in Vietnam from 2007 to 2017.ResultsBetween 2007 and 2017, the age-standardised incidence rate of all injuries increased by 14.6% (11.5%–18.2%), while the age-standardised mortality rate decreased by 11.6% (3.0%–20.2%). Interpersonal violence experienced the largest increase in age-standardised incidence (28.3% (17.6%–40.1%)), while exposure to forces of nature had the largest decrease in age-standardised mortality (47.1% (37.9%–54.6%)). The five leading causes of injury in both 2007 and 2017 were road injuries, falls, exposure to mechanical forces, interpersonal violence and other unintentional injuries, all of which increased in incidence from 2007 to 2017. Injury burden varied markedly by age and sex.ConclusionsThe rapid expansions of economic growth in Vietnam as well as improvements in the Sociodemographic Index have occurred alongside dynamic patterns in injury burden. These results should be used to develop and implement prevention and treatment programme.
Published: 2020

45. A randomized open label trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

Author: Nguyen Phu Huong Lan, Le Thanh Hoang Nhat, Tran Quang Binh, Evelyne Kestelyn, Justin Beardsley, Nguyen Thi Thuy Ngan, David G. Lalloo, Marcel Wolbers, Luong Thi Hue Tai, Nguyen Le Nhu Tung, Nguyen Hoan Phu, Guy E. Thwaites, Damian J. Krysan, Ronald B. Geskus, William W. Hope, Nicholas J. White, Jeremy N. Day, Nguyen Van Vinh Chau, Le Quoc Hung, and Nguyen Thi Hoang Mai
Subjects: 0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Medicine (miscellaneous), General Biochemistry, Genetics and Molecular Biology, Flucytosine, law.invention, Study Protocol, 03 medical and health sciences, Breast cancer, cryptococcal meningitis, Randomized controlled trial, law, Internal medicine, Amphotericin B, fluconazole, medicine, Clinical endpoint, business.industry, Mortality rate, Articles, drug re-purposing, medicine.disease, amphotericin B, 3. Good health, antifungal therapy, Tamoxifen, Crytococcus, 030104 developmental biology, business, Fluconazole, medicine.drug
Abstract: Background: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combinedin vitrowith amphotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with amphotericin and fluconazole.Method: A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with amphotericin (1mg/kg/day) and fluconazole (800mg/day) for the first 2 weeks therapy for HIV infected or uninfected adults with cryptococcal meningitis. The study recruits at Cho Ray Hospital and the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. The primary end point is Early Fungicidal Activity (EFA-the rate of yeast clearance from CSF), over the first two weeks of treatment. 50 patients will be recruited providing ≈80% and 90% power to detect a difference in the EFA of -0.11 or -0.13 log10CFU/ml/day, respectively.Discussion:The results of the study will inform the decision to proceed to a larger trial powered to mortality. The size of effect detectable has previously been associated with reduced mortality from this devastating disease. Particular side effects of interest include QT prolongation.Trial registration: Clinicaltrials.govNCT03112031(11/04/2017)
Published: 2019

46. Correction for Stott et al., 'Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis'

Author: Katharine E. Stott, Freddie Kibengo, Ngo Thi Kim Cuc, Jeremy N. Day, Nguyen Thi Hoang Mai, Nguyen Le Nhu Tung, Justin Beardsley, Ruwanthi Kolamunnage-Dona, Sarah Whalley, and William W. Hope
Subjects: Pharmacology, medicine.medical_specialty, education.field_of_study, business.industry, Population, Gastroenterology, meta-analysis, amphotericin B deoxycholate, Infectious Diseases, cryptococcal meningitis, Pharmacokinetics, population pharmacokinetics, Internal medicine, Amphotericin B deoxycholate, Meta-analysis, pharmacodynamics, medicine, Pharmacology (medical), Cryptococcal meningitis, education, business, pharmacokinetics
Abstract: There is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAmB) for cryptococcal meningitis. A PK study was conducted in n = 42 patients receiving DAmB (1 mg/kg of body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) × weight + 0.67 (0.01) liters/h; volume, 0.82 (0.80) × weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h−1; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h−1. The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility outcomes but not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC144–168) resulted in median (interquartile range) values of 5.83 mg · h/liter (4.66 to 8.55), 10.16 mg · h/liter (8.07 to 14.55), and 14.51 mg · h/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg/kg q24h, respectively. DAmB PK is described adequately by a linear model that incorporates weight with clearance and volume. Interpatient PK variability is modest and unlikely to be responsible for variability in clinical outcomes. There is discordance between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables.
Published: 2018
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47. Correction for Stott et al., 'Population Pharmacokinetics and Cerebrospinal Fluid Penetration of Fluconazole in Adults with Cryptococcal Meningitis'

Author: Justin Beardsley, Jeremy N. Day, Nguyen Le Nhu Tung, William W. Hope, Nguyen Thi Hoang Mai, Ruwanthi Kolamunnage-Dona, Anahi Santoyo Castelazo, Freddie Kibengo, Katharine E. Stott, and Ngo Thi Kim Cuc
Subjects: 0301 basic medicine, Pharmacology, Pediatrics, medicine.medical_specialty, business.industry, Population pharmacokinetics, 03 medical and health sciences, 030104 developmental biology, Infectious Diseases, medicine, Cerebrospinal fluid penetration, Pharmacology (medical), business, Cryptococcal meningitis, Fluconazole, medicine.drug
Abstract: Volume 62, no. 9, e00885-18, 2018, [https://doi.org/10.1128/AAC.00885-18][1]. Page 1: This article was published on 27 August 2018 without Nguyen Le Nhu’ Tung and Ngo Thi Kim Cuc in the author list. The byline was updated in the current version, posted on 5 November 2018. [1]: /lookup/doi/10
Published: 2018
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48. Population Pharmacokinetics and Cerebrospinal Fluid Penetration of Fluconazole in Adults with Cryptococcal Meningitis

Author: Freddie Kibengo, Katharine E. Stott, Ngo Thi Kim Cuc, William W. Hope, Ruwanthi Kolamunnage-Dona, Anahi Santoyo Castelazo, Jeremy N. Day, Justin Beardsley, Nguyen Le Nhu Tung, and Nguyen Thi Hoang Mai
Subjects: Adult, Central Nervous System, Male, 0301 basic medicine, medicine.medical_specialty, Antifungal Agents, 030106 microbiology, Population, Microbial Sensitivity Tests, Meningitis, Cryptococcal, Gastroenterology, Young Adult, 03 medical and health sciences, Pharmacokinetics, Interquartile range, Amphotericin B, Amphotericin B deoxycholate, Internal medicine, medicine, Humans, Uganda, Pharmacology (medical), Author Correction, education, Fluconazole, Aged, Pharmacology, education.field_of_study, business.industry, Liter, Middle Aged, 3. Good health, Drug Combinations, Infectious Diseases, Vietnam, Pharmacodynamics, Cryptococcus neoformans, Cerebrospinal fluid penetration, Drug Therapy, Combination, Female, business, Deoxycholic Acid, medicine.drug
Abstract: Robust population pharmacokinetic (PK) data for fluconazole are scarce. The variability of fluconazole penetration into the central nervous system (CNS) is not known. A fluconazole PK study was conducted in 43 patients receiving oral fluconazole (usually 800 mg every 24 h [q24h]) in combination with amphotericin B deoxycholate (1 mg/kg q24h) for cryptococcal meningitis (CM). A four-compartment PK model was developed, and Monte Carlo simulations were performed for a range of fluconazole dosages. A meta-analysis of trials reporting outcomes of CM patients treated with fluconazole monotherapy was performed. Adjusted for bioavailability, the PK parameter means (standard deviation) were the following: clearance, 0.72 (0.24) liters/h; volume of the central compartment, 18.07 (6.31) liters; volume of the CNS compartment, 32.07 (17.60) liters; first-order rate constant from the central to peripheral compartment, 12.20 (11.17) h-1, from the peripheral to central compartment, 18.10 (8.25) h-1, from the central to CNS compartment, 35.43 (13.74) h-1, and from the CNS to central the compartment, 28.63 (10.03) h-1 Simulations of the area under concentration-time curve resulted in median (interquartile range) values of 1,143.2 (range, 988.4 to 1,378.0) mg · h/liter in plasma (AUCplasma) and 982.9 (range, 781.0 to 1,185.9) mg · h/liter in cerebrospinal fluid (AUCCSF) after a dosage of 1,200 mg q24h. The mean simulated ratio of AUCCSF/AUCplasma was 0.89 (standard deviation [SD], 0.44). The recommended dosage of fluconazole for CM induction therapy fails to attain the pharmacodynamic (PD) target in respect to the wild-type MIC distribution for C. neoformans The meta-analysis suggested modest improvements in both CSF sterility and mortality outcomes with escalating dosage. This study provides the pharmacodynamic rationale for the long-recognized fact that fluconazole monotherapy is an inadequate induction regimen for CM.
Published: 2018

49. Genomics ofCryptococcus neoformans

Author: Lam Tuan Thanh, G Thwaites, Phan Hai Trieu, Nguyen Mai Trinh, Gordon Dougan, Freddie Kibengo, Le Thanh Hoang Nhat, Justin Beardsley, Wirongrong Chierakul, Simon R. Harris, Stephen Baker, David G. Lalloo, Van Anh D, Adrienne K. Chan, Philip M. Ashton, Nguyen Le Nhu Tung, Jeremy N. Day, John R. Perfect, David A. B. Dance, N.V.V. Chau, Catherine Anscombe, and Le Quoc Hung
Subjects: 0303 health sciences, 03 medical and health sciences, 030306 microbiology, Genomics, Computational biology, Biology, 3. Good health, 030304 developmental biology
Abstract: C. neoformansvar.grubii(C. neoformans) is an environmentally acquired pathogen causing 181 000 HIV-associated deaths each year. We used whole genome sequencing (WGS) to characterise 699 isolates, primarilyC. neoformansfrom HIV-infected patients, from 5 countries in Asia and Africa. We found that 91% of our clinical isolates belonged to one of three highly clonal sub-clades of VNIa, which we have termed VNIa-4, VNIa-5 and VNIa-93. Parsimony analysis revealed frequent, long distance transmissions ofC. neoformans; international transmissions took place on 13% of VNIa-4 branches, and intercontinental transmissions on 7% of VNIa-93 branches. The median length of within sub-clade internal branches was 3-6 SNPs, while terminal branches were 44.5-77.5 SNPs. The short median internal branches were partly driven by the large number (12-15% of internal branches) of polytomies in the within-sub-clade trees. To simultaneously explain our observation of no apparent molecular clock, short internal branches and frequent polytomies we hypothesise thatC. neoformansVNIa spends much of its time in the environment in a quiescent state, while, when it is sampled, it has almost always undergone an extended period of growth. Infections with VNIa-93 were associated with a significantly reduced risk of death by 10 weeks compared with infections with VNIa-4 (Hazard Ratio = 0.45, p = 0.003). We detected a recombination in the mitochondrial sequence of VNIa-5, suggesting that mitochondria could be involved in the propensity of this sub-clade to infect HIV-uninfected patients. These data highlight the insight into the biology and epidemiology of pathogenic fungi which can be gained from WGS data.
Published: 2018
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50. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013

Author: Yong Zhao, Hadi Danawi, Bach Xuan Tran, Gene Bukhman, Vasiliki Stathopoulou, Taavi Tillmann, Nelson Alvis-Guzman, Yongmei Li, Jerry Puthenpurakal Abraham, Sudan Prasad Neupane, Jack Caravanos, Ben Schöttker, Rafael Lozano, Damian G Hoy, Yoshihiro Kokubo, Nicholas J K Breitborde, Sergey Soshnikov, Yukito Shinohara, Randall V. Martin, Michael Brainin, Fernando Perez-Ruiz, Yingfeng Zheng, Santosh Mishra, Julio Cesar Montañez Hernandez, Michael Phillips, Belinda J. Gabbe, Hebe N. Gouda, Ziad A. Memish, Rupert R A Bourne, Guoqing Hu, Emmanuel A. Ameh, Abigail McLain, Michelle L. Bell, Christopher Margono, Marissa Iannarone, Wilkister N. Moturi, Donald H. Silberberg, Carl Abelardo T. Antonio, Nataliya Foigt, Anand Dayama, Yanping Wang, Amanda J. Mason-Jones, Bolajoko O. Olusanya, Monica S. Vavilala, Katherine B Gibney, David Tanne, Sidibe S Kany Roseline, Marcella Montico, Abhishek Singh, Sarah Derrett, Alireza Esteghamati, Seok Jun Yoon, Corine Karema, Rakhi Dandona, David M. Pereira, Kazem Rahimi, Gitanjali M. Singh, Vivekanand Jha, John Hornberger, Anne M. Riederer, Kathryn H. Jacobsen, Andrea Pedroza, Lily Alexander, Fiona M. Blyth, Tommi Vasankari, Kyle J Foreman, Rana J. Asghar, Tilahun Nigatu Haregu, Yousef Khader, Rafael Alfonso-Cristancho, Suzanne Barker-Collo, Lydia S. Atkins, Simerjot K. Jassal, Mohammad Ali Sahraian, Peter Scarborough, Hans W. Hoek, E. Ray Dorsey, Muluken Dessalegn, David C. Schwebel, Gavin Shaddick, Thomas D. Fleming, Mohammad Tavakkoli, Dorairaj Prabhakaran, Mohammad H. Forouzanfar, Christopher C. Mapoma, Jost B. Jonas, Erin C Mullany, Gene F. Kwan, Johanna M. Geleijnse, Antonio Luiz Pinho Ribeiro, Roberto Tchio Talongwa, Tolesa Bekele, Jed D. Blore, Gunn Marit Aasvang, Philimon Gona, Miguel Angel Alegretti, Babak Eshrati, Mitsuru Mukaigawara, Richard F. Gillum, Odgerel Chimed-Ochir, Ubai Alsharif, Richard C. Franklin, Felix Masiye, Richard T. Burnett, Sanjay Krishnaswami, Martin McKee, John J Huang, Lucía Cuevas-Nasu, Wagner Marcenes, Walid Ammar, Knud Juel, Joseph R. Zunt, Martha M Téllez Rojo, Mamta Swaroop, Noela M Prasad, Azmeraw T. Amare, Tim Driscoll, Michael Kravchenko, Heresh Amini, Amir Sapkota, Theo Vos, Charlotte Watts, Dennis Odai Laryea, D. Alex Quistberg, Justin Beardsley, Cheng Huang, Adnan M. Durrani, Sarah V Thackway, Rita Van Dingenen, Manami Inoue, Martha Híjar, Honglei Chen, Amany H. Refaat, Yichong Li, Vineet K. Chadha, Wenzhi Wang, Louisa Degenhardt, Kingsley N. Ukwaja, Nayu Ikeda, James D. Wilkinson, Linh N Bui, Maria Hagströmer, Gonghuan Yang, Ann Kristin Knudsen, David J. Margolis, Soewarta Kosen, Hans Kromhout, Atsushi Goto, Man Mohan Mehndiratta, Thomas N. Williams, Michael Soljak, Yun Jin Kim, Hideaki Toyoshima, Jeyaraj D Pandian, Borja del Pozo-Cruz, Soufiane Boufous, Ivy Shiue, Anders Larsson, Guilherme V. Polanczyk, John Powles, Yara A. Halasa, Robin Room, Ratilal Lalloo, Carolina Batis Ruvalcaba, Panniyammakal Jeemon, Elisabete Weiderpass, Jürgen Rehm, Ejaz Ahmad Khan, Alicia Aleman, Zacharie Tsala Dimbuene, Elena Alvarez, Rachelle Buchbinder, Randah R. Hamadeh, Bryan Hubbell, Sadaf G. Sepanlou, Farhad Islami, Costas A. Christophi, Heidi Stöckl, Ismael R. Campos-Nonato, Nigel Bruce, Edward J Mills, Samuel A L Perry, Taavi Lai, Baffour Awuah, Mete Saylan, Karen J. Courville, Arindam Basu, Vanessa De la Cruz-Góngora, Teresita González de Cosío, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Muluken Azage Yenesew, Atte Meretoja, Michael Brauer, Cyrus Cooper, Giorgia Giussani, Valentina S. Arsic Arsenijevic, Vasiliy Victorovich Vlassov, André Karch, Leilei Duan, Matthew M Coates, Omid Ameli, Gelin Xu, Matthias Endres, Ganesan Karthikeyan, Ione Jayce Ceola Schneider, Mohamed Hsairi, Palwasha Anwari, Mazin J. Al Khabouri, Dariush Mozaffarian, Juan R. Sanabria, Pablo M. Lavados, Sumeet S. Chugh, Johan Ärnlöv, Ivo Rakovac, Maurice Giroud, Haidong Kan, Ibrahim Abdelmageem Mohamed Ginawi, José Luis Texcalac-Sangrador, Luigi Naldi, Erica Leigh Slepak, Deena Alasfoor, James E. Saunders, Richard Matzopoulos, Talal Bakfalouni, Stein Emil Vollset, Andrea Werdecker, Lennert J. Veerman, Lorenzo Monasta, Henrica A. F. M. Jansen, Reyna A Gutiérrez, Brittany Wurtz, Luz Maria Sanchez, Lijing L. Yan, M. Patrice Lindsay, Michele Meltzer, Sanjay Basu, Steven van de Vijver, Alaa Badawi, Thomas Claßen, Young-Ho Khang, Brett M. Kissela, Jun Zhu, In-Hwan Oh, Fiona J Charlson, Maria Cecilia Bahit, Dinorah González-Castell, Rosario Cárdenas, Dan Poenaru, Sayed Saidul Alam, Mitchell T. Wallin, Harish Chander Gugnani, James Leigh, Ferrán Catalá-López, Lidia Morawska, Jim van Os, Stephanie J. London, Kaire Innos, Isabelle Romieu, Fiorella Cavalleri, Adrian Davis, Hwee Pin Phua, Chakib Nejjari, Héctor Gómez Dantés, Boris I. Pavlin, Karen Sliwa, Lynne Gaffikin, Constance D. Pond, Michael F. MacIntyre, Blake Thomson, Norberto Perico, Ronny Westerman, Samantha M. Colquhoun, Michael H. Criqui, Ana Maria Nogales Vasconcelos, Wubegzier Mekonnen, Bulat Idrisov, Ana Basto-Abreu, Andrew G. M. Bulloch, Jasvinder A. Singh, Vinod K. Paul, Emin Murat Tuzcu, Svetlana Popova, Hmwe H Kyu, Richard L. Guerrant, Mohammed I. Albittar, Srikanth Mangalam, Steven E. Lipshultz, Lela Sturua, Semaw Ferede Abera, Eduardo Bernabé, George D. Thurston, Bruno F. Sunguya, Tiffany Ku, Alejandra G. Contreras, Abdullah Sulieman Terkawi, Charles Atkinson, Ashkan Afshin, Heidi J. Larson, Abdullatif Husseini, Jose C. Adsuar, Reza Assadi, Ademola Lukman Adelekan, Joshua A. Salomon, Yousef M. Elshrek, Gokalp Kadri Yentur, Devina Nand, Narayanaswamy Venketasubramanian, Graça Maria Ferreira De Lima, Maheswar Satpathy, Fotis Topouzis, Traolach S. Brugha, Hywel C Williams, Coen H. Van Gool, Andrew H. Kemp, Awoke Misganaw, Amado D Quezada, Norito Kawakami, Bert Brunekreef, Peter Burney, Tati S. Warouw, Jongmin Lee, Inga Dora Sigfusdottir, Marcel Tanner, Solveig A. Cunningham, Benjamin O. Anderson, Tariku Jibat Beyene, Lars Barregard, Xia Wan, Giuseppe Remuzzi, Bernadette Thomas, Lilia S Pedraza, Massimo Cirillo, Alina Rodriguez, Ricky Leung, Farshad Pourmalek, K. Srinath Reddy, Charles D.A. Wolfe, Ulrich O Mueller, Neeraj Bedi, Al Artaman, Lucia Hernandez, Itamar S. Santos, C. Arden Pope, Norlinah Mohamed Ibrahim, Carlo Irwin A. Panelo, Selen Begüm Uzun, Miltiadis K. Tsilimbaris, Anwar Rafay, Daniel Dicker, Melvin Barrientos Marzan, Sajjad Ur Rahman, Mohammed O. Basulaiman, Edgar P. Simard, Mohammad T Mashal, Maysaa El Sayed Zaki, Shiwei Liu, Don C. Des Jarlais, Bo Norrving, Salvador Villalpando, Miia Kivipelto, Yang Liu, Carolina Maria Teixeira, Catalina Medina, Sudha Jayaraman, Josep Maria Haro, Diego De Leo, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Mukesh Dherani, Ljiljana Pejin Stokic, Vinay Nangia, Sukanta Saha, Juan Liang, Elisabeth Cardis, Zourkaleini Younoussi, José R Nogueira, Braden Te Ao, Vasco Manuel Pedro Machado, Lionel Racapé, Ting Wu Chuang, Shahab Khatibzadeh, E Filipa de Castro, Barthelemy Kuate Defo, Ulises Trujillo, Alan D. Lopez, Soraya Seedat, Lope H Barrero, Linhong Wang, Daniel Pope, Alexandra Brazinova, Faris Lami, Valentina Colistro, G Anil Kumar, Derek F J Fay, Haidong Wang, Hwashin H. Shin, Raimundas Lunevicius, Suzanne Polinder, Dietrich Plass, David Rojas-Rueda, Stephen S Lim, Tania G Sánchez-Pimienta, K.M. Venkat Narayan, Yuantao Hao, Jung-Chen Chang, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Luciano A. Sposato, Stan Biryukov, Kunihiro Matsushita, Beth E. Ebel, Cleusa P. Ferri, Soumya Swaminathan, K. Ryan Wessells, Gustavo Velasquez-Melendez, Leslie T. Cooper, David O. Carpenter, Nancy Lopez, Bryan L. Sykes, Sandra Nolte, Murray B. Stein, Paul N. Jensen, Fabiola Mejía-Rodríguez, Xiaonong Zou, Bradford D. Gessner, Dhruv S. Kazi, Dragos Virgil Davitoiu, Alejandra Jáuregui, Pouria Heydarpour, Megan Bohensky, Harvey Whiteford, Berrak Bora Basara, Zhengming Chen, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Nima Hafezi-Nejad, John Nelson Opio, Scott Weichenthal, Deborah Salvo, Jun She, Tea Lallukka, Carolyn C. Gotay, Stephen G. Waller, Christian Kieling, Shivanthi Balalla, Valery L. Feigin, Qing Lan, Matias Trillini, Adam D M Briggs, Sungroul Kim, Niveen M E Abu-Rmeileh, Renata Micha, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Zulfiqar A Bhutta, Paul S. F. Yip, Grant Nguyen, Ralph L. Sacco, Biju Abraham, Ken Takahashi, Jixiang Ma, Peter A. Meaney, Ayse Abbasoglu Ozgoren, Kimberly Cooperrider, M Rifat Kose, Shams Eldin Ali Hassan Khalifa, Rasmus Havmoeller, Alize J. Ferrari, Kebede Deribe, Nadim E. Karam, George A. Mensah, Bongani M. Mayosi, Konrad Pesudovs, Joanna Moschandreas, Ziad Nahas, James Damsere-Derry, Nsanzimana Sabin, Tonatiuh Barrientos-Gutiérrez, Ying Jiang, Andre Pascal Kengne, Peter Allebeck, Jonas Minet Kinge, Shankuan Zhu, Guy B. Marks, Daniel C Casey, Marco A Avila, Anna Roca, Lalit Dandona, Ami R. Moore, Adansi A. Amankwaa, David Gunnell, Andre Keren, Yohannes Adama Melaku, Nhung T Nguyen, Anthony D. Woolf, Mayuree Rao, Peter J. Allen, Christina Papachristou, Karzan Abdulmuhsin Mohammad, Ravi Kumar Balu, Marie Ng, Marcello Tonelli, Maziar Moradi-Lakeh, Maigeng Zhou, Emmanuela Gakidou, Mohammed K. Ali, Amanda W Pain, Dan J. Stein, Kawkab Shishani, Fortuné Gbètoho Gankpé, Howard J. Hoffman, James Scott, Nadine Steckling, Samia Alhabib, Deborah Jarvis, Kara Estep, Arsène Kouablan Adou, Ricardo Orozco, Holly Hagan, K. C. Astha, Reza Malekzadeh, Klara Dokova, Aliya Naheed, Ernst J. Kuipers, Valeria Caso, Derrick A Bennett, Andrea B. Feigl, Uche S. Uchendu, Holly E. Erskine, Shireen Sindi, Arjun Lakshmana Balaji, Francesco Saverio Violante, Monika Sawhney, Alejandra Cantoral, Ketevan Goginashvili, Raghib Ali, Fan Jiang, Robert G. Weintraub, Homie Razavi, Myriam Tobollik, Howard Hu, Emerito Jose A. Faraon, Irma Khonelidze, Patricia M. Riccio, Eun-Kee Park, Julio Cesar Campuzano, Ibrahim Abubakar, Jürgen C Schmidt, Konstantinos Stroumpoulis, Aref A. Bin Abdulhak, Graeme J. Hankey, Natan M. Bornstein, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Alanur Çavlin, Ruth W Kimokoti, Samir Soneji, Mark J. Nieuwenhuijsen, John Q. Wong, Joseph Frostad, Tom Achoki, Rahman Shiri, Ashish Bhalla, Kurt Straif, Simon I. Hay, Scott B. Patten, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Chandrashekhar T Sreeramareddy, Ryan M Barber, Rosana E. Norman, JianLi Wang, Siyi Shangguan, Luke Nyakarahuka, Kovin Naidoo, Charles D. H. Parry, Mercedes Colomar, H. Ross Anderson, Carlos Magis-Rodriguez, Joan M. Nolla, Muhammad Imran Nisar, Karen Devries, Andrew L. Thorne-Lyman, Denis Nash, Marape Marape, Rajiv Chowdhury, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Daniel Kim, Yuichiro Yano, Luke D. Knibbs, Margaret Robinson, Hilda L Harb, Rogelio Pérez-Padilla, Janet L Leasher, Jonathan L. Wright, Peter Brooks, Cristiana Abbafati, Belinda K Lloyd, Victor Aboyans, Nikhil Tandon, Charles R. Newton, Simón Barquera, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Glen Mola, Paulo A. Lotufo, Burcu Kucuk Bicer, Peggy Pei-Chia Chiang, Alexander Kraemer, Solomon Meseret Woldeyohannes, Saman Fahimi, Lesley Rushton, Kim Moesgaard Iburg, Vafa Rahimi-Movaghar, Logan Sandar, Bruce Neal, Teresa Shamah Levy, Karen M. Tabb, Jeffrey A. Towbin, Christopher J L Murray, Ramesh Sahathevan, Aaron Cohen, Chanda Kulkarni, Van C. Lansingh, François Alla, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Uchechukwu K.A. Sampson, Rajeev Gupta, Neil Pearce, Mustafa Z. Younis, Veena S. Kulkarni, Francisco A García-Guerra, Amanda G. Thrift, Stefan Ma, Samaya Ismayilova, Evariste Gasana, Amitava Banerjee, Aslam Pervaiz, Emilie Agardh, Abraham D. Flaxman, Farshad Farzadfar, Peter W. Gething, Ileana Heredia-Pi, Boris Bikbov, Wanqing Chen, Saad B. Omer, Ruben Castro, Neeraj Bhala, Sara Sheikhbahaei, Hilton Lam, Urbano Fra Paleo, Lidia Sanchez-Riera, Alicia Elena Beatriz Lawrynowicz, Kristen Delwiche, Richard G. Ellenbogen, Max Petzold, Yuri Y Varakin, Guilherme Borges, Guohong Jiang, Francis Guillemin, Kyle R. Heuton, Yohannes Kinfu, Victoria F Bachman, Joseph A Wagner, Carlos A Castañeda-Orjuela, Leonardo Trasande, Abbas Ali Mahdi, Josef Coresh, Chuanhua Yu, Kenji Shibuya, Berrin Serdar, Laetitia Huiart, Xiaofeng Liang, Jean de Dieu Ngirabega, Takayoshi Ohkubo, Natalie Stephens, Francis Apolinary Mhimbira, Jefferson Traebert, Amiran Gamkrelidze, Kjetil Søreide, Samath D Dharmaratne, Robert P. Dellavalle, George Mugambage Ruhago, Lakshmi Vijayakumar, Joannie Lortet-Tieulent, Dipan Bose, Tania C Aburto, Saleem M Rana, Miriam Levi, Mohammad Taghi Hedayati, Rodolfo S Pagcatipunan, Ron T. Gansevoort, H. D. Hosgood, Michael Burch, Mohsen Naghavi, Vegard Skirbekk, Ayfer Pekericli, Walter Mendoza, Pengpeng Ye, Gabrielle deVeber, Ali H. Mokdad, David M. Broday, Koranteng Adofo, Zewdie Aderaw Alemu, Shifalika Goenka, Carrie Beth Peterson, Nicolas J. C. Stapelberg, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Giancarlo Logroscino, Kardiyoloji, Peterson, Carrie B., Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Wisconsin Division of Public Health, Laboratoire de psychologie sociale et de psychologie cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), London South Bank University, Metropolitan Police Service, Hong Kong Baptist University (HKBU), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Insight Centre for Data Analytics [Galway] (INSIGHT), National University of Ireland [Galway] (NUI Galway), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institute, karolinska institute, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Computer Science Department [Bristol], University of Bristol [Bristol], Universität Mannheim [Mannheim], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Computational Science and Engineering Department [Daresbury] (STFC), Science & Technologie Facilities Council, Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Southampton, Imperial College London, Neurology Department, Ichilov Medical Center, Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Risk Assessment Sciences Institute, Utrecht University [Utrecht], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], CIBER de Epidemiología y Salud Pública (CIBERESP), STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tennent Institute of Ophthalmology, National University of Singapore (NUS), Centre de Robotique (CAOR), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Multidisciplinary Nanotechnology Centre, Swansea University, Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Genomics Research Center, Academia Sinica, Neuro Rehab Services LLP [New Delhi], Department of Signal Theory and Communications (TSC), Univ. Politec. de Catalunya, King‘s College London, Dept. Mat. Engn. De Ma, Sao Carlos, Fed. Univ. Sao Carlos UFSCar, RESPEC (RESPEC), RESPEC, Advanced Laboratories on Embedded Systems [Roma] (ALES), Department of Biology [Miami], University of Miami [Coral Gables], Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Department of Nephrology, University Medical Center, University of Groningen, Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] (WUR), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], College of Medicine, University of Hail, Saudi Arabia, Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] (UPC), Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University-Shahid Beheshti University, Center for Applied Medical Research (CIMA), University of Tehran, Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, George Washington University (GW), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent [Ghent], Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Fachbereich Physik [Berlin], Freie Universität Berlin, Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), Univ New Delhi, School of Physics and Astronomy, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center (TRDDC), TCS Innovation Labs, University of Helsinki, Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency (FOI), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Novartis Pharmaceutical Corporation, Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble [1985-2015] (OSUG [1985-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), College of Information and Electrical Engineering [Beijing] (CIEE), China Agricultural University (CAU), Thales Research and Technology [Palaiseau], THALES, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), École supérieure du professorat et de l'éducation - Académie de Grenoble [2013-2019] (ESPE Grenoble [2013-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], American University of Beirut [Beyrouth] (AUB), Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Mailman School of Public Health, Columbia University [New York], The Georges Institute for International Health, The University of Sydney, Department of epidemiology and Public Health, Faculty of Medicine, Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Department of Neurology Lunds University Hospital Lund, Unit of Functional Bionanomaterials, School of Biosciences, University of Birmingham [Birmingham], Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], World Health Organization, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nordic School of Public Health, The James Hutton Institute, Horia Hulubei National Institute for Physics and Nuclear Engineering, Department of Pediatrics, University of Washington [Seattle], Institute of Public Health, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Dept.of Computer Science, Indian Institute of Technology Madras (IIT Madras), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut geològic de Catalunya (IGC), Institut Geològic de Catalunya-IGC, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Politecnico di Milano [Milan] (POLIMI), Symantec, University of Oviedo, European Microsoft Innovation Center (EMIC), Microsoft Corporation [Redmond, Wash.], Technion - Israel Institute of Technology [Haifa], Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Department of Physics, Cavendish Laboratory, University of Cambridge [UK] (CAM), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling (CMM), Department of Global Health and Development, London School of Hygiene and Tropical Medicine (LSHTM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Universidade Federal de Pernambuco [Recife] (UFPE), Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute (NEST), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology (LICB), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] (KTH ), NICTA [Eveleigh], National ICT Australia [Sydney] (NICTA), Division of Solid Mechanics, Lund University [Lund], University of Calgary, BioWare Corp, Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Neurorestoration Group, Wolfson Centre for Age-related Diseases-King‘s College London, Electronic Navigation Research Institute (ENRI), Ministry of Land, Infrastructure, Transport and Tourism, Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Centre for Undergraduate Studies, University of the Punjab, Siemens Corporate Research, Siemens AG [Munich], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), Department of Materials Science, Sichuan University [Chengdu] (SCU), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Shahid Beheshti University of Medical Sciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH)-Universidad del Desarrollo, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), California Institute of Technology (CALTECH)-NASA, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), King‘s College London-Wolfson Centre for Age-related Diseases, Sichuan University, Universitat de Barcelona, Interne Geneeskunde, Medische Sociologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), RS: MHeNs - R2 - Mental Health, Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychologie sociale et de psychologie cognitive ( LAPSCO ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Erosion torrentielle neige et avalanches ( UR ETGR ), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), Hong Kong Baptist University ( HKBU ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Insight Centre for Data Analytics (National University of Ireland Galway (NUIG)) ( INSIGHT ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oslo ( UiO ) -University of Oslo ( UiO ), Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Computational Science and Engineering Department [Daresbury] ( STFC ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], University of Southampton [Southampton], Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University Medical Center Utrecht, Biologie Fonctionnelle et Adaptative ( BFA ), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), National University of Singapore ( NUS ), Centre de Robotique ( CAOR ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Department of Signal Theory and Communications ( TSC ), RESPEC ( RESPEC ), Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Wageningen University and Research Centre [Wageningen] ( WUR ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Freie Universität Berlin [Berlin], Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Tata Research Development and Design Center ( TRDDC ), Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Swedish Defense Research Agency ( FOI ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Novartis Pharmaceutical Corp., East Hanover NJ 07936, USA, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mechanical and Automation Engineering ( CAD Laboratory ), National Institutes of Health ( NIH ), Centre d'étude et de recherche en informatique et communications ( CEDRIC ), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise ( ENSIIE ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), College of Information and Electrical Engineering [Beijing] ( CIEE ), China Agricultural University ( CAU ), Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), PennState University [Pennsylvania] ( PSU ), Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), American University of Beirut [Beyrouth], The University of Sydney [Sydney], Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Center for Research in Environmental Epidemiology ( CREAL ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Indian Institute of Technology Madras ( IIT Madras ), Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Laboratoire de Génie Informatique et Ingénierie de Production ( LGI2P ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Institut geològic de Catalunya ( IGC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie et Génomique des Poissons ( LPGP ), Institut National de la Recherche Agronomique ( INRA ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Politecnico di Milano [Milan], European Microsoft Innovation Center ( EMIC ), Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), University of Cambridge [UK] ( CAM ), Laboratoire de Probabilités et Modèles Aléatoires ( LPMA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), London School of Hygiene and Tropical Medicine ( LSHTM ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Nanoscience Institute ( NEST ), Laboratory Of Immune Cell Biology ( LICB ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ), Bonn Universität [Bonn], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), Royal Institute of Technology [Stockholm] ( KTH ), National ICT Australia [Sydney] ( NICTA ), Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), Children’s Hospital of Philadelphia ( CHOP ), Univeristy of Pennsylvania Medical School, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Medical College of Georgia, Electronic Navigation Research Institute ( ENRI ), Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), University of Massachusetts [Boston] ( UMass Boston ), Forouzanfar, Mohammad H, Alexander, Lily, Anderson, H. Ro, Bachman, Victoria F, Biryukov, Stan, Brauer, Michael, Burnett, Richard, Casey, Daniel, Coates, Matthew M, Cohen, Aaron, Delwiche, Kristen, Estep, Kara, Frostad, Joseph J, Kc, Astha, Kyu, Hmwe H, Moradi Lakeh, Maziar, Ng, Marie, Slepak, Erica Leigh, Thomas, Bernadette A, Wagner, Joseph, Aasvang, Gunn Marit, Abbafati, Cristiana, Ozgoren, Ayse Abbasoglu, Abd Allah, Foad, Abera, Semaw F, Aboyans, Victor, Abraham, Biju, Abraham, Jerry Puthenpurakal, Abubakar, Ibrahim, Abu Rmeileh, Niveen M. E, Aburto, Tania C, Achoki, Tom, Adelekan, Ademola, Adofo, Koranteng, Adou, Arsène K, Adsuar, José C, Afshin, Ashkan, Agardh, Emilie E, Al Khabouri, Mazin J, Al Lami, Faris H, Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I, Alegretti, Miguel A, Aleman, Alicia V, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Ali, Mohammed K, Alla, Françoi, Allebeck, Peter, Allen, Peter J, Alsharif, Ubai, Alvarez, Elena, Alvis Guzman, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Ameh, Emmanuel A, Ameli, Omid, Amini, Heresh, Ammar, Walid, Anderson, Benjamin O, Antonio, Carl Abelardo T, Anwari, Palwasha, Cunningham, Solveig Argeseanu, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Atkinson, Charle, Avila, Marco A, Awuah, Baffour, Badawi, Alaa, Bahit, Maria C, Bakfalouni, Talal, Balakrishnan, Kalpana, Balalla, Shivanthi, Balu, Ravi Kumar, Banerjee, Amitava, Barber, Ryan M, Barker Collo, Suzanne L, Barquera, Simon, Barregard, Lar, Barrero, Lope H, Barrientos Gutierrez, Tonatiuh, Basto Abreu, Ana C, Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O, Ruvalcaba, Carolina Bati, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Benjet, Corina, Bennett, Derrick A, Benzian, Habib, Bernabé, Eduardo, Beyene, Tariku J, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A, Bikbov, Bori, Abdulhak, Aref A. Bin, Blore, Jed D, Blyth, Fiona M, Bohensky, Megan A, Başara, Berrak Bora, Borges, Guilherme, Bornstein, Natan M, Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J, Brenner, Hermann, Briggs, Adam D. M, Broday, David M, Brooks, Peter M, Bruce, Nigel G, Brugha, Traolach S, Brunekreef, Bert, Buchbinder, Rachelle, Bui, Linh N, Bukhman, Gene, Bulloch, Andrew G, Burch, Michael, Burney, Peter G. J, Campos Nonato, Ismael R, Campuzano, Julio C, Cantoral, Alejandra J, Caravanos, Jack, Cárdenas, Rosario, Cardis, Elisabeth, Carpenter, David O, Caso, Valeria, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chen, Honglei, Chen, Wanqing, Chen, Zhengming, Chiang, Peggy P, Chimed Ochir, Odgerel, Chowdhury, Rajiv, Christophi, Costas A, Chuang, Ting Wu, Chugh, Sumeet S, Cirillo, Massimo, Claßen, Thomas Kd, Colistro, Valentina, Colomar, Mercede, Colquhoun, Samantha M, Contreras, Alejandra G, Cooper, Cyru, Cooperrider, Kimberly, Cooper, Leslie T, Coresh, Josef, Courville, Karen J, Criqui, Michael H, Cuevas Nasu, Lucia, Damsere Derry, Jame, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I, Davis, Adrian, Davitoiu, Dragos V, Dayama, Anand, de Castro, E. Filipa, De la Cruz Góngora, Vanessa, De Leo, Diego, de Lima, Graça, Degenhardt, Louisa, Del Pozo Cruz, Borja, Dellavalle, Robert P, Deribe, Kebede, Derrett, Sarah, Jarlais, Don C. De, Dessalegn, Muluken, Deveber, Gabrielle A, Devries, Karen M, Dharmaratne, Samath D, Dherani, Mukesh K, Dicker, Daniel, Ding, Eric L, Dokova, Klara, Dorsey, E. Ray, Driscoll, Tim R, Duan, Leilei, Durrani, Adnan M, Ebel, Beth E, Ellenbogen, Richard G, Elshrek, Yousef M, Endres, Matthia, Ermakov, Sergey P, Erskine, Holly E, Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose A, Farzadfar, Farshad, Fay, Derek F. 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Subjects: Male, Fine particulate matter, Nutrition and Disease, MESH : Sanitation, Health Behavior, Diseases, MESH: Metabolic Diseases, MESH: Global Health, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Global Health, MESH : Nutritional Status, MESH: Occupational Exposure, 0302 clinical medicine, Unsafe Sex, MESH: Risk Factors, Risk Factors, Voeding en Ziekte, Medicine, Air-pollution, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, Sanitation, Wasting, 2. Zero hunger, Factors de risc en les malalties, Medicine (all), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, MESH : Occupational Diseases, MESH: Nutritional Status, All-cause mortality, MESH : Risk Factors, humanities, Environmental Exposure, Female, Humans, Metabolic Diseases, Nutritional Status, Occupational Diseases, Occupational Exposure, Risk Assessment, Tobacco smoking, 3. Good health, Nutritional Statu, MESH : Occupational Exposure, MESH : Metabolic Diseases, Cohort, medicine.symptom, Risk assessment, Blood-pressure, Human, MESH: Occupational Diseases, Risk factors in diseases, Coronary-heart-disease, MESH : Male, MESH: Health Behavior, MESH: Environmental Exposure, Population health, Body-mass index, 03 medical and health sciences, Household cooking, Cardiovascular-disease, Environmental health, General & Internal Medicine, parasitic diseases, Life Science, MESH: Sanitation, Risk factor, MESH : Health Behavior, VLAG, GBD2013, MESH: Humans, business.industry, Risk Factor, Global Burden of Disease Study, 79 behavioural, environmental and occupational, and metabolic risks, Long-term exposure, MESH : Humans, CAUSE-SPECIFIC MORTALITY, MESH: Male, Metabolic Disease, Occupational Disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MALE BRITISH DOCTORS, Years of potential life lost, Relative risk, Malalties, MESH : Global Health, OUTDOOR AIR-POLLUTION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Environmental Exposure, MESH: Female
Abstract: Summary Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation. Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the fi rst of a series of annual updates of the GBD. Risk factor quantifi cation, particularly of modifi able risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the fi rst level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular fi ltration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation.
Published: 2015
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