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6. Estimating the COVID-19 infection fatality ratio accounting for seroreversion using statistical modelling

Author

Brazeau, Nicholas F., Verity, Robert, Jenks, Sara, Fu, Han, Whittaker, Charles, Winskill, Peter, Dorigatti, Ilaria, Walker, Patrick G. T., Riley, Steven, Schnekenberg, Ricardo P., Hoeltgebaum, Henrique, Mellan, Thomas A., Mishra, Swapnil, Unwin, H. Juliette T., Watson, Oliver J., Cucunubá, Zulma M., Baguelin, Marc, Whittles, Lilith, Bhatt, Samir, Ghani, Azra C., Ferguson, Neil M., and Okell, Lucy C.

Published
2022
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7. Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

Author

Lavezzo, Enrico, Pacenti, Monia, Manuto, Laura, Boldrin, Caterina, Cattai, Margherita, Grazioli, Marco, Bianca, Federico, Sartori, Margherita, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Vanuzzo, Maria Cristina, Lisi, Vittoria, Antonello, Maria, Grimaldi, Carmela Ileana, Zulian, Chiara, Del Vecchio, Claudia, Plebani, Mario, Padoan, Andrea, Cirillo, Daniela Maria, Brazzale, Alessandra R., Tonon, Giovanni, Toppo, Stefano, Dorigatti, Ilaria, and Crisanti, Andrea

Published
2022
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12. Database of epidemic trends and control measures during the first wave of COVID-19 in mainland China

Author

Fu, Han, Wang, Haowei, Xi, Xiaoyue, Boonyasiri, Adhiratha, Wang, Yuanrong, Hinsley, Wes, Fraser, Keith J., McCabe, Ruth, Olivera Mesa, Daniela, Skarp, Janetta, Ledda, Alice, Dewé, Tamsin, Dighe, Amy, Winskill, Peter, van Elsland, Sabine L., Ainslie, Kylie E.C., Baguelin, Marc, Bhatt, Samir, Boyd, Olivia, Brazeau, Nicholas F., Cattarino, Lorenzo, Charles, Giovanni, Coupland, Helen, Cucunuba, Zulma M., Cuomo-Dannenburg, Gina, Donnelly, Christl A., Dorigatti, Ilaria, Eales, Oliver D., FitzJohn, Richard G., Flaxman, Seth, Gaythorpe, Katy A.M., Ghani, Azra C., Green, William D., Hamlet, Arran, Hauck, Katharina, Haw, David J., Jeffrey, Benjamin, Laydon, Daniel J., Lees, John A., Mellan, Thomas, Mishra, Swapnil, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Okell, Lucy, Parag, Kris V., Ragonnet-Cronin, Manon, Riley, Steven, Schmit, Nora, Thompson, Hayley A., Unwin, H.Juliette T., Verity, Robert, Vollmer, Michaela A.C., Volz, Erik, Walker, Patrick G.T., Walters, Caroline E., Watson, Oliver J., Whittaker, Charles, Whittles, Lilith K., Imai, Natsuko, Bhatia, Sangeeta, and Ferguson, Neil M.

Published
2021
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13. Estimates of the severity of coronavirus disease 2019: a model-based analysis

Author

Verity, Robert, Okell, Lucy C, Dorigatti, Ilaria, Winskill, Peter, Whittaker, Charles, Imai, Natsuko, Cuomo-Dannenburg, Gina, Thompson, Hayley, Walker, Patrick G T, Fu, Han, Dighe, Amy, Griffin, Jamie T, Baguelin, Marc, Bhatia, Sangeeta, Boonyasiri, Adhiratha, Cori, Anne, Cucunubá, Zulma, FitzJohn, Rich, Gaythorpe, Katy, Green, Will, Hamlet, Arran, Hinsley, Wes, Laydon, Daniel, Nedjati-Gilani, Gemma, Riley, Steven, van Elsland, Sabine, Volz, Erik, Wang, Haowei, Wang, Yuanrong, Xi, Xiaoyue, Donnelly, Christl A, Ghani, Azra C, and Ferguson, Neil M

Published
2020
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15. Unveiling Post-COVID-19 Syndrome: Incidence, Biomarkers, and Clinical Phenotype in a Thai Population

Author

Sangkaew, Sorawat, primary, Tamviriyakul, Hathaitip, additional, Cheranakorn, Chutima, additional, Songumpai, Nopporn, additional, Pinpathomrat, Nawamin, additional, Seeyankem, Bunya, additional, Yasharad, Kameelah, additional, Loomcharoen, Palanthorn, additional, Pakdee, Wisitsak, additional, Changawej, Chanunya, additional, Dumrongkullachart, Dararat, additional, Limheng, Amornrat, additional, and Dorigatti, Ilaria, additional

Published
2024
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16. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

Author

Flasche, Stefan, Jit, Mark, Rodríguez-Barraquer, Isabel, Coudeville, Laurent, Recker, Mario, Koelle, Katia, Milne, George, Hladish, Thomas J, Perkins, T Alex, Cummings, Derek AT, Dorigatti, Ilaria, Laydon, Daniel J, España, Guido, Kelso, Joel, Longini, Ira, Lourenco, Jose, Pearson, Carl AB, Reiner, Robert C, Mier-Y-Terán-Romero, Luis, Vannice, Kirsten, and Ferguson, Neil

Subjects
Humans, Vaccines, Synthetic, Vaccines, Attenuated, Vaccination, Seroepidemiologic Studies, Public Health, Safety, Models, Theoretical, Child, Cost-Benefit Analysis, Dengue Vaccines, Vaccines, Synthetic, Attenuated, Models, Theoretical, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundLarge Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.Methods and findingsThe models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines.ConclusionsDengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.

Published
2016

17. Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment

Author

Ferguson, Neil M, Rodríguez-Barraquer, Isabel, Dorigatti, Ilaria, Mier-Y-Teran-Romero, Luis, Laydon, Daniel J, and Cummings, Derek AT

Subjects
Rare Diseases, Infectious Diseases, Biotechnology, Clinical Research, Immunization, Vector-Borne Diseases, Orphan Drug, Prevention, Biodefense, Emerging Infectious Diseases, Vaccine Related, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adolescent, Child, Child, Preschool, Clinical Trials as Topic, Dengue, Dengue Vaccines, Dengue Virus, Hospitalization, Humans, Immunogenicity, Vaccine, Models, Theoretical, Risk Assessment, Vaccination, Vaccines, Attenuated, General Science & Technology
Abstract

The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe "secondary-like" infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when seronegative. However, in high-transmission settings, vaccination benefits both the whole population and seronegative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.

Published
2016

19. Reduction in mobility and COVID-19 transmission

Author

Nouvellet, Pierre, Bhatia, Sangeeta, Cori, Anne, Ainslie, Kylie E. C., Baguelin, Marc, Bhatt, Samir, Boonyasiri, Adhiratha, Brazeau, Nicholas F., Cattarino, Lorenzo, Cooper, Laura V., Coupland, Helen, Cucunuba, Zulma M., Cuomo-Dannenburg, Gina, Dighe, Amy, Djaafara, Bimandra A., Dorigatti, Ilaria, Eales, Oliver D., van Elsland, Sabine L., Nascimento, Fabricia F., FitzJohn, Richard G., Gaythorpe, Katy A. M., Geidelberg, Lily, Green, William D., Hamlet, Arran, Hauck, Katharina, Hinsley, Wes, Imai, Natsuko, Jeffrey, Benjamin, Knock, Edward, Laydon, Daniel J., Lees, John A., Mangal, Tara, Mellan, Thomas A., Nedjati-Gilani, Gemma, Parag, Kris V., Pons-Salort, Margarita, Ragonnet-Cronin, Manon, Riley, Steven, Unwin, H. Juliette T., Verity, Robert, Vollmer, Michaela A. C., Volz, Erik, Walker, Patrick G. T., Walters, Caroline E., Wang, Haowei, Watson, Oliver J., Whittaker, Charles, Whittles, Lilith K., Xi, Xiaoyue, Ferguson, Neil M., and Donnelly, Christl A.

Published
2021
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20. Author Correction: SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

Author

Dorigatti, Ilaria, Lavezzo, Enrico, Manuto, Laura, Ciavarella, Constanze, Pacenti, Monia, Boldrin, Caterina, Cattai, Margherita, Saluzzo, Francesca, Franchin, Elisa, Del Vecchio, Claudia, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Guglielmo, Simone, Fascina, Mariateresa, Grazioli, Marco, Alvisi, Gualtiero, Vanuzzo, Maria Cristina, Zupo, Tiziano, Calandrin, Reginetta, Lisi, Vittoria, Rossi, Lucia, Castagliuolo, Ignazio, Merigliano, Stefano, Unwin, H. Juliette T., Plebani, Mario, Padoan, Andrea, Brazzale, Alessandra R., Toppo, Stefano, Ferguson, Neil M., Donnelly, Christl A., and Crisanti, Andrea

Published
2021
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21. SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

Author

Dorigatti, Ilaria, Lavezzo, Enrico, Manuto, Laura, Ciavarella, Constanze, Pacenti, Monia, Boldrin, Caterina, Cattai, Margherita, Saluzzo, Francesca, Franchin, Elisa, Del Vecchio, Claudia, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Guglielmo, Simone, Fascina, Mariateresa, Grazioli, Marco, Alvisi, Gualtiero, Vanuzzo, Maria Cristina, Zupo, Tiziano, Calandrin, Reginetta, Lisi, Vittoria, Rossi, Lucia, Castagliuolo, Ignazio, Merigliano, Stefano, Unwin, H. Juliette T., Plebani, Mario, Padoan, Andrea, Brazzale, Alessandra R., Toppo, Stefano, Ferguson, Neil M., Donnelly, Christl A., and Crisanti, Andrea

Published
2021
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22. A simulation-based method to inform serosurvey designs for estimating the force of infection using existing blood samples

Author

Vicco, Anna, primary, McCormack, Clare P., additional, Pedrique, Belen, additional, Amuasi, John H., additional, Awuah, Anthony Afum-Adjei, additional, Obirikorang, Christian, additional, Struck, Nicole S., additional, Lorenz, Eva, additional, May, Jürgen, additional, Ribeiro, Isabela, additional, Malavige, Gathsaurie Neelika, additional, Donnelly, Christl A., additional, and Dorigatti, Ilaria, additional

Published
2023
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23. Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018

Author

Moreira, Filipe Romero Rebello, primary, Menezes, Mariane Talon de, additional, Salgado-Benvindo, Clarisse, additional, Whittaker, Charles, additional, Cox, Victoria, additional, Chandradeva, Nilani, additional, Paula, Hury Hellen Souza de, additional, Martins, André Frederico, additional, Chagas, Raphael Rangel das, additional, Brasil, Rodrigo Decembrino Vargas, additional, Cândido, Darlan da Silva, additional, Herlinger, Alice Laschuk, additional, Ribeiro, Marisa de Oliveira, additional, Arruda, Monica Barcellos, additional, Alvarez, Patricia, additional, Tôrres, Marcelo Calado de Paula, additional, Dorigatti, Ilaria, additional, Brady, Oliver, additional, Voloch, Carolina Moreira, additional, Tanuri, Amilcar, additional, Iani, Felipe, additional, Souza, William Marciel de, additional, Cardozo, Sergian Vianna, additional, Faria, Nuno Rodrigues, additional, and Aguiar, Renato Santana, additional

Published
2023
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26. State-level tracking of COVID-19 in the United States

Author

Unwin, H. Juliette T., Mishra, Swapnil, Bradley, Valerie C., Gandy, Axel, Mellan, Thomas A., Coupland, Helen, Ish-Horowicz, Jonathan, Vollmer, Michaela A. C., Whittaker, Charles, Filippi, Sarah L., Xi, Xiaoyue, Monod, Mélodie, Ratmann, Oliver, Hutchinson, Michael, Valka, Fabian, Zhu, Harrison, Hawryluk, Iwona, Milton, Philip, Ainslie, Kylie E. C., Baguelin, Marc, Boonyasiri, Adhiratha, Brazeau, Nick F., Cattarino, Lorenzo, Cucunuba, Zulma, Cuomo-Dannenburg, Gina, Dorigatti, Ilaria, Eales, Oliver D., Eaton, Jeffrey W., van Elsland, Sabine L., FitzJohn, Richard G., Gaythorpe, Katy A. M., Green, William, Hinsley, Wes, Jeffrey, Benjamin, Knock, Edward, Laydon, Daniel J., Lees, John, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Okell, Lucy, Parag, Kris V., Siveroni, Igor, Thompson, Hayley A., Walker, Patrick, Walters, Caroline E., Watson, Oliver J., Whittles, Lilith K., Ghani, Azra C., Ferguson, Neil M., Riley, Steven, Donnelly, Christl A., Bhatt, Samir, and Flaxman, Seth

Published
2020
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27. Heterogeneities in the case fatality ratio in the West African Ebola outbreak 2013–2016

Author

Garske, Tini, Cori, Anne, Ariyarajah, Archchun, Blake, Isobel M., Dorigatti, Ilaria, Eckmanns, Tim, Fraser, Christophe, Hinsley, Wes, Jombart, Thibaut, Mills, Harriet L., Nedjati-Gilani, Gemma, Newton, Emily, Nouvellet, Pierre, Perkins, Devin, Riley, Steven, Schumacher, Dirk, Shah, Anita, Van Kerkhove, Maria D., Dye, Christopher, Ferguson, Neil M., and Donnelly, Christi A.

Published
2017

28. Key data for outbreak evaluation: building on the Ebola experience

Author

Cori, Anne, Donnelly, Christl A., Dorigatti, Ilaria, Ferguson, Neil M., Fraser, Christophe, Garske, Tini, Jombart, Thibaut, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Riley, Steven, Van Kerkhove, Maria D., Mills, Harriet L., and Blake, Isobel M.

Published
2017

30. Response to COVID-19 in South Korea and implications for lifting stringent interventions

Author

Dighe, Amy, Cattarino, Lorenzo, Cuomo-Dannenburg, Gina, Skarp, Janetta, Imai, Natsuko, Bhatia, Sangeeta, Gaythorpe, Katy A. M., Ainslie, Kylie E. C., Baguelin, Marc, Bhatt, Samir, Boonyasiri, Adhiratha, Brazeau, Nicholas F., Cooper, Laura V., Coupland, Helen, Cucunuba, Zulma, Dorigatti, Ilaria, Eales, Oliver D., van Elsland, Sabine L., FitzJohn, Richard G., Green, William D., Haw, David J., Hinsley, Wes, Knock, Edward, Laydon, Daniel J., Mellan, Thomas, Mishra, Swapnil, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Pons-Salort, Margarita, Thompson, Hayley A., Unwin, H. Juliette T., Verity, Robert, Vollmer, Michaela A. C., Walters, Caroline E., Watson, Oliver J., Whittaker, Charles, Whittles, Lilith K., Ghani, Azra C., Donnelly, Christl A., Ferguson, Neil M., and Riley, Steven

Published
2020
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34. A simulation-based method to inform serosurvey designs for estimating dengue force of infection using existing blood samples

Author

Vicco, Anna, primary, McCormack, Clare, additional, Pedrique, Belen, additional, Amuasi, John H., additional, Awuah, Anthony Afum-Adjei, additional, Obirikorang, Christian, additional, Struck, Nicole S., additional, Lorenz, Eva, additional, May, Jurgen, additional, Ribeiro, Isabela, additional, Malavige, Gathsaurie Neelika, additional, Donnelly, Christl A., additional, and Dorigatti, Ilaria, additional

Published
2023
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37. Countering the Zika epidemic in Latin America

Author

Ferguson, Neil M., Cucunubá, Zulma M., Dorigatti, Ilaria, Nedjati-Gilani, Gemma L., Donnelly, Christl A., Basáñez, Maria-Gloria, Nouvellet, Pierre, and Lessler, Justin

Published
2016

41. Impact of early phase COVID-19 precautionary behaviors on seasonal influenza in Hong Kong: A time-series modeling approach

Author

Lin, Chun-Pang, Dorigatti, Ilaria, Tsui, Kwok-Leung, Xie, Min, Ling, Man-Ho, and Yuan, Hsiang-Yu

Subjects
infectious disease modeling, face mask, social distancing, COVID-19, time-series analysis, influenza
Abstract

BackgroundBefore major non-pharmaceutical interventions were implemented, seasonal incidence of influenza in Hong Kong showed a rapid and unexpected reduction immediately following the early spread of COVID-19 in mainland China in January 2020. This decline was presumably associated with precautionary behavioral changes (e.g., wearing face masks and avoiding crowded places). Knowing their effectiveness on the transmissibility of seasonal influenza can inform future influenza prevention strategies. MethodsWe estimated the effective reproduction number (R-t) of seasonal influenza in 2019/20 winter using a time-series susceptible-infectious-recovered (TS-SIR) model with a Bayesian inference by integrated nested Laplace approximation (INLA). After taking account of changes in underreporting and herd immunity, the individual effects of the behavioral changes were quantified. FindingsThe model-estimated mean R-t reduced from 1.29 (95%CI, 1.27-1.32) to 0.73 (95%CI, 0.73-0.74) after the COVID-19 community spread began. Wearing face masks protected 17.4% of people (95%CI, 16.3-18.3%) from infections, having about half of the effect as avoiding crowded places (44.1%, 95%CI, 43.5-44.7%). Within the current model, if more than 85% of people had adopted both behaviors, the initial R-t could have been less than 1. ConclusionOur model results indicate that wearing face masks and avoiding crowded places could have potentially significant suppressive impacts on influenza. Health and Medical Research Fund [COVID190215]; City University of Hong Kong [7200573, 9610416]; Wellcome Trust; Royal Society [213494/Z/18/Z]; Hong Kong Innovation and Technology Commission (InnoHK Project CIMDA) Published version This research was funded by the Health and Medical Research Fund (COVID190215), the City University of Hong Kong (7200573 and 9610416), the Wellcome Trust and the Royal Society (213494/Z/18/Z), and Hong Kong Innovation and Technology Commission (InnoHK Project CIMDA).

Published
2022

44. The role of rapid diagnostics in managing Ebola epidemics

Author

Nouvellet, Pierre, Garske, Tini, Mills, Harriet L., Nedjati-Gilani, Gemma, Hinsley, Wes, Blake, Isobel M., Van Kerkhove, Maria D., Cori, Anne, Dorigatti, Ilaria, Jombart, Thibaut, Riley, Steven, Fraser, Christophe, Donnelly, Christl A., and Ferguson, Neil M.

Subjects
Ebola virus infections -- Health aspects -- Risk factors -- Care and treatment -- Diagnosis, RNA -- Research, Company business management, Environmental issues, Science and technology, Zoology and wildlife conservation, World Health Organization -- Management
Abstract

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third. Nature 528, S109-S116 (3 December 2015), DOI: 10.1038/nature16041 This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided., The unprecedented scale of the 2014-15 West African Ebola epidemic has posed major challenges for delivering rapid diagnosis--an essential component of controlling Ebola epidemics, given the non-specific nature of early [...]

Published
2015
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47. Exploring the role of ferroptosis in B cell malignancies

Author

Dorigatti, Ilaria and Dorigatti, Ilaria

Abstract

Ferroptose ist eine Art des Zelltods, die sich genetisch, biochemisch und morphologisch von anderen Formen des regulierten Zelltods unterscheidet. Dabei führt eine exzessive Peroxidation von mehrfach ungesättigten Fettacylgruppen zur Anhäufung von reaktiven Sauerstoffspezies (ROS) in Lipiden, welche die Dysfunktion von zellulären Membranen auslösen und letztendlich zum ferroptotischen Zelltod führen. Das Enzym Glutathionperoxidase 4 (GPX4) ist ein zentraler Mechanismus um Lipidperoxide in Zellmembranen zu entgiften, und damit um Ferroptose zu verhindern. In den letzten Jahren wurden Inhibitoren des GPX4-Signalwegs entwickelt, die sowohl in vitro als auch in vivo Ferroptose auslösen. Ferroptose-induzierende Medikamente könnten daher einen neuen therapeutischen Ansatz zur Behandlung bösartiger Erkrankungen darstellen. Dies trifft insbesondere auf Tumore zu, die eine Resistenz gegen Standardtherapien entwickelt haben. Um herauszufinden, ob unterschiedliche Ferroptosesensitivität von Krebszellen auf bestimmte molekulare Veränderungen in den Tumorzellen zurückzuführen ist, haben wir eine Reihe von gentechnisch veränderten Leukämiezelllinien erzeugt, sogenannte BaF3 Zellen. Dabei haben wir die MYC- oder v-ABL-Onkoproteine oder eine konstitutiv aktive Version von RAS in die Zellen gebracht, oder das Tumorsuppressor-Gen p53 entfernt. Um zu untersuchen, ob eine erworbene Apoptose Resistenz die Anfälligkeit für Ferroptose beeinflusst, haben wir die mitochondriale Apoptose durch Überexpression von BCL2 oder durch kombinierte Entfernung von BAX und BAK blockiert. Unsere Daten zeigen, dass speziell MYC- und v-ABL-bedingte Veränderungen in den Leukämiezellen nach pharmakologischer Ferroptoseauslösung die mitochondriale Fitness verbessern, die Akkumulation von Lipidperoxiden reduzieren und das Überleben eines Teiles der Zellen in Kultur fördern. Mechanistisch spielt eine Deregulierung des GPX4-gesteuerten Entgiftungssystems keine Rolle für das Überleben dieser wenigen Zellen. Trot, Ferroptosis is an iron-dependent cell death mode, genetically, biochemically and morphologically distinct from other forms of regulated cell death. Excessive peroxidation of polyunsaturated fatty acyl moieties prompts cellular membrane dysfunction, ultimately causing ferroptotic cell death. Upon accumulation of lipid reactive oxygen species (ROS), glutathione peroxidase 4 (GPX4)-mediated detoxification of lipid peroxides is a cardinal mechanism to prevent ferroptosis. In the recent years, small molecule inhibitors of the GPX4 pathway have been developed aiming at ferroptosis induction, both in vitro and in vivo. Thus, ferroptosisinducing drugs may represent a novel therapeutic approach to treat malignancies, in particular cancers that have developed resistance to standard therapies which commonly induce apoptotic cell death. To explore whether differential ferroptosis sensitivity arises from established tumor drivers, we generated a panel of genetically engineered BaF3 cell lines, which are progenitor B cells, by expressing the MYC or v-ABL oncoproteins or a constitutive active version of RAS, or by deleting the p53 tumor suppressor gene. To investigate whether acquired apoptosis resistance would impact ferroptosis susceptibility, we blocked mitochondrial apoptosis by overexpression of BCL2 or by combined deletion of BAX and BAK. Our data straighten out that specifically MYC- and v-ABL-driven cellular reprogramming enhance mitochondrial fitness, reduce lipid ROS accumulation and foster the survival of a subset of cells in culture during prolonged pharmacological ferroptosis induction. Mechanistically, deregulation of the GPX4-driven detoxification system is not the cause for cellular persistence. Despite partial prevention of ferroptotic cell death and lipid ROS accumulation, combined elimination of BAX and BAK did not promote the outgrowth of persisting cells upon ferroptosis induction. Altogether, our data suggest that pharmacologic induction of ferroptosis may be, Masterarbeit Universität Innsbruck 2022

Published
2022

48. Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

Author

Vecchio, Claudia Del, primary, Daniels, Bethan Cracknell, additional, Brancaccio, Giuseppina, additional, Brazzale, Alessandra, additional, Lavezzo, Enrico, additional, Ciavarella, Constanze, additional, Onelia, Francesco, additional, Franchin, Elisa, additional, Manuto, Laura, additional, Bianca, Federico, additional, Cianci, Vito, additional, Cattelan, Annamaria, additional, Dorigatti, Ilaria, additional, Toppo, Stefano, additional, and Crisanti, Andrea, additional

Published
2022
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49. Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe

Author

Flaxman, Seth, Mishra, Swapnil, Gandy, Axel, Unwin, H. Juliette T., Mellan, Thomas A., Coupland, Helen, Whittaker, Charles, Zhu, Harrison, Berah, Tresnia, Eaton, Jeffrey W., Monod, Mélodie, Perez-Guzman, Pablo N., Schmit, Nora, Cilloni, Lucia, Ainslie, Kylie E. C., Baguelin, Marc, Boonyasiri, Adhiratha, Boyd, Olivia, Cattarino, Lorenzo, Cooper, Laura V., Cucunubá, Zulma, Cuomo-Dannenburg, Gina, Dighe, Amy, Djaafara, Bimandra, Dorigatti, Ilaria, van Elsland, Sabine L., FitzJohn, Richard G., Gaythorpe, Katy A. M., Geidelberg, Lily, Grassly, Nicholas C., Green, William D., Hallett, Timothy, Hamlet, Arran, Hinsley, Wes, Jeffrey, Ben, Knock, Edward, Laydon, Daniel J., Nedjati-Gilani, Gemma, Nouvellet, Pierre, Parag, Kris V., Siveroni, Igor, Thompson, Hayley A., Verity, Robert, Volz, Erik, Walters, Caroline E., Wang, Haowei, Wang, Yuanrong, Watson, Oliver J., Winskill, Peter, Xi, Xiaoyue, Walker, Patrick G. T., Ghani, Azra C., Donnelly, Christl A., Riley, Steven, Vollmer, Michaela A. C., Ferguson, Neil M., Okell, Lucy C., Bhatt, Samir, Medical Research Council (MRC), and Wellcome Trust

Subjects
0301 basic medicine, medicine.medical_specialty, General Science & Technology, Population, Pooling, Psychological intervention, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Case fatality rate, Pandemic, Epidemiology, Imperial College COVID-19 Response Team, Medicine, 030212 general & internal medicine, education, education.field_of_study, Science & Technology, Multidisciplinary, business.industry, Multidisciplinary Sciences, 030104 developmental biology, Transmission (mechanics), Science & Technology - Other Topics, business, Basic reproduction number, Demography
Abstract

Following the detection of the new coronavirus1 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics of coronavirus disease 2019 (COVID-19). In response, many European countries have implemented non-pharmaceutical interventions, such as the closure of schools and national lockdowns. Here we study the effect of major interventions across 11 European countries for the period from the start of the COVID-19 epidemics in February 2020 until 4 May 2020, when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks previously, allowing for the time lag between infection and death. We use partial pooling of information between countries, with both individual and shared effects on the time-varying reproduction number (Rt). Pooling allows for more information to be used, helps to overcome idiosyncrasies in the data and enables more-timely estimates. Our model relies on fixed estimates of some epidemiological parameters (such as the infection fatality rate), does not include importation or subnational variation and assumes that changes in Rt are an immediate response to interventions rather than gradual changes in behaviour. Amidst the ongoing pandemic, we rely on death data that are incomplete, show systematic biases in reporting and are subject to future consolidation. We estimate that-for all of the countries we consider here-current interventions have been sufficient to drive Rt below 1 (probability Rt

Published
2020

50. Additional file 1 of Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

Author

Lavezzo, Enrico, Pacenti, Monia, Manuto, Laura, Boldrin, Caterina, Cattai, Margherita, Grazioli, Marco, Bianca, Federico, Sartori, Margherita, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Vanuzzo, Maria Cristina, Lisi, Vittoria, Antonello, Maria, Grimaldi, Carmela Ileana, Zulian, Chiara, Del Vecchio, Claudia, Plebani, Mario, Padoan, Andrea, Cirillo, Daniela Maria, Brazzale, Alessandra R., Tonon, Giovanni, Toppo, Stefano, Dorigatti, Ilaria, and Crisanti, Andrea

Abstract

Additional file 1: Figure S1. Anti-N antibody titres and dynamics in vaccinated and unvaccinated subjects; Figure S2. Anti-N antibody titres of vaccinated and unvaccinated individuals previously exposed to SARS-CoV-2 infection differ according to age; Figure S3. Correlation among DiaSorin S1/S2, DiaSorin trimeric tests and neutralisation assay; Figure S4. Features of the cohorts analysed in this study. Table S1. Concordance between S1/S2 and trimericS DiaSorin assays.

Published
2022
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