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1. Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults

Author

Thomas, Amy C., Oliver, Elizabeth, Baum, Holly E., Gupta, Kapil, Shelley, Kathryn L., Long, Anna E., Jones, Hayley E., Smith, Joyce, Hitchings, Benjamin, di Bartolo, Natalie, Vasileiou, Kate, Rabi, Fruzsina, Alamir, Hanin, Eghleilib, Malak, Francis, Ore, Oliver, Jennifer, Morales-Aza, Begonia, Obst, Ulrike, Shattock, Debbie, Barr, Rachael, Collingwood, Lucy, Duale, Kaltun, Grace, Niall, Livera, Guillaume Gonnage, Bishop, Lindsay, Downing, Harriet, Rodrigues, Fernanda, Timpson, Nicholas, Relton, Caroline L., Toye, Ashley, Woolfson, Derek N., Berger, Imre, Goenka, Anu, Davidson, Andrew D., Gillespie, Kathleen M., Williams, Alistair J. K., Bailey, Mick, Brooks-Pollock, Ellen, Finn, Adam, and Halliday, Alice

Published
2023
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2. Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

Author

Adams, Kirsty, Alaee, Seema, Aley, Parvinder K., Allum, Emma, Anthony, Sally, Ashton, Kate, Awal, Tanya, Barnett, Liz, Barratt, Alison, Barron, Charlotte, Baum, Holly, Beard, Chloe, Bennett, Lorna, Bird, Samuel, Bishop, Sarah, Bisset, Jess, Bodalia, Pritesh, Bowles, Jane, Bowyer, Catherine, Bradburn, Kirstie, Bray, Jonathan J.H., Bressington, Catherine, Brimfield, Matthew, Broad, Lauren, Brown, Pauline, Brydon-Hill, Ruth, Burge, Sharon, Carmichael, David, Chohan, Gurjit, Clark, Tonia, Close, Adrianne, Coleman, Tom, Cowley, Claire, Cranfield, Charlotte, Cross, Eleanor, D'Agostino, Alyssa, D'Arcangelo, Silvia, David Otter, Ashley, Davies, Kate, Davies, Catrin, Davies, Ru, Davies, Louisa, Driver, Kimberley, Eglinton, Charlotte, Ekblad, Charlotte, Eldridge, Emma, Evans, Teriann, Evans, Mim, Evans, Isabel, F Mujadidi, Yama, Farrow, Amanda, Faulkner, Beverley, Feltham, Sally, Figueirido, Susan, Ford, Jamie, Foxwell, David, Frayling, Sharon, Gardiner, Sophie, Gooch, Karen E., Goodwin, Jayne, Halliday, Alice, Hamal, Shama, Harrhy, Sarah, Harris, Andrew, Haxton, Lesley, Haynes, Matthew, Hazell, Mae, Hembrough, Tracey, Hewson, Jacqueline, Hicks, Bethany, Higgins, Thomas, Hill, Michelle, Hills, Alex, Hilton, Zoe, Hitchings, Benjamin, Hua, Cheryl, Iftikhar, Hina, Iqbal, Attya, Jones, Laura, Jones, Nicola, Kellett Wright, Johanna, Kidd, Sarah, Kirby, Alison, Knibbs, Lucy, Lamb, Jenny, Langton, Helen, Leach, Rwth, Lewis-Clarke, Phoebe, Lloyd, Amy, Maclean, Kirsty, Manning, Nicola, Marriott, Anthony, McFadzean, Isobel Joy, McLaughlin, Maeve, McQueen, Alison, Mills, Bianca, Naik, Gurudutt, Nicholls, Lisa, Norman, Chris, Northcott, Keren, Nyland, Kerry, Oliver, Catherine, Oliver, Elizabeth, Oliver, Jennifer, Owen, Diana, Paterson, Jemma, Pearce, Lauren, Pegler, Suzannah, Price, Zoe, Pynsent, William B., Ramos, Lidia, Rampling, Tommy, Rea, David, Regan, Karen, Riaz, Tawassal, Ricamara, Marivic, Rice, Danielle, Rich, Melody, Roots, Marianne, Ryan, Kathryn Ann, Sakagami, Yukari, Salem, Ahmed, Salter-Hewitt, Jade, Samuels, Michelle, Santoloce, Silvia, Seaman, Siwan, Seneviratne, Michael, Shankland, Sara, Silva, Louise, Smart, Katie, Smith, Rachel M., Smith, Joyce, Stringer, Rebecca, Talbot, Helen, Tarling, Teresa, Taylor, Sarah Louise, Thomas, Amy, Tilzey, Grace, Townley, Gina, Trembath, Lisa, Turkentine, Kate, Turner, Kelly, Tyler, Jenny, Ugoji, Jacinta, Wale, Katharine, Walker-Smith, Terrie, Walton, Maggie, Warnes, Barbara, Whittley, Sarah, Williams, Jennie, Williams, Gail, Williamson, Kevin, Yim, Yee Ting Nicole, Youlden, Nicola, Lazarus, Rajeka, Baos, Sarah, Cappel-Porter, Heike, Carson-Stevens, Andrew, Clout, Madeleine, Culliford, Lucy, Emmett, Stevan R, Garstang, Jonathan, Gbadamoshi, Lukuman, Hallis, Bassam, Harris, Rosie A, Hutton, David, Jacobsen, Nick, Joyce, Katherine, Kaminski, Rachel, Libri, Vincenzo, Middleditch, Alex, McCullagh, Liz, Moran, Ed, Phillipson, Adrian, Price, Elizabeth, Ryan, John, Thirard, Russell, Todd, Rachel, Snape, Matthew D, Tucker, David, Williams, Rachel Lauren, Nguyen-Van-Tam, Jonathan S, Finn, Adam, and Rogers, Chris A

Published
2021
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6. The role of TLR2 in cutaneous leishmaniasis and as a target for vaccine adjuvants

Author

Halliday, Alice, Taylor, Mark, and Craig, Alister

Subjects
616.9, RC Internal medicine
Abstract

After the introduction of clean water, vaccination is thought to be the most effective public health tool ever introduced, responsible for preventing millions of cases of disease, disability and death each year. Unfortunately there remain a number of important human diseases for which we have no vaccine, particularly parasitic diseases, such as leishmaniasis, which primarily affect poor communities in tropical regions. There are many complex reasons why we have failed to develop effective vaccines for parasitic diseases, but there is hope that with our improved understanding of the immune system alongside the development of a new generation of vaccines, we will soon develop new vaccines which are effective enough to prevent such diseases. Toll-like receptors (TLRs) are major targets for adjuvants and have been shown to be crucial for defence against a number of infections. TLR2 recognises bacterial lipopeptides in a heterodimer with either TLR1 or TLR6, and its function has been linked to protection against various bacterial infections and to the efficacy of the BCG vaccine. TLR2 has been shown to recognise surface glycoconjugates of Leishmania parasites in vitro, particularly lipophosphoglycan (LPG). In this study, in vivo experimental infections show that TLR2 has a protective role in controlling cutaneous leishmaniasis (CL), as shown by increased lesion sizes and parasite burdens in TLR2-/- mice infected with L. major and L. mexicana. Furthermore, it appears that LPG is not the major mediator of TLR2 activation during infection with L. mexicana, as parasites lacking LPG also resulted in exacerbated disease in TLR2-/- mice. Mice lacking TLR2 co-receptors TLR1 and TLR6 did not show increased susceptibility to infection, suggesting either mono-TLR2 function or alternative co-receptor involvement. Infected TLR2-/- mice show a skewed Th2 immune response to Leishmania, as demonstrated by elevated IL-4, IL-13 and IL-10 production by draining lymph node (DLN) cells in response to antigen. These results suggest that TLR2 is involved in promoting protective immune responses to Leishmania parasites during primary infection in vivo, and is a potential target for protective and therapeutic vaccine adjuvants. Paradoxically, however, TLR2-targeting lipopeptides Pam2 and Pam3 were ineffective adjuvants for use in a whole-cell vaccine to protect against CL, as whole-cell autoclaved L. major (ALM) vaccines containing lipopeptides resulted in exacerbated disease upon challenge when compared to unvaccinated controls and in contrast to effective vaccination when CpG adjuvants were used. The ratio of antigen specific IgG1:IgG2c antibody isotypes, which is a marker of the type of adaptive immune response (Th1 or Th2), was elevated in mice that received vaccines containing lipopeptide adjuvants, suggesting that these adjuvants drive non-protective Th2 responses to Leishmania. In a Th2-dependent vaccine model using Brugia malayi, the use of Pam2 as an adjuvant resulted in an enhanced protective phenotype with similar efficacy to the Th2-driving adjuvant Alum. Thus, in the context of CL infection TLR2 has a protective role in late-stage primary infections with L. major and L. mexicana, yet when targeted with lipopeptide adjuvants in whole-cell vaccines promotes exacerbated disease in challenge infections, through driving Th2 immune responses. Lipopeptides that target TLR2, such as Pam2, are therefore more appropriate for use as adjuvants in vaccines where Th2 protective immunity is required.

Published
2013
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10. Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months

Author

Santopaolo, Marianna, primary, Gregorova, Michaela, primary, Hamilton, Fergus, additional, Arnold, David, additional, Long, Anna, additional, Lacey, Aurora, additional, Oliver, Elizabeth, additional, Halliday, Alice, additional, Baum, Holly, additional, Hamilton, Kristy, additional, Milligan, Rachel, additional, Pearce, Olivia, additional, Knezevic, Lea, additional, Morales Aza, Begonia, additional, Milne, Alice, additional, Milodowski, Emily, additional, Jones, Eben, additional, Lazarus, Rajeka, additional, Goenka, Anu, additional, Finn, Adam, additional, Maskell, Nicholas, additional, Davidson, Andrew D, additional, Gillespie, Kathleen, additional, Wooldridge, Linda, additional, and Rivino, Laura, additional

Published
2023
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11. Old World cutaneous leishmaniasis treatment response varies depending on parasite species, geographical location and development of secondary infection

Author

Al-Salem, Waleed S., Solórzano, Carla, Weedall, Gareth D., Dyer, Naomi A., Kelly-Hope, Louise, Casas-Sánchez, Aitor, Alraey, Yasser, Alyamani, Essam J., Halliday, Alice, Balghonaim, Salah M., Alsohibany, Khalid S., Alzeyadi, Zeyad, Alzahrani, Mohamed H., Al-Shahrani, Ali M., Assiri, Abdullah M., Memish, Ziad, and Acosta-Serrano, Álvaro

Published
2019
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12. Prolonged T-cell activation and long COVID symptoms independently associate with severe disease at 3 months in a UK cohort of hospitalized COVID-19 patients

Author

Santopaolo, Marianna, primary, Gregorova, Michaela, additional, Hamilton, Fergus, additional, Arnold, David, additional, Long, Anna, additional, Lacey, Aurora, additional, Oliver, Elizabeth, additional, Halliday, Alice, additional, Baum, Holly, additional, Hamilton, Kristy, additional, Milligan, Rachel, additional, Pearce, Olivia, additional, Knezevic, Lea, additional, Aza, Begonia Morales, additional, Milne, Alice, additional, Milodowski, Emily, additional, Lazarus, Rajeka, additional, Goenka, Anu, additional, Finn, Adam, additional, Maskell, Nick, additional, Davidson, Andrew, additional, Gillespie, Kathleen, additional, Wooldridge, Linda, additional, and Rivino, Laura, additional

Published
2022
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13. Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2

Author

Halliday, Alice, primary, Long, Anna E., additional, Baum, Holly E., additional, Thomas, Amy C., additional, Shelley, Kathryn L., additional, Oliver, Elizabeth, additional, Gupta, Kapil, additional, Francis, Ore, additional, Williamson, Maia Kavanagh, additional, Di Bartolo, Natalie, additional, Randell, Matthew J., additional, Ben-Khoud, Yassin, additional, Kelland, Ilana, additional, Mortimer, Georgina, additional, Ball, Olivia, additional, Plumptre, Charlie, additional, Chandler, Kyla, additional, Obst, Ulrike, additional, Secchi, Massimiliano, additional, Piemonti, Lorenzo, additional, Lampasona, Vito, additional, Smith, Joyce, additional, Gregorova, Michaela, additional, Knezevic, Lea, additional, Metz, Jane, additional, Barr, Rachael, additional, Morales-Aza, Begonia, additional, Oliver, Jennifer, additional, Collingwood, Lucy, additional, Hitchings, Benjamin, additional, Ring, Susan, additional, Wooldridge, Linda, additional, Rivino, Laura, additional, Timpson, Nicholas, additional, McKernon, Jorgen, additional, Muir, Peter, additional, Hamilton, Fergus, additional, Arnold, David, additional, Woolfson, Derek N., additional, Goenka, Anu, additional, Davidson, Andrew D., additional, Toye, Ashley M., additional, Berger, Imre, additional, Bailey, Mick, additional, Gillespie, Kathleen M., additional, Williams, Alistair J. K., additional, and Finn, Adam, additional

Published
2022
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14. Predicting progression to active tuberculosis: A rate-limiting step on the path to elimination

Author

Lalvani, Ajit, Berrocal-Almanza, Luis C., and Halliday, Alice

Subjects
Epidemiologic methods -- Usage, Tuberculosis -- Diagnosis -- Development and progression -- Patient outcomes -- Control -- Care and treatment, Mortality, Disease transmission, Rifapentine, Communicable diseases, Biological sciences
Abstract

Author(s): Ajit Lalvani 1,2,*, Luis C. Berrocal-Almanza 1, Alice Halliday 2,3 Current tools are not fit for purpose to deliver tuberculosis elimination Tuberculosis (TB) is the leading cause of mortality [...]

Published
2019
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15. Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

Author

Lazarus, Rajeka, primary, Baos, Sarah, additional, Cappel-Porter, Heike, additional, Carson-Stevens, Andrew, additional, Clout, Madeleine, additional, Culliford, Lucy, additional, Emmett, Stevan R, additional, Garstang, Jonathan, additional, Gbadamoshi, Lukuman, additional, Hallis, Bassam, additional, Harris, Rosie A, additional, Hutton, David, additional, Jacobsen, Nick, additional, Joyce, Katherine, additional, Kaminski, Rachel, additional, Libri, Vincenzo, additional, Middleditch, Alex, additional, McCullagh, Liz, additional, Moran, Ed, additional, Phillipson, Adrian, additional, Price, Elizabeth, additional, Ryan, John, additional, Thirard, Russell, additional, Todd, Rachel, additional, Snape, Matthew D, additional, Tucker, David, additional, Williams, Rachel Lauren, additional, Nguyen-Van-Tam, Jonathan S, additional, Finn, Adam, additional, Rogers, Chris A, additional, Adams, Kirsty, additional, Alaee, Seema, additional, Aley, Parvinder K., additional, Allum, Emma, additional, Anthony, Sally, additional, Ashton, Kate, additional, Awal, Tanya, additional, Barnett, Liz, additional, Barratt, Alison, additional, Barron, Charlotte, additional, Baum, Holly, additional, Beard, Chloe, additional, Bennett, Lorna, additional, Bird, Samuel, additional, Bishop, Sarah, additional, Bisset, Jess, additional, Bodalia, Pritesh, additional, Bowles, Jane, additional, Bowyer, Catherine, additional, Bradburn, Kirstie, additional, Bray, Jonathan J.H., additional, Bressington, Catherine, additional, Brimfield, Matthew, additional, Broad, Lauren, additional, Brown, Pauline, additional, Brydon-Hill, Ruth, additional, Burge, Sharon, additional, Carmichael, David, additional, Chohan, Gurjit, additional, Clark, Tonia, additional, Close, Adrianne, additional, Coleman, Tom, additional, Cowley, Claire, additional, Cranfield, Charlotte, additional, Cross, Eleanor, additional, D'Agostino, Alyssa, additional, D'Arcangelo, Silvia, additional, David Otter, Ashley, additional, Davies, Kate, additional, Davies, Catrin, additional, Davies, Ru, additional, Davies, Louisa, additional, Driver, Kimberley, additional, Eglinton, Charlotte, additional, Ekblad, Charlotte, additional, Eldridge, Emma, additional, Evans, Teriann, additional, Evans, Mim, additional, Evans, Isabel, additional, F Mujadidi, Yama, additional, Farrow, Amanda, additional, Faulkner, Beverley, additional, Feltham, Sally, additional, Figueirido, Susan, additional, Ford, Jamie, additional, Foxwell, David, additional, Frayling, Sharon, additional, Gardiner, Sophie, additional, Gooch, Karen E., additional, Goodwin, Jayne, additional, Halliday, Alice, additional, Hamal, Shama, additional, Harrhy, Sarah, additional, Harris, Andrew, additional, Haxton, Lesley, additional, Haynes, Matthew, additional, Hazell, Mae, additional, Hembrough, Tracey, additional, Hewson, Jacqueline, additional, Hicks, Bethany, additional, Higgins, Thomas, additional, Hill, Michelle, additional, Hills, Alex, additional, Hilton, Zoe, additional, Hitchings, Benjamin, additional, Hua, Cheryl, additional, Iftikhar, Hina, additional, Iqbal, Attya, additional, Jones, Laura, additional, Jones, Nicola, additional, Kellett Wright, Johanna, additional, Kidd, Sarah, additional, Kirby, Alison, additional, Knibbs, Lucy, additional, Lamb, Jenny, additional, Langton, Helen, additional, Leach, Rwth, additional, Lewis-Clarke, Phoebe, additional, Lloyd, Amy, additional, Maclean, Kirsty, additional, Manning, Nicola, additional, Marriott, Anthony, additional, McFadzean, Isobel Joy, additional, McLaughlin, Maeve, additional, McQueen, Alison, additional, Mills, Bianca, additional, Naik, Gurudutt, additional, Nicholls, Lisa, additional, Norman, Chris, additional, Northcott, Keren, additional, Nyland, Kerry, additional, Oliver, Catherine, additional, Oliver, Elizabeth, additional, Oliver, Jennifer, additional, Owen, Diana, additional, Paterson, Jemma, additional, Pearce, Lauren, additional, Pegler, Suzannah, additional, Price, Zoe, additional, Pynsent, William B., additional, Ramos, Lidia, additional, Rampling, Tommy, additional, Rea, David, additional, Regan, Karen, additional, Riaz, Tawassal, additional, Ricamara, Marivic, additional, Rice, Danielle, additional, Rich, Melody, additional, Roots, Marianne, additional, Ryan, Kathryn Ann, additional, Sakagami, Yukari, additional, Salem, Ahmed, additional, Salter-Hewitt, Jade, additional, Samuels, Michelle, additional, Santoloce, Silvia, additional, Seaman, Siwan, additional, Seneviratne, Michael, additional, Shankland, Sara, additional, Silva, Louise, additional, Smart, Katie, additional, Smith, Rachel M., additional, Smith, Joyce, additional, Stringer, Rebecca, additional, Talbot, Helen, additional, Tarling, Teresa, additional, Taylor, Sarah Louise, additional, Thomas, Amy, additional, Tilzey, Grace, additional, Townley, Gina, additional, Trembath, Lisa, additional, Turkentine, Kate, additional, Turner, Kelly, additional, Tyler, Jenny, additional, Ugoji, Jacinta, additional, Wale, Katharine, additional, Walker-Smith, Terrie, additional, Walton, Maggie, additional, Warnes, Barbara, additional, Whittley, Sarah, additional, Williams, Jennie, additional, Williams, Gail, additional, Williamson, Kevin, additional, Yim, Yee Ting Nicole, additional, and Youlden, Nicola, additional

Published
2021
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17. Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2

Author

Goenka, Anu, Halliday, Alice, Gregorova, Michaela, Milodowski, Emily, Thomas, Amy, Williamson, Maia Kavanagh, Baum, Holly, Oliver, Elizabeth, Long, Anna E., Knezevic, Lea, Williams, Alistair J.K., Lampasona, Vito, Piemonti, Lorenzo, Gupta, Kapil, Di Bartolo, Natalie, Berger, Imre, Toye, Ashley M., Vipond, Barry, Muir, Peter, Bernatoniene, Jolanta, Bailey, Mick, Gillespie, Kathleen M., Davidson, Andrew D., Wooldridge, Linda, Rivino, Laura, and Finn, Adam

Published
2021
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18. Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis

Author

Halliday, Alice, primary, Masonou, Tereza, additional, Tolosa-Wright, Mica R, additional, Guo, Yanping, additional, Hoang, Long, additional, Parker, Robert, additional, Boakye, Aime, additional, Takwoingi, Yemisi, additional, Badhan, Amarjit, additional, Jain, Pooja, additional, Marwah, Ishita, additional, Berrocal-Almanza, Luis C, additional, Deeks, Jonathan, additional, Beverley, Peter, additional, Kon, Onn Min, additional, and Lalvani, Ajit, additional

Published
2021
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19. Additional file 1 of Predisposing factors to acquisition of acute respiratory tract infections in the community: a systematic review and meta-analysis

Author

Hammond, Ashley, Halliday, Alice, Thornton, Hannah V., and Hay, Alastair D.

Abstract

Additional file 1: Table S1. Medline and Embase search strategy (searched 20th July 2020). Table S2. Population, Intervention, Comparator, Outcome and Study design criteria for inclusion and exclusion. Table S3. Study characteristics for all included risk factor papers (n=23).

Published
2021
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20. Additional file 2 of Predisposing factors to acquisition of acute respiratory tract infections in the community: a systematic review and meta-analysis

Author

Hammond, Ashley, Halliday, Alice, Thornton, Hannah V., and Hay, Alastair D.

Abstract

Additional file 2: Figure S1. Quality assessment charts for risk factor studies included in the review. Figure S2. Non-pooled demographic risk factor data from included studies. Figure S3. Non-pooled environmental risk factor data from included studies. Figure S4. Non-pooled lifestyle and health related risk factor data from included studies measured using non-odds ratio estimates. Figure S5. Non-pooled lifestyle-related risk factor data from included studies. Figure S6. Non-pooled social risk factor data from included studies. Figure S7. Non-pooled health condition-related risk factor data from included studies. Figure S8. Non-pooled medical history-related risk factor data from included studies.

Published
2021
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21. Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis.

Author

Halliday, Alice, Masonou, Tereza, Tolosa-Wright, Mica R, Guo, Yanping, Hoang, Long, Parker, Robert, Boakye, Aime, Takwoingi, Yemisi, Badhan, Amarjit, Jain, Pooja, Marwah, Ishita, Berrocal-Almanza, Luis C, Deeks, Jonathan, Beverley, Peter, Kon, Onn Min, and Lalvani, Ajit

Subjects
*LATENT tuberculosis, *INTERFERON gamma release tests, *LATENT infection, *MYCOBACTERIUM tuberculosis, *CONTACT tracing, *TUBERCULOSIS, *TUBERCULOUS meningitis, *TUBERCULOSIS diagnosis, *RESEARCH, *RESEARCH methodology, *CASE-control method, *EVALUATION research, *COMPARATIVE studies, *RESEARCH funding, *LONGITUDINAL method
Abstract

Background: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown.Methods: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry.Results: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects.Conclusions: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB. [ABSTRACT FROM AUTHOR]

Published
2022
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22. New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study

Author

Halliday, Alice, primary, Jain, Pooja, additional, Hoang, Long, additional, Parker, Robert, additional, Tolosa-Wright, Mica, additional, Masonou, Tereza, additional, Green, Nathan, additional, Boakye, Aime, additional, Takwoingi, Yemisi, additional, Hamilton, Shea, additional, Mandagere, Vinay, additional, Fries, Anastasia, additional, Coin, Lachlan, additional, Deeks, Jon, additional, White, Peter J, additional, Levin, Michael, additional, Beverley, Peter, additional, Kon, Onn Min, additional, and Lalvani, Ajit, additional

Published
2021
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23. Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia

Author

Gregorova, Michaela, primary, Morse, Daniel, additional, Brignoli, Tarcisio, additional, Steventon, Joseph, additional, Hamilton, Fergus, additional, Albur, Mahableshwar, additional, Arnold, David, additional, Thomas, Matthew, additional, Halliday, Alice, additional, Baum, Holly, additional, Rice, Christopher, additional, Avison, Matthew B, additional, Davidson, Andrew D, additional, Santopaolo, Marianna, additional, Oliver, Elizabeth, additional, Goenka, Anu, additional, Finn, Adam, additional, Wooldridge, Linda, additional, Amulic, Borko, additional, Boyton, Rosemary J, additional, Altmann, Daniel M, additional, Butler, David K, additional, McMurray, Claire, additional, Stockton, Joanna, additional, Nicholls, Sam, additional, Cooper, Charles, additional, Loman, Nicholas, additional, Cox, Michael J, additional, Rivino, Laura, additional, and Massey, Ruth C, additional

Published
2020
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24. Author response: Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia

Author

Gregorova, Michaela, primary, Morse, Daniel, additional, Brignoli, Tarcisio, additional, Steventon, Joseph, additional, Hamilton, Fergus, additional, Albur, Mahableshwar, additional, Arnold, David, additional, Thomas, Matthew, additional, Halliday, Alice, additional, Baum, Holly, additional, Rice, Christopher, additional, Avison, Matthew B, additional, Davidson, Andrew D, additional, Santopaolo, Marianna, additional, Oliver, Elizabeth, additional, Goenka, Anu, additional, Finn, Adam, additional, Wooldridge, Linda, additional, Amulic, Borko, additional, Boyton, Rosemary J, additional, Altmann, Daniel M, additional, Butler, David K, additional, McMurray, Claire, additional, Stockton, Joanna, additional, Nicholls, Sam, additional, Cooper, Charles, additional, Loman, Nicholas, additional, Cox, Michael J, additional, Rivino, Laura, additional, and Massey, Ruth C, additional

Published
2020
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26. Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia

Author

Turner, Joseph D, Pionnier, Nicolas, Furlong-Silva, Julio, Sjoberg, Hanna, Cross, Stephen, Halliday, Alice, Guimaraes, Ana F, Cook, Darren A N, Steven, Andrew, Van Rooijen, Nico, and Allen, Judith E

Subjects
Male, Mice, Inbred BALB C, Cytokines/genetics, Eosinophilia/drug therapy, Interleukin-4/pharmacology, Mice, SCID, respiratory system, Receptors, CCR3/genetics, Mice, Macrophages/drug effects, Brugia malayi/drug effects, parasitic diseases, Animals, Female, Antineoplastic Agents/pharmacology, Filariasis/drug therapy
Abstract

Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.

Published
2018

27. Interleukin-4 activated macrophages mediate immunity to helminth infection by sustaining CCR3-dependent eosinophilia

Author

Turner, Joseph D., Pionnier, Nicolas, Furlong-Silva, Julio, Sjoberg, Hanna, Cross, Stephen, Halliday, Alice, Guimaraes, Ana, Cook, Darren, Steven, Andrew, Van Rooijen, Nico, Allen, Judith, Jenkins, Stephen, and Taylor, Mark J.

Subjects
parasitic diseases, respiratory system
Abstract

Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarialrecruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4RD activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.

Published
2018

31. Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia

Author

Turner, Joseph D., primary, Pionnier, Nicolas, additional, Furlong-Silva, Julio, additional, Sjoberg, Hanna, additional, Cross, Stephen, additional, Halliday, Alice, additional, Guimaraes, Ana F., additional, Cook, Darren A. N., additional, Steven, Andrew, additional, Van Rooijen, Nico, additional, Allen, Judith E., additional, Jenkins, Stephen J., additional, and Taylor, Mark J., additional

Published
2018
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32. Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways

Author

Reuschl, Ann-Kathrin, primary, Edwards, Michael R., additional, Parker, Robert, additional, Connell, David W., additional, Hoang, Long, additional, Halliday, Alice, additional, Jarvis, Hannah, additional, Siddiqui, Nazneen, additional, Wright, Corrina, additional, Bremang, Samuel, additional, Newton, Sandra M., additional, Beverley, Peter, additional, Shattock, Robin J., additional, Kon, Onn Min, additional, and Lalvani, Ajit, additional

Published
2017
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33. Toll-like receptor 2 (TLR2) plays a role in controlling cutaneous leishmaniasis in vivo, but does not require activation by parasite lipophosphoglycan

Author

Halliday, Alice, Bates, Paul A., Chance, Michael L., Taylor, Mark J., Halliday, Alice, Bates, Paul A., Chance, Michael L., and Taylor, Mark J.

Abstract

BACKGROUND: Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. Despite several studies reporting involvement of the innate immune receptor Toll-like receptor 2 (TLR2) in the recognition of surface glycolipids from Leishmania parasites in vitro, the role of TLR2 and its co-receptors during cutaneous leishmaniasis infection in vivo is unknown. METHODS: To explore the role of TLR2 and its co-receptors in cutaneous leishmaniasis, mice deficient in either TLR2, 4, 1 or 6, or wild-type (WT) controls, were infected with either Leishmania major promastigotes, L. mexicana promastigotes, L. mexicana amastigotes, or LPG1 (-/-) L. mexicana promastigotes. For each infection, lesion sizes were monitored and parasite burden was assessed at various time points. To assess immune responses, draining lymph node (DLN) cells were re-stimulated with parasite antigens and the production of cytokines and parasite-specific antibody isotypes in blood was determined by ELISA. RESULTS: Mice deficient in TLR2 and TLR4 presented with larger lesions and higher parasite burdens than WT controls. Mice lacking TLR2 co-receptors TLR1 or TLR6 did not show exacerbated infection, suggesting that TLR2 does not require either co-receptor in the recognition of Leishmania infection. Furthermore, it appears that lipophosphoglycan (LPG) is not the major mediator of TLR2 activation during infection with L. mexicana, as parasites lacking LPG (axenic amastigotes and LPG1 (-/-) promastigotes) also resulted in exacerbated disease in TLR2(-/-) mice. Infected TLR2(-/-) mice show a skewed Th2 immune response to Leishmania parasites, as demonstrated by elevated IL-4, IL-13 and IL-10 production by DLN cells from L. mexicana infected mice in response to antigen. Furthermore, L. major infected TLR2(-/-) mice have elevated antigen-specific IgG1 antibodies. CONCLUSIONS: TLR2 deficiency leads to exacerbation of disease and parasite burden through promotion of Th2 immunity. TLR2 activa

Published
2016

34. The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine models

Author

Halliday, Alice, Turner, Joseph D., Guimarães, Ana, Bates, Paul Andrew, Taylor, Mark J., Halliday, Alice, Turner, Joseph D., Guimarães, Ana, Bates, Paul Andrew, and Taylor, Mark J.

Abstract

Background Toll-like receptors (TLRs) play an important role in the innate and adaptive immune responses to pathogens, and are the target of new vaccine adjuvants. TLR2 plays a role in parasite recognition and activation of immune responses during cutaneous leishmaniasis infection, suggesting that TLR2 could be targeted by adjuvants for use in Leishmania vaccines. We therefore explored using Pam2CSK4 (Pam2) and Pam3CSK4 (Pam3) lipopeptide adjuvants, which activate TLR2/6 and TLR2/1 heterodimers respectively, in vaccine models for parasitic infections. Methods The use of lipopeptide adjuvants was explored using two vaccine models. For cutaneous leishmaniasis, the lipopeptide adjuvants Pam2 and Pam3 were compared to that of the Th1-driving double-stranded DNA TLR9 agonist CpG for their ability to improve the efficacy of the autoclaved Leishmania major (ALM) vaccine to protect against L. major infection. The ability of Pam2 to enhance the efficacy of a soluble Brugia malayi microfilariae extract (BmMfE) vaccine to protect against filarial infection was also assessed in a peritoneal infection model of B. malayi filariasis. Parasite antigen-specific cellular and humoral immune responses were assessed post-challenge. Results The use of lipopeptides in ALM-containing vaccines did not provide any protection upon infection with L. major, and Pam2 exacerbated the disease severity in vaccinated mice post-challenge. Pam2, and to a lesser extent Pam3, were able to elevate antigen-specific immune responses post-challenge in this model, but these responses displayed a skewed Th2 phenotype as characterised by elevated levels of IgG1. In the B. malayi vaccine model, the use of Pam2 as an adjuvant with BmMfE induced significant protective immunity to the same level as inclusion of an Alum adjuvant. Here, both Pam2 and Alum were found to enhance antigen-specific antibody production post-challenge, and Pam2 significantly elevated levels of antigen-specific IL-4, IL-5 and IL-13 produced

Published
2016

35. The role of TLR2 in cutaneous leishmaniasis and as a target for vaccine adjuvants

Author

Halliday, Alice, Taylor, Mark, and Craig, Alister

Subjects
RC
Abstract

After the introduction of clean water, vaccination is thought to be the most effective public health tool ever introduced, responsible for preventing millions of cases of disease, disability and death each year. Unfortunately there remain a number of important human diseases for which we have no vaccine, particularly parasitic diseases, such as leishmaniasis, which primarily affect poor communities in tropical regions. There are many complex reasons why we have failed to develop effective vaccines for parasitic diseases, but there is hope that with our improved understanding of the immune system alongside the development of a new generation of vaccines, we will soon develop new vaccines which are effective enough to prevent such diseases. Toll-like receptors (TLRs) are major targets for adjuvants and have been shown to be crucial for defence against a number of infections. TLR2 recognises bacterial lipopeptides in a heterodimer with either TLR1 or TLR6, and its function has been linked to protection against various bacterial infections and to the efficacy of the BCG vaccine. TLR2 has been shown to recognise surface glycoconjugates of Leishmania parasites in vitro, particularly lipophosphoglycan (LPG). In this study, in vivo experimental infections show that TLR2 has a protective role in controlling cutaneous leishmaniasis (CL), as shown by increased lesion sizes and parasite burdens in TLR2-/- mice infected with L. major and L. mexicana. Furthermore, it appears that LPG is not the major mediator of TLR2 activation during infection with L. mexicana, as parasites lacking LPG also resulted in exacerbated disease in TLR2-/- mice. Mice lacking TLR2 co-receptors TLR1 and TLR6 did not show increased susceptibility to infection, suggesting either mono-TLR2 function or alternative co-receptor involvement. Infected TLR2-/- mice show a skewed Th2 immune response to Leishmania, as demonstrated by elevated IL-4, IL-13 and IL-10 production by draining lymph node (DLN) cells in response to antigen. These results suggest that TLR2 is involved in promoting protective immune responses to Leishmania parasites during primary infection in vivo, and is a potential target for protective and therapeutic vaccine adjuvants. Paradoxically, however, TLR2-targeting lipopeptides Pam2 and Pam3 were ineffective adjuvants for use in a whole-cell vaccine to protect against CL, as whole-cell autoclaved L. major (ALM) vaccines containing lipopeptides resulted in exacerbated disease upon challenge when compared to unvaccinated controls and in contrast to effective vaccination when CpG adjuvants were used. The ratio of antigen specific IgG1:IgG2c antibody isotypes, which is a marker of the type of adaptive immune response (Th1 or Th2), was elevated in mice that received vaccines containing lipopeptide adjuvants, suggesting that these adjuvants drive non-protective Th2 responses to Leishmania. In a Th2-dependent vaccine model using Brugia malayi, the use of Pam2 as an adjuvant resulted in an enhanced protective phenotype with similar efficacy to the Th2-driving adjuvant Alum. Thus, in the context of CL infection TLR2 has a protective role in late-stage primary infections with L. major and L. mexicana, yet when targeted with lipopeptide adjuvants in whole-cell vaccines promotes exacerbated disease in challenge infections, through driving Th2 immune responses. Lipopeptides that target TLR2, such as Pam2, are therefore more appropriate for use as adjuvants in vaccines where Th2 protective immunity is required.

Published
2014
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38. A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis

Author

Halliday, Alice, Guimaraes, Ana F, Tyrer, Hayley, Metuge, Haelly Mejane, Patrick, Chounna Ndongmo Winston, Arnaud, Kengne-Ouafo Jonas, Kwenti, Tayong Dizzle Bita, Forsbrook, George, Steven, Andrew, Cook, Darren, Enyong, Peter, Wanji, Samuel, Taylor, Mark J, Turner, Joseph D, Halliday, Alice, Guimaraes, Ana F, Tyrer, Hayley, Metuge, Haelly Mejane, Patrick, Chounna Ndongmo Winston, Arnaud, Kengne-Ouafo Jonas, Kwenti, Tayong Dizzle Bita, Forsbrook, George, Steven, Andrew, Cook, Darren, Enyong, Peter, Wanji, Samuel, Taylor, Mark J, and Turner, Joseph D

Abstract

Background: New drugs effective against adult filariae (macrofilaricides) would accelerate the elimination of lymphatic filariasis and onchocerciasis. Anti-Onchocerca drug development is hampered by the lack of a facile model. We postulated that SCID mice could be developed as a fmacrofilaricide screening model. Methods: The filaricides: albendazole (ABZ), diethylcarbamazine (DEC), flubendazole (FBZ), ivermectin (IVM) and the anti-Wolbachia macrofilaricide, minocycline (MIN) were tested in Brugia malayi (Bm)-parasitized BALB/c SCID mice vs vehicle control (VC). Responses were compared to BALB/c wild type (WT). Onchocerca ochengi male worms or onchocercomata were surgically implanted into BALB/c SCID, CB.17 SCID, BALB/c WT mice or Meriones gerbils. Survival was evaluated at 7–15 days. BALB/c SCID were tested to evaluate the responsiveness of pre-clinical macrofilaricides FBZ and rifapentine (RIFAP) against male Onchocerca. Results: WT and SCID responded with >95% efficacy following ABZ or DEC treatments against Bm larvae (P < 0.0001). IVM was partially filaricidal against Bm larvae in WT and SCID (WT; 39.8%, P = 0.0356 and SCID; 56.7%, P = 0.026). SCID responded similarly to WT following IVM treatment of microfilaraemias (WT; 79%, P = 0.0194. SCID; 76%, P = 0.0473). FBZ induced a total macrofilaricidal response against adult Bm in WT and SCID (WT; P = 0.0067, SCID; P = 0.0071). MIN induced a >90% reduction in Bm Wolbachia burdens (P < 0.0001) and a blockade of microfilarial release (P = 0.0215) in SCID. Male Onchocerca survival was significantly higher in SCID vs WT mice, but not gerbils, after +15 days (60% vs 22% vs 39% P = 0.0475). Onchocercoma implants had engrafted into host tissues, with evidence of neovascularisation, after +7 days and yielded viable macro/microfilariae ex vivo. FBZ induced a macrofilaricidal effect in Onchocerca male implanted SCID at +5 weeks (FBZ; 1.67% vs VC; 43.81%, P = 0.0089). Wolbachia loads within male Onchocerca were reduced by 99% i

Published
2014

39. A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis

Author

Halliday, Alice, primary, Guimaraes, Ana F, additional, Tyrer, Hayley E, additional, Metuge, Haelly Mejane, additional, Patrick, Chounna Ndongmo Winston, additional, Arnaud, Kengne-Ouafo Jonas, additional, Kwenti, Tayong Dizzle Bita, additional, Forsbrook, George, additional, Steven, Andrew, additional, Cook, Darren, additional, Enyong, Peter, additional, Wanji, Samuel, additional, Taylor, Mark J, additional, and Turner, Joseph D, additional

Published
2014
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42. A murine macrofilaricide screening model for onchocerciasis and lymphatic filariasis.

Author

Halliday, Alice, Guimaraes, Ana F., Tyrer, Hayley E., Metuge, Haelly Mejane, Winston Patrick, Chounna Ndongmo, Arnaud, Kengne-Ouafo Jonas, Bita Kwenti, Tayong Dizzle, Forsbrook, George, Steven, Andrew, Cook, Darren, Enyong, Peter, Wanji, Samuel, Taylor, Mark J., and Turner, Joseph D.

Subjects
*ONCHOCERCIASIS, *LYMPH, *FILARIASIS, *LYMPHATICS, *BRUGIA malayi
Abstract

Background New drugs effective against adult filariae (macrofilaricides) would accelerate the elimination of lymphatic filariasis and onchocerciasis. Anti-Onchocerca drug development is hampered by the lack of a facile model. We postulated that SCID mice could be developed as a fmacrofilaricide screening model. Methods The filaricides: albendazole (ABZ), diethylcarbamazine (DEC), flubendazole (FBZ), ivermectin (IVM) and the anti-Wolbachia macrofilaricide, minocycline (MIN) were tested in Brugia malayi (Bm)-parasitized BALB/c SCID mice vs vehicle control (VC). Responses were compared to BALB/c wild type (WT). Onchocerca ochengi male worms or onchocercomata were surgically implanted into BALB/c SCID, CB.17 SCID, BALB/c WT mice or Meriones gerbils. Survival was evaluated at 7-15 days. BALB/c SCID were tested to evaluate the responsiveness of pre-clinical macrofilaricides FBZ and rifapentine (RIFAP) against male Onchocerca. Results WT and SCID responded with >95% efficacy following ABZ or DEC treatments against Bm larvae (P < 0.0001). IVM was partially filaricidal against Bm larvae in WT and SCID (WT; 39.8%, P = 0.0356 and SCID; 56.7%, P = 0.026). SCID responded similarly to WT following IVM treatment of microfilaraemias (WT; 79%, P = 0.0194. SCID; 76%, P = 0.0473). FBZ induced a total macrofilaricidal response against adult Bm in WT and SCID (WT; P = 0.0067, SCID; P = 0.0071). MIN induced a >90% reduction in Bm Wolbachia burdens (P < 0.0001) and a blockade of microfilarial release (P = 0.0215) in SCID. Male Onchocerca survival was significantly higher in SCID vs WT mice, but not gerbils, after +15 days (60% vs 22% vs 39% P = 0.0475). Onchocercoma implants had engrafted into host tissues, with evidence of neovascularisation, after +7 days and yielded viable macro/microfilariae ex vivo. FBZ induced a macrofilaricidal effect in Onchocerca male implanted SCID at +5 weeks (FBZ; 1.67% vs VC; 43.81%, P = 0.0089). Wolbachia loads within male Onchocerca were reduced by 99% in implanted SCID receiving RIFAP for +2 weeks. Conclusions We have developed a 'pan-filarial' small animal research model that is sufficiently robust, with adequate capacity and throughput, to screen existing and future pre-clinical candidate macrofilaricides. Pilot data suggests a murine onchocercoma xenograft model is achievable. [ABSTRACT FROM AUTHOR]

Published
2014
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45. Onchocerciasis: the Role of WolbachiaBacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment

Author

Tamarozzi, Francesca, Halliday, Alice, Gentil, Katrin, Hoerauf, Achim, Pearlman, Eric, and Taylor, Mark J.

Abstract

SUMMARYThe discovery of Wolbachiaintracellular bacteria within filarial nematodes, including Onchocerca volvulus, the causative agent of onchocerciasis or “river blindness,” has delivered a paradigm shift in our understanding of the parasite's biology, to where we now know that the bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms. The apparent mutualistic dependency has also offered a novel approach to the treatment of onchocerciasis through the use of antibiotics to eliminate Wolbachia, delivering for the first time a treatment which has significant macrofilaricidal efficacy. Studies with other filarial nematode species have also highlighted a role for Wolbachiain transmission and infection of the mammalian host through a fascinating manipulation of mast cell-mediated vasodilation to enhance infectivity of vector-borne larvae. Wolbachiahas also been identified as the principal driver of innate and adaptive Th1 inflammatory immunity, which can either contribute to disease pathogenesis or, with the Wolbachia-mediated recruitment of mast cells, enhance infectivity. The Wolbachiaactivation of innate inflammation also drives inflammatory adverse events in response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In this review we summarize the experimental and field trial data which have uncovered the importance of Wolbachiasymbiosis in onchocerciasis.

Published
2011
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46. MOESM2 of Old World cutaneous leishmaniasis treatment response varies depending on parasite species, geographical location and development of secondary infection

Author

Al-Salem, Waleed, Solórzano, Carla, Weedall, Gareth, Dyer, Naomi, Kelly-Hope, Louise, Casas-Sánchez, Aitor, Alraey, Yasser, Alyamani, Essam, Halliday, Alice, Balghonaim, Salah, Alsohibany, Khalid, Alzeyadi, Zeyad, Alzahrani, Mohamed, Al-Shahrani, Ali, Assiri, Abdullah, Memish, Ziad, and Acosta-Serrano, Álvaro

Subjects
parasitic diseases, 3. Good health
Abstract

Additional file 2: Figure S1. Scheme representing the current leishmaniasis treatment policy in KSA. Figure S2. Leishmania spp. identification in Central Region by PCR-RFLP analysis of parasite ITS1 region. Lane Lt: L. tropica positive control; Lane Lm: L. major positive control; Lanes 1–10: different examples of Leishmania isolates from Rass, Dwadmi and Muzahmyyah. Figure S3. Leishmania spp identification in Al Madinah Province by PCR-RFLP analysis of parasite ITS1 region. Lanes 1–4: different examples of Leishmania isolates from Aljadaida and Sulailah, Al Madinah Province; Lanes 1 and 2: L. tropica samples; Lanes 3 and 4: L. major samples; Lane Lm: L. major positive control; Lane Lt: L. tropica positive control. Figure S4. Leishmania spp. identification in Al Ahsa Region by PCR-RFLP analysis of parasite ITS1 region. Lanes 1–13: different examples of Leishmania isolates from Al Ahsa Region; Lane Lt: L. tropica positive control; Lane Lm: L. major positive control. Figure S5. Leishmania spp identification in Asir Region by PCR-RFLP analysis of parasite ITS1 region. Lanes 1–5: different examples of Leishmania isolates from Asir Province. Figure S6. Distribution of Leishmania species (a) and patient response to anti-leishmanial treatment (b) within the Eastern region of Saudi Arabia. The map was created using software ArcGIS 10 (ESRI, Redlands, CA). Figure S7. Distribution of Leishmania species (a) and patient response to anti-leishmanial treatment (b) within the Northwest region of Saudi Arabia. The map was created using software ArcGIS 10 (ESRI, Redlands, CA). Figure S8. Distribution of Leishmania species (a) and patient response to anti-leishmanial treatment (b) within the southwest region of Saudi Arabia. The map was created using software ArcGIS 10 (ESRI, Redlands, CA).

47. MOESM2 of Old World cutaneous leishmaniasis treatment response varies depending on parasite species, geographical location and development of secondary infection

Author

Al-Salem, Waleed, Solórzano, Carla, Weedall, Gareth, Dyer, Naomi, Kelly-Hope, Louise, Casas-Sánchez, Aitor, Alraey, Yasser, Alyamani, Essam, Halliday, Alice, Balghonaim, Salah, Alsohibany, Khalid, Alzeyadi, Zeyad, Alzahrani, Mohamed, Al-Shahrani, Ali, Assiri, Abdullah, Memish, Ziad, and Acosta-Serrano, Álvaro

Subjects
parasitic diseases, 3. Good health
Abstract

Additional file 2: Figure S1. Scheme representing the current leishmaniasis treatment policy in KSA. Figure S2. Leishmania spp. identification in Central Region by PCR-RFLP analysis of parasite ITS1 region. Lane Lt: L. tropica positive control; Lane Lm: L. major positive control; Lanes 1–10: different examples of Leishmania isolates from Rass, Dwadmi and Muzahmyyah. Figure S3. Leishmania spp identification in Al Madinah Province by PCR-RFLP analysis of parasite ITS1 region. Lanes 1–4: different examples of Leishmania isolates from Aljadaida and Sulailah, Al Madinah Province; Lanes 1 and 2: L. tropica samples; Lanes 3 and 4: L. major samples; Lane Lm: L. major positive control; Lane Lt: L. tropica positive control. Figure S4. Leishmania spp. identification in Al Ahsa Region by PCR-RFLP analysis of parasite ITS1 region. Lanes 1–13: different examples of Leishmania isolates from Al Ahsa Region; Lane Lt: L. tropica positive control; Lane Lm: L. major positive control. Figure S5. Leishmania spp identification in Asir Region by PCR-RFLP analysis of parasite ITS1 region. Lanes 1–5: different examples of Leishmania isolates from Asir Province. Figure S6. Distribution of Leishmania species (a) and patient response to anti-leishmanial treatment (b) within the Eastern region of Saudi Arabia. The map was created using software ArcGIS 10 (ESRI, Redlands, CA). Figure S7. Distribution of Leishmania species (a) and patient response to anti-leishmanial treatment (b) within the Northwest region of Saudi Arabia. The map was created using software ArcGIS 10 (ESRI, Redlands, CA). Figure S8. Distribution of Leishmania species (a) and patient response to anti-leishmanial treatment (b) within the southwest region of Saudi Arabia. The map was created using software ArcGIS 10 (ESRI, Redlands, CA).

48. New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study

Author

Halliday A, Jain P, Hoang L, Parker R, Tolosa-Wright M, Masonou T, Green N, Boakye A, Takwoingi Y, Hamilton S, Mandagere V, Fries A, Coin L, Deeks J, White PJ, Levin M, Beverley P, Kon OM, and Lalvani A

Abstract

Background: Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed., Objective: To validate promising new technologies [namely whole-blood transcriptomics, proteomics, flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)] and existing signatures for the detection of active TB in samples obtained from individuals with suspected active TB., Design: Four substudies, each of which used samples from the biobank collected as part of the interferon gamma release assay (IGRA) in the Diagnostic Evaluation of Active TB study, which was a prospective cohort of patients recruited with suspected TB., Setting: Secondary care., Participants: Adults aged ≥ 16 years presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham, with suspected active TB., Interventions: New tests using genome-wide gene expression microarray (transcriptomics), surface-enhanced laser desorption ionisation time-of-flight mass spectrometry/liquid chromatography–mass spectrometry (proteomics), flow cytometry or qRT-PCR., Main Outcome Measures: Area under the curve (AUC), sensitivity and specificity were calculated to determine diagnostic accuracy. Positive and negative predictive values were calculated in some cases. A decision tree model was developed to calculate the incremental costs and quality-adjusted life-years of changing from current practice to using the novels tests., Results: The project, and four substudies that assessed the previously published signatures, measured each of the new technologies and performed a health economic analysis in which the best-performing tests were evaluated for cost-effectiveness. The diagnostic accuracy of the transcriptomic tests ranged from an AUC of 0.81 to 0.84 for detecting all TB in our cohort. The performance for detecting culture-confirmed TB or pulmonary TB was better than for highly probable TB or extrapulmonary tuberculosis (EPTB), but was not high enough to be clinically useful. None of the previously described serum proteomic signatures for active TB provided good diagnostic accuracy, nor did the candidate rule-out tests. Four out of six previously described cellular immune signatures provided a reasonable level of diagnostic accuracy (AUC = 0.78–0.92) for discriminating all TB from those with other disease and latent TB infection in human immunodeficiency virus-negative TB suspects. Two of these assays may be useful in the IGRA-positive population and can provide high positive predictive value. None of the new tests for TB can be considered cost-effective., Limitations: The diagnostic performance of new tests among the HIV-positive population was either underpowered or not sufficiently achieved in each substudy., Conclusions: Overall, the diagnostic performance of all previously identified ‘signatures’ of TB was lower than previously reported. This probably reflects the nature of the cohort we used, which includes the harder to diagnose groups, such as culture-unconfirmed TB or EPTB, which were under-represented in previous cohorts., Future Work: We are yet to achieve our secondary objective of deriving novel signatures of TB using our data sets. This was beyond the scope of this report. We recommend that future studies using these technologies target specific subtypes of TB, specifically those groups for which new diagnostic tests are required., Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership., (Copyright © Queen’s Printer and Controller of HMSO 2021. This work was produced by Halliday et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)

Published
2021
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