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1. Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population

Author

Nyirenda, James, Hardy, Olympia M., Silva Filho, João Da, Herder, Vanessa, Attipa, Charalampos, Ndovi, Charles, Siwombo, Memory, Namalima, Takondwa Rex, Suwedi, Leticia, Ilia, Georgios, Nyasulu, Watipenge, Ngulube, Thokozile, Nyirenda, Deborah, Mvaya, Leonard, Phiri, Joseph, Chasweka, Dennis, Eneya, Chisomo, Makwinja, Chikondi, Phiri, Chisomo, Ziwoya, Frank, Tembo, Abel, Makwangwala, Kingsley, Khoswe, Stanley, Banda, Peter, Morton, Ben, Hilton, Orla, Lawrence, Sarah, dos Reis, Monique Freire, Melo, Gisely Cardoso, de Lacerda, Marcus Vinicius Guimaraes, Trindade Maranhão Costa, Fabio, Monteiro, Wuelton Marcelo, Ferreira, Luiz Carlos de Lima, Johnson, Carla, McGuinness, Dagmara, Jambo, Kondwani, Haley, Michael, Kumwenda, Benjamin, Palmarini, Massimo, Denno, Donna M., Voskuijl, Wieger, Kamiza, Steve Bvuobvuo, Barnes, Kayla G., Couper, Kevin, Marti, Matthias, Otto, Thomas D., and Moxon, Christopher A.

Published
2024
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2. Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever

Author

Kotliar, Dylan, Raju, Siddharth, Tabrizi, Shervin, Odia, Ikponmwosa, Goba, Augustine, Momoh, Mambu, Sandi, John Demby, Nair, Parvathy, Phelan, Eric, Tariyal, Ridhi, Eromon, Philomena E., Mehta, Samar, Robles-Sikisaka, Refugio, Siddle, Katherine J., Stremlau, Matt, Jalloh, Simbirie, Gire, Stephen K., Winnicki, Sarah, Chak, Bridget, Schaffner, Stephen F., Pauthner, Matthias, Karlsson, Elinor K., Chapin, Sarah R., Kennedy, Sharon G., Branco, Luis M., Kanneh, Lansana, Vitti, Joseph J., Broodie, Nisha, Gladden-Young, Adrianne, Omoniwa, Omowunmi, Jiang, Pan-Pan, Yozwiak, Nathan, Heuklom, Shannon, Moses, Lina M., Akpede, George O., Asogun, Danny A., Rubins, Kathleen, Kales, Susan, Happi, Anise N., Iruolagbe, Christopher O., Dic-Ijiewere, Mercy, Iraoyah, Kelly, Osazuwa, Omoregie O., Okonkwo, Alexander K., Kunz, Stefan, McCormick, Joseph B., Khan, S. Humarr, Honko, Anna N., Lander, Eric S., Oldstone, Michael B. A., Hensley, Lisa, Folarin, Onikepe A., Okogbenin, Sylvanus A., Günther, Stephan, Ollila, Hanna M., Tewhey, Ryan, Okokhere, Peter O., Schieffelin, John S., Andersen, Kristian G., Reilly, Steven K., Grant, Donald S., Garry, Robert F., Barnes, Kayla G., Happi, Christian T., and Sabeti, Pardis C.

Published
2024
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3. Utilizing river and wastewater as a SARS-CoV-2 surveillance tool in settings with limited formal sewage systems

Author

Barnes, Kayla G., Levy, Joshua I., Gauld, Jillian, Rigby, Jonathan, Kanjerwa, Oscar, Uzzell, Christopher B., Chilupsya, Chisomo, Anscombe, Catherine, Tomkins-Tinch, Christopher, Mbeti, Omar, Cairns, Edward, Thole, Herbert, McSweeney, Shannon, Chibwana, Marah G., Ashton, Philip M., Jere, Khuzwayo C., Meschke, John Scott, Diggle, Peter, Cornick, Jennifer, Chilima, Benjamin, Jambo, Kondwani, Andersen, Kristian G., Kawalazira, Gift, Paterson, Steve, Nyirenda, Tonney S., and Feasey, Nicholas

Published
2023
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5. A comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study

Author

Anscombe, Catherine, Lissauer, Samantha, Thole, Herbert, Rylance, Jamie, Dula, Dingase, Menyere, Mavis, Kutambe, Belson, van der Veer, Charlotte, Phiri, Tamara, Banda, Ndaziona P., Mndolo, Kwazizira S., Mponda, Kelvin, Phiri, Chimota, Mallewa, Jane, Nyirenda, Mulinda, Katha, Grace, Mwandumba, Henry, Gordon, Stephen B., Jambo, Kondwani C., Cornick, Jennifer, Feasey, Nicholas, Barnes, Kayla G., Morton, Ben, and Ashton, Philip M.

Published
2023
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6. Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics

Author

Kotliar, Dylan, Lin, Aaron E., Logue, James, Hughes, Travis K., Khoury, Nadine M., Raju, Siddharth S., Wadsworth, Marc H., II, Chen, Han, Kurtz, Jonathan R., Dighero-Kemp, Bonnie, Bjornson, Zach B., Mukherjee, Nilanjan, Sellers, Brian A., Tran, Nancy, Bauer, Matthew R., Adams, Gordon C., Adams, Ricky, Rinn, John L., Melé, Marta, Schaffner, Stephen F., Nolan, Garry P., Barnes, Kayla G., Hensley, Lisa E., McIlwain, David R., Shalek, Alex K., Sabeti, Pardis C., and Bennett, Richard S.

Published
2020
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7. Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response

Author

Nyirenda, James, primary, Hardy, Olympia, additional, Da Silva Filho, João, additional, Herder, Vanessa, additional, Attipa, Charalampos, additional, Ndovi, Charles, additional, Siwombo, Memory, additional, Namalima, Takondwa, additional, Suwedi, Leticia, additional, Nyasulu, Watipenge, additional, Ngulube, Thokozile, additional, Nyirenda, Deborah, additional, Mvaya, Leonard, additional, Phiri, Joseph, additional, Chasweka, Dennis, additional, Eneya, Chisomo, additional, Makwinja, Chikondi, additional, Phiri, Chisomo, additional, Ziwoya, Frank, additional, Tembo, Abel, additional, Makwangwala, Kingsley, additional, Khoswe, Stanley, additional, Banda, Peter, additional, Morton, Ben, additional, Hilton, Orla, additional, Lawrence, Sarah, additional, dos Reis, Monique Freire, additional, Melo, Gisely Cardoso, additional, de Lacerda, Marcus Vinicius Guimaraes, additional, Costa, Fabio Trindade Maranhão, additional, Monteiro, Wuelton Marcelo, additional, de Lima Ferreira, Luiz Carlos, additional, Johnson, Carla, additional, McGuinness, Dagmara, additional, Jambo, Kondwani, additional, Haley, Michael, additional, Kumwenda, Benjamin, additional, Palmarini, Massimo, additional, Barnes, Kayla G., additional, Denno, Donna M., additional, Voskuijl, Wieger, additional, Kamiza, Steve, additional, Couper, Kevin, additional, Marti, Matthias, additional, Otto, Thomas, additional, and Moxon, Christopher A., additional

Published
2023
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8. Field-deployable viral diagnostics using CRISPR-Cas13

Author

Myhrvold, Cameron, Freije, Catherine A., Gootenberg, Jonathan S., Abudayyeh, Omar O., Metsky, Hayden C., Durbin, Ann F., Kellner, Max J., Tan, Amanda L., Paul, Lauren M., Parham, Leda A., Garcia, Kimberly F., Barnes, Kayla G., Chak, Bridget, Mondini, Adriano, Nogueira, Mauricio L., Isern, Sharon, Michael, Scott F., Lorenzana, Ivette, Yozwiak, Nathan L., MacInnis, Bronwyn L., Bosch, Irene, Gehrke, Lee, Zhang, Feng, and Sabeti, Pardis C.

Published
2018

9. Retrospective Cohort Study of Lassa Fever in Pregnancy, Southern Nigeria

Author

Okogbenin, Sylvanus, Okoeguale, Joseph, Akpede, George, Colubri, Andres, Barnes, Kayla G., Mehta, Samar, Eifediyi, Reuben, Okogbo, Felix, Eigbefoh, Joseph, Momoh, Mojeed, Rafiu, Mojeed, Adomeh, Donatus, Odia, Ikponmwosa, Aire, Chris, Atafo, Rebecca, Okonofua, Martha, Pahlman, Meike, Becker-Ziaja, Beate, Asogun, Danny, Okokhere, Peter, Happi, Christian, Gunther, Stephan, Sabeti, Pardis C., and Ogbaini-Emovon, Ephraim

Subjects
Infant mortality, Obstetrics, Lassa fever, Medical research, Pregnancy, Pregnant women, Death, Urination disorders, Hospital patients, Ribavirin, Teachers, Fetal death, Convulsions, Health
Abstract

Lassa fever (LF), a viral hemorrhagic fever endemic to West Africa (1-3), was first reported in 1969 from northern Nigeria (4,5). Since that time, LF has been documented in several [...]

Published
2019

10. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design

Author

Metsky, Hayden C., Siddle, Katherine J., Gladden-Young, Adrianne, Qu, James, Yang, David K., Brehio, Patrick, Goldfarb, Andrew, Piantadosi, Anne, Wohl, Shirlee, Carter, Amber, Lin, Aaron E., Barnes, Kayla G., Tully, Damien C., Corleis, Bjӧrn, Hennigan, Scott, Barbosa-Lima, Giselle, Vieira, Yasmine R., Paul, Lauren M., Tan, Amanda L., Garcia, Kimberly F., Parham, Leda A., Odia, Ikponmwosa, Eromon, Philomena, Folarin, Onikepe A., Goba, Augustine, Simon-Lorière, Etienne, Hensley, Lisa, Balmaseda, Angel, Harris, Eva, Kwon, Douglas S., Allen, Todd M., Runstadler, Jonathan A., Smole, Sandra, Bozza, Fernando A., Souza, Thiago M. L., Isern, Sharon, Michael, Scott F., Lorenzana, Ivette, Gehrke, Lee, Bosch, Irene, Ebel, Gregory, Grant, Donald S., Happi, Christian T., Park, Daniel J., Gnirke, Andreas, Sabeti, Pardis C., and Matranga, Christian B.

Published
2019
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11. Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum.

Author

Van Tyne, Daria, Park, Daniel J, Schaffner, Stephen F, Neafsey, Daniel E, Angelino, Elaine, Cortese, Joseph F, Barnes, Kayla G, Rosen, David M, Lukens, Amanda K, Daniels, Rachel F, Milner, Danny A, Johnson, Charles A, Shlyakhter, Ilya, Grossman, Sharon R, Becker, Justin S, Yamins, Daniel, Karlsson, Elinor K, Ndiaye, Daouda, Sarr, Ousmane, Mboup, Souleymane, Happi, Christian, Furlotte, Nicholas A, Eskin, Eleazar, Kang, Hyun Min, Hartl, Daniel L, Birren, Bruce W, Wiegand, Roger C, Lander, Eric S, Wirth, Dyann F, Volkman, Sarah K, and Sabeti, Pardis C

Subjects
Plasmodium falciparum, Malaria, Falciparum, Ethanolamines, Mefloquine, Fluorenes, Phenanthrenes, Antimalarials, Gene Expression, Drug Resistance, Genotype, Gene Dosage, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genetic Variation, Selection, Genetic, Genetic Loci, Genetic Association Studies, Lumefantrine, Malaria, Falciparum, Polymorphism, Single Nucleotide, Selection, Genetic, Genetics, Developmental Biology
Abstract

The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (∼ 1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.

Published
2011

13. Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time

Author

Barnes, Kayla G., Lachenauer, Anna E., Nitido, Adam, Siddiqui, Sameed, Gross, Robin, Beitzel, Brett, Siddle, Katherine J., Freije, Catherine A., Dighero-Kemp, Bonnie, Mehta, Samar B., Carter, Amber, Uwanibe, Jessica, Ajogbasile, Fehintola, Olumade, Testimony, Odia, Ikponmwosa, Sandi, John Demby, Momoh, Mambu, Metsky, Hayden C., Boehm, Chloe K., Lin, Aaron E., Kemball, Molly, Park, Daniel J., Branco, Luis, Boisen, Matt, Sullivan, Brian, Amare, Mihret F., Tiamiyu, Abdulwasiu B., Parker, Zahra F., Iroezindu, Michael, Grant, Donald S., Modjarrad, Kayvon, Myhrvold, Cameron, Garry, Robert F., Palacios, Gustavo, Hensley, Lisa E., Schaffner, Stephen F., Happi, Christian T., Colubri, Andres, and Sabeti, Pardis C.

Published
2020
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14. Field evaluation of a Pan-Lassa rapid diagnostic test during the 2018 Nigerian Lassa fever outbreak

Author

Boisen, Matthew L., Uyigue, Eghosa, Aiyepada, John, Siddle, Katherine J., Oestereich, Lisa, Nelson, Diana K. S., Bush, Duane J., Rowland, Megan M., Heinrich, Megan L., Eromon, Philomena, Kayode, Adeyemi T., Odia, Ikponmwosa, Adomeh, Donatus I., Muoebonam, Ekene B., Akhilomen, Patience, Okonofua, Grace, Osiemi, Blessing, Omoregie, Omigie, Airende, Michael, Agbukor, Jacqueline, Ehikhametalor, Solomon, Aire, Chris Okafi, Duraffour, Sophie, Pahlmann, Meike, Böhm, Wiebke, Barnes, Kayla G., Mehta, Samar, Momoh, Mambu, Sandi, John Demby, Goba, Augustine, Folarin, Onikepe A., Ogbaini-Emovan, Ephraim, Asogun, Danny A., Tobin, Ekaete A., Akpede, George O., Okogbenin, Sylvanus A., Okokhere, Peter O., Grant, Donald S., Schieffelin, John S., Sabeti, Pardis C., Günther, Stephan, Happi, Christian T., Branco, Luis M., and Garry, Robert F.

Published
2020
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15. Acute rotavirus infection is associated with the induction of circulating memory CD4+ T cell subsets

Author

Malamba-Banda, Chikondi, primary, Mhango, Chimwemwe, additional, Benedicto-Matambo, Prisca, additional, Mandolo, Jonathan J., additional, Chinyama, End, additional, Kumwenda, Orpha, additional, Barnes, Kayla G., additional, Cunliffe, Nigel A., additional, Iturriza-Gomara, Miren, additional, Jambo, Kondwani C., additional, and Jere, Khuzwayo C., additional

Published
2023
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16. Comparative whole genome analysis reveals re-emergence of human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi.

Author

Mhango, Chimwemwe, primary, Banda, Akuzike, additional, Chinyama, End, additional, Mandolo, Jonathan J, additional, Kumwenda, Orpha, additional, Malamba-Banda, Chikondi, additional, Barnes, Kayla G, additional, Kumwenda, Benjamin, additional, Jambo, Kondwani, additional, Donato, Celeste M, additional, Esona, Mathew D, additional, Mwangi, Peter N, additional, Steele, A Duncan, additional, Iturriza-Gomara, Miren, additional, Cunliffe, Nigel A, additional, Ndze, Valentine N, additional, Kamng’ona, Arox W, additional, Dennis, Francis E, additional, Nyaga, Martin M, additional, Chaguza, Chrispin, additional, and Jere, Khuzwayo C, additional

Published
2023
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18. Different clinical features in Malawian outpatients presenting with COVID-19 prior to and during Omicron variant dominance: A prospective observational study

Author

Epi Infectieziekten Team 1, Chibwana, Marah G., Thole, Herbert W., Anscombe, Cat, Ashton, Philip M., Green, Edward, Barnes, Kayla G., Cornick, Jen, Turner, Ann, Witte, Desiree, Nthala, Sharon, Thom, Chikondi, Kanyandula, Felistas, Ainani, Anna, Mtike, Natasha, Tambala, Hope, N'goma, Veronica, Mwafulirwa, Dorah, Asima, Erick, Morton, Ben, Gmeiner, Markus, Gundah, Zaziwe, Kawalazira, Gift, French, Neil, Feasey, Nicholas, Heyderman, Robert S., Swarthout, Todd D., Jambo, Kondwani C., Epi Infectieziekten Team 1, Chibwana, Marah G., Thole, Herbert W., Anscombe, Cat, Ashton, Philip M., Green, Edward, Barnes, Kayla G., Cornick, Jen, Turner, Ann, Witte, Desiree, Nthala, Sharon, Thom, Chikondi, Kanyandula, Felistas, Ainani, Anna, Mtike, Natasha, Tambala, Hope, N'goma, Veronica, Mwafulirwa, Dorah, Asima, Erick, Morton, Ben, Gmeiner, Markus, Gundah, Zaziwe, Kawalazira, Gift, French, Neil, Feasey, Nicholas, Heyderman, Robert S., Swarthout, Todd D., and Jambo, Kondwani C.

Published
2023

19. Different clinical features in Malawian outpatients presenting with COVID-19 prior to and during Omicron variant dominance: A prospective observational study

Author

Chibwana, Marah G., primary, Thole, Herbert W., additional, Anscombe, Cat, additional, Ashton, Philip M., additional, Green, Edward, additional, Barnes, Kayla G., additional, Cornick, Jen, additional, Turner, Ann, additional, Witte, Desiree, additional, Nthala, Sharon, additional, Thom, Chikondi, additional, Kanyandula, Felistas, additional, Ainani, Anna, additional, Mtike, Natasha, additional, Tambala, Hope, additional, N’goma, Veronica, additional, Mwafulirwa, Dorah, additional, Asima, Erick, additional, Morton, Ben, additional, Gmeiner, Markus, additional, Gundah, Zaziwe, additional, Kawalazira, Gift, additional, French, Neil, additional, Feasey, Nicholas, additional, Heyderman, Robert S., additional, Swarthout, Todd D., additional, and Jambo, Kondwani C., additional

Published
2023
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20. Additional file 2 of A comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study

Author

Anscombe, Catherine, Lissauer, Samantha, Thole, Herbert, Rylance, Jamie, Dula, Dingase, Menyere, Mavis, Kutambe, Belson, van der Veer, Charlotte, Phiri, Tamara, Banda, Ndaziona P., Mndolo, Kwazizira S., Mponda, Kelvin, Phiri, Chimota, Mallewa, Jane, Nyirenda, Mulinda, Katha, Grace, Mwandumba, Henry, Gordon, Stephen B., Jambo, Kondwani C., Cornick, Jennifer, Feasey, Nicholas, Barnes, Kayla G., Morton, Ben, and Ashton, Philip M.

Abstract

Additional file 2. Supplementary figures.

Published
2023
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21. Circulating cytokine-producing VP6-specific CD4+ T cells are rarely detectable in Rotarix -vaccinated Malawian children with severe rotavirus diarrhoea

Author

Banda, Chikondi Malamba-, primary, Mhango, Chimwemwe, additional, Benedicto-Matambo, Prisca, additional, Mandolo, Jonathan J., additional, Chinyama, End, additional, Kumwenda, Orpha, additional, Barnes, Kayla G., additional, Cunliffe, Nigel A., additional, Iturriza-Gomara, Miren, additional, Jambo, Kondwani C., additional, and Jere, Khuzwayo C., additional

Published
2022
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22. Comparative whole genome analysis reveals re-emergence of typical human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi

Author

Mhango, Chimwemwe, primary, Banda, Akuzike, additional, Chinyama, End, additional, Mandolo, Jonathan J., additional, Kumwenda, Orpha, additional, Malamba-Banda, Chikondi, additional, Barnes, Kayla G., additional, Kumwenda, Benjamin, additional, Jambo, Kondwani, additional, Donato, Celeste M., additional, Esona, Mathew D., additional, Mwangi, Peter N., additional, Steele, A. Duncan, additional, Iturriza-Gomara, Miren, additional, Cunliffe, Nigel A., additional, Ndze, Valentine N., additional, Kamng’ona, Arox W., additional, Dennis, Francis E., additional, Nyaga, Martin M., additional, Chaguza, Chrispin, additional, and Jere, Khuzwayo C., additional

Published
2022
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24. Acute rotavirus infection is associated with the induction of circulating memory CD4+ T cell subsets.

Author

Malamba-Banda, Chikondi, Mhango, Chimwemwe, Benedicto-Matambo, Prisca, Mandolo, Jonathan J., Chinyama, End, Kumwenda, Orpha, Barnes, Kayla G., Cunliffe, Nigel A., Iturriza-Gomara, Miren, Jambo, Kondwani C., and Jere, Khuzwayo C.

Subjects
ROTAVIRUS diseases, T cells, IMMUNOLOGIC memory, T helper cells, SYMPTOMS, CHILD development
Abstract

Strong CD4+ T cell-mediated immune protection following rotavirus infection has been observed in animal models, but its relevance in humans remains unclear. Here, we characterized acute and convalescent CD4+ T cell responses in children who were hospitalized with rotavirus-positive and rotavirus-negative diarrhoea in Blantyre, Malawi. Children presenting with laboratory-confirmed rotavirus infection had higher proportions of effector and central memory T helper 2 cells during acute infection i.e., at disease presentation compared to convalescence, 28 days post-infection defined by a follow-up 28 days after acute infection. However, circulating cytokine-producing (IFN-γ and/or TNF-α) rotavirus-specific VP6-specific CD4+ T cells were rarely detectable in children with rotavirus infection at both acute and convalescent stages. Moreover, following whole blood mitogenic stimulation, the responding CD4+ T cells were predominantly non-cytokine producers of IFN-γ and/or TNF-α. Our findings demonstrate limited induction of anti-viral IFN-γ and/or TNF-α-producing CD4+ T cells in rotavirus-vaccinated Malawian children following the development of laboratory-confirmed rotavirus infection. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Differential symptoms among COVID-19 outpatients before and during periods of SARS-CoV-2 Omicron variant dominance in Blantyre, Malawi: a prospective observational study

Author

Chibwana, Marah G., primary, Thole, Herbert W., additional, Anscombe, Cat, additional, Ashton, Philip M., additional, Green, Edward, additional, Barnes, Kayla G., additional, Cornick, Jen, additional, Turner, Ann, additional, Witte, Desiree, additional, Nthala, Sharon, additional, Thom, Chikondi, additional, Kanyandula, Felistas, additional, Ainani, Anna, additional, Mtike, Natasha, additional, Tambala, Hope, additional, N’goma, Veronica, additional, Mwafulirwa, Dorah, additional, Asima, Erick, additional, Morton, Ben, additional, Gmeiner, Markus, additional, Gundah, Zaziwe, additional, Kawalazira, Gift, additional, French, Neil, additional, Feasey, Nicholas, additional, Heyderman, Robert S., additional, Swarthout, Todd D, additional, and Jambo, Kondwani C., additional

Published
2022
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27. Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics

Author

Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Kotliar, Dylan, Lin, Aaron E, Logue, James, Hughes, Travis K, Khoury, Nadine M, Raju, Siddharth S, Wadsworth, Marc H, Chen, Han, Kurtz, Jonathan R, Dighero-Kemp, Bonnie, Bjornson, Zach B, Mukherjee, Nilanjan, Sellers, Brian A, Tran, Nancy, Bauer, Matthew R, Adams, Gordon C, Adams, Ricky, Rinn, John L, Melé, Marta, Schaffner, Stephen F, Nolan, Garry P, Barnes, Kayla G, Hensley, Lisa E, McIlwain, David R, Shalek, Alex K, Sabeti, Pardis C, Bennett, Richard S, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Kotliar, Dylan, Lin, Aaron E, Logue, James, Hughes, Travis K, Khoury, Nadine M, Raju, Siddharth S, Wadsworth, Marc H, Chen, Han, Kurtz, Jonathan R, Dighero-Kemp, Bonnie, Bjornson, Zach B, Mukherjee, Nilanjan, Sellers, Brian A, Tran, Nancy, Bauer, Matthew R, Adams, Gordon C, Adams, Ricky, Rinn, John L, Melé, Marta, Schaffner, Stephen F, Nolan, Garry P, Barnes, Kayla G, Hensley, Lisa E, McIlwain, David R, Shalek, Alex K, Sabeti, Pardis C, and Bennett, Richard S

Abstract

© 2020 The Author(s) Single-cell profiling of circulating immune cells during Ebola virus (EBOV) infection in non-human primates resolves molecular correlates of viral tropism, characterizes replication dynamics within infected cells, and distinguishes expression changes that are mediated by viral infection from those due to cytokine signaling.

Published
2022

28. In vivo single-cell profiling of lncRNAs during Ebola virus infection

Author

Santus, Luisa, primary, García-Pérez, Raquel, additional, Sopena-Rios, Maria, additional, Lin, Aaron E, additional, Adams, Gordon C, additional, Barnes, Kayla G, additional, Siddle, Katherine J, additional, Wohl, Shirlee, additional, Reverter, Ferran, additional, Rinn, John L, additional, Bennett, Richard S, additional, Hensley, Lisa E, additional, Sabeti, Pardis C, additional, and Melé, Marta, additional

Published
2022
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29. Distinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa

Author

Morton, Ben, Barnes, Kayla G., Anscombe, Catherine, Jere, Khuzwayo, Matambo, Prisca, Mandolo, Jonathan, Kamng’ona, Raphael, Brown, Comfort, Nyirenda, James, Phiri, Tamara, Banda, Ndaziona P., Van Der Veer, Charlotte, Mndolo, Kwazizira S., Mponda, Kelvin, Rylance, Jamie, Phiri, Chimota, Mallewa, Jane, Nyirenda, Mulinda, Katha, Grace, Kambiya, Paul, Jafali, James, Mwandumba, Henry C., Gordon, Stephen B., Cornick, Jennifer, Jambo, Kondwani C., Phulusa, Jacob, Mkandawire, Mercy, Kaimba, Sylvester, Thole, Herbert, Nthala, Sharon, Nsomba, Edna, Keyala, Lucy, Mandala, Peter, Chinoko, Beatrice, Gmeiner, Markus, Kaudzu, Vella, Lissauer, Samantha, Freyne, Bridget, MacPherson, Peter, Swarthout, Todd D., Iroh Tam, Pui-Ying, Sichone, Simon, Ahmadu, Ajisa, Kanjewa, Oscar, Nyasulu, Vita, Chinyama, End, Zuza, Allan, Denis, Brigitte, Storey, Evance, Bondera, Nedson, Matchado, Danford, Chande, Adams, Chingota, Arthur, Ntwea, Chimenya, Mkandawire, Langford, Mhango, Chimwemwe, Lakudzala, Agness, Chaponda, Mphatso, Mwenechanya, Percy, Mvaya, Leonard, Tembo, Dumizulu, Henrion, Marc Y. R., Chirombo, James, Masesa, Clemens, and Gondwe, Joel

Subjects
wa_105, qw_568, mental disorders, wc_505, qw_160, wa_395
Abstract

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.

Published
2021

30. Zika virus evolution and spread in the Americas

Author

Metsky, Hayden C., Matranga, Christian B., Wohl, Shirlee, Schaffner, Stephen F., Freije, Catherine A., Winnicki, Sarah M., West, Kendra, Qu, James, Baniecki, Mary Lynn, Gladden-Young, Adrianne, Lin, Aaron E., Tomkins-Tinch, Christopher H., Ye, Simon H., Park, Daniel J., Luo, Cynthia Y., Barnes, Kayla G., Shah, Rickey R., Chak, Bridget, Barbosa-Lima, Giselle, Delatorre, Edson, Vieira, Yasmine R., Paul, Lauren M., Tan, Amanda L., Barcellona, Carolyn M., Porcelli, Mario C., Vasquez, Chalmers, Cannons, Andrew C., Cone, Marshall R., Hogan, Kelly N., Kopp, Edgar W., Anzinger, Joshua J., Garcia, Kimberly F., Parham, Leda A., Ramrez, Rosa M. Glvez, Montoya, Maria C. Miranda, Rojas, Diana P., Brown, Catherine M., Hennigan, Scott, Sabina, Brandon, Scotland, Sarah, Gangavarapu, Karthik, Grubaugh, Nathan D., Oliveira, Glenn, Robles-Sikisaka, Refugio, Rambaut, Andrew, Gehrke, Lee, Smole, Sandra, Halloran, M. Elizabeth, Villar, Luis, Mattar, Salim, Lorenzana, Ivette, Cerbino-Neto, Jose, Valim, Clarissa, Degrave, Wim, Bozza, Patricia T., Gnirke, Andreas, Andersen, Kristian G., Isern, Sharon, Michael, Scott F., Bozza, Fernando A., Souza, Thiago M. L., Bosch, Irene, Yozwiak, Nathan L., MacInnis, Bronwyn L., and Sabeti, Pardis C.

Subjects
America -- Health aspects, Zika virus -- Natural history, Zika virus infection -- Distribution, Company distribution practices, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Hayden C. Metsky [1, 2]; Christian B. Matranga [1]; Shirlee Wohl [1, 3]; Stephen F. Schaffner [1, 3, 4]; Catherine A. Freije [1, 3]; Sarah M. Winnicki [1]; Kendra [...]

Published
2017
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31. Genomic epidemiology reveals multiple introductions of Zika virus into the United States

Author

Grubaugh, Nathan D., Ladner, Jason T., Kraemer, Moritz U. G., Dudas, Gytis, Tan, Amanda L., Gangavarapu, Karthik, Wiley, Michael R., White, Stephen, Thz, Julien, Magnani, Diogo M., Prieto, Karla, Reyes, Daniel, Bingham, Andrea M., Paul, Lauren M., Robles-Sikisaka, Refugio, Oliveira, Glenn, Pronty, Darryl, Barcellona, Carolyn M., Metsky, Hayden C., Baniecki, Mary Lynn, Barnes, Kayla G., Chak, Bridget, Freije, Catherine A., Gladden-Young, Adrianne, Gnirke, Andreas, Luo, Cynthia, MacInnis, Bronwyn, Matranga, Christian B., Park, Daniel J., Qu, James, Schaffner, Stephen F., Tomkins-Tinch, Christopher, West, Kendra L., Winnicki, Sarah M., Wohl, Shirlee, Yozwiak, Nathan L., Quick, Joshua, Fauver, Joseph R., Khan, Kamran, Brent, Shannon E., Reiner, Robert C., Jr, Lichtenberger, Paola N., Ricciardi, Michael J., Bailey, Varian K., Watkins, David I., Cone, Marshall R., Kopp, Edgar W., IV, Hogan, Kelly N., Cannons, Andrew C., Jean, Reynald, Monaghan, Andrew J., Garry, Robert F., Loman, Nicholas J., Faria, Nuno R., Porcelli, Mario C., Vasquez, Chalmers, Nagle, Elyse R., Cummings, Derek A. T., Stanek, Danielle, Rambaut, Andrew, Sanchez-Lockhart, Mariano, Sabeti, Pardis C., Gillis, Leah D., Michael, Scott F., Bedford, Trevor, Pybus, Oliver G., Isern, Sharon, Palacios, Gustavo, and Andersen, Kristian G.

Subjects
Zika virus -- Health aspects -- Genetic aspects, Gene expression -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Nathan D. Grubaugh [1]; Jason T. Ladner [2]; Moritz U. G. Kraemer [3, 4, 5]; Gytis Dudas [6]; Amanda L. Tan [7]; Karthik Gangavarapu [1]; Michael R. Wiley [2, [...]

Published
2017
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32. Rotavirus Genotypes in Hospitalized Children With Acute Gastroenteritis Before and After Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997-2019.

Author

Mhango, Chimwemwe, Mandolo, Jonathan J, Chinyama, End, Wachepa, Richard, Kanjerwa, Oscar, Malamba-Banda, Chikondi, Matambo, Prisca B, Barnes, Kayla G, Chaguza, Chrispin, Shawa, Isaac T, Nyaga, Martin M, Hungerford, Daniel, Parashar, Umesh D, Pitzer, Virginia E, Kamng'ona, Arox W, Iturriza-Gomara, Miren, Cunliffe, Nigel A, and Jere, Khuzwayo C

Abstract

Background: Rotavirus vaccine (Rotarix [RV1]) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution.Methods: Data on rotavirus-positive stool specimens among children aged <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997-October 2012, n = 1765) and after (November 2012-October 2019, n = 934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse-transcription polymerase chain reaction.Results: A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H') and Simpson diversity (D') indices did not differ between the pre- and postvaccine periods (H' P < .149; D' P < .287). Overall, G1 (n = 268/924 [28.7%]), G2 (n = 308/924 [33.0%]), G3 (n = 72/924 [7.7%]), and G12 (n = 109/924 [11.8%]) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 reemerged and became the predominant genotype from 2017 onward. No evidence of genotype selection was observed 7 years post-RV1 introduction.Conclusions: Rotavirus strain diversity and genotype variation in Malawi are likely driven by natural mechanisms rather than vaccine pressure. [ABSTRACT FROM AUTHOR]

Published
2022
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34. Rotavirus Genotypes in Hospitalized Children With Acute Gastroenteritis Before and After Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997–2019

Author

Mhango, Chimwemwe, primary, Mandolo, Jonathan J, additional, Chinyama, End, additional, Wachepa, Richard, additional, Kanjerwa, Oscar, additional, Malamba-Banda, Chikondi, additional, Matambo, Prisca B, additional, Barnes, Kayla G, additional, Chaguza, Chrispin, additional, Shawa, Isaac T, additional, Nyaga, Martin M, additional, Hungerford, Daniel, additional, Parashar, Umesh D, additional, Pitzer, Virginia E, additional, Kamng’ona, Arox W, additional, Iturriza-Gomara, Miren, additional, Cunliffe, Nigel A, additional, and Jere, Khuzwayo C, additional

Published
2020
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35. Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics

Author

Kotliar, Dylan, primary, Lin, Aaron E., additional, Logue, James, additional, Hughes, Travis K., additional, Khoury, Nadine M., additional, Raju, Siddharth S., additional, Wadsworth, Marc H., additional, Chen, Han, additional, Kurtz, Jonathan R., additional, Dighero-Kemp, Bonnie, additional, Bjornson, Zach B., additional, Mukherjee, Nilanjan, additional, Sellers, Brian A., additional, Tran, Nancy, additional, Bauer, Matthew R., additional, Adams, Gordon C., additional, Adams, Ricky, additional, Rinn, John L., additional, Melé, Marta, additional, Nolan, Garry P., additional, Barnes, Kayla G., additional, Hensley, Lisa E., additional, McIlwain, David R., additional, Shalek, Alex K., additional, Sabeti, Pardis C., additional, and Bennett, Richard S., additional

Published
2020
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36. Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time

Author

Barnes, Kayla G., primary, Lachenauer, Anna E., additional, Nitido, Adam, additional, Siddiqui, Sameed, additional, Gross, Robin, additional, Beitzel, Brett, additional, Siddle, Katherine J., additional, Freije, Catherine A., additional, Dighero-Kemp, Bonnie, additional, Mehta, Samar, additional, Carter, Amber, additional, Uwanibe, Jessica, additional, Ajogbasile, Fehintola, additional, Olumade, Testimony J., additional, Odia, Ikponmwosa, additional, Sandi, John Demby, additional, Momoh, Mambu, additional, Metsky, Hayden C., additional, Boehm, Chloe K., additional, Lin, Aaron E., additional, Kemball, Molly, additional, Park, Daniel J., additional, Grant, Donald S., additional, Happi, Christian T., additional, Branco, Luis, additional, Boisen, Matt, additional, Sullivan, Brian M., additional, Amare, Mihret, additional, Tiamiyu, Abdulwasiu, additional, Parker, Zahra, additional, Iroezindu, Michael, additional, Modjarrad, Kayvon, additional, Myhrvold, Cameron, additional, Garry, Robert F., additional, Palacios, Gustavo, additional, Hensley, Lisa E., additional, Schaffner, Stephen F., additional, Colubri, Andres, additional, and Sabeti, Pardis C., additional

Published
2020
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37. Field-deployable viral diagnostics using CRISPR-Cas13

Author

McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Biological Engineering, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Myhrvold, Cameron, Freije, Catherine A., Gootenberg, Jonathan S, Abudayyeh, Omar O., Metsky, Hayden C., Durbin, Ann F, Kellner, Max J., Tan, Amanda L., Paul, Lauren M., Parham, Leda A., Garcia, Kimberly F., Barnes, Kayla G., Chak, Bridget, Mondini, Adriano, Nogueira, Mauricio L., Isern, Sharon, Michael, Scott F., Lorenzana, Ivette, Yozwiak, Nathan L., MacInnis, Bronwyn L., Bosch, Irene, Gehrke, Lee, Zhang, Feng, Sabeti, Pardis C., McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Biological Engineering, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Myhrvold, Cameron, Freije, Catherine A., Gootenberg, Jonathan S, Abudayyeh, Omar O., Metsky, Hayden C., Durbin, Ann F, Kellner, Max J., Tan, Amanda L., Paul, Lauren M., Parham, Leda A., Garcia, Kimberly F., Barnes, Kayla G., Chak, Bridget, Mondini, Adriano, Nogueira, Mauricio L., Isern, Sharon, Michael, Scott F., Lorenzana, Ivette, Yozwiak, Nathan L., MacInnis, Bronwyn L., Bosch, Irene, Gehrke, Lee, Zhang, Feng, and Sabeti, Pardis C.

Abstract

Mitigating global infectious disease requires diagnostic tools that are sensitive, specific, and rapidly field deployable. In this study, we demonstrate that the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. We developed HUDSON (heating unextracted diagnostic samples to obliterate nucleases), a protocol that pairs with SHERLOCK for viral detection directly from bodily fluids, enabling instrument-free DENV detection directly from patient samples in <2 hours. We further demonstrate that SHERLOCK can distinguish the four DENV serotypes, as well as region-specific strains of ZIKV from the 2015–2016 pandemic. Finally, we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms., NIH (Grants AI-100190, 1R01-HG009761, 1R01-MH110049, and 1DP1-HL141201)

Published
2020

38. Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

Author

Milner Danny A, Vareta Jimmy, Valim Clarissa, Montgomery Jacqui, Daniels Rachel F, Volkman Sarah K, Neafsey Daniel E, Park Daniel J, Schaffner Stephen F, Mahesh Nira C, Barnes Kayla G, Rosen David M, Lukens Amanda K, Van-Tyne Daria, Wiegand Roger C, Sabeti Pardis C, Seydel Karl B, Glover Simon J, Kamiza Steve, Molyneux Malcolm E, Taylor Terrie E, and Wirth Dyann F

Subjects
Plasmodium falciparum, Cerebral malaria, Genotyping, Molecular barcode, Histopathology, Autopsy, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Cerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype. Methods The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria. Results Single genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients. Conclusions Cerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.

Published
2012
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39. Implementation of the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) study: Lessons learned for vision health systems strengthening in Sierra Leone.

Author

Shantha, Jessica G., Crozier, Ian, Kraft, Colleen S., Grant, Donald G., Goba, Augustine, Hayek, Brent R., Hartley, Caleb, Barnes, Kayla G., Uyeki, Timothy M., Schieffelin, John, Garry, Robert F., Bausch, Daniel G., Farmer, Paul E., Mattia, John G., Vandy, Matthew J., and Yeh, Steven

Subjects
EBOLA virus, EBOLA virus disease, VISUAL acuity, VISION disorders, INFECTION prevention, CATARACT surgery, EYE care, HIV prevention
Abstract

Background: Following the West African Ebola virus disease (EVD) outbreak of 2013–2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. Methodology/Principal findings: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. Conclusions/Significance: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings. [ABSTRACT FROM AUTHOR]

Published
2021
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40. Genome sequencing reveals Zika virus diversity and spread in the Americas

Author

Metsky, Hayden C, Matranga, Christian B, Wohl, Shirlee, Schaffner, Stephen F., Freije, Catherine A, Winnicki, Sarah, West, Kendra, Qu, J, Baniecki, Mary Lynn, Gladden-Young, Adrianne, Lin, Aaron E., Christopher, Tomkins-Tinch, Ye, S.H, Park, Daniel J, Luo, Cynthia, Barnes, Kayla G, Shah, R.R., Chak, Bridget, Barbosa-Lima, G., Delatorre, E., Vieira, Y.R., Paul, Lauren M, Tan, Amanda L, Barcellona, Carolyn M, Porcelli, Mario C, Vasquez, Chalmers, Cannons, Andrew C, Cone, Marshall R, Hogan, Kelly N, Kopp IV, Edgar W, Anzinger, J.J., Garcia, K.F., Parhap, L.A., Gelvez Ramirez, R.M., Montoya, Miranda, Rojas, D.P., Brown, C.M., Hennigan, S., Sabina, B., Scotland, S., Gangavarapu, K., Grubaugh, N.D., Oliveira, G., Robles-Sikisaka, R., Rambaut, Andrew, Gehrke, L., Smole, S., Halloran, M.E., Villar Centeno, L.A., Mattar, S., Lorenzana, I., Cerbino-Neto, J., Valim, C., Degrave, W., Bozza, P.T., Souza, T.M.L., Bosch, I., Yozwiak, N.L., MacInnis, B.L., and Sabeti, P.C.

Abstract

Despite great attention given to the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects1,2, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part due to a lack of genomic data. We applied multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analyzed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental US. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of viral surveillance. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those potentially relevant to the effectiveness of diagnostic tests.

Published
2017
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41. Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control

Author

Barnes, Kayla G., Weedall, Gareth D., Ndula, Miranda, Irving, Helen, Mzihalowa, Themba, Hemingway, Janet, and Wondji, Charles S.

Subjects
Malawi, Insecticides, Heredity, Epidemiology, Disease Vectors, Mosquitoes, Geographical Locations, Insecticide Resistance, Cytochrome P-450 Enzyme System, Pyrethrins, Medicine and Health Sciences, qu_460, Mozambique, Phylogeny, Agriculture, Genomics, Insects, Genetic Mapping, Insect Proteins, Agrochemicals, Research Article, RM, Arthropoda, lcsh:QH426-470, Quantitative Trait Loci, wc_765, Host-Parasite Interactions, Sequence Homology, Nucleic Acid, qx_600, Anopheles, parasitic diseases, Genetics, Animals, Humans, Selection, Genetic, Evolutionary Biology, Population Biology, Base Sequence, Models, Genetic, Organisms, wa_240, Biology and Life Sciences, Genetic Variation, R1, Invertebrates, wc_750, Insect Vectors, Malaria, lcsh:Genetics, qx_650, Haplotypes, Genetic Loci, People and Places, Africa, Population Genetics, Microsatellite Repeats
Abstract

Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the ‘resistance curve’ and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistance-associated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised., Author Summary Malaria control currently relies heavily on insecticide-based vector control interventions. Unfortunately, resistance to insecticides threatens the continued effectiveness of these measures. Metabolic resistance, caused by increased detoxification of insecticides, presents the greatest threat to vector control, yet it remains unclear how these mechanisms are linked to underlying genetic changes driven by the massive selection pressure from these interventions, such as the widespread use of Long Lasting Insecticide Nets (LLINs) across Africa. Therefore, understanding the direction and speed at which this operationally important form of resistance spreads through mosquito populations is essential if we are to get ahead of the ‘resistance curve’ and avert a public health catastrophe. Here, using microsatellite markers, whole genome sequencing and fine-scale sequencing at a major resistance locus, we elucidated the Africa-wide population structure of Anopheles funestus, a major African malaria vector, and detected a strong selective sweep occurring in a genomic region controlling cytochrome P450-based metabolic pyrethroid resistance in this species. Furthermore, we demonstrated that this selective sweep is driven by the scale-up of insecticide-based malaria control in Africa, highlighting the risk that if this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised.

Published
2017

42. Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018

Author

Siddle, Katherine J., primary, Eromon, Philomena, additional, Barnes, Kayla G., additional, Mehta, Samar, additional, Oguzie, Judith U., additional, Odia, Ikponmwosa, additional, Schaffner, Stephen F., additional, Winnicki, Sarah M., additional, Shah, Rickey R., additional, Qu, James, additional, Wohl, Shirlee, additional, Brehio, Patrick, additional, Iruolagbe, Christopher, additional, Aiyepada, John, additional, Uyigue, Eghosa, additional, Akhilomen, Patience, additional, Okonofua, Grace, additional, Ye, Simon, additional, Kayode, Tolulope, additional, Ajogbasile, Fehintola, additional, Uwanibe, Jessica, additional, Gaye, Amy, additional, Momoh, Mambu, additional, Chak, Bridget, additional, Kotliar, Dylan, additional, Carter, Amber, additional, Gladden-Young, Adrianne, additional, Freije, Catherine A., additional, Omoregie, Omigie, additional, Osiemi, Blessing, additional, Muoebonam, Ekene B., additional, Airende, Michael, additional, Enigbe, Rachael, additional, Ebo, Benevolence, additional, Nosamiefan, Iguosadolo, additional, Oluniyi, Paul, additional, Nekoui, Mahan, additional, Ogbaini-Emovon, Ephraim, additional, Garry, Robert F., additional, Andersen, Kristian G., additional, Park, Daniel J., additional, Yozwiak, Nathan L., additional, Akpede, George, additional, Ihekweazu, Chikwe, additional, Tomori, Oyewale, additional, Okogbenin, Sylvanus, additional, Folarin, Onikepe A., additional, Okokhere, Peter O., additional, MacInnis, Bronwyn L., additional, Sabeti, Pardis C., additional, and Happi, Christian T., additional

Published
2018
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43. Field validation of recombinant antigen immunoassays for diagnosis of Lassa fever

Author

Boisen, Matthew L., primary, Hartnett, Jessica N., additional, Shaffer, Jeffrey G., additional, Goba, Augustine, additional, Momoh, Mambu, additional, Sandi, John Demby, additional, Fullah, Mohamed, additional, Nelson, Diana K. S., additional, Bush, Duane J., additional, Rowland, Megan M., additional, Heinrich, Megan L., additional, Koval, Anatoliy P., additional, Cross, Robert W., additional, Barnes, Kayla G., additional, Lachenauer, Anna E., additional, Lin, Aaron E., additional, Nekoui, Mahan, additional, Kotliar, Dylan, additional, Winnicki, Sarah M., additional, Siddle, Katherine J., additional, Gbakie, Michael, additional, Fonnie, Mbalu, additional, Koroma, Veronica J., additional, Kanneh, Lansana, additional, Kulakosky, Peter C., additional, Hastie, Kathryn M., additional, Wilson, Russell B., additional, Andersen, Kristian G., additional, Folarin, Onikepe O., additional, Happi, Christian T., additional, Sabeti, Pardis C., additional, Geisbert, Thomas W., additional, Saphire, Erica Ollmann, additional, Khan, S. Humarr, additional, Grant, Donald S., additional, Schieffelin, John S., additional, Branco, Luis M., additional, and Garry, Robert F., additional

Published
2018
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44. Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study: Reverse Transcription-Polymerase Chain Reaction and Cataract Surgery Outcomes of Ebola Survivors in Sierra Leone

Author

Shantha, Jessica G., primary, Mattia, John G., additional, Goba, Augustine, additional, Barnes, Kayla G., additional, Ebrahim, Faiqa K., additional, Kraft, Colleen S., additional, Hayek, Brent R., additional, Hartnett, Jessica N., additional, Shaffer, Jeffrey G., additional, Schieffelin, John S., additional, Sandi, John D., additional, Momoh, Mambu, additional, Jalloh, Simbirie, additional, Grant, Donald S., additional, Dierberg, Kerry, additional, Chang, Joyce, additional, Mishra, Sharmistha, additional, Chan, Adrienne K., additional, Fowler, Rob, additional, O'Dempsey, Tim, additional, Kaluma, Erick, additional, Hendricks, Taylor, additional, Reiners, Roger, additional, Reiners, Melanie, additional, Gess, Lowell A., additional, ONeill, Kwame, additional, Kamara, Sarian, additional, Wurie, Alie, additional, Mansaray, Mohamed, additional, Acharya, Nisha R., additional, Liu, William J., additional, Bavari, Sina, additional, Palacios, Gustavo, additional, Teshome, Moges, additional, Crozier, Ian, additional, Farmer, Paul E., additional, Uyeki, Timothy M., additional, Bausch, Daniel G., additional, Garry, Robert F., additional, Vandy, Matthew J., additional, and Yeh, Steven, additional

Published
2018
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45. Restriction to gene flow is associated with changes in the molecular basis of pyrethroid resistance in the malaria vector Anopheles funestus

Author

Barnes, Kayla G, Irving, Helen, Chiumia, Martin, Mzilahowa, Themba, Coleman, Michael, Hemingway, Janet, and Wondji, Charles

Subjects
qx_650, parasitic diseases, qx_600, qu_475, qx_515, wc_750
Abstract

Resistance to pyrethroids, the sole insecticide class recommended for treating bed nets, threatens the control of major malaria vectors, including Anopheles funestus Effective management of resistance requires an understanding of the dynamics and mechanisms driving resistance. Here, using genome-wide transcription and genetic diversity analyses, we show that a shift in the molecular basis of pyrethroid resistance in southern African populations of this species is associated with a restricted gene flow. Across the most highly endemic and densely populated regions in Malawi, An. funestus is resistant to pyrethroids, carbamates, and organochlorides. Genome-wide microarray-based transcription analysis identified overexpression of cytochrome P450 genes as the main mechanism driving this resistance. The most up-regulated genes include cytochrome P450s (CYP) CYP6P9a, CYP6P9b and CYP6M7. However, a significant shift in the overexpression profile of these genes was detected across a south/north transect, with CYP6P9a and CYP6P9b more highly overexpressed in the southern resistance front and CYP6M7 predominant in the northern front. A genome-wide genetic structure analysis of southern African populations of An. funestus from Zambia, Malawi, and Mozambique revealed a restriction of gene flow between populations, in line with the geographical variation observed in the transcriptomic analysis. Genetic polymorphism analysis of the three key resistance genes, CYP6P9a, CYP6P9b, and CYP6M7, support barriers to gene flow that are shaping the underlying molecular basis of pyrethroid resistance across southern Africa. This barrier to gene flow is likely to impact the design and implementation of resistance management strategies in the region.

Published
2016

46. Multiple introductions of Zika virus into the United States revealed through genomic epidemiology

Author

Grubaugh, Nathan D, primary, Ladner, Jason T, additional, Kraemer, Moritz UG, additional, Dudas, Gytis, additional, Tan, Amanda L, additional, Gangavarapu, Karthik, additional, Wiley, Michael R, additional, White, Stephen, additional, Thézé, Julien, additional, Magnani, Diogo M, additional, Prieto, Karla, additional, Reyes, Daniel, additional, Bingham, Andrea, additional, Paul, Lauren M, additional, Robles-Sikisaka, Refugio, additional, Oliveira, Glenn, additional, Pronty, Darryl, additional, Metsky, Hayden C, additional, Baniecki, Mary Lynn, additional, Barnes, Kayla G, additional, Chak, Bridget, additional, Freije, Catherine A, additional, Gladden-Young, Adrianne, additional, Gnirke, Andreas, additional, Luo, Cynthia, additional, MacInnis, Bronwyn, additional, Matranga, Christian B, additional, Park, Daniel J, additional, Qu, James, additional, Schaffner, Stephen F, additional, Tomkins-Tinch, Christopher, additional, West, Kendra L, additional, Winnicki, Sarah M, additional, Wohl, Shirlee, additional, Yozwiak, Nathan L, additional, Quick, Joshua, additional, Fauver, Joseph R, additional, Khan, Kamran, additional, Brent, Shannon E, additional, Reiner, Robert C, additional, Lichtenberger, Paola N, additional, Ricciardi, Michael, additional, Bailey, Varian K, additional, Watkins, David I, additional, Cone, Marshall R, additional, Kopp, Edgar W, additional, Hogan, Kelly N, additional, Cannons, Andrew C, additional, Jean, Reynald, additional, Garry, Robert F, additional, Loman, Nicholas J, additional, Faria, Nuno R, additional, Porcelli, Mario C, additional, Vasquez, Chalmers, additional, Nagle, Elyse R, additional, Cummings, Derek AT, additional, Stanek, Danielle, additional, Rambaut, Andrew, additional, Sanchez-Lockhart, Mariano, additional, Sabeti, Pardis C, additional, Gillis, Leah D, additional, Michael, Scott F, additional, Bedford, Trevor, additional, Pybus, Oliver G, additional, Isern, Sharon, additional, Palacios, Gustavo, additional, and Andersen, Kristian G, additional

Published
2017
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47. The highly polymorphic CYP6M7 cytochrome P450 gene partners with the directionally selected CYP6P9a and CYP6P9b genes to expand the pyrethroid resistance front in the malaria vector Anopheles funestus in Africa

Author

Riveron, Jacob M, Ibrahim, Sulaiman S, Chanda, Emmanuel, Mzilahowa, Themba, Cuamba, Nelson, Irving, Helen, Barnes, Kayla G, Ndula, Miranda, and Wondji, Charles S

Subjects
Insecticides, Insecticide resistance, Drug Resistance, Cytochrome P450, wa_395, Directional selection, wc_765, Real-Time Polymerase Chain Reaction, Anopheles funestus, Animals, Genetically Modified, Cytochrome P-450 Enzyme System, Anopheles, Pyrethrins, parasitic diseases, qx_600, Genetics, Pyrethroids, CYP6M7, Animals, Genome, Polymorphism, Genetic, qu_500, Gene Expression Profiling, Genetic Variation, wa_240, Recombinant Proteins, Malaria, Kinetics, Drosophila melanogaster, Haplotypes, Africa, Female, qx_515, Research Article, Biotechnology
Abstract

Background Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Knowledge of the origin, mechanisms and evolution of resistance are crucial to designing successful resistance management strategies. Results Here, we established the resistance profile of a Zambian An. funestus population at the northern range of the resistance front. Similar to other Southern African populations, Zambian An. funestus mosquitoes are resistant to pyrethroids and carbamate, but in contrast to populations in Mozambique and Malawi, these insects are also DDT resistant. Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible for extending pyrethroid resistance northwards. Indeed, CYP6M7 is more over-expressed in Zambia [fold-change (FC) 37.7; 13.2 for qRT-PCR] than CYP6P9a (FC15.6; 8.9 for qRT-PCR) and CYP6P9b (FC11.9; 6.5 for qRT-PCR), whereas CYP6P9a and CYP6P9b are more highly over-expressed in Malawi and Mozambique. Transgenic expression of CYP6M7 in Drosophila melanogaster coupled with in vitro assays using recombinant enzymes and assessments of kinetic properties demonstrated that CYP6M7 is as efficient as CYP6P9a and CYP6P9b in conferring pyrethroid resistance. Polymorphism patterns demonstrate that these genes are under contrasting selection forces: the exceptionally diverse CYP6M7 likely evolves neutrally, whereas CYP6P9a and CYP6P9b are directionally selected. The higher variability of CYP6P9a and CYP6P9b observed in Zambia supports their lesser role in resistance in this country. Conclusion Pyrethroid resistance in Southern Africa probably has multiple origins under different evolutionary forces, which may necessitate the design of different resistance management strategies. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-817) contains supplementary material, which is available to authorized users.

Published
2014

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