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2. Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

Author

Milighetti, Martina, Peng, Yanchun, Tan, Cedric, Mark, Michal, Nageswaran, Gayathri, Byrne, Suzanne, Ronel, Tahel, Peacock, Tom, Mayer, Andreas, Chandran, Aneesh, Rosenheim, Joshua, Whelan, Matthew, Yao, Xuan, Liu, Guihai, Felce, Suet Ling, Dong, Tao, Mentzer, Alexander J., Knight, Julian C., Balloux, Francois, Greenstein, Erez, Reich-Zeliger, Shlomit, Pade, Corinna, Gibbons, Joseph M., Semper, Amanda, Brooks, Tim, Otter, Ashley, Altmann, Daniel M., Boyton, Rosemary J., Maini, Mala K., McKnight, Aine, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Noursadeghi, Mahdad, and Chain, Benny

Published
2023
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6. STROBE-metagenomics: a STROBE extension statement to guide the reporting of metagenomics studies

Author

Bharucha, Tehmina, Oeser, Clarissa, Balloux, Francois, Brown, Julianne R, Carbo, Ellen C, Charlett, Andre, Chiu, Charles Y, Claas, Eric C J, de Goffau, Marcus C, de Vries, Jutte J C, Eloit, Marc, Hopkins, Susan, Huggett, Jim F, MacCannell, Duncan, Morfopoulou, Sofia, Nath, Avindra, O'Sullivan, Denise M, Reoma, Lauren B, Shaw, Liam P, Sidorov, Igor, Simner, Patricia J, Van Tan, Le, Thomson, Emma C, van Dorp, Lucy, Wilson, Michael R, Breuer, Judith, and Field, Nigel

Published
2020
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8. Panel stacking is a threat to consensus statement validity

Author

Kepp, Kasper P., Aavitsland, Preben, Ballin, Marcel, Balloux, Francois, Baral, Stefan, Bardosh, Kevin, Bauchner, Howard, Bendavid, Eran, Bhopal, Raj, Blumstein, Daniel T., Boffetta, Paolo, Bourgeois, Florence, Brufsky, Adam, Collignon, Peter J., Cripps, Sally, Cristea, Ioana A., Curtis, Nigel, Djulbegovic, Benjamin, Faude, Oliver, Flacco, Maria Elena, Guyatt, Gordon H., Hajishengallis, George, Hemkens, Lars G., Hoffmann, Tammy, Joffe, Ari R., Klassen, Terry P., Koletsi, Despina, Kontoyiannis, Dimitrios P., Kuhl, Ellen, La Vecchia, Carlo, Lallukka, Tea, Lambris, John, Levitt, Michael, Makridakis, Spyros, Maltezou, Helena C., Manzoli, Lamberto, Marusic, Ana, Mavragani, Clio, Moher, David, Mol, Ben W., Muka, Taulant, Naudet, Florian, Noble, Paul W., Nordström, Anna, Nordström, Peter, Pandis, Nikolaos, Papatheodorou, Stefania, Patel, Chirag J., Petersen, Irene, Pilz, Stefan, Plesnila, Nikolaus, Ponsonby, Anne-Louise, Rivas, Manuel A., Saltelli, Andrea, Schabus, Manuel, Schippers, Michaéla C., Schünemann, Holger, Solmi, Marco, Stang, Andreas, Streeck, Hendrik, Sturmberg, Joachim P., Thabane, Lehana, Thombs, Brett D., Tsakris, Athanasios, Wood, Simon N., and Ioannidis, John P.A.

Published
2024
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10. Multiple independent introductions of Plasmodium falciparum in South America

Author

Yalcindag, Erhan, Elguero, Eric, Arnathau, Céline, Durand, Patrick, Akiana, Jean, Anderson, Timothy J, Aubouy, Agnes, Balloux, François, Besnard, Patrick, Bogreau, Hervé, Carnevale, Pierre, D'Alessandro, Umberto, Fontenille, Didier, Gamboa, Dionicia, Jombart, Thibaut, Le Mire, Jacques, Leroy, Eric, Maestre, Amanda, Mayxay, Mayfong, Ménard, Didier, Musset, Lise, Newton, Paul N, Nkoghé, Dieudonné, Noya, Oscar, Ollomo, Benjamin, Rogier, Christophe, Veron, Vincent, Wide, Albina, Zakeri, Sedigheh, Carme, Bernard, Legrand, Eric, Chevillon, Christine, Ayala, Francisco J, Renaud, François, and Prugnolle, Franck

Subjects
Malaria, Rare Diseases, Genetics, Vector-Borne Diseases, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Bayes Theorem, Cluster Analysis, Demography, Emigration and Immigration, Genetic Variation, Genetics, Population, Humans, Logistic Models, Microsatellite Repeats, Models, Genetic, Phylogeny, Phylogeography, Plasmodium falciparum, Polymorphism, Single Nucleotide, Principal Component Analysis, South America, malaria origin, New World, human migrations, genetic diversity
Abstract

The origin of Plasmodium falciparum in South America is controversial. Some studies suggest a recent introduction during the European colonizations and the transatlantic slave trade. Other evidence--archeological and genetic--suggests a much older origin. We collected and analyzed P. falciparum isolates from different regions of the world, encompassing the distribution range of the parasite, including populations from sub-Saharan Africa, the Middle East, Southeast Asia, and South America. Analyses of microsatellite and SNP polymorphisms show that the populations of P. falciparum in South America are subdivided in two main genetic clusters (northern and southern). Phylogenetic analyses, as well as Approximate Bayesian Computation methods suggest independent introductions of the two clusters from African sources. Our estimates of divergence time between the South American populations and their likely sources favor a likely introduction from Africa during the transatlantic slave trade.

Published
2012

25. Large Clones of Pre-Existing T Cells Drive Early Immunity Against SARS-COV-2 and LCMV Infection

Author

Milighetti, Martina, primary, Peng, Yanchun, additional, Tan, Cedric, additional, Mark, Michal, additional, Nageswaran, Gayathri, additional, Byrne, Suzanne, additional, Ronel, Tahel, additional, Peacock, Tom, additional, Mayer, Andreas, additional, Chandran, Aneesh, additional, Rosenheim, Joshua, additional, Whelan, Matthew V.X., additional, Yao, Xuan, additional, Liu, Guihai, additional, Felce, Suet Ling, additional, Dong, Tao, additional, Mentzer, Alexander J., additional, Knight, Julian, additional, Balloux, François, additional, Greenstein, Erez, additional, Reich-Zeliger, Shlomit, additional, Pade, Corinna, additional, Gibbons, Joseph, additional, Semper, Amanda, additional, Brooks, Tim, additional, Otter, Ashley, additional, Altmann, Daniel M., additional, Boyton, Rosemary J., additional, Maini, Mala K., additional, McKnight, Aine, additional, Manisty, Charlotte, additional, Treibel, Thomas A., additional, Moon, James C., additional, Investigators, COVIDsortium, additional, Noursadeghi, Mahdad, additional, and Chain, Benny, additional

Published
2023
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26. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis

Author

Cui, Yujun, Yu, Chang, Yan, Yanfeng, Li, Dongfang, Li, Yanjun, Jombart, Thibaut, Weinert, Lucy A., Wang, Zuyun, Guo, Zhaobiao, Xu, Lizhi, Zhang, Yujiang, Zheng, Hancheng, Qin, Nan, Xiao, Xiao, Wu, Mingshou, Wang, Xiaoyi, Zhou, Dongsheng, Qi, Zhizhen, Du, Zongmin, Wu, Honglong, Yang, Xianwei, Cao, Hongzhi, Wang, Hu, Wang, Jing, Yao, Shusen, Rakin, Alexander, Li, Yingrui, Falush, Daniel, Balloux, Francois, Achtman, Mark, Song, Yajun, Wang, Jun, and Yang, Ruifu

Published
2013

27. The population genomic legacy of the second plague pandemic

Author

Carlsberg Foundation, Danish National Research Foundation, Lundbeck Foundation, European Research Council, Research Council of Norway, Science Foundation Ireland, Gopalakrishnan, Shyam, Ebenesersdóttir, Sigríður Sunna, Lundstrøm, Inge K.C., Turner-Walker, Gordon, Moore, Kristjan H.S., Luisi, Pierre, Margaryan, Ashot, Martin, Michael D., Ellegaard, Martin Rene, Magnusson, Olafur þ., Sigurðsson, Ásgeir, Snorradóttir, Steinunn, Magnúsdóttir, Droplaug N., Laffoon, Jason, van Dorp, Lucy, Liu, Xiaodong, Moltke, Ida, Ávila-Arcos, María C., Schraiber, Joshua G., Rasmussen,Simon, Juan, David, Gelabert, Pere, De-Dios, Toni, Fotakis, Anna K., Iraeta-Orbegozo, Miren, Vågene, Åshild J., Dexter Denham, Sean, Christophersen, Axel, Stenøien, Hans K., Vieira, Filipe Garrett, Liu, Shanlin, Günther, Torsten, Kivisild, Toomas, Moseng, Ole Georg, Skar, Birgitte, Cheung, Christina, Sandoval-Velasco, Marcela, Wales, Nathan, Schroeder, Hannes, Campos, Paula F., Guðmundsdóttir, Valdís B., Sicheritz-Ponten, Thomas, Petersen, Bent, Halgunset, Jostein, Gilbert, Edmund, Cavalleri, Gianpiero L., Hovig, Eivind, Kockum, Ingrid, Olsson, Tomas, Alfredsson, Lars, Hansen, Thomas F., Werge, Thomas, Willerslev, Eske, Balloux, François, Marqués-Bonet, Tomàs, Lalueza-Fox, Carles, Nielsen, Rasmus, Stefánsson, Kári, Helgason, Agnar, Gilbert, M. Thomas P., Carlsberg Foundation, Danish National Research Foundation, Lundbeck Foundation, European Research Council, Research Council of Norway, Science Foundation Ireland, Gopalakrishnan, Shyam, Ebenesersdóttir, Sigríður Sunna, Lundstrøm, Inge K.C., Turner-Walker, Gordon, Moore, Kristjan H.S., Luisi, Pierre, Margaryan, Ashot, Martin, Michael D., Ellegaard, Martin Rene, Magnusson, Olafur þ., Sigurðsson, Ásgeir, Snorradóttir, Steinunn, Magnúsdóttir, Droplaug N., Laffoon, Jason, van Dorp, Lucy, Liu, Xiaodong, Moltke, Ida, Ávila-Arcos, María C., Schraiber, Joshua G., Rasmussen,Simon, Juan, David, Gelabert, Pere, De-Dios, Toni, Fotakis, Anna K., Iraeta-Orbegozo, Miren, Vågene, Åshild J., Dexter Denham, Sean, Christophersen, Axel, Stenøien, Hans K., Vieira, Filipe Garrett, Liu, Shanlin, Günther, Torsten, Kivisild, Toomas, Moseng, Ole Georg, Skar, Birgitte, Cheung, Christina, Sandoval-Velasco, Marcela, Wales, Nathan, Schroeder, Hannes, Campos, Paula F., Guðmundsdóttir, Valdís B., Sicheritz-Ponten, Thomas, Petersen, Bent, Halgunset, Jostein, Gilbert, Edmund, Cavalleri, Gianpiero L., Hovig, Eivind, Kockum, Ingrid, Olsson, Tomas, Alfredsson, Lars, Hansen, Thomas F., Werge, Thomas, Willerslev, Eske, Balloux, François, Marqués-Bonet, Tomàs, Lalueza-Fox, Carles, Nielsen, Rasmus, Stefánsson, Kári, Helgason, Agnar, and Gilbert, M. Thomas P.

Abstract

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.

Published
2022

31. An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia

Author

Rasmussen, Morten, Guo, Xiaosen, Wang, Yong, Lohmueller, Kirk E., Rasmussen, Simon, Albrechtsen, Anders, Skotte, Line, Lindgreen, Stinus, Metspalu, Mait, Jombart, Thibaut, Kivisild, Toomas, Zhai, Weiwei, Eriksson, Anders, Manica, Andrea, Orlando, Ludovic, De La Vega, Francisco M., Tridico, Silvana, Metspalu, Ene, Nielsen, Kasper, Ávila-Arcos, María C., Moreno-Mayar, J. Víctor, Muller, Craig, Dortch, Joe, Gilbert, M. Thomas P., Lund, Ole, Wesolowska, Agata, Karmin, Monika, Weinert, Lucy A., Wang, Bo, Li, Jun, Tai, Shuaishuai, Xiao, Fei, Hanihara, Tsunehiko, van Driem, George, Jha, Aashish R., Ricaut, François-Xavier, de Knijff, Peter, Migliano, Andrea B, Romero, Irene Gallego, Kristiansen, Karsten, Lambert, David M., Brunak, Søren, Forster, Peter, Brinkmann, Bernd, Nehlich, Olaf, Bunce, Michael, Richards, Michael, Gupta, Ramneek, Bustamante, Carlos D., Krogh, Anders, Foley, Robert A., Lahr, Marta M., Balloux, Francois, Sicheritz-Pontén, Thomas, Villems, Richard, Nielsen, Rasmus, Wang, Jun, and Willerslev, Eske

Published
2011
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34. Influenza: Making Privileged Data Public [with Response]

Author

Ormsby, Christopher E., Reyes-Terán, Gustavo, Fraser, Christophe, Donnelly, Christl A., Cauchemez, Simon, Hanage, William P., van Kerkhove, Maria D., Hollingsworth, T. Déirdre, Griffin, Jamie, Baggaley, Rebecca F., Jenkins, Helen E., Lyons, Emily J., Jombart, Thibaut, Hinsley, Wes R., Grassly, Nicholas C., Balloux, Francois, Ghani, Azra C., Rambaut, Andrew, and Ferguson, Neil M.

Published
2009

35. Pandemic Potential of a Strain of Influenza a (H1N1): Early Findings

Author

The WHO Rapid Pandemic Assessment Collaboration, Fraser, Christophe, Donnelly, Christl A., Cauchemez, Simon, Hanage, William P., Van Kerkhove, Maria D., Hollingsworth, T. Déirdre, Griffin, Jamie, Baggaley, Rebecca F., Jenkins, Helen E., Lyons, Emily J., Jombart, Thibaut, Hinsley, Wes R., Grassly, Nicholas C., Balloux, Francois, Ghani, Azra C., Ferguson, Neil M., Rambaut, Andrew, Pybus, Oliver G., Lopez-Gatell, Hugo, Alpuche-Aranda, Celia M., Chapela, Ietza Bojorquez, Zavala, Ethel Palacios, Guevara, Dulce Ma. Espejo, Checchi, Francesco, Garcia, Erika, Hugonnet, Stephane, and Roth, Cathy

Published
2009
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39. Genomic Analysis of 18th-Century Kazakh Individuals and Their Oral Microbiome

Author

White, Anna E., primary, de-Dios, Toni, additional, Carrión, Pablo, additional, Bonora, Gian Luca, additional, Llovera, Laia, additional, Cilli, Elisabetta, additional, Lizano, Esther, additional, Khabdulina, Maral K., additional, Tleugabulov, Daniyar T., additional, Olalde, Iñigo, additional, Marquès-Bonet, Tomàs, additional, Balloux, François, additional, Pettener, Davide, additional, van Dorp, Lucy, additional, Luiselli, Donata, additional, and Lalueza-Fox, Carles, additional

Published
2021
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40. Salmonella enterica from a soldier from the 1652 siege of Barcelona (Spain) supports historical transatlantic epidemic contacts

Author

de Dios, Toni, Carrión, Pablo, Olalde, Iñigo, Llovera, Laia, Lizano, Esther, Pàmies, Dídac, Marques-Bonet, Tomas, Balloux, François, van Dorp, Lucy, Lalueza-Fox, Carles, de Dios, Toni, Carrión, Pablo, Olalde, Iñigo, Llovera, Laia, Lizano, Esther, Pàmies, Dídac, Marques-Bonet, Tomas, Balloux, François, van Dorp, Lucy, and Lalueza-Fox, Carles

Abstract

Ancient pathogen genomics is an emerging field allowing reconstruction of past epidemics. The demise of post-contact American populations may, at least in part, have been caused by paratyphoid fever brought by Europeans. We retrieved genome-wide data from two Spanish soldiers who were besieging the city of Barcelona in 1652, during the Reapers' War. Their ancestry derived from the Basque region and Sardinia, respectively, (at that time, this island belonged to the Spanish kingdom). Despite the proposed plague epidemic, we could not find solid evidence for the presence of the causative plague agent in these individuals. However, we retrieved from one individual a substantial fraction of the Salmonella enterica serovar Paratyphi C lineage linked to paratyphoid fever in colonial period Mexico. Our results support a growing body of evidence that Paratyphi C enteric fever was more prevalent in Europe and the Americas in the past than it is today.

Published
2021

41. Genomic analysis of 18th-century Kazakh individuals and their oral microbiome

Author

White, Anna E., de Dios, Toni, Carrión, Pablo, Bonora, Gian Luca, Llovera, Laia, Cilli, Elisabetta, Lizano, Esther, Khabdulina, Maral K., Tleugabulov, Daniyar T., Olalde, Iñigo, Marques-Bonet, Tomas, Balloux, François, Pettener, Davide, van Dorp, Lucy, Luiselli, Donata, Lalueza-Fox, Carles, White, Anna E., de Dios, Toni, Carrión, Pablo, Bonora, Gian Luca, Llovera, Laia, Cilli, Elisabetta, Lizano, Esther, Khabdulina, Maral K., Tleugabulov, Daniyar T., Olalde, Iñigo, Marques-Bonet, Tomas, Balloux, François, Pettener, Davide, van Dorp, Lucy, Luiselli, Donata, and Lalueza-Fox, Carles

Abstract

Altres ajuts: CERCA Programme/Generalitat de Catalunya, The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome.

Published
2021

42. Salmonella enterica from a soldier from the 1652 siege of Barcelona (Spain) supports historical transatlantic epidemic contacts

Author

Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Generalitat de Catalunya, Dios Martínez, Antonio de, Carrión, Pablo, Olalde, Iñigo, Llovera, Laia, Lizano, Esther, Pàmies, Dídac, Marqués-Bonet, Tomàs, Balloux, François, Dorp, Lucy van, Lalueza-Fox, Carles, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Generalitat de Catalunya, Dios Martínez, Antonio de, Carrión, Pablo, Olalde, Iñigo, Llovera, Laia, Lizano, Esther, Pàmies, Dídac, Marqués-Bonet, Tomàs, Balloux, François, Dorp, Lucy van, and Lalueza-Fox, Carles

Abstract

Ancient pathogen genomics is an emerging field allowing reconstruction of past epidemics. The demise of post-contact American populations may, at least in part, have been caused by paratyphoid fever brought by Europeans. We retrieved genome-wide data from two Spanish soldiers who were besieging the city of Barcelona in 1652, during the Reapers' War. Their ancestry derived from the Basque region and Sardinia, respectively, (at that time, this island belonged to the Spanish kingdom). Despite the proposed plague epidemic, we could not find solid evidence for the presence of the causative plague agent in these individuals. However, we retrieved from one individual a substantial fraction of the Salmonella enterica serovar Paratyphi C lineage linked to paratyphoid fever in colonial period Mexico. Our results support a growing body of evidence that Paratyphi C enteric fever was more prevalent in Europe and the Americas in the past than it is today.

Published
2021

43. Genomic analysis of 18th-century kazakh individuals and their oral microbiome

Author

European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Generalitat de Catalunya, White, Anna E., Dios Martínez, Antonio de, Carrión, Pablo, Bonora, Gian Luca, Llovera, Laia, Cilli, Elisabetta, Lizano, Esther, Khabdulina, Maral K., Tieugabulov, Daniyar, Olalde, Iñigo, Marqués-Bonet, Tomàs, Balloux, François, Pettener, Davide, Dorp, Lucy van, Luiselli, Donata, Lalueza-Fox, Carles, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Generalitat de Catalunya, White, Anna E., Dios Martínez, Antonio de, Carrión, Pablo, Bonora, Gian Luca, Llovera, Laia, Cilli, Elisabetta, Lizano, Esther, Khabdulina, Maral K., Tieugabulov, Daniyar, Olalde, Iñigo, Marqués-Bonet, Tomàs, Balloux, François, Pettener, Davide, Dorp, Lucy van, Luiselli, Donata, and Lalueza-Fox, Carles

Abstract

The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome.

Published
2021

46. 31,600-year-old human virus genomes support a Pleistocene origin for common childhood infections

Author

Nielsen, Sofie Holtsmark, primary, van Dorp, Lucy, additional, Houldcroft, Charlotte J., additional, Pedersen, Anders G., additional, Allentoft, Morten E., additional, Vinner, Lasse, additional, Margaryan, Ashot, additional, Pavlova, Elena, additional, Chasnyk, Vyacheslav, additional, Nikolskiy, Pavel, additional, Pitulko, Vladimir, additional, Pimenoff, Ville N., additional, Balloux, François, additional, and Sikora, Martin, additional

Published
2021
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48. A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2

Author

Richard, Damien, primary, Shaw, Liam P, additional, Lanfear, Rob, additional, Corbett-Detig, Russell, additional, Hinrichs, Angie, additional, McBroome, Jakob, additional, Turakhia, Yatish, additional, Acman, Mislav, additional, Owen, Christopher J, additional, Tan, Cedric CS, additional, van Dorp, Lucy, additional, and Balloux, François, additional

Published
2021
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49. Population-level emergence of bedaquiline and clofazimine resistance-associated variants among patients with drug-resistant tuberculosis in southern Africa: a phenotypic and phylogenetic analysis

Author

Nimmo, Camus, Millard, James, van Dorp, Lucy, Brien, Kayleen, Moodley, Sashen, Wolf, Allison, Grant, Alison D, Padayatchi, Nesri, Pym, Alexander S, Balloux, François, and O'Donnell, Max

Abstract

BACKGROUND: Bedaquiline and clofazimine are important drugs in the treatment of drug-resistant tuberculosis and are commonly used across southern Africa, although drug susceptibility testing is not routinely performed. In this study, we did a genotypic and phenotypic analysis of drug-resistant Mycobacterium tuberculosis isolates from cohort studies in hospitals in KwaZulu-Natal, South Africa, to identify resistance-associated variants (RAVs) and assess the extent of clofazimine and bedaquiline cross-resistance. We also used a comprehensive dataset of whole-genome sequences to investigate the phylogenetic and geographical distribution of bedaquiline and clofazimine RAVs in southern Africa. METHODS: In this study, we included M tuberculosis isolates reported from the PRAXIS study of patients with drug-resistant tuberculosis treated with bedaquiline (King Dinuzulu Hospital, Durban) and three other cohort studies of drug-resistant tuberculosis in other KwaZulu-Natal hospitals, and sequential isolates from six persistently culture-positive patients with extensively drug-resistant tuberculosis at the KwaZulu-Natal provincial referral laboratory. Samples were collected between 2013 and 2019. Microbiological cultures were done as part of all parent studies. We sequenced whole genomes of included isolates and measured bedaquiline and clofazimine minimum inhibitory concentrations (MICs) for isolates identified as carrying any Rv0678 variant or previously published atpE, pepQ, and Rv1979c RAVs, which were the subject of the phenotypic study. We combined all whole-genome sequences of M tuberculosis obtained in this study with publicly available sequence data from other tuberculosis studies in southern Africa (defined as the countries of the Southern African Development Community), including isolates with Rv0678 variants identified by screening public genomic databases. We used this extended dataset to reconstruct phylogenetic relationships across lineage 2 and 4 M tuberculosis isolates. FINDINGS: We sequenced the whole genome of 648 isolates from 385 patients with drug-resistant tuberculosis recruited into cohort studies in KwaZulu-Natal, and 28 isolates from six patients from the KwaZulu-Natal referral laboratory. We identified 30 isolates with Rv0678 RAVs from 16 (4%) of 391 patients. We did not identify any atpE, pepQ, or Rv1979c RAVs. MICs were measured for 21 isolates with Rv0678 RAVs. MICs were above the critical concentration for bedaquiline resistance in nine (43%) of 21 isolates, in the intermediate category in nine (43%) isolates, and within the wild-type range in three (14%) isolates. Clofazimine MICs in genetically wild-type isolates ranged from 0·12-0·5 μg/mL, and in isolates with RAVs from 0·25-4·0 μg/mL. Phylogenetic analysis of the extended dataset including M tuberculosis isolates from southern Africa resolved multiple emergences of Rv0678 variants in lineages 2 and 4, documented two likely nosocomial transmission events, and identified the spread of a possibly bedaquiline and clofazimine cross-resistant clone in eSwatini. We also identified four patients with pepQ frameshift mutations that may confer resistance. INTERPRETATION: Bedaquiline and clofazimine cross-resistance in southern Africa is emerging repeatedly, with evidence of onward transmission largely due to Rv0678 mutations in M tuberculosis. Roll-out of bedaquiline and clofazimine treatment in the setting of limited drug susceptibility testing could allow further spread of resistance. Designing strong regimens would help reduce the emergence of resistance. Drug susceptibility testing is required to identify where resistance does emerge. FUNDING: Wellcome Trust, National Institute of Allergy and Infectious Diseases and National Center for Advancing Translational Sciences of the National Institutes of Health.

Published
2020

50. Plasmodium vivax Malaria Viewed through the Lens of an Eradicated European Strain

Author

Fundación la Caixa, Generalitat de Catalunya, Ministerio de Ciencia, Innovación y Universidades (España), European Research Council, Newton Fund, National Natural Science Foundation of China, Biotechnology and Biological Sciences Research Council (UK), Agencia Estatal de Investigación (España), van Dorp, Lucy, Gelabert, Pere, Rieux, Adrien, Manuel, Marc de, De-Dios, Toni, Gopalakrishnan, Shyam, Carøe, Christian, Sandoval-Velasco, Marcela, Fregel, Rosa, Olalde, Iñigo, Escosa, Raül, Aranda, Carles, Huijben, Silvia, Mueller, Ivo, Marqués-Bonet, Tomàs, Balloux, François, Gilbert, M. Thomas P., Lalueza-Fox, Carles, Fundación la Caixa, Generalitat de Catalunya, Ministerio de Ciencia, Innovación y Universidades (España), European Research Council, Newton Fund, National Natural Science Foundation of China, Biotechnology and Biological Sciences Research Council (UK), Agencia Estatal de Investigación (España), van Dorp, Lucy, Gelabert, Pere, Rieux, Adrien, Manuel, Marc de, De-Dios, Toni, Gopalakrishnan, Shyam, Carøe, Christian, Sandoval-Velasco, Marcela, Fregel, Rosa, Olalde, Iñigo, Escosa, Raül, Aranda, Carles, Huijben, Silvia, Mueller, Ivo, Marqués-Bonet, Tomàs, Balloux, François, Gilbert, M. Thomas P., and Lalueza-Fox, Carles

Abstract

The protozoan Plasmodium vivax is responsible for 42% of all cases of malaria outside Africa. The parasite is currently largely restricted to tropical and subtropical latitudes in Asia, Oceania, and the Americas. Though, it was historically present in most of Europe before being finally eradicated during the second half of the 20th century. The lack of genomic information on the extinct European lineage has prevented a clear understanding of historical population structuring and past migrations of P. vivax. We used medical microscope slides prepared in 1944 from malaria-affected patients from the Ebro Delta in Spain, one of the last footholds of malaria in Europe, to generate a genome of a European P. vivax strain. Population genetics and phylogenetic analyses placed this strain basal to a cluster including samples from the Americas. This genome allowed us to calibrate a genomic mutation rate for P. vivax, and to estimate the mean age of the last common ancestor between European and American strains to the 15th century. This date points to an introduction of the parasite during the European colonization of the Americas. In addition, we found that some known variants for resistance to antimalarial drugs, including Chloroquine and Sulfadoxine, were already present in this European strain, predating their use. Our results shed light on the evolution of an important human pathogen and illustrate the value of antique medical collections as a resource for retrieving genomic information on pathogens from the past.

Published
2020

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