Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally
Identifieur interne : 001B87 ( Istex/Corpus ); précédent : 001B86; suivant : 001B88Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally
Auteurs : Colin J. Sutherland ; Naowarat Tanomsing ; Debbie Nolder ; Mary Oguike ; Charlie Jennison ; Sasithon Pukrittayakamee ; Christiane Dolecek ; Tran Tinh Hien ; Virgilio E. Do Rosário ; Ana Paula Arez ; João Pinto ; Pascal Michon ; Ananias A. Escalante ; Francois Nosten ; Martina Burke ; Rogan Lee ; Marie Blaze ; Thomas Dan Otto ; John W. Barnwell ; Arnab Pain ; John Williams ; Nicholas J. White ; Nicholas P. J. Day ; Georges Snounou ; Peter J. Lockhart ; Peter L. Chiodini ; Mallika Imwong ; Spencer D. PolleySource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2010-05-15.
Abstract
Background. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. Methods. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. Results. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. Conclusions. We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.
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DOI: 10.1086/652240
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title><author><name sortKey="Sutherland, Colin J" sort="Sutherland, Colin J" uniqKey="Sutherland C" first="Colin J." last="Sutherland">Colin J. Sutherland</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation><affiliation><mods:affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation><affiliation><mods:affiliation>Hospital for Tropical Diseases, London</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: colin.sutherland@lshtm.ac.uk</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Colin Sutherland, Immunology Unit, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: colin.sutherland@lshtm.ac.uk</mods:affiliation></affiliation></author><author><name sortKey="Tanomsing, Naowarat" sort="Tanomsing, Naowarat" uniqKey="Tanomsing N" first="Naowarat" last="Tanomsing">Naowarat Tanomsing</name><affiliation><mods:affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Nolder, Debbie" sort="Nolder, Debbie" uniqKey="Nolder D" first="Debbie" last="Nolder">Debbie Nolder</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Oguike, Mary" sort="Oguike, Mary" uniqKey="Oguike M" first="Mary" last="Oguike">Mary Oguike</name><affiliation><mods:affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Jennison, Charlie" sort="Jennison, Charlie" uniqKey="Jennison C" first="Charlie" last="Jennison">Charlie Jennison</name><affiliation><mods:affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Pukrittayakamee, Sasithon" sort="Pukrittayakamee, Sasithon" uniqKey="Pukrittayakamee S" first="Sasithon" last="Pukrittayakamee">Sasithon Pukrittayakamee</name><affiliation><mods:affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation><affiliation><mods:affiliation>The Royal Institute, Bangkok</mods:affiliation></affiliation></author><author><name sortKey="Dolecek, Christiane" sort="Dolecek, Christiane" uniqKey="Dolecek C" first="Christiane" last="Dolecek">Christiane Dolecek</name><affiliation><mods:affiliation>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</mods:affiliation></affiliation></author><author><name sortKey="Hien, Tran Tinh" sort="Hien, Tran Tinh" uniqKey="Hien T" first="Tran Tinh" last="Hien">Tran Tinh Hien</name><affiliation><mods:affiliation>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</mods:affiliation></affiliation></author><author><name sortKey="Do Rosario, Virgilio E" sort="Do Rosario, Virgilio E" uniqKey="Do Rosario V" first="Virgilio E." last="Do Rosário">Virgilio E. Do Rosário</name><affiliation><mods:affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Arez, Ana Paula" sort="Arez, Ana Paula" uniqKey="Arez A" first="Ana Paula" last="Arez">Ana Paula Arez</name><affiliation><mods:affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Pinto, Joao" sort="Pinto, Joao" uniqKey="Pinto J" first="João" last="Pinto">João Pinto</name><affiliation><mods:affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Michon, Pascal" sort="Michon, Pascal" uniqKey="Michon P" first="Pascal" last="Michon">Pascal Michon</name><affiliation><mods:affiliation>Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea</mods:affiliation></affiliation></author><author><name sortKey="Escalante, Ananias A" sort="Escalante, Ananias A" uniqKey="Escalante A" first="Ananias A." last="Escalante">Ananias A. Escalante</name><affiliation><mods:affiliation>School of Life Sciences, Arizona State University, Tempe, Arizona</mods:affiliation></affiliation></author><author><name sortKey="Nosten, Francois" sort="Nosten, Francois" uniqKey="Nosten F" first="Francois" last="Nosten">Francois Nosten</name><affiliation><mods:affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</mods:affiliation></affiliation><affiliation><mods:affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation><affiliation><mods:affiliation>Shoklo Malaria Research Unit, Mae Sot, Thailand</mods:affiliation></affiliation></author><author><name sortKey="Burke, Martina" sort="Burke, Martina" uniqKey="Burke M" first="Martina" last="Burke">Martina Burke</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Lee, Rogan" sort="Lee, Rogan" uniqKey="Lee R" first="Rogan" last="Lee">Rogan Lee</name><affiliation><mods:affiliation>Westmead Hospital, Sydney, Australia</mods:affiliation></affiliation></author><author><name sortKey="Blaze, Marie" sort="Blaze, Marie" uniqKey="Blaze M" first="Marie" last="Blaze">Marie Blaze</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Otto, Thomas Dan" sort="Otto, Thomas Dan" uniqKey="Otto T" first="Thomas Dan" last="Otto">Thomas Dan Otto</name><affiliation><mods:affiliation>Sanger Genome Centre, Hinxton, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Barnwell, John W" sort="Barnwell, John W" uniqKey="Barnwell J" first="John W." last="Barnwell">John W. Barnwell</name><affiliation><mods:affiliation>Centers for Disease Control and Prevention, Atlanta, Georgia, United States</mods:affiliation></affiliation></author><author><name sortKey="Pain, Arnab" sort="Pain, Arnab" uniqKey="Pain A" first="Arnab" last="Pain">Arnab Pain</name><affiliation><mods:affiliation>Sanger Genome Centre, Hinxton, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Williams, John" sort="Williams, John" uniqKey="Williams J" first="John" last="Williams">John Williams</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="White, Nicholas J" sort="White, Nicholas J" uniqKey="White N" first="Nicholas J." last="White">Nicholas J. White</name><affiliation><mods:affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</mods:affiliation></affiliation><affiliation><mods:affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Day, Nicholas P J" sort="Day, Nicholas P J" uniqKey="Day N" first="Nicholas P. J." last="Day">Nicholas P. J. Day</name><affiliation><mods:affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</mods:affiliation></affiliation><affiliation><mods:affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Snounou, Georges" sort="Snounou, Georges" uniqKey="Snounou G" first="Georges" last="Snounou">Georges Snounou</name><affiliation><mods:affiliation>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S945</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre and Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, National University of Singapore, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Lockhart, Peter J" sort="Lockhart, Peter J" uniqKey="Lockhart P" first="Peter J." last="Lockhart">Peter J. Lockhart</name><affiliation><mods:affiliation>Alan Wilson Centre, Massey University, Palmerston North, New Zealand</mods:affiliation></affiliation></author><author><name sortKey="Chiodini, Peter L" sort="Chiodini, Peter L" uniqKey="Chiodini P" first="Peter L." last="Chiodini">Peter L. Chiodini</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation><affiliation><mods:affiliation>Hospital for Tropical Diseases, London</mods:affiliation></affiliation></author><author><name sortKey="Imwong, Mallika" sort="Imwong, Mallika" uniqKey="Imwong M" first="Mallika" last="Imwong">Mallika Imwong</name><affiliation><mods:affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Polley, Spencer D" sort="Polley, Spencer D" uniqKey="Polley S" first="Spencer D." last="Polley">Spencer D. Polley</name><affiliation><mods:affiliation>Hospital for Tropical Diseases, London</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:934AE9AC3FE9987720CDD21CD1D7141C54A6538D</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1086/652240</idno><idno type="url">https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001B87</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001B87</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title><author><name sortKey="Sutherland, Colin J" sort="Sutherland, Colin J" uniqKey="Sutherland C" first="Colin J." last="Sutherland">Colin J. Sutherland</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation><affiliation><mods:affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation><affiliation><mods:affiliation>Hospital for Tropical Diseases, London</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: colin.sutherland@lshtm.ac.uk</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Colin Sutherland, Immunology Unit, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: colin.sutherland@lshtm.ac.uk</mods:affiliation></affiliation></author><author><name sortKey="Tanomsing, Naowarat" sort="Tanomsing, Naowarat" uniqKey="Tanomsing N" first="Naowarat" last="Tanomsing">Naowarat Tanomsing</name><affiliation><mods:affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Nolder, Debbie" sort="Nolder, Debbie" uniqKey="Nolder D" first="Debbie" last="Nolder">Debbie Nolder</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Oguike, Mary" sort="Oguike, Mary" uniqKey="Oguike M" first="Mary" last="Oguike">Mary Oguike</name><affiliation><mods:affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Jennison, Charlie" sort="Jennison, Charlie" uniqKey="Jennison C" first="Charlie" last="Jennison">Charlie Jennison</name><affiliation><mods:affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Pukrittayakamee, Sasithon" sort="Pukrittayakamee, Sasithon" uniqKey="Pukrittayakamee S" first="Sasithon" last="Pukrittayakamee">Sasithon Pukrittayakamee</name><affiliation><mods:affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation><affiliation><mods:affiliation>The Royal Institute, Bangkok</mods:affiliation></affiliation></author><author><name sortKey="Dolecek, Christiane" sort="Dolecek, Christiane" uniqKey="Dolecek C" first="Christiane" last="Dolecek">Christiane Dolecek</name><affiliation><mods:affiliation>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</mods:affiliation></affiliation></author><author><name sortKey="Hien, Tran Tinh" sort="Hien, Tran Tinh" uniqKey="Hien T" first="Tran Tinh" last="Hien">Tran Tinh Hien</name><affiliation><mods:affiliation>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</mods:affiliation></affiliation></author><author><name sortKey="Do Rosario, Virgilio E" sort="Do Rosario, Virgilio E" uniqKey="Do Rosario V" first="Virgilio E." last="Do Rosário">Virgilio E. Do Rosário</name><affiliation><mods:affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Arez, Ana Paula" sort="Arez, Ana Paula" uniqKey="Arez A" first="Ana Paula" last="Arez">Ana Paula Arez</name><affiliation><mods:affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Pinto, Joao" sort="Pinto, Joao" uniqKey="Pinto J" first="João" last="Pinto">João Pinto</name><affiliation><mods:affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</mods:affiliation></affiliation></author><author><name sortKey="Michon, Pascal" sort="Michon, Pascal" uniqKey="Michon P" first="Pascal" last="Michon">Pascal Michon</name><affiliation><mods:affiliation>Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea</mods:affiliation></affiliation></author><author><name sortKey="Escalante, Ananias A" sort="Escalante, Ananias A" uniqKey="Escalante A" first="Ananias A." last="Escalante">Ananias A. Escalante</name><affiliation><mods:affiliation>School of Life Sciences, Arizona State University, Tempe, Arizona</mods:affiliation></affiliation></author><author><name sortKey="Nosten, Francois" sort="Nosten, Francois" uniqKey="Nosten F" first="Francois" last="Nosten">Francois Nosten</name><affiliation><mods:affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</mods:affiliation></affiliation><affiliation><mods:affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation><affiliation><mods:affiliation>Shoklo Malaria Research Unit, Mae Sot, Thailand</mods:affiliation></affiliation></author><author><name sortKey="Burke, Martina" sort="Burke, Martina" uniqKey="Burke M" first="Martina" last="Burke">Martina Burke</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Lee, Rogan" sort="Lee, Rogan" uniqKey="Lee R" first="Rogan" last="Lee">Rogan Lee</name><affiliation><mods:affiliation>Westmead Hospital, Sydney, Australia</mods:affiliation></affiliation></author><author><name sortKey="Blaze, Marie" sort="Blaze, Marie" uniqKey="Blaze M" first="Marie" last="Blaze">Marie Blaze</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="Otto, Thomas Dan" sort="Otto, Thomas Dan" uniqKey="Otto T" first="Thomas Dan" last="Otto">Thomas Dan Otto</name><affiliation><mods:affiliation>Sanger Genome Centre, Hinxton, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Barnwell, John W" sort="Barnwell, John W" uniqKey="Barnwell J" first="John W." last="Barnwell">John W. Barnwell</name><affiliation><mods:affiliation>Centers for Disease Control and Prevention, Atlanta, Georgia, United States</mods:affiliation></affiliation></author><author><name sortKey="Pain, Arnab" sort="Pain, Arnab" uniqKey="Pain A" first="Arnab" last="Pain">Arnab Pain</name><affiliation><mods:affiliation>Sanger Genome Centre, Hinxton, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Williams, John" sort="Williams, John" uniqKey="Williams J" first="John" last="Williams">John Williams</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation></author><author><name sortKey="White, Nicholas J" sort="White, Nicholas J" uniqKey="White N" first="Nicholas J." last="White">Nicholas J. White</name><affiliation><mods:affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</mods:affiliation></affiliation><affiliation><mods:affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Day, Nicholas P J" sort="Day, Nicholas P J" uniqKey="Day N" first="Nicholas P. J." last="Day">Nicholas P. J. Day</name><affiliation><mods:affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</mods:affiliation></affiliation><affiliation><mods:affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Snounou, Georges" sort="Snounou, Georges" uniqKey="Snounou G" first="Georges" last="Snounou">Georges Snounou</name><affiliation><mods:affiliation>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S945</mods:affiliation></affiliation><affiliation><mods:affiliation>Université Pierre and Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, National University of Singapore, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Lockhart, Peter J" sort="Lockhart, Peter J" uniqKey="Lockhart P" first="Peter J." last="Lockhart">Peter J. Lockhart</name><affiliation><mods:affiliation>Alan Wilson Centre, Massey University, Palmerston North, New Zealand</mods:affiliation></affiliation></author><author><name sortKey="Chiodini, Peter L" sort="Chiodini, Peter L" uniqKey="Chiodini P" first="Peter L." last="Chiodini">Peter L. Chiodini</name><affiliation><mods:affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</mods:affiliation></affiliation><affiliation><mods:affiliation>Hospital for Tropical Diseases, London</mods:affiliation></affiliation></author><author><name sortKey="Imwong, Mallika" sort="Imwong, Mallika" uniqKey="Imwong M" first="Mallika" last="Imwong">Mallika Imwong</name><affiliation><mods:affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</mods:affiliation></affiliation></author><author><name sortKey="Polley, Spencer D" sort="Polley, Spencer D" uniqKey="Polley S" first="Spencer D." last="Polley">Spencer D. Polley</name><affiliation><mods:affiliation>Hospital for Tropical Diseases, London</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published" when="2010-05-15">2010-05-15</date><biblScope unit="volume">201</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1544">1544</biblScope><biblScope unit="page" to="1550">1550</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. Methods. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. Results. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. Conclusions. We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Colin J. Sutherland</name><affiliations><json:string>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string><json:string>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string><json:string>Hospital for Tropical Diseases, London</json:string><json:string>E-mail: colin.sutherland@lshtm.ac.uk</json:string><json:string>Reprints or correspondence: Colin Sutherland, Immunology Unit, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom</json:string><json:string>E-mail: colin.sutherland@lshtm.ac.uk</json:string></affiliations></json:item><json:item><name>Naowarat Tanomsing</name><affiliations><json:string>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</json:string></affiliations></json:item><json:item><name>Debbie Nolder</name><affiliations><json:string>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string></affiliations></json:item><json:item><name>Mary Oguike</name><affiliations><json:string>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string></affiliations></json:item><json:item><name>Charlie Jennison</name><affiliations><json:string>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string></affiliations></json:item><json:item><name>Sasithon Pukrittayakamee</name><affiliations><json:string>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</json:string><json:string>The Royal Institute, Bangkok</json:string></affiliations></json:item><json:item><name>Christiane Dolecek</name><affiliations><json:string>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</json:string></affiliations></json:item><json:item><name>Tran Tinh Hien</name><affiliations><json:string>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</json:string></affiliations></json:item><json:item><name>Virgilio E. do Rosário</name><affiliations><json:string>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</json:string></affiliations></json:item><json:item><name>Ana Paula Arez</name><affiliations><json:string>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</json:string></affiliations></json:item><json:item><name>João Pinto</name><affiliations><json:string>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</json:string></affiliations></json:item><json:item><name>Pascal Michon</name><affiliations><json:string>Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea</json:string></affiliations></json:item><json:item><name>Ananias A. Escalante</name><affiliations><json:string>School of Life Sciences, Arizona State University, Tempe, Arizona</json:string></affiliations></json:item><json:item><name>Francois Nosten</name><affiliations><json:string>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</json:string><json:string>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</json:string><json:string>Shoklo Malaria Research Unit, Mae Sot, Thailand</json:string></affiliations></json:item><json:item><name>Martina Burke</name><affiliations><json:string>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string></affiliations></json:item><json:item><name>Rogan Lee</name><affiliations><json:string>Westmead Hospital, Sydney, Australia</json:string></affiliations></json:item><json:item><name>Marie Blaze</name><affiliations><json:string>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string></affiliations></json:item><json:item><name>Thomas Dan Otto</name><affiliations><json:string>Sanger Genome Centre, Hinxton, United Kingdom</json:string></affiliations></json:item><json:item><name>John W. Barnwell</name><affiliations><json:string>Centers for Disease Control and Prevention, Atlanta, Georgia, United States</json:string></affiliations></json:item><json:item><name>Arnab Pain</name><affiliations><json:string>Sanger Genome Centre, Hinxton, United Kingdom</json:string></affiliations></json:item><json:item><name>John Williams</name><affiliations><json:string>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string></affiliations></json:item><json:item><name>Nicholas J. White</name><affiliations><json:string>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</json:string><json:string>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</json:string></affiliations></json:item><json:item><name>Nicholas P. J. Day</name><affiliations><json:string>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</json:string><json:string>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</json:string></affiliations></json:item><json:item><name>Georges Snounou</name><affiliations><json:string>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S945</json:string><json:string>Université Pierre and Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France</json:string><json:string>Department of Microbiology, National University of Singapore, Singapore</json:string></affiliations></json:item><json:item><name>Peter J. Lockhart</name><affiliations><json:string>Alan Wilson Centre, Massey University, Palmerston North, New Zealand</json:string></affiliations></json:item><json:item><name>Peter L. Chiodini</name><affiliations><json:string>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</json:string><json:string>Hospital for Tropical Diseases, London</json:string></affiliations></json:item><json:item><name>Mallika Imwong</name><affiliations><json:string>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</json:string></affiliations></json:item><json:item><name>Spencer D. Polley</name><affiliations><json:string>Hospital for Tropical Diseases, London</json:string></affiliations></json:item></author><arkIstex>ark:/67375/HXZ-65CPQFX9-9</arkIstex><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. Methods. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. Results. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. Conclusions. We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.</abstract><qualityIndicators><score>9.352</score><pdfWordCount>5366</pdfWordCount><pdfCharCount>33750</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>196</abstractWordCount><abstractCharCount>1307</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title><pmid><json:string>20380562</json:string></pmid><genre><json:string>research-article</json:string></genre><host><title>The Journal of Infectious Diseases</title><language><json:string>unknown</json:string></language><issn><json:string>0022-1899</json:string></issn><eissn><json:string>1537-6613</json:string></eissn><publisherId><json:string>jid</json:string></publisherId><volume>201</volume><issue>10</issue><pages><first>1544</first><last>1550</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2006</json:string><json:string>1000</json:string><json:string>2007</json:string><json:string>from 1987 through 2006</json:string><json:string>2010</json:string><json:string>1922</json:string></date><geogName></geogName><orgName><json:string>Health Protection Agency Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, United Kingdom</json:string><json:string>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</json:string><json:string>Mahidol University</json:string><json:string>Massey University</json:string><json:string>Department of Clinical Medicine, Churchill Hospital, Oxford</json:string><json:string>Guinea Institute of Medical Research, Madang, Papua New Guinea</json:string><json:string>Health Protection Agency Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine</json:string><json:string>World Health Organization (WHO)</json:string><json:string>Society for Parasitology Malaria Meeting</json:string><json:string>Royal Institute, Bangkok</json:string><json:string>Hospital for Tropical Diseases, London</json:string><json:string>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</json:string><json:string>Westmead Hospital, Sydney, Australia</json:string><json:string>Arizona State University</json:string><json:string>Department of Clinical Tropical Medicine</json:string><json:string>Department of Microbiology, National University of Singapore, Singapore</json:string><json:string>Commission on Higher Education</json:string><json:string>Mahidol University’s Department of Clinical Tropical Medicine</json:string><json:string>Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme</json:string><json:string>University College London Hospitals Comprehensive Biomedical Research Centre Infection Theme</json:string><json:string>Georgia, United States</json:string><json:string>Shoklo Malaria Research Unit, Mae Sot, Thailand</json:string><json:string>Ghana, Nigeria, Sao Tome, Sierra Leone, and Uganda and have</json:string><json:string>Thailand Research Fund</json:string><json:string>United Kingdom Health Protection Agency</json:string><json:string>Wellcome Trust of Great Britain</json:string></orgName><orgName_funder><json:string>United Kingdom Health Protection Agency</json:string><json:string>Wellcome Trust of Great Britain</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Christiane Dolecek</json:string><json:string>Peter J. Lockhart</json:string><json:string>Ana Paula</json:string><json:string>Debbie Nolder</json:string><json:string>Joao Pinto</json:string><json:string>Tran Tinh</json:string><json:string>Nova de Lisboa</json:string><json:string>E. do Rosario</json:string><json:string>Georges Snounou</json:string><json:string>Peter L. Chiodini</json:string><json:string>John Williams</json:string><json:string>Nucleotides</json:string><json:string>Nicholas J. White</json:string><json:string>London School</json:string><json:string>Marie Curie</json:string><json:string>Pascal Michon</json:string><json:string>Colin Sutherland</json:string><json:string>P. J. Day</json:string><json:string>Ananias A. Escalante</json:string><json:string>Wilson Centre</json:string><json:string>Universite Pierre</json:string><json:string>Linda Duval</json:string><json:string>Charlie Jennison</json:string><json:string>Marie Blaze</json:string><json:string>Francois Nosten</json:string><json:string>Dan Otto</json:string><json:string>Kingdom</json:string><json:string>Martina Burke</json:string><json:string>John W. Barnwell</json:string><json:string>Spencer D. Polley</json:string></persName><placeName><json:string>Paris</json:string><json:string>Vietnam</json:string><json:string>Papua New Guinea</json:string><json:string>Thailand</json:string><json:string>Bangkok</json:string><json:string>Edinburgh</json:string><json:string>London</json:string><json:string>Benin</json:string><json:string>Atlanta</json:string><json:string>America</json:string><json:string>Nigeria</json:string><json:string>Lisbon</json:string><json:string>New Zealand</json:string><json:string>United Kingdom</json:string><json:string>Portugal</json:string><json:string>France</json:string></placeName><ref_url><json:string>http://plasmodb.org/plasmo/</json:string></ref_url><ref_bibl><json:string>[15, 25]</json:string><json:string>Stevens 1922</json:string><json:string>[12]</json:string><json:string>[11]</json:string><json:string>[17]</json:string><json:string>[21]</json:string><json:string>[11, 13]</json:string><json:string>[16]</json:string><json:string>[20]</json:string><json:string>[7, 8]</json:string><json:string>[5]</json:string><json:string>[26]</json:string><json:string>[9, 10]</json:string><json:string>[18, 19]</json:string><json:string>[9]</json:string><json:string>[27, 28]</json:string><json:string>[4, 32, 33]</json:string><json:string>[35]</json:string><json:string>[19]</json:string><json:string>Sutherland et al</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/HXZ-65CPQFX9-9</json:string></ark><categories><wos><json:string>science</json:string><json:string>microbiology</json:string><json:string>infectious diseases</json:string><json:string>immunology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>biomedical research</json:string><json:string>microbiology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Immunology and Allergy</json:string></scopus></categories><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1086/652240</json:string></doi><id>934AE9AC3FE9987720CDD21CD1D7141C54A6538D</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://publisher-list.data.istex.fr">The University of Chicago Press</publisher><availability><licence><p>© 2010 by the Infectious Diseases Society of America</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</p></availability><date>2010</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title><author xml:id="author-0000" corresp="yes"><persName><forename type="first">Colin J.</forename><surname>Sutherland</surname></persName><email>colin.sutherland@lshtm.ac.uk</email><email>colin.sutherland@lshtm.ac.uk</email><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><affiliation>Hospital for Tropical Diseases, London</affiliation><affiliation>Reprints or correspondence: Colin Sutherland, Immunology Unit, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Naowarat</forename><surname>Tanomsing</surname></persName><affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Debbie</forename><surname>Nolder</surname></persName><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Mary</forename><surname>Oguike</surname></persName><affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Charlie</forename><surname>Jennison</surname></persName><affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Sasithon</forename><surname>Pukrittayakamee</surname></persName><affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</affiliation><affiliation>The Royal Institute, Bangkok</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Christiane</forename><surname>Dolecek</surname></persName><affiliation>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Tran Tinh</forename><surname>Hien</surname></persName><affiliation>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Virgilio E.</forename><surname>do Rosário</surname></persName><affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Ana Paula</forename><surname>Arez</surname></persName><affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</affiliation></author><author xml:id="author-0010"><persName><forename type="first">João</forename><surname>Pinto</surname></persName><affiliation>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal</affiliation></author><author xml:id="author-0011"><persName><forename type="first">Pascal</forename><surname>Michon</surname></persName><affiliation>Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea</affiliation></author><author xml:id="author-0012"><persName><forename type="first">Ananias A.</forename><surname>Escalante</surname></persName><affiliation>School of Life Sciences, Arizona State University, Tempe, Arizona</affiliation></author><author xml:id="author-0013"><persName><forename type="first">Francois</forename><surname>Nosten</surname></persName><affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</affiliation><affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</affiliation><affiliation>Shoklo Malaria Research Unit, Mae Sot, Thailand</affiliation></author><author xml:id="author-0014"><persName><forename type="first">Martina</forename><surname>Burke</surname></persName><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation></author><author xml:id="author-0015"><persName><forename type="first">Rogan</forename><surname>Lee</surname></persName><affiliation>Westmead Hospital, Sydney, Australia</affiliation></author><author xml:id="author-0016"><persName><forename type="first">Marie</forename><surname>Blaze</surname></persName><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation></author><author xml:id="author-0017"><persName><forename type="first">Thomas Dan</forename><surname>Otto</surname></persName><affiliation>Sanger Genome Centre, Hinxton, United Kingdom</affiliation></author><author xml:id="author-0018"><persName><forename type="first">John W.</forename><surname>Barnwell</surname></persName><affiliation>Centers for Disease Control and Prevention, Atlanta, Georgia, United States</affiliation></author><author xml:id="author-0019"><persName><forename type="first">Arnab</forename><surname>Pain</surname></persName><affiliation>Sanger Genome Centre, Hinxton, United Kingdom</affiliation></author><author xml:id="author-0020"><persName><forename type="first">John</forename><surname>Williams</surname></persName><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation></author><author xml:id="author-0021"><persName><forename type="first">Nicholas J.</forename><surname>White</surname></persName><affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</affiliation><affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</affiliation></author><author xml:id="author-0022"><persName><forename type="first">Nicholas P. J.</forename><surname>Day</surname></persName><affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</affiliation><affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</affiliation></author><author xml:id="author-0023"><persName><forename type="first">Georges</forename><surname>Snounou</surname></persName><affiliation>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S945</affiliation><affiliation>Université Pierre and Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France</affiliation><affiliation>Department of Microbiology, National University of Singapore, Singapore</affiliation></author><author xml:id="author-0024"><persName><forename type="first">Peter J.</forename><surname>Lockhart</surname></persName><affiliation>Alan Wilson Centre, Massey University, Palmerston North, New Zealand</affiliation></author><author xml:id="author-0025"><persName><forename type="first">Peter L.</forename><surname>Chiodini</surname></persName><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><affiliation>Hospital for Tropical Diseases, London</affiliation></author><author xml:id="author-0026"><persName><forename type="first">Mallika</forename><surname>Imwong</surname></persName><affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</affiliation></author><author xml:id="author-0027"><persName><forename type="first">Spencer D.</forename><surname>Polley</surname></persName><affiliation>Hospital for Tropical Diseases, London</affiliation></author><idno type="istex">934AE9AC3FE9987720CDD21CD1D7141C54A6538D</idno><idno type="ark">ark:/67375/HXZ-65CPQFX9-9</idno><idno type="DOI">10.1086/652240</idno></analytic><monogr><title level="j">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="pISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><idno type="publisher-id">jid</idno><idno type="PublisherID-hwp">jinfdis</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published" when="2010-05-15"></date><biblScope unit="volume">201</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1544">1544</biblScope><biblScope unit="page" to="1550">1550</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><abstract><p>Background. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. Methods. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. Results. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. Conclusions. We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.</p></abstract></profileDesc><revisionDesc><change when="2010-05-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article">
<front>
<journal-meta>
<journal-id journal-id-type="hwp">jinfdis</journal-id>
<journal-id journal-id-type="publisher-id">jid</journal-id>
<journal-title>The Journal of Infectious Diseases</journal-title>
<abbrev-journal-title>The Journal of Infectious Diseases</abbrev-journal-title>
<issn pub-type="ppub">0022-1899</issn>
<issn pub-type="epub">1537-6613</issn>
<publisher>
<publisher-name>The University of Chicago Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1086/652240</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Major Articles and Brief Reports</subject>
<subj-group subj-group-type="heading">
<subject>Parasites</subject>
<subj-group subj-group-type="heading">
<subject>Major Articles</subject>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Two Nonrecombining Sympatric Forms of the Human Malaria Parasite <italic>Plasmodium ovale</italic> Occur Globally</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Sutherland</surname><given-names>Colin J.</given-names>
</name><xref ref-type="aff" rid="AFF1">1</xref><xref ref-type="aff" rid="AFF2">2</xref><xref ref-type="aff" rid="AFF3">3</xref><xref rid="cor1" ref-type="corresp"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tanomsing</surname><given-names>Naowarat</given-names>
</name><xref ref-type="aff" rid="AFF6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nolder</surname><given-names>Debbie</given-names>
</name><xref ref-type="aff" rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Oguike</surname><given-names>Mary</given-names>
</name><xref ref-type="aff" rid="AFF2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jennison</surname><given-names>Charlie</given-names>
</name><xref ref-type="aff" rid="AFF2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pukrittayakamee</surname><given-names>Sasithon</given-names>
</name><xref ref-type="aff" rid="AFF6">6</xref><xref ref-type="aff" rid="AFF8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dolecek</surname><given-names>Christiane</given-names>
</name><xref ref-type="aff" rid="AFF10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hien</surname><given-names>Tran Tinh</given-names>
</name><xref ref-type="aff" rid="AFF10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>do Rosário</surname><given-names>Virgilio E.</given-names>
</name><xref ref-type="aff" rid="AFF11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Arez</surname><given-names>Ana Paula</given-names>
</name><xref ref-type="aff" rid="AFF11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pinto</surname><given-names>João</given-names>
</name><xref ref-type="aff" rid="AFF11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Michon</surname><given-names>Pascal</given-names>
</name><xref ref-type="aff" rid="AFF12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Escalante</surname><given-names>Ananias A.</given-names>
</name><xref ref-type="aff" rid="AFF13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nosten</surname><given-names>Francois</given-names>
</name><xref ref-type="aff" rid="AFF4">4</xref><xref ref-type="aff" rid="AFF7">7</xref><xref ref-type="aff" rid="AFF9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Burke</surname><given-names>Martina</given-names>
</name><xref ref-type="aff" rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname><given-names>Rogan</given-names>
</name><xref ref-type="aff" rid="AFF15">15</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Blaze</surname><given-names>Marie</given-names>
</name><xref ref-type="aff" rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Otto</surname><given-names>Thomas Dan</given-names>
</name><xref ref-type="aff" rid="AFF5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Barnwell</surname><given-names>John W.</given-names>
</name><xref ref-type="aff" rid="AFF14">14</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pain</surname><given-names>Arnab</given-names>
</name><xref ref-type="aff" rid="AFF5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Williams</surname><given-names>John</given-names>
</name><xref ref-type="aff" rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>White</surname><given-names>Nicholas J.</given-names>
</name><xref ref-type="aff" rid="AFF4">4</xref><xref ref-type="aff" rid="AFF7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Day</surname><given-names>Nicholas P. J.</given-names>
</name><xref ref-type="aff" rid="AFF4">4</xref><xref ref-type="aff" rid="AFF7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Snounou</surname><given-names>Georges</given-names>
</name><xref ref-type="aff" rid="AFF16">16</xref><xref ref-type="aff" rid="AFF17">17</xref><xref ref-type="aff" rid="AFF18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lockhart</surname><given-names>Peter J.</given-names>
</name><xref ref-type="aff" rid="AFF19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chiodini</surname><given-names>Peter L.</given-names>
</name><xref ref-type="aff" rid="AFF1">1</xref><xref ref-type="aff" rid="AFF3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Imwong</surname><given-names>Mallika</given-names>
</name><xref ref-type="aff" rid="AFF6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Polley</surname><given-names>Spencer D.</given-names>
</name><xref ref-type="aff" rid="AFF3">3</xref>
</contrib>
<aff id="AFF1"><label>1</label><institution>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</institution></aff>
<aff id="AFF2"><label>2</label><institution>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</institution></aff>
<aff id="AFF3"><label>3</label><institution>Hospital for Tropical Diseases</institution>, <addr-line>London</addr-line></aff>
<aff id="AFF4"><label>4</label><institution>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital</institution>, <addr-line>Oxford</addr-line></aff>
<aff id="AFF5"><label>5</label><institution>Sanger Genome Centre</institution>, <addr-line>Hinxton, United Kingdom</addr-line></aff>
<aff id="AFF6"><label>6</label><institution>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</institution></aff>
<aff id="AFF7"><label>7</label><institution>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</institution></aff>
<aff id="AFF8"><label>8</label><institution>The Royal Institute</institution>, <addr-line>Bangkok</addr-line></aff>
<aff id="AFF9"><label>9</label><institution>Shoklo Malaria Research Unit, Mae Sot</institution>, <addr-line>Thailand</addr-line></aff>
<aff id="AFF10"><label>10</label><institution>Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City</institution>, <addr-line>Vietnam</addr-line></aff>
<aff id="AFF11"><label>11</label><institution>Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa</institution>, <addr-line>Lisbon, Portugal</addr-line></aff>
<aff id="AFF12"><label>12</label><institution>Papua New Guinea Institute of Medical Research</institution>, <addr-line>Madang, Papua New Guinea</addr-line></aff>
<aff id="AFF13"><label>13</label><institution>School of Life Sciences, Arizona State University</institution>, <addr-line>Tempe, Arizona</addr-line></aff>
<aff id="AFF14"><label>14</label><institution>Centers for Disease Control and Prevention</institution>, <addr-line>Atlanta, Georgia, United States</addr-line></aff>
<aff id="AFF15"><label>15</label><institution>Westmead Hospital</institution>, <addr-line>Sydney, Australia</addr-line></aff>
<aff id="AFF16"><label>16</label><institution>Institut National de la Santé et de la Recherche Médicale</institution>, <addr-line>Unité Mixte de Recherche S945</addr-line></aff>
<aff id="AFF17"><label>17</label><institution>Université Pierre and Marie Curie, Faculté de Médecine Pitié-Salpêtrière</institution>, <addr-line>Paris, France</addr-line></aff>
<aff id="AFF18"><label>18</label><institution>Department of Microbiology, National University of Singapore</institution>, <addr-line>Singapore</addr-line></aff>
<aff id="AFF19"><label>19</label><institution>Alan Wilson Centre, Massey University</institution>, <addr-line>Palmerston North, New Zealand</addr-line></aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Reprints or correspondence: Colin Sutherland, <institution>Immunology Unit, London School of Hygiene and Tropical Medicine</institution>, <addr-line>Keppel St, London WC1E 7HT, United Kingdom</addr-line> (<email>colin.sutherland@lshtm.ac.uk</email>).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>15</day>
<month>5</month>
<year>2010</year>
</pub-date>
<volume>201</volume>
<issue>10</issue>
<fpage>1544</fpage>
<lpage>1550</lpage>
<history>
<date date-type="received">
<day>14</day>
<month>9</month>
<year>2009</year>
</date>
<date date-type="accepted">
<day>8</day>
<month>12</month>
<year>2009</year>
</date>
</history>
<copyright-statement>© 2010 by the Infectious Diseases Society of America</copyright-statement>
<copyright-year>2010</copyright-year>
<abstract>
<p><bold><italic>Background</italic></bold>. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus <italic>Plasmodium</italic>. Infections with <italic>Plasmodium ovale</italic> are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to <italic>P. ovale</italic> parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species.</p>
<p><bold><italic>Methods</italic></bold>. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries.</p>
<p><bold><italic>Results</italic></bold>. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts.</p>
<p><bold><italic>Conclusions</italic></bold>. We propose that <italic>P. ovale</italic> comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic <italic>P. ovale</italic> infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.</p>
</abstract>
</article-meta>
</front>
<body>
<p>One of 5 parasite species that causes human malaria [<xref rid="R1" ref-type="bibr">1</xref>, <xref rid="R2" ref-type="bibr">2</xref>], Plasmodium ovale (Stevens 1922) is widely distributed across tropical regions [<xref rid="R3" ref-type="bibr">3</xref>, <xref rid="R4" ref-type="bibr">4</xref>], although there have been no confirmed cases in the Americas [<xref rid="R5" ref-type="bibr">5</xref>]. The global burden of ovale malaria is considered to be slight, principally because the prevalence of <italic>P. ovale</italic> as detected by microscopy is low. Difficulty of diagnosis is partly the result of the low parasite density that is characteristic of clinical malaria caused by ovale malaria parasites [<xref rid="R3" ref-type="bibr">3</xref>, <xref rid="R6" ref-type="bibr">6</xref>–<xref rid="R8" ref-type="bibr">8</xref>]. <italic>P. ovale</italic> can be differentiated from other parasite species by amplification of species- specific sequences within genes encoding the parasite's small subunit ribosomal RNA (ssrRNA) [<xref rid="R9" ref-type="bibr">9</xref>]. However, a number of isolates microscopically identified as <italic>P. ovale</italic> could not be detected by this method [<xref rid="R10" ref-type="bibr">10</xref>] because of sequence variations in the ssrRNA gene target. It has since been demonstrated that the dimorphism into classic and variant ssrRNA types extended to other genes-specifically, the mitochondrial locus cytochrome b and the nuclear genes encoding both lactate dehydrogenase and the ookinete surface antigens of <italic>P. ovale</italic> [<xref rid="R11" ref-type="bibr">11</xref>–<xref rid="R13" ref-type="bibr">13</xref>]. Such dimorphism may simply reflect a regional discontinuity in the distribution of ovale malaria, and indeed most reports of variant parasites to date have been from regions of endemicity in Asia [<xref rid="R11" ref-type="bibr">11</xref>, <xref rid="R13" ref-type="bibr">13</xref>].</p>
<p>We hypothesized that the dimorphic forms of <italic>P. ovale</italic> actually comprise distinct species and that these might be geographically restricted. Two independent studies were initiated at Mahidol University, Bangkok, Thailand (MUB), and at the Health Protection Agency Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, London, United Kingdom (UKMRL), to address this hypothesis. Multilocus genetic analysis was used to explore the genetic diversity exhibited among 55 <italic>P. ovale</italic> isolates from 15 countries. The combined results of these 2 studies led us to conclude that <italic>P. ovale</italic> consists of 2 nonrecombining species but that these are sympatric in both Africa and Asia.</p>
<sec sec-type="methods">
<title>Methods</title>
<p><bold><italic>Parasite isolates</italic></bold>. The UKMRL sample set was collected by the Health Protection Agency Malaria Reference Laboratory at the London School of Hygiene and Tropical Medicine, the reference center for all imported cases of malaria in the United Kingdom. DNA from <italic>Plasmodium</italic> isolates is extracted and stored for use in validating new molecular diagnostic techniques and for surveillance purposes. No patient identifiers or data were linked to this sample set apart from the presumed country of origin of the infection. The sequence data shown were obtained from <italic>P. ovale</italic> isolates imported in 2007.</p>
<p>The MUB samples were provided by study authors and collaborators in the country of origin and were sent to Mahidol University's Department of Clinical Tropical Medicine. <italic>P. ovale</italic> DNA was isolated, and DNA sequences at loci of interest were determined by direct sequencing of polymerase chain reaction (PCR) products.</p>
<p><bold><italic>Genomic data</italic></bold>. Data were accessed via the PlasmoDB Blast server (<ext-link ext-link-type="uri" xlink:href="http://plasmodb.org/plasmo/">http://plasmodb.org/plasmo/</ext-link>), using <italic>Plasmodium falciparum</italic> sequences as bait. Where frameshifts were evident in <italic>Plasmodium gallinaceum</italic> or <italic>Plasmodium reichenowi</italic> contigs, these were altered to match the coding sequence of the <italic>P. falciparum</italic> homologue. Prerelease unannotated draft <italic>P. ovale</italic> genome sequence data from the CDC/Nigeria isolate of <italic>P. ovale</italic> [<xref rid="R14" ref-type="bibr">14</xref>] were searched by simple text queries for genes encoding putative erythrocyte-binding proteins and for regions coding amino acid repeats, which might be suitable for analysis of intraspecific polymorphism. The CDC/Nigeria isolate is a classic type.</p>
<p><bold><italic>Locus amplification and sequencing</italic></bold>. Conserved primers based on published sequences from the homologous loci in <italic>Plasmodium vivax</italic> and <italic>Plasmodium malariae</italic> were used to first identify <italic>pog3p</italic> sequences; <italic>podhfr-ts</italic> sequences were amplified using degenerate primers designed specifically for this study. Primers for <italic>potra</italic> and <italic>porbp2</italic> were also designed specifically for this study, on the basis of the unpublished draft genome sequence of the CDC/Nigeria isolate (classic type). All primer sequences used for amplification of each locus are given in <xref rid="fig3" ref-type="fig">Table 1</xref>. PCR products were purified and DNA sequences determined using BigDye chemistry (Applied Biosystems) followed by fractionation on capillary sequencers, as described elsewhere [<xref rid="R15" ref-type="bibr">15</xref>]. All novel DNA sequences were submitted to GenBank; accession numbers are shown in <xref rid="fig4" ref-type="fig">Table 2</xref>.</p>
<p><bold><italic>Phylogenetic analysis</italic></bold>. Split decomposition graphs were constructed from <italic>pocytb</italic> and <italic>pog3p</italic> data, using the computer program SplitsTree (version 4.0) [<xref rid="R16" ref-type="bibr">16</xref>]. Data from pocytb and pog3p sequences were analyzed independently by 2 investigators using different methods to estimate convergence times of <italic>P. ovale</italic> classic and variant types. First, unrooted trees were generated from maximum likelihood and parsimony methods, using the DNAML and FITCH programs in the PHYLIP program package (version 3.69) [<xref rid="R17" ref-type="bibr">17</xref>]. Different tree structures, together with alternative root positions and the imposition of a strict molecular clock, were tested for goodness of fit using the likelihood ratio and Kishino and Hasegawa tests within the CODEML program (version 4.3) [<xref rid="R18" ref-type="bibr">18</xref>, <xref rid="R19" ref-type="bibr">19</xref>]. The same program was used to date the divergence between the 2 <italic>P. ovale</italic> sequences, using a calibration date between <italic>P. falciparum</italic> and <italic>P. reichenowi</italic> of 5 million years ago (MYA); 95% confidence intervals were assigned by calculating the divergence date of this node within 1000 pseudorandom data sets generated from the data, and the same data set was used for calculating bootstrap values for individual nodes. Second, an estimate of divergence time was obtained by independent strict-clock analyses, using BEAST software (version 1.4) [<xref rid="R20" ref-type="bibr">20</xref>]. In these analyses, additional <italic>P. vivax</italic> and chimpanzee parasite sequences (CPZcam89 and CPZcam91) [<xref rid="R21" ref-type="bibr">21</xref>] were included. A general time-reversible model with invariant sites and γ correction was selected using Modeltest software (version 3.7) [<xref rid="R22" ref-type="bibr">22</xref>], and 3 tree nodes were calibrated assuming (1) a normal distribution; (2) that Asian primate parasites and African simian parasites (represented by <italic>Plasmodium gonderi</italic>) diverged 8.0 (±1.0) MYA; (3) that parasites of <italic>Pan</italic> and <italic>Homo</italic> species (represented by <italic>P. reichenowi</italic> and <italic>P. falciparum</italic>) diverged 4.1 (±0.4) MYA; and (4) that <italic>P. vivax</italic> strains diverged from each other 0.25 (±0.05) MYA.</p>
</sec>
<sec sec-type="results|discussion">
<title>Results and Discussion</title>
<p>On the basis of patterns of ssrRNA amplification [<xref rid="R9" ref-type="bibr">9</xref>, <xref rid="R10" ref-type="bibr">10</xref>], the classic or variant status was determined for the 35 isolates from patients with imported symptomatic ovale malaria cases (mainly African in origin) referred to the UKMRL. For these isolates, <italic>pocytb</italic> (which encodes the cytochrome b protein), <italic>pog3p</italic> (which encodes the glyceraldehyde-3-phosphatase, an enzyme that is highly conserved across the genus <italic>Plasmodium</italic>), <italic>porbp2</italic> (which encodes a homologue of reticulocyte-binding proteins in <italic>P. vivax</italic> and <italic>Plasmodium knowlesi</italic>), and <italic>potra</italic> (which encodes a tryptophan-rich antigen containing a variable-length 3-amino acid repeat) were analyzed. A similar study was independently initiated for 20 isolates collected at MUB and a number of collaborating centers, but for these sequence analysis was confined to the ssrRNA gene, <italic>podhfr-ts</italic> (which encodes dihydrofolate reductase-thymidylate synthase), and, for some isolates, the mitochondrial gene <italic>pocytb</italic>.</p>
<p>There was segregation of all dimorphic characters, such that each of the 55 parasite isolates was either of variant type or of classic type for all determined characters (<xref rid="fig5" ref-type="fig">Tables 3</xref> and <xref rid="fig6" ref-type="fig">4</xref>). Thus, there was no evidence of inter- or intragenic recombination between the classic and variant haplotypes sampled from 2 distinct biogeographic regions of the world. This confirmed that the multigenic haplotypes are stable and is consistent with the existence of a bona fide species barrier, illustrated by split decomposition graphs for <italic>pocytb</italic> (from Africa and Asia) and <italic>pog3p</italic> (from Africa only), which indicate a strong bifurcation separating the 2 <italic>P. ovale</italic> forms (<xref rid="fig1" ref-type="fig">Figure 1</xref>). Contrary to a priori predictions, classic and variant <italic>P. ovale</italic> parasites were found to be sympatric across Africa, occurring together in 5 of the countries from which our isolates were obtained (<xref rid="fig6" ref-type="fig">Table 4</xref>). The MUB isolates were found to harbor variant and classic <italic>pocytb</italic> alleles identical to those in the UKMRL sample set, and these segregated perfectly with ssrRNA genes of the variant and classic types. The only exception was a single isolate from Papua New Guinea—this isolate harbored the variant allele of <italic>podhfr-ts</italic>, but its ssrRNA gene included 8 residues characteristic of the classic allele from a total of 25 polymorphic sites, with the remaining 17 sites being identical to the variant allele (<xref rid="fig6" ref-type="fig">Table 4</xref>). Further analyses of this sample were not possible because of a lack of material. The <italic>pocytb</italic> sequences from 3 classic and 3 variant <italic>P. ovale</italic> isolates from Myanmar and Thailand described by Win et al [<xref rid="R11" ref-type="bibr">11</xref>] showed perfect concordance with the 22 classic and 18 variant <italic>pocytb</italic> sequences described here. We conclude that these 2 parasite types are sympatric in Africa and Asia and that allopatry cannot explain the lack of recombination between the multilocus haplotypes we have described.</p>
<p>We reconstructed gene trees for <italic>Plasmodium cytb</italic> sequences, using both maximum likelihood-based and distance-based methodologies to ensure congruency of topologies [<xref rid="R17" ref-type="bibr">17</xref>, <xref rid="R23" ref-type="bibr">23</xref>]. Alternative roots and the goodness of fit of molecular clocks on both local and global scales were tested [<xref rid="R18" ref-type="bibr">18</xref>, <xref rid="R19" ref-type="bibr">19</xref>]. The single optimum bifurcating tree with <italic>P. gallinaceum</italic> as the outgroup supported a global molecular clock (<xref rid="fig2" ref-type="fig">Figure 2</xref>). After calibrating this clock on the assumption of a divergence time of <italic>P. falciparum</italic> and <italic>P. reichenowi</italic> of 5 MYA [<xref rid="R15" ref-type="bibr">15</xref>, <xref rid="R25" ref-type="bibr">25</xref>], the 2 <italic>P. ovale</italic> forms converged on a mean estimate of 2.1–2.2 MYA (95% highest posterior density interval, 0.9–3.6 MYA). This finding was supported by an alternative strict-clock analysis [<xref rid="R20" ref-type="bibr">20</xref>] that used divergence among the rodent malaria parasites <italic>Plasmodium yoelli</italic>, <italic>Plasmodium chabaudi</italic>, <italic>Plasmodium berghei</italic>, and <italic>Plasmodium vinckei</italic> to calibrate the clock. Calibration of the original analysis with a more recent <italic>P. falciparum/P. reichenowi</italic> divergence estimate of 3 MYA [<xref rid="R26" ref-type="bibr">26</xref>] suggested a slightly more recent divergence of the <italic>P. ovale</italic> forms, at 1.3 MYA (95% highest posterior density interval, 0.67–2.1 MYA).</p>
<p>We conclude that the classic and variant <italic>P. ovale</italic> forms are in fact 2 distinct nonrecombining globally sympatric species, and we propose to name these species <italic>Plasmodium ovale curtisi</italic> (classic type) and <italic>Plasmodium ovale wallikeri</italic> (variant type), in honor of Christopher F. Curtis (1939–2008) and DavidWalliker (1940–2007), respectively.We have adopted the trinomial forms to maintain ovale in the nomenclature for the sake of continuity and to minimize any confusion that might arise from altering the name of a long-established taxon of clinical importance, particularly because it is unclear which of these should be considered the agent of “true” ovale malaria, originally described by Stevens in 1922.</p>
<p>It is difficult to conceive of an explanation for our results if all the parasites analyzed are of the same species. Although selffertilization may occur between identical parasite genotypes (particularly under conditions of low transmission), no truly clonal natural population of any <italic>Plasmodium</italic> species parasite has been described. We conclude that sexual recombination is an obligate event for <italic>P. ovale</italic> parasites, as it is for all other <italic>Plasmodium</italic> species. The following points summarize our evidence that the 2 forms of <italic>P. ovale</italic> should be considered distinct species:
<list list-type="bullet">
<list-item>
<p>Perfect segregation of 5 loci into 2 distinct types was found among 55 isolates.</p>
</list-item>
<list-item>
<p>Both types are widespread in both Africa and Asia and were documented here as being sympatric in many African countries and in at least 1 Southeast Asian country (Myanmar).</p>
</list-item>
<list-item>
<p>Indirect evidence from imported ovale malaria cases in the United Kingdom suggests that, as Trape and colleagues have previously argued [<xref rid="R7" ref-type="bibr">7</xref>, <xref rid="R8" ref-type="bibr">8</xref>], transmission intensity of ovalemalaria is not uniformly low, as is usually assumed. This strongly supports the notion that the 2 <italic>P. ovale</italic> types have the opportunity to mate and recombine but do not do so.</p>
</list-item>
<list-item>
<p>The extent of the diversity in the cytochrome b gene (12 single-nucleotide polymorphisms), which presents as complete dimorphism between classic and variant <italic>P. ovale</italic>, is difficult to explain away as within-species polymorphism for a gene that is highly conserved among members of the genus <italic>Plasmodium</italic>.</p>
</list-item>
<list-item>
<p>Only minor differences are observed among <italic>dhfr-ts</italic> sequences of <italic>P. falciparum</italic>, <italic>P. vivax</italic>, and <italic>P. malariae</italic> isolates collected from different continents. However, our <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> isolates carry very distinct DHFR-TS enzymes (29 nonsynonymous mutations and a different amino acid repeat length in the coding region), suggesting real biochemical differences between them.</p>
</list-item>
<list-item>
<p>Definitive proof of a biological species barrier ideally comes from cross-mating experiments; these are in fact virtually impossible, because <italic>P. ovale</italic> parasites cannot currently be cultured. Although <italic>P. ovale curtisi</italic> is established in experimental chimpanzee models, <italic>P. ovale wallikeri</italic> is not; consequently, primate-based crosses could not be performed ethically at this time either. Thus, molecular analyses offer the only avenue to analyze the relationship between the dimorphic forms of <italic>P. ovale</italic>.</p>
</list-item>
</list>
</p>
<p>Therefore, we consider that the weight of evidence favors the proposition that the 2 <italic>P. ovale</italic> types are actually 2 distinct species.</p>
<p>Allopatry may have contributed to the initial putative speciation event between <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic>, with the 2 geographically separated populations moving back into sympatry subsequent to divergence, perhaps as a result of migration of their simian or hominid hosts. Alternatively, assuming that the common ancestral parasite lineage of both species was in early hominids, 2 independent host transitions separated in time may have occurred between ape and human lineages. The intervening period of evolution in different hosts could have led to speciation, which then prevented recombination when both lineages later occupied the same primate hosts.</p>
<p>The nature of the mechanism(s) keeping <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> apart in the present is of great interest but remains speculative. There are 3 possible scenarios. First, subtle regional, ecological, or seasonal differences in their distribution could be maintaining a physical barrier between the 2 species. Second, the 2 species may have mutually exclusive mosquito or human host specificities. The occurrence of <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> across Asia and Africa, where many different <italic>Anopheles</italic> species transmit malaria to humans, makes it less likely that nonoverlapping vector specificities alone prevent the 2 parasite species from recombining. A possible restriction at the level of the human host is suggested from the differences noted for the <italic>porbp2</italic> genes of the 2 species. This locus encodes a putative erythrocyte/reticulocyte-binding molecule. The majority of differences were nonsynonymous (a pattern in stark contrast to the other loci analyzed [<xref rid="fig5" ref-type="fig">Table 3</xref>]), which implies that <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> may differ in host red cell invasion phenotype. Thus, if each species were an obligate invader of erythrocytes with distinct but mutually exclusive characteristics, the 2 parasite types would never occupy the same human host. However, an erythrocyte-based restriction would not necessarily prevent hybridization between the 2 species because of incomplete feeding. This occurs when a mosquito feeds in >1 human host in the same night, allowing ingestion of both species and thus the chance for recombination. This scenario requires that people carrying infective gametocytes of <italic>P. ovale curtisi</italic> and of <italic>P. ovale wallikeri</italic> are in very close proximity to each other on the same night.</p>
<p>Laboratory-based investigations of erythrocyte invasion are limited for <italic>P. ovale</italic>, because this species cannot at present be maintained in vitro or manipulated genetically. It is interesting to note that host restriction does not prevent infection in the chimpanzee; the <italic>P. ovale curtisi</italic> isolate currently undergoing genome sequencing was propagated in a chimpanzee [<xref rid="R14" ref-type="bibr">14</xref>], and recent data confirm that <italic>P. ovale wallikeri</italic> retains the ability to naturally infect chimpanzees [<xref rid="R21" ref-type="bibr">21</xref>]. It of course remains possible that host partitioning due to erythrocyte-invasion requirements also occurs between the 2 species in <italic>Pan</italic>.</p>
<p>A third mechanism for maintenance of the 2 distinct species could be mating incompatibility between the gametocytes of <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> or the production of noninfective sporozoites from cross-fertilization events. However, the occurrence of such phenomena among <italic>Plasmodium</italic> parasites has not been documented, to our knowledge. Our observations suggest that propagation of these 2 parasites may involve frequent self-fertilization, given that relatively low within-species diversity is observed. This may assist in the maintenance of 2 distinct <italic>P. ovale</italic> species, because the multigenic haplotypes we have described are remarkably stable across large geographic distances. However, this cannot explain the original divergence of these 2 types, and we assume that <italic>P. ovale</italic> undergoes obligate sexual recombination (as in all <italic>Plasmodium</italic> species studied to date), a view supported by the presence of homologues of sexual-stage antigens from <italic>P. vivax</italic> and <italic>P. malariae</italic> [<xref rid="R13" ref-type="bibr">13</xref>]. Some deviation from strict segregation of genetic markers was found for the ssrRNA gene, particularly for a single <italic>P. ovale wallikeri</italic> parasite collected in Papua New Guinea (<xref rid="fig5" ref-type="fig">Tables 3</xref><italic>A</italic> and <xref rid="fig6" ref-type="fig">4</xref>), but in our view this represents intraspecific polymorphism in a nonprotein coding gene, because the 8 substitutions observed that were not of the <italic>P. ovale wallikeri</italic> type were not contiguous. More detailed studies of <italic>P. ovale</italic> species in Melanesia are planned and may be crucial to understanding these newly recognized sibling species.</p>
<p>The existence of 2 distinct species, <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic>, cocirculating across global malaria transmission zones raises a number of important questions. Do these species differ in clinical presentation? Are both species adequately identified by pangenus rapid diagnostic tests [<xref rid="R12" ref-type="bibr">12</xref>]? Do they have different drug susceptibility profiles, and do they differ in their relapse periodicity? The eventual publication of the genome sequences of <italic>P. ovale curtisi</italic> should help obtain meaningful data on the genetic diversity of different isolates from the 2 species and assist in answering these questions. The ability of <italic>P. ovale</italic> to relapse from persisting hepatic forms makes this species important in the context of malaria control and its eventual eradication. <italic>P. ovale</italic> and <italic>P. falciparum</italic> often exist in the same host simultaneously [<xref rid="R27" ref-type="bibr">27</xref>, <xref rid="R28" ref-type="bibr">28</xref>]. The widespread use of highly effective artemisinin combination therapies to treat <italic>P. falciparum</italic> infections may provide an opportunity for <italic>P. ovale</italic> to emerge from the liver after drug levels subside in treated people, as does <italic>P. vivax</italic> [<xref rid="R29" ref-type="bibr">29</xref>–<xref rid="R31" ref-type="bibr">31</xref>]. <italic>P. ovale</italic> has been described as having relapse intervals from 17 days to >2 years after exposure [<xref rid="R4" ref-type="bibr">4</xref>, <xref rid="R32" ref-type="bibr">32</xref>, <xref rid="R33" ref-type="bibr">33</xref>], but it is possible that the 2 species differ in their relapse periodicity and frequency. Prospective studies of treated cases of <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> infection with adequate follow-up are required to address this question.</p>
<p>Our present investigation also led us to agree with Trape and colleagues that the contribution of <italic>P. ovale</italic> infections to malaria morbidity is significantly underestimated, probably as a result of misdiagnosis [<xref rid="R7" ref-type="bibr">7</xref>, <xref rid="R8" ref-type="bibr">8</xref>]. Recent improvements in the quality of malaria microscopy in countries of nonendemicity, together with the use of PCR to confirm species identification, indicates that <italic>P. ovale</italic> infections are more prevalent among imported cases than would be expected on the basis of surveys conducted in malaria-endemic countries [<xref rid="R5" ref-type="bibr">5</xref>, <xref rid="R32" ref-type="bibr">32</xref>–<xref rid="R34" ref-type="bibr">34</xref>]. For example, among 39,300 malaria cases imported into the United Kingdom from 1987 through 2006, Smith et al [<xref rid="R5" ref-type="bibr">5</xref>] reported 2101 confirmed symptomatic cases of <italic>P. ovale</italic> infection, acquired mainly in Africa. More recent data from the UKMRL showed that 45 of the 488 clinical cases of single-species malarial infection imported into the United Kingdom from Nigeria in 2007 were caused by <italic>P. ovale</italic>. If this prevalence of 9.2% held true for all clinical malaria recorded in Nigeria, where the annual malaria burden in 2006 was reported to be 57.5 million cases [<xref rid="R35" ref-type="bibr">35</xref>], this would correspond to 5 million symptomatic cases of <italic>P. ovale</italic> malaria per annum. Extending this estimate to the other malaria- endemic countries would predict an Africa-wide burden that exceeds 15 million cases annually. Thus, <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> together constitute a substantial public health problem, and there is ample justification to allocate scientific and financial resources to further understanding to aid control of these hitherto-neglected malaria parasites.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgments</title>
<p>We thank a number of colleagues for useful discussions, particularly Douglas Futuyma, Chris Newbold, and Richard Culleton. We are grateful to Linda Duval and Frederic Ariey for providing the chimpanzee isolate <italic>cytb</italic> sequences CPZcam89 and CPZcam91.</p>
</ack>
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<title>Figures and Tables</title>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Split decomposition graphs of 41 pocytb (<italic>A</italic>) and 35 <italic>pog3p</italic> (<italic>B</italic>) sequences. Graphs were constructed using the computer program SplitsTree (version 4.0) [<xref rid="R16" ref-type="bibr">16</xref>]. Scale bars show relative sequence dissimilarity. Data on <italic>pocytb</italic> are from both the Health Protection Agency Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, United Kingdom (UKMRL), sample set (<italic>n</italic> = 34) and the Mahidol University, Bangkok, sample set (<italic>n</italic> = 6). Data on <italic>pog3p</italic> are from the UKMRL sample set only; DNA was not available for sequencing of <italic>pocytb</italic> in 2 UKMRL isolates. The numbers of sequences in each node are shown in italics</p>
</caption>
<graphic mimetype="image" xlink:href="201-10-1544-fig001.tif"></graphic>
</fig>
<fig position="float" id="fig2">
<label>Figure 2</label>
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<p>Unrooted phylogenetic tree representing the relationship of <italic>Plasmodium ovale curtisi</italic> and <italic>Plasmodium ovale wallikeri</italic> to 14 other taxa, on the basis of <italic>cytb</italic> sequence data. Bootstrap values calculated from 1000 pseudorandom data sets are given where >85%; the position of the root derived for molecular clock fitting is shown (<italic>black arrow</italic>). Alternative trees derived from maximum likelihood and parsimony methods, together with alternative root positions, were tested for goodness of fit by maximum likelihood (CODEML program) [<xref rid="R19" ref-type="bibr">19</xref>]. With the topology shown, a strict molecular clock was not rejected (<italic>P</italic> = .48). Calibration of the molecular clock using a divergence time between <italic>Plasmodium reichenowi</italic> and <italic>Plasmodium falciparum</italic> of 5 million years ago (MYA) gave an estimated divergence between <italic>P. ovale curtisi</italic> and <italic>P. ovale wallikeri</italic> of 2.1 MYA (95% confidence interval, 1.0–3.5 MYA). A similar estimate (2.2 MYA [95% highest posterior density interval, 0.9–3.6 MYA]) for the divergence of the 2 <italic>P. ovale</italic> forms was obtained in independent strictclock analyses, using BEAST software [<xref rid="R20" ref-type="bibr">20</xref>]. In these analyses, additional Plasmodium vivax and chimpanzee parasite sequences (CPZcam89 and CPZcam91) [<xref rid="R21" ref-type="bibr">21</xref>] were included. A general time-reversible model with invariant sites and γ correction was selected using Modeltest [<xref rid="R22" ref-type="bibr">22</xref>], and 3 tree nodes were calibrated assuming a normal distribution and that Asian primate parasites and African simian parasites (represented by Plasmodium gonderi) diverged 8.0 (±1.0) MYA; that parasites of <italic>Pan</italic> and <italic>Homo species</italic> (represented by <italic>P. reichenowi</italic> and <italic>P. falciparum</italic>) diverged 4.1 (±0.4) MYA; and that <italic>P. vivax</italic> strains diverged from each other 0.25 (±0.05) MYA. To investigate potential site saturation in the third position, LogDet values [<xref rid="R24" ref-type="bibr">24</xref>] were calculated. None were found to be undefined. Those distances with larger values concerned the paths between <italic>P. falciparum</italic>, <italic>P. reichenowi</italic>, and the rodent <italic>Plasmodium</italic> sequences. These paths were not associated with the node calibrations used.</p>
</caption>
<graphic mimetype="image" xlink:href="201-10-1544-fig002.tif"></graphic>
</fig>
<fig position="float" id="fig3">
<label>Table 1</label>
<caption>
<p>Primer Sequences Used for Amplification of Each <italic>Plasmodium ovale</italic> Locus</p>
</caption>
<graphic mimetype="image" xlink:href="201-10-1544-fig003.tif"></graphic>
</fig>
<fig position="float" id="fig4">
<label>Table 2</label>
<caption>
<p>GenBank Accession Numbers for All DNA Sequences Determined in the Present Study</p>
</caption>
<graphic mimetype="image" xlink:href="201-10-1544-fig004.tif"></graphic>
</fig>
<fig position="float" id="fig5">
<label>Table 3</label>
<caption>
<p>Segregation of 5 Dimorphic Characters among 31 UKMRL <italic>Plasmodium ovale</italic> Isolates and of 3 Dimorphic Characters among 20 MUB <italic>P. ovale</italic> Isolates</p>
</caption>
<graphic mimetype="image" xlink:href="201-10-1544-fig005.tif"></graphic>
</fig>
<fig position="float" id="fig6">
<label>Table 4</label>
<caption>
<p>Genotype Summary for All <italic>Plasmodium ovale</italic> Isolates Evaluated in the Present Study</p>
</caption>
<graphic mimetype="image" xlink:href="201-10-1544-fig006.tif"></graphic>
</fig>
</sec>
<fn-group>
<fn fn-type="conflict"><p>Potential conflicts of interest: none reported.</p></fn>
<fn fn-type="presented-at"><p>Presented in part: British Society for Parasitology Malaria Meeting, Edinburgh, Scotland, 6–8 April 2009.</p></fn>
<fn fn-type="financial-disclosure"><p>Financial support: This work was supported by the United Kingdom Health Protection Agency and was part of the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme, which is supported by the Wellcome Trust of Great Britain. P.L.C. is supported by the University College London Hospitals Comprehensive Biomedical Research Centre Infection Theme. N.T. and M.I. are supported by the Thailand Research Fund and the Commission on Higher Education. G.S. is supported by Centre National de la Recherche Scientifique and Institut National de la Santé et de la Recherche Médicale, France.</p></fn>
</fn-group>
</back>
</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Two Nonrecombining Sympatric Forms of the Human Malaria Parasite Plasmodium ovale Occur Globally</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Colin J.</namePart><namePart type="family">Sutherland</namePart><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><affiliation>Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><affiliation>Hospital for Tropical Diseases, London</affiliation><affiliation>E-mail: colin.sutherland@lshtm.ac.uk</affiliation><affiliation>Reprints or correspondence: Colin Sutherland, Immunology Unit, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom</affiliation><affiliation>E-mail: colin.sutherland@lshtm.ac.uk</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Naowarat</namePart><namePart type="family">Tanomsing</namePart><affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Debbie</namePart><namePart type="family">Nolder</namePart><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mary</namePart><namePart 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type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Francois</namePart><namePart type="family">Nosten</namePart><affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</affiliation><affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</affiliation><affiliation>Shoklo Malaria Research Unit, Mae Sot, Thailand</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martina</namePart><namePart type="family">Burke</namePart><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rogan</namePart><namePart type="family">Lee</namePart><affiliation>Westmead Hospital, Sydney, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marie</namePart><namePart type="family">Blaze</namePart><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas Dan</namePart><namePart type="family">Otto</namePart><affiliation>Sanger Genome Centre, Hinxton, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John W.</namePart><namePart type="family">Barnwell</namePart><affiliation>Centers for Disease Control and Prevention, Atlanta, Georgia, United States</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Arnab</namePart><namePart type="family">Pain</namePart><affiliation>Sanger Genome Centre, Hinxton, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Williams</namePart><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicholas J.</namePart><namePart type="family">White</namePart><affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</affiliation><affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicholas P. J.</namePart><namePart type="family">Day</namePart><affiliation>Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford</affiliation><affiliation>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Georges</namePart><namePart type="family">Snounou</namePart><affiliation>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S945</affiliation><affiliation>Université Pierre and Marie Curie, Faculté de Médecine Pitié-Salpêtrière, Paris, France</affiliation><affiliation>Department of Microbiology, National University of Singapore, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter J.</namePart><namePart type="family">Lockhart</namePart><affiliation>Alan Wilson Centre, Massey University, Palmerston North, New Zealand</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter L.</namePart><namePart type="family">Chiodini</namePart><affiliation>Health Protection Agency Malaria Reference Laboratory, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</affiliation><affiliation>Hospital for Tropical Diseases, London</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mallika</namePart><namePart type="family">Imwong</namePart><affiliation>Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Spencer D.</namePart><namePart type="family">Polley</namePart><affiliation>Hospital for Tropical Diseases, London</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>The University of Chicago Press</publisher><dateIssued encoding="w3cdtf">2010-05-15</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><abstract>Background. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. Methods. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. Results. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. Conclusions. We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.</abstract><relatedItem type="host"><titleInfo><title>The Journal of Infectious Diseases</title></titleInfo><titleInfo type="abbreviated"><title>The Journal of Infectious Diseases</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0022-1899</identifier><identifier type="eISSN">1537-6613</identifier><identifier type="PublisherID">jid</identifier><identifier type="PublisherID-hwp">jinfdis</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>201</number></detail><detail type="issue"><caption>no.</caption><number>10</number></detail><extent unit="pages"><start>1544</start><end>1550</end></extent></part></relatedItem><identifier type="istex">934AE9AC3FE9987720CDD21CD1D7141C54A6538D</identifier><identifier type="DOI">10.1086/652240</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010 by the Infectious Diseases Society of America</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</recordContentSource><recordOrigin>© 2010 by the Infectious Diseases Society of America</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/metadata/json</uri></json:item></metadata><covers><json:item><extension>tiff</extension><original>true</original><mimetype>image/tiff</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/covers/tiff</uri></json:item><json:item><extension>html</extension><original>true</original><mimetype>text/html</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/covers/html</uri></json:item></covers><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/934AE9AC3FE9987720CDD21CD1D7141C54A6538D/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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