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Programme","doi-asserted-by":"publisher","award":["602843"],"award-info":[{"award-number":["602843"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"European Union Seventh Framework Programme","doi-asserted-by":"publisher","award":["602843"],"award-info":[{"award-number":["602843"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how P. falciparum infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of twenty healthy Africans with lifelong exposure to malaria and five malaria-na\u00efve Europeans, who were all challenged with direct venous inoculation of live P. falciparum sporozo\u00eftes (PfSPZ) and followed up until they developed symptoms or became thick blood smear positive (TBS). Urine samples were collected before and at 2, 5, 9 and 11 days post challenge and were analysed. Upon infection, all Europeans became TBS positive, while Africans showed either a delay in time to parasitaemia or controlled infection. Our metabolic data showed that Europeans and Africans had distinct alterations in metabolite patterns, with changes mostly seen on days 5 and 9 post PfSPZ infection, and more prominently in Europeans. Within the African group, the levels of formate, urea, trimethylamine, threonine, choline, myo-inositol and acetate were significantly higher in TBS positive whereas the levels of pyruvate, 3-methylhistidine and dimethylglycine were significantly lower in individuals who remained TBS negative. Notably, before inoculation with PfSPZ, a group of metabolites including phenylacetylglutamine can potentially be used to predict parasitaemia control among Africans. Taken together, this study highlights the difference in urinary metabolic changes in response to malaria infection as a consequence of lifelong exposure to malaria and that change detectable before challenge might predict the control of parasitaemia in malaria-endemic areas.<\/jats:p>","DOI":"10.3390\/metabo12121224","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T01:47:46Z","timestamp":1670377666000},"page":"1224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4206-1333","authenticated-orcid":false,"given":"Madeleine Eunice","family":"Betouke Ongwe","sequence":"first","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9 P.O. Box 242, Gabon"},{"name":"Institut de Recherches en \u00c9cologie Tropicale, Centre National de la Recherche Scientifique et Technologique (CENAREST), Libreville P.O. Box 13354, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3629-1597","authenticated-orcid":false,"given":"Isabelle","family":"Kohler","sequence":"additional","affiliation":[{"name":"Division of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Center for Analytical Sciences Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhael D.","family":"Manurung","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0373-9372","authenticated-orcid":false,"given":"Aswin","family":"Verhoeven","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rico","family":"Derks","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-5881","authenticated-orcid":false,"given":"Jacqueline J.","family":"Janse","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5827-419X","authenticated-orcid":false,"given":"Yoanne D.","family":"Mouwenda","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9 P.O. Box 242, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Kremsner","sequence":"additional","affiliation":[{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9 P.O. Box 242, Gabon"},{"name":"Institut f\u00fcr Tropenmedizin, Eberhard-Karls-Universit\u00e4t T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-5946","authenticated-orcid":false,"given":"Ayola A.","family":"Adegnika","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9 P.O. Box 242, Gabon"},{"name":"Institut f\u00fcr Tropenmedizin, Eberhard-Karls-Universit\u00e4t T\u00fcbingen, 72074 T\u00fcbingen, Germany"},{"name":"German Center for Infection Research (DZIF), 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1427-3002","authenticated-orcid":false,"given":"Bertrand","family":"Lell","sequence":"additional","affiliation":[{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9 P.O. 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