{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T19:13:18Z","timestamp":1771960398926,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013342","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000}}],"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, India","award":["BT\/PR7520\/BRB\/10\/481\/2006"],"award-info":[{"award-number":["BT\/PR7520\/BRB\/10\/481\/2006"]}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["PID:2021-12909"],"award-info":[{"award-number":["PID:2021-12909"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    <jats:italic>vir<\/jats:italic>\n                    genes, a multigene family in\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    that are a part of a larger superfamily of genes called the\n                    <jats:italic>pir<\/jats:italic>\n                    (\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    interspersed repeat) genes, have been reported earlier to be potentially involved in cyto-adherence and evasion of splenic clearance.\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    , historically characterised as a \u201cbenign\u201d malaria parasite, has been associated with clinical outcomes including hepatic dysfunction, renal failure, and cerebral malaria in India and several global regions. It constitutes an economic burden and presents a public health challenge alongside other\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    species. Here, we present a part of global transcriptomic studies using custom-designed microarrays that compare the transcriptome of the parasite responsible for severe\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    manifestations, specifically hepatic dysfunction and cerebral malaria from India, with an emphasis on the\n                    <jats:italic>pir<\/jats:italic>\n                    genes, some of which are reported to play a role in cyto-adherence. The RNA of the parasite isolated from 23 patients (uncomplicated group\u2009=\u20096, hepatic dysfunction group\u2009=\u200912, and cerebral malaria group\u2009=\u20095) was subjected to microarray hybridisation, and the data obtained showed a wide range of\n                    <jats:italic>pir<\/jats:italic>\n                    subfamilies to have been differentially expressed. We report the upregulation of 24\n                    <jats:italic>pir<\/jats:italic>\n                    genes in the cerebral malaria group (n\u2009=\u20095) and 28\n                    <jats:italic>pir<\/jats:italic>\n                    genes in the hepatic dysfunction group (n\u2009=\u200912), which belong to different subfamilies in at least 50% of the severe malaria patients\u2019 group. Out of the upregulated\n                    <jats:italic>pir<\/jats:italic>\n                    genes in the cerebral malaria group, members of\n                    <jats:italic>vir<\/jats:italic>\n                    subfamily E (n\u2009=\u20098 genes) and the\n                    <jats:italic>pvpir<\/jats:italic>\n                    subfamily H (n\u2009=\u20096 genes) are expressed in a higher proportion compared to the hepatic dysfunction group, where members of\n                    <jats:italic>vir<\/jats:italic>\n                    subfamily E (n\u2009=\u20099) and C (n\u2009=\u20096) are expressed in a major proportion.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0013342","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T18:41:02Z","timestamp":1771440062000},"page":"e0013342","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative clinical transcriptome of pir genes in severe Plasmodium vivax malaria"],"prefix":"10.1371","volume":"20","author":[{"given":"Pon Arunachalam","family":"Boopathi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saurabh","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sampreeti","family":"Tahbildar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay Kumar","family":"Kochar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhanpat Kumar","family":"Kochar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-1827","authenticated-orcid":true,"given":"Ashis","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"pntd.0013342.ref001","volume-title":"World malaria report 2025: Addressing the threat of antimalarial drug resistance"},{"issue":"3","key":"pntd.0013342.ref002","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/pathogens12030373","article-title":"Analysis of fifty years of severe malaria worldwide research","volume":"12","author":"JA Garrido-Cardenas","year":"2023","journal-title":"Pathogens Basel Switz"},{"issue":"10483","key":"pntd.0013342.ref003","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S0140-6736(25)00038-8","article-title":"Mapping the global 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[cited 2026 Jan 14]. 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