{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T08:38:21Z","timestamp":1759826301477,"version":"3.37.3"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Haem detoxification protein (HDP) is a significant protein in the erythrocytic stage of the Plasmodium lifecycle. HDP could be of paramount interest as a diagnostic biomarker for accurate diagnosis of malaria. We thus explored HDP genetic variation, expression levels of HDP and immune response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Phylogenetic analysis was carried out using Pfhdp orthologues sequences of various Plasmodium species. Blood samples were collected from patients in central India. Pfhdp gene was amplified, and sequenced by sanger DNA sequencing. B-cell epitopes were identified in PfHDP using Bepipred Linear Epitope Prediction 2.0, and median-joining network was constructed using global PfHDP sequences. Pfhdp expression levels during erythrocytic stage were assessed using real-time qPCR at 4-h intervals. An IgG immune response against synthetic PfHDP peptides was analysed using ELISA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Phylogenetic analysis revealed the conserved nature of Pfhdp gene. Diversity analysis revealed one non-synonymous mutation (F91L) among all isolates. Neutrality tests indicated negative selection for Pfhdp gene. HDP was expressed throughout the erythrocytic cycle, and comparatively, high expression was observed in the late trophozoite and schizont stages. High IgG response against both peptides was observed, and no polymorphism was seen in any of the seven predicted B-cell epitopes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Findings of the present study indicate the possibility of HDP being exploited as a diagnostic biomarker for Plasmodium falciparum malaria after proteomic validation studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/trstmh\/trac055","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T17:21:28Z","timestamp":1655745688000},"page":"1162-1171","source":"Crossref","is-referenced-by-count":5,"title":["Limited genetic diversity and expression profile of <i>Plasmodium falciparum<\/i> haem detoxification protein: a possible diagnostic target"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-8296","authenticated-orcid":false,"given":"Shrikant","family":"Nema","sequence":"first","affiliation":[{"name":"Division of Vector-Borne Diseases, ICMR-National Institute of Research in Tribal Health , Jabalpur 482 003, Madhya Pradesh, India"},{"name":"School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya (State Technological University of Madhya Pradesh) , Bhopal, 462 023, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sri","family":"Krishna","sequence":"additional","affiliation":[{"name":"Division of Vector-Borne Diseases, ICMR-National Institute of Research in Tribal Health , Jabalpur 482 003, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Archana","family":"Tiwari","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya (State Technological University of Madhya Pradesh) , Bhopal, 462 023, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-6673","authenticated-orcid":false,"given":"Praveen Kumar","family":"Bharti","sequence":"additional","affiliation":[{"name":"Division of Vector-Borne Diseases, ICMR-National Institute of Research in Tribal Health , Jabalpur 482 003, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"year":"2021","key":"2022120214251863700_bib1"},{"issue":"7","key":"2022120214251863700_bib2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s13312-020-1888-5","article-title":"Malaria elimination in India: bridging the gap between control and elimination","volume":"57","author":"Nema","year":"2020","journal-title":"Indian Pediatr"},{"issue":"1","key":"2022120214251863700_bib3","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1038\/s41598-020-62850-x","article-title":"Glutamate dehydrogenase: a novel candidate to diagnose Plasmodium falciparum through rapid diagnostic test in blood specimen from fever patients","volume":"10","author":"Kori","year":"2020","journal-title":"Sci Rep"},{"issue":"4","key":"2022120214251863700_bib4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00430-012-0272-z","article-title":"Malaria and human red blood cells","volume":"201","author":"Mohandas","year":"2012","journal-title":"Med Microbiol Immunol"},{"issue":"14","key":"2022120214251863700_bib5","doi-asserted-by":"crossref","first-page":"5392","DOI":"10.1073\/pnas.1218412110","article-title":"Protein complex directs hemoglobin-to-hemozoin formation in plasmodium falciparum","volume":"110","author":"Chugh","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2022120214251863700_bib6","doi-asserted-by":"crossref","first-page":"e1000053","DOI":"10.1371\/journal.ppat.1000053","article-title":"HDP\u2014A novel haem detoxification protein from the malaria parasite","volume":"4","author":"Jani","year":"2008","journal-title":"PLOS Pathog"},{"key":"2022120214251863700_bib7","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.meegid.2008.12.004","article-title":"Limited genetic variation in the Plasmodium falciparum haem detoxification protein (HDP)","volume":"9","author":"Vinayak","year":"2009","journal-title":"Infect Genet Evol"},{"issue":"1","key":"2022120214251863700_bib8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-16974-2","article-title":"Prevalence of malaria in two highly endemic community health centers in the Bastar district, Chhattisgarh showing mixed infections with Plasmodium species","volume":"7","author":"Krishna","year":"2017","journal-title":"Sci Rep"},{"author":"Malaria Situation in India","key":"2022120214251863700_bib9","article-title":"National vector borne disease control programme (NVBDCP)"},{"key":"2022120214251863700_bib10","first-page":"102","article-title":"Rapid staining of malarial parasites by a water soluble stain","volume":"79","author":"Singh","year":"1944","journal-title":"Indian Med Gaz"},{"key":"2022120214251863700_bib11","doi-asserted-by":"crossref","first-page":"D539","DOI":"10.1093\/nar\/gkn814","article-title":"PlasmoDB: a functional genomic database for malaria parasites","volume":"37","author":"Aurrecoechea","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2022120214251863700_bib12","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol Biol Evol"},{"issue":"2","key":"2022120214251863700_bib13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0166-6851(93)90050-8","article-title":"Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections","volume":"58","author":"Snounou","year":"1993","journal-title":"Mol Biochem Parasitol"},{"key":"2022120214251863700_bib14","first-page":"95","article-title":"BioEdit: a user friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT","volume":"41","author":"Hall","year":"1999","journal-title":"Nucleic Acids Symp Ser"},{"author":"Nicholas","key":"2022120214251863700_bib15","article-title":"Genedoc: a tool for editing and annoting multiple sequence alignments\u2014scienceopen"},{"issue":"9","key":"2022120214251863700_bib16","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1111\/2041-210X.12410","article-title":"popart: full-feature software for haplotype network construction","volume":"6","author":"Leigh","year":"2015","journal-title":"Methods Ecol Evol"},{"issue":"1","key":"2022120214251863700_bib17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/oxfordjournals.molbev.a026036","article-title":"Median-joining networks for inferring intraspecific phylogenies","volume":"16","author":"Bandelt","year":"1999","journal-title":"Mol Biol Evol"},{"issue":"7","key":"2022120214251863700_bib18","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol Biol Evol"},{"issue":"2","key":"2022120214251863700_bib19","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/genetics\/135.2.599","article-title":"Simple methods for testing the molecular evolutionary clock hypothesis","volume":"135","author":"Tajima","year":"1993","journal-title":"Genetics"},{"issue":"3","key":"2022120214251863700_bib20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/genetics\/133.3.693","article-title":"Statistical tests of neutrality of mutations","volume":"133","author":"Fu","year":"1993","journal-title":"Genetics"},{"issue":"12","key":"2022120214251863700_bib21","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1093\/molbev\/msx248","article-title":"DnaSP 6: DNA sequence polymorphism analysis of large data sets","volume":"34","author":"Rozas","year":"2017","journal-title":"Mol Biol Evol"},{"issue":"1","key":"2022120214251863700_bib22","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/1475-2875-12-386","article-title":"An alternative protocol for Plasmodium falciparum culture synchronization and a new method for synchrony confirmation","volume":"12","author":"Childs","year":"2013","journal-title":"Malar J"},{"issue":"1","key":"2022120214251863700_bib23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1365-2958.2003.03570.x","article-title":"Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering plasmodium falciparum involved in pregnancy-associated malaria","volume":"49","author":"Salanti","year":"2003","journal-title":"Mol Microbiol"},{"issue":"1","key":"2022120214251863700_bib24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1745-7580-2-2","article-title":"Improved method for predicting linear B-cell epitopes","volume":"2","author":"Larsen","year":"2006","journal-title":"Immunome Res"},{"issue":"1","key":"2022120214251863700_bib25","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1186\/1471-2105-7-336","article-title":"ProtRepeatsDB: a database of amino acid repeats in genomes","volume":"7","author":"Kalita","year":"2006","journal-title":"BMC Bioinformatics"},{"issue":"8","key":"2022120214251863700_bib26","doi-asserted-by":"crossref","first-page":"e0182674","DOI":"10.1371\/journal.pone.0182674","article-title":"Genetic diversity and antibody responses against Plasmodium falciparum vaccine candidate genes from Chhattisgarh, central India: implication for vaccine development","volume":"12","author":"Patel","year":"2017","journal-title":"PloS One"},{"issue":"8","key":"2022120214251863700_bib27","doi-asserted-by":"crossref","first-page":"e0157949","DOI":"10.1371\/journal.pone.0157949","article-title":"Prevalence of pfhrp2 and\/or pfhrp3 gene deletion in Plasmodium falciparum population in eight highly endemic states in India","volume":"11","author":"Bharti","year":"2016","journal-title":"Plos One"},{"issue":"12","key":"2022120214251863700_bib28","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S1473-3099(19)30544-4","article-title":"Strengthening diagnosis is key to eliminating malaria in India","volume":"19","author":"Nema","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2022120214251863700_bib29","first-page":"trac007","article-title":"Unreported mixed Plasmodium species infection may increase vivax malaria in India: a challenge for malaria elimination","author":"Nema","year":"2022","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"12","key":"2022120214251863700_bib30","doi-asserted-by":"crossref","first-page":"e115266","DOI":"10.1371\/journal.pone.0115266","article-title":"Burden of complicated malaria in a densely forested Bastar region of Chhattisgarh state (Central India)","volume":"9","author":"Jain","year":"2014","journal-title":"PloS One"},{"issue":"5","key":"2022120214251863700_bib31","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/trstmh\/trv015","article-title":"Sympatric distribution of Plasmodium ovale curtisi and P. ovale wallikeri in India: implication for the diagnosis of malaria and its control","volume":"109","author":"Chaturvedi","year":"2015","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"11","key":"2022120214251863700_bib32","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1111\/tmi.12184","article-title":"First report of detection and molecular confirmation of Plasmodium ovale from severe malaria cases in central India","volume":"18","author":"Singh","year":"2013","journal-title":"Trop Med Int Health"},{"key":"2022120214251863700_bib33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3389\/fgene.2017.00139","article-title":"The empirical distribution of singletons for geographic samples of DNA sequences","volume":"8","author":"Cubry","year":"2017","journal-title":"Front Genet"},{"issue":"1","key":"2022120214251863700_bib34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1672-0229(07)60009-6","article-title":"A brief review of short tandem repeat mutation","volume":"5","author":"Fan","year":"2007","journal-title":"Gen Prot Bioinform"},{"issue":"6","key":"2022120214251863700_bib35","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/femsre\/fux046","article-title":"Repetitive sequences in malaria parasite proteins","volume":"41","author":"Davies","year":"2017","journal-title":"FEMS Microbiol Rev"},{"issue":"12","key":"2022120214251863700_bib36","doi-asserted-by":"crossref","first-page":"6725","DOI":"10.1073\/pnas.111144998","article-title":"Evidence for clonal propagation in natural isolates of Plasmodium falciparum from Venezuela","volume":"98","author":"Urdaneta","year":"2001","journal-title":"Proc Natl Acad Sci"},{"key":"2022120214251863700_bib37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cophys.2018.03.010","article-title":"The evolution of greater humoral immunity in females than males: implications for vaccine efficacy","volume":"6","author":"Fink","year":"2018","journal-title":"Curr Opin Physiol"},{"key":"2022120214251863700_bib38","first-page":"1","article-title":"Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases","volume":"5","author":"Lu","year":"2015","journal-title":"Sci Rep"},{"key":"2022120214251863700_bib39","doi-asserted-by":"crossref","first-page":"6760830","DOI":"10.1155\/2016\/6760830","article-title":"An introduction to B-Cell epitope mapping and in silico epitope prediction","volume":"2016","author":"Potocnakova","year":"2016","journal-title":"J Immunol Res"},{"key":"2022120214251863700_bib40","doi-asserted-by":"crossref","first-page":"643501","DOI":"10.3389\/fmicb.2021.643501","article-title":"Application of 23 novel serological markers for identifying recent exposure to Plasmodium vivax parasites in an endemic population of western Thailand","volume":"12","author":"Chotirat","year":"2021","journal-title":"Front Microbiol"},{"issue":"1","key":"2022120214251863700_bib41","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4161\/mabs.4.1.18529","article-title":"New developments in malaria diagnostics","volume":"4","author":"Kattenberg","year":"2012","journal-title":"mAbs"},{"key":"2022120214251863700_bib42","doi-asserted-by":"crossref","first-page":"852645","DOI":"10.1155\/2014\/852645","article-title":"Potential biomarkers and their applications for rapid and reliable detection of malaria","volume":"2014","author":"Jain","year":"2014","journal-title":"BioMed Res Int"},{"key":"2022120214251863700_bib43","first-page":"747","article-title":"Hemoglobin degradation in malaria-infected erythrocytes determined from live cell magnetophoresis","volume":"20","author":"Moore","year":"2006","journal-title":"Fed Am Soc Exp Biol"},{"issue":"2","key":"2022120214251863700_bib44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-019-1342-6","article-title":"Haem detoxification by haem oxygenase-1 reinstates proliferative and immune balances upon genotoxic tissue injury","volume":"10","author":"Hedblom","year":"2019","journal-title":"Cell Death Dis"},{"issue":"1","key":"2022120214251863700_bib45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gene.2015.04.037","article-title":"Cloning, expression and functional characterization of haem detoxification protein (HDP) from the rodent malaria parasite Plasmodium vinckei","volume":"566","author":"Soni","year":"2015","journal-title":"Gene"},{"issue":"6906","key":"2022120214251863700_bib46","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nature01107","article-title":"A proteomic view of the Plasmodium falciparum life cycle","volume":"419","author":"Florens","year":"2002","journal-title":"Nature"},{"issue":"6906","key":"2022120214251863700_bib47","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence of the human malaria parasite Plasmodium falciparum","volume":"419","author":"Gardner","year":"2002","journal-title":"Nature"}],"container-title":["Transactions of The Royal Society of Tropical Medicine and Hygiene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/trstmh\/article-pdf\/116\/12\/1162\/47535503\/trac055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/trstmh\/article-pdf\/116\/12\/1162\/47535503\/trac055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T15:08:56Z","timestamp":1669993736000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/trstmh\/article\/116\/12\/1162\/6611854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,20]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6,20]]},"published-print":{"date-parts":[[2022,12,2]]}},"URL":"https:\/\/doi.org\/10.1093\/trstmh\/trac055","relation":{},"ISSN":["0035-9203","1878-3503"],"issn-type":[{"type":"print","value":"0035-9203"},{"type":"electronic","value":"1878-3503"}],"subject":[],"published-other":{"date-parts":[[2022,12]]},"published":{"date-parts":[[2022,6,20]]}}}