{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:07:56Z","timestamp":1789063676712,"version":"build-2803163510"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n \n HLA-G (Human Leukocyte Antigen-G) is a non-classical molecule belonging to the major histocompatibility complex (MHC) class I family, located on chromosome 6 within the MHC region, which is pivotal in promoting immune tolerance. The immune-suppressive ability of Human Leukocyte Antigen (HLA-G) and its binding to fetal maternal interface predispose pregnant women to\n Plasmodium falciparum<\/jats:italic>\n (\n Pf<\/jats:italic>\n ) infection and pregnancy loss, respectively. Alterations in hematological parameters may accelerate the severity of malaria infection. Limited data is available about the effects of malaria infection on hepatocytes and how this endangers the lives of the mother and the fetus due to liver injury. Thus, this study evaluated HLA-G and Hematobiochemical levels and their association with malaria infection and miscarriage among pregnant women in the Ghanaian population.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n This case-control study recruited forty-six (46)\n Pf<\/jats:italic>\n -infected pregnant women and forty-six (46)\n Pf<\/jats:italic>\n -uninfected pregnant women from the Bibiani Anhwiaso Bekwai Municipality, Ghana. A well-structured questionnaire was administered to obtain sociodemographic and clinical data from 21\n st<\/jats:sup>\n December 2022\u201320\n th<\/jats:sup>\n December 2023. 10 ml venous blood samples were collected from each participant for\n Pf<\/jats:italic>\n parasite testing using the\n Pf<\/jats:italic>\n HRP2 RDT test kit (CareStart TM Malaria PfHRP2\/pLDH Ag RDT, Access Bio, Inc., USA), and the results were confirmed with microscopy. Hematobiochemical profile analyses were done using the Sysmex automated hematology and chemistry analyser. Plasma HLA-G levels were quantified using a sandwich ELISA (Maxisop ELISA plate), and their corresponding concentrations were determined.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The results shows a significant difference in the use of IPT-SP and\n Pf<\/jats:italic>\n infection, with 31(67.4%) for\n Pf<\/jats:italic>\n positive vs 18(39.1%) for\n Pf<\/jats:italic>\n negative among those who were not on IPT-SP and 15(32.6%) for\n Pf<\/jats:italic>\n positive vs 28(60.9%) for\n Pf<\/jats:italic>\n negative for those who were on IPT-SP (p\u2009=\u20090.007)., Multivariate regression crude analysis shows increased ALT levels among the malaria-infected pregnant women [\u03b2\u2009=\u20097.091(95% CI\u2009=\u20091.563\u201332.182) p\u2009=\u20090.011] compared to the negative group. This finding was insignificant after adjusting for age, IPT-SP use and Trimester. ALP, on the other hand, shows significantly increased levels among the malaria-infected pregnant women compared to the malaria-negative pregnant women for both crude [\u03b2\u2009=\u200913.301(95% CI\u2009=\u20091.577\u2013112.208) p\u2009=\u20090.017] and adjusted [\u03b2\u2009=\u200917.524(95% CI\u2009=\u20091.534\u2013200.20), p\u2009=\u20090.02] analysis. In a comparative analysis, we found that GLR (G) and PLR (H) levels were significantly higher in participants with\n Pf<\/jats:italic>\n infections compared to participants without\n Pf<\/jats:italic>\n infection (\n p<\/jats:italic>\n \u2009<\u20090.05). We also found that women with a history of miscarriage had considerably higher sHLA-G levels [50.14 (36.30\u201371.00) vs. 35.44(31.84\u201342.72)] than women with no history of miscarriage.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Pf<\/jats:italic>\n infection in pregnant Ghanaian women was associated with elevated ALP, GLR, and PLR, indicating hepatic dysfunction and systemic inflammation. The non-use of IPTp-SP among pregnant women was significantly associated with active\n Pf<\/jats:italic>\n infection, highlighting the importance of chemoprophylaxis. Increased sHLA-G levels in women with miscarriage suggest an immunological link to pregnancy loss. Further prospective investigation of sHLA-G as a biomarker of adverse pregnancy outcome in malaria-endemic settings with a larger sample size is required.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0355847","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:29:18Z","timestamp":1789061358000},"page":"e0355847","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of HLA-G and Hematobiochemical levels and their association with malaria and miscarriage among pregnant women: A Ghanaian case-control study"],"prefix":"10.1371","volume":"21","author":[{"given":"Richmond","family":"Kwakye","sequence":"first","affiliation":[{"name":"KAAF University","place":["Gomoa Fetteh, Ghana"],"department":["Department of medical laboratory sciences, Faculty of health and Allied sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Courtin","sequence":"additional","affiliation":[{"name":"UMR 261 MERIT, Universit\u00e9 de Paris, Institut de Recherche pour le D\u00e9veloppement (IRD)","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Asamoah","family":"Sakyi","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Kwame Nkrumah University of Science and Technology","place":["Kumasi, Ghana"],"department":["Department of Molecular Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faustina","family":"Pappoe","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of Cape Coast","place":["Cape Coast, Ghana"],"department":["Department of Microbiology and Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon Kwesi","family":"Nakotey","sequence":"additional","affiliation":[{"name":"Central College of Science and Technology","place":["Agona Swedru, Ghana"],"department":["Department of Medical Laboratory Technology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7236-6533","authenticated-orcid":true,"given":"Naa Adjeley","family":"Frempong","sequence":"additional","affiliation":[{"name":"University of Ghana","place":["Accra, Ghana"],"department":["Department of Parasitology, Noguchi Memorial Institute for Medical Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prince Amoah","family":"Barnie","sequence":"additional","affiliation":[{"name":"College of Agriculture and Natural Sciences, University of Cape Coast","place":["Cape Coast, Ghana"],"department":["Department of Forensic Science, School of Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-3033","authenticated-orcid":true,"given":"Benjamin","family":"Amoani","sequence":"additional","affiliation":[{"name":"Central College of Science and Technology","place":["Agona Swedru, Ghana"],"department":["Department of Medical Laboratory Technology"]},{"name":"School of Allied Health Sciences, University of Cape Coast","place":["Cape Coast, Ghana"],"department":["Department of Biomedical Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"pone.0355847.ref001","volume-title":"World malaria report","author":"WHO","year":"2023"},{"issue":"2","key":"pone.0355847.ref002","first-page":"39","article-title":"Impact of placental Plasmodium falciparum malaria on pregnancy and perinatal outcome in sub-Saharan Africa: I: introduction to placental malaria","volume":"80","author":"CJ Uneke","year":"2007","journal-title":"Yale J Biol Med"},{"issue":"6","key":"pone.0355847.ref003","first-page":"69","article-title":"Maternal malaria: implications for fetal health","volume":"2","author":"E Obeagu","year":"2024","journal-title":"Elite Journal of Nursing and Health Science"},{"issue":"1","key":"pone.0355847.ref004","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1186\/s12936-017-2040-4","article-title":"Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes","volume":"16","author":"J Kapisi","year":"2017","journal-title":"Malar J"},{"issue":"8","key":"pone.0355847.ref005","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s00018-022-04491-z","article-title":"Evolution and molecular interactions of major histocompatibility complex (MHC)-G, -E and -F genes","volume":"79","author":"A Arnaiz-Villena","year":"2022","journal-title":"Cell Mol Life Sci"},{"issue":"4","key":"pone.0355847.ref006","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.it.2017.01.009","article-title":"HLA-G: At the Interface of Maternal-Fetal Tolerance","volume":"38","author":"LMR Ferreira","year":"2017","journal-title":"Trends Immunol"},{"key":"pone.0355847.ref007","doi-asserted-by":"crossref","first-page":"298569","DOI":"10.1155\/2014\/298569","article-title":"Immunomodulatory properties of HLA-G in infectious diseases","volume":"2014","author":"L Amiot","year":"2014","journal-title":"J Immunol Res"},{"issue":"3","key":"pone.0355847.ref008","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.3390\/ijms24032557","article-title":"HLA-G and Recurrent Pregnancy Loss","volume":"24","author":"G Barbaro","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"9","key":"pone.0355847.ref009","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.17219\/acem\/69692","article-title":"Fetal HLA-G alleles and their effect on miscarriage","volume":"27","author":"A Koc","year":"2018","journal-title":"Adv Clin Exp Med"},{"key":"pone.0355847.ref010","doi-asserted-by":"crossref","first-page":"001","DOI":"10.17352\/gjidcr.000021","article-title":"Effects of Malaria Infection on some Haematological and Biochemical Parameters in the General Population and Pregnant Malaria Patients Attending Two District Hospitals in Niger State, Nigeria","author":"J Adamu","year":"2019","journal-title":"Glob J Infect Dis Clin Res"},{"key":"pone.0355847.ref011","article-title":"Impact of Plasmodium falciparum infection on haematological parameters in children living in Western Kenya","author":"RN Maina","year":"2010","journal-title":"Malar J"},{"issue":"9","key":"pone.0355847.ref012","first-page":"1","article-title":"Assessment of some haematological parameters in malaria infected pregnant women in Imo state Nigeria","volume":"3","author":"H Okorie","year":"2018","journal-title":"Int J Curr Res Biol Med"},{"key":"pone.0355847.ref013","volume-title":"Liver function abnormalities and its prognostic significance in malaria","author":"G Anoosha","year":"2016"},{"issue":"5","key":"pone.0355847.ref014","doi-asserted-by":"crossref","first-page":"257","DOI":"10.9734\/AJEA\/2015\/16388","article-title":"Farmers\u2019 Perceptions of the Effectiveness of the Cocoa Disease and Pest Control Programme (CODAPEC) in Ghana and Its Effects on Poverty Reduction","volume":"7","author":"E Kumi","year":"2015","journal-title":"AJEA"},{"key":"pone.0355847.ref015","unstructured":"Service GS. Sefwi bibiani-anhwiaso- bekwai district 2022 [."},{"key":"pone.0355847.ref016","unstructured":"Ba EH, Baird JK, Barnwell J, Bell D, Carter J, Dhorda M, et al. Microscopy for the detection, identification and quantification of malaria parasites on stained thick and thin blood films in research settings: procedure: methods manual. 2015."},{"issue":"7","key":"pone.0355847.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0270685","article-title":"Common hematological parameters reference intervals for apparently healthy pregnant and non-pregnant women of South Wollo Zone, Amhara Regional State, Northeast Ethiopia","volume":"17","author":"M Fiseha","year":"2022","journal-title":"PLoS One"},{"key":"pone.0355847.ref018","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/1475-2875-13-312","article-title":"High plasma levels of HLA-G are associated with low birth weight and with an increased risk of malaria in infancy","volume":"13","author":"I Sadissou","year":"2014","journal-title":"Malar J"},{"issue":"4","key":"pone.0355847.ref019","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s12639-019-01142-2","article-title":"A comparative study assessing the effect of haematological and biochemical parameters on the pathogenesis of malaria","volume":"43","author":"S Das","year":"2019","journal-title":"J Parasit Dis"},{"issue":"10","key":"pone.0355847.ref020","article-title":"Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment","volume":"2014","author":"D Radeva-Petrova","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"pone.0355847.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009438","article-title":"Malaria prevention with IPTp during pregnancy reduces neonatal mortality","volume":"5","author":"C Men\u00e9ndez","year":"2010","journal-title":"PLoS One"},{"key":"pone.0355847.ref022","volume-title":"WHO guidelines for malaria","author":"WHO","year":"2022"},{"key":"pone.0355847.ref023","doi-asserted-by":"crossref","first-page":"20503121231199653","DOI":"10.1177\/20503121231199653","article-title":"Interventions for malaria prevention in pregnancy; factors influencing uptake and their effect on pregnancy outcomes among post-natal women in a tertiary facility in the Volta Region of Ghana","volume":"11","author":"GD Ampofo","year":"2023","journal-title":"SAGE Open Med"},{"issue":"5","key":"pone.0355847.ref024","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1473-3099(11)70339-5","article-title":"Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study","volume":"12","author":"R McGready","year":"2012","journal-title":"Lancet Infect Dis"},{"issue":"12","key":"pone.0355847.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0310339","article-title":"Effects on maternal and pregnancy outcomes of first-trimester malaria infection among nulliparous women from Kenya, Zambia, and the Democratic Republic of the Congo","volume":"19","author":"SI Leuba","year":"2024","journal-title":"PLoS One"},{"issue":"8","key":"pone.0355847.ref026","article-title":"Incidental Finding of Extreme Elevation of Serum Alkaline Phosphatase in Pregnancy","volume":"13","author":"B Ferro","year":"2021","journal-title":"Cureus"},{"issue":"7","key":"pone.0355847.ref027","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.pt.2025.05.010","article-title":"Malaria-associated liver dysfunction: a forgotten challenge","volume":"41","author":"F Prenen","year":"2025","journal-title":"Trends Parasitol"},{"key":"pone.0355847.ref028","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/RRTM.S351268","article-title":"Liver enzymes and lipid profile of malaria patients before and after antimalarial drug treatment at Dembia Primary Hospital and Teda Health Center, Northwest, Ethiopia","author":"F Megabiaw","year":"2022","journal-title":"Research and Reports in Tropical Medicine"},{"issue":"9","key":"pone.0355847.ref029","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3390\/jpm13091388","article-title":"Diagnostic Approach to Elevated Liver Function Tests during Pregnancy: A Pragmatic Narrative Review","volume":"13","author":"E Dajti","year":"2023","journal-title":"J Pers Med"},{"issue":"1","key":"pone.0355847.ref030","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12936-025-05474-8","article-title":"Variations in haematological and inflammatory biomarkers and their association with Plasmodium falciparum malaria: a cross-sectional comparative study at a clinic in Ghana","volume":"24","author":"JK Bohli","year":"2025","journal-title":"Malar J"},{"key":"pone.0355847.ref031","article-title":"Diagnostic value of full blood count derived systemic inflammatory biomarkers in malaria infection","volume":"46","author":"J Boachie","year":"2025","journal-title":"Pract Lab Med"},{"key":"pone.0355847.ref032","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1590\/S0074-02762011000900007","article-title":"Thrombocytopenia in malaria: who cares?","volume":"106","author":"MVG Lacerda","year":"2011","journal-title":"Mem\u00f3rias do Instituto Oswaldo Cruz"},{"issue":"1","key":"pone.0355847.ref033","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1186\/s12936-018-2569-x","article-title":"Correlation of malaria parasitaemia with peripheral blood monocyte to lymphocyte ratio as indicator of susceptibility to severe malaria in Ghanaian children","volume":"17","author":"S Antwi-Baffour","year":"2018","journal-title":"Malar J"},{"key":"pone.0355847.ref034","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/bs.ai.2015.04.001","article-title":"HLA-G: An Immune Checkpoint Molecule","volume":"127","author":"ED Carosella","year":"2015","journal-title":"Adv Immunol"},{"key":"pone.0355847.ref035","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/1475-2875-13-312","article-title":"High plasma levels of HLA-G are associated with low birth weight and with an increased risk of malaria in infancy","volume":"13","author":"I Sadissou","year":"2014","journal-title":"Malar J"},{"issue":"1","key":"pone.0355847.ref036","doi-asserted-by":"crossref","first-page":"9160","DOI":"10.1038\/s41598-019-45688-w","article-title":"High level of soluble human leukocyte antigen (HLA)-G at beginning of pregnancy as predictor of risk of malaria during infancy","volume":"9","author":"TC d\u2019Almeida","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0355847.ref037","doi-asserted-by":"crossref","first-page":"70","DOI":"10.15171\/apb.2019.009","article-title":"The Study of HLA-G Gene and Protein Expression in Patients with Recurrent Miscarriage","volume":"9","author":"E Mosaferi","year":"2019","journal-title":"Adv Pharm Bull"},{"issue":"4","key":"pone.0355847.ref038","doi-asserted-by":"crossref","DOI":"10.1111\/sji.13095","article-title":"Association of reduced maternal sHLA-G5 isoform levels and elevated TNF-\u03b1\/IL-4 cytokine ratio with Recurrent Pregnancy Loss: A study on South Indian women","volume":"94","author":"D Madduru","year":"2021","journal-title":"Scand J Immunol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:29:24Z","timestamp":1789061364000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355847"}},"subtitle":[],"editor":[{"given":"Enoch","family":"Aninagyei","sequence":"first","affiliation":[{"name":"University of Health and Allied Sciences","place":["GHANA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355847","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}