{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:27:09Z","timestamp":1787621229200,"version":"build-2736575974"},"reference-count":87,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Leprosy continues to be an important public health problem, particularly in endemic regions such as Brazil, India, and Indonesia. Household contacts of multibacillary (MB) patients represent a high\u2010risk group for subclinical infection due to prolonged exposure and high bacillary load. Host biomarkers have emerged as promising tools for identifying early infections and guiding prophylactic interventions. This systematic review aimed to identify and synthesize evidence on inflammatory and immune biomarkers associated with susceptibility to leprosy and disease progression among contacts of index cases, evaluating their potential predictive and diagnostic value. The study followed the Preferred Reporting Items for Systematic Reviews (PRISMA) 2020 guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251111469). We searched CAPES, SciELO, PubMed, ScienceDirect, EMBASE, Scopus, and EBSCO databases for original studies published between 2012 and 2025, with no language restrictions. Two review authors independently selected studies using the Rayyan software, and methodological quality was assessed using the ROBIS tool. The biomarkers most frequently investigated in the studies were particularly tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) and interleukin (IL)\u201010, which play regulatory roles in the host. Elevated levels of TNF\u2010\u03b1, interferon\u2010\u03b3 (IFN\u2010\u03b3), IL\u20106, and IL\u20104 were associated with a higher risk of subclinical infection among contacts of MB patients, indicating a polyfunctional immune profile. On the other hand, paucibacillary (PB) contacts exhibited lower cytokine activation, suggesting partial protection. Additional promising markers included anti\u2010Mce1A, PGL\u2010I IgM, and CCL4, detected primarily by enzyme\u2010linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods. In summary, inflammatory and immune biomarkers\u2014especially TNF\u2010\u03b1, IL\u201010, IFN\u2010\u03b3, and anti\u2010Mce1A\u2014demonstrate potential as predictive indicators of subclinical leprosy infection. Their combined use may increase risk stratification and allow early therapeutic intervention in endemic settings. However, longitudinal validation studies are required prior to clinical application.<\/jats:p>","DOI":"10.1155\/mi\/6163972","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:04:55Z","timestamp":1771391095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Predictive Role of Biomarkers for Leprosy Prophylaxis in Contacts of Patients Who Are Indices of the Disease: A Systematic Review of the Literature"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-1687","authenticated-orcid":false,"given":"Luiza Raquel Tapaj\u00f3s","family":"Figueira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-3474","authenticated-orcid":false,"given":"Marcos Jess\u00e9 Abrah\u00e3o","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Vinicius Moraes da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca Lobato","family":"Marinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keitty Anne Silva","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Augusto Ferreira dos","family":"Anjos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Cristina Santos Sinfronio da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele Melo","family":"Sardinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everaldina Cordeiro dos","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Nepomuceno Gondim Costa","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_9_1_2","unstructured":"https:\/\/aal.org.br\/hanseniase\/."},{"key":"e_1_2_9_2_2","unstructured":"https:\/\/www.paho.org\/pt\/topicos\/hanseniase."},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0104-12902004000200008"},{"key":"e_1_2_9_4_2","volume-title":"Protocolo Cl\u00ednico e Diretrizes Terap\u00eauticas da Hansen\u00edase","author":"Da Sa\u00fade M.","year":"2024"},{"key":"e_1_2_9_5_2","unstructured":"https:\/\/www.cureus.com\/articles\/176433-leprosy-classification-clinical-features-epidemiology-and-host-immunological-responses-failure-of-eradication-in-2023#!\/."},{"key":"e_1_2_9_6_2","unstructured":"https:\/\/www.gov.br\/saude\/pt-br\/centrais-de-conteudo\/publicacoes\/boletins\/epidemiologicos\/especiais\/2023\/boletim_hanseniase-2023_internet_completo.pdf\/view."},{"key":"e_1_2_9_7_2","unstructured":"https:\/\/www.gov.br\/saude\/pt-br\/centrais-de-conteudo\/publicacoes\/svsa\/hanseniase\/estrategia-nacional-para-enfrentamento-a-hanseniase-2024-2030\/view."},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.33448\/rsd-v13i4.45585"},{"key":"e_1_2_9_9_2","unstructured":"https:\/\/www.bbc.com\/portuguese\/articles\/cjr1gx29421o."},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.3.5880.557"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.852579"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1590\/0034-7167-2016-0607"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0365-05962008000400010"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-018-3056-2"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2019.1768"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0037-86822002000400014"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2022.2141987"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-020-00763-7"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac010"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2019.05.002"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2018.10.003"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00585"},{"key":"e_1_2_9_23_2","unstructured":"https:\/\/www.prisma-statement.org."},{"key":"e_1_2_9_24_2","unstructured":"WhitingP. Guidance on How to use ROBIS."},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1411"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762012000900014"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1462-0"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762012000900010"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep34260"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw570"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005375"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760160549"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006494"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36323-1"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.009"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01811"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104725"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.698495"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.855787"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.714396"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103379"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2018.0162"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.10.027"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac036"},{"key":"e_1_2_9_45_2","doi-asserted-by":"crossref","unstructured":"da Silva PrataR. B. MendesM. A. andSoaresV. C. et al.Arginase 1 is a Marker of Protection Against Illness in Contacts of Leprosy Patients Scientific Reports 2022 12 no. 1 https:\/\/doi.org\/10.1038\/s41598-022-11944-9.","DOI":"10.1038\/s41598-022-11944-9"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S405932"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1130137"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-023-08862-0"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1476450"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760230129"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1513060"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.47276\/lr.96.1.2024088"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-023-08124-z"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0104-42302013000100016"},{"key":"e_1_2_9_55_2","doi-asserted-by":"publisher","DOI":"10.1590\/1980-549720210039"},{"key":"e_1_2_9_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01305-15"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/tmi.14020"},{"key":"e_1_2_9_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0285450"},{"key":"e_1_2_9_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1361641"},{"key":"e_1_2_9_60_2","doi-asserted-by":"crossref","unstructured":"SainiC. TariqueM. RameshV. KhannaN. andSharmaA. \u03b3\u03b4 T Cells are Associated With Inflammation and Immunopathogenesis of Leprosy Reactions 2018 200 55\u201365 https:\/\/doi.org\/10.1016\/j.imlet.2018.07.005 2-s2.0-85050094172.","DOI":"10.1016\/j.imlet.2018.07.005"},{"key":"e_1_2_9_61_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0365-05962004000600002"},{"key":"e_1_2_9_62_2","doi-asserted-by":"publisher","DOI":"10.29184\/1980-7813.rcfmc.312.vol.15.n3.2020"},{"key":"e_1_2_9_63_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.647832"},{"key":"e_1_2_9_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abd.2021.08.006"},{"key":"e_1_2_9_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2014.07.005"},{"key":"e_1_2_9_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1416177"},{"key":"e_1_2_9_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004345"},{"key":"e_1_2_9_68_2","first-page":"230","article-title":"Leprosy: Too Complex a Disease for a Simple Elimination Paradigm","volume":"83","author":"Lockwood D. N. J.","year":"2005","journal-title":"Bulletin of the World Health Organization"},{"key":"e_1_2_9_69_2","doi-asserted-by":"publisher","DOI":"10.33448\/rsd-v12i3.40664"},{"key":"e_1_2_9_70_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0037-86822008000700004"},{"key":"e_1_2_9_71_2","doi-asserted-by":"publisher","DOI":"10.5123\/S2176-62232017000200003"},{"key":"e_1_2_9_72_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/352689"},{"key":"e_1_2_9_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004934"},{"key":"e_1_2_9_74_2","doi-asserted-by":"publisher","DOI":"10.7860\/NJLM\/2023\/59409.2686"},{"key":"e_1_2_9_75_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1497319"},{"key":"e_1_2_9_76_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0037-86822008000700012"},{"key":"e_1_2_9_77_2","doi-asserted-by":"publisher","DOI":"10.47276\/lr.82.4.389"},{"key":"e_1_2_9_78_2","doi-asserted-by":"publisher","DOI":"10.25259\/IJDVL_915_2024"},{"key":"e_1_2_9_79_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026618666181025100434"},{"key":"e_1_2_9_80_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-020-03979-5"},{"key":"e_1_2_9_81_2","doi-asserted-by":"publisher","DOI":"10.1177\/15353702231209422"},{"key":"e_1_2_9_82_2","doi-asserted-by":"publisher","DOI":"10.9789\/2175-5361"},{"key":"e_1_2_9_83_2","volume-title":"ML Flow Serological Test: Complementary Tool in Leprosy","author":"Montanha J. O. M.","year":"2023"},{"key":"e_1_2_9_84_2","volume-title":"Sensibilidade do Teste ELISA Anti-PGL-1 com dois Ant\u00edgenos Sint\u00e9ticos Derivados do PGL-1 do Mycobacterium leprae","author":"Amador S. C.","year":"2012"},{"key":"e_1_2_9_85_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12966"},{"key":"e_1_2_9_86_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010756"},{"key":"e_1_2_9_87_2","doi-asserted-by":"publisher","DOI":"10.1007\/s44197-024-00188-7"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/6163972","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/mi\/6163972","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/6163972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:03:41Z","timestamp":1772971421000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/mi\/6163972"}},"subtitle":[],"editor":[{"given":"Mirella","family":"Giovarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":87,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/mi\/6163972"],"URL":"https:\/\/doi.org\/10.1155\/mi\/6163972","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6163972"}}