{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:03:20Z","timestamp":1785431000213,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":210,"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"}],"funder":[{"DOI":"10.13039\/100008321","name":"Pennsylvania State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Canadian Journal of Infectious Diseases and Medical Microbiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection (CDI) significantly contributes to healthcare\u2010associated morbidity and mortality. Vaccination against\n                      <jats:italic>C. difficile<\/jats:italic>\n                      toxins may provide an effective preventive strategy, yet current data remain inconclusive. This meta\u2010analysis evaluates the efficacy, immunogenicity, and safety of the\n                      <jats:italic>C. difficile<\/jats:italic>\n                      toxoid vaccine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from inception through August 2024. Eligible studies were randomized controlled trials enrolling adults aged 50\u201385\u2009years that compared genetically detoxified\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      toxoid vaccines (50\u2013200\u2009\u00b5g) with placebo and reported clinical efficacy, immunogenicity, or safety outcomes. Random\u2010effects meta\u2010analyses were performed, with risk of bias assessed using RoB 2.0 and certainty of evidence graded using GRADE. The study was prospectively registered in PROSPERO (CRD42024597465). No external funding was received for this study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight trials (11,717 participants) showed no significant vaccine effect on overall CDI incidence (RR\u2009=\u20090.86; 95% CI 0.56\u20131.32; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%) or severe CDI (RR\u2009=\u20090.25; 95% CI 0.02\u20133.75; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200971%), though severe CDI risk trended lower in vaccinated groups. Immunogenicity analyses demonstrated significant seroconversion rates for toxin A (RR\u2009=\u200923.28; 95% CI 7.62\u201371.16; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%) and toxin B (RR\u2009=\u200919.23; 95% CI 4.84\u201376.38; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%). Vaccine recipients exhibited significantly elevated geometric mean concentrations (GMCs) for antitoxin A and B antibodies across various dosing regimens, particularly at higher doses (200\u2009\u00b5g). Local adverse events, including pain (RR\u2009=\u20093.02; 95% CI 2.47\u20133.70), swelling (RR\u2009=\u20098.53; 95% CI 3.15\u201323.14), and erythema (RR\u2009=\u20096.78; 95% CI 2.35\u201319.61), were significantly increased postvaccination, but serious systemic reactions, infections, gastrointestinal disturbances, and mortality rates showed no significant differences compared to placebo. Interpretation of vaccine efficacy is limited by imprecision of effect estimates, heterogeneity in immunogenicity reporting, and the small number of trials evaluating severe CDI outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      toxoid vaccines induce strong humoral immune responses and demonstrate an acceptable safety profile but do not significantly reduce the overall CDI incidence. Evidence suggests a potential role in mitigating severe disease; however, clinical benefit remains uncertain due to imprecision and heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/cjid\/1160340","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:21:36Z","timestamp":1785428496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Evaluation of the Efficacy and Safety of the\n                    <i>Clostridioides difficile<\/i>\n                    Toxoid Vaccine: A Meta\u2010Analysis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-7545","authenticated-orcid":false,"given":"Muhammad","family":"Shahzil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3596-6300","authenticated-orcid":false,"given":"Zainab","family":"Jamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-6048","authenticated-orcid":false,"given":"Saleha","family":"Azeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5876-2900","authenticated-orcid":false,"given":"Minahel","family":"Shehzadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Shabbir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4785-7922","authenticated-orcid":false,"given":"Muhammad Saad","family":"Faisal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8186-0106","authenticated-orcid":false,"given":"Fariha","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2863-8352","authenticated-orcid":false,"given":"Muhammad Ali","family":"Khaqan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-3988","authenticated-orcid":false,"given":"Ammad Javaid","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8108-7408","authenticated-orcid":false,"given":"Syed-Mohammed","family":"Jafri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"e_1_2_13_1_2","volume-title":"Harrison\u2019s Principles of Internal Medicine"},{"key":"e_1_2_13_2_2","unstructured":"FAQs (Frequently Asked Questions) Clostridium difficile https:\/\/stacks.cdc.gov\/view\/cdc\/12127."},{"key":"e_1_2_13_3_2","article-title":"Nosocomial Clostridium difficile Colonisation and Disease","author":"Johnson S.","journal-title":"Lancet"},{"key":"e_1_2_13_4_2","unstructured":"KellyC. 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