{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:50:03Z","timestamp":1788483003350,"version":"build-2803163510"},"reference-count":23,"publisher":"AOSIS","issue":"1","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Background:\u00a0Classical toxin-mediated respiratory diphtheria has become less common because of widespread effective vaccination globally but invasive disease as a result of non-toxigenic strains of\u00a0Corynebacterium diphtheriae\u00a0is not prevented by vaccination and may result in severe disease, including infective endocarditis (IE).\n\nObjectives:\u00a0To describe the outbreak and subsequent investigation of a cluster of five cases of non-toxigenic\u00a0C. diphtheriae\u00a0endocarditis.\n\nMethod:\u00a0A retrospective observational case series of five cases of non-toxigenic\u00a0C. diphtheriae\u00a0endocarditis identified in the rural West Coast district of the Western Cape province of South Africa between May 2021 and June 2021.\n\nResults:\u00a0Non-toxigenic\u00a0C. diphtheriae\u00a0IE had an aggressive clinical course with high mortality in this cohort. Only one of five patients survived to hospital discharge. The surviving patient received a prompt diagnosis with early surgical intervention but still had a complicated clinical course. Notably, only one case had a pre-existing risk factor for IE, namely a prosthetic valve. Whole genome sequencing of clinical isolates confirmed that all isolates were of the same novel sequence type of non-toxigenic\u00a0C. diphtheriae\u00a0but despite a thorough investigation no epidemiological link was ever found between the cases.\n\nConclusion:\u00a0Non-toxigenic strains of\u00a0C. diphtheriae\u00a0are less well known but may be highly virulent and cause severe invasive disease.\n\nContribution:\u00a0This is the largest cluster of non-toxigenic\u00a0C. diphtheriae\u00a0IE ever described in South Africa and expands the body of literature on this unusual but possibly emerging infection.<\/jats:p>","DOI":"10.4102\/sajid.v39i1.539","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T05:04:26Z","timestamp":1708578266000},"update-policy":"https:\/\/doi.org\/10.4102\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Non-toxigenic Corynebacterium diphtheriae endocarditis: A cluster of five cases"],"prefix":"10.4102","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3730-1646","authenticated-orcid":false,"given":"Tamsin","family":"Lovelock","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bk57929","id-type":"ROR","asserted-by":"publisher"}],"name":"Stellenbosch University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9186-0679","authenticated-orcid":false,"given":"Mignon","family":"du Plessis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03rp50x72","id-type":"ROR","asserted-by":"publisher"}],"name":"University of the Witwatersrand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4529-2879","authenticated-orcid":false,"given":"Clinton","family":"van der Westhuizen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01hs8x754","id-type":"ROR","asserted-by":"publisher"}],"name":"Tygerberg Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6029-9487","authenticated-orcid":false,"given":"Jacques T.","family":"Janson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01hs8x754","id-type":"ROR","asserted-by":"publisher"}],"name":"Tygerberg Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-0097","authenticated-orcid":false,"given":"Charlene","family":"Lawrence","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02nys7898","id-type":"ROR","asserted-by":"publisher"}],"name":"Western Cape Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-698X","authenticated-orcid":false,"given":"Arifa","family":"Parker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bk57929","id-type":"ROR","asserted-by":"publisher"}],"name":"Stellenbosch University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6549-9402","authenticated-orcid":false,"given":"Alfonso","family":"Pecoraro","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bk57929","id-type":"ROR","asserted-by":"publisher"}],"name":"Stellenbosch University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9715-3449","authenticated-orcid":false,"given":"Hans","family":"Prozesky","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bk57929","id-type":"ROR","asserted-by":"publisher"}],"name":"Stellenbosch University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0243-7455","authenticated-orcid":false,"given":"Anne","family":"von Gottberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/007wwmx82","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute for Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-9054","authenticated-orcid":false,"given":"Jantjie","family":"Taljaard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bk57929","id-type":"ROR","asserted-by":"publisher"}],"name":"Stellenbosch University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2580","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Sharma NC, Efstratiou A, Mokrousov I, Mutreja A, Das B, Ramamurthy T. Diphtheria. Nat Rev Dis Primers. 2019;5(1):81. https:\/\/doi.org\/10.1038\/s41572-019-0131-y","DOI":"10.1038\/s41572-019-0131-y"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Howard WT. A case of acute ulcerative endocarditis due to the bacillus diphtheria. Am J Med Sci. 1894;108(6):651\u2013663. https:\/\/doi.org\/10.1097\/00000441-189412000-00002","DOI":"10.1097\/00000441-189412000-00002"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Jephcott AE, Gillespie EH, Davenport C, Emerson JW, Moroney PJ. Non-toxigenic Corynebacterium diphtheriae in a boarding school. Lancet. 1975;305(7914):1025\u20131026. https:\/\/doi.org\/10.1016\/S0140-6736(75)91962-5","DOI":"10.1016\/S0140-6736(75)91962-5"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Guard RW. Non-toxigenic Corynebacterium diphtheriae causing subacute bacterial endocarditis: Case report. Pathology. 1979;11(3):533\u2013535. https:\/\/doi.org\/10.3109\/00313027909059028","DOI":"10.3109\/00313027909059028"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Trepeta RW, Edberg SC. Corynebacterium diphtheriae endocarditis: Sustained potential of a classical pathogen. Am J Clin Pathol. 1984;81(5):679\u2013683. https:\/\/doi.org\/10.1093\/ajcp\/81.5.679","DOI":"10.1093\/ajcp\/81.5.679"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Zasada AA, Zaleska M, Podlasin RB, Sefery\u0144ska I. The first case of septicemia due to nontoxigenic Corynebacterium diphtheriae in Poland: Case report. Ann Clin Microbiol Antimicrob. 2005;4:8. https:\/\/doi.org\/10.1186\/1476-0711-4-8","DOI":"10.1186\/1476-0711-4-8"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Menon T, Senthilkumar S, Pachaiyappan P. Native valve endocarditis caused by a non-toxigenic strain of Corynebacterium diphtheriae. Indian J Pathol Microbiol. 2010;53(4):899\u2013900. https:\/\/doi.org\/10.4103\/0377-4929.72056","DOI":"10.4103\/0377-4929.72056"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Pachirat O, Kaewkes D, Pussadhamma B, Watt G. Corynebacterium diphtheriae native aortic valve endocarditis in a patient with prosthetic mitral valve: A rare presentation. Cardiol Res. 2018;9(5):314\u2013317. https:\/\/doi.org\/10.14740\/cr741w","DOI":"10.14740\/cr741w"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Gubler J, Huber-Schneider C, Gruner E, Altwegg M. An outbreak of nontoxigenic Corynebacterium diphtheriae infection: Single bacterial clone causing invasive infection among Swiss drug users. Clin Infect Dis. 1998;27(5):1295\u20131298. https:\/\/doi.org\/10.1086\/514997","DOI":"10.1086\/514997"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Tiley SM, Kociuba KR, Heron LG, Munro R. Infective endocarditis due to nontoxigenic Corynebacterium diphtheriae: Report of seven cases and review. Clin Infect Dis. 1993;16(2):271\u2013275. https:\/\/doi.org\/10.1093\/clind\/16.2.271","DOI":"10.1093\/clind\/16.2.271"},{"key":"ref10","unstructured":"Marcus J, Spector I, Chin W, Levin S. Infective endocarditis due to non-toxigenic Corynebacterium diphtheriae in a child. S Afr Med J. 1983;63(8):285\u2013287."},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"El-Hazmi MM. Late-onset prosthetic valve endocarditis caused by nontoxigenic Corynebacterium diphtheriae. J Infect Dev Ctries. 2015;9(8):905\u2013909. https:\/\/doi.org\/10.3855\/jidc.5976","DOI":"10.3855\/jidc.5976"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"De Santis A, Siciliano RF, Sampaio RO, et al. Non-toxigenic Corynebacterium diphtheriae infective endocarditis with embolic events: A case report. BMC Infect Dis. 2020;20(1):907. https:\/\/doi.org\/10.1186\/s12879-020-05652-w","DOI":"10.1186\/s12879-020-05652-w"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Alexander D. Splenic abscess caused by Corynebacterium diphtheriae. Clin Pediatr (Phila). 1984;23(10):591\u2013592. https:\/\/doi.org\/10.1177\/000992288402301013","DOI":"10.1177\/000992288402301013"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Barakett V, Morel G, Lesage D, Petit JC. Septic arthritis due to a nontoxigenic strain of Corynebacterium diphtheriae subspecies mitis. Clin Infect Dis. 1993;17(3):520\u2013521. https:\/\/doi.org\/10.1093\/clinids\/17.3.520","DOI":"10.1093\/clinids\/17.3.520"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Isaac-Renton JL, Boyko WJ, Chan R, Crichton E. Corynebacterium diphtheriae septicemia. Am J Clin Pathol. 1981;75(4):631\u2013634. https:\/\/doi.org\/10.1093\/ajcp\/75.4.631","DOI":"10.1093\/ajcp\/75.4.631"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Romney MG, Roscoe DL, Bernard K, Lai S, Efstratiou A, Clarke AM. Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada. J Clin Microbiol. 2006;44(5):1625\u20131629. https:\/\/doi.org\/10.1128\/JCM.44.5.1625-1629.2006","DOI":"10.1128\/JCM.44.5.1625-1629.2006"},{"key":"ref17","unstructured":"CLSI. Performance standards for antimicrobial susceptibility testing, CLSI supplement M100. 31st ed. Wayne, PA: Clinical Laboratory Standards Institute; 2021."},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Williams MM, Waller JL, Aneke JS, et al. Detection and characterization of diphtheria toxin gene-bearing Corynebacterium species through a new real-time PCR assay. J Clin Microbiol. 2020;58(10):e00639\u201320. https:\/\/doi.org\/10.1128\/JCM.00639-20","DOI":"10.1128\/JCM.00639-20"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Du Plessis M, Wolter N, Allam M, et al. Molecular characterization of Corynebacterium diphtheriae outbreak isolates, South Africa, March\u2013June 2015. Emerg Infect Dis. 2017;23(8):1308\u20131315. https:\/\/doi.org\/10.3201\/eid2308.162039","DOI":"10.3201\/eid2308.162039"},{"key":"ref20","unstructured":"Western Cape Government. Circular: H91\/2021 - Diphtheria alert: Non-toxigenic diphtheria cluster IDENTIFIED IN the West Coast and Cape Winelands districts. Annexure 1 [homepage on the Internet]. 2021 [cited n.d.]. Available form: https:\/\/www.westerncape.gov.za\/assets\/departments\/health\/FP\/wcgh_circular_h91_of_2021_-_diphtheria_alert_non-toxigenic_diphtheria_cluster_identified_in_the_west_coast_and_cape_winelands_districts.pdf"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Pecoraro AJK, Herbst PG, Janson JT, et al. Early surgery determines prognosis in patients with infective endocarditis: Outcome in patients managed by an endocarditis team \u2013 A prospective cohort study background: Infective endocarditis (IE) in South Africa is associated with significant morbidity and. Cardiovasc Diagn Ther. 2022;12(4):453\u2013463. https:\/\/doi.org\/10.21037\/cdt-21-590","DOI":"10.21037\/cdt-21-590"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Sangal V, Blom J, Sutcliffe IC, Von Hunolstein C, Burkovski A, Hoskisson PA. Adherence and invasive properties of Corynebacterium diphtheriae strains correlates with the predicted membrane-associated and secreted proteome. 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