{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:06:06Z","timestamp":1785409566502,"version":"3.56.0"},"reference-count":17,"publisher":"AOSIS","issue":"1","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"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>We describe a case of a 22-year-old woman living with human immunodeficiency virus (HIV) who presented with classical features of secondary syphilis. Initial Rapid Plasma Reagin (RPR) testing was unexpectedly non-reactive; however, repeat RPR testing with serum dilution yielded a reactive result, illustrating the prozone phenomenon.\nContribution:\u00a0The prozone phenomenon is uncommon. We aim to encourage clinician\u2013laboratory communication when there is a high pretest probability of syphilis, with serological discordance, to facilitate prompt diagnosis and treatment.<\/jats:p>","DOI":"10.4102\/sajid.v41i1.800","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:08:37Z","timestamp":1776938917000},"update-policy":"https:\/\/doi.org\/10.4102\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unexpected non-reactive nontreponemal serology in secondary syphilis: The prozone phenomenon and clinician\u2013laboratory communication"],"prefix":"10.4102","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8825-8259","authenticated-orcid":false,"given":"Mahomed A.","family":"Aboo","sequence":"first","affiliation":[{"name":"Tambo Memorial Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8297-0403","authenticated-orcid":false,"given":"Matilda","family":"Mphahlele","sequence":"additional","affiliation":[{"name":"Tambo Memorial Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9827-1225","authenticated-orcid":false,"given":"Melanie","family":"Louw","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047x96110","id-type":"ROR","asserted-by":"publisher"}],"name":"Johannesburg Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-212X","authenticated-orcid":false,"given":"Nicholas","family":"Aikman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047x96110","id-type":"ROR","asserted-by":"publisher"}],"name":"Johannesburg Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2580","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Peters RPH, Nel JS, Sadiq E, et al. Southern African HIV clinicians society guideline for the clinical management of syphilis. S Afr J HIV Med. 2024;25(1):1577. https:\/\/doi.org\/10.4102\/sajhivmed.v25i1.1577","DOI":"10.4102\/sajhivmed.v25i1.1577"},{"key":"ref1","unstructured":"Kufa T, Thabane E, Leshaba D, Makhubele M, Puren A. Congenital syphilis annual surveillance report, South Africa 2023. Public Health Bull S Africa [serial online]. 2025 [cited 2025 May 31];3(1). Available from: https:\/\/www.phbsa.ac.za\/wp-content\/uploads\/2025\/01\/Congenital-syphilis-annual-surveillance-report-South-Africa-2023.pdf"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Khaliq OP, Jassen A, Tabane N, Moodley J. Prevalence and management of syphilis at primary healthcare level in the Free State, South Africa. S Afr J Infect Dis. 2025;40(1):724. https:\/\/doi.org\/10.4102\/sajid.v40i1.724","DOI":"10.4102\/sajid.v40i1.724"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Satyaputra F, Hendry S, Braddick M, Sivabalan P, Norton R. The laboratory diagnosis of syphilis. J Clin Microbiol. 2021;59(10):e0010021. https:\/\/doi.org\/10.1128\/JCM.00100-21","DOI":"10.1128\/JCM.00100-21"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Cao W, Thorpe PG, O\u2019Callaghan K, Kersh EN. Advantages and limitations of current diagnostic laboratory approaches in syphilis and congenital syphilis. Expert Rev Anti Infect Ther. 2023;21(12):1339\u20131354. https:\/\/doi.org\/10.1080\/14787210.2023.2280214","DOI":"10.1080\/14787210.2023.2280214"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC laboratory recommendations for syphilis testing, United States, 2024. MMWR Recomm Rep. 2024;73(1):1\u201332. https:\/\/doi.org\/10.15585\/mmwr.rr7301a1","DOI":"10.15585\/mmwr.rr7301a1"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Treger RS, Menza TW, Truong TT, Lieberman JA. Advances in syphilis diagnostics to address the 21st-century epidemic. Clin Chem. 2025;71(9):935\u2013948. https:\/\/doi.org\/10.1093\/clinchem\/hvaf072","DOI":"10.1093\/clinchem\/hvaf072"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Chevalier FJ, Bacon O, Johnson KA, Cohen SE. Syphilis: A review. J Am Med Assoc. 2025;334(21):1927\u20131940. https:\/\/doi.org\/10.1001\/jama.2025.17362","DOI":"10.1001\/jama.2025.17362"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Whiting C, Schwartzman G, Khachemoune A. Syphilis in dermatology: Recognition and management. Am J Clin Dermatol. 2023;24(2):287\u2013297. https:\/\/doi.org\/10.1007\/s40257-022-00755-3","DOI":"10.1007\/s40257-022-00755-3"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Smith G, Holman RP. The prozone phenomenon with syphilis and HIV-1 co-infection. South Med J. 2004;97(4):379\u2013382. https:\/\/doi.org\/10.1097\/01.SMJ.0000121204.58881.60","DOI":"10.1097\/01.SMJ.0000121204.58881.60"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Awake P, Angadi K, Sen S, Bhadange P. Prozone phenomenon in secondary syphilis with HIV co-infection: Two cases. Indian J Sex Transm Dis AIDS. 2022;43(2):183\u2013185. https:\/\/doi.org\/10.4103\/ijstd.ijstd_43_22","DOI":"10.4103\/ijstd.ijstd_43_22"},{"key":"ref11","unstructured":"el-Zaatari MM, Martens MG, Anderson GD. Incidence of the prozone phenomenon in syphilis serology. Obstet Gynecol. 1994;84(4):609\u2013612."},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Liu LL, Lin LR, Tong ML, et al. Incidence and risk factors for the prozone phenomenon in serologic testing for syphilis in a large cohort. Clin Infect Dis. 2014;59(3):384\u2013389. https:\/\/doi.org\/10.1093\/cid\/ciu325","DOI":"10.1093\/cid\/ciu325"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol. 2009;9(4):235\u2013245. https:\/\/doi.org\/10.1038\/nri2524","DOI":"10.1038\/nri2524"},{"key":"ref14","unstructured":"Centers for Disease Control and Prevention (CDC). Discordant results from reverse sequence syphilis screening \u2013 Five laboratories, United States, 2006\u20132010. MMWR Morb Mortal Wkly Rep. 2011;60(5):133\u2013137."},{"key":"ref15","unstructured":"World Health Organization. Laboratory quality management system: Handbook [homepage on the Internet]. Geneva: World Health Organization; 2011 [cited 2026 Feb 15]. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789241548274"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Gandla S, Nakka R, Khan RA, Salboukh F, Ghebremichael M. The association between syphilis infection and HIV acquisition and HIV disease progression in sub-Saharan Africa. Trop Med Infect Dis. 2025;10(3):65. https:\/\/doi.org\/10.3390\/tropicalmed10030065","DOI":"10.3390\/tropicalmed10030065"}],"container-title":["Southern African Journal of Infectious Diseases"],"original-title":[],"link":[{"URL":"https:\/\/sajid.co.za\/index.php\/sajid\/article\/view\/800\/2060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:08:48Z","timestamp":1776938928000},"score":1,"resource":{"primary":{"URL":"https:\/\/sajid.co.za\/index.php\/sajid\/article\/view\/800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.4102\/sajid.v41i1.800","relation":{},"ISSN":["2312-0053","2313-1810"],"issn-type":[{"value":"2312-0053","type":"print"},{"value":"2313-1810","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"article-number":"a800"}}