{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:38:27Z","timestamp":1791844707451,"version":"4.3.4"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"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":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Information about the use of flow cytometry in the diagnosis of male urethritis is scarce. The current study aims to evaluate the performance of flow cytometry on first-voided urine in males with infectious urethritis (<jats:italic>Chlamydia trachomatis<\/jats:italic>,<jats:italic>Neisseria gonorrhoeae<\/jats:italic>,<jats:italic>Mycoplasma genitalium<\/jats:italic>and<jats:italic>Trichomonas vaginalis<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Male patients of the Andrology Centre (Tartu University Hospital, Estonia) were recruited during the period March 2015 \u2013January 2018. Cases included 306 patients with infectious urethritis caused by<jats:italic>Chlamydia trachomatis<\/jats:italic>,<jats:italic>Neisseria gonorrhoeae<\/jats:italic>,<jats:italic>Mycoplasma genitalium<\/jats:italic>and\/or<jats:italic>Trichomonas vaginalis<\/jats:italic>. The control group consisted of 192 patients without uro-genital complaints, negative tests for<jats:italic>C<\/jats:italic>.<jats:italic>trachomatis<\/jats:italic>,<jats:italic>N<\/jats:italic>.<jats:italic>gonorrhoeae<\/jats:italic>,<jats:italic>M<\/jats:italic>.<jats:italic>genitalium<\/jats:italic>and<jats:italic>T<\/jats:italic>.<jats:italic>vaginalis<\/jats:italic>from first-voided urine and no inflammation in first-voided urine, mid-stream urine and urine after prostate massage.<jats:italic>C<\/jats:italic>.<jats:italic>trachomatis<\/jats:italic>,<jats:italic>N<\/jats:italic>.<jats:italic>gonorrhoeae<\/jats:italic>,<jats:italic>M<\/jats:italic>.<jats:italic>genitalium<\/jats:italic>and<jats:italic>T<\/jats:italic>.<jats:italic>vaginalis<\/jats:italic>were detected from first-voided urine using polymerase chain reaction (PCR) method. First-voided urine was analysed using urine particle analyzer Sysmex UF-500i.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>The most prevalent infection was chlamydia (64.1%), followed by<jats:italic>Mycoplasma genitalium<\/jats:italic>(20.9%), gonorrhoea (7.8%) and trichomoniasis (1.6%). Gonorrhoea caused the highest flow-cytometric leucocyte\/bacteria count, followed by chlamydia and<jats:italic>Mycoplasma genitalium<\/jats:italic>.<jats:italic>Trichomonas vaginalis<\/jats:italic>showed nearly absent inflammation in first-voided urine. Using an empiric flow-cytometry diagnostic threshold for urethritis in first-voided urine (leucocytes \u2265 15\/\u03bcl and bacteria \u2265 20\/\u03bcl) the total calculated sensitivity was over 90%. However, when applying such criteria for deciding whether to perform first-voided urine PCR for<jats:italic>C<\/jats:italic>.<jats:italic>trachomatis<\/jats:italic>,<jats:italic>N<\/jats:italic>.<jats:italic>gonorrhoeae<\/jats:italic>,<jats:italic>M<\/jats:italic>.<jats:italic>genitalium<\/jats:italic>and<jats:italic>T<\/jats:italic>.<jats:italic>vaginalis<\/jats:italic>or not, we could miss 23 cases with infectious urethritis that makes up 7,5% of all proven cases.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Flow cytometry of first-voided urine can be considered as a rapid and objective screening method in case of suspected male infectious urethritis.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0242227","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T18:39:22Z","timestamp":1606934362000},"page":"e0242227","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Profile of sexually transmitted infections causing urethritis and a related inflammatory reaction in urine among heterosexual males: A flow-cytometry study"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-990X","authenticated-orcid":true,"given":"Stanislav","family":"Tjagur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reet","family":"M\u00e4ndar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margus","family":"Punab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"issue":"8","key":"pone.0242227.ref001","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016","volume":"97","author":"J. Rowley","year":"2019","journal-title":"Bull World Health Organ"},{"issue":"11","key":"pone.0242227.ref002","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1177\/0956462416648585","article-title":"2016 European guideline on the management of non-gonococcal urethritis","volume":"27","author":"P. J. Horner","year":"2016","journal-title":"Int J STD AIDS"},{"issue":"2","key":"pone.0242227.ref003","first-page":"134","article-title":"Observer variation in the interpretation of Gram-stained urethral smears: implications for the diagnosis of non-specific urethritis","volume":"57","author":"J. R. Willcox","year":"1981","journal-title":"Br J Vener Dis"},{"issue":"6","key":"pone.0242227.ref004","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/sti.79.6.487","article-title":"Poor sensitivity and consistency of microscopy in the diagnosis of low grade non-gonococcal urethritis","volume":"79","author":"R. Smith","year":"2003","journal-title":"Sex Transm Infect"},{"issue":"1","key":"pone.0242227.ref005","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3343\/alm.2019.39.1.15","article-title":"Progress in Automated Urinalysis","volume":"39","author":"M. Oyaert","year":"2019","journal-title":"Ann Lab Med"},{"issue":"3","key":"pone.0242227.ref006","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2672.2012.05369.x","article-title":"Performance of the Sysmex UF1000i system in screening for significant bacteriuria before quantitative culture of aerobic\/facultative fast-growth bacteria in a reference hospital","volume":"113","author":"J. Gutierrez-Fernandez","year":"2012","journal-title":"J Appl Microbiol"},{"issue":"12","key":"pone.0242227.ref007","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.jiac.2014.08.002","article-title":"Usefulness of quantifying leukocytes in first-voided urine to predict positivity for Chlamydia trachomatis in asymptomatic men at high risk for chlamydial infection","volume":"20","author":"S. Ito","year":"2014","journal-title":"J Infect Chemother"},{"issue":"2","key":"pone.0242227.ref008","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/23744235.2017.1366044","article-title":"Prevalence of Mycoplasma genitalium and other sexually transmitted infections causing urethritis among high-risk heterosexual male patients in Estonia","volume":"50","author":"S. Tjagur","year":"2018","journal-title":"Infect Dis (Lond)"},{"key":"pone.0242227.ref009","unstructured":"Trevor G Cooper. WHO laboratory manual for the examination and processing of human semen, Fifth Edition. s.l.: World Health Organization, 2010."},{"key":"pone.0242227.ref010","unstructured":"EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam the Netherlands 2020. ISBN 978-94-92671-07-3. EAU Guidelines Office, Arnhem, the Netherlands. http:\/\/uroweb.org\/guidelines\/compilations-of-all-guidelines\/"},{"key":"pone.0242227.ref011","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/3-540-33713-X_49","volume-title":"Andrology for the Clinician","author":"M.C. Bishop","year":"2006"},{"issue":"Suppl 8","key":"pone.0242227.ref012","doi-asserted-by":"crossref","first-page":"S763","DOI":"10.1093\/cid\/civ755","article-title":"Advances in the Understanding and Treatment of Male Urethritis","volume":"61","author":"L. H. Bachmann","year":"2015","journal-title":"Clin Infect Dis"},{"issue":"6","key":"pone.0242227.ref013","first-page":"399","article-title":"Mechanical urethritis and ascendent genitourinary infections due to sexual stimulation of the urethra by inserted foreign bodies","volume":"68","author":"J P\u00e9c","year":"1992","journal-title":"Genitourin Med"},{"key":"pone.0242227.ref014","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cca.2015.06.020","article-title":"Urine flow cytometry can rule out urinary tract infection, but cannot identify bacterial morphologies correctly","volume":"448","author":"N Geerts","year":"2015","journal-title":"Clin Chim Acta"},{"issue":"8","key":"pone.0242227.ref015","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.disamonth.2016.03.011","article-title":"Non-gonococcal urethritis","volume":"62","author":"M. J. Perkins","year":"2016","journal-title":"Dis Mon"},{"issue":"1","key":"pone.0242227.ref016","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3109\/00365513.2010.535011","article-title":"Urine particles analysis: Performance evaluation of Sysmex UF-1000i and comparison among urineflow cytometer, dipstick, and visual microscopic examination","volume":"71","author":"T. Jiang","year":"2011","journal-title":"Scand J Clin Lab Invest"},{"issue":"3","key":"pone.0242227.ref017","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00345-012-0883-4","article-title":"Urine flow cytometry as a primary screening method to exclude urinary tract infections","volume":"31","author":"K. Boonen","year":"2013","journal-title":"World J Urol"},{"issue":"3","key":"pone.0242227.ref018","first-page":"188","article-title":"Experimental evaluation of the Sysmex UF-1000i for ruling out nongonococcal urethritis","volume":"20","author":"S. Grosso","year":"2012","journal-title":"Infez Med"},{"issue":"4","key":"pone.0242227.ref019","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/iju.13044","article-title":"Male non-gonococcal urethritis: From microbiological etiologies to demographic and clinical features","volume":"23","author":"S. Ito","year":"2016","journal-title":"Int J Urol"},{"issue":"3","key":"pone.0242227.ref020","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1136\/sextrans-2014-051761","article-title":"Performance evaluation of automated urine microscopy as a rapid, non-invasive approach for the diagnosis of non-gonococcal urethritis","volume":"91","author":"M.J. Pond","year":"2015","journal-title":"Sex Transm Infect"},{"issue":"10","key":"pone.0242227.ref021","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1097\/01.olq.0000175390.45315.a1","article-title":"Chlamydial and Gonococcal Infection in Men Without Polymorphonuclear Leukocytes on Gram Stain: Implications for Diagnostic Approach and Management","volume":"32","author":"W. M. Geisler","year":"2005","journal-title":"Sex Transm Dis"},{"issue":"3","key":"pone.0242227.ref022","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1136\/sti.2003.006924","article-title":"Polymorph count for predicting non-gonococcal urethral infection: a model using Chlamydia trachomatis diagnosed by ligase chain reaction","volume":"80","author":"L. J. Haddow","year":"2004","journal-title":"Sex Transm Infect"},{"key":"pone.0242227.ref023","article-title":"Microscopy of Gram-stained urethral smear in the diagnosis of urethritis: Which threshold value should be selected?","author":"M. Sarier","journal-title":"Andrologia."},{"issue":"1","key":"pone.0242227.ref024","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/OLQ.0b013e3182354da3","article-title":"Recalibrating the Gram Stain Diagnosis of Male Urethritis in the Era of Nucleic Acid Amplification Testing","volume":"39","author":"C. A. Rietmeijer","year":"2012","journal-title":"Sex Transm Dis"},{"key":"pone.0242227.ref025","first-page":"1","article-title":"Sexually Transmitted Diseases Treatment Guidelines, 2015","volume":"Vol. 64","author":"S. A. Rasmussen","year":"2015","journal-title":"Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report"},{"issue":"3","key":"pone.0242227.ref026","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/OLQ.0000000000000565","article-title":"Microscopy of Stained Urethral Smear in Male Urethritis; Which Cutoff Should be Used?","volume":"44","author":"H. Moi","year":"2017","journal-title":"Sex Transm Dis"},{"issue":"Pt 12","key":"pone.0242227.ref027","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1099\/jmm.0.059378-0","article-title":"A misleading urethral smear with polymorphonuclear leucocytes and intracellular diplococci; case report of urethritis caused by Neisseria meningitidis","volume":"62","author":"RE Genders","year":"2013","journal-title":"J Med Microbiol"},{"issue":"5","key":"pone.0242227.ref028","doi-asserted-by":"crossref","first-page":"e19709","DOI":"10.1371\/journal.pone.0019709","article-title":"The microbial communities in male first catch urine are highly similar to those in paired urethral swab specimens","volume":"6","author":"Q Dong","year":"2011","journal-title":"PLoS One"},{"issue":"5","key":"pone.0242227.ref029","doi-asserted-by":"crossref","first-page":"e36298","DOI":"10.1371\/journal.pone.0036298","article-title":"Bacterial communities of the coronal sulcus and distal urethra of adolescent males","volume":"7","author":"DE Nelson","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"pone.0242227.ref030","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.phrs.2012.10.019","article-title":"Microbiota of male genital tract: Impact on the health of man and his partner","volume":"69","author":"R. M\u00e4ndar","year":"2013","journal-title":"Pharmacol Res"},{"issue":"9\u201310","key":"pone.0242227.ref031","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.resmic.2017.04.004","article-title":"Aerobic vaginitis: no longer a stranger","volume":"168","author":"G. Donders","year":"2017","journal-title":"Res Microbiol"},{"issue":"5","key":"pone.0242227.ref032","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1439-0272.2003.tb00856.x","article-title":"The limit of leucocytospermia from the microbiological viewpoint","volume":"35","author":"M. Punab","year":"2003","journal-title":"Andrologia"},{"issue":"5","key":"pone.0242227.ref033","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.mehy.2009.04.035","article-title":"Urethral dysbacteriosis as an underlying, primary cause of chronic prostatitis: potential implications for probiotic therapy","volume":"73","author":"L. Liu","year":"2009","journal-title":"Med Hypotheses"},{"issue":"12","key":"pone.0242227.ref034","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41585-019-0250-y","article-title":"The seminal microbiome in health and disease","volume":"16","author":"S. Altm\u00e4e","year":"2019","journal-title":"Nat Rev Urol"},{"issue":"6","key":"pone.0242227.ref035","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s11255-019-02140-2","article-title":"Classification of non-gonococcal urethritis: a review","volume":"51","author":"M. Sarier","year":"2019","journal-title":"Int Urol Nephrol"},{"issue":"2","key":"pone.0242227.ref036","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jri.2011.01.006","article-title":"Innate and acquired immunity in the human penile urethra","volume":"88","author":"J. Pudney","year":"2011","journal-title":"J Reprod Immunol"},{"key":"pone.0242227.ref037","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.3389\/fimmu.2017.01732","article-title":"The Human Penis Is a Genuine Immunological Effector Site","volume":"8","author":"A. Sennepin","year":"2017","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0242227.ref038","doi-asserted-by":"crossref","first-page":"7178","DOI":"10.1128\/IAI.69.11.7178-7181.2001","article-title":"Urethral cytokine and immune responses in Chlamydia trachomatis-infected males","volume":"69","author":"M. S. Pate","year":"2001","journal-title":"Infect Immun"},{"issue":"4","key":"pone.0242227.ref039","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1136\/sti.2003.006817","article-title":"Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis","volume":"80","author":"L. Falk","year":"2004","journal-title":"Sex Transm Infect"},{"key":"pone.0242227.ref040","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12967-015-0475-3","article-title":"Diagnosing inflammation and infection in the urinary system via proteomics","volume":"13","author":"Y. Yu","year":"2015","journal-title":"J Transl Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T06:36:53Z","timestamp":1618555013000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0242227"}},"subtitle":[],"editor":[{"given":"Colette","family":"Kanellopoulos-Langevin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,2]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0242227","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,2]]}}}