Navigating genitourinary tuberculosis: lessons from a 2023 case

Navigating genitourinary tuberculosis: lessons from a 2023 case | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Navigating genitourinary tuberculosis: lessons from a 2023 case Natalia Ramos Ospina, Sofia Alexandra Montes Tello, John Harold Suarez Vélez, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4535237/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Genitourinary tuberculosis (GU-TB), an extrapulmonary manifestation of Mycobacterium tuberculosis (Mtb) infection, often presents insidiously, posing diagnostic challenges and leading to progressive tissue destruction, chronic kidney disease, and urogenital dysfunction. Case presentation: We report a case of a patient initially diagnosed with endometriosis due to dysmenorrhea and chronic pelvic pain. Despite multiple surgical interventions, symptoms worsened. Misdiagnoses of urinary infections resulted in ineffective treatments. Subsequent testing revealed Mtb, prompting a six-month regimen of four-drug therapy (2HRZE/4HR), leading to significant improvement. Conclusion – take away lesson(s): This case underscores the importance of considering GU-TB in patients with persistent urogenital symptoms, even with initial negative tests. It emphasizes the necessity of a multidisciplinary approach and consideration of uncommon conditions for successful outcomes in complex scenarios. infectious diseases extrapulmonary tuberculosis genitourinary tuberculosis endometriosis Figures Figure 1 1. Introduction Tuberculosis (TB), caused by mycobacteria from the Tuberculosis complex ( M. bovis, M. africanum, M. microti, M. caprae , and M. pinnipedii ), represents a significant global health burden, being the second leading cause of death by infectious agent in 2022, particularly in low- and middle-income countries such as Colombia, as reported by the World Health Organization (WHO) ( 1 ). In 2023, Colombia recorded an incidence of 35.17 cases per 100,000 inhabitants, with Cali being the second city with the highest contribution to this figure, with an incidence of 68.65 cases per 100,000 inhabitants ( 2 ). Extrapulmonary tuberculosis (EP-TB), comprising 15–20% of global cases ( 3 ) and 13.7% in Colombia in 2022 ( 2 ), is associated with risk factors like immunosuppression and chronic diseases ( 3 ). Among these, GU-TB emerges as a challenging clinical entity, representing up to 13% of extrapulmonary cases globally ( 3 ). GU-TB is characterized by nonspecific symptoms including proteinuria, hematuria, abdominal pain, infertility, and menstrual irregularities, alongside signs such like impaired renal function ( 4 ), complicating its diagnosis and potentially leading to severe complications such as renal lesions and chronic renal failure. Despite the limitations in urine culture sensitivity, molecular tests offer better diagnostic performance ( 5 , 6 ). The six-month, four-drug regimen remains effective in such scenarios ( 7 ). It is crucial to raise awareness among healthcare professionals about GU-TB, its accurate diagnosis, and the prevention of severe complications. This case report underscores the importance of considering GU-TB as a differential diagnosis, especially in endemic areas like ours, to enhance early diagnosis and subsequently improve patient’s quality of life. 2. Case presentation A 42-year-old female from Cali, Colombia, with no significant medical history, presented with moderate chronic dysmenorrhea since the age of 32. At 34, a transvaginal ultrasound revealed ovarian enlargements and cysts, leading to pelvic laparoscopy confirming endometriosis. Treatment oral contraceptives, followed by hormonal injections due to adverse effects. Persistent dysmenorrhea and right flank pain led to an abdominal hysterectomy, during which a distal ureteral lesion was discovered, necessitating reimplantation. Post-surgery, pelvic pain persisted, alongside worsening urinary symptoms, misdiagnosed urinary infections and management empirically with antibiotics. Urological evaluation revealed overactive detrusor and bladder abnormalities, right hydronephrosis, ureteral dilation, and severe cortical atrophy, leading to nephrectomy indications. Kidney pathology showed chronic granulomatous inflammation with central necrosis, with negative staining. Over the course of a year, the patient received pelvic floor therapies and pregabalin, which improved urinary symptoms and pelvic pain. Concurrently, gynecology managed endometriosis with leuprolide acetate. Despite the received management, the patient reported three episodes of macroscopic hematuria during prolonged periods of urinary continence, leading to cystoscopies, which showed vesical mucosa with bullous edema, white membranes, and bleeding, with pathology describing the bladder as having chronic inflammation and epithelioid granuloma formation. An abdominal CT scan showed concentric thickening of the bladder walls and post-surgical changes. Suspecting urogenital tuberculosis, bacilloscopy and cultures (Automated MGIT, Lowenstein-Jensen) were requested, which were negative. The case was referred to infectious diseases, where a molecular test for Mtb in urine (GenXpert MTB/RIF) was performed, showing the presence of mycobacteria from the Tuberculosis complex , without resistance to rifampicin. The patient was diagnosed with GU-TB and treated with 2HRZE/4HR for 6 months with good tolerance. A follow-up culture nine months later was negative for Mtb , and the patient showed satisfactory evolution, with no evidence of relapse during 17 months of follow-up ( Fig. 1 ) 3. Discussion GU-TB is the third most frequent form of extrapulmonary TB, following lymphatic and pleural manifestations ( 8 ). Between 2–20% of patients with pulmonary TB may develop urogenital disease via hematogenous dissemination ( 9 ). Due to this, there is typically a long latency period (5 to 40 years), making this diagnosis rare in children ( 10 ). The most common age of presentation is between 50–60 years, with sex preference varying according to different studies ( 7 , 11 ). Risk factors for GU-TB include immunosuppression, malnutrition, chronic kidney and liver disease, substance abuse, and low socioeconomic status ( 13 ). Co-infection with human immunodeficiency virus (HIV), with up to 75% of patients with GU-TB being affected, necessitating routine HIV testing ( 14 ). In our patient’s case, no additional comorbidities were identified beyond residing in an endemic region. Hematogenous dissemination from the pulmonary focus results in renal parenchyma colonization, initially forming cortical, glomerular, and pericapillary lesions. These foci typically heal, leading to a latent period unless immunodeficiency triggers symptomatic miliary systemic TB. Reactivation of renal foci progresses unilaterally, descending through the urinary tract, potentially causing ureteral stenosis, hydronephrosis, and progressive renal damage ( 16 , 17 ). Clinical manifestations of GU-TB encompass a broad spectrum of symptoms, including dysuria, urinary frequency, incontinence, lumbar pain, and hematuria ( 7 ), all present in our patient. Female genital manifestations may include chronic pelvic pain, abnormal vaginal bleeding or discharge, infertility, dyspareunia, menstrual irregularities ( 17 ). Pregnancy outcomes can include live birth, spontaneous abortion, or ectopic pregnancies ( 18 ). Constitutional symptoms of pulmonary TB, such as fever, weight loss, and night sweats, are rare in GU-TB and should raise suspicion of Mtb infection outside the genitourinary tract, including concomitant pulmonary TB ( 19 ). Diagnosing GU-TB is challenging since symptoms often appear in advanced stages, with some cases presenting initially as acute renal failure. No single specific test exists for GU-TB, and detecting the tuberculosis bacillus is not always possible due to the paucibacillary nature. Therefore, a combination of clinical history, imaging, microbiological, molecular, and histopathological tests are needed to gather evidence supporting GU-TB likehood. Certain urine findings, like pyuria, hematuria, acidic urine, and negative cultures, suggest urogenital tuberculosis in up to 93% of patients ( 16 ). While acid-fast bacilli (AFB) stains such as Ziehl-Neelsen (ZN) or auramine stains, are rapid and cost-effective, they have variable sensitivity, ranging from 10–40% ( 17 ). Although useful as initial tests, their low sensitivity limits their efficacy as standalone diagnostic tools. Solid culture media like Lowenstein-Jensen are considered the gold standard for TB diagnosis, with high specificity but moderate sensitivity (65%) ( 20 ). Liquid culture systems, such as the BACTEC MGIT system, offer higher sensitivity and the ability to yield results in about two weeks ( 17 ). Molecular tests, such as real-time Polymerase Chain Reaction (PCR) (e.g., GeneXpert MTB/RIF), provide rapid have and sensitive results. Urine PCR can have a sensitivity of up to 90%, with results available in 24 to 48 hours ( 20 ). This technique is particularly useful in samples with a low bacillary load, where stains and cultures may be negative. Additionally, molecular tests can detect drug resistance, allowing for a more precise therapeutic approach. Radiological findings aid GU-TB diagnosis, the presence of lobular calcifications and signs of papillary necrosis on intravenous urography are suggestive of the disease, while ureteral tuberculosis is characterized by wall thickening and luminal strictures. Bladder tuberculosis manifests with wall thickening and filling defects due to granulomatous material ( 3 ). Cystoscopy with biopsy is a low-morbidity technique that can be performed when there is clinical suspicion of tuberculosis, and urine cultures are negative for bacilli, being more useful in the acute phase. Common findings include local hyperemia, mucosal erosion and ulceration, tubercle formation, and irregularities in the ureteral orifices ( 21 ). Although the diagnosis should be presumptively clinical, up to 50% of patients may have asymptomatic infection ( 22 ). Despite nonspecific manifestations, it is important to consider GU-TB in the differential diagnosis spectrum to avoid treatment delays, complications, and associated morbidity. Our patient’s case presented a diagnostic challenge due to the complexity of her clinical manifestations and the need to rule out multiple gynecological and urological conditions. Although endometriosis was initially suspected, intraoperative evaluation revealed multiple adhesions and a distal ureteral lesion, leading to an abdominal hysterectomy and additional urinary tract procedures. Subsequent urology evaluation showed findings consistent with GU-TB, highlighting the importance of considering this disease in the differential diagnosis of patients with persistent gynecological and urinary symptoms, especially in tuberculosis-endemic areas and even with initially negative microbiological tests. GU-TB cases sensitive to standard anti-tuberculosis therapy respond well to treatment. A randomized controlled trial demonstrated that rifapentine-based regimens with moxifloxacin for four months could offer a therapeutic option as the 12-month TB-free survival rate did not significantly differ from the group receiving the six-month four-drug regimen ( 23 ). Additionally, another non-inferiority study showed that in children with non-severe, drug-sensitive tuberculosis, a 4-month anti-tuberculosis treatment regimen could be non-inferior to the standard 6-month regimen ( 24 ). However, these studies were conducted in patients with exclusively pulmonary TB. More evidence is needed regarding the management of GU-TB. Surgical treatment of GU-TB is essential in cases where pharmacological therapy fails to control the disease or when severe complications arise. Surgery can be both ablative and reconstructive, aiming to unblock the urinary collecting system or improve contracted bladder capacity. Nephrectomy without ureterectomy is recommended in cases of unilateral renal dysfunction, especially after 4 to 6 weeks of initiating pharmacological treatment, which can help prevent relapses, treat hypertension, and avoid abscess formation. Hysterectomy may be necessary in women with extensive genital involvement as part of a comprehensive surgical approach to control the disease and improve the patient’s quality of life ( 7 , 16 , 17 ). The optimal timing for surgery remains controversial, but a delay of several weeks after starting medical treatment is suggested to reduce active inflammation and stabilize lesions ( 16 ). Long-term follow-up of GU-TB is mainly conducted through radiological and clinical findings. Relapses, which can occur in up to 22% of GU-TB cases even after 12 months of therapy, underline the need for prolonged follow-up for at least 10 years due to the possibility of late relapses, with an average of 5 years for their occurrence ( 9 ). 4. Conclusions In summary, urogenital tuberculosis is an important extrapulmonary manifestation of tuberculosis that presents diagnostic and management challenges. Considering this entity in patients with risk factors and nonspecific symptoms is essential to avoid delays in diagnosis and the severe consequences associated. A multidisciplinary evaluation and management are necessary to effectively address this complex disease. Abbreviations - GU-TB Genitourinary tuberculosis - Mtb Mycobacterium tuberculosis - TB Tuberculosis - WHO World Health Organization - EP-TB Extrapulmonary tuberculosis - HIV Human immunodeficiency virus - AFB Acid-fast bacilli - ZN Ziehl-Neelsen - PCR Polymerase Chain Reaction Declarations 5.1. Availability of data and materials: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. 5.2. Ethics approval: Our paper was approved by the Biomedical Research Committee of Fundación Valle del Lili. 5.3. Consent for publication: Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editor of this journal. 5.4. Declaration of Competing Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 5.5. Acknowledgements: The authors would like to extend their gratitude to the Clinical Research Center at Fundación Valle del Lili for their invaluable contributions and support in the completion of this manuscript. 5.6. Authors contributions: NRO and JHS were responsible for obtaining patient consent, gathering clinical information, and, along with SMT, drafted the initial version of the manuscript. JFG participated in the critical review of the intellectual content. All authors contributed, read, and approved the version of the manuscript submitted. 5.7. Funding: none. References World Health Organization. Global Report TB 2022 [Internet]. 2022. Accessed on: March 18, 2024. https://www.who.int/teams/global-tuberculosisprogramme/tb-reports/global-tuberculosis-report-2022 . Instituto Nacional de Salud. Informe de evento Tuberculosis - A período epidemiológico XIII de 2023 [Internet]. 2023. Accessed on: March 18, 2024. https://www.ins.gov.co/buscador-eventos/Informesdeevento/TUBERCULOSIS%20PE%20XIII%202023.pdf . Baykan AH, Sayiner HS, Aydin E, Koc M, Inan I, Erturk SM. Extrapulmonary tuberculosis: an old but resurgent problem. Insights Imaging. 2022;13(1):39. Sharma SK, Mohan A, Kohli M. Extrapulmonary tuberculosis. Expert Rev Respir Med. 2021;15(7):931–48. Green C, Huggett JF, Talbot E, Mwaba P, Reither K, Zumla AI. Rapid diagnosis of tuberculosis through the detection of mycobacterial DNA in urine by nucleic acid amplification methods. Lancet Infect Dis. 2009;9(8):505–11. Pang Y, Shang Y, Lu J, Liang Q, Dong L, Li Y, et al. GeneXpert MTB/RIF assay in the diagnosis of urinary tuberculosis from urine specimens. Sci Rep. 2017;7(1):6181. Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis—epidemiology, pathogenesis and clinical features. Nat Rev Urol. 2019;16(10):573–98. Parra Gordo DML, Tejedor Segura DD, Cayón Somacarrera DS, Iniesta González DC, Paz Calzada DE, Alonso Rodríguez DC. Imaging diagnosis of abdominal and genitourinary tuberculosis: Common and uncommon manifestations. [Internet]. 2023. Accessed on: March 18, 2024. https://piper.espacio-seram.com/index.php/seram/article/view/3851 . Mantica G, Ambrosini F, Riccardi N, Vecchio E, Rigatti L, De Rose AF, et al. Genitourinary tuberculosis: a comprehensive review of a neglected manifestation in low-endemic countries. Antibiotics. 2021;10(11):1399. Lenk S, Schroeder J. Genitourinary tuberculosis. Curr Opin Urol. 2001;11(1):93–6. Merchant S, Bharati A, Merchant N. Tuberculosis of the genitourinary system-urinary tract tuberculosis: renal tuberculosis-part I. Indian J Radiol Imaging. 2013;23(01):46–63. Psihramis KE, Donahoe PK. Primary genitourinary tuberculosis: rapid progression and tissue destruction during treatment. J Urol. 1986;135(5):1033–6. Furin J, Cox H, Pai M, Tuberculosis. Lancet. 2019;393(10181):1642–56. Nzerue C, Drayton J, Oster R, Hewan-Lowe K. Genitourinary tuberculosis in patients with HIV infection: clinical features in an inner-city hospital population. Am J Med Sci. 2000;320(5):299–303. Mert A, Guzelburc V, Guven S. Urinary tuberculosis: still a challenge. World J Urol. 2020;38(11):2693–8. Figueiredo AA, Lucon AM. Urogenital tuberculosis: update and review of 8961 cases from the world literature. Rev Urol. 2008;10(3):207–17. Nieto-Ríos JF, Zea-Lopera J, Sánchez-López S, Barrientos-Henao S, Bello-Márquez DC, Vélez-Hoyos A, et al. Tuberculosis urogenital en un paciente con falla renal, estado del arte. Iatreia. 2020;33(4):360–9. Grace GA, Devaleenal DB, Natrajan M. Genital tuberculosis in females. Indian J Med Res. 2017;145(4):425–36. Wise GJ, Marella VK. Genitourinary manifestations of tuberculosis. Urol Clin North Am. 2003;30(1):111–21. Hemal AK, Gupta NP, Rajeev TP, Kumar R, Dar L, Seth P. Polymerase chain reaction in clinically suspected genitourinary tuberculosis: comparison with intravenous urography, bladder biopsy, and urine acid fast bacilli culture. Urology. 2000;56(4):570–4. Shapiro AL, Viter VI. Tsitoskopiia i éndovezikal'naia biopsiia pri tuberkuleze pochki [Cystoscopy and endovesical biopsy in renal tuberculosis]. Urol Nefrol (Mosk). 1989 Jan-Feb;(1):12 – 5. Singh V, Kumar M, Pavan Kumar SK, Jain M. All in one, a rare case presentation of genitourinary tuberculosis. Afr J Urol. 2021;27(1):62. Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384(18):1705–18. Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, et al. Shorter treatment for nonsevere tuberculosis in African and Indian children. N Engl J Med. 2022;386(10):911–22. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 10 Jul, 2024 Reviews received at journal 09 Jul, 2024 Reviewers agreed at journal 20 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviews received at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers invited by journal 06 Jun, 2024 Editor invited by journal 06 Jun, 2024 Editor assigned by journal 05 Jun, 2024 Submission checks completed at journal 05 Jun, 2024 First submitted to journal 05 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Introduction","content":"\u003cp\u003eTuberculosis (TB), caused by mycobacteria from the \u003cem\u003eTuberculosis complex\u003c/em\u003e (\u003cem\u003eM. bovis, M. africanum, M. microti, M. caprae\u003c/em\u003e, and \u003cem\u003eM. pinnipedii\u003c/em\u003e), represents a significant global health burden, being the second leading cause of death by infectious agent in 2022, particularly in low- and middle-income countries such as Colombia, as reported by the World Health Organization (WHO) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 2023, Colombia recorded an incidence of 35.17 cases per 100,000 inhabitants, with Cali being the second city with the highest contribution to this figure, with an incidence of 68.65 cases per 100,000 inhabitants (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eExtrapulmonary tuberculosis (EP-TB), comprising 15\u0026ndash;20% of global cases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) and 13.7% in Colombia in 2022 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), is associated with risk factors like immunosuppression and chronic diseases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Among these, GU-TB emerges as a challenging clinical entity, representing up to 13% of extrapulmonary cases globally (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). GU-TB is characterized by nonspecific symptoms including proteinuria, hematuria, abdominal pain, infertility, and menstrual irregularities, alongside signs such like impaired renal function (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), complicating its diagnosis and potentially leading to severe complications such as renal lesions and chronic renal failure.\u003c/p\u003e \u003cp\u003eDespite the limitations in urine culture sensitivity, molecular tests offer better diagnostic performance (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The six-month, four-drug regimen remains effective in such scenarios (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). It is crucial to raise awareness among healthcare professionals about GU-TB, its accurate diagnosis, and the prevention of severe complications. This case report underscores the importance of considering GU-TB as a differential diagnosis, especially in endemic areas like ours, to enhance early diagnosis and subsequently improve patient\u0026rsquo;s quality of life.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eA 42-year-old female from Cali, Colombia, with no significant medical history, presented with moderate chronic dysmenorrhea since the age of 32. At 34, a transvaginal ultrasound revealed ovarian enlargements and cysts, leading to pelvic laparoscopy confirming endometriosis. Treatment oral contraceptives, followed by hormonal injections due to adverse effects.\u003c/p\u003e \u003cp\u003ePersistent dysmenorrhea and right flank pain led to an abdominal hysterectomy, during which a distal ureteral lesion was discovered, necessitating reimplantation. Post-surgery, pelvic pain persisted, alongside worsening urinary symptoms, misdiagnosed urinary infections and management empirically with antibiotics. Urological evaluation revealed overactive detrusor and bladder abnormalities, right hydronephrosis, ureteral dilation, and severe cortical atrophy, leading to nephrectomy indications. Kidney pathology showed chronic granulomatous inflammation with central necrosis, with negative staining. Over the course of a year, the patient received pelvic floor therapies and pregabalin, which improved urinary symptoms and pelvic pain. Concurrently, gynecology managed endometriosis with leuprolide acetate.\u003c/p\u003e \u003cp\u003eDespite the received management, the patient reported three episodes of macroscopic hematuria during prolonged periods of urinary continence, leading to cystoscopies, which showed vesical mucosa with bullous edema, white membranes, and bleeding, with pathology describing the bladder as having chronic inflammation and epithelioid granuloma formation. An abdominal CT scan showed concentric thickening of the bladder walls and post-surgical changes. Suspecting urogenital tuberculosis, bacilloscopy and cultures (Automated MGIT, Lowenstein-Jensen) were requested, which were negative.\u003c/p\u003e \u003cp\u003eThe case was referred to infectious diseases, where a molecular test for \u003cem\u003eMtb\u003c/em\u003e in urine (GenXpert MTB/RIF) was performed, showing the presence of mycobacteria from the \u003cem\u003eTuberculosis complex\u003c/em\u003e, without resistance to rifampicin. The patient was diagnosed with GU-TB and treated with 2HRZE/4HR for 6 months with good tolerance. A follow-up culture nine months later was negative for \u003cem\u003eMtb\u003c/em\u003e, and the patient showed satisfactory evolution, with no evidence of relapse during 17 months of follow-up \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eGU-TB is the third most frequent form of extrapulmonary TB, following lymphatic and pleural manifestations (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Between 2\u0026ndash;20% of patients with pulmonary TB may develop urogenital disease via hematogenous dissemination (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Due to this, there is typically a long latency period (5 to 40 years), making this diagnosis rare in children (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The most common age of presentation is between 50\u0026ndash;60 years, with sex preference varying according to different studies (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRisk factors for GU-TB include immunosuppression, malnutrition, chronic kidney and liver disease, substance abuse, and low socioeconomic status (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Co-infection with human immunodeficiency virus (HIV), with up to 75% of patients with GU-TB being affected, necessitating routine HIV testing (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In our patient\u0026rsquo;s case, no additional comorbidities were identified beyond residing in an endemic region.\u003c/p\u003e \u003cp\u003eHematogenous dissemination from the pulmonary focus results in renal parenchyma colonization, initially forming cortical, glomerular, and pericapillary lesions. These foci typically heal, leading to a latent period unless immunodeficiency triggers symptomatic miliary systemic TB. Reactivation of renal foci progresses unilaterally, descending through the urinary tract, potentially causing ureteral stenosis, hydronephrosis, and progressive renal damage (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eClinical manifestations of GU-TB encompass a broad spectrum of symptoms, including dysuria, urinary frequency, incontinence, lumbar pain, and hematuria (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), all present in our patient. Female genital manifestations may include chronic pelvic pain, abnormal vaginal bleeding or discharge, infertility, dyspareunia, menstrual irregularities (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Pregnancy outcomes can include live birth, spontaneous abortion, or ectopic pregnancies (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Constitutional symptoms of pulmonary TB, such as fever, weight loss, and night sweats, are rare in GU-TB and should raise suspicion of \u003cem\u003eMtb\u003c/em\u003e infection outside the genitourinary tract, including concomitant pulmonary TB (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDiagnosing GU-TB is challenging since symptoms often appear in advanced stages, with some cases presenting initially as acute renal failure. No single specific test exists for GU-TB, and detecting the tuberculosis bacillus is not always possible due to the paucibacillary nature. Therefore, a combination of clinical history, imaging, microbiological, molecular, and histopathological tests are needed to gather evidence supporting GU-TB likehood. Certain urine findings, like pyuria, hematuria, acidic urine, and negative cultures, suggest urogenital tuberculosis in up to 93% of patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile acid-fast bacilli (AFB) stains such as Ziehl-Neelsen (ZN) or auramine stains, are rapid and cost-effective, they have variable sensitivity, ranging from 10\u0026ndash;40% (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Although useful as initial tests, their low sensitivity limits their efficacy as standalone diagnostic tools. Solid culture media like Lowenstein-Jensen are considered the gold standard for TB diagnosis, with high specificity but moderate sensitivity (65%) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Liquid culture systems, such as the BACTEC MGIT system, offer higher sensitivity and the ability to yield results in about two weeks (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMolecular tests, such as real-time Polymerase Chain Reaction (PCR) (e.g., GeneXpert MTB/RIF), provide rapid have and sensitive results. Urine PCR can have a sensitivity of up to 90%, with results available in 24 to 48 hours (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). This technique is particularly useful in samples with a low bacillary load, where stains and cultures may be negative. Additionally, molecular tests can detect drug resistance, allowing for a more precise therapeutic approach.\u003c/p\u003e \u003cp\u003eRadiological findings aid GU-TB diagnosis, the presence of lobular calcifications and signs of papillary necrosis on intravenous urography are suggestive of the disease, while ureteral tuberculosis is characterized by wall thickening and luminal strictures. Bladder tuberculosis manifests with wall thickening and filling defects due to granulomatous material (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Cystoscopy with biopsy is a low-morbidity technique that can be performed when there is clinical suspicion of tuberculosis, and urine cultures are negative for bacilli, being more useful in the acute phase. Common findings include local hyperemia, mucosal erosion and ulceration, tubercle formation, and irregularities in the ureteral orifices (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough the diagnosis should be presumptively clinical, up to 50% of patients may have asymptomatic infection (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Despite nonspecific manifestations, it is important to consider GU-TB in the differential diagnosis spectrum to avoid treatment delays, complications, and associated morbidity. Our patient\u0026rsquo;s case presented a diagnostic challenge due to the complexity of her clinical manifestations and the need to rule out multiple gynecological and urological conditions. Although endometriosis was initially suspected, intraoperative evaluation revealed multiple adhesions and a distal ureteral lesion, leading to an abdominal hysterectomy and additional urinary tract procedures. Subsequent urology evaluation showed findings consistent with GU-TB, highlighting the importance of considering this disease in the differential diagnosis of patients with persistent gynecological and urinary symptoms, especially in tuberculosis-endemic areas and even with initially negative microbiological tests.\u003c/p\u003e \u003cp\u003eGU-TB cases sensitive to standard anti-tuberculosis therapy respond well to treatment. A randomized controlled trial demonstrated that rifapentine-based regimens with moxifloxacin for four months could offer a therapeutic option as the 12-month TB-free survival rate did not significantly differ from the group receiving the six-month four-drug regimen (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Additionally, another non-inferiority study showed that in children with non-severe, drug-sensitive tuberculosis, a 4-month anti-tuberculosis treatment regimen could be non-inferior to the standard 6-month regimen (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). However, these studies were conducted in patients with exclusively pulmonary TB. More evidence is needed regarding the management of GU-TB.\u003c/p\u003e \u003cp\u003eSurgical treatment of GU-TB is essential in cases where pharmacological therapy fails to control the disease or when severe complications arise. Surgery can be both ablative and reconstructive, aiming to unblock the urinary collecting system or improve contracted bladder capacity. Nephrectomy without ureterectomy is recommended in cases of unilateral renal dysfunction, especially after 4 to 6 weeks of initiating pharmacological treatment, which can help prevent relapses, treat hypertension, and avoid abscess formation. Hysterectomy may be necessary in women with extensive genital involvement as part of a comprehensive surgical approach to control the disease and improve the patient\u0026rsquo;s quality of life (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The optimal timing for surgery remains controversial, but a delay of several weeks after starting medical treatment is suggested to reduce active inflammation and stabilize lesions (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLong-term follow-up of GU-TB is mainly conducted through radiological and clinical findings. Relapses, which can occur in up to 22% of GU-TB cases even after 12 months of therapy, underline the need for prolonged follow-up for at least 10 years due to the possibility of late relapses, with an average of 5 years for their occurrence (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e"},{"header":"4. Conclusions","content":"\u003cp\u003eIn summary, urogenital tuberculosis is an important extrapulmonary manifestation of tuberculosis that presents diagnostic and management challenges. Considering this entity in patients with risk factors and nonspecific symptoms is essential to avoid delays in diagnosis and the severe consequences associated. A multidisciplinary evaluation and management are necessary to effectively address this complex disease.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- GU-TB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGenitourinary tuberculosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- Mtb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMycobacterium tuberculosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- TB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTuberculosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- WHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- EP-TB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExtrapulmonary tuberculosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- HIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- AFB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcid-fast bacilli\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- ZN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eZiehl-Neelsen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e- PCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolymerase Chain Reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e5.1. Availability of data and materials:\u0026nbsp;\u003c/strong\u003eData sharing is not applicable to this article as no datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.2. Ethics approval:\u0026nbsp;\u003c/strong\u003eOur paper was approved by the Biomedical Research Committee of Fundaci\u0026oacute;n Valle del Lili.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.3. Consent for publication:\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editor of this journal. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.4. Declaration of Competing Interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.5. Acknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors would like to extend their gratitude to the Clinical Research Center at Fundaci\u0026oacute;n Valle del Lili for their invaluable contributions and support in the completion of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.6. Authors contributions:\u0026nbsp;\u003c/strong\u003eNRO and JHS were responsible for obtaining patient consent, gathering clinical information, and, along with SMT, drafted the initial version of the manuscript. JFG participated in the critical review of the intellectual content. All authors contributed, read, and approved the version of the manuscript submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.7. Funding:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. Global Report TB 2022 [Internet]. 2022. Accessed on: March 18, 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/teams/global-tuberculosisprogramme/tb-reports/global-tuberculosis-report-2022\u003c/span\u003e\u003cspan address=\"https://www.who.int/teams/global-tuberculosisprogramme/tb-reports/global-tuberculosis-report-2022\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInstituto Nacional de Salud. Informe de evento Tuberculosis - A per\u0026iacute;odo epidemiol\u0026oacute;gico XIII de 2023 [Internet]. 2023. 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Indian J Radiol Imaging. 2013;23(01):46\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePsihramis KE, Donahoe PK. Primary genitourinary tuberculosis: rapid progression and tissue destruction during treatment. J Urol. 1986;135(5):1033\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFurin J, Cox H, Pai M, Tuberculosis. Lancet. 2019;393(10181):1642\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNzerue C, Drayton J, Oster R, Hewan-Lowe K. Genitourinary tuberculosis in patients with HIV infection: clinical features in an inner-city hospital population. Am J Med Sci. 2000;320(5):299\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMert A, Guzelburc V, Guven S. Urinary tuberculosis: still a challenge. World J Urol. 2020;38(11):2693\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFigueiredo AA, Lucon AM. Urogenital tuberculosis: update and review of 8961 cases from the world literature. Rev Urol. 2008;10(3):207\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNieto-R\u0026iacute;os JF, Zea-Lopera J, S\u0026aacute;nchez-L\u0026oacute;pez S, Barrientos-Henao S, Bello-M\u0026aacute;rquez DC, V\u0026eacute;lez-Hoyos A, et al. Tuberculosis urogenital en un paciente con falla renal, estado del arte. Iatreia. 2020;33(4):360\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrace GA, Devaleenal DB, Natrajan M. Genital tuberculosis in females. Indian J Med Res. 2017;145(4):425\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWise GJ, Marella VK. Genitourinary manifestations of tuberculosis. Urol Clin North Am. 2003;30(1):111\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHemal AK, Gupta NP, Rajeev TP, Kumar R, Dar L, Seth P. Polymerase chain reaction in clinically suspected genitourinary tuberculosis: comparison with intravenous urography, bladder biopsy, and urine acid fast bacilli culture. Urology. 2000;56(4):570\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShapiro AL, Viter VI. Tsitoskopiia i \u0026eacute;ndovezikal'naia biopsiia pri tuberkuleze pochki [Cystoscopy and endovesical biopsy in renal tuberculosis]. Urol Nefrol (Mosk). 1989 Jan-Feb;(1):12\u0026thinsp;\u0026ndash;\u0026thinsp;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh V, Kumar M, Pavan Kumar SK, Jain M. All in one, a rare case presentation of genitourinary tuberculosis. Afr J Urol. 2021;27(1):62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384(18):1705\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, et al. Shorter treatment for nonsevere tuberculosis in African and Indian children. N Engl J Med. 2022;386(10):911\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"infectious diseases, extrapulmonary tuberculosis, genitourinary tuberculosis, endometriosis","lastPublishedDoi":"10.21203/rs.3.rs-4535237/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4535237/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Genitourinary tuberculosis (GU-TB), an extrapulmonary manifestation of \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e \u003cem\u003e(Mtb)\u003c/em\u003e infection, often presents insidiously, \u0026nbsp;posing diagnostic challenges and leading to progressive tissue destruction, chronic kidney disease, and urogenital dysfunction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e We report a case of a patient initially diagnosed with endometriosis due to dysmenorrhea and chronic pelvic pain. \u0026nbsp;Despite multiple surgical interventions, symptoms \u0026nbsp;worsened. Misdiagnoses of urinary infections resulted in ineffective treatments. Subsequent testing revealed\u003cstrong\u003e \u003c/strong\u003e\u003cem\u003eMtb, \u003c/em\u003eprompting a six-month regimen of four-drug therapy (2HRZE/4HR), leading to \u0026nbsp;significant improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion – take away lesson(s):\u003c/strong\u003e This case underscores the importance of considering GU-TB in patients with persistent urogenital symptoms, even with initial negative tests. It emphasizes the necessity of a multidisciplinary approach and consideration of uncommon conditions for successful outcomes in complex scenarios.\u003c/p\u003e","manuscriptTitle":"Navigating genitourinary tuberculosis: lessons from a 2023 case","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-25 20:16:01","doi":"10.21203/rs.3.rs-4535237/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-10T04:57:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-09T07:53:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"14173892870414361884895546513224428271","date":"2024-06-20T06:12:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194751661680858570672329767980965401144","date":"2024-06-17T17:59:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-17T17:20:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190836453161525783571938800307675517813","date":"2024-06-17T14:52:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-06T13:04:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-06T12:09:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-05T23:59:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-05T23:58:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2024-06-05T15:46:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d866610d-ec49-4b92-a660-bcf2c132a56d","owner":[],"postedDate":"June 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-07-16T06:37:10+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-25 20:16:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4535237","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4535237","identity":"rs-4535237","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}