Serologic and urinary characteristics of laboratory-confirmed genitourinary tuberculosis at a tertiary hospital in the Philippines.

BACKGROUND: Genitourinary tuberculosis (GUTB) is known to cause high rates of structural organ damage, however, literature on its biochemical manifestations is limited. Additionally, local studies in the Philippine setting, where cases are rampant, are few and dated. This study aimed to determine the serologic and urinary profile of patients with GUTB admitted at a tertiary hospital within January 2009 to March 2020 and their association with short-term outcomes. METHODS: This retrospective study included 112 patients with laboratory-confirmed GUTB (i.e., positivity in acid-fast smear, polymerase chain reaction, culture, or histology). Demographic data, clinical characteristics, laboratory and radiologic findings, histopathology reports, treatment, and short-term outcomes were recorded. RESULTS: Bladder (54.5%) and kidney (36.4%) were the most affected organs. The male:female ratio was 1:1.15, and the mean age was 35.79 ± 18.29 years. Weakness (14.29%) was the most common chief complaint. A majority presented with anemia (83.04%), while several had leukocytosis (41.96%) and thrombocytosis (26.79%). Hypoalbuminemia (58.10%), impairment of renal function (36.94%), and electrolyte abnormalities such as hyponatremia (50.93%), hypercalcemia (20.19%), and hypokalemia (21.82%) were common. Proteinuria (67.96%) and pyuria (67.96%) were the most frequent abnormal findings, followed by hematuria (51.46%), acidic urine (45.63%) and low specific gravity (31.07%). Age, leukocytosis, and the need for pressors were all significantly associated with mortality (p values of <0.001, 0.010, and <0.001, respectively). CONCLUSIONS: The young age at presentation with severe clinical and laboratory manifestations may reflect local epidemiology as TB continues to be widespread in the country. Apart from the more commonly cited abnormalities in literature, multiple electrolyte imbalances and urinary concentration defects were also observed in many cases, possibly indicating tubulointerstitial involvement-a complication increasingly mentioned in case reports. As several patient characteristics were found to be associated with the high mortality rates observed in the study, further research is recommended to explore predictive modeling.

A long journey to be diagnosed as a case of tuberculous cystitis: A Bangladeshi case report and review of literatures.

Urinary bladder tuberculosis (UB-TB) is one of the gravest public health issues of renal TB, and it is diagnosed with <50% of urogenital TB. Unsatisfactory and delayed diagnosis with imprudent medications for bladder TB frequently resulted in several urinary and complications, including contraction of the UB. The objectives of this research were to build awareness among medical professionals and subsequently minimize the sufferings of patients. This was a case report-based study regarding UB-TB. All routine tests for cystitis were conducted. In addition, 24-h urine sample for TB identification, including a polymerase chain reaction test, was performed. Twenty-four hours of urine sample revealed confirmatory findings of TB. The patient had responded well with the national TB guideline-designated medication. Recurrent cystitis had a higher possibility of tuberculous origin. Medical doctors must rethink when a patient visited multiple times for cystitis for the etiology of the disease.

Is sterile pyuria another minor diagnostic criterion in urinary tuberculosis?

INTRODUCTION: Composite reference standard (CRS) is used for diagnosis of urinary tract tuberculosis (UTB). We examined if addition of a new 'component test' as minor criterion in the form of SP could improve the yield. METHODS: We identified patients admitted with a diagnosis of UTB from January 2009 to February 2016 from our patient database. We performed the validation of addition of a new 'component' "sterile pyuria" to the existing basic CRS. RESULTS: SP was seen in 50 patients (65.7%). Forty (52.6%) of these patients had one major criterion positive and 10 (13.1%) were diagnosed based on minor criteria. If SP was added as a minor criterion, an additional 8 (9.2%) patients would have been diagnosed based on minor criteria alone without the need for a histopathology. CONCLUSIONS: SP could improve the diagnostic yield of existing CRS by 8% with a 70% decrease in reliance on histopathology for diagnosis.

The incidence of subclinical forms of urogenital tuberculosis in patients with pulmonary tuberculosis.

The aim of our study was to determine whether patients with pulmonary tuberculosis may have subclinical forms of urogenital tuberculosis. Between 2011 and 2012, a prospective study was conducted. Basic demographic parameters were recorded and the following investigations were performed: direct bacilloscopy of sputum, evaluation of affected lung fields and presence of cavities on chest X-ray, Mantoux tuberculin skin test II, and interferon gamma release assay. Culture and molecular methods for Mycobacterium tuberculosis in urine were performed. In cases with a positive urine test, an ultrasound examination, computed tomography scan of the abdomen, and endoscopy of the urinary tract were performed. A total of 102 patients (75 men and 27 women) were included in the study, with a median age of 46.8 years. Subclinical forms of urogenital TB were detected in 7 patients; 5 by molecular methods, 1 by urine culture, and 1 with both methods The presence of subclinical forms of genitourinary TB was found in 4 patients without and 3 patients with findings on imaging methods corresponding to TB. A significant number of patients with pulmonary tuberculosis may simultaneously have subclinical forms of urogenital TB.

Diagnostic accuracy of nucleic acid amplification tests (NAATs) in urine for genitourinary tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Genitourinary tuberculosis is the third most common form of extrapulmonary tuberculosis. Diagnosis is difficult because of unspecific clinical manifestations and low accuracy of conventional tests. Unfortunately, the delayed diagnosis impacts the urinary tract severely. Nucleic acid amplification tests yield fast results, and among these, new technologies can also detect drug resistance. There is lack of consensus regarding the use of these tests in genitourinary tuberculosis; we therefore aimed to assess the accuracy of nucleic acid amplification tests in the diagnosis of genitourinary tuberculosis and to evaluate the heterogeneity between studies. METHODS: We did a systematic review and meta-analysis of research articles comparing the accuracy of a reference standard and a nucleic acid amplification test for diagnosis of urinary tract tuberculosis. We searched Medline, EMBASE, Web of Science, LILACS, Cochrane Library, and Scopus for articles published between Jan 1, 1990, and Apr 14, 2016. Two investigators identified eligible articles and extracted data for individual study sites. We analyzed data in groups with the same index test. Then, we generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when studies were not heterogeneous. RESULTS: We identified eleven relevant studies from ten articles, giving information on PCR, LCR and Xpert MTB/RIF tests. All PCR studies were "in-house" tests, with different gene targets and had several quality concerns therefore we did not proceed with a pooled analysis. Only one study used LCR. Xpert studies were of good quality and not heterogeneous, pooled sensitivity was 0·87 (0·66-0·96) and specificity was 0·91 (0·84-0·95). CONCLUSION: PCR studies were highly heterogeneous. Among Xpert MTB/RIF studies, specificity was favorable with an acceptable confidence interval, however new studies can update meta-analysis and get more precise estimates. Further high-quality studies are urgently needed to improve diagnosis of genitourinary tuberculosis. PROTOCOL REGISTRATION: PROSPERO CRD42016039020.

Growth of mycobacteria in urine determined by isothermal microcalorimetry: implications for urogenital tuberculosis and other mycobacterial infections.

OBJECTIVE: To overcome the limitations of current urine-based diagnostic assays of urogenital tuberculosis, we used isothermal microcalorimetry to detect the metabolic activity of Mycobacterium tuberculosis and other commonly neglected pathogenic mycobacteria in urine and accurately determine their growth parameters. METHODS: A microcalorimeter equipped with 48 channels was used. Detection was accomplished, and growth was monitored for 4 different Mycobacterium species in sterilized and modified urine at 37 °C by measuring metabolic heat flow (µW = µJ/s) as a function of time. These strains were M. smegmatis, M. phlei, M. kansasii, and M. tuberculosis. The data were integrated to perform curve fitting and extract the growth parameter from the raw data. RESULTS: In sterilized urine, M. smegmatis showed the fastest growth rate (0.089 ± 0.017 [h(-1)]), followed by M. phlei (0.072 ± 0.016 [h(-1)]) and M. kansasii (0.007 ± 0.001 [h(-1)]). No growth of M. tuberculosis was detected in sterilized urine. However, in serum-supplemented urine, growth of M. tuberculosis was observed within 3 weeks at a growth rate of 0.008 ± 0.001 [h(-1)]. Biofilm formation was enhanced in the serum supplemented urine. CONCLUSION: Isothermal microcalorimetry allows rapid and accurate detection of mycobacterial growth in urine. Given the absence of data on the mycobacterial growth in urine, isothermal microcalorimetry could be used to unravel key aspects of Mycobacterium physiology in the urinary tract and potentially contribute to improvement in the diagnosis and treatment of urogenital tuberculosis.

Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment.

OBJECTIVE: • To report a late bacille Calmette-Guérin (BCG) complication previously not described in the literature. PATIENTS AND METHODS: • We reviewed our database with 858 patients treated with BCG from 1986 to 2008 and identified 13 male patients (1.8% of all male patients) who had a large tuberculous-like bladder ulcer. RESULTS: • All patients had high-grade tumours and seven had tumours invading lamina propria before BCG treatment. A solitary ulceration or inflammatory lesion, 10-50 mm in diameter, was seen at routine follow-up cystoscopy 2-34 months (median 8 months) after the first instillation. Significantly more patients had been treated with BCG-RIVM than with BCG-Tice (10/320 vs. three of 454, P < 0.01). BCG was cultured from urine 3-34 months (median 14 months) after the last instillation. • So far, eight patients have been successfully treated with rifampicin and isoniazid. Nine patients are still tumour-free 15-66 months (median 44 months) after the last transurethral resection before BCG treatment. • Another three patients had one to two non-invasive recurrences. One patient had an invasive recurrence and underwent cystectomy. The present study is limited by biases associated with its retrospective design. CONCLUSIONS: • This is the first report on persisting BCG infections with large inflammatory lesions in the bladder. Treatment is effective and the oncological outcome is good. • Mycobacterial cultures of the urine should be performed in BCG-patients with unclear inflammatory lesions in the bladder since a delayed diagnosis of a persistent BCG infection could result in a permanently reduced bladder capacity. • Large studies are warranted to study differences in efficacy and side-effects between different BCG strains.

[Isolation and identification of Mycobacterium tuberculosis from the urine samples by conventional and molecular methods]. / Konvansiyonel ve moleküler yöntemler ile idrar örneklerinden Mycobacterium tuberculosis izolasyonu ve tanimlanmasi.

Genitourinary tuberculosis presents a challenge in diagnosis and treatment due to variations in clinical and radiological signs, insufficient patient history and difficulty in the isolation of the bacilli. The aim of this study was to isolate and identify Mycobacterium tuberculosis from the urine samples obtained from patients with suspected urinary tuberculosis admitted to our hospital by using Ehrlich-Ziehl-Neelsen (EZN), culture and polymerase chain reaction-restriction analysis (PCR-RFLP) methods. A total of 1004 urine samples collected from 437 patients who were admitted to our hospital between January 2004-July 2006, were inoculated on Löwenstein-Jensen (LJ) and/or BACTEC 12B (Becton Dickinson, USA) after decontamination and, direct preparations stained with EZN method were evaluated microscopically. M. tuberculosis complex (MTC) and mycobacteria other than tuberculosis (MOTT) were differentiated by nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) test and the susceptibility testing for the MTC strains to primary antituberculosis drugs were performed by BACTEC 460 TB (Becton Dickinson, USA) system. PCR-RFLP method was performed for the identification of Mycobacterium spp. Twenty-two (5%) patients have yielded positive results by at least one of the conventional methods (EZN, LJ and/or BACTEC). Fifteen samples were positive for acido-resistant bacilli (ARB) by EZN method, and 17 samples were positive for mycobacterial growth in the cultures. Ten of 22 patients were found positive by both of the methods, while seven were culture positive but ARB negative and five were culture negative but ARB positive. These five patients received BCG treatment because of the presence of bladder tumor. Twelve (70.5%) of 17 strains isolated from culture were identified as MTC, while five (29.4%) were identified as M. fortuitum. Of 12 MTC isolates, eight (66.7%) were found susceptible to all of the antituberculosis agents, while one was found resistant to isoniazide (INH) and ethambutole (ETB), one was resistant to INH and rifampicin (RIF), and two were resistant to only INH. It is concluded that, in order to identify mycobacteria and to perform antituberculous susceptibility tests, cultivation of mycobacteria is a prerequisite.

[Sensitivity of PCR method for detection of mycobacteria tuberculosis in patients with lung tuberculosis].

Both hospitalized patients and outpatient clinic patients at the National Centre of Tuberculosis and Lung Diseases of Georgia have been investigated. The group of patients with the tuberculosis of urogenital system, has been studied (newly detected cases), 70 cases in total. The examination of the urine was carried out by the Polymerase Chain Reaction (PCR) method in order to detect Kochi bacillus and by three-time bacterioscopy of urine on acid resistant bacterium. Mycobacterium tuberculosis in urine has been detected in 57 (81,43%) patients by PCR method, and by urine bacterioscopy acid fast bacilli (AFB)(+) in 36 (51,43%) patients. 50 hospitalized patients were examined as a separate group. They had the tuberculosis of lungs and insignificant pathological changes in urogenital system. Among them there was active bacillus secretion in 45 cases by phlegm bacterioscopy AFB(+). Out of 50 patients the mycobacterium tuberculosis in urine was detected in 30 (60%) cases by PCR method. It should be mentioned that according to the urine two-time bacterioscopy, carried out on 50 patients, has not been detected AFB(-) bacillus secretion. It may be concluded that the PCR method is advantageous in detecting of Kochi bacillus in urine. Introduction of this method in medical practice will give us the possibility to determine the risk-group for development of tubercular changes in urinary system associated with lung tuberculosis, in order to control such patients and to carry out the adequate urological examinations.

[Detection of mycobacteria tuberculosis in patients with urogenital tuberculosis by PCR method].

The study was carried out in hospital patients as well as in outpatients at the National Centre of Tuberculosis and Lung Diseases of Georgia (2002-2004). The group consisting of 32 patients with tuberculosis of urogenital system has been studied (newly detected forms). Except clinical laboratory, culture and X-ray contrast methods, two additional methods were used in testing of this group of patients. The examination of their urine, at the same time, was carried out by the Polymerase Chain Reaction method in order to detect Kochi bacillus and by three-time bacterioscopy of urine for acid resistant bacteria. Mycobacterium tuberculosis in urine has been detected in 26 (81,25%) patients by PCR method, and by urine bacterioscopy--acid fast bacilli (AFB+) in 18 (56,25%) patients. The histo-morphological investigation of specimens obtained by surgery confirmed the TB diagnosis in all patients. This study on patients suspected of Tuberculosis of genital-urinary system gives us an opportunity to update the diagnostic algorithm by including the modern molecular methods. This algorithm will help in timely detection of Tuberculosis, in selection of adequate therapy and in prevention of the further progression of the disease.

[Unexpected complication in an elderly lady suffering from rheumatoid arthritis]. / Unerwartete Komplikation bei einer älteren Dame mit chronischer Polyarthritis.

A 66-year old female suffering from rheumatoid arthritis was treated with methotrexate and intra-articular steroid injections. She had gone through pulmonary tuberculosis at the age of 2 years, also, surgery had been performed 2 years ago because of perforated sigmoid diverticulitis. The patient now presented with episodes of abdominal pain and diarrhea as well as occasional night sweats. Laboratory investigation (normal BSR, CRP and white blood cell counts) did not indicate the presence of an inflammatory process, such as reoccurrence of diverticulitis. However, leukocyturia was repetitively found in this patient with the conventional urine culture yielding no significant bacterial growth. Further urine investigation did not indicate infection with Chlamydia trachomatis or Neisseria gonorrhoeae. Ziehl Neelson stains of morning urinary samples did not show acid-fast rods, however, Mycobacterium tuberculosis was finally isolated by culture. Thus, urogenital tuberculosis was finally diagnosed in this patient. Infection, hematogenic dissemination, and spontaneous remission of pulmonary tuberculosis had occurred more than 60 years ago. After a long latent period, reactivation of tuberculosis happened during drug-induced immunosuppression. The patient was successfully treated with an anti-tuberculosis triple-drug therapy during 2 months followed by a double-drug therapy during 4 months.

[A severe form of urinary tuberculosis in children]. / Forme grave de la tuberculose urinaire chez l'enfant.

Urinary tuberculosis is a rare disease in children. It poses major diagnostic problems because of clinical symptoms, which are often atypical and misleading. It causes serious lesions which are often multifocal and extensive, requiring complex surgical excision and urinary tract reconstruction. Prevention of this disease is based on generalized vaccination with BCG and adequate treatment of pulmonary tuberculosis. The authors report a case of urinary tuberculosis in a fourteen-year-old child who presented episodes of cystitis and hematuria refractory to treatment. The diagnosis, confirmed by the positive test for AFB in the urine was established late, at the stage of silent kidney and scleroatrophic bladder. The patient was treated with antituberculous chemotherapy (Isoniazid; Rifampicin, PZA) and nephro-ureterectomy with augmentation enterocystoplasty.

Rapid identification of Mycobacterium tuberculosis complex on urine samples by Gen-Probe amplification test.

The aim of the study was to evaluate the applicability to urine samples of the Amplified Mycobacterium tuberculosis Direct Detection Test (AMTD), which is currently used to identify this organism in respiratory specimens within a few hours. The study was performed on 95 patients, comprising 35 subjects with a high index of suspicion for active tuberculosis of the urinary tract and 60 subjects with evidence of non-mycobacterial disease. One urine specimen from each subject was examined by microscopy, culture and AMTD. AMTD was positive in 38 specimens and negative in 57. Assuming culture as the reference standard, the sensitivity, specificity, positive predictive value and negative predictive value of AMTD were 100%, 91.93%, 86.84% and 100%, respectively. Reassessing the discrepancies between AMTD and culture by review of patients' charts, the sensitivity, specificity, positive predictive value and negative predictive value of AMTD were 100%, 93.44%, 89.47% and 100%. The results of the study as well as the characteristics of AMTD encourage its use for the rapid recognition of urinary tract tuberculosis, although its findings should be interpreted cautiously when the clinical picture is not consistent with an active tuberculosis.

[Organization of early diagnosis of urinary tract tuberculosis at general medical institutions]. / Organizatsiia rannego vyiavleniia bol'nykh tuberkulezom mochevykh organov v uchrezhdeniiakh obshchei lechebnoi seti.

Out-patient records of 1006 patients representing urologic tuberculosis risk groups and those of 104 persons never treated for urologic diseases before were analysed. Subjects with multiple and long-term aggravations of a urologic process and persistent pyuria were at higher risk for urinary tuberculosis. This group of patients made up 20-25% of those registered as having nonspecific diseases of the urinary system. A high risk group should also include patients who are observed and treated for different nonurologic conditions. At the same time their clinical urinalyses indicate stable abnormalities, including leukocyturia, albuminuria and hematuria.

[The osmolarity of the blood and urine in patients with tuberculosis of the urinary system and chronic kidney failure]. / Osmoliarnost' krovi i mochi u bol'nykh tuberkulezom mochevoi sistemy s khronicheskoi pochechnoi nedostatochnost'iu.

Osmolarity and its constituents were followed up during the treatment course in 43 patients with tuberculosis of the urinary system and in 14 controls. The authors confirmed the relation of the blood and urinary osmolarity to the stage of chronic renal failure (CRF). CRF aggravation was evidenced by the development of hypo-osmolarity in the urine and a progressing decrease in the ratio coefficient between the osmolarity in the urine and in the plasma. Stability of plasma hyperosmolarity continued to be more than 340 mosmol/kg H2O and a decrease in the aforementioned coefficient to less than 1 despite the treatment evidenced the terminal stage of CRF and unfavourable outcome of surgical intervention.