Overview of GUTB

Mycobacterium tuberculosis bacilli are inhaled through the lungs to the alveoli, where they are phagocytosed by polymorphonuclear leukocytes and macrophages. Although most bacilli are initially contained, some are carried to the region's lymph nodes. Eventually, the thoracic duct may deliver mycobacteria to the venous blood; this may result in seeding of different organs. In addition, multiple granuloma form at the site of metastatic foci.

Renal, ureteral, and bladder TB

In the kidneys, when multiple granuloma form at the site of metastatic foci, they are typically bilateral, cortical, and adjacent to the glomeruli, and they may remain inactive for decades. Although both kidneys are seeded, clinically significant disease, which is caused by capillary rupture and delivery of proliferating bacilli into the proximal tubules, usually develops in only one kidney. The medullary hypertonic environment impairs the phagocytic function. Growing granuloma may erode into the calyceal system, spreading the bacilli to the renal pelvis, ureters, bladder, and other genitourinary organs. Depending on the status of the patient's defense mechanisms, fibrosis and strictures may develop with chronic abscess formation. Extensive lesions can result in nonfunctioning kidneys. Hypertension in persons with renal tuberculosis (TB) is twice as common as it is in the general population. Ureteral TB is an extension of the disease from the kidneys, generally to the ureterovesical junction, and develops in about one half of all patients with renal TB. It only rarely affects the middle third of the ureter. Ureteral TB often causes ureteral strictures and, sometimes, hydronephrosis. Occasionally, severe cases can cause stricture of virtually the entire ureter. Bladder TB is secondary to renal TB and usually starts at the ureteral orifice. It initially manifests as superficial inflammation with bullous edema and granulation. Fibrosis of the ureteral orifice can lead to stricture formation with hydronephrosis or scarification (ie, golf-hole appearance) with vesicoureteral reflux. Severe cases involve the entire bladder wall, where deep layers of muscle are eventually replaced by fibrous tissue, thus producing a thick fibrous bladder. Tubercles are rare in the bladder; if present, they usually appear at the ureteral orifice. Malignancy should be considered with any isolated tubercles away from the ureteral orifices.

Epididymal and testicular TB

The higher frequency of isolated epididymal TB lesions in children favors the possibility of hematologic spread of infection , whereas adults seem to develop tuberculous epididymoorchitis caused by direct spread from the urinary tract.[1]The formation of a draining sinus is uncommon in developed countries, but epididymal induration and beading of the vas are common. Involvement of the testis is usually due to direct extension. Infertility may result from bilateral vasal obstruction. Nodular beading of the vas is a characteristic physical finding, and orchitis and the resulting testicular swelling can be difficult to differentiate from other mass lesions of the testes.

Prostatic TB
Prostatic TB is also spread hematogenously, but involvement is rare; however, of those with affected, 85% also have renal TB. The affected prostate is nodular and not tender to palpation. Severe cases may cavitate and form a perineal sinus, although this development is rare. Decreased semen volume may indicate extensive prostatic disease or ejaculatory duct obstruction.[3]

Genital and urethral TB

Urethral TB is secondary to genital TB. Patients with genital and urethral TB present with a superficial tuberculous ulcer on the penis or in the female genital tract secondary to mycobacteria exposure during intercourse. The penile ulcer may cause cavernositis that extends to the urethra. This form of TB may involve the uterus and fallopian tubes, causing strictures. Consider malignancy if genital ulcers are

present. Acute urethritis manifests as mycobacterial discharge and often results in chronic stricture formation.

Causative Factors in GUTB

The most common pathogen associated with tuberculosis (TB) is Mycobacterium tuberculosis, a strictly aerobic nonmotile bacterium. The bacterium grows slowly, dividing only once every 24 hours, and is capable of surviving within immune cells after phagocytosis. Uncommonly implicated pathogens include M kansasii, M fortuitum, M bovis, M avium-intracellulare (MAI), M xenopi, M celatum. Male genital TB is usually a manifestation of the usual pulmonary acquisition of TB. Venereal acquisition of male genital tuberculosis is unlikely, although cases of male-to-female transmission of genital TB have been reported. Human immunodeficiency virus (HIV) infection increases the risk for active TB and has been suggested to increase the risk for reactivation of dormant foci; epididymal TB most commonly develops in sexually active young men. In very rare cases, TB epididymitis[4, 5, 6] and prostatic TB[7] have been reported following intravesical bacille Calmette-Gurin (BCG) therapy for superficial bladder tumors, presumably due to retrocanalicular descent of organisms from the prostatic urethra. Generally, TB prostatitis results from hematogenous dissemination of M tuberculosis from the site of the primary infection. Thus, previous infection with TB is the most important risk factor. Historically, 10-12% of men with TB had pathologic evidence of prostatic involvement during autopsy. Theories of descending spread via infected urine have been abandoned, largely in light of animal studies demonstrating hematogenous spread and the scarcity of prostatic urethral TB in association with prostatic parenchymal TB. Prolonged steroid use and immunosuppressive therapy may increase the risk of reactivation of dormant foci.

Prevalence of GUTB
Approximately 4000 cases of extrapulmonary tuberculosis (TB) are reported annually in the United States, a stable incidence despite a decreasing incidence of pulmonary TB. Genitourinary (GU) TB comprises approximately 6% of the extrapulmonary cases. Large autopsy studies from the first half of the 20th century reported a 10-12% incidence of prostatic involvement in men with TB. However, direct data are lacking. More recent small series suggest a lower rate of clinically detected prostatic TB. Much of the increase in the relative incidence of genital TB can be attributed to TB in men with human immunodeficiency (HIV) infection. Overall, individuals infected with HIV account for about 50% of the total TB population, and 70% of patients with acquired immunodeficiency syndrome (AIDS) and TB had extrapulmonary disease, accounting for an overall incidence of 2.3%. Worldwide, the incidence of TB in some developing countries is 30 times greater than that in the US; GUTB comprises approximately 15-20% of extrapulmonary cases of TB in these areas, approximately 2 times that in developed areas.

Age distribution
Before the age of anti-TB chemotherapy, the typical patient was aged 16-40 years. Now, more than 70% of men with genital TB are older than 35 years, and 15-20% are older than 65 years. In 1937, Moore described prostatic TB as "a disease of young adults" when he presented the age distribution of 243 cases, in which 79% of patients were younger than 50 years. [8] In 1998, Kostakopoulos et al presented 5 cases of unsuspected prostatic TB, all in patients aged 60-71 years.[9] Although this starkly contrasts with Moore's earlier data, all 5 cases were incidental findings at the time of transurethral resection of the prostate (TURP), and they do not necessarily reflect the age at which the disease first developed.

Over the last 2 decades, case reports of prostatic TB in immunocompetent men note patient age ranges of 26-85 years. Reported cases of prostatic TB in men with HIV infection document presentation in men aged 30-47 years. Most recently, Kulchavenya and Khomyakov reported on a series of 58 Siberian men with prostatic TB whose mean age was 49 years.[10]

Evaluation of GUTB
The presentation of genitourinary tuberculosis (GUTB) is often vague, and physicians must have a high degree of awareness to make the diagnosis. See also Special Considerations.

General presentation
Persons with GUTB rarely display the typical symptoms of TB. GUTB Symptoms are generally chronic, intermittent, and nonspecific, although asymptomatic patients are not uncommon. GUTB often manifests as repeated urinary tract infections that do not respond to the usual antibiotics. The most common symptoms of GUTB, in descending order of frequency, include increased frequency of urination (during the day initially but at night later in the disease course), dysuria, frank pain, suprapubic pain, blood or pus in the urine, and fever. Urinary urgency is relatively uncommon unless the bladder is extensively involved. Patients with GUTB may also present with a painful testicular swelling, perianal sinus, or genital ulcer. Unexplained infertility in both men and women is sometimes attributable to GUTB.[11] Physicians have also diagnosed endometrial TB while seeking the cause of congenital TB in the newborn.

Epididymal TB presentation
The formation of granulomas in the epididymis is responsible for the clinical manifestations of epididymal TB, as in other organ systems. The typical presentation in a patient with epididymal TB is painful unilateral enlargement of the scrotum. Malaise, fevers, and chills are also common in affected patients. Voiding problems are usually absent when only the external genitalia are involved. However, associated renal, vesical, or prostatic TB may contribute to irritative voiding symptoms. Epididymal TB can result in infertility.[1]

Prostatic TB presentation
The often-incidental finding of TB in chips from transurethral resection of the prostate (TURP) procedures suggests that many men may not have symptoms attributable to prostatic TB. Nonspecific symptoms, including irritative voiding, may be the only complaints. Of men with prostatic TB, 50% have dysuria and 40% have perineal pain. Sterile urethral discharge and terminal hematuria may herald TB prostatitis. Perineal pain, swelling, and drainage can account for a less common but more overt presentation. In addition, patients may present with male factor infertility, a well-described complication of prostatic TB. Perineal urinary fistula has also been reported. Renal TB, which is a common comorbidity of prostatic TB, may manifest as flank pain. Significant differential diagnostic overlap requires maintaining a high index of suspicion for prostatic TB, particularly in men with a history of exposure to or infection with TB. The most dramatic presentations of prostatic TB may be those in men with acquired immunodeficiency syndrome (AIDS). At least 6 cases of TB prostatic abscesses have been reported in men with human immunodeficiency virus (HIV) infection. Unlike the more insidious presentations noted in immunocompetent men, these patients presented with fever, perineal pain, and urinary hesitancy; 2 of the patients also presented with mental status changes.

Physical findings

Although the hallmark of GUTB is sterile pyuria, up to 20% of patients develop a secondary coliform infection. Gross hematuria occurs in 10% of cases and is usually total and painless; microscopic hematuria is present in 50% of cases. Tender testicular or epididymal swelling, beading of the spermatic cord, and epididymocutaneous sinus formations may develop. In the early phases, TB epididymitis is indistinguishable from bacterial epididymo-orchitis. The scrotal contents are enlarged and tender, with loss of definition between the epididymis and testicle. Secondary TB involvement of the testicle can be observed in advanced cases. Prostatic examination may reveal induration or bogginess of the prostate if this organ is involved. The vas deferens may be enlarged and beaded. Occasionally, a draining sinus is based posteriorly upon the epididymis. Most patients with prostatic TB in contemporary series have a prostate that may be hard, irregular, nodular, or granular. In patients with a prostatic TB abscess, a soft fluctuant mass has been noted. Tenderness varies with the acuity of the process. Prostatic TB should be suspected in patients who have a draining perineal fistula.

Diagnosis of GUTB
As discussed earlier, the presentation of genitourinary tuberculosis (GUTB) is often vague, and physicians must have a high degree of awareness to make the diagnosis. Patient history is key (see Evaluation of GUTB). Significant differential diagnostic overlap requires maintaining a high index of suspicion for prostatic TB, particularly in men with a history of exposure to or infection with TB. Because TB epididymitis often goes unsuspected during management of refractory epididymo-orchitis in developed countries, the ultimate diagnosis of TB epididymitis is usually made when the pathologic specimen from epididymo-orchiectomy is examined. Conditions that should be considered include bladder, testicular, renal, and urethral cancer; fungal and bacterial infections of the GU tract; pyonephrosis; scrotal or testicular trauma; postsurgical granulomatous prostatitis; postbacille Calmette-Gurin (BCG); and granulomatous and bacterial prostatitis. See also the Differentials list below. In addition to the patient history, a combination of laboratory and imaging studies, as well as other diagnostic studies can pin down the diagnosis.

Differentials
Renal Cell Carcinoma Epididymitis Hydrocele Spermatocele Testicular Torsion Testicular Tumors: Nonseminomatous Infertility Prostate Hyperplasia, Benign Urethral Strictures Urethritis

Routine Tests

Tuberculin skin test results are positive in about 90% of patients, but this finding denotes only previous inhalation of mycobacteria rather than active disease (see PPD). Complete blood cell (CBC) count, erythrocyte sedimentation rate (ESR), serum chemistry, and C-reactive protein (CRP) studies are helpful to assess the severity of disease, renal function, and response to treatment. The ESR is commonly elevated in patients with epididymal tuberculosis, and its normalization can be used to follow the course of therapy.

Urine Studies
Serial early-morning urine cultures (at least 3) for acid-fast bacilli (AFB) are still considered the criterion standard for evidence of active tubercular (TB) disease, with a sensitivity of 65% and a specificity of 100%. Every effort should be made to process the samples immediately after collection. Sending cultures before starting anti-TB treatment and adjusting therapy according to sensitivity in case of resistance is always recommended. The following methods are available: Solid media: The Lowenstein-Jensen medium yields results in more than 4 weeks. Radiometric media: The BACTEC 460 medium yields results in 2-3 days. Standard microbiologic identification of prostatic involvement of M tuberculosis also relies on culture and AFB staining results of semen and urine. Findings that demonstrate microscopic hematuria, albuminuria, or sterile pyuria should raise suspicion for genitourinary TB but do not definitively establish the diagnosis.

Semen Analysis and PSA

Although it is not a required test, semen analysis may be useful in the evaluation of male infertility associated with prostatic tuberculosis (TB). Standard microbiologic identification of prostatic involvement of M tuberculosis also relies on culture and acid-fast bacilli staining results of semen and urine. The reported semen analyses of 53 patients with genital TB revealed low volume in 89% of patients and azoospermia or oligospermia in 53% of patients. Significant leukocytospermia was identified in 77.6% of patients with prostatic TB. Prostate-specific antigen (PSA) levels are elevated in only one third of patients with prostatic TB. In 18 patients from a contemporary series, the median PSA level was 2.7 ng/mL (range, 0.3-31 ng/mL).

Sputum Testing
Patients with confirmed genitourinary tuberculosis should also undergo sputum testing.

PPD Skin Test

Intradermal injection of purified protein derivative of tuberculin (PPD) is an important component of the tuberculosis (TB) evaluation. An indurated area larger than 10 mm in diameter is considered a positive result, and an area greater than 15 mm in diameter may indicate active disease. However, a positive test result, in and of itself, is not confirmatory of the diagnosis of active TB. Furthermore, false-negative test results in the setting of malignancy, immunosuppression, liver disease, and nutritional deficiencies must be considered. When prostatic involvement is suspected in patients without a previous diagnosis of TB, a PPD test is a standard means of documenting exposure. False-negative results are possible, particularly during the 4-6 weeks before hypersensitivity develops and in persons who are immunosuppressed owing to various sources.

Polymerase Chain Reaction and DNA Probes

Polymerase chain reaction (PCR) has been extensively studied and has been proven highly sensitive, specific, and rapid. In various studies, data show a sensitivity ranging from 87% to 100% (usually >90%)

and a specificity from 92% to 99.8% (usually >95%). Compare this with cultures (37%), bladder biopsies (47%), and intravenous pyelography (IVP) examinations (88%). [12] Along with an accurate clinical assessment, PCR is the best tool available for avoiding a treatment delay, because results are available in only about 6 hours. The following PCR tests are available with nearequivalent quality: Genus-specific 16S rRNA PCR test Species-specific IS6110 PCR test Roche Amplicor MTB PCR test[13, 14, 15] Amplified Mycobacterium tuberculosis Direct Detection Test (AMDT) DNA probes provide species specification in a few hours.

Luciferase and Fluorescent Techniques

Staining with auramine or rhodamine and examining via fluorescence microscopy can be used to detect low numbers of mycobacteria. Luciferase bioluminescence is used to diagnose tuberculosis and aid in susceptibility testing.

High-Performance Liquid Chromatography HPLC Test

High-performance liquid chromatography (HPLC) quickly reveals qualitative and quantitative differences in mycolic acid in cell walls.

Radiography
Chest and spine radiographs may show old or active pulmonary tubercular (TB) lesions. However, in 50% of patients, chest radiographic findings are negative. Kidney, ureter, and bladder (KUB) radiographs reveal calcifications in the kidney and ureter in approximately 50% of patients. Calcifications are intraluminal, as opposed to schistosomiasis cases, which produce intramural calcifications. Calcifications in the bladder are uncommon. Plain abdominal radiography is useful to search for evidence of renal or ureteral tuberculosis (ie, renal or ureteral calcifications).

IVP, Voiding Cystography, and Retrograde Pyelography

Intravenous pyelography (IVP) and voiding cystography are the standard diagnostic imaging studies for renal tuberculosis (TB) and have 88-95% sensitivity. These studies also help define the extent and severity of the disease. The earliest radiographically detectable changes are cavitary lesions that progress to the papilla and invade the collecting system, causing calyceal disruption. Findings of infundibular stenosis and multiple ureteral strictures are highly suggestive of renal TB. Later findings may include cortical necrosis, calcifications, and coalesced cavitary lesions with scarring, stricture, sinus, or abscess formation. A small contracted bladder suggests extensive bladder TB. An IVP or a computed tomography scan should also be obtained to determine the presence of concurrent renal and prostatic TB. Of patients with prostatic TB, 72% have pathologic evidence of renal TB during autopsy. Voiding cystography has also been used to confirm and delineate the extent of a vesicoperineal fistula associated with prostatic TB. Retrograde pyelography is rarely indicated except in patients with renal failure in whom the kidneys cannot excrete contrast and to evaluate stricture in the upper urinary tract. It also helps for sampling urine from individual kidneys for microbiology.

CT Scanning With Contrast

This imaging study is a useful adjunct to intravenous pyelography (IVP) and is helpful in late or advanced disease for assessing the extent of disease and the indirect functional status of the affected kidney compared with the normal opposite kidney. This study is very sensitive for detecting calcification and thickened walls of the ureter and bladder. Nonvisualization of the affected kidney via excretory urography indicates advanced disease. On a contrast-enhanced computed tomography (CT) scans, prostatic tuberculosis (TB) may appear as hypodense lesions within the prostate. Additionally, focal calcifications may be identified.

Magnetic Resonance Imaging

Magnetic resonance imaging is sometimes useful to reveal radiographic changes in genitourinary tuberculosis and may reveal low signal-intensity lesions suggestive of abscess in prostatic tuberculosis. These studies may also be useful in delineating the extent of any renal disease .

Ultrasonography
Ultrasonography may reveal cystic or cavitary lesions, cortical scarring, hydronephrosis, and abscess in the kidneys; ultrasonography is also very sensitive in testicular tuberculosis (TB). In cases of female genital TB, an adnexal mass, thickened omentum or peritoneum, peritoneal tubercles, loculated or free fluid in the pelvic cavity, and adhesions are common ultrasonographic findings. High-resolution transrectal ultrasonography (TRUS) has become a very useful noninvasive technique in the evaluation of the subfertile man who has severe oligospermia or azoospermia associated with a lowvolume ejaculate.[16] TRUS can reveal abnormalities in the seminal vesicles and ejaculatory duct and can help assess the status of the prostate. It may show dilatation or fibrosis of the epididymis, atrophy, thickening or calcification of the seminal vesicles, or prostatitis. In persons with a soft or fluctuant prostate in whom an abscess is suspected, TRUS is particularly useful, as this modality allows demonstration and localization of the collection and can then guide transrectal aspiration and drainage of any fluid for culture and microscopic examination. Although scrotal ultrasonography is helpful in assessing for complications of epididymal tuberculosis, such as fistula or abscess formation, the appearance of epididymal TB on ultrasonography is not distinct from that of bacterial epididymo-orchitis.

Angiography
Angiography is useful when focal lesions mimic a primary renal mass or when partial nephrectomy is planned. Angiography also shows obliterated interlobar arteries and avascular lesions.

Renal Nuclear Scanning

Renal nuclear scan findings are nonspecific but can be used to assess kidney function and to monitor the effects of therapy.

Vasography
Vasography in association with transrectal ultrasonography may demonstrate mechanical obstruction of the vas deferens.

Hysterosalpingography and Image-Intensifier Endoscopy

Hysterosalpingography and image-intensifier endoscopy are sometimes useful to reveal radiographic changes in genitourinary tuberculosis.

Laparoscopy
The discovery of peritoneal tubercles during tubal ligation is not uncommon in developing countries.

Biopsy
Consider biopsies of genital ulcers; tubercles in the bladder, especially if scattered away from the ureteric orifice (an uncommon feature of bladder tuberculosis [TB]); and any lesion with even a slight possibility of malignancy. The yield of biopsy for TB is about 45%.

Fine-Needle Aspiration
Fine-needle aspiration (FNA) as a minimally invasive technique plays a prime role in the diagnosis of tubercular (TB) epididymitis and epididymo-orchitis.[17] Acid-fast bacilli (AFB) may be detected on FNA smears in up to 60% of these patients. However, because of the risk of tumor spillage, FNA should be avoided if a neoplasm is suspected.[17, 18] Histologic findings of TB epididymitis are similar to those of TB elsewhere in the body (granuloma formation, nonspecific inflammatory infiltrate). Additionally, mycobacteria are present. The granulomas appear with central Langerhans cells surrounded by lymphocytes, fibrocytes, and epithelioid cells, which later progress to central caseous formation and varying degrees of fibrosis and calcification. Similar histologic changes can be seen in the prostates of patients treated with intravesical bacillus CalmetteGurin (BCG) for transitional cell carcinoma of the bladder. Transrectal ultrasonographyguided needle biopsies have been used to obtain tissue for a definitive diagnosis of prostatic disease, to monitor response to therapy, and to ensure eradication of the prostatic TB.

Management Considerations
The primary aims of treatment are to preserve renal parenchyma and function, to make the patient noninfectious, and to manage comorbid conditions. Genitourinary tuberculosis (GUTB) responds better to a short course of treatment than pulmonary TB, because GUTB carries a lower mycobacterial load. Also, isoniazid (INH) and rifampin penetrate well into the cavitary lesions associated with GUTB. A high concentration of INH, rifampin, and pyrazinamide are maintained in the urine. To prevent the emergence of resistant organisms, a multidrug regimen is the primary treatment. Because of the length of therapy and the adverse effects, maintaining patient compliance is difficult; therefore, directly observed therapy is often recommended. Standard treatment of TB is rifampin, INH, pyrazinamide, and ethambutol for 2 months, then rifampin and INH for 4 more months unless resistance to either agent exists; if so, obtain a follow-up sensitivity report. Monitor culture and sensitivity reports and change the regimen if necessary. In general, a 4-month course of chemotherapy is recommended for GUTB (see Short-Course Therapy). In patients who are positive for human immunodeficiency virus (HIV), continue treatment for a total of 9 months. In malnourished patients, institute a high-nutrition diet.

Consultations
A urologist should provide constant follow-up care to prevent further irreversible parenchymal damage, and consultation with an infectious disease specialist is recommended for physicians who are not familiar with the treatment of TB.

Short-Course Therapy
A 4-month course generally is recommended for genitourinary tuberculosis. Examples of short-course therapy are as follows: Prescribe 2 months of daily therapy with isoniazid (INH) (300 mg/d), rifampin (450 mg/d), and pyrazinamide (25 mg/kg/d, maximum dose 2 g/d), then 2 months at 3 times per week with INH (600 mg tiw) and rifampin (900 mg tiw).

Prescribe 4 months of therapy at 3 times per week with INH, rifampin, and pyrazinamide. This course is cost-effective in developing countries if compliance is ensured, although it may promote multidrug resistance. Prescribe 2 months of daily therapy with INH (300 mg/d), rifampin (450 mg/d), pyrazinamide (25 mg/kg/d, maximum dose 2 g/d for 2 mo, and streptomycin (1 g/d) or ethambutol, then 2 months at 3 times per week with INH (600 mg tiw) and rifampin (900 mg tiw). Add streptomycin or ethambutol if resistance to INH or rifampin is a possibility.

Steroid Administration
Indications for prescribing steroids include severe bladder symptoms and tubular structure involvement (eg, ureter, fallopian tubes, spermatic cord). High-dose prednisone (ie, at least 20 mg tid) for 4-6 weeks is recommended, because rifampicin reduces effectiveness and bioavailability of prednisone by 66%.

Management of Epididymal TB
The typical presentation of acute tuberculous (TB) epididymitis usually prompts antibiotic therapy for presumed acute bacterial epididymo-orchitis. A more insidious onset of symptoms, although not suggestive of acute bacterial epididymo-orchitis, often prompts the same therapy, because TB is usually not considered by the treating physician. If no improvement occurs after 2-3 weeks of therapy for bacterial epididymo-orchitis, scrotal ultrasonography is useful to assess for complications of inadequately treated bacterial epididymo-orchitis. Ultrasonography also assists in the diagnosis of other elements in the differential diagnoses, including hydrocele,spermatocele, scrotal trauma, testicular malignancy, and neoplasms of the epididymis (see Ultrasonography). If no such findings are noted, TB epididymitis or a resistant bacterial infection should be considered. Obtaining the purified protein derivative of tuberculin (PPD) skin test, serial first morning urine cultures for acid-fast bacilli (AFB), chest radiography, and abdominal radiography would be reasonable at this point. Additionally, a higher index of suspicion for epididymal TB is appropriate in men with HIV infection because of its increased incidence in this setting. Chemotherapy may be instituted upon strong clinical suspicion of TB. Alternatively, fine-needle aspiration (FNA) of the epididymis can be performed to obtain material for smear examination (see Fine-Needle Aspiration). However, avoid this procedure if malignancy is suspected as seeding of the neoplasm may occur.

Management of TB Prostatitis
Once the diagnosis of tuberculous (TB) prostatitis is confirmed, the treatment is similar to that of other TB infections. This condition must be viewed as a systemic disease, and the treatment is primarily medical. Hospitalization is usually unnecessary but may be required to treat noncompliant patients. Patients should be isolated in a negative-pressure room, if available. In addition, the local health department should be notified to aid in identifying patient contacts. Drug susceptibility testing should be performed on the isolates obtained from the prostate.

Patients with Impaired Renal Function

Special considerations apply to patients with impaired renal function. Rifampicin, isoniazid, pyrazinamide, ethionamide, and prothionamide may be given in normal doses, because these agents are either eliminated in the bile or broken down to metabolites that are not excreted by the kidney. Ethambutol causes optic neuritis, which may be irreversible, and reduced doses should be given according to the glomerular filtration rate (GFR). Streptomycin and other aminoglycosides are ototoxic and nephrotoxic and should be avoided if possible in patients with impaired renal function.

Surgical Management

Although chemotherapy is the mainstay of treatment, surgical intervention, either as ablation or reconstruction, is often required during the course of genitourinary tuberculosis (GUTB). Generally, at least 4-6 weeks of chemotherapy with appropriate agents is first tried if immediate surgery is not necessary (see Management Considerations and Short-Course Therapy). In a European series, the overall frequency of surgical management in GUTB in the past 20 years was 0.5% of total urologic surgical procedures.

Indications for surgical intervention

Indications for surgery include hydronephrosis, progressive renal insufficiency secondary to obstruction, nonfunctioning or poorly functioning kidneys, stricture of the fallopian tube or vas deferens that is causing infertility, persistent pain, possible neoplasm, recurrence of endometrial TB, and severe, persistent, or recurrent uterine bleeding. During the course of treatment for epididymal TB, if the lesion loses its tenderness while maintaining nodularity, consider a testicular malignancy, in which case operative exploration is indicated. Additionally, because TB epididymitis often goes unsuspected in the management of refractory epididymo-orchitis in developed countries, the ultimate diagnosis of TB epididymitis is usually made when the pathologic specimen from epididymo-orchiectomy is examined. Alternative techniques, such as epididymectomy or fine-needle aspiration of the epididymis, can be offered if TB is suspected preoperatively. In prostatic TB, some urologists advocate resection of the prostate, although only medical therapy is usually needed. In patients with obstructive symptomatology, resecting the prostate is reasonable. In addition, in resistant TB, prostate resection can theoretically lessen the infected tissue burden. Surgical treatment should be undertaken only once anti-TB therapy has been initiated to reduce the risk of exposure to the surgical team. In persons infected with human immunodeficiency virus (HIV), prostatic TB can present as an abscess. Surgical drainage of an abscess collection is required. Wolf[19] and Moreno et al[20] described transrectal ultrasonography (TRUS)-guided needle drainage, and Trauzzi et al successfully treated one such patient with transurethral unroofing of the collection.[21] The surgeon should obtain intraoperative samples of any abscess fluid for acid-fast bacilli (AFB) staining, culture, and polymerase chain reaction (PCR), if available.

Ablative and reconstructive surgery

Ablative surgery is generally associated with partial or total nephrectomy, epididymectomy, salpingectomy, as well as other procedures. Reconstructive surgery is considered for ureteric or urethral dilatation, stent placement, replacement or reimplantation, resection, urinary diversion, and augmentation cystoplasty.

Prevention of GUTB
Maintain a high degree of clinical awareness for genitourinary tuberculosis (GUTB). Screen emigrants from endemic areas as well as their sex partners and family members. Condom use is encouraged to prevent possible transmission to sexual partners. If an emigrant from a TB-endemic area has intermittent recurrent urinary tract infections after several courses of antibiotics, obtain a purified protein derivative (PPD) skin test and at least 3 serial earlymorning urine samples to test for acid-fast bacilli to evaluate for GUTB. Researchers now question the use of Bacille Calmette-Gurin (BCG) vaccine, even in developing countries, because TB is diagnosed in vaccinated persons. Additionally, the BCG vaccine is not costeffective in developing countries. Before starting medications, investigate regional drug-resistance data. The chemoprophylaxis protocol for unconfirmed clinical disease is isoniazid (INH) for 6 months (9 mo in patients who are positive for human immunodeficiency virus [HIV]), INH and rifampin for 3 months, or rifampin and pyrazinamide for 2 months.

Complications of GUTB
Complications of genitourinary tuberculosis (GUTB) include the following: Superinfection Abscess Sinus formation Renal hypertension Scarring of renal parenchyma, loss of renal function, and, eventually, end-stage renal disease Stricture and obstruction of ejaculatory duct or vas deferens may cause azoospermia and sterility. Similarly, involvement of fallopian tubes or endometrium may lead to infertility, which is common in developing countries. Congenital TB: Culture-positive pulmonary TB in newborns and endometrial TB in mothers have been documented. Sexual transmission Complications of advanced TB epididymitis include epididymal abscess and fistula formation. Both complications are usually treated with scrotal surgery. Failure of the anti-TB regimen to achieve satisfactory local response is also treated surgically.

Surveillance Measures
Patient education and monitoring are crucial to eradicating tubercular disease.

Patient education
Crucial education issues include long-term compliance, preventive measures, and early detection in other persons. In addition, patients should be advised to use condoms during intercourse. Sexual transmission of tuberculosis (TB) via infected semen has been reported to result in a vaginal TB ulcer. GUTB can be sexually transmitted until treatment clears mycobacteria from semen, urine, or other genital secretions. Mycobacteria usually clear approximately 4 weeks after appropriate medications are started.

Patient monitoring
If the patient is not complying with therapy, use direct observation therapy 2-3 times a week. Patients treated for epididymal TB should be monitored for resolution of symptoms and swelling of induration, which should begin within a few weeks. The urine generally clears of infectious organisms within 2 weeks. In cases of prostatic TB, periodically check semen cultures to monitor treatment, and, if results are positive after 3 months, bacterial resistance to the current drug regimen or patient noncompliance should be strongly suspected. Histologic follow-up via repeat transrectal ultrasound-guided prostate biopsies has been recommended to ensure the efficacy of treatment.

GUTB Outcomes
Worldwide, 10 million people per year contract tuberculosis (TB), of which 3 million die annually. The ultimate prognosis is determined by the degree of systemic illness. However, good outcomes can generally be achieved in young patients, individuals without comorbid conditions, those who comply with medications and follow-up care, and patients with a good social support system. Early detection of the disease and sensitivity to first-line medications are also associated with a good. There is a poorer prognosis in older patients, individuals from low socioeconomic groups, and those with comorbid immunocompromising conditions. Late detection with complications is also associated with a poor outcome. In cases of epididymal and testicular TB, scrotal surgery may be required, which could include removal of the epididymis and testicle.

Male factor infertility, which manifests as decreased ejaculate volume, oligospermia, azoospermia, and leukocytospermia, has been observed in association with TB prostatitis. A perineal urinary fistula may result from tubercular cavern formation within or behind the prostate. Reports note perineal swelling, pain, and discharge preceding the development of the urinary fistula. Prostatic TB abscess formation has been noted, particularly in men with acquired immunodeficiency syndrome (AIDS). Most patients with prostatic TB can be cured with early treatment with a multiple-drug regimen. Mortality directly attributable to prostatic TB has not been reported in the recent literature; however, a case report by Lanjewar and Maheshwari described 2 patients with human immunodeficiency virus (HIV) infection who died of disseminated TB during hospitalization.[22] Unsuspected tuberculous prostatic abscesses were noted in both patients during the postmortem examination.

Special Considerations
Offer human immunodeficiency virus (HIV) testing to all patients with TB. Physicians should consider renal tuberculosis (TB) in any patient with a nondiscrete renal calcification. In addition, perform a full workup for malignancies if tubercles or ulcers are present away from ureteric orifices, if genital ulcers are present, or with suspicious renal lesions. Inform patients that genitourinary tuberculosis (GUTB) may cause sterility in females, and consider genital TB in a male sex partner if the female has persistent, swollen, painful inguinal lymph nodes and no obvious source of infection. Fine-needle aspiration (FNA) of the epididymis may be useful to distinguish epididymal TB from bacterial epididymo-orchitis, but, because of the risk of tumor spillage, avoid FNA if a neoplasm is suspected. Physicians should alert to recognize, prevent, and treat any adverse medication effects.