Urogenital tuberculosis

Author

Ekaterina Kulchavenya (Novosibirsk Tuberculosis Research Institute of the Ministry of Health of the Russian Federation, Novosibirsk Medical University, Russia)

Executive summary

Epidemiology and Pathogenesis

1. Urogenital tuberculosis (UGTB) is a second-third frequent form of tuberculosis (TB), but a large proportion of patients is underdiagnosed (LE: 2).

2. UGTB includes urinary tract TB and male and female genital TB; exact wording is necessary for correct estimation of the epidemic situation (LE: 1).

3. UGTB is often (about 40%) associated with pulmonary TB (PTB) and/or other localizations of TB (actual or cured) (LE: 1).

4. Male genital tuberculosis (MGTB) is usually (over 50%) associated with PTB and/or renal TB (actual or cured), but isolated forms are also possible. More often the epididymis and prostate are involved (LE: 1).

5. The main route of infection is via hematogenous and lymphatic spread, but direct extension from infected urine and ejaculate spread is also possible (LE: 1).

Diagnosis

1. All patients with genital TB should be screened for chest and upper urinary tract involvement and human immunodeficiency virus (HIV) infection (GR: A).

2. At least three, but preferably five serial microbiologic studies with urine (including postejaculate and post-massage urine), ejaculate and prostate secretion including smears, cultures, including automated system Bactec (GR: A) and polymerase chain reaction (PCR), including geneXpert (GR: B) should be performed to make the diagnosis of UGTB.

3. In isolated external genital TB without renal and prostate involvement, diagnosis of MGBT is often only possible by histo-pathomorphology (GR: B).

4. In difficult cases a provocative subcutaneous tuberculin test is recommended (GR: B).

5. Radiologic studies are not useful for diagnosis of UGTB on early stages, before development of the tissue destruction (LE: 2).

6. For cavernous prostate tuberculosis retrograde urethrography is crucial (GR: A)

7. Fine needle aspiration cytology (FNAC) is an accurate and rapid diagnostic tool for scrotal TB, but may be complicated by TB generalization (GR: C).

8. If there is no evidence of M. tuberculosis (Mtb) diagnosis of UGTB may be made on the basis of skin-test, histological picture, caverns revealed by urography, sterile pyuria etc (GR: B).

9. Diagnosis of the iatrogenic (Bacillus Calmette–Guérin (BCG) - induced) bladder TB (complication of the BCG-therapy for bladder cancer) may be made by clinical features - significant dysuria and decrease of the bladder volume; confirmation only by histology, not by bacteriology (GR: C).

Treatment

1. Short term treatment for six to nine months is suitable in uncomplicated cases in regions with low incidence of TB (GR: B).

2. In complicated cases (relapse, immunosuppression, drug-resistance) and in epidemic regions anti-TB therapy should be longer, up to 12-14 months with four to five drugs (GR: B).

3. Multi-drug resistant tuberculosis (MDR-TB) should be treated with at least 5 anti-TB drugs for at least 18 months (GR: B).

4. BCG-induced bladder TB should be treated with 2 -3 anti-TB drugs for 2-4 months, if the volume is normal; if microcystis developed – cystectomy and following enteroplastic reconstructions are indicated with the same anti-TB therapy (GR: B).

Introduction

According to World Health Organization (WHO) reports, reviewed March 2014, about one-third of the world's population has latent TB, which means people have been infected by Mtb but are not (yet) ill with disease and cannot transmit the disease. People infected with Mtb have a lifetime risk of falling ill with TB of 10%. However persons with compromised immune systems, such as people living with human immunodeficiency virus (HIV), malnutrition or diabetes, or people who use tobacco, have a much higher risk of falling ill^[1].

TB is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent. In 2012, 8.6 million people fell ill with TB and 1.3 million died from TB. TB is a leading killer of people living with HIV causing one fifth of all deaths^[1].

In 2012, the largest number of new TB cases occurred in Asia, accounting for 60% of new cases globally. UGTB is frequent form of TB, but it is a mostly overlooked disease. Despite major efforts to increase case detection, an estimated one third of new TB cases are still being missed each year, and the unavailability of a rapid, low-cost, accurate diagnostic assay that can be used at the point of care is a major hindrance. There are a very few multicenter randomized studies on UGTB because of absence of unique approach to definition, diagnosis, therapy and management of this disease.

Terms and definitions

The first note of UGTB was made by Porter in 1894^[2]; in 1937 Wildbolz^[3] suggested the term genitourinary TB. However, the term UGTB is more correct, because kidney TB (KTB), which is usually primary, is diagnosed more often than genital TB.

Urogenital tuberculosis (UGTB) - infectious inflammation of any urogenital organ - isolated or in combination (kidney and/or male or female genitals), - caused by Mtb or M. bovis.

Genital tuberculosis (GTB) – infectious inflammation of the female or male genitals – accordingly female genital tuberculosis (FGTB) or male genital tuberculosis (MGTB) caused by Mtb or M. bovis.

Kidney tuberculosis (KTB) - infectious inflammation of kidney parenchyma, caused by Mtb or M. bovis.

Urinary tract tuberculosis (UTTB) – infectious-allergic inflammation of calyx, pelvic and upper and lower urinary tract caused by Mtb or M. bovis, always secondary to kidney TB and should be considered as a complication of kidney TB.

Generalized urogenital tuberculosis (gUGTB) – generalized tuberculosis of the kidney and the male or female genitals, respectively.

Etiology of UGTB

There is a big family of Mycobacterium – but not all members of this family are pathogenic for human. Mycobacterium tuberculosis and M. bovis are combined in mycobacterial complex; they are obligatory pathogens for human organizm. In 80–95% UGTB is caused by Mtb, but M. bovis is also an etiological agent of TB^[4][5][6], because tuberculosis is an anthropozoonotic infection.

Bacillus Calmette–Guérin (BCG), which are in fact attenuated M. bovis, are widely used for the therapy of superficial bladder cancer. In some conditions BCG-therapy may be complicated by iatrogenic BCG-induced UGTB - mainly bladder or prostate TB, but in rare cases also BCG sepsis is possible^{[7][8][9][10]}.

Epidemiology of UGTB

Before anti-TB drugs were available, UGTB was an extremely frequent disease: every fifth patient treated in urological department had kidney TB (KTB), more than one third of all pyonephrosis were by TB etiology^[11]. Now UGTB is the second most common form of TB in countries with a severe epidemic situation and the third most common form in regions with low incidence of TB;the share of UGTB among extrapulmonary TB accounts for 33.7–45.5%. In developed countries 2–10% pulmonary TB (PTB) patients have also UGTB^[12][13]. In 20% PTB patients UGTB will develop later, after recovery from the first disease^[14]. In Russia TB of bone and joints and UGTB has about the same frequency now^[15].

Classifications of UGTB

UGTB includes many forms of TB with its own clinical features requiring specific therapy and management. Therefore correct clinical classification and staging are important for optimal management and therapy^[16]. UGTB can be subclassified into the following entities: kidney tuberculosis and genital tuberculosis.

Kidney tuberculosis

There are four stages to be considered for Kidney tuberculosis:

Stage 1: TB of kidney parenchyma (non-destructive form, KTB-1).

Stage 2: TB papillitis (small-destructive form, KTB-2).

Stage 3: Cavernous kidney TB (destructive form, KTB-3).

Stage 4: Polycavernous kidney TB (widespread-destructive form, KTB-4).

Complications of kidney TB are chronic renal failure, fistula, high blood pressure.

Urinary tract TB includes

1) TB of ureter.

2) TB of the bladder is divided into 4 stages^[16]:

Stage 1: tubercle-infiltrative;

Stage 2: erosive-ulcerous;

Stage 3: spastic cystitis, which in fact means overactive bladder;

Stage 4: contracted bladder up to full obliteration.

There is one more form of bladder TB, the iatrogenic BCG-induced bladder TB, which develops as a complication of BCG therapy for bladder cancer.

3) TB of urethra.

Male genital tuberculosis (MGTB) is subdivided into 4 categories

1) TB epididymitis (uni- or bilateral).

2) TB orchiepididymitis (uni- or bilateral).

3) TB of the prostate (infiltrative or cavernous forms).

4) TB of seminal vesicles.

5) TB of the penis.

Complications of MGTB are strictures, fistula, infertility, sexual dysfunction.

Female genital tuberculosis (FGTB) (is not included in this Chapter).

Generalized urogenital tuberculosis (gUGTB): simultaneous lesion of the kidney and the genital organs; gUGTB is always considered as a complicated TB.

Clinical features

Clinical features of UGTB have no specific signs, are instable and depend on many factors; this is one of the reasons for late diagnosis.

Clinical features of kidney TB

As whole KTB patients complain of flank pain (up to 80%) and/or dysuria (up to 54%). If the urinary tract is involved, then renal colic (24%) and gross-hematuria (up to 20%) are possible.

Prostate TB manifests by perineal pain and dysuria, and in half of the cases by hemospermia. TB orchiepididymitis always starts from epididymitis, isolated TB orchitis does not exist. Oedema and swelling of the scrotal organs and pain are most often the first symptoms. In 68% there is an acute debut of the disease. Nevertheless, in 32-40% the disease has a chronic or asymptomatic course^{[15][16][17][18]}.

1) KTB-1 has minimal lesion without destruction, full recovery is possible by anti-TB drugs.

Intravenous urography (IVU) is normal. Urinalysis in children is often normal, but in adults low level leucocyturia may be found. Usually patients have no complaints and are diagnosed by chance. KTB-1 is complicated very rarely. Prognosis is good, usually outcome is full recovery. With inappropriate therapy KTB-1 may progress to destructive form. KTB-1 should be confirmed by bacteriology in any case. Usually Mtb in KTB-1 patients are sensitive to anti-Tb drugs. Mtb detection in urine is always necessary for diagnosing kidney TB stage 1, but may not always be revealed in other forms of UGTB.

2) KTB-2 is subject to conservative therapy, but if KTB-2 is complicated by urinary tract TB, than reconstructive surgery is indicated. Prognosis is good; usual outcome is recovery with fibrous deformation and post-tuberculous pyelonephritis. With inappropriate therapy KTB-2 may progress to the next stage. Mtb is not detected in all cases and may be resistant.

3) KTB-3 has two ways of pathogenesis, from TB of parenchyma or from papillitis. The first way means development of a sub-cortical cavern without connection to the collecting system. The clinical manifestation of a sub-cortical cavern is similar to a renal carbuncle, thus the diagnosis is usually made after the operation. The second way is the destruction of the papilla until a cavern is developed. Complications develop in more than half of the patients. Full recovery by anti-TB drugs is impossible, surgery is generally indicated. The best outcome is the formation of a sterile cyst; a negative outcome is further destruction upto polycavernous TB.

4) KTB-4 means several caverns in the kidney; nevertheless overall renal function may be sufficient. KTB-4 may result in fistulas due to pyonephrosis. Self-recovery is also possible, when a stricture of the ureter locks the kidney and caseation in the caverns is impregnated by calcium, the so-called auto-amputation of the kidney. KTB-4 is almost always complicated; very often the contralateral kidney is involved. Recovery with anti-TB drugs only is impossible; surgery is necessary, basically nephrectomy.

Urinary tract TB

Urinary tract TB is a specific complication of KTB and so is always secondary to KTB. Urinary tract TB with any localization first appears as an oedema; the next stages are infiltration, ulceration and fibrosis.

1) TB of ureter usually develops in the lower third, but multiple lesions are possible, too. Incorrect therapy may lead to development of a ureteral stricture which may result in loss of the kidney, even if TB is finally cured.

2) TB of the bladder. The main symptom is frequency, then urgency, hematuria. The first two stages should be treated by standard anti-TB drugs; the 3-rd stage with standard anti-TB drugs and trospium chloride, and the 4-th stage is indicated for cystectomy with following enteroplasty.

3) TB of urethra. TB of the urethra is nowadays not a frequent complication; usually it is diagnosed at the stage of a stricture.

Male genital tuberculosis (MGTB)

1) TB epididymitis may be mono- bilateral; bilateral TB epididymitis is always secondary to prostate TB. Isolated TB epididymitis was found in 22% as accidental surgical finding^[16][19].

2) TB of the testis is always secondary to infection of the epididymis, which in most cases is blood-borne because of the extensive blood supply of the epididymis, particularly the lobus minor. In 62% of patients with orchiepididymitis KTB is diagnosed as well. Every third patient has bilateral lesions. In about 12% the disease is complicated by fistulas^[16][19]

3) TB of the prostate is an often under-diagnosed disease. Three quarters of men died from all forms of TB, had prostate TB, mostly overlooked alive^[20]. Prostate TB is important due to the following:

• It may also be a sexually transmitted disease. Up to 50% of prostate TB patients have Mtb in their ejaculate if they are co-morbid with hepatitis and syphilis[21].

• It leads to infertility.

• It causes chronic pelvic pain like any other prostatitis, reducing significantly the quality of life^[22].

• It decreases the sexual function, also reducing the quality of life^[19]. In 79% prostate TB was accompanied by KTB, in 31% by TB orchiepididymitis, and in 5% isolated prostate TB was diagnosed^[16].

4) TB of seminal vesicles is secondary to prostate TB and leads to infertility. As drainage of caseous ejaculate is difficult, TB of seminal vesicles exhibits a tendency to calcification^[23].

5) TB of the penis is very rare, but can occur after sexual intercourse with infected females^[24] or via a direct infection through a penile wound during ritual circumcision. Penile lesions present as ulcers on the glans or penile skin. Currently it is mainly a complication of BCG-therapy^[25][26][27].

Risk factors for UGTB

UGTB has several risk and suspicious factors:

• contact with TB infection,

• TB of any other localization, whether active or cured, especially in disseminated forms,

• urinary tract infection (UTI) with frequent recurrences and resistant to standard therapy,

• UTI with persistent dysuria, leading to decreasing bladder volume,

• sterile pyuria,

• pyuria in all portions of 3-glass test in patient with epididymitis / orchiepididymitis,

• pyospermia and/or hemospermia,

• scrotal, perineal and lumbar fistulas.

Diagnosis

History

Risk factors for UGTB should be evaluated carefully.

Physical examination

A special attention should be paid to any fistula. In acute course of TB epididymitis hard painful enlarged epididymis intimate welded with testis is palpated. In chronic course epididymis is hard, enlarged, and painless with clear border from the testis; in 35–40% the lesion is bilateral. Digital rectal examination of the patient with prostate TB shows moderate enlarged tuberous prostate gland with weak pain. Again – scrotal and perineal fistulae are highly suspicious for TB^[28].

Laboratory tests

1) Urinalysis. Leucocyturia was found in 90–100% of patients with KTB, and hematuria in 50–60%^[16].

2) Bacteriology. In “before-antibacterial era” sterile pyuria was specific for KTB, but now up to 75% patients have non-specific pyelonephritis alongside with KTB and therefore common microflora and Mtb may be found in urine together^[29][30][31]. To diagnose common UTI a bacterial growth of at least 10³ CFU/ml is needed, but even one single Mtb is evidentiary of UGTB^[16][32]. The diagnosis of UGTB is absolutely confirmed when Mtb is revealed, but in recent years only in half of TB patients Mtb could be found. Therefore in patients suspected of UGTB, but without documented evidence of Mtb, the clinical diagnosis of UGTB has to be made on the basis of other clinical features, such as skin-test, histological picture, caverns revealed by urography, sterile pyuria etc^[16]. The spectrum of the methods for identification of Mtb is shown in the table 1. Table 1. Spectrum of bacteriological investigations for UGTB diagnosis

3) Histology. Histological investigation may reveal epithelioid granuloma, caseous necrosis, but they are fast replaced with fibrous tissue especially due to non-optimal previous therapy. If the patient was treated with fluoroquinolones and amikacin for common UTI, which in fact masks UGTB, specific histological changes transform into fibrosis, and pathomorphological confirmation of the disease becomes impossible.

4) Ultrasound investigation. Renal ultrasound may give indirect evidence of UGTB only. As prostate TB in 79% is accompanied by KTB^[19], pathological findings detected by renal ultrasound in patients with “chronic prostatitis” are very suspicious for UGTB. TB epididymitis and orchitis present as diffusely enlarged lesions, which may be homogeneous or heterogeneous and can also occur as nodular enlarged heterogeneously hypoechoic lesions^[33]. Transrectal ultrasound may reveal hypo- and hyperechoic lesions of the prostate, predominately in the peripheral zone, but also as prostatolithiasis which in fact may be calcified zones of TB inflammation^[34].

5) Radiological investigations is indicated for patients suspected of UGTB: plain X-ray films of the urinary tract may detect calcification in the renal areas and in the lower urogenital tract; IVU is indicated for patients with leucocyturia and/or abnormality on ultrasound investigations.

Retrograde urethrography should be performed in all patients with genital TB to exclude caverns of the prostate. X-ray examination is very useful to detect cavernous forms of UGTB, both in KTB intravenous urogram (IVU) and prostate TB (urethrography), but multi-sliced computer tomography is significantly more informative. In contrast-enhanced CT scan TB of the prostate or seminal vesicles can be seen as low density or cavitation lesions due to necrosis and caseation with or without calcification. Without calcification, the findings may be similar to pyogenic prostatic abscesses^[35][36]. UGTB in early stages, however, has no specific radiological image.

6) Instrumental interventions for UGTB diagnostics are of limited value, especially nowadays.

6.1) Cystoscopy is indicated for all UGTB patients with dysuria. Persistent dysuria in KTB patient is suspicious of bladder TB, even without histological confirmation, which may be obtained in 12% of the patients with bladder TB stage 4 only^[37]. Any mucosal pathology should be biopsied and investigated both by histology and bacteriology, although the absence of specific findings do not exclude the diagnosis of TB as was shown above.

6.2) Ureteropyeloscopy may accidentally reveal TB ulcers, especially when the procedure is performed to the patients with renal colic because of roentgen-negative stone.

6.3) Prostate biopsy should be performed only after urethrography in order to exclude caverns.

Tissue of the prostate gland should be investigated by histology and bacteriology, at least by PCR^[38][39].

6.4) Biopsy of scrotal organs. Fine needle aspiration cytology (FNAC) may be useful to diagnose TB of the external male genitals^[40]. However, scrotal violation should be considered if the mass is malignant. Fatal complications due to fulminant generalization of TB have occurred after biopsies performed in non-treated patients with active UGTB.

7) Provocative tests. The Mantoux test is positive in more than 90% of TB patients, but it has no value in regions with a severe epidemic situation (e.g. China, Russia, India, and Pakistan), where almost all adults are infected with Mtb and thus all have positive skin tuberculin test. New Diaskintest has high specificity, but low sensitivity, and is not recommended for diagnosis of UGTB. Subcutaneous tuberculin provocative test is recommended^[41].

8) Therapy ex juvantibus If the patient is suspected on UGTB, but there are no evidence of Mtb or typical histological findings, and data of tuberculin provocative test as well as X-ray imaging are unconvincing, the clinical diagnosis of UGTB has to be made on the basis of therapy ex juvantibus, which is sub-classified on two types. Therapy ex juvantibus 1st type is indicated to the patient with low suspicion for UGTB. Antibiotic which does not inhibit Mtb (fosfomycin, cefalosporins, and nitrofurantoin) is prescribed; a positive result allows excluding the diagnosis UGTB. If there remains doubt about the etiology of UTI, therapy ex juvantibus 2nd type is indicated. Therapy ex juvantibus 2nd type includes 2-4 antibiotics which inhibit only Mtb (isoniazid, PAS, protionamid, etionamid, ethambutol, pyrazinamide); positive result in two months allows establishing UGTB^[41]. Detailed diagnostic algorithm is exhibited in the table 2.

Table 2. Recommendation for examination of the patients suspicious for UGTB

If there is no evidence of Mtb diagnosis UGTB in patient with high risk of the development of the disease may be made on the basis of results of skin-test, histological picture, caverns revealed by urography, sterile pyuria etc^[16].

Therapy

The main principles of anti-TB chemotherapy are: continuity, controllability, succession of the treatment. The patient has to take minimum 4 anti-TB drugs simultaneously during a minimum of 4 months, depending on the form UGTB. Neglecting of these principles leads to development of drug-resistance of Mtb and relapse of TB. The classification of the anti-TB drugs is given in Table 3.

Table 3. The classification of the anti-TB drugs

Etiotropic therapy

The therapy for UGTB differs from the therapy of PTB. Thus, streptomycin and kanamycin are not recommended for UGTB; among fluoroquinolones ofloxacin or levofloxacin only are suitable for UGTB therapy. Moxifloxacin and sparfloxacin are respiratory fluoroquinolones, so they are good for PTB, but not optimal for UGTB.

PAS is highly recommended for UGTB with involvement of pelvic organs, amoxicillin/clavulanate should be prescribed together with meropenem or imipenem, as they potentiate anti-TB effect.

Cycloserin is highly recommended, if the patient has comorbidity of UGTB and non-specific UTI. Patient with comorbidity of UGTB and HIV and receiving anti-retrovirus therapy should be treated with rifabutin instead of rifampicin. Rifampicin and streptomycin are contraindicated for patients after organ transplantation. Amikacin as well as streptomycin and kanamycin are contraindicated for UTTB patients.

Depending on the form of UGTB 5 regimes of chemotherapy are defined:

Regime I is applied in new-revealed treatment-naive patients with drug-susceptible (or if there was no growth of Mtb) non-complicated KTB 1-2 stages, isolated TB epididymitis, patients who were diagnosed by histology after organ-removed surgery performed in general urology, if there is no other TB focus. Regime II is applied in new-revealed treatment-naive patients with drug-susceptible (or if there was no growth of Mtb) non-complicated KTB 3-4 stages.

Regime III is applied in new-revealed treatment-naive patients with drug-susceptible (or if there was no growth of Mtb) KTB 4 stage, KTB any stage complicated by UTTB, prostate TB, gUGTB.

Regime IV is applied in patients with relapse of UGTB, with high risk of MDR, independent on stage and form.

Regime V is applied in patients with MDR-UGTB, independent on the stage and form.

Every regime includes the phase of intensive therapy followed by the continuation phase (see Table 4).

Table 4. Standard schemes of a chemotherapy for UGTB

• Abbreviations: see Table 3.

Abbreviations see Table 3

The dosage depends on the weight; recommended ones are given in Table 5.

Table 5. Recommended daily dosage of antituberculous drugs for adults (mg)

Anti-TB drugs may be prescribed per os, but parenteral administration (optimal intravenous infusion) is preferable, as it provides better control and minimizes side effects.

Pathogenetic therapy

Some pathogenetic medications are used as additional treatment: tocopferol, canephron;trospium chloride for bladder TB 3 stage, afala and prostanorm for prostate TB etc^[16][42].

Surgery for UGTB

UGTB like any other UTI may and should be cured conservatively (if it is diagnosed in-time).

Surgical intervention is indicated for KTB 3-4 stages, for correction of complications (UTTB).

Table 6. Surgical treatment for UGTB

All surgical interventions should be performed on the background of anti-TB therapy, the exact time point will be estimated after histological investigation of the removed tissue^[37][39][40].

BCG-induced UGTB

The intravesical bacillus Calmette-Guerin (BCG) after transurethral resection in Ta and T1 bladder cancer provides a significantly better prophylaxis of tumor recurrence than TUR alone, and superiority of BCG over mitomycin C for prevention of tumor recurrences has been shown as well. Instillation of BCG causes specific inflammation of the bladder mucosa that kills cancer cells – but it should be controlled local temporary inflammation. The loss of the control results in the spread of infection. Systemic dissemination of bacilli may lead to development of generalized BCG-induced TB, when all organs, including meninges are involved in TB inflammation. Among urogenital complications of BCG-therapy bladder TB is most common, TB orchiepididymitis and TB of penis and rare. Frequency of BCG induced granulomatous prostatitis differs from 3 to 75%. In the majority of the cases the patients are asymptomatic and only rarely (0.9–1.3%) are there clinical complaints, slight induration of the prostate or elevated PSA level[43]. Mycobacterial prostatitis does not require anti-TB therapy as it is clinically insignificant, but rather close monitoring^[44][45].

Diagnostic criteria for BCG-induced bladder TB are: dysuria and pyuria in 3 weeks after the instillation of BCG, decreasing of the bladder volume. Patho-histological confirmation is crucial, but in about 50% only fibrosis and inflammation may be found in the biopsies. Microbiology is not helpful. Involvement of the detrusor and development of a shrinked bladder represent the clinical background or the so-called iatrogenic BCG-induced bladder TB.

Iatrogenic BCG-induced bladder TB should be treated with rifampicin 0.6 and isoniazid 0.6 for 2 months; if there is also growth of non-specific microflora in urine – in addition levofloxacin 0.5 daily should be prescribed. If in 8 weeks patients became well – without dysuria and normal urinalysis – anti-TB therapy is finished. If in 8 weeks the dynamic is good, but patient isn’t still recovery – anti-TB therapy should be continued for more two months. If in 8 weeks of the therapy with rifampicin and isoniazid result is poor and bladder volume is 100 ml and less – cystectomy (in male patients – cystprostatectomy) is indicated with following enteroplastic; after surgery therapy with rifampicin, isoniazid and levofloxacin should me continued for at least 2 months – till full recovery (normal urinalysis, sufficient bladder volume).

Figure 1. Algorithm of the management of BCG-induced UGTB patient

To prevent this complication vaccine shouldn’t be introduced in time of cystitis. If a patient has dysuria and leucocyturia – BCG-instillation is contra-indicated, and therapy with non-steroid antiinflammatory drugs and nitrofurantoin or fosfomycin for 3-5 days should be prescribed. BCGtherapy may be continued only when symptoms of cystitis improved. The scheduled BCG regimen shouldn’t be resumed after recovering of BCG-induced TB.

Patients with BCG-induced orchiepididymitis should be treated with rifampicin 0.6 + isoniazid 0.6 + levofloxacin 0.5 daily for 2 months, in case of abscess formation orchiectomy is indicated. Patients with symptomatic BCG-induced prostatitis should be treated with rifampicin 0.6 + isoniazid 0.6 + levofloxacin 0.5 daily for 4 -6 months up to dissolving symptoms, with following surveillance for 2 years with control examination each 6 months.

Follow-up and prevention

Patients with UGTB should be followed-up for control of eradication or if symptoms persist or recur after completion of the therapy every 6 months for 1-3 years, depending on form and stage of the disease.

To prevent a relapse repeated short-course (for 2 months) therapy with isoniazid and rifampicin is recommended for patients with complicated UGTB; in MDR-UGTB preventive therapy is prescribed accordingly to the sensitivity of Mtb.

Specific prophylaxis from UGTB is absent now.

Abbreviations

BCG: Bacillus Calmette–Guérin, FGTB: female genital tuberculosis, FNAC: Fine needle aspiration cytology, gUGTB: Generalized urogenital tuberculosis, HIV: human immunodeficiency virus, IVU:Intravenous urography, KTB: Kidney tuberculosis, MGTB: male genital tuberculosis, MDR: multidrug resistant, Mtb:Mycobacterium tuberculosis, PCR: polymerase chain reaction, PTB: pulmonary tuberculosis, TB: tuberculosis, UGTB: Urogenital tuberculosis, UTI: urogenital tract infection, UTTB:urinary tract tuberculosis, WHO: World Health Organization

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