Genito-urinary tuberculosis

1. DR. SOMENNDRA BANSAL
DR. SHALU GUPTA
SMS MEDICAL COLLEGE, JAIPUR
GENITOURINARY
TUBERCULOSIS
(GUTB)

2.  March 24, 1882, the first successful isolation
and identification of the tubercle bacillus by
Robert Koch
 World Tuberculosis Day- March 24

3.  Mycobacterium tuberculosis complex
(MTBC)- group of closely related acid-fast
bacteria
 M. tuberculosis and M. africanum infect only
humans, whereas the others infect humans
and additional mammals.

4.  GUTB has been found in patients with
pulmonary TB in
2% -10% in developed countries and
15%-20% in developing countries
 Active GUTB presents 5-25 years after
primary infection. So it is uncommon in
young children

5.  GUTB is the second MC form of extrapulmonary
TB after lymph node involvement
 Kidney is usually primary organ infected in
urinary disease
 Epididymis in men and fallopian tubes in women
are the primary sites of genital infection
 The usual frequency of organ involvement is:
kidney, bladder, fallopian tube, and scrotum

6. DEVELOPMENT OF GENITOURINARY DISEASE
4 routes by which GU TB develops:
1) Hematogenous spread (principal route)
 Typical sites for GU seeding are kidneys and epididymis
2) Ascending or retrograde infection through urinary system
 (bladder irrigation with BCG for T/t of bladder cancer- 0.9%)
3) Contiguous spread from other organ systems like spine,
psoas, GIT
 TB do not respect anatomic boundaries. GIT-TB can extend
into the GU tract to form enterorenal and enterovesical
fistulae
4) Direct inoculation
 Cases include autoinoculation of external genitalia from
infected stool or urine, and person-to-person genital
inoculation after contact with infected genital or oral lesions

7. Primary infection (droplet infection) to lungs or bowel
Blood borne metastatic spread to kidneys
Organisms settle in periglomerular capillaries
End-arteritis
Caseating granulomas
Caseous necrosis
Erosion of papilla
Erosion of calyx (Ulcerocavernous lesion)
PATHOGENESIS

8. C/F OF GUTB
The GUTB has varied presentation:
1. Recurrent or resistant UTI, sterile pyuria with or without hematuria
2. Irritative voiding symptoms, i.e., frequency, urgency, and dysuria
3. An incidental diagnosis in a known case of TB
4. Renal (hydronephrosis/pyonephrosis) or epididymal mass
5. Infertility and pelvic inflammatory disease
6. Renal failure (CKD due to parenchymal infection and obstructive
uropathy
7. Other ways of presentation: flank pain with acute pyelonephritis,
non-healing wounds, sinuses, or fistulae (nephrocutaneous fistula
or vesicovaginal fistula), and hemospermia
 MC presenting symptoms- irritative voiding, which are found in
>50% of the patients.
 The other symptoms in GUTB can be fever, weight loss, anorexia,
backache, and abdominal pain

9. KIDNEY
 MC site of GUTB
 With disease progression, kidney becomes
nonfunctional, a process called
autonephrectomy (up to 33% of patients of
GUTB )
 2 types of autonephrectomy.
Caseo-cavernous type: viable tissue is
replaced with granulomas
Fibrotic: severe scarring and calcification
resulting in a shrunken kidney

10.  Chronic sterile pyuria
 Gross hematuria is seen in only 10%
 Microscopic hematuria up to 50% of the cases
 Acute renal pain usually occurs secondary to luminal
obstruction by blood clots, sloughed renal papilla, or
flakes of calcification.
 Chronic dull ache may be due to infundibular,
pelviureteric, or ureteric stricture
 Hypertension
 ESRD develops in approximately 7% of patients
 CRF which can be either due to renal parenchymal
destruction secondary to infection or due to
obstructive uropathy

11. URETER
 Inflammation leads to scarring and strictures,
commonly in distal end of ureter at VUJ
 Strictures can also occur throughout ureter in a
“pan-ureteral” fashion leading to a “beaded
corkscrew” appearance
 When ureters are distorted from scarring, both
obstruction and urinary reflux can develop
 In the late stages, as ureteric orifices become
fibrotic and fixed, leads to development of VUR
 Urinary obstruction resulting from strictures is
an important cause of renal failure in GU TB

12. BLADDER
 Early stage( acute phase): irritative voiding
symptoms
 Late stage: reduced compliance and capacity,
manifesting as frequency,
Urgency develops if bladder is extensively
involved
 “Thimble bladder" (due to mural fibrosis and
contracture) may present with urinary
incontinence
 "Golf-hole ureter: Chronic inflammation and
extensive fibrosis at VUJ

13. EPIDIDYMIS, VAS DEFERENS, TESTES, AND
SCROTUM
 Epididymis- 2nd mc GUTB site (10% to 55% of
GU TB patients)
 Initially affects the more vascular globus minor
 Infertility due to epididymal and/or vasal
obstruction
 Nodular beading of the vas is a characteristic
physical finding
 Neglected cases may present as scrotal sinus in
posterior surface

14. PROSTATE AND SEMINAL VESICLES
 TB should be suspected in patients with chronic prostatitis
that persists despite antibiotics
 TB of prostate may cause nodularity on DRE mimicking
cancer
 Tuberculous prostatitis and urethritis can cause ''beefy
redness'' and superficial ulcerations on endoscopic
examination
 Dilatation of the prostatic urethra, and ''golf hole''
dilatation of prostatic ducts
 Fulminating prostatic involvement can cause abscess
formation and subsequent perineal fistulization
 TB of seminal vesicles may cause infertility, which can be
first symptom of GU TB
 Low-volume ejaculate, oligospermia, azoospermia, or
hemospermia

15. PENIS AND URETHRA
 Urethra appears somewhat resistant to TB
 It is typically associated with prostate
infection and can manifest with stricture
formation, urethroscrotal fistulae
 Penis: ulcer, cavernositis ,cold abscess
,penile deformity or impotence

16. ADRENAL GLANDS
 Adrenocortical insufficiency
 Addison's disease

17. DIAGNOSIS
 In developed countries, the primary goal of
diagnostic workup is isolation of MTBC in
culture for drug susceptibility testing
 Because up to 20% of GU TB occurs
concurrently with pulmonary TB. it is useful to
also assess for the presence of pulmonary
disease.

18. DIAGNOSTIC WORKUP
1. Urinalysis – Sterile pyuria
2. CBC, ESR, RFT’s, X ray chest
3. Urine for acid fast bacilli (AFB) and culture x 3
(preferably 5)
4. Nucleic Acid Amplification Tests
5. Histopathology
6. Screening Tests
7. Radiography-plain radiography, IVP, CT
urography,
8. Retrograde and Antegrade Pyelography
9. USG
10. MRI
11. Cystoscopy and Ureteroscopy

19. CULTURE
 Current gold standard for diagnosis of GUTB is urine acid
fast bacilli (AFB) culture
 First-void urine is best sample because urine is most
concentrated at that time.
 3-5 samples on consecutive early morning should be
collected for maximum yield (because of intermittent
shedding of bacilli)
 These should be cultured immediately after collection
because prolonged exposure to urine acidity can retard
mycobacterial growth
 The sensitivity of urine AFB cultures is as high as 80%
when done in this manner
 Ziehl-Neelsen stains for urine AFB (sensitivity is <50%)
 urine AFB yield = 30% , urine culture yield = 60 %
 In addition, any tissue obtained from biopsy or surgery
should also be cultured.

20. Culture media
a) Solid based
 Löwenstein-Jensen (LJ) medium (egg-based)- 4-6 weeks
 Middlebrook 7H10 (agar based)- 1 week earlier than LJ
media
b) Liquid based
 BACTEC (Culture results: 9-15 days and
Sensitivity results: 21 days
 Mycobacteria Growth Indicator Tube (MGIT)- 10 days
 Current guidelines recommend culturing on at least one
solid medium concurrently with the liquid system to
maximize yield

21. NUCLEIC ACID AMPLIFICATION TESTS (NAAT)
• Providing results within 1 to 2 days
• This can also aid detection in cases with low
bacillary load, in which culture might fail to
isolate organisms
• Sensitivities- 87% to 96%
• Urine contain natural inhibitors that interfere
with the DNA or RNA amplification process,
potentially resulting in false-negative test

22.  Unlike cultures, NAATs cannot be used to
monitor response to treatment because nucleic
acids are shed from dead organisms and test
results can remain positive despite adequate
treatment
 In 2010, WHO endorsed the newest TB PCR
assay
GeneXpert MTB/RIF (It simultaneously
detects presence of MTBC and rifampin
resistance)

23. YIELD
 Urine AFB= 30 -40 %, specificity = 95%
 Urine culture= 40 - 60%,
 BACTEC= Sensitivity- 95%, Specificity- 97%
 PCR= Sensitivity- 95%, Specificity- 97%

24. SCREENING TESTS
 Do not differentiate between latent and active
TB
 Ideal use for these tests in screening of
individuals for presence of latent TB infection
 Tuberculin skin test (TST)-89%
 Interferon-gamma release assays (IGRAs)-
results available after 24 hrs
QuantiFERON-TB Gold In-Tube test (QFT-
GIT)-83%
T-SPOT TB test-91%

25. RADIOGRAPHY- PLAIN RADIOGRAPHY KUB
 Plain Radiography (KUB)- demonstrate
calcifications caused by TB, which are present in
>50% of patients
 Pseudo calculi ( calcification)
 Faint punctate calcifications, globular calcifications,
cement, putty kidney
 Papillary necrosis appears as triangular ringlike
(Curvillinear)calcifications in the collecting system
 Ureteral calcifications, which are characteristically
intraluminal as opposed to the mural calcifications
of schistosomiasis

26. RADIOGRAPHY- INTRAVENOUS UROGRAPHY (IVU)
 Gold standard for imaging early renal TB.
 The earliest radiographic changes of GUTB: changes in
minor renal calyces with loss of sharpness and blunting
 Calyceal erosions have a moth-eaten appearance and
lost calyx due to infundibular stenosis
 When a calyx or infundibulum is stenosed, contrast
excretion by renal parenchyma may fail, creating a
“phantom calyx” in location where the calyx should be
visible
 Nonfunctional kidneys
 Filling defects
 MC findings on IVU are obstructive changes resulting
from scarring and distortion of collecting system: calyceal
obliteration, infundibular narrowing, hydrocalycosis,
segmental or total hydronephrosis, and hydroureter

27.  Ureteral TB can manifest as a rigid, calcified,
straightened, pipestem ureter that is tubular
and lacks normal peristaltic activity on IVU.
 The ureter may also take on the appearance
of a beaded corkscrew as a result of nodular
fibrosis along entire ureter.
 Stricture of ureter (number, site, length) –
proximal HDN
 Reduced capacity – Thimble bladder

28. (A) IVU showing lower ureteric stricture (arrow head).
(B) Cystogram showing thimble bladder with massive
VUR

29. RADIOGRAPHY- CT UROGRAPHY
 Most frequently used modality for imaging TB
in developed countries, where it has largely
replaced IVU
 CT reveals calcifications, scarring, and signs
of obstruction
 CT is less sensitive for detecting the minimal
urothelial thickening, subtle papillary
necrosis, and other changes of early renal
TB, for which IVU is still the preferred study

30. RADIOGRAPHY- RETROGRADE AND ANTEGRADE
PYELOGRAPHY
 Replaced by CT urography.
 Indicated in renal insufficiency or contrast allergy, where IVU
or CT not possible
Retrograde Pyelography:-
 Ureteral stricture – number, site, length, prox. Dilatation
 Non visualized kidney on IVU (occasionally)
 Ureteral catheterization to obtain urine sample for culture
Percutaneous antegrade Pyelography:-
 Poor or non- functioning hydronephritic kidneys
 Aspirate contents for culture

31. RADIOGRAPHY- VOIDING CYSTOURETHROGRAM
 Reduced bladder capacity
 Thimble bladder
 Trabeculations and cystitis
 Vesico ureteral reflux

32. USG
 Limited role in diagnosis of GU TB
 Hydronephrosis / Pyonephrosis
 Perinephric abscess
 Restriction of renal movement during breathing
suggests a perinephric or psoas abscess
 A primary use of US in GU TB is to follow
hydronephrosis in patients who are receiving
medical treatment because fibrosis during healing
can worsen urinary obstruction.

33. MRI
 MRI is not commonly used in workup of GU
TB
 MRU can be more sensitive than IVU in
showing urothelial thickening and caliectasis
 Addition of DWI can help distinguish
hydronephrosis from pyonephrosis
 MRI with DWI can be used to monitor renal
fibrosis

34. CYSTOSCOPY AND URETEROSCOPY
 Limited role in the diagnosis of TB
Cystoscopic findings:
 Reduced bladder capacity and patulous ureteral
orifice
 Granulations or tubercles around ureteral orifices
 TB ulcer or scar of healed ulcer
 A “golf-hole” ureteric orifice is suggestive of TB,
and, when found, upper tract imaging or endoscopy
should be performed
 Biopsy is needed if there is suspicion of
malignancy. It should be done only after 4-6 weeks
of medical therapy to prevent dissemination of the
disease (i.e., tubercular meningitis).

35. TB Golf-hole ureter

36. RADIOISOTOPE SCANNING
 Function
 Assessment of response to treatment

37. DIAGNOSTIC ALGORITHM FOR URINARY TRACT TB

38.  Criteria for definitive diagnosis of GUTB: on
the basis of presence of one major and/or
two minor criteria.
 Major criteria: granulomatous lesion on
histopathology, AFB positivity in urine or
histopathology and a positive PCR.
 Minor criteria: changes suggestive of TB on
IVU/CT or MRI, hematuria, raised ESR,
and/or pulmonary changes of old healed
granulomas.
Indian Journal Of Urology 2008

39. MEDICAL MANAGEMENT
Successful medical t/t of TB requires multiple drugs for
several reasons:
 First, the tubercle bacilli exist in different micro-
environments within host. These apply different pressures
on organism and cause it to exhibit different metabolic
needs and replication speeds.
 The drugs vary in their activity against MTBC; some are
bactericidal, whereas others are only bacteriostatic.
 Some drugs work best on rapidly replicating bacteria,
whereas others are more effective against dormant bacilli.
 The drugs also penetrate differently into various tissues
and perform optimally at different pHs.
 In addition, multiple drug therapy prevents the emergence
of drug-resistant strains.

40. FIRST-LINE ATT
DRUG ADULT DOSAGE
(DAILY)
ADULT DOSAGE
(INTERMITTENT)
Isoniazid (INH) 5 mg/kg (max 300 mg) 15 mg/kg (max 900 mg)
3 times/wk
Rifampin 10 mg/kg (max 600
mg)
10 mg/kg (max 600 mg)
3 times/wk
Rifabutin 5 mg/kg (max 300 mg) 5 mg/kg (max 300 mg)
3 times/wk
Rifapentine (C/I in HIV positive,
cavitary pulmonary ds.
Extrapulmonary TB)
10 mg/kg/wk PO (max 600 mg)
Continuation phase only in
very select patients
Pyrazinamide 40-55 kg: 1000 mg
56-75 kg: 1500 mg
76-90 kg: 2000 mg
3 times/wk:
40-55 kg: 1500 mg
56-75 kg: 2500 mg
76-90 kg: 3000 mg
Ethambutol 40-55 kg: 800 mg
56-75 kg: 1200 mg
76-90 kg: 1600 mg
3 times/wk:
40-55 kg: 1200 mg
56-75 kg: 2000 mg
76-90 kg: 2400 mg

41. SECOND LINE ATT
DRUG ADULT DOSAGE
(DAILY)
MAIN ADVERSE EFFECTS
Streptomycin
Capreomycin
Kanamycin/ Amikacin
15 mg/kg IM, IV (max 1
g)
Vestibular and auditory toxicity, renal
damage
Cycloserine 10-15 mg/kg in 2 doses
(max 500 mg bid) PO
Psychiatric symptoms, seizures
Ethionamide 15-20 mg/kg in 1 or 2
doses (max 500 mg bid)
PO
GIT and hepatic toxicity, hypothyroidism,
optic neuritis, neurotoxicity
Levofloxacin 500-1000 mg PO, IV GIT toxicity, CNS, rash, dysglycemia, QT
prolongation, tendinitis or tendon rupture
Moxifloxacin 400 mg PO, IV Same as Levofloxacin
Aminosalicylic acid
(PAS)
8-12 g in 2 or 3 doses
PO
GI disturbance, hepatitis, hypothyroidism
Linezolid 600 mg PO bid Bone marrow suppression, peripheral
and optic neuropathy, hepatic toxicity
Bedaquiline
(Drug resistance
pulmonary TB)
400 mg PO Headache, nausea, arthralgias, QT
prolongation, hepatic toxicity

42. Drug Mech. Of Action Adverse effect
1)Isoniazid Inhibits mycolic acid synthesis Hepatic toxicity,
peripheral neuropathy
2) Rifampicin Inhibits RNA polymerization Hepatic toxicity, Flu like
syndrome, pruritis
3) Pyrazinamide Inhibits fatty acid synthesis Hepatic toxicity, arthralgia,
hyper uricemia, pruritis
4) Ethambutol Inhibits cell wall synthesis Decreased red-green
color discrimination,
decreased visual
acuity,Optic neuritis
5) Streptomycin Inhibits protein synthesis Nephrotoxicity, vestibular
& auditory toxicity

43.  All are bactericidal except ethambutol (static)
 Before ATT, baseline measurements
CBC
LFTs, RFTs
HIV, Hepatitis B and C

44.  GUTB can be successfully treated with standard
short-course regimen of 6 months of first-line ATT
 Treatment begins with an intensive phase of 2
months of daily INH, rifampin, and pyrazinamide,
followed by a
 Continuation phase of 4 months of INH and rifampin
given daily, or alternatively thrice weekly.
 Pyridoxine (vitamin B6) administration minimizes the
risk of INH-induced peripheral neuropathy.
 First-line drugs reach high concentrations in the urine
and work well in acidic environments. The intensive
phase of treatment targets rapidly multiplying
bacteria, whereas the continuation phase attempts to
eradicate slow, sporadic multipliers and persistent

45.  Treatment for at least 9 months is recommended for
extensive pockets of infection, concurrent smear-
positive cavitary pulmonary disease, CNS
involvement, or a delay in positive cultures converting
to negative.
 If the patient is unable to take pyrazinamide for at
least 2 months, because of either side effects or drug
resistance, the duration of therapy should also be 9
months or longer
 During therapy, liver enzymes should be monitored
monthly in those with preexisting liver disease
because all first-line agents except ethambutol can
cause hepatic toxicity that can be reversed with drug
discontinuation

46. Role of steroids
 anti-inflammatory effects of corticosteroids
prevent an unchecked host immune response
from causing excessive tissue destruction and
scarring
 They are strongly recommended for TB
meningitis and TB pericarditis, and they are
sometimes used in patients with severe
pulmonary TB, when antibiotic treatment leads
to a paradoxic worsening of symptoms, in a few
patients to prevent ureteral strictures and
bladder contraction

47. PREGNANCY AND LACTATION
 avoid pregnancy while being treated for active TB
 If the diagnosis is discovered during pregnancy,
prompt therapy should be initiated because the risk to
the fetus from TB outweighs the risk of adverse drug
effects.
 Treatment consists of INH, ethambutol, rifampin, and
pyridoxine, for 9 months.
 Pyrazinamide is avoided because the effects on the
fetus are unknown.
 Postpartum, women may breastfeed their infants
because drug concentrations in breast milk are too
low to cause toxicity

48. MONITORING FOR TUBERCULOSIS RELAPSE
 TB can relapse in 2% to 6% of pulmonary TB
patients, particularly within first year after t/t
 GU TB patients may relapse at a higher rate
than pulmonary TB patients, in 6.3% to 22% of
cases, even after 12 months of medical therapy
 Pulmonary TB patients are usually followed for 2
years after completing treatment; for GU TB
patients, some investigators have
recommended 10 years of follow-up, because
the average time of relapse was 5.3 years

49. DRUG RESISTANCE
 MDR-TB :- Resistance to rifampicin & INH
(T/t- > 18 months)
 XDR-TB ( extensively drug resistance):-
R,INH,FQs, AGA/Capreomycin
 XDR-TB is resistant to INH, rifampin, any
fluoroquinolone, and at least one of the
injectable second-line aminoglycosides
(amikacin, kanamycin, or capreomycin).
 XDR-TB is exceedingly difficult to cure, with
complicated regimens involving five or six drugs
for 2 years or more.

50. SURGERY
 About 55% of patients with GU TB will require surgical
management during the course of their disease
 Surgical procedures are performed
1) to relieve urinary obstruction and drain infected material,
2) to remove nonworking infected kidneys in cases resisting cure,
3) to improve medically resistant hypertension secondary to a
functionally excluded kidney,
4) to reconstruct the urinary tract (uretero-calycostomy, ureteric
reimplantation, ileal ureteric replacement).
 The optimal timing of surgery is 4 to 6 weeks after the initiation of
medical therapy. This delay allows active inflammation to subside,
the bacillary load to decrease, and lesions to stabilize.

51. SALVAGE OF KIDNEY
 Cortical thickness > 10 mm
 GFR > 15 ml/min
 Distal ureteric stricture
Good potential for recovery

52. PROCEDURES TO RELIEVE OBSTRUCTION
 Temporary and immediate drainage of
obstruction is recommended, preferably by
retrograde ureteric stenting. If it fails, then
PCN
 High-contrast injection pressures during stent
and PCN placement should be avoided to
prevent possible dissemination of infection

53. NEPHRECTOMY
Indications
 Patient with a nonfunctional kidney and
recalcitrant or recurrent TB despite optimal
medical therapy.
 Nonfunctional kidney and medically resistant
hypertension.

54. URETEROPELVIC AND URETERAL SURGERY
1) Endoscopic Management
 Balloon dilatation + Stenting by retrograde or antegrade access
 Corticosteroids may be added if deterioration is detected.
 Failure to improve or progression after 6 weeks of medical
treatment is an indication for open surgical management.
2) Open Surgical Options
 Dismembered pyeloplasty is feasible for extrarenal pelves with
short-segment scarring
 Nondismembered (flap) pyeloplasty is preferred for longer
strictures but may not be feasible because of excessive scarring
of the pelvis.
 When anatomic reconstruction is not possible, ureterocalicostomy
 Upper and middle ureter stricture- ureteroureterostomy/ Davis
intubated ureterotomy
 Lower ureter strictures- ureteroneocystostomy

55.  Simple mobilization of lateral attachments of the
bladder on C/L side, accompanied by division of
superior vesical artery, may provide 2 to 3 cm of
length to bridge a small gap.
 In patients with good bladder capacity, a psoas hitch
may also be performed. Care must be taken to avoid
the genitofemoral and femoral nerves when placing
these sutures (upto 5 cm)
 Boari flap is bridging a longer gap of 10 to 15 cm and
may be performed in combination with a psoas hitch
 Ileal interposition (ileal ureteric replacement) can be
done in patients with multiple or recurrent strictures
when the native ureter is no longer an adequate
conduit

56. BLADDER SURGERY
 Augmentation cystoplasty and bladder substitution in
m/m of TB contracted bladder.
 Augmentation is indicated when frequency, nocturia,
urgency, pain, and hematuria become intolerable—
typically when bladder capacity is <100 mL
 For severely contracted bladders, ileocecum or
sigmoid segments are most suitable. When only half
the bladder is diseased, ileum is often used. Other
segments used in augmentation include stomach and
cecum.
 Thimble bladders with capacity <20 mL are best
managed by orthotopic bladder substitution
 Complications of either bladder augmentation or
substitution include mucus production, electrolyte
derangements, and secondary bacterial infection.

57. URETHRAL PROCEDURES
 Bladder neck contracture- TUI of contracture
 Urethral strictures- endoscopically and often
require repeated procedures.
 Tuberculous urethral fistulae are treated by
initiation of medical therapy and suprapubic
bladder drainage. Delayed reconstruction is
preferred.

58. Ejaculatory duct obstruction
 TURED
 combined incision-resection (TUIRED)
 assisted reproduction with an Intrauterine
insemination (IUI), In-vitro fertilization (IVF)
Epididymal obstruction
microsurgical reconstruction.
vasovasal anastomosis
vaso-epididymal anastomosis

59. THANK
YOU