HIV and Tuberculosis of Urinary Tract: What is The Role of Urologists?

Advanced Urology Course (AUC), Malaysian Board of Urology
AIDS and Tuberculosis in
Genitourinary Tract:
What is The Role of Urologists?
Dr. Vincent Khor Wei Sheng
Medical Officer / Urology Trainee (UT1)
Department of Urology
Universiti Putra Malaysia (UPM) Teaching Hospital
Serdang Hospital

Outlines of Presentation
• HIV and AIDS
• HAART
• Urological Diseases / Complications in HIV
(including infection, malignancy)
• HIV and Men (Andrological Aspect) –
circumcision, sexual dysfunction and infertility
• Renal Dysfunction and Transplant for HIV Patients
• Urogenital TB
• Pathophysiology and Classification
• Spectrum of Disease Presentation
• Laboratory and Imaging Assessment
• Management
• Conclusion – What is The Role of Urologist?

HIV and AIDS
• First described in 1981 and HIV discovered in 1986, HIV
pandemic has affected millions of people worldwide.
• The introduction of highly active anti-retroviral therapy
(HAART) in mid-1990s has transformed HIV infection
from an invariably fatal disease to a chronic disorder with
relatively benign course.
• Due to the prolonged life expectancy, urologists are
increasingly likely to encounter HIV-positive patients who
present with the same urological problems as general
population. Performing surgery in HIV-infected individual
raises safety issues for both patients and the surgeon.

HAART
References:
1. Campbell and Walsh Urology, 10th Edition
2. Heyns CF, Smit SG, van der Merwe A, Zarrabi AD. Urological aspects of HIV and AIDS. Nat Rev Urol. 2013;10(12):713-722.
• Recommended to start in symptomatic patients with AIDS-defining illness and in
asymptomatic patients with CD4 count < 350 or if blood viral load (BVL) > 100,000
copies / ml.
• Deferring until low CD4 count increases the risk AIDS-related mortality due to the
increased risk of immune reconstitution inflammatory syndrome (IRIS)

Urological Manifestations of HIV
Infections and Treatment
• STDs – Genital Herpes, HPV > warts and condylomata, Syphilis,
Chancroid, Urethritis, Molluscum Contagisum
• Urogenital infection - kidney, bladder infection, prostatitis, epididymo-
orchitis, perineal skin infection / Fournier’s Gangrene
• Voiding dysfunction
• Urolithiasis
• Renal Impairment and HIV-Associated Nephropathy
• HIV-related malignancies including Kaposi sarcoma, Non-Hodgkin
lymphoma, germ cell testicular tumour
• Urological cancer including prostate, bladder and renal cancer
• Andrological complications - erectile dysfunction, hypogonadism,
infertility

Urogenital Infection in HIV
• UTI is common in HIV +ve patients, particularly if CD4 count
< 200 or BVL is high.
• Common pathogen: E. coli (80%), Pseudomonas (33%) and
other gram negative enterobacteria.
• Salmonella spp. sometimes can cause bacteremia and urosepsis
• Opportunistic infection including fungal, parasites and
mycobacterium can cause renal abscesses, iliopsoas abscesses,
prostate abscesses.
• Nosocomial infections are common in HIV patients - UTI is the
2nd most common nosocomial infection after bacteremia,
more likely caused by S. aureus than any other pathogen.
References:
1. Heyns CF, Groeneveld AE, Sigarroa NB. Urologic complications of HIV and AIDS [published correction appears in Nat Clin Pract Urol. 2010 Apr;7(4):178]. Nat Clin Pract
Urol. 2009;6(1):32-43.

Urogenital Infection in HIV
References:
Urol. 2009;6(1):32-43.
3. Campbell and Walsh Urology, 10th Edition.

Urolithiasis
• Protease inhibitor can cause crystal nephropathy but risk is highest
with indinavir.
• 5-25% of patients on indinavir treatment
• Radiolucent even on CT scan > hydroneprhosis, renal parenchymal
defects, scarring, atrophy, and perirenal or periureteric stranding.
• RPG typically filling defect
• Nephrocalcinosis / cortical calcification might be seen in renal TB
or with Pneumocystis or CMV infection.
• Other contributing factors: malnutrition, diarrhoea, dehydration,
urinary acidification, hypocitraturia, hyperuricosuria 2’ cell lysis
after chemotherapy for AIDS-associated lymphoma
References:
Urol. 2009;6(1):32-43.

Urolithiasis
• Treatment of Indinavir-induced urolithiasis:
• Stop indinavir temporarily - can restart after resolution of
acute symptoms and passage of stone with aggressive oral
hydration.
• Increase oral intake > urine production 2L/day or more
• Urine acidification with amino-acid L-methionine
• Double J stent if persistent fever / intractable pain
• Indinavir stones are usually gelatinous in consistency,
ESWL will not be effective
• Ureteroscopic stone extraction or percutaneous
nephrolithotomy might be required in some cases
References:
Urol. 2009;6(1):32-43.

HIV-Associated Cancer
• Malignancy more common in HIV +ve patients probably due to:
decreased immune surveillance, direct effect of viral proteins /
cystokine dysregulation.
• Kaposi sarcoma (Herpesvirus 8), Non-Hodgkin Lymphoma (EBV),
Cervical / Penile / Anal Ca (HPV)
• HAART has dramatically reduced incidence of mortality of Kaposi
sarcoma and NHL (increased CD4 count and decreased BVL)
• Longer life expectancy > non-HIV associated cancer including
prostate, bladder, renal cell carcinoma
• Currently, non-HIV associated cancers comprise about 70% of
cancers in HIV-infected patients on HAART compared with about
20% pre-HAART era.
References:
Urol. 2009;6(1):32-43.

HIV-Associated Cancer
• Testicular tumour incidence in
immunocompromised is 20-57 times
more than normal population
• Germ-cell testicular tumours are
3rd most common HIV-associated
cancer.
• NHL of testes can present bilaterally
or dissemination. Treatment
outcomes equal to those without HIV
and complete remission reported in
50-75% with systemic treatment; but
replaces and rapid progression might
be higher than general population.
References:
Urol. 2009;6(1):32-43.

Prostate Cancer in HIV Men
• Increasingly more important men health problem with HAART
• Similar disease course with HIV-ve patients
• Standard PSA testing without the need for adjustment
• Should be offered all possible treatment options including surgery, radiation,
ADT and observation.
• Treatment considerations: tumour grade, stage, PSA levels, comorbidities and
HIV considerations: CD4 count, viral load, opportunistic infections,
medications)
• Patients with AIDS and metastatic disease may respond poorly to ADT if they
are hypogonadal before treatment.
• SR shows no increased in morbidity in all treatment modalities in HIV patient
but long term outcomes have not been reported.
References:
Urol. 2009;6(1):32-43.
3. Wosnitzer MS, Lowe FC. Management of prostate cancer in HIV-positive patients. Nat Rev Urol. 2010;7(6):348-357.
4. Silberstein J, Downs T, Lakin C, Kane CJ. HIV and prostate cancer: a systematic review of the literature. Prostate Cancer Prostatic Dis. 2009;12(1):6-12.

Circumcision and HIV
Prevention
• Cochrane analysis showed strong evidence that circumcision
reduces the risk of HIV acquisition by heterosexual men by 38-
66% over 24 months but there is no enough evidence for HIV
prevention among MSM at present.
• Latest meta-analysis by Sharma et al. in 2018 shows circumcision to
be effective in reducing HIV risk for both heterosexual and
homosexual men.
• Mechanisms: numerous HIV target cells are present under the
dermis of foreskin; inner surface of foreskin poorly keratinised and
prone for laceration (site of HIV entry) and infection of the prepuce
with anaerobic bacteria > infiltration of Langerhans cells (HIV target
cells)
References:
2. Siegfried N, Muller M, Deeks JJ, Volmink J. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2009;(2):CD003362.
Published 2009 Apr 15.
3. Wiysonge CS, Kongnyuy EJ, Shey M, et al. Male circumcision for prevention of homosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2011;(6):CD007496.
Published 2011 Jun 15.
4. Sharma SC, Raison N, Khan S, Shabbir M, Dasgupta P, Ahmed K. Male circumcision for the prevention of human immunodeficiency virus (HIV) acquisition: a meta-
analysis. BJU Int. 2018;121(4):515-526.

Circumcision and HIV
Prevention
• Another meta-analysis by Yuan et al. found that circumcision is
likely to protect MSM from HIV infection especially in low and
middle income countries and might also protect them from HIV
and penile HPV infection
• Meta-analysis by Lei et al. shows that male circumcision provided
a 70% protective effect to HIV(-) men but not females from HIV
acquisition at the population level.
• Ethical concern to offer medical circumcision? The promotion
of circumcision as HIV preventive measure does not appear to
increase higher-risk sexual behaviours in heterosexual men.
Ongoing sexual health education and avoidance of high-risk
behaviours are essential.
References:
1. Lei JH, Liu LR, Wei Q, et al. Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse for Both Males and Females: A Meta-Analysis. PLoS One.
2015;10(5):e0125436. Published 2015 May 5.
2. Yuan T, Fitzpatrick T, Ko NY, et al. Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-
analysis of global data. Lancet Glob Health. 2019;7(4):e436-e447
3. Gao Y, Yuan T, Zhan Y, et al. Association between medical male circumcision and HIV risk compensation among heterosexual men: a systematic review and meta-analysis
[published online ahead of print, 2021 Apr 30]. Lancet Glob Health. 2021;S2214-109X(21)00102-9.

Andrological Complications of HIV
• ED - relatively high incidence in HIV
+ve especially those with AIDS or
depressed CD4 counts.
• Men with HIV more likely to have
depression and the antidepressant
medications can decrease libido and
sexual performance
• Effective treatment of ED can increase
risk of spreading HIV - ethical
dilemma: important to educate for safe
sex and compliance to HAART
References:
Urol. 2009;6(1):32-43.
3. Cimen HI, Parnham AS, Serefoglu EC. HIV and Men. Sex Med Rev. 2016;4(1):45-52.

Infertility in HIV
• Infertility - HPA dysfunction, inflammation, infection of testes,
chronicity of disease, malnutrition or direct cytotoxic effect of HIV on
germinal tissue.
• Sperm washing for HIV+ve men followed by ART has proved to be
the safest method for infertility treatment in HIV +ve couples.
• Tested sperm carry a 5-10% risk of harbouring the virus > offspring
still at risk
• Intracytoplasmic sperm injection further reduces the risk of virus
transfer
• HIV +ve men on HAART has a very low risk of transmitting HIV to
his serodiscordant wife > unprotected sex at the time of maximum
fertility is an option compared to the expensive sperm washing + ART
•
References:
Urol. 2009;6(1):32-43.

Renal Dysfunction and HIV-
Associated Nephropathy
• Renal dysfunction can be due to HIV infection and its treatment, caused by
ischemic or nephrotoxic ATN in 26-46% of cases
• Causes include: volume depletion from diarrhoea, vomiting, sepsis,
obstructive uropathy from crystal depositions in tubular lumens,
retroperitoneal lymphoma, fibrosis or AKI with drug interactions with
HAART.
• In CKD patients, both peritoneal dialysis and haemodialysis increase the risk
of HIV transmission, risks of bacteremia due to immunosuppression.
• HIV-associated nephropathy (HIVAN) occurs in 10-30% of HIV patients
with high mortality even after treatment (30%). It is characterised by acute
renal failure, high grade proteinuria (>3.5g/day), edema, hypertension,
anemia and associated with CD4 counts < 350.
• Diagnosis of HIVAN is confirmed with renal biopsy (focal segmental
glomerulosclerosis and usually with tubulointerstitial nephritis)
References:
Urol. 2009;6(1):32-43.

Renal Transplant in HIV
• Some developed countries have include selected HIV patients for
renal transplant
• Clinical trial and meta-analysis have shown that kidney
transplantation can be performed with good outcomes in HIV-
infected patients. The mean graft survivals at 1 and 3 years were
90-91% and 73.7-81%
• Patients well controlled with HAART prior to transplantation who
are negative for HBV and HCV infections are ideal candidates
• The balance between the use of immunosuppression to prevent
graft rejection and preventing HIV complications of further
immunosuppression remains a challenge in this group of patients.
•
References:
1. Alameddine M, Jue JS, Zheng I, Ciancio G. Challenges of kidney transplantation in HIV positive recipients. Transl Androl Urol. 2019;8(2):148-154.
2. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients [published correction appears in N Engl J Med. 2011 Mar
17;364(11):1082]. N Engl J Med. 2010;363(21):2004-2014.
3. Zheng X, Gong L, Xue W, et al. Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis. AIDS Res Ther. 2019;16(1):37. Published 2019
Nov 20.

Urogenital Tuberculosis
• Curable and preventable disease but remains the leading
infectious disease cause of death worldwide.
• 15-40% of global burden 10 million annual cases of TB present
with Extrapulmonary TB (EPTB) – Urogenital TB (UG-TB) is
the 3rd most common presentation of EPTB.
• Neglected clinical issue, lack of awareness among physician
and delays in diagnosis results in disease progression, tissue
and end-organ damage and renal failure.
• Non-specific chronic symptoms, insidious onset in nature –
important to have the awareness of this disease entity in
endemic country like Malaysia.
References:
1. Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis - epidemiology, pathogenesis and clinical features. Nat Rev Urol. 2019;16(10):573-598.

Risk Factors of UG-TB
• Previously known as Genitourinary TB (including TB of KUB,
prostate, urethra, penis, scrotum, testicles, epididymis, vas deferent,
ovaries, FT, uterus, cervix and vulva. Currently, UG-TB is thought
to be more appropriate as urinary tract TB occurs more often
than genital TB.
• Risk factors: malnutrition, HIV infection, diabetes, chronic
renal and liver disease, alcohol and substance abuse,
smoking, homelessness, poor housing, pneumoconiosis,
genetics, vitamin deficiency, immunosuppressive drugs,
renal transplantation, dialysis.
• Epidemiology varies according to age, gender, geographical
region, HIV prevalence in community.
References:

Risk Factors of UG-TB
• Study 4 states in
Malaysia
• Females (1.5 times more
than Males), Malays and
Indians 1.3 and 1.5
times more common,
HIV infection, DM,
Hepatitis Infection, no
formal education and
those living in urban
areas (urban residents)
have increased risk of
EPTB of EPTB
References:
1. Khan AH, Sulaiman SAS, Laghari M, et al. Treatment outcomes and risk factors of extra-pulmonary tuberculosis in patients with co-morbidities. BMC Infect Dis.
2019;19(1):691. Published 2019 Aug 5.

Epidemiology of UG-TB
• Caused by Mycobacterium tuberculosis complex (including M.
tuberculosis, M. bovis, M. africanum (causes human TB in West and
East Africa), M. caprae, M.pinnipedii, M. microti and BCG (the
derivative of M. bovis used in vaccine)
• 98% human TB by M.tb and M.africanum while 1.8% by M.bovis
• Difficult to measure – underdiagnosed
• Varies from 2-10% in US / Europe to 15-20% in Africa, Asia, eastern
Europe and Russian Federation
• In Sabah (2012-2018, n=33193), most common site for EPTB -
lymphatics (33%), pleura (17%), bone/joints (15%) and GI (13%).
UG, pericardium and eyes only < 2%.
• 2-years study in Penang, Selangor, Sabah and Sarawak: Lymphatics
(26.5%), pleural (18.6%) and CNS involvement of EPTB more
common than UG. (UG + other sites collectively only 9%)
References:
2. Goroh MMD, Rajahram GS, Avoi R, et al. Epidemiology of tuberculosis in Sabah, Malaysia, 2012-2018. Infect Dis Poverty. 2020;9(1):119. Published 2020 Aug 26.
3. Khan AH, Sulaiman SAS, Laghari M, et al. Treatment outcomes and risk factors of extra-pulmonary tuberculosis in patients with co-morbidities. BMC Infect Dis.
2019;19(1):691. Published 2019 Aug 5.

Pathogenesis of UG-TB
• Primary infection at any organ site or secondary infection
(Inhalation of Mtb infected aerosol, ingestion of M.bovis-infected
milk and/or other dairy products rarely intravesical BCG or BCG
vaccination in HIV / immunocompromised patients) > direct
hematogenous or lymphatic spread > Mtb seeding into various
parts of UG tract.
• Mtb from kidney > urothelium > ureter, bladder, urethra, seminal
vesicles and testes (flowing downstream).
• Direct local extension from adjacent foci > genital involvement
• Reactivation of Latent TB Infection (LTBI) in
immunocompromised patients (HIV<, DM, smoking, malnutrition,
stress, transplant)
References:

References:
1. Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis - epidemiology, pathogenesis and
clinical features. Nat Rev Urol. 2019;16(10):573-598.
• Mtb-induced granulomas and
granulation tissue with caseous
necrosis are particularly seen in
renal TB.
• TB of the bladder can also
occur via retrograde spread
from prostate / testicular TB.
• Prostatic TB can occur via
hematogenous or lymphatic
spread from pulmonary TB or
local spread from epididymal
TB.
• TB of the testes, epididymis,
vas deferens, SVs can occur via
hematogenous or retrograde
spread from the prostate via the
vas, peri-vas lymphatics or
capillaries.

Renal TB
• Most frequently diagnosed clinical presentation of UG-TB.
• Up to 10% has active pulmonary TB and 50% has abnormal CXR
• Granuloma and caseous necrosis can occur throughout renal tissue,
particularly in the cortex, adjacent to glomeruli or peritubular
capillary bed.
• Granuloma less well-formed in HIV or immunocompromised.
• Granulomatous inflammation > chronic tubulointerstitial nephritis
> papillary necrosis > fibrosis + extensive caseous necrosis of renal
parenchyma > formation of lobules, dilated calyces and cavities.
• Scarring of the renal pelvis / PUJ > obstruction
• In 20-40% renal TB, varying degrees of ill-defined, irregular renal
parenchymal calcification occur, can be seen on imaging / surgery.
References:

Renal TB
• Kidney TB (KTB) classification (according to extent of tissue
destruction):
• Stage 1 (KTB-1): non-destructive form / TB of renal parenchyma
• Stage 2 (KTB-2): small destructive form / TB papillitis
• Stage 3 (KTB-3): destructive form / cavernous kidney TB
• Stage 4 (KTB-4): widespread destructive form / polycavernous kidney TB
• Untreated eventually leads to ESRF ; or it can also extend into
psoas sheath and perirenal / pararenal spaces > cold abscesses,
sinus tracts and fistulae.
References:

TB Ureter
• Lower 3rd ureter most frequently affected
followed by PUJ.
• 50% of renal TB has ureteric involvement
• Inflammation > oedema > granulomatous
ulceration > fibrosis > irregular ureteric
strictures / segmental dilatation and reflux.
• ‘Sawtooth ureter’: alternating areas of non-
confluent dilatations and strictures > cock-screw
or beaded configuration
• ‘Pipe-stem ureter’: ureteral shortening and
rigid fibrotic ureter lacking peristaltic movement
• Ureteric stricture with obstructive uropathy
is an important complication that needs to be
differentiated from other causes of stricture.
References:
2. Gibson MS, Puckett ML, Shelly ME. Renal tuberculosis. Radiographics. 2004;24(1):251-256.

TB Bladder
• Usually 2’ KTB, 21% of patients
• Primary bladder TB has been reported in CIS treated with
intravesical BCG instillation.
• Present as cystitis, focal or generalized, seen as filling defect on
imaging.
• Chronic inflammation of VUJ > progressive fibrosis > narrowing,
stenosis and stricture formation, scarification (golf-hole
appearance of UO) > VUR > hydroureteronephrosis
• Chronic inflammation of wall and detrusor muscle > reduction of
bladder capacity (thimble bladder)
• Fibrosis of trigone > gaping of VUJ > VUR
References:

TB Bladder
• Rare complications: vesicovaginal / vesicocolic / enterovesical
fistula and bladder perforation.
• TB bladder can be classified into 4 stages:
• Stage 1: tubercle-infiltrative bladder TB
• Stage 2: erosive-ulcerous bladder TB
• Stage 3: interstitial cystitis / painful bladder syndrome
• Stage 4: contracted bladder up to full obliteration
• TB cystitis indistinguishable from other infection – always a
differential when patients with recurrent UTI fail to respond to
antibiotics.
References:
1. Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis -
epidemiology, pathogenesis and clinical features. Nat Rev Urol.
2019;16(10):573-598.
2. Mariappan K, Indiran V. Thimble bladder. Abdom Radiol (NY).
2019;44(7):2669-2670.

TB Prostate, Scrotal, SV
• TB prostate usually has KTB and TB epididymo-orchitis. This condition has
been reported in patients who had intravesical BCG.
• Formation of cavities / abscesses > drains into surrounding tissues and
fistulae formation in perineum, urethra or scrotum > urine flow through
multiple fistulae (water-can effect)
• Scrotal TB (TB of testis, epididymis, vas deferens) > infertility
• TB-induced orchitis following intravesical BCG can occur.
• Spermatic cord tuberculoma can mimics testicular tumour.
• TB epididymitis / vas deferens > obstructive azoospermia
• TB seminal vesicle can cause calculi and abscess formation
References:

TB Penis / Urethra
• TB penis is rare and usually occurs 2’ renal TB or following
intravesical BCG therapy.
• Urethral TB is rare despite constant flow of Mtb-infected urine.
• Co-involvement in 4.5% patients with renal TB
• Acute urethritis with associated TB prostate or urethral stenosis
and fistulae are the common presentations.
References:
1. Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis - epidemiology, pathogenesis
and clinical features. Nat Rev Urol. 2019;16(10):573-598.

Symptoms and Signs
• Not always defined by anatomical site of disease; non-localizing
symptoms and signs and can be asymptomatic during early stages
• In renal, bladder, prostatic TB – dysuria, urinary hesitancy and
increased urinary frequency
• Renal TB – often associated with flank and renal angle pain
• Urinalysis – culture negative, sterile pyuria, microscopic or gross
haematuria.
• Constitutional symptoms of TB uncommon unless patients has
concomitant active pulmonary TB.
• Secondary bacterial infection in 50% of patients
• Suspicion when conventional antibiotics for suspected UTI is
not effective or sterile pyuria is present.
References:

Symptoms and Signs
• Renal TB can lead to chronic renal failure, fistula, hypertension.
• In HIV-infected or immunocompromised patients, abscesses and
fistula formation can occur
• Scrotal TB – usually unilateral (66%). Scrotal fistula and sinuses
discharging thin and odourless pus are suggestive of TB.
• Penile TB – painless or painful single of multiple swellings/ ulcers
(can mimic penile cancer)
• Tuberculids: asymptomatic, symmetrical, dusky red papules and
pustules over the glans penis which occurs in crops and heals with
scarring as a result of acute leukocystoclastic vasculitis and
thrombosis of dermal vessels.
• Urethral TB – discomfort, discharge and strictures
References:

Diagnostic Workup UG-TB
• No single specific diagnostic test exists. Diagnosis requires a
combination of good clinical history, imaging, microbiological,
molecular and histopathological tests.
• Smear microscopy of urine (diagnostic yield < 40% as number of
Mtb is small in urine) for AFB using Ziehl-Neelsen stain with
conventional fluorescence / LED microscopy.
• TB cultures: gold standard diagnostic method
References:
• 3 early morning urines on consecutive days
• Traditional culture using Lowenstein-Jenson
medium or liquid culture replaced with Mtb
culture system (e.g. BACTEC MGIT 960) –
result available within 2 weeks (and 6
weeks for being considered negative)
• MGIT – WHO recommended gold
standard confirmatory test for TB

GeneXpert MTB/RIF Assay
• Rapid, affordable POCT for detecting Mtb
and rifampicin resistance simultaneously.
• One of the urine-based TB diagnostic tests which
detects Mtb DNA in urine and give result in 2
hours.
• In HIV-infected individuals, this assay increases
detection of TB, facilitates earlier diagnosis and
reduces time-to-initiation of TB treatment.
• Facilitates early initiation of MDR-TB treatment
• Is replacing smear microscopy as first-line TB
diagnostic test for detection of PTB and EPTB
disease worldwide.
• Using urine sample from culture positive with
clinically diagnosed UG-TB – sensitivity 63%
(microscopy 18.5% and culture 45.7%) and
specificity 98%
References:
GeneXpert MTB/RIF Assay Procedure [Ref. Boehme et al , NEJM
2010]

Urine-based LAM Assay
• LAM is part of the Mtb cell wall and can
be detected in the urine using lateral flow
assay (an immunochromatographic
assay comprising colloidal gold-labelled
antibodies attached to LAM which are
captured by immobilized LAM antibodies
further along the test strip and form a
visual band). Result available in 30 mins.
• Recommended by WHO for the
diagnosis of HIV-associated TB in
patients with CD4 count < 200.
• Patient with advanced immunosuppression
is at increased risk of disseminated Mtb
infection with consequent renal
involvement releasing Mtb LAM
glycolipid into the urine.
References:
1. Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis - epidemiology, pathogenesis and clinical features. Nat Rev Urol. 2019;16(10):573-598
2. Dheda K, Ruhwald M, Theron G, Peter J, Yam WC. Point-of-care diagnosis of tuberculosis: past, present and future. Respirology. 2013;18(2):217-232.

Diagnostic Workup UG-TB
• Drug susceptibility tests (DST):
• To detect rifampicin and isoniazid resistance: GenoType MTBDRplus
V1, GenoType MTBDRplusV2 and Nipro
• To detect 2nd line drug resistance: Hain MRBDRsl assay (using Mtb
isolates od smear +ve samples), array-based methods and next generation
whole-genome sequencing (WGS)
• Histopathological examination: granulomatous inflammation is
hallmark
• Identification of AFB does not confirm Mtb and biopsy / HPE
samples must be processed simultaneously through the GeneXpert
MTB/RIF assay and culture to identify the species and DST.
• Histological examination is an important adjunct to culture and
maximizes identification of Mtb.
References:

Imaging for UG-TB
• To help localize the site of disease or tissue destruction, assess
the extent of involvement, to monitor the effect of treatment
and to discover complications.
• Chest XR to detect active pulmonary TB. Abdominal XR can
detect renal calcification in renal TB.
• Ultrasonography:
• Granulomas are seen as small, hypoechoic intrarenal masses; mucosal
thickening and stenosis of calyces in advanced TB
• Calcification is common in late stage disease: varies from fine punctate
calcific foci to calcification of whole kidney.
• Bladder – low-capacity bladder with thick wall, associated with VUR.
• Scrotal wall and tunica albuginea thickening, hydrocele and intratesticular
abscess can be seen in scrotal TB
References:

Imaging for UG-TB
• IVU – provides anatomical and functional drainage details
• CT IVU – detect cortical mass, granuloma, calcification,
obstructive uropathy, level of strictures.
• PET-CT imaging using 18F-FDG – provides functional
information about sites with active inflammatory and immune
cells that use glucose during metabolism. It is however not
specific for TB and cannot differentiate from cancer or other
infectious causes.
• MRI – low sensitivity for detecting early lesions of UG-TB and
is used primarily for evaluation of renal TB because of its
superior soft-tissue resolution and multiplanar acquisition.
• MRI is also useful in prostate or scrotal TB with complex fistulae
formation
References:

Putty Kidney
• Amorphous dystrophic calcification eventually involves the entire
kidney (end stage) > autonephrectomy

Diagnosis of LTBI
• Important for urologist when we manage immunocompromised
patients e.g. CKD, transplant, HIV, uncontrolled DM (these group
has considerably increased risk of LTBI)
• Interferon-gamma release assays (IGRA): screening for LTBI
for pre-transplant and post-transplant
• No gold standard diagnostic test for diagnosis of LTBI.
• WHO recommends: tuberculin skin test, two IGRAs
(QuantiFERON-TB Gold In-Tube and T-SPOT TB)
• These tests cannot differentiate LTBI and active disease and
should not be used as diagnostic test for active TB.
References:

Principles of Treatment
• Eradicate with anti-TB, treat complications and manage
comorbidities and risk factors
• MDT management with respiratory / TB physician, infectious
disease physician or HIV specialist.
• Close follow-up: track adherence, monitor treatment response
and side effects and detect the development of drug resistance.
• Drug-sensitive TB: 2 months intensive phase of quadruple
therapy with daily 1st line TB drugs (rifampicin, isoniazid,
pyrazinamide, ethambutol), followed by 4 months maintenance
with 2 drugs (rifampicin and isoniazid) or can extended up to 7
months for immunosuppressed patients.
• Drug-resistant TB (MDR or XDR-TB): treat with 2nd line drugs
with longer treatment duration.
References:

Principles of Treatment
• LTBI: isoniazid monotherapy for 6 months in both adults and
children in countries with high and low TB incidence; or
rifampicin + isoniazid daily for 3 months as preventive
treatment for children and adolescents aged < 15 years in
countries with high TB incidence; or rifapentine + isoniazid
weekly for 3 months for preventive treatment in both adults and
children in countries with high TB incidence.
• LTBI in countries with low TB incidence: 6 - 9 months of
isoniazid monotherapy; 3 month regimen of weekly
rifapentine + isoniazid; 3-4 months of isoniazid + rifampicin;
or 3-4 months of rifampicin alone.
References:

Surgery in UG-TB
• Adjunct to TB drugs and required for following indications:
drainage of obstructed pelvi-calyceal system, drainage of
abscesses, nephrectomy for non-functioning kidneys,
reconstruction of ureters (ureterocalicostomy, pyeloplasty,
reimplantation of ureters and ileal replacement of ureter) and
reconstructive surgery of the bladder to improve the reduction in
functional bladder capacity.
• Reconstruction in UG-TB has major challenges. Suture materials
might not adhere to an inflamed renal pelvis.
• Dense perinephric adhesions and adjacent organ involvement can
make nephrectomies even more challenging.
• In patients with renal failure requiring bowel interposition, a short
ileal conduit is preferred over an augmentation of bladder.
References:

Prevention Among HCWs
• Follow infection control measures to prevent spread.
• For patients with UG-TB who needs surgery, no clear
guidelines for reducing the risk of spread.
• Starting anti-TB treatment at least 8 weeks before surgery
is essential to reduce Mtb bacillary load.
• Standard infection control procedures and isolation protocols
apply for nursing in patients with UG-TB.
• BCG vaccination among the HCW.
References:

What is the role of Urologist?
• Urologist should be able to recognise the different urological
manifestation and complications of HIV infections.
• With HAART > longer life expectancy > presenting with
common urological problems as general population hence
increasingly likely to perform procedures in HIV patients.
• Surgical outcomes in patients with CD4 counts > 200 or
BVL < 10,000 copies/ml are similar to those of the general
population.
• We should also identify population at risks of UG-TB since
Malaysia is endemic for TB.
• Having the awareness of this disease > high suspicion when
infection does not respond to standard antibiotics therapy.
• MDT approach is important in the successful management of
HIV with urological problems and UG-TB.

HIV and Tuberculosis of Urinary Tract: What is The Role of Urologists?

HIV and Tuberculosis of Urinary Tract: What is The Role of Urologists?

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to HIV and Tuberculosis of Urinary Tract: What is The Role of Urologists?

Similar to HIV and Tuberculosis of Urinary Tract: What is The Role of Urologists? (20)

Recently uploaded

Recently uploaded (20)

HIV and Tuberculosis of Urinary Tract: What is The Role of Urologists?