India is the highest TB burden country accounting for more than one-fourth of the global incidence .Genital TB is found in 5-10% of women with infertility problems, with low rates in Australia (1%) and high rates of up to 19% in India (ICMR,2011)
2. There is a dread disease ….in which life and
death are so strongly blended that death takes
the glow and hue of life and life the gaunt and
grisly form of death
- CHARLE’S DICKENS
3. HISTORY
In Ancient Vedas tuberculosis
was known as Rakshasman-King
of diseases
Word ‘TUBERCULOSIS’ was
coined by Johann Lukas
Schönle in 1834.
-ROBERT KOCH discovered
tubercle bacilli in 1882.
4. MILE STONES --- BEING THE FIRSTS
First case of genital TB was recognised and
described by Morgagni in 1744.
First case of tubercular endometritis was reported
by kwisch in 1847.
Spencer Wales (1862) first operated on clinically
diagnosed ovarian cyst – TB loculated cyst.
Hegar (1883) removed tubercular tube.
Sutherland (1943)-tested endometrial biopsy for
TB.
Raymond described TB cervicitis.
5. INCIDENCE
INDIA IS THE HIGHEST TB BURDEN COUNTRY ACCOUNTING FOR
MORE THAN ONE-FOURTH OF THE GLOBAL INCIDENCE
India
26%
China
13%
Indonesia
6%
Nigeria
5%
South Africa
5%
Bangladesh
4%
Ethiopia
3%
Pakistan
3%
Phillipines
3%
other 13 HBCs
15%
other countries
18%
Source: WHO Geneva; WHO Report 2014:
Global annual incidence = 8.6
million
India annual incidence = 2.2 million
India is 17th among 22 High Burden
Countries (in terms of TB incidence
rate)
6. In 2013, 8.6 million people fell ill with TB and 1.5
million died from it.(WHO,2014).
India alone accounted for 26% of total TB cases
globally(WHO,2014).
HIV has altered the dynamics of TB worldwide
Patients co-infected with HIV contributed about 8.5%
of the increase in tuberculosis cases per
year.(RCOG,2011).
7. Genital tuberculosis is the second most common
form of extrapulmonary TB after peripheral
lymphadenopathy.
Genital TB is found in 5-10% of women with
infertility problems, with low rates in Australia (1%)
and high rates of up to 19% in India (ICMR,2011)
Genital tuberculosis in India has increased to 30 per
cent in 2015 from 19 per cent in 2011(ICMR,2015).
8. PATHOPHYSIOLOGY
Tuberculosis organism is
- non-motile obligate aerobe
replicating cycle of 17-24 hours
(slow growing)
-Non capsulated
-Acid-fast due to the surface
lipids. So resistant to common
antibacterial agents and lytic
enzymes.
9. PATHOPHYSIOLOGY
AGE GROUP-
-Can occur in any age group, 75% being in the 20–45 yrs .
Postmenopausal women ( 7–11%) .
o if primary infection occurs close to menarche increased chance of
genital T.B
Mycobacterium tuberculosis of human type.(90–95%)
Rarely M.bovine.(5-10%).
Almost always of secondary type.(RCOG,2005)
If the bacilli are not eradicated, risk of reactivation, especially in
conjunction with diseases (e.g. Hodgkin’s lymphoma, AIDS,
steroids, stress, or malnutrition
10. ORGAN FREQUENCY
Fallopian tubes 90-100%
Endometrium 50-60%
Ovaries 20-30%
Cervix 5-15%
Vulva and Vagina 1%
Schaefer G: Female genital tuberculosis. Clin Obstet Gynecol 19:23, 1976)
Fallopian tubes -primary sites
Mode of spread : Hematogenous (90%)
Lymphatic/ Direct
Ascending
Frequency of tuberculosis in genital organs
11. TUBERCULOSIS OF THE FALLOPIAN TUBES
Both tubes are involved in 100 % of cases.
14. TYPES OF TUBERCULOUS SALPINGITIS
Exudative
-Acute phase of the process.
- large pyosalpinx may form. Frequently, the organs contain a large
amount of caseous material plus purulent exudate.
-show few adhesions .
Productive-Adhesive
-Found most frequently at laparoscopy or laparotomy.
- Tubes are studded with tubercles and are densely adherent to the
surrounding organs.
- The tube wall is thickened and nodular.
- Eventually, when the process starts healing, it results in
calcification and fibrosis.
16. TUBERCULOSIS OF ENDOMETRIUM
Uterus
Tubercles at basal layer of
endometrium
Shed at each menstruation
Reinfection
Endometrial ulceration
Asherman’s syndrome
17. Tubercles at basal layer of endometrium
Myometrium(2-3%)
Caseation
Pyometra(postmenopausal woman)
18. TUBERCULOSIS OF THE OVARY
The involvement is bilateral.
Two forms :
PERIOOPHORITIS
-Extension of the tuberculosis
from the tube
- Most common form of
tuberculosis.
- From the periphery toward the
center
- Resulting in a tuboovarian mass,
which is frequently adherent to
omentum and intestines.
19. OOPHORITIS
-Follows hematogenous spread.
-A relatively rare condition
- Infection starts in the stroma of the
ovary,
-Typical tubercles or larger foci with
caseous centers may be recognized
on cross section in the hilum of the
ovary
20. TUBERCULOSIS OF CERVIX
Descending infection from fallopian
tubes and uterus.
Sexual parteners may be source of
infection.
No macroscopic changes in the
cervix specific for TB.
The cervix may appear normal or
inflamed, may resemble invasive
carcinoma.
Three forms
-Ulcerative –most common
-Papillomatous
-Miliary
21. TUBERCULOUS PERITONITIS
In combination with female genital tract TB approximately 45%
of the time.
Often extensive adhesions seen.
Two types
Serous variety-
- more common
- Characterized by ascitis, signs of peritoneal inflammation, fever,
abdominal pain, weight loss, and anorexia.
Plastic variety-
- Less common
- Characterized by tender abdominal masses and an abdomen
“doughy” to palpation.
22. TUBERCULOSIS OF THE VULVA AND
VAGINA
Rarest form of genital TB(1%).
Sexual partners may be source of
infection.
In the vulva begins as a nodule on the
labia or in the vestibular region-breaks
down - irregular ragged ulcer.
-sometimes with sinuses discharging
caseous material and pus.
- as a hypertrophic, irregular warty growth.
In the vagina may simulate carcinoma in
its gross appearance.
23. TB OF PELVIS
Tubercular adenitis of mesenteric or pelvic lymph nodes.
Pelvic T.B. is not the same disease as Genital T.B.
‘FROZEN PELVIS’
DDs of frozen pelvis?
Florid genital tuberculosis
Grade III/IV pelvic endometriosis
Advance invasive carcinoma of cervix
Following radiotherapy for invasive carcinoma of cervix
24. CLINICAL FEATURES
20% have history of T.B. in immediate family.
Past history of tuberculosis.
Asymptomatic-10-11%
Systemic- A history of poor general health persisting over a
period of months or years and associated with weight loss, undue
fatigue, low-grade fever, or vague lower abdominal pain
Infertility
Menstrual disturbances
Abdominal swelling
Postcoital bleeding
Vaginal discharge
Dyspareunia
25. INFERTILITY
Most common initial symptom.
In most large studies: Infertility presenting c/o in 40% - 50%
Past h/o TB /family .
LOWER ABDOMINAL PAIN
Second common symptom.
Pain present for several months which is not usually severe.
M/c associated with swelling of abdomen.
Episodes of acute lower abdominal pain owing to secondary
infection by pyogenic org.
In advanced disease pelvic pain becomes severe and gets
aggravated by coitus, exercise & mensus.
26. MENSTRUAL COMPLAINTS
Third common symptom.
Menorragia/ Menometrorragia/ Intermenstrual
bleeding/ Oligomenorrhoea/ Postmenopausal
bleeding.
Menstrual cycle may be normal.
AMMENORRHOEA
Advanced active pulmonary T.B. produce amen. but
concomitant genital T.B. is rare.
Complete destruction of ovary by genital T.B. seldom
occurs so ovarian failure is not the cause.
‘End organ failure’ secondary to endometrial caseation
27. H/o primary infertility with no apparent cause on
examination & family H/o or personal H/o T.B.
H/o vague lower abdominal discomfort with low grade
fever/undue fatigue/persistent ill health over months to
years associated with weight loss.
Adolescent female presenting with ascites pain and low
grade fever.
Menopausal female enlarged uterus that is tense and tender
on examination (pyometra formation)
Recurrent Pelvic inflammatory disease not responding to
antibiotic therapy.
28. SIGNS
Normal in 50%..
Abdominal examination-doughy feeling.
Abdominal mass
Pelvic mass
Adnexal mass
Abdominal tenderness
Pelvic/adnexal tenderness
31. CLINICAL SUSPICION
Unexplained infertility
Infertility of any duration with
High risk factors
- history of previous pulmonary TB infection.
- contact with a pulmonary TB sufferer.
- recent travel to or migration from high prevalence countries.
- residence in high prevalence areas .
- low socioeconomic background.
- drug abuse.
- HIV positive status.
32. - Generalised s/s
loss of wt / appetite
low grade fever / malaise
night sweats
persistent vaginal discharge
non healing of wounds , unexplained ascites
chronicity of symptoms
Adnexal disease with ascites in virgins
Chronic PID refractory to standard antibiotic treatment
Postmenopausal women with bleeding, persistent leucorrhoea
and pyometra where endometrial neoplasia has been excluded.
34. Hemogram is usually normal,may show lymphocytosis ,low
Hb
ESR is usually normal but may be raised
Urine microscopy may show abacteruric pyuria in concomitant
GUTB.
Raised serum CA125 level
35. CHEST X RAY
Most chest X-rays are normal
Old healed scarred lesions
Current or past tuberculous lesions in
the lungs
o Milliary tubercles if disseminated
tuberculosis.
36. ENDOMETRIAL BIOPSY
Sampled by endometrial aspiration ,
biopsy Curettage ,premenstrual biopsy/
menstrual blood on1st day within 12 hrs of
menses
+ive in 50-60 % cases of GTB
Reveals granulation , caseation , dilated
glands, inflammatory cells
,lymphocytes , plasma cells,
destruction of epithelium , fibrosis
Microscopic appearance of the granuloma:
Multinucleated giant cells, Langhans cells
Chr. Inflammatory cell,Epitheloid
cells,Central area of caseation necrosis.
+ive HPE indicates 100% TB salpingitis
-ive HPE does not rule out endometrial /
tubal TB
37. CULTURE
Decisive step for diagnosis, treatment & control of TB
Combination of solid and liquid media-Gold Standard
For isolation of bacteria – a surest test
More sensitive requiring 10 -100 org / ml
Sensitivity is 30-40%
CONVENTIONAL
o Egg based media 3-8 weeks
eg Lowenstein Jensen media
Agar based < 3 weeks
eg- BACTEC medium
MGIT: more rapid and sensitive than other methods of
culture.
38. RADIOMETRIC CULTURE METHOD
BACTEC -- is based on measurement of
carbon dioxide released by bacteria during
growth in liquid medium
Radioactive carbon labelled substrate like
palmitic acid or formic acid is used as
marker for bacterial growth
Diagnosis is made in 1-2 weeks
Sensitivity is 80-90%
39. BACT/ALERT 3D MB
Fully automated,Non-
invasive,Continuously monitored non-
radiometric system.
Revised antibiotic supplement kit
Medium - modified Middlebrook 7H9
broth with supplements
Direct inoculation
No processing
Decontaminated clinical specimen and
sterile body fluid specimen (other than
blood)
-10 ml Middlebrook 7H9 Broth
BSA, Catalase
40. For blood and sterile body fluids
-30 ml Middlebrook 7H9 Broth
SPS, Glycerol.
CO2 released by mycobacteria
detected by sensor
Colour changes - increase in
reflectance units
Positive broth - 106-107 orgs/ml
Mean detection time (days)-11 to15
days.
41. SMEAR MICROSCOPY
Ziehl-Neelsen
Fluorochrome - Auramine-rhodamine
(direct fluorescence)
Simple & rapid procedure
Higher sensitivity; faster screening
Requires 10000 mycobacteria/ml for +
ive smear
Or 1-9 AFB / HPF -- +++
Or 1-9 AFB / 10 HPF ++
Or 1-9 AFB / 100HPF +
- ive smear does not rule out GTB
Cyto centrifugation enhances
sensitivity
42. TUBERCULIN (MANTOUX) TESTS
0.1 ML PPD IS INJECTED INTRADERMALLY
Delayed hypersensitivity reaction
Read between 48 and 72 hours after
the injection
The tuberculin skin test has a
sensitivity of 55%
and specificity of 80% in patients
with genital
tuberculosis.(RCOG ,2005)
44. QUANTIFERON-GOLD
In vitro assay that measure interferon (IFN-γ)
released by sensitized T cells after stimulation
by M. tuberculosis antigens.
FDA-approved in 2001,for detection of latent
tuberculosis infection.
Indirect test for M. tuberculosis complex
Tuberculosis disease OR latent tuberculosis
infection (LTBI)- cannot distinguish between
them
Intended for use in conjunction with risk
assessment, radiography, and other medical
and diagnostic evaluations
45. PRINCIPLE OF QUANTIFERON GOLD
Fresh heparinised whole blood from sensitised persons
Incubated with mixtures of synthetic peptides
(two proteins present in M. tuberculosis)
ESAT-6 (early secretory antigenic target-6)
CFP-10 (culture filtrate protein-10)
Lymphocytes recognize these mycobacterial antigens –
Generation and secretion of interferon-γ (IFN-γ)
Detection and subsequent quantification of IFN-γ by ELISA
46. Result Interpretation
Positive
(ESAT-6 and/or CFP-10
responsiveness detected)
M. tuberculosis infection likely
Negative
(No ESAT-6 or CFP-10
responsiveness detected)
M. tuberculosis infection unlikely,
but cannot be excluded in immunocompromised patients, or
highly probable cases
Indeterminate Test not interpretable
47. ADVANTAGES
Single patient visit
Rapid results (within 24 hours)
Higher specificity than Mantoux
No booster response (measured by subsequent tests -
which can happen with Mantoux)
No reader bias (cf Mantoux)
Not affected by prior BCG vaccination
or Impaired or altered immune function
48. T-SPOT®.TB TEST (T-SPOT)
T-SPOT®.TB test (T-Spot) - Counts the cells releasing IFN-G
visualized as spots with the enzyme-linked immunospot
(ELISPOT) technique.
Clinical Utility:
Can detect both latent and active pulmonary and extra-
pulmonary cases.
Useful for screening person who has symptoms of TB.
Screening suspected Extra-Pulmonary tuberculosis eg: GTB
49. ULTRASONOGRAPHY
Loculated ascites: The presence of fine lacy strands or
particulate matter in fluid is due to thin fibrin strands
Bilateral or unilateral tubo-ovarian mass
Hydrosalpinx
Fluid in cul de sac , peritoneal cavity
Mesenteric lymphadenopathy
Small uterus with atrophic endometrium
Enlarged uterus with caseous pyometra
50. HYSTEROSALPINGOGRAPHY (HSG)
Hysterosalpingography is contraindicated
-in the presence of recent acute pelvic infection
-If Tuberculosis is suspected.
Vascular or lymphatic extravasation of the dye
Rigid (lead-pipe) tubes with nodulations
Tobacco-pouch appearance
Leopard skin appearance
Rosette appearance
Moth eaten appearance
Sperm head appearance
Beaded appearance of the tube
Distal tube obstruction
Coiling/ calcified shadows
Bilateral cornual block
Irregular, honey-comb appearance of the uterine cavity
51. TOBACCO POUCH
•Tube is enlarged and
distended, ostium remain
patent with recognizable
everted fimbriae.
52. COTTON WOOL PLUG APPEARANCE..
Focal irregularity and areas
of calcification occur within
the lumen of the fallopian
tubes.
53. TUFTED APPEARANCE..
Caseous ulceration of the mucosa
of the fallopian tube produces an
irregular contour of the lumen of
the tubes.
Diverticular cavities may
surround the ampulla and give a
“tuft” like appearance.
Thick arrow – hydrosalphinx.
61. HYSTEROSCOPY
Ostia not visualized
Caseous material coming out of
ostia
Periosteal fibrosis
Caseation/ tubercles
Endometrial calcification
Scanty endometrium
Intrauterine adhesions
Irregular uterine cavity
62. LAPAROSCOPY
Blue uterus” when chromopertubation test done with
methylene blue.
Acute salpingitis: red, swollen edematous tubes.
Tiny tubercles 1-4 mm on surface of organs: tubes,
uterus.
Hydrosalpinx, pyosalpinx.
Tobacco-pouch appearance.
Unilateral / bilateral TO masses.
Straw colored thick jelly like exudate in POD.
Fimbrial biopsy, peritoneal fluid may be taken to
confirm the diagnosis .
63. SEROLOGICAL TESTS
Based on recognition of host response
Antibodies tested against mycobacterial antigens by ELISA
using mono /polyclonal Abs
A-60 & 38 kDa –are usual purified Ags tested
Useful in chronic & inaccessible disease
Active infection IgM develops before ESR is raised or
Montoux is +ive
Sensitivity is 80-90% in extra pulmonary TB
64. PCR MOLECULAR DIAGNOSTIC TESTS
PCR based sequencing
- Amplification of DNA using specific primers
- Highly sensitive ( > 90% ) & specific ( 95% )
- Few bacterial cells used for amplification
- Detectable with even 1-10 organisms / ml
- Results available in 2-3 days
- Cumbersome and expensive
- False –ive if contaminated with heparin or high salt
concentration
- False +ive as can not distinguish between live or dead
bacilli
65. MOLECULAR DIAGNOSTIC TESTS
DNA probes -
- Species specific probes that hybridise with RNA
- Combined with short term culture
- Used for rapid detection of myco TB
- Highly sensitive & specific
DNA microarrays
- Identify mutation rapidly & accurately
- By Ligase chain reaction where fragmented primers are
amplified
66. PCR GENOTYPIC MOLECULAR TESTS
PCR assays targetting various gene segments are
-- a 65 kDa protein encoding gene
-- DNA IS 6110 element -myco TB has 10 -20
copies of this sequence.PCR detect less than 10 pg of DNA =3
genomes
-- mpb 64 gene –a specific Ag -- as patch test . Becomes +ive in
3-4 days & lasts for 1 week (100% specific & 98% sensitive)
67. Advantages:
High specificity and sensitivity, requires only < 10 bacteria/mL
Rapid method, results are available within a day of the DNA being
extracted from the specimen.
Can be applied to sterile fluids like peritoneal fluid where the
culture is difficult due to a low bacterial load.
Disadvantages:
False Negative - absence of even a single AFB in the sample
collected, and high salt concentration of a
specimen which interferes with the PCR results.
False Positive- PCR cannot distinguish between live and killed
bacilli
68. BIOCHEMICAL MARKERS
Adenosine Deaminase activity
- Tested in associated peritoneal TB
- Levels of > 30 u/L in ascitic fluid significant
- Rapid , highly sensitive & specific
- Pending confirmatory tests - therapy can be initiated
Tuberculstearic acid test
- Fatty acid present in mycobacteria only
- Gas chromatography /mass spectrometry done with
samples containing small number of bacteria
69. COMPLICATIONS
Subfertility or Sterility
Even in patients considered to be “cured,” extensive damage
to the fallopian tubes and the endometrium is often
irreversible, and chances of successful intrauterine pregnancy
drop significantly.
Ectopic Pregnancy
Congenital Tuberculosis
A rare but potentially serious complication .
transmission from maternal tuberculous endometrium to the
fetus .
70. ANTI TUBERCULAR TREATMENT
3 basic principles for chemotherapy for T.B.
Regimen must contain multiple drugs to which
organism is susceptible.
Drugs are to be taken regularly.
Drugs should continue for a sufficient period of time.
75. RESERVE LINE/SECOND LINE DRUGS USED IN
TREATMENT OF TB
Drug <50 Kg >50 Kg
Thiacetazone 150 mg 150 mg
Ethionamide 500 mg 750 mg
Cyclocerine 750 mg 1000 mg
Inj. Kanamycin 750 mg 1000 mg
Inj. Capreomycin 750 mg 1000 mg
Inj. Viomycin 750 mg 1000 mg
76. NEWER DRUGS USED IN THE TREATMENT OF
DRUG RESISTANT TB
Fluoroquinolones: Ciprofloxacin (1500 mg/day), and
Ofloxacin (400-600 mg/day) for 6 months
Anti-leprosy drugs: Clofazimine (100-200 mg/day)
Beta-lactam antibiotics: amoxicillin+ clavulanic acid
(Augmentin)
Macrolides: azithromycin, roxithromycin, and clarithromycin
77. SURGICAL MANAGEMENT
Tubal reconstructive surgery is contraindicated
because there is usually irreparable damage of tubes
(cilia are destroyed)
May result in reactivation and dissemination
Those with infertility must be treated with medical
treatment; and if this does not help artificial
reproductive techniques may be considered.
78. SURGICAL MANAGEMENT
Indications:-
Persistent & recurrent disease/pelvic masses/pelvic
pain/abnormal bleeding despite adequate treatment
Persistent non healing fistula
Multi drug resistant disease
Concomitant neoplasia of genital tract
Chemotherapy should precede surgery by 1-2 weeks.
Surgery should be done at mid cycle in premenopausal.
Chemotherapy should be continued for 6-12 months post
op.
Premenopausal-save ovaries if normal, otherwise TAH
with BSO followed by HRT.
(Glob. libr. women's med., The International Federation of Gynecology and
Obstetrics,2008)
79. GTB & ENDOMETRIAL RECEPTIVITY
Implantation failure reasons are
Inability to express Integrin molecules in the endometrium
during implantation window
Inhibition by Myco. TB. Of basal production of progesterone
& stimulatory effect of HCG leading to ovulation failure
Fibrosis , endometrial atrophy , adhesion formation .
80.
81.
82. UTERINE BIOPHYSICAL PROFILE
Applebaum uterine scoring system for
reproduction
(USSR on USG )
Endometrial thickness > 7mm in A.P. diameter
5 lined appearance of endometrium -from D1 to midcycle –
progressive increase in thickness
Blood flow within zone 3 on color doppler
Myometrial contractions giving wave like motion of
endometrium
Uterine arterial blood flow as Pulsatility Index <3.0
Homogenous myometrial echogenicity
Myometrial blood flow seen on grey scale exam.
(internal to arcuate vessel)
83. POOR PREDICTORS FOR CONCEPTION
Poor endometrial receptivity
Blocked tubes
Elderly age
Infertility of longer duration
Sec. amenorrhea / oligomenorrhea
Endometrial atrophy , caseation
Endometrial scarring , synechiae
84. PREDICTORS OF GOOD RECEPTIVITY
Endometrial thickness
Endometrial layering
Myometrial echogenicity
85. Each parameter is scored as follows:
1. endometrial thickness
a. < 7 mm = 0
b. 7 - 9 mm = 2
c. 10 - 14 mm = 3
d. > 14 mm = 1
2. endometrial layering
a. no layering = 0
b. hazy 5-line appearance = 1
c. distinct 5-line appearance = 3
3. myometrial contractions (seen as wave-like endometrial
motion high-speed playback from videotape)
a. < 3 contractions in 2 minutes (real-time) = 0
b. > 3 contractions in 2 minutes (real-time) = 3
86. 4. myometrial echogenicity
a. coarse/inhomogeneous echogenicity = 1
b. relatively homogeneous echogenicity = 2
5. uterine artery Doppler flow evaluation
a. PI > 3.0 = 0
b. PI< 2.5 - 2.99 = 0
c. PI < 2.2 - 2.49 = 1
d. PI < 2.19 = 2
6. endometrial blood flow within Zone 3
a. absent = 0
b. present, but sparse = 2
c. present multifocally = 5
7. myometrial blood flow internal to the arcuate vessels seen on
gray-scale examination
a. absent = 0
b. present = 2