Presented By:-

Dr nazima saloda…

GENTAL TUBERCULOSIS…

DIAGNOSIS & TREATMENT…

Genital T.B. 1st recognized by MORGAGNI in 1744.

Incidence in infertility clinics:-

5% in world and 19% in India. 80% – 90% in females aged 20 – 40 years.

INTRODUCTION…

Almost always secondary usually primaries are pulmonary other sites renal, GIT, bone, etc. occasionally part of miliary T.B.

MODE OF SPREAD:- 1. Hematogenous

2. Lymphatic

3. Direct Evidence suggest if primary infection occurs

close to menarche increased chance of genital T.B.

PATHOGENESIS…

HISTOPATHOLOGY…

Tubercular adenitis of mesenteric or pelvic lymph nodes.

Superficial involvement of serosa does not impair reproductive function.

Pelvic T.B. is not the same disease as Genital T.B.

T.B. OF PELVIS…

ORGAN FREQUENCY(%)

Fallopian tube. 90 - 100

Endometrium. 50 - 60

Ovaries. 20 - 30

Cervix. 5 - 15

Vulva & Vagina. 1

FREQUENCY OF T.B. IN ORGANS…

Usually the ampullary region shows the earliest and most extensive changes.

The fimbrial processes become greatly swollen and Ostia remain open or closed.

Gross appearance – 1. TOBACCO POUCH

APPEARANCE.

2. PRODUCTIVE

ADHESIVE FORM.Gross appearance varies and is non-diagnostic.Microscopy, hyperplastic adenomatous pattern may be

confused with adenocarcinoma.

T.B. OF FALLOPIAN TUBES…

Gross size and shape of uterus may appear normal.Endometrium on gross appearance may show

ulcerative, granular or fungating lesion resembling carcinoma.

Endometrial cavity may be obliterated with intrauterine adhesions.

Microscopy classic lesion is the non caseating granuloma.

The granulomatous lesions are best recognized on 24 – 26 cycle days or within 12 hrs. of onset of menses.

T.B. OF ENDOMETRIUM…

Usually bilateral.2 types:- 1. Perioophoritis.

2. Ophoritis.

T.B. OF OVARY…

High degree of suspicion.20% have history of T.B. in immediate family.4 major presenting complaints:-

1. Infertility.

2. Abnormal

bleeding .

3. Pelvic pain.

4.Amennorrhea.

CLINICAL PICTURE…

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 (pyrometra formation)

Recurrent Pelvic inflammatory disease not responding to antibiotic therapy.

CLINICAL SITUATIONS…

Most common initial symptom.

In most large studies:

Infertility presenting c/o in 40% - 50%.

85% never became pregnant & 15%

developed symptoms of genital T.B.

within a year of last pregnancy.

INFERTILITY…

Second common symptom.Pain present for several months which is not usually

severe.M/b 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.No. of women c/o pain is proportional to no. of women

having abdominal findings on physical examination.

LOWER ABDOMINAL

PAIN…

Third common symptom.Menorragia/ Menometrorragia/ Intermenstrual

bleeding/ Oligomenorrhoea/ Postmenopausal bleeding.

Menstrual cycle may be normal. Superficial T.B. Endometritis does not interfere with secretory response of endometrium to hormonal stimulation.

MENSTRUAL DISORDER…

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.

AMENNORRHOEA…

Normal in 50%..

Bi manual examination-adenexal mass/fixation

of pelvic organs less tender.

Abdominal examination-doughy feeling.

CLINICAL EXAMINATION…

CBC, ESR, KFT, CRPCXRPelvic ultrasound / hystero-salpingography LaparoscopyHistopathologyMicrobiology:-

Mantoux testQTG-TSerologyAFB microscopy / culture

INVESTIGATION…

EA / EB / EC / menstrual bloodUrine – 3 consecutive days (smear vs. culture -

St: 52% / 65%; Sp: 89-96 / 100%)Molecular testsHIV

Mantoux

QuantiFERON-TB Gold

Microscopy

Culture

Molecular tests – Gen-probe / PCR

Identification by Accuprobe

FAST Plaque TB

MICROBIOLOGICAL TEST…

Diagnostic role of a positive Mantoux (PPD) is controversial

Almost 45% of infertile women with strong indirect evidence of pelvic TB, such as laparoscopic findings (thickened tubes, areas of caseation, etc) - negative Mantoux

In 27 infertile women with a positive Mantoux, only 11 had clear laparoscopic findings suggestive of FGTB

Mantoux test in women with laparoscopically diagnosed tuberculosis sensitivity - 55% specificity - 80%

MANTOUX TEST…

Ziehl-Neelsen, KinyounFluorochrome - Auramine-rhodamine (direct

fluorescence)Higher sensitivity; faster screening

ST: 22-78% (cf culture)MC Detection limit in sputum: 5000-10000 orgs/ml

Culture: 100 orgs/mlPresumptive identification; confirmation by culture /

NAA test

MICROSCOPY…

Decisive step for diagnosis, treatment & control of TB

Combination of solid & liquid media- “gold standard” for primary isolation

Recommended turn around time (CDC)14 days (culture)21-30 days (identification & susceptibility)

CULTURE…

Fully automated

Non-invasive

Continuously monitored non-radiometric

system

Revised antibiotic supplement kit

Medium - modified Middlebrook 7H9 broth

with supplements

BacT/ALERT 3D MB…

CO2 released by mycobacteria detected by sensorColor changes - increase in reflectance unitsPositive broth - 106-107 orgs/ml

Higher biomass - direct inoculation of identification panels & susceptibility tests

In vitro laboratory diagnostic test (May ’05)Indirect test for M. tuberculosis complex

M. tuberculosisM. bovis, M. africanum, M. Microti, M. Canetti

infectionTuberculosis disease OR latent tuberculosis infection

(LTBI)- cannot distinguish between themIntended for use in conjunction with risk assessment,

radiography, and other medical and diagnostic evaluations

QUANTIFERON-TB GOLD…

Single patient visit - whole blood sample - 4 ml of heparinised whole blood

Must be transported to lab to allow initiation of testing within 12 hours (viable lymphocytes)

Rapid results (within 24 hours)No booster response (measured by subsequent tests -

which can happen with Mantoux)No reader bias (cf Mantoux)Not affected by prior BCG vaccinationImpaired or altered immune functionST: 80-95% (Mantoux 75-90%)SP: 95-100% (Mantoux 70-95%)

DNA probesFrom culturesDirect samples > 10,000 organisms

rRNA probesGene amplification

PCRIsothermal amplification

Gen-probe AMTD, NASBA, SDA (IS6110), QB replicase

MOLECULAR DIAGNOSIS OF TB...

UsesRapid diagnosis in smear negative samples

65 kDA protein encoding genempt64 gene

Differentiate M. tb / NTMSpecies specific IS6110

Genetic markers for drug resistanceRifampicin – rpoBINH – codon 315 of katG

False positives & false negatives (inhibitors)Negative result cannot rule out TB & positive result is

not always confirmatory

PCR…

Based on hybridisation of nucleic acids4 steps

Sample preparationHybridisationSelection of the hybridDetection of the hybrid

ACCUPROBE TEST…

Mycobacteriophage detection systemM. smegmatis lytic cycle: 90 minsNot expensive; safeViable bacilli, intact phage receptorsAffected by effective ATT – monitor trt successPhage inhibitory substancesAnalytical ST: 100-300 bacilli/mlMixed results

Good sp (96-99%)Less st (70-87%)

FASTPlaque TB…

Rigid pipe-stem tubesA clubbed ampulla with retort-shaped

hydrosalpingxVascular or lymphatic intravasation of contrastSmall shrunken uterine cavity with filling defectsLong and dilated cervical canal & dye in cervical

cryptsBilateral cornual blockPunctate opacification of crypts and diverticulae

in lumen of tubes

HSG…

A combination of PCR with the other available techniques is the best method of achieving sufficient sensitivity and specificity for the diagnosis of female genital tuberculosis

PCR positive + culture negative – warrants therapy as PCR can detect very few bacilli & even dead bacilli.

PCR negative + culture positive – this result cannot be dismissed as contamination carry false negative rate of PCR. Culture remains gold standard.

CONCLUSION…

Clinical:• Acute and chronic bacterial infection.• Ascites / peritonitis / hepatitis/ chloecystitis /

appendicitis / ovarian / cancer/ renal dz / cardiac dz.

HPR: Granulomatous lesion- Sarcoidosis / leprosy

/ syphilis / FB reaction.

DIFFRENTIAL DIAGNOSIS…

Subfertility & Infertility- Residual damage of the fallopian tubes is often irreversible even following medical regimens, unless genital T.B. is diagnosed and treated early in its course. Symptoms of pain and menstrual disorder respond to medical treatment.

Ectopic pregnancy- Risk of ectopic pregnancy following medical treatment is estimated to be 33%- 72%.

Congenital T.B.- Rare but potentially serious complication. Over whelming systemic infection in the new born has considerable morbidity &mortality.

COMPLICATIONS…

Once diagnosed a gynecologist must consider following points:- Rule out active T.B. at any other site.Know the extent of genital lesion.Will medical management cure the lesion?Is pregnancy possible following treatment?

MANAGEMENT…

Experts suggest that it is easier to treat these cases because they are paucibacillary.

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.

MEDICAL TREATMENT…

For patients who are compliant and the

organism is fully susceptible.

INH+RIF+PZA--- 2 months

INH+RIF --- 4 monthsFor patients who cannot tolerate PZA

INH+RIF--- 9 monthsEthambutol or SM should be included in above

regimen till results of drug susceptibility are

available.Add pyridoxine 25-50mg in regimen including

INH.Multi drug resistance drug used are-PAS/cycloserine/capreomycin/kanamycin/amikacin/thioacetazone

Indications:-Persistent & recurrent disease/pelvic masses/pelvic

pain/abnormal bleeding despite adequate treatmentPersistent non healing fistulaMulti drug resistant diseaseConcomitant neoplasia of genital tract

Chemotherapy should precede surgery by 1-2 weeks.Surgery should be done at mid cycle in premenopausal.C.T. should be continued for 6-12 months post op.Premenopausal-save ovaries if normal, otherwise TAH

with BSO followed by HRT.

SURGICAL TREATMENT

Thank

you….