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female Genital tuberculosis,TB-PCR, female infertility,
 

female Genital tuberculosis,TB-PCR, female infertility,

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female genital TB poses stiffest challenge in the diagnosis, rapid molecular techniques have helped in arriving at a definitive diagnosis in suspicious clinical setting

female genital TB poses stiffest challenge in the diagnosis, rapid molecular techniques have helped in arriving at a definitive diagnosis in suspicious clinical setting

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    female Genital tuberculosis,TB-PCR, female infertility, female Genital tuberculosis,TB-PCR, female infertility, Presentation Transcript

    • Veerendrakumar C M MD,DNB Professor Dept of Obstetrics and Gynecology VIMS,Bellary veerendrakumarcm@gmail.com
    •  TB recognized as clinical entity in 1000BC  Morgagni postmortem examination of a WOMAN IN 1744 , Her uterus tubes filled with caseous material..  TB word coined in 1834  Robert Koch discovered bacilli in 1884
    • Indonesia 6% Nigeria 5% Other countries 20% Other 13 HBCs 16% China 14% South Africa 5% Bangladesh 4% Ethiopia 3% Pakistan 3% Phillipines 3% India 21% Global annual incidence = 9.4 million India annual incidence = 1.96 million India is 17th among 22 High Burden Countries (in terms of TB incidence rate)
    • Estimated burden per year  Indirect costs to society $3 billion  Direct costs to society $300 million  Productive work days lost due to TB illness 100 million  Productive work days lost due to TB deaths 1.3 billion  School drop-outs due to parental TB 300,000  Women rejected by families due to TB 100,000
    •  50% of Indian Population has TB  Every one minute one person dies of TB
    •  Mostly secondary manifestation of Primary Tb  5-13% of PTB develop into GTB  Genital tract vulnerable after puberty
    •  Meningeal TB gravest manifestation  Genital TB poses stiffest diagnostic challenge.
    •  Varied clinical presentation  diverse results on imaging, laparoscopy, HPE and mixed bag of bacteriological and serological tests.
    •  Disease discovered incidentally  Physician’s interest in searching for the disease Fransis J obstet gynecol Br Commonw 1964
    •  5% incidence world wide  < 1% in USA  19% in India  Cli obstet gynecol 1976
    •  Frequency of Genital TB in surgically removed adnexa 2-20%  Depends on care with which examination done..
    •  Infertility cases 17.8% Khilani et al 1988  GTB -3.5% Ojo et al 1966  Gini from nigeria reported 0.2% Int J obstet gynecol 1990
    •  GTB a major health problem in developing countries. Am J obstet Gynecol 1990
    •  Almost always secondary to primary Tb elsewhere in the body.  If bacilli not eradicated may get reactivated later in life esp in the presence of - Hodgkin’s Lymphoma - AIDS -Steroids - Stress - Malnutrition
    •  Fallopian TB most favorable nidus with earliest lesion in Mucosa
    •  Bovine genital tuberculosis may spread thru GIT by drinking raw milk.
    •  When primary infection occurs closer to Menarche genital tract more likely to be involved. Burnie 1956
    •  Sexual partners may be source of infection  4% of husbands had active genitourinary TB Sutherland 1982
    •  May exist as adenitis of mesenteric or pelvic lymphnodes.  May not involve genital tract
    • ORGAN FREQUENCY Fallopian tubes 90-100% Endometrium 50-60% Ovaries 20-30% Cervix 5-15% Vulva and Vagina 1% Schaefer 1976
    •  Exudative salpingitis – acute phase  Adhesive salpingitis- studded with tubercles and densely adherent to adjacent organs.
    •  Further involvement of uterus and ovaries by direct spread  Most extensive TB involvement in the fundus  Shed endometrium is reinfected from the tubes.
    •  Total destruction of the endometrium can result in amenorrhea (2.5% cases of TB endometritis) Obstet gynecol 1979 Fertil steril 1982
    • Infrequent,extremely scanty, isolated, scattered small tubercles are seen. Careful search thru all the curettings may show 1-2 foci TB !!!!
    •  Granuloma are best recognised on Day 24-26  Or within 12 hrs of the onset of menses. Fertil steril 1978
    •  Plastic variety - less common, tender abdominal mass, “doughy” to palpation  Serous variety more common, ascites,fever , wt loss , anorexia
    •  66 % women were between 25-35 yrs 11% were postmenopausal Obstet gynecol 1979  In recent times incidence in older women is increasing.. Sutherland 1982
    •  High index of suspicion  20% give family history  30-50% might have had some form of TB and give H/o ATT. Int J Obstet Gynecol 1991
    •  Systemic  Infertility  Menstrual disturbances  Abdominal swelling , postcoital bleeding, vaginal discharge,dyspareunia
    •  Infertility  AUB  CPP  Amenorrhea
    •  85% of GTB patients were never pregnant  Infertility is the leading complaint in 50% Sutherland AM 1983  64% complained of infertility Tripathy ,JIMA 1987
    •  25-50%  Chronic in nature  May get aggravated by coitus,exercise,menses
    •  Oligohypomenorrhea -54%  Menorrhagia – 20%  Amenorrhea – 14 % JIMA 2000  High degree of suspicion and efficient investigation
    •  Endorgan failure due to caseation  Ovary function normally Malkani et al 1966
    • Poor health Wt loss Undue fatigue Low grade fever Vague abdominal discomfort
    •  Uterovesical,tubointestinal,tuboperitoneal fistula may be present  GTB can mimick ovarian malignancy  Ca 125 can also be raised  Sheth SS Int J obstet Gynecol 1996
    •  Normal 35- 50 %  Abdominal mass  Pelvic mass  Adnexal mass/ tenderness  Ascites  Excessive Vaginal discharge  Ulcer vagina cervix vulva Simon et al Am J Med 1977
    •  Superimposition of bacterial infection, gynecological operative procedures trauma to the pelvis Am J obstet gynecol 1972
    •  in postmenopauasal women  Senile endometritis ca cervix J clin Ultrasound 1983
    •  Unexplained infertilty  Chronic PID refractory to standard antibiotic treatment  Adnexal disease with ascites in virgins
    •  Little value  Counts usually normal, tendency towards Rt side  Urine microscopy may show abacteriuric pyuria in concommitant GUTB Burnie 1956
    •  Egg based media 3-8 weeks eg Lowenstein Jensen media  Agar based < 3 weeks eg- BACTEC medium  BacT/ALERT 3D MB  modified Middlebrook 7H9 broth with supplements
    •  Prior evidence of Pulmonary TB may be present in 10- 50% of the cases  Simultaneous active PTB and GTB are rare. Chattopadhyaya 1986
    •  Not 100 % sensitive or specific  A positive test is read as discrete wheal > 10mm between 48 - 78 hrs
    •  Mantoux test in women with laparoscopically diagnosed tuberculosis sensitivity - 55% specificity - 80% Int J Gynaecol Obstet 2001
    •  Endometrium readily accessible  < 12 hrs collection showed positive for MTB in 10% of the cases.  Other AFB may be mistaken for MTB NTM -non tubercular mycobacteria MOTT- mycobacteria other than tubercular
    •  Frequent first diagnostic test  False negetive bcoz of sampling errors  Diagnosis either MTB isolation or histological Granulomata.
    •  Cornual curettage yields atleast 50% possibilty of rapid histological diagnosis  Optimum time late menses period or < 12 hrs of menses  positive culutre was seen in 25 % cases of Tb endometritis. Am J Obstet gynecol 1980
    •  110 cases of endometrial sampling  13.6% culture  Smear positive in 1.8% cases  HPE in 3.6% cases Albert H 1990
    •  Avoid if TB is suspected , exacerbation following the procedure. Winifred 1977
    •  Irregular uterine cavity  Intrauterine adhesions  Scanty endometrium  Endometrial calcification  Caseation/ tubercles  Periosteal fibrosis  Caseous material coming out of ostia  Ostia not visualized JIMA july 2013
    • ADHESIONS AFTER ADHESIOLYSIS
    • Normal ostia Intrauterine adhesions
    •  Adhesions  Pelvic congestion  Tubercles  Frozen pelvis  Edematous inflammed tubes  Beaded tubes  TO mass  Straw colored fluid inPOD JIMA july 2013
    •  Conventional cultures take 3-8 weeks to yield definitive result.
    •  Genotypic Methods :  PCR  NAA Dr.T.V.Rao MD 68
    •  Detection is based on multiplication not of whole bacilli, as in culture, but of their genetic material, chromosomal DNA or ribosomal RNA.  In principle, from one target sequence, of one bacillus, the reaction can produce millions of copies and thus yield a positive result Dr.T.V.Rao MD 69
    •  in principle, only 1-2 days are needed. Dr.T.V.Rao MD 73
    •  Gen –probe M.tuberculosis test – transcription mediated amplification of rRNA good in smear positive samples  Ampiclor test – PCR amplification of DNA
    •  Real time PCR eg: Mycosure Dr.Lal Pathlab detects both mycobacterium tuberculosis and Non tuberculosis mycobacteria  Multiplex PCR eg TB PCR –SRL laboratory detects mycobacteria tuberculosis complex
    •  Nested DNA PCR Eg. Reliance laboratory targets IS61110 gene region in TB DNA
    •  False positive PCR may be due to NTM  False negative due to sampling error blood contamination paucibacillary specimens PCR inhibitors ineffective primers
    •  Repeat tissue sampling  Go for different diagnostic technique
    •  new class of in vitro assay that measure interferon (IFN-γ) released by sensitized T cells after stimulation by M. tuberculosis antigens.  Measures immune reactivity to M.tb. 83
    •  provide the best available method of diagnosing TB infection using blood.  Used for screening.. 84
    •  QuantiFERON-TB ® test – Commercially available. – Measures amount of IFN-γ produced. (ELISA) – FDA-approved for the detection of LTBI, 2001. 85
    •  Initial therapy with 4 drugs INH+RIF+PZA add EMB/SM  Maintenance therapy INH +RIF
    •  Histologically cured between 4-12 weeks  Recurrence of cases within 2-5 yrs if tubes are not removed. Kardos et al
    •  Careful compliance is the most important to prevent drug resistance
    •  Persistent /recurrent disease  Recurrent pelvic masses  Recurrent pelvic pain and AUB  Non healing fistula  Concomittant neoplasia
    •  Start ATT immediately for 6-12 months
    •  Sutherland 1976 – 6.7% livebirth rate 206 women treatment for 18-24 months 26 conceived 23 live births,11 ectopic, 11 miscarriage  Tripathy-2006 Conception rate 19.2% livebirth rate- 7.2%
    •  BETTER chance of conception Frydman et al - 49 attempts 6 conceived
    •  FGTB underdiagnosed.  Strong suspicion is key to diagnosis  Prompt treatment of primary TB decreases incidence of EPTB  Routine blood tests, Mantoux test, smear, histology and culture pick up very low % cases  Modern NAAT tests are rapid and help in the diagnosis and treatment  Infertility with poor pregnancy rate is seen in FGTB.