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

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female Genital tuberculosis,TB-PCR, female infertility,

  1. 1. Veerendrakumar C M MD,DNB Professor Dept of Obstetrics and Gynecology VIMS,Bellary veerendrakumarcm@gmail.com
  2. 2.  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
  3. 3. 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)
  4. 4. 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
  5. 5.  50% of Indian Population has TB  Every one minute one person dies of TB
  6. 6.  Mostly secondary manifestation of Primary Tb  5-13% of PTB develop into GTB  Genital tract vulnerable after puberty
  7. 7.  Meningeal TB gravest manifestation  Genital TB poses stiffest diagnostic challenge.
  8. 8.  Varied clinical presentation  diverse results on imaging, laparoscopy, HPE and mixed bag of bacteriological and serological tests.
  9. 9.  Disease discovered incidentally  Physician’s interest in searching for the disease Fransis J obstet gynecol Br Commonw 1964
  10. 10.  5% incidence world wide  < 1% in USA  19% in India  Cli obstet gynecol 1976
  11. 11.  Frequency of Genital TB in surgically removed adnexa 2-20%  Depends on care with which examination done..
  12. 12.  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
  13. 13.  GTB a major health problem in developing countries. Am J obstet Gynecol 1990
  14. 14.  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
  15. 15.  Fallopian TB most favorable nidus with earliest lesion in Mucosa
  16. 16.  Bovine genital tuberculosis may spread thru GIT by drinking raw milk.
  17. 17.  When primary infection occurs closer to Menarche genital tract more likely to be involved. Burnie 1956
  18. 18.  Sexual partners may be source of infection  4% of husbands had active genitourinary TB Sutherland 1982
  19. 19.  May exist as adenitis of mesenteric or pelvic lymphnodes.  May not involve genital tract
  20. 20. ORGAN FREQUENCY Fallopian tubes 90-100% Endometrium 50-60% Ovaries 20-30% Cervix 5-15% Vulva and Vagina 1% Schaefer 1976
  21. 21.  Exudative salpingitis – acute phase  Adhesive salpingitis- studded with tubercles and densely adherent to adjacent organs.
  22. 22.  Further involvement of uterus and ovaries by direct spread  Most extensive TB involvement in the fundus  Shed endometrium is reinfected from the tubes.
  23. 23.  Total destruction of the endometrium can result in amenorrhea (2.5% cases of TB endometritis) Obstet gynecol 1979 Fertil steril 1982
  24. 24. Infrequent,extremely scanty, isolated, scattered small tubercles are seen. Careful search thru all the curettings may show 1-2 foci TB !!!!
  25. 25.  Granuloma are best recognised on Day 24-26  Or within 12 hrs of the onset of menses. Fertil steril 1978
  26. 26.  Plastic variety - less common, tender abdominal mass, “doughy” to palpation  Serous variety more common, ascites,fever , wt loss , anorexia
  27. 27.  66 % women were between 25-35 yrs 11% were postmenopausal Obstet gynecol 1979  In recent times incidence in older women is increasing.. Sutherland 1982
  28. 28.  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
  29. 29.  Systemic  Infertility  Menstrual disturbances  Abdominal swelling , postcoital bleeding, vaginal discharge,dyspareunia
  30. 30.  Infertility  AUB  CPP  Amenorrhea
  31. 31.  85% of GTB patients were never pregnant  Infertility is the leading complaint in 50% Sutherland AM 1983  64% complained of infertility Tripathy ,JIMA 1987
  32. 32.  25-50%  Chronic in nature  May get aggravated by coitus,exercise,menses
  33. 33.  Oligohypomenorrhea -54%  Menorrhagia – 20%  Amenorrhea – 14 % JIMA 2000  High degree of suspicion and efficient investigation
  34. 34.  Endorgan failure due to caseation  Ovary function normally Malkani et al 1966
  35. 35. Poor health Wt loss Undue fatigue Low grade fever Vague abdominal discomfort
  36. 36.  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
  37. 37.  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
  38. 38.  Superimposition of bacterial infection, gynecological operative procedures trauma to the pelvis Am J obstet gynecol 1972
  39. 39.  in postmenopauasal women  Senile endometritis ca cervix J clin Ultrasound 1983
  40. 40.  Unexplained infertilty  Chronic PID refractory to standard antibiotic treatment  Adnexal disease with ascites in virgins
  41. 41.  Little value  Counts usually normal, tendency towards Rt side  Urine microscopy may show abacteriuric pyuria in concommitant GUTB Burnie 1956
  42. 42.  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
  43. 43.  Prior evidence of Pulmonary TB may be present in 10- 50% of the cases  Simultaneous active PTB and GTB are rare. Chattopadhyaya 1986
  44. 44.  Not 100 % sensitive or specific  A positive test is read as discrete wheal > 10mm between 48 - 78 hrs
  45. 45.  Mantoux test in women with laparoscopically diagnosed tuberculosis sensitivity - 55% specificity - 80% Int J Gynaecol Obstet 2001
  46. 46.  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
  47. 47.  Frequent first diagnostic test  False negetive bcoz of sampling errors  Diagnosis either MTB isolation or histological Granulomata.
  48. 48.  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
  49. 49.  110 cases of endometrial sampling  13.6% culture  Smear positive in 1.8% cases  HPE in 3.6% cases Albert H 1990
  50. 50.  Avoid if TB is suspected , exacerbation following the procedure. Winifred 1977
  51. 51.  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
  52. 52. ADHESIONS AFTER ADHESIOLYSIS
  53. 53. Normal ostia Intrauterine adhesions
  54. 54.  Adhesions  Pelvic congestion  Tubercles  Frozen pelvis  Edematous inflammed tubes  Beaded tubes  TO mass  Straw colored fluid inPOD JIMA july 2013
  55. 55.  Conventional cultures take 3-8 weeks to yield definitive result.
  56. 56.  Genotypic Methods :  PCR  NAA Dr.T.V.Rao MD 68
  57. 57.  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
  58. 58.  in principle, only 1-2 days are needed. Dr.T.V.Rao MD 73
  59. 59.  Gen –probe M.tuberculosis test – transcription mediated amplification of rRNA good in smear positive samples  Ampiclor test – PCR amplification of DNA
  60. 60.  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
  61. 61.  Nested DNA PCR Eg. Reliance laboratory targets IS61110 gene region in TB DNA
  62. 62.  False positive PCR may be due to NTM  False negative due to sampling error blood contamination paucibacillary specimens PCR inhibitors ineffective primers
  63. 63.  Repeat tissue sampling  Go for different diagnostic technique
  64. 64.  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
  65. 65.  provide the best available method of diagnosing TB infection using blood.  Used for screening.. 84
  66. 66.  QuantiFERON-TB ® test – Commercially available. – Measures amount of IFN-γ produced. (ELISA) – FDA-approved for the detection of LTBI, 2001. 85
  67. 67.  Initial therapy with 4 drugs INH+RIF+PZA add EMB/SM  Maintenance therapy INH +RIF
  68. 68.  Histologically cured between 4-12 weeks  Recurrence of cases within 2-5 yrs if tubes are not removed. Kardos et al
  69. 69.  Careful compliance is the most important to prevent drug resistance
  70. 70.  Persistent /recurrent disease  Recurrent pelvic masses  Recurrent pelvic pain and AUB  Non healing fistula  Concomittant neoplasia
  71. 71.  Start ATT immediately for 6-12 months
  72. 72.  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%
  73. 73.  BETTER chance of conception Frydman et al - 49 attempts 6 conceived
  74. 74.  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.

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