Drug Sensitive Tuberculosis updates now.pptx

DSTB

1. DRUG SENSITIVE TUBERCULOSIS DR DEBJYOTI DEY DNB RESIDENT RESPIRATORY MEDICINE

2. DEFINITIONS

3. Presumptive Pulmonary TB It refers to a person with any of the symptoms and signs suggestive of TB cough for 2 weeks or more fever for 2 weeks or more significant weight loss Haemoptysis any abnormality in chest radiograph. The following patients are also to be investigated as presumptive PTB Contacts of Microbiologically confirmed TB patients having cough of any duration Presumptive /confirmed extra-pulmonary TB having cough of any duration HIV positive patient having cough of any duration Note: Contacts of microbiologically-confirmed TB Patients, PLHIV, diabetics, malnourished, cancer patients, patients on immune-suppressants or steroid should be regularly screened for sign and symptoms of TB

4. Presumptive Extra Pulmonary TB It refers to the presence of organ-specific symptoms and signs like swelling of lymph node, pain and swelling in joints, neck stiffness, disorientation, etc., and/or constitutional symptoms like significant weight loss, persistent fever for 2 weeks or more, night sweats.

5. Presumptive Paediatric TB It refers to children with Persistent fever and/ or cough for 2 weeks or more Loss of weight (loss of more than 5% body weight as compared to highest weight recorded in last 3 months)/ no weight gain and/ or history of contact with infectious TB cases. Note: In a symptomatic child, contact with a person with any form of active TB within last 2 years may be significant

6. Presumptive DR TB It refers to the patient who is eligible for Rifampicin resistant screening at the time of diagnosis or/and during the course of treatment for DS TB or H mono/poly resistance. This includes following patients: All Notified TB patients (Public and private) - Follow-up positive on microscopy including treatment failures on standard first line treatment and all oral H mono/poly regimen Any clinical non-responder including paediatric patients

7. Microbiologically confirmed TB It refers to a presumptive TB case from whom a biological specimen is positive for acid fast bacilli positive for Mycobacterium tuberculosis on culture positive for tuberculosis through Rapid Diagnostic molecular test

8. Clinically Diagnosed TB It refers to a presumptive TB case who is not microbiologically confirmed has been diagnosed with active TB by a clinician on the basis of X-ray abnormalities histopathology clinical signs with a decision to treat the patient with a full course of Anti-TB treatment. In children, this is based on the presence of abnormalities consistent with TB on radiography history of exposure to an infectious case evidence of TB infection (positive TST) clinical findings suggestive of TB in the event of negative or unavailable microbiological results

9. Pulmonary tuberculosis (PTB) It refers to any microbiologically confirmed or clinically diagnosed TB involving the lung parenchyma or the tracheo -bronchial tree. A patient with both pulmonary and extra-pulmonary TB should be classified as a case of Pulmonary TB. Miliary TB is classified as PTB because there are lesions in the lungs.

10. Extra Pulmonary tuberculosis (EPTB) It refers to any microbiologically confirmed or clinically diagnosed TB involving organs other than the lungs such as pleura, lymph nodes, intestine, genitourinary tract, joint and bones, meninges of the brain etc.

11. New TB patient A TB patient who has never had treatment for TB or has taken anti-TB drugs for less than one month is considered as a new TB patient.

12. Previously treated TB A patient who has received one month or more of anti-TB drugs from any source in the past. Recurrent TB patient - A TB Patient previously declared as successfully treated (cured/treatment completed) and is subsequently found to be microbiologically confirmed TB is a recurrent TB patient. Treatment after failure patients – A TB patient who have previously been treated for TB and whose treatment failed at the end of their most recent course of treatment. Treatment after lost to follow-up - A TB patient previously treated for TB for one month or more and was declared lost to follow-up (LFU) in their most recent course of treatment and subsequently found to be microbiologically confirmed TB IV. Other previously treated patients are those who have previously been treated, who cannot be classified into any of the above.

13. Transfer in A TB patient A TB patient who has been received for treatment in a Tuberculosis Unit, after starting treatment in another TB unit where s/he has been registered is considered as transferred in.

14. ALGORITHM

15. TREATMENTS

16. Drug Sensitivity Tuberculosis Treatment Clinicians should follow Standards for TB care in India (STCI) guidelines for TB treatment. Administer daily fixed dose combinations of first – line anti-tuberculosis drugs in appropriate weight bands. Regimen for Drug-Sensitive TB (DSTB) cases: 2HRZE/4HRE This regimen is for H & R sensitive TB cases and cases with unknown sensitivity pattern. Loose Drugs could be used as substitutions in case of adverse drug reaction or with comorbid conditions. Steroids as an adjunctive therapy is useful in patients with TB pericarditis and meningeal TB, with an initial high dose tapered downwards gradually over 6 - 8 weeks.

17. Actions of Anti-TB drugs: Early bactericidal activity Sterilizing activity Ability to prevent emergence of drug resistance

18. Drugs Action Early bactericidal Sterilizing activity Prevention of emergence of drug resistance Isoniazide (H) exerting early bactericidal activity prevents emergence of drug resistant mutants to any companion drug has low rates of adverse drug reactions + + + + + + + + + + Rifampicin (R) a potent bactericidal and sterilizing drug acting on semi- dormant bacilli which multiply intermittently and causing relapse. + + + + + + + + + + Pyrazinamide (Z) a bactericidal and sterilizing drug effective in eliminating the semi dormant bacilli multiplying slowly in an acidic environment. + + + - + + Ethambutol (E) an effective bacteriostatic drug preventing emergence of resistance to other companion drugs. + + + + + + Streptomycin (S) a bactericidal drug reduce septicaemia and toxicity + - + +

19. Two phases of treatment: Intensive phase (IP) consists of 8 weeks (56 doses) of isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given under direct observation in daily dosages as per weight band categories. Continuation phase (CP) consists of 16 weeks (112 doses) of isoniazid, rifampicin and ethambutol in daily dosages. The CP may be extended by 12-24 weeks in certain forms of TB like CNS TB, Skeletal TB, Disseminated TB etc. Extension beyond 12 weeks should only be on recommendation of specialists

20. Roles of Intensive Phase To achieve rapid killing of actively multiplying bacillary population To eliminate naturally occurring drug resistant mutants To prevent the further emergence of drug resistant mutants Role of continuation phase To elimination of persisters which are responsible for relapses.

21. Fixed Dose Combinations (FDCs) It refer to products containing two or more active ingredients in fixed doses, used for a particular indication(s). IN NTEP, for Adults - 4-FDC (given in IP) consists of HRZE and 3-FDC (given in CP) consists of HRE For paediatric patients -Dispersible 3 FDC consists of HRZ and Dispersible 2 FDC consists of HR.

22. Advantages of FDCs Simplicity of treatment Increased patient acceptance – Fewer tablets to swallow – Prevents 'concealed' irregularity Increased health worker compliance – Fewer tablets to handle, hence quicker supervision of DOT Easier drug management Reduced use of monotherapy – Lower risk of misuse of single drugs Lower risk of emergence of drug resistance Easier to adjust dosages by body weight

23. Drug dosages for first line anti- TB drugs Drugs Adult (mg/kg daily ) Children (mg/kg daily ) Max. dose for children (mg) ISONIAZIDE 5 (4 - 6) 10 (7 – 15) 300 RIFAMPICIN 10 (8 - 12) 15 (10 – 20) 600 PYRAZINAMIDE 25 (20 - 30) 35 (30 – 40) 2000 ETHAMBUTOL 15 (12 - 18) 20 (15 – 25) 1500 STREPTOMYCIN 15 (15 - 20) 20 (15 – 20) 1000 Streptomycin is administered only in certain situations, like TB meningitis or if any first line drug need to be replaced due to ADR as per weight of the patient. Ethambutol is given separately for children to monitor ophthalmic ADR.

24. Daily Dose Schedule for Adults (as per weight bands)

25. Drug Dosage for Paediatric TB

26. Treatment outcomes for drug susceptible TB Patients Cured: Microbiologically confirmed TB patients at the beginning of treatment who was smear or culture negative at the end of the complete treatment Treatment completed: A TB patient who has completed treatment without evidence of failure or clinical deterioration BUT with no record to show that the smear or culture results of biological specimen in the last month of treatment was negative, either because test was not done or because result is unavailable. Failure: A TB patient whose biological specimen is positive by smear or culture at end of treatment. Failure to Respond: A case of paediatric TB who fails to have microbiological conversion to negative status or fails to respond clinically / or deteriorates after 12 weeks of compliant treatment shall be deemed to have failed response provided alternative diagnosis/ reasons for nonresponse have been ruled out.

27. Treatment outcomes for drug susceptible TB Patients Lost to follow up: A TB patient whose treatment was interrupted continuously for ONE month or more. Not Evaluated - A TB Patient for whom no treatment outcome is assigned. This includes former “transfer-out”. Treatment Regimen Changed - A TB patient who is on first line regimen and has been diagnosed as having DRTB and switched to drug resistant TB regimen prior to being declared as failed. Died: A patient who has died during the course of anti-TB treatment Treatment Success: TB patients either cured or treatment completed are accounted in treatment success. It is an indicator and not an outcome.

28. SIDE EFFECTS OF ANTI TUBERCULAR DRUGS AND THEIR MANAGEMENT

29. Side effects of first line anti-TB drugs: Drug Main effects Rare effects Isoniazid Peripheral neuropathy, Skin rash, Hepatitis, Sleepiness and lethargy Convulsions, Psychosis, Arthralgia, Anaemia Rifampicin Gastrointestinal: abdominal pain, nausea, vomiting Hepatitis Generalised cutaneous reactions Thrombocytopenic purpura Osteomalacia , Pseudomemberanous colitis, Pseudoadrenal crisis Acute renal failure Haemolytic anaemia Pyrazinamide Arthralgia, Hepatitis, Gastrointestina Cutaneous reactions, Sideroblastic anaemia Ethambutol Retrobulbar neuritis Generalised cutaneous reactions, Arthralgia, Peripheral neuropathy, Hepatitis (very rare) Streptomycin Allergy, severe fever, Burning or tingling sensation, Vertigo, Nausea and vomiting, Difficult or painful urination, Blurred or double vision,Hearing impairment – SEVERE, Fast/irregular heart beats

30. Symptom-based approach to evaluation of possible side effects of anti-TB drugs Symptoms Cause Action to be taken by HW Action to be taken by MO Vomiting or epigastric discomfort Any oral medications Reassure patient. Give drugs with less water and over a longer period of time (e.g. 20 minutes). Do not give drugs on an empty stomach Maintain hydration Consider treatment with anti-emetics (e.g. domperidone ) and proton pump inhibitors (e.g. Omeprazole) Itching / Rashes Isoniazid (and other drugs also) Reassure patient Itching without rash or a mild rash: • Continue treatment and give antihistamines Itching with moderate to severe rash • Stop all drugs till symptoms subside and give antihistamines • Patients with mucosal involvement, fever and hypotension will require treatment with corticosteroids • When the reaction subsides reintroduce drugs one by one in this order (INH > Rifampicin > Pyrazinamide > Ethambutol) • Re-introduce each drug in a small dose and gradually increase over 3 days before introducing the next drug.

31. Symptom-based approach to evaluation of possible side effects of anti-TB drugs Symptoms Cause Action to be taken by HW Action to be taken by MO Tingling / burning / numbness in the hands and feet Isoniazid P yridoxine 100 mg/day orally or parenterally until symptoms subside. If not responding to pyridoxine > require treatment with amitryptiline . Joint pains Pyrazinamide Reassure Increase intake of liquids NSAIDs like Paracetamol, Aspirin or Ibuprofen and in severe cases Indomethacin for a week to 10 days In severe cases estimate serum uric acid levels - If significantly raised treat with NSAIDs and colchicine. In severe cases with normal or slightly elevated uric acid consider reduction of the dose of Pyrazinamide.

32. Symptom-based approach to evaluation of possible side effects of anti-TB drugs Symptoms Cause Action to be taken by HW Action to be taken by MO Impaired vision Ethambutol Stop Ethambutol Refer to ophthalmologist for evaluation Impaired vision may, within a few weeks, or may not return to normal after stopping ethambutol. Don’t restart ethambutol. Ringing in the ears Loss of hearing Dizziness and loss of balance Streptomycin Stop Streptomycin Refer to ENT specialist for opinion As hearing loss is usually not reversible do not restart Streptomycin

33. Symptom-based approach to evaluation of possible side effects of anti-TB drugs Symptoms Cause Action to be taken by HW Action to be taken by MO Hepatitis: Anorexia, Nausea, vomiting, Jaundice Isoniazid, Rifampicin or Pyrazinamide STOP all anti TB drugs, Refer patient for evaluation • Rule out other causes of hepatitis • Do not restart treatment till symptoms resolve and liver enzymes return to baseline levels • If liver enzymes cannot be performed wait for 2 weeks after jaundice has disappeared to restart treatment • Restart treatment with one drug at a time starting with Rifampicin > INH > Pyrazinamide. • In patients with severe disease in whom treatment cannot be stopped use a non-hepatotoxic regimen consisting of Streptomycin and Ethambutol

34. EXTRAPULMONARY TUBERCULOSIS

35. Tuberculous Lymphadenitis Lymph node tuberculosis ( LNTB) is the most common form of EPTB in India, accounting for around 35% of EPTB cases. Among all tuberculous lymphadenitis, cervical adenopathy is most common (45-75% cases), but inguinal, axillary, mesenteric and mediastinal involvement have also been described.

36. Clinical features In addition to common constitutional symptoms TB of the deep lymph nodes in the chest ( mediastinal TB) may present with cough or shortness of breath. Abdominal LNTB patients may have abdominal pain or distension. The most common presentation is isolated chronic non-tender lymphadenopathy in a young adult without systemic symptoms other than fever, most commonly in the cervical region.

37. Pathogenesis Various portals of entries of infection are described for acquiring mycobacterium tuberculous lymphadenitis: Via respiratory tract - haematogenous and lymphatic dissemination. Hilar and mediastinal lymph nodes are usually involved initially. Via tonsil - spreads via the lymphatics to the draining cervical lymph nodes. (TB infection involving the tonsils, adenoids, and Waldeyer’s ring → Cervical tuberculous lymphadenitis → cervical lymphadenopathy) Abdominal tuberculous lymphadenopathy may occur via swallowing of sputum or milk infected with M. tuberculosis/M. bovis .

38. Progressions

39. Jones and Campbell classified peripheral tuberculous lymph nodes: Stage 1: Reactive lymphadenitis - enlarged, firm, mobile, discrete nodes showing non-specific reactive hyperplasia Stage 2: Peri adenitis -large rubbery nodes fixed to surrounding tissue Stage 3: Cold abscess -central softening due to abscess formation Stage 4: Collar-stud abscess formation Stage 5: Sinus tract formation

40. History Taking Points Duration of swelling: usually variable, can be acute (1-2 weeks) in some cases to chronic (months) in some cases. Associated symptoms such as fever, weight loss and loss of appetite. Contact/past history of tuberculosis must be sought for. History of tobacco/alcohol/drug abuse Treatment history includes the history of previous ATT intake (including drug, dose, duration and compliance).

41. Examination Size of lymph node: Significant if >2 cm diameter in the inguinal region and >1 cm in other regions. Consistency of lymph node: Hard – Malignancy/ Metastasis/ Chronic infection Firm / Rubbery – Lymphoma/ Chronic Leukemia Soft – Acute Leukemia Fixation: Fixed - malignancy/inflammation Matted - tuberculosis (conglomerated group of lymph node)/ sarcoidosis/ lymphoma/ metastatic carcinoma Tenderness: Acute viral/ bacterial infection Rapid tumor expansion/ bleeding into nodes Organomegaly: Liver/spleen In deep-seated lymphadenopathy surveillance of all peripheral lymph node is recommended.

42. Investigations Routine investigation: CBC, LFT, KFT, ESR, RBS, HIV serology Radiology: Chest X-ray, Ultrasonography, CT Scan, MRI/PET- CT Sampling: FNA, Biopsy ( Excisional biopsy > Incisional biopsy ) , EBUS-TBNA/ cTBNA Microbiological and pathological: FNAC, Molecular (NAAT), Culture (solid/liquid), Cyto-histopathology

43. Treatment Standard first-line regimen is recommended for peripheral lymph node TB Six months ATT: 2 months IP (HRZE) + 4 months CP (HRE) Continuation phase may be extended by 3 months

44. Follow Up Follow up of clinical response should be done at 1, 2, 4 and 6 months. Consider the possibility of treatment failure in patients who have worsened or deteriorated after initial improvement. Imaging to be repeated if clinically indicated. Development of LN fluctuation – should undergo aspiration. Sinus tracts - Any worsening after 8 weeks of therapy – en-bloc resection of the involved lymph node chain to avoid sinus tract formation. Some patients with LNTB have residual lymphadenopathy at the end of treatment, >1 cm in size: Partial responders (clinical features have persisted or reappeared): Additional 3 months of HRE, followed by a biopsy sent for histology and TB culture. Residual fibrotic LN (clinical features have resolved): ATT need not be extended.

45. Pleural Tuberculosis Pleural TB is a leading cause of exudative pleural effusion in our country pleural involvement is the second most common EPTB.

46. Pathophysiology Immunological factors: Delayed hypersensitivity type phenomenon to nucleic acids of TB bacilli Due to the rupture of subpleural foci with the entry of mycobacterial antigen into the pleural space Contiguous spread from lung - Haematogenous and lymphatic spread Reactivation of dormant TB foci

47. Clinical Features Symptoms: Most common clinical symptom is cough followed by chest pain. Fever Shortness of breath Constitutional symptoms like Night sweats, Weight loss On examination, Around 90% of tuberculous effusions are unilateral involving less than 2/3 of the hemithorax. Less than half (20-50%) of the patients have associated pulmonary lesions.

48. Investigations CXR (to confirm pleural effusion) Sputum for AFB/NAAT Pleural tap/ Thoracentesis (ultrasound-assisted) with Pleural fluid analysis : Cell Types Cell count (total and differential) Protein Glucose Gram stain Bacterial cultures Stain for acid-fast bacilli Adenosine deaminase (ADA) NAAT Cytology evaluation CT chest (before pleural biopsy) Pleural biopsy (image-guided/ thoracoscopic) (If diagnosis is uncertain) and Histopathology HIV serology CBC, LFT, KFTs, PT/INR

49. Management Anti Tubercular Therapy - 2HRZE + 4HRE (Total: 6 Months) Pleural Fluid Drainage (for symptomatic relief) via chest tube drainage/ pigtail catheter drainage

50. Complications Lack Of Response Drug Resistance Immune reconstitution inflammatory syndrome (IRIS) Superadded infection Pleural Thickening → restrictive lung pathology, fibrothorax → need decortication Empyema Hydro-Pneumothorax

51. Follow Up Monthly visits with monitoring for adverse drug events, documentation of vitals, fever, weight, examination findings. Chest radiographs should be done for monitoring at 2 months and 6 months. Improvement: significant/near-complete resolution of symptoms or calcification/pleural thickening. In spite of treatment for 2 months if the patient is having worsening of symptoms, lack of improvement or increasing effusion; clinical failure should be suspected. Such patients should be: Evaluated for drug-resistant tuberculosis Evaluate for alternate diagnosis by pleural biopsy, USG , CT scan etc.

52. Pericardial Tuberculosis The most common presentation of pericardial tuberculosis is in the form of pericardial effusion.

53. Pathophysiology Tubercle bacilli can enter the pericardium via one of the following routes: 1. Retrograde lymphatic spread from adjacent lymph nodes 2. Hematogenous spread 3. Adjacent spread from lung, spine or pleural involvement

54. Clinical features Tuberculous pericarditis most commonly present as form of pericardial effusion of variable duration, followed by constrictive pericarditis, myopericarditis and rarely cardiac tamponade. Constrictive pericarditis may have a subacute or chronic presentation. Myopericarditis usually presents as pericarditis with concurrent abnormal cardiac ejection fraction and/or elevated serum levels of cardiac enzymes.

55. Clinical features Clinical features attributable to pericardial disease: Chest discomfort, shortness of breath, orthopnoea Features of congestive heart failure, ascites out of proportion to minimal or absent pedal oedema Tamponade – hypotension, muffled heart sound, raised JVP, tachycardia, pulsus paradoxus (>10 mm of Hg drop in SBP with inspiration) Constitutional symptoms: fever with night sweats, significant weight loss, loss of appetite Pericardial calcification, cardiomegaly

56. Investigations CBC, LFT, RFT HIV Serology Chest X-Ray CECT Thorax ECG Echocardiogram Cardiac MRI Pericardiocentesis and Pericardial fluid analysis for Cell types Cell counts and Differential counts LDH Malignant cytology Cultures GeneXpert ADA

57. INVESTIGATION ALGORITHM

58. INVESTIGATION ALGORITHM

59. Treatment 2HRZE + 4HRE (for a total duration of at least 6 months). Use of Corticosteroid: an initial adjuvant corticosteroid therapy may be used (Conditional recommendation, very low certainty in the evidence). In HIV negative pt – corticosteroids may reduce deaths from all causes and the need for repeat pericardiocentesis. Prednisone in a dose of 1mg/kg for 4 weeks followed by 0.5mg/kg for 4 weeks and tapers gradually over next two to four weeks. Surgical Intervention: Pericardiocentesis – indicated as an urgent intervention in cardiac tamponade Pericardiectomy – on treatment option in constrictive pericardial disease as a late complication

60. Central Nervous System Tuberculosis TB of Central Nervous System (CNS) is the most severe form of TB and is almost always fatal if left untreated. The leptomeningeal form is the most common and most severe form of CNS TB. Tuberculomas and brain abscesses are less common than Tuberculous meningitis (TBM) and have lower mortality and morbidity.

61. Pathogenesis

62. Spectrum Of CNS TB Meningeal Involvement: most common form of CNS TB. Meningeal involvement may be further divided into:- Leptomeningeal involvement: It implies the involvement of pia-arachnoid layers and it is the most severe form of CNS TB. Patchy-meningeal involvement: It implies the involvement of dura mater. Parenchymal involvement – it includes Cerebritis & TB abscess Tuberculomas Miliary TB TB encephalopathy Spinal TB TB radiculomyelitis Myelitic tuberculomas Extrinsic (epidural abscess)

63. Clinical Features TB Meningitis: Vomiting Altered sensorium Anorexia Seizures Vision impairment Meningeal signs Papilledema 1 or more cranial nerve palsy Optic atrophy Constitutional symptoms History of recent (within the past year) close contact with an individual with PTB or positive TST or IGRA ( only in children Tuberculomas And Abscess Mass lesion causing focal neurological deficits depending on anatomical location and/or seizure found in concurrence with TBM

64. A. Contrast-enhanced CT scan demonstrates an intense enhancement of the basal meninges. Note the widening of the temporal horns, due to communicating hydrocephalus. B. Axial gadolinium-enhanced T1-weighted MR image demonstrates marked enhancement in the basal subarachnoidal cisterns BASAL EXUDATES

65. Tuberculoma Gadolinium enhanced MRI showed a ring-enhancing mass in the right parietal lobe Magnetic resonance imaging (MRI) of the brain with gadolinium contrast showing multiple ring enhancing lesions

66. Tuberculous arachnoiditis Tuberculous arachnoiditis , on sagittal T1-weighted (A) T2-weighted (B) short tau inversion recovery (C) images

67. Investiagtions CBC, CRP, LFT, RFT, Electrolytes HIV Serology Chest X Ray- PA view USG whole abdomen Mantoux (optional) NCCT/CECT head- Preferred as initial investigation MRI brain (and spine if indicated) in selective cases Lumber puncture with CSF analysis (Perform CT head prior to procedure) Cell count & type Protein Sugar Gene Xpert / TrueNat Grams stain Bacterial culture AFB stain AFB culture/sensitivity India Ink Cryptococcal antigen Fungal smear & culture Cytopathology Wet mount VDRL Toxoplasma PCR Viral PCR

68. TBM diagnostic criteria A. Clinical 1. Fever and headache lasting for more than 14 days (mandatory). 2. Vomiting, alteration of sensorium or focal deficit (optional). B. Cerebrospinal fluid 1. Pleocytosis with more than 20 cells, predominantly (greater than 60%) lymphocytes, protein greater than 100mg%, sugars less than 60% of corresponding blood sugars. 2. Negative India ink studies and cytology for malignant cells (in relevant situations). C. Radiological CT head showing 2 or more: 1. Exudates in basal cisterns or in Sylvian fissures 2. Hydrocephalus 3. Infarcts 4. Gyral enhancement D. Extra neural tuberculosis 1. Active TB of lungs, G.I.T, G.U.T, lymph nodes, skeletal system or skin - by radiological or 2. Microbiological tests or by presence of caseation necrosis on histopathological examination. Based on presence of these features in combination of one or more, TBM can be clinically categorised as: 1. Definite tuberculous meningitis ( i ) Clinical criteria (A) (ii) Bacterial isolation from CSF or diagnosis at autopsy 2. Highly probable tuberculous meningitis ( i ) Clinical criteria (A) (ii) All 3 of (B), (C) and (D) 3. Probable tuberculous meningitis ( i ) Clinical criteria (A) (ii) Any 2 of (B), (C) and (D) 4. Possible tuberculous meningitis ( i ) Clinical criteria (A) (ii) Any one of (B), (C) and (D) .

69. British MRC Grading (Severity) Grade 1 TBM: MILD - Glasgow coma score (GCS) of 15 with no focal neurological deficit; those without altered consciousness or focal neurological signs Grade 2 TBM: MODERATE - GCS of 15 with a focal neurological deficit, or a GCS of 11–14; those with altered consciousness who are not comatose and those with moderate neurological signs, e.g. single cranial nerve palsies, paraparesis, and hemiparesis Grade 3 TBM: SEVERE - GCS of ≤10; for comatose patients and those with multiple cranial nerve palsies, hemiplegia or paraplegia, or both. Severity assessment helps to stratify patients and is useful to predict prognosis

70. Management Primary therapy: Antitubercular drugs Intensive phase - 4 drugs HRZ + E/S x 2 months Continuation phase - 3 drugs HRE x at least 8-10 months ATT should be continued for a minimum duration of 12 months, which may be further extended in case of partial or no response in confirmed cases. Experts recommend therapy for a duration of at least 12-18 months in case of tuberculomas or abscesses. Lesions may persist after therapy; therefore, extended therapy beyond 18 months may not be required in most of the cases.

71. Management Steroids : Use of steroids was found to be associated with a reduced risk of death. Such benefits were not statistically significant in HIV positive patients. The following recommendations have been made regarding the use of steroids in TBM 1. HIV negative patients – recommended for at least 4 weeks 2. HIV positive patients – may be used after ruling out opportunistic infections e.g., cryptococcal meningitis and cerebral toxoplasmosis Steroids are indicated in TBM at a dose of 0.4mg/Kg (dexamethasone), to be tapered over 6-8 weeks. Most accepted regimen - IV DEXAMETHASONE 0.4mg /Kg x 2 weeks followed by 0.3mg/kg x 1 week followed by 0.2mg/Kg x 1 week followed by 4mg/day x 1 week followed by 3mg/day x 1 week followed by 2mg/day x 1 week followed by 1mg/day x 1 week and stop.

72. Management Surgery - indicated in special situations - Presence of associated obstructive hydrocephalus Features of raised ICP Large space-occupying tuberculomas with raised ICT In addition – if features of associated compartmental shifts Complications – physician need to assess and manage the metabolic or pathological complications such as a) Metabolic - electrolyte disturbances, Pituitary dysfunction b) Medical – vasculitis related stroke, drugs toxicity & interactions, seizures, co-infections c) Surgical – hydrocephalus, raised intracranial pressure.

73. Follow Up For further follow-up, repeat imaging may not be required unless clinically indicated (new-onset seizures, neurological signs or symptoms). Assessment for response to therapy is based on clinical assessment. If clinically no response within 6 - 8 weeks of effective therapy, further evaluation should be done to rule out the following: Drug-resistant TB Other infectious causes Neurocysticercosis Toxoplasmosis Cryptococcomas Malignancy – primary or metastatic IRIS – usually within 3-6 months of therapy

74. Abdominal Tuberculosis Intestinal TB is the most commonly encountered sub-type, followed by peritoneal and lymph node TB. Presumptive Abdominal TB: A patient with abdominal pain, distension, fever, unexplained weight loss, chronic diarrhoea or an abdominal mass.

75. Classifications PERITONEAL INTESTINAL ESOPHAGEAL GASTRO-DUODENAL PERIANAL PANCREATIC HEPATO-BILIARY • Abdominal distension • Pain abdomen • Fever • Recurrent intestinal colic • Partial/ incomplete intestinal obstruction • Chronic diarrhoea • Weight loss • Palpable mass abdomen • Lower gastrointestinal bleeding • Dysphagia Odynophagia • Hematemesis • Constitutional symptoms • Gastric outlet obstruction • Gastrointestinal bleed • Simple/ Complex peri-anal fistula • Persistent discharge • Fistulae which recur after multiple surgeries • Abdominal pain • Obstructive jaundice • Dilated pancreatic or bile duct with (peri )-pancreatic mass or cyst • Constitutional symptoms • FUO • Hepatomegaly . Jaundice • Elevated ALP • SOL • Hepatic abscess

76. Management Of Peritoneal Tuberculosis Medical management (the cornerstone of treatment): Intestinal and peritoneal: 6 months of first-line ATT (2 HRZE+ 4 HRE), with the decision to extend treatment made on a case to case basis. Pancreatic and hepato-biliary TB: 6 months with the decision to extend treatment made on a case to case basis. Referral: Presumptive intestinal and presumptive peritoneal TB where the diagnosis is uncertain require referral to a gastroenterologist or radiologist for further evaluation and tissue sampling for testing. Follow-up: Patients are assessed at 2 months (end of IP) and at 6 months after starting treatment

77. Management Of Intestinal Tuberculosis Recommended standard treatment for adult and children with ITB: 2RHZE/4RHE. Duration of the treatment may be extended depending on the clinical response as per clinician discretion. Management of complications: Strictures can be managed with endoscopic dilatation, but some cases require resection of the stricture or hemicolectomy. Oesophageal and gastroduodenal TB patients rarely require surgery; ATT alone is usually adequate. Duodenal strictures may be treated with balloon dilatation. Bypass surgery may be required if this is not successful.

78. Management Of Intestinal Tuberculosis It is also important to understand that successful treatment of ITB need not necessarily result in resolution of strictures. Endoscopic evaluation when feasible may show mucosal healing which can be taken as an end point for ATT. Diffusion weighted MRI is an alternative. Endoscopic or surgical interventions may be needed. Monitoring Response Routinely, patients should be monitored for drug induced liver injury(DILI) at 2, 3 and 6 months. There are no standard guidelines regarding the frequency and modality of assessing response and is left to the discretion of the treating physician. In a confirmed case response should be monitored clinically at 3 and 6 months, if required imaging may be done in selected patients. Worsening or no clinical response after initial treatment may indicate treatment failure. However, in the first 3 months deterioration may be due to paradoxical reaction.

79. Management Of Pancreatic and Hepatobiliary Tuberculosis ATT is the mainstay of treatment The duration of treatment is controversial with differences of opinion amongst various guideline bodies. Index TB guidelines endorse a standard 6 months therapy, which can be extended up to 1 year as per clinician discretion. Role of surgery Tuberculous abscesses may need surgical drainage TB causing biliary obstruction frequently requires initial decompression with endoscopic retrograde cholangio -pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) Biliary strictures may necessitate the placement of stents Biliary diversion surgery is an alternative treatment for extensive strictures

80. The treatment regimen has to be modified according to the degree of liver dysfunction, as follows: Child Turcotte Pugh score Liver disease Treatment recommended Child’s grade A cirrhosis CTP </=7 Stable MELD score <18 Regimens containing 2 hepatotoxic drugs (rather than the three in the standard regimen): Avoid Pyrazinamide • 9 months of isoniazid and rifampicin, plus ethambutol (until or unless isoniazid susceptibility is documented) • 2 months of isoniazid, rifampicin, streptomycin, and ethambutol, followed by 6 months of isoniazid, rifampicin, and ethambutol Child’s grade B cirrhosis or CTP 8-10 Advanced MELD score 18–25 Regimens containing only 1 potentially hepatotoxic drug: Rifampicin preferred over isoniazid, Pyrazinamide not to be used Child’s grade C cirrhosis or CTP >/=11 Very advanced, MELD score >25 Regimens containing no potentially hepatotoxic drugs: 18-24 months therapy using a combination of Streptomycin/Amikacin/Kanamycin, Ethambutol, and levofloxacin, or other second-line oral drugs

81. Skeletal Tuberculosis Skeletal tuberculosis is the 3rd most common form of Extrapulmonary Tuberculosis and it is the most disabling form of TB.

82. Pathophysiology It is paucibacillary Predominantly hematogenous spread, followed by the lymphatic or contiguous spread. The primary site of disease lies almost always in the lungs and rarely at other sites like genito -urinary sources.

83. Clinical Features SPINE TUBERCULOSIS Persistent localized pain in spine region >6 weeks, night pains ( most common symptom ) Local tenderness / cold abscess Recent onset deformity in the back Recent neurological deficit (lower limb motor or sensory loss/ bowel and bladder incontinence and possibly respiratory paralysis) Persistent heaviness around the waist / Girdle pain Fever, cough, weight loss & night pains History of close contact with TB OTHER JOINTS/BONES Persistent localized pain & swelling >6 weeks Mono-articular joint involvement Discharging sinus (+/-) Fluctuant swelling with or without inflammation Painful restriction of involved joint movements Wasting around the area Fever, cough, weight loss & night pains History of close contact with TB

84. Pott’s Spine

85. Classification of Spinal Tuberculosis Spinal TB is classified into four types based on location within the vertebrae: Paradiscal : most common variety, due arterial spread (disc and adjacent para-discal body is supplied by the same artery) Central: due to venous spread Anterior: subperiosteal spread Appendiceal or posterior: least common, structural instability of the spine

86. Investigations CBC, LFT, KFT, FBS, PPBS, HbA1C, ESR, CRP HIV serology Imaging is a cornerstone for diagnosis for spinal TB . Gadolinium contrast enhanced MRI (CE-MRI): It is the investigation of choice Non contrast MRI CT scan X-rays PET-CT scan CT guided or C-arm guided biopsy is the preferred procedure to access tissue for microbiological / histopathological diagnosis. Bacterial culture AFB staining NAAT Mycobacterial culture Histopathological examination LPA

87. Management of Spinal TB Drug Therapy: Drugs: 2HRZE (Intensive phase) plus 10 HRE (Continuation phase) Duration: 12 months (extendable to 18 months on case-by-case basis)

88. Surgical management and its indications In patients with neurological deficit 1. Neural complications developing or getting worse or remaining stationary during the course of non-operative treatment (3-4 weeks) 2. Paraplegia of rapid onset 3. Severe neurological deficits i . flaccid paraplegia ii. Complete sensory/motor loss iii. Bowel or bladder incontinence 4. Painful paraplegia in elderly patients In absence of neurological deficit a. When diagnosis is uncertain and open biopsy is indicated b. Mechanical instability of spine c. Suspected drug resistance d. Spinal deformity – severe kyphotic deformity at presentation (example >60 degrees) or progressive kyphotic deformity e. Mass effect - dysphagia/stridor f. Cold abscess - not responsive to repeated aspiration with ATT

89. Complications and sequelae: Early onset paraplegia : Secondary to acute inflammation, good prognosis with treatment. Late onset paraplegia : Reappearance of neural deficit after a disease-free period of at least 2 years in patients who completed ATT and achieved healed status. Occurs due to progression of deformity in healed patients, or a result of relapse of infection. Deformity : Kyphosis is the most common deformity occurring due to collapse of vertebrae. Predominantly the anterior spine is involved. Deformities interfere with lung function. Surgical correction is required in most cases. Cold abscess can be formed on either side of the spine, anteriorly or posteriorly. It can extend to involve loco-regional structures according to the level of spinal lesion. cold abscess may lead to pseudo-flexion deformity at the hip joint. In addition to ATT, it requires drainage (USG or CT guided). Extended drainage using a pigtail is better than a single time aspiration.

90. Follow Up: The protocolized follow up of spinal TB patients is as follows: (Regular follow up of spinal TB patients is essential in order to take a timely call on surgical intervention) 1. Patients with neurological deficits require staging and grading of their deficit on each visit. 2. Patients without neurological deficit should be assessed weekly for neurological signs. 3. Repeat X-rays of the spine every 3 months. 4. Repeat CE-MRI a. After 6 months, if there is suspicion of poor treatment response (but is not required in most) b. At treatment completion (12 months) it would be prudent to assess healing before discontinuation of therapy. c. Findings of quiescent burnt out infection which do not warrant continuation of ATT such as bony/fibrous ankylosis or thin walled cysts without enhancement must be identified. 5. After completion of treatment, follow up every 6 months for at least 2 years.

91. Follow Up: Drug resistance is to be suspected in patients with spinal tuberculosis on ATT for 5 months or more showing: 1. Poor clinical and radiological response. 2. Appearance of a fresh lesion of osteoarticular tuberculosis 3. Deterioration of spinal deformity 4. Appearance of discharging sinus 5. Wound dehiscence of previously operated scar

92. Treatment Of TB Of Other Joints And Bones: Non surgical treatment: 12 months of ATT: 2HRZE/10HRE analgesia rest to the joint above-knee skin traction or skeletal traction for around 4 weeks Surgical treatment: In cases with synovitis and early arthritis, surgery is rarely required Synovectomy and joint debridement are indicated if the response to nonoperative treatment is inadequate at 6 to 8 weeks. In advanced arthritis, arthrolysis with joint debridement is applicable In subluxation/dislocation, excision arthroplasty (e.g., Girdlestone ), arthrodesis or total hip replacement are indicated.

93. Cutaneous Tuberculosis Cutaneous tuberculosis is rare and thereby a high index of suspicion should be kept. ETIOLOGY M.tuberculosis M.bovis BCG (rarely)

94. Classification of Cutaneous Tuberculosis

95. Lupus vulgaris

96. Scrofuloderma

97. Verrucous TB

98. Clinical features Presence of ulcer or discharging sinus over lymph node, bone & joints Persistent asymptomatic reddish/ reddish brown lesion of >6 months duration which may show scarring Persistent warty or verrucous lesion of > 6 months duration Note: Fever and other constitutional symptoms are generally absent in isolated cutaneous TB To ask for past history of tuberculosis To elicit the exposure to known or suspected tuberculosis cases and to look for other sites of dissemination

99. Investigations Routine investigations: Complete blood counts, liver/kidney function tests, ESR, Mantoux Test Chest radiograph Skin Biopsy taken from active edge Histopathological examination (if compatible with TB, mainstay of diagnosis) Microbiological tests GeneXpert AFB stain and culture (poor sensitivity)

100. Treatment 6 months of ATT; 2HRZE followed by 4HRE No role of topical or oral steroids First Follow up at 4-6 weeks - majority improves To look for ADRs Subsequently every 6-8 weeks to look for resolution, if no response after 8 weeks - alternate diagnosis/DR-TB; refer to higher centre

101. Otorhinolaryngeal Tuberculosis The common forms of extra-nodal ENT TB include laryngeal, sinonasal , oropharyngeal, para/retropharyngeal TB, salivary gland TB, thyroid gland TB, TB otitis media and TB mastoiditis. Laryngeal TB is highly infectious and needs appropriate precautions.

102. Clinical features SUSPECTED TB OTITIS MEDIA SUSPECTED LARYGEAL TB SUSPECTED SINONASAL/OROPHARYNGEAL /DEEP NECK TB ABSCESS Chronic painless otorrhea Early hearing loss Facial nerve palsy Mastoid bone necrosis Multiple tympanic membrane perforations Pale exuberant granulation tissue Chronic hoarseness Productive cough Dysphagia/odynophagia Stridor Vocal cords Ulcerative lesions Nodular lesions Polypoidal lesions Edema Erythema Moth-eaten appearance with distorted architecture Nasal discharge/obstruction Epistaxis Dysphagia/odynophagia Drooling of saliva Polypoidal granulation tissue Edema of uvula/palate/epiglottis Deep neck abscess Past history of tuberculosis or any exposure to known or suspected tuberculosis cases

103. Investigations Routine investigations: Complete blood counts, liver/kidney function tests, ESR, CRP, HIV, Mantoux Test, chest radiograph Complete ENT review: Rhinoscopy + otoscopy + laryngoscopy followed by tissue sampling(preferably PUNCH BIOPSY) Pure tone audiometry (if indicated) CT PNS/temporal bone/head/ Cervical spine with contrast (as indicated) Processing of tissue sample: NAAT/AFB staining/MGIT culture Histopathology other relevant cultures (fungal/bacterial)

104. Management Unlike other EPTB, laryngeal TB is highly infectious and needs appropriate precautions. Anti-tubercular therapy: 2HRZE + 4-10 HRE. Total duration: 6-12months. Longer duration preferred in bony involvement as in TB Otitis Media, osteomyelitis of nasal bones/petrous apex/anterior skull base/cervical spine etc. Treatment may be stopped after completion of entire duration of treatment and resolution of all signs and symptoms. No role of steroids. Aspiration of large abscesses in case of impending complications, preferably ultrasound guided to avoid procedure related complication.

105. Follow Up If no adequate response by 2 months, suspect and investigate for drug-resistant TB. Drug related complications Primarily vestibulotoxic – Streptomycin Primarily ototoxic – Kanamycin, Amikacin Pure tone audiometry is investigation of choice In resource limited setting, screen with Rinne/Weber tests In case of lack of a suitable alternative drug, the risk of further hearing loss versus risk and benefit of adding drugs from DR-TB regimen should be weighed.

106. Ocular Tuberculosis Ocular Tuberculosis can cause moderate-severe visual impairment. Posterior uveitis is the most common presentation

107. Pathogenesis Primary ocular TB is rare. Most cases of ocular TB are secondary due to hematogenous spread from tuberculosis elsewhere in the body. Posterior uveitis is the most common presentation of intraocular TB. Ocular TB is usually paucibacillary.

108. Clinical Features The common presentations of ocular TB are choroid tubercle, choroidal tuberculoma and granulomatous uveitis. Less common presentations include subretinal abscess, recurrent non granulomatous uveitis, scleritis, eyelid granuloma, etc. Ocular TB may present with red eye blurred vision Photophobia eye pain Floaters flashing lights (photopsia).

109. Investigations Principle of investigations: To identify the ocular pathology To identify/rule out coexisting tuberculosis of other organs of the body Chest X-ray, Contrast-enhanced CT (CECT) : To identify coexisting pulmonary tuberculosis USG or CECT of the abdomen: To identify peritoneal or intra-abdominal lymph node tuberculosis. If any neck lymph nodes are present, an FNAC or biopsy should be done An HIV test should be done in all cases of ocular TB Ocular diagnostic modalities: Help in characterising the type of involvement in ocular TB Slit-lamp microscopy Optical Coherence Tomography (OCT) Fundus Fluorescein Angiography (FFA).

110. Treatment ATT: 2 months of RHEZ + 4 months of RH The total duration of treatment is a minimum of 6 months which can be extended up to 9 months Add pyridoxine 10 mg/day Corticosteroids : Topical steroids eye drops for severe/anterior chamber inflammation and Systemic corticosteroids for severe inflammation. Paramacular and optic nerve head TB requires treatment with ATT together with systemic corticosteroids (oral prednisolone 1 mg/kg/day) followed by tapering doses depending on the clinical response.

111. Treatment Among the ATT drugs, ethambutol and linezolid can produce optic neuritis as adverse effects. Development of neovascularization warrants photocoagulation of the retina. Indications for surgery: complications of retinal vasculitis: vitreous haemorrhage , tractional or combined retinal detachment, epiretinal membrane, etc. complications of uveitis: cataract and glaucoma

112. Follow Up Frequency of follow up: 1-2 weeks in 1st month followed by monthly for 3 months & then 3 monthly Eye: Clinical grading of inflammation using fundus photographs & OCT scans (if available) Steroids: Topical: Monitor IOP, cataract and any signs of bacterial/ fungal infection Systemic steroids: Monitor body weight, blood sugar & blood pressure

113. Urogenital Tuberculosis It is classified into three broad categories Urinary tuberculosis: Involvement of the kidneys, ureters, bladder and/ or urethra. Female genital tuberculosis: Involvement uterus, fallopian tubes, ovaries, vulva and/ or vagina. Male genital tuberculosis: Involvement of the epididymis, prostate, testes and/or penis.

114. Urinary Tuberculosis Pathophysiology

115. Clinical Features Of Urinary Tuberculosis Urinary tuberculosis is mostly asymptomatic(till the ureter and/or bladder is involved) Urinary tuberculosis is suspected when patients present with the following symptoms for 2 weeks or more with no response with antibiotics for 3-7 days: Lower urinary tract symptoms like dysuria, increased frequency, nocturia etc. Hematuria Flank pain Systemic systems like fever, weight loss, night sweat may also present. On clinical examination Suprapubic pain Renal angle tenderness - present in case of pyelonephritis.

116. Urinary Tuberculosis Investigations Urine Analysis: Urine R/M, C/S: concurrent bacterial infection with coliforms Urine for NAAT Urine AFB: ZN staining Urine C/S for TB: Liquid MGIT CBC with ESR, Liver Function Tests, Renal Function Tests Chest X-ray: for evidence of pulmonary focus HIV (ICTC): higher association with EPTB Imaging: Ultrasonography of the urinary tract: Initial imaging of choice - to identify any lesions in the urinary tract/kidney Intravenous urography and/or cystography CECT with CT urography Cystourethroscopy with or without biopsy (may be considered) MR Urography (only in special cases e.g., patients with deranged KFT)

117. Urinary Tuberculosis Management The aim of the management: to achieve cure to prevent long term sequelae to restore functionality of the kidneys and the urogenital tract, wherever possible. Anti-tubercular therapy (ATT) daily regimen to be given for 6 months in the following regimen: HRZE: 2 months (Intensive phase) + HRE: 4 months (Continuation Phase) Urology consultation : In case of urinary tract abnormalities. Reconstruction surgeries are indicated for ureteric strictures and reduced bladder capacity

118. Urinary Tuberculosis Algorithm

119. Urinary Tuberculosis Complications Progression to end-stage renal disease.(Major complication) hypertension secondary amyloidosis

120. Urinary Tuberculosis Follow Up All patients with urinary tuberculosis will be followed up after 4 weeks after treatment initiation. The following parameters will be monitored during the follow-up visits: Improvement in urinary symptoms Resolution of systemic symptoms Improvement in renal function Repeat urine mycobacterial C/S (if positive at the time of diagnosis) A repeat ultrasonography KUB to be performed after 4-6 weeks of ATT. To refer to urology, if the USG comes abnormal. Repeat urine mycobacterial C/S should be done at 2 months and 6 months

121. Male Genital Tuberculosis Male Genital Tuberculosis (MGTB) is defined as a patient with scrotal pain or swelling for 2 weeks or more not responding to a 7-to-14-day course of antibiotics.

122. Pathophysiology of MGTB The most common route of spread is hematogenous From a primary pulmonary focus to the epididymis (highly vascular) and the prostate followed by contiguous, canalicular or urinary spread to testes, seminal vesicles, urethra and penis. Isolated testicular involvement is uncommon due to the presence of blood testis barrier Malignancy should be ruled out if testes is involved in isolation.

123. Clinical Features of MGTB Men present with the symptoms (non responsive to antibiotics) Scrotal swelling(most common) Scrotal pain Discharging scrotal sinuses Pelvic pain Increased urinary frequency Nocturia Dysuria Hematuria Hematospermia Infertility Systemic symptoms may/may not be present. On Examination: Enlarged, hard epididymis +/-Tenderness Thickened, beaded vas deferens Prostatic indurations or nodules on Digital Rectal Exam. Non tender testicular mass Perineal or scrotal fistula Hydrocele Inguinal lymphadenopathy(rare)

124. Diagnostic Algorithm for Male Genital TB

125. Male Genital TB treatment Anti-Tubercular Therapy (ATT): Weight based Daily Regimen: (H/R/Z/E) for 2 months during the intensive phase H/R/E for 4 months, during the continuation Phase Aspiration of abscesses: Done against gravity - to prevent fistula formation. Surgical intervention: Strictures Fistulae

126. Complications And Follow Up of MGTB Patients on treatment are followed up after 8 weeks to assess response. There can be improvement in constitutional symptoms if present initially. Resolution of infertility may not be seen Long term complications: Infertility Sexual dysfunction Scrotal and perineal fistulas and strictures

127. Female Genital Tuberculosis Occurs more commonly in pre-menopausal women. It is generally secondary to pulmonary involvement with hematogenous spread. It may also spread by lymphatic route or by direct spread from abdominal TB. FGTB may even develop after sexual intercourse with a man with tuberculosis of the penis or epididymis(rare). Fallopian tubes are most commonly involved followed by uterine endometrium.

128. Clinical Features of FGTB May be asymptomatic Constitutional symptoms Fever Malaise Anorexia weight loss. The most common form of presentation: Infertility (either primary or secondary) long standing menstrual disturbances Chronic abdominal/pelvic pain Palpable abdominal mass Vaginal discharge of varying duration and quality Urinary disturbances such as incontinence. On Examination: General examination Fever Lymphadenopathy Abdominal examination Mass abdomen (vague or definite) Ascites Doughy feel of abdomen Vaginal examination Uterine enlargement (Pyometra) Adnexal masses and induration Tubo -ovarian mass Fullness and tenderness in pouch of Douglas

129. Investigations of FGTB CXR: To look for coexisting Pulmonary TB. HIV Testing USG pelvis: To look for anatomic changes. Urine Pregnancy Test: to rule out pregnancy Endometrial aspirate: It is to be taken preferably during the luteal phase of Menstrual Cycle. Endometrial biopsy/curettage The following samples are to be subjected to saline for: WHO approved NAAT – [Sensitivity - 35-46%; Specificity - 100%] Microscopy (Fluorescent/ZN staining) Culture (MGIT/LJ) and drug sensitivity Note: A positive Xpert is confirmatory but a negative test does not always rule out TB

130. Diagnostic Criteria of FGTB Based on any one of: Laparoscopic appearance typical for FGTB (tubercles, caseation or beaded tubes). Any gynaecological specimen positive for AFB on microscopy, GeneXpert or positive for M. tuberculosis on culture. Any gynaecological specimen with findings consistent with FGTB on histopathological examination.

131. Treatment of FGTB ATT: HRZE (2 months) + HRE (4 months). Gynecological assessment for diagnosis and treat complications. Surgical Management: Large, persistent tubo -ovarian abscesses(despite medical treatment): For drainage. Removal of the uterus, both tubes and ovaries – in case of Persistent disease Tubercles Pyosalpinx Tubo -ovarian mass Non-healing ulcers.

132. Follow Up of FGTB Assess response to treatment at completion of 6 months of ATT by USG pelvis. If persistent tubo -ovarian masses: Rule out drug resistance by FNAC Infertility: Permanent consequence of FGTB Does not indicate treatment failure or re-infection Does not warrant repeated courses of ATT. Indications of laparoscopy: Assessing the prognosis and fertility outcome: If tubes, ovaries and uterus are normal: Spontaneous conception or ovulation induction If fallopian tubes are still not patent: In-Vitro Fertilization and Embryo Transfer. If ovaries are normal but tubes and uterus are damaged: Surrogacy. If both ovaries are destroyed by the disease process, or endometrium is involved: Adoption.

133. Diagnostic Algorithm for FGTB

134. Reference National TB elimination Programme, Central TB division, Training modules for programme managers and medical officers (https://tbcindia.gov.in)

135. Thank You