Chapter 3 TB In adults Sept 2022 [Autosaved].pptx

Tuberculosis in adutls and adolescents

1. Chapter 3 Tuberculosis in adults and adolescents Updates in the 2021 guidelines

2. Focus on Quality in Diagnosis Enhanced clinician guidance on history taking, physical examination and investigations Guidance on interpretation of results and management of discordance in results e.g. microscopy vs Culture; vs GeneXpert Introduction of new diagnostics e.g GeneXpert Ultra, Truenat Chest X-ray has a role in clinical diagnosis of TB in adults. However GeneXpert remains the initial test of choice for TB diagnosis TB LAM should be used to improve TB diagnosis among HIV infected (as an add-on test to GeneXpert testing ) Truenat is a molecular test for TB DSTB in Adults

3. Treatment of DSTB in Adults TB treatment regimen choice with updated dosing guide ( Includes guidance on pack adjustment and supply box management ) Treatment monitoring/ patient follow-up and management of common adverse drug reactions to first line anti-TB medicines Guidance provided on: Baseline patient preparation and work up, TB patient education, and how to conduct patient counselling 01 03 02 Management of treatment interruption 04

4. Introduction Tuberculosis is the leading single infectious disease killer globally However, it is preventable and treatable! Understanding the principles and concepts in treatment of TB is key Systematic screening of TB is key in TB detection Diagnosis requires a good index of suspicion for TB Treatment preparation is key to ensure good treatment outcomes and prevention of post TB sequelae and community transmission Follow up of TB patients is key to achieve good treatment outcomes and prevent community transmission of TB and possibly acquired DR TB (following poor management of DS TB)

5. Diagnosis of TB TB screening is key in detection of TB in Kenya History TB symptoms Evaluate for exposure to TB/DR TB Evaluate for socio-economic issues likely to affect adherence and outcome to treatment Evaluate for comorbidities Screen and Evaluate for mental illness, substance abuse, alcohol use Physical examination Imaging Laboratory work up

6. History taking TB diagnosis begins with taking a thorough medical history of individual who screen positive for presumptive TB TB should be ruled in or out in any individual presenting with: Any of the signs and symptoms of TB, History of contact with a TB patient History taking should also aim at evaluation of differential diagnoses Patients may present with both TB and other conditions consider evaluation

7. Differential diagnosis of TB 1/2 Disease Presentation Distinguishing From PTB Chronic Obstructive Pulmonary Disease (chronic bronchitis /emphysema) Exertional dyspnea, chronic cough and sputum production Lung function tests (spirometry), imaging Heart failure Exertional dyspnea, chronic cough, orthopnea, edema Imaging (CXR, echocardiogram) shows cardiomegaly, ECG, laboratory tests Bronchiectasis Chronic cough, daily mucopurulent sputum production Lung function tests (spirometry), CT scan imaging Lung abscess Fever, cough and sputum production Culture results, imaging usually shows infiltrates with a cavity

8. Differential diagnosis of TB 2/2 Disease Presentation Distinguishing From PTB Lymphoma Rapidly growing mass with fever, night sweats and weight loss CXR CT scan Histopathology Lung cancer Cough, hemoptysis, chest pain and dyspnea Histopathology Sarcoidosis Chronic cough, dyspnea, chest pain Histopathologic detection of noncaseating granulomas Fungal pneumonia e.g. Aspergillus , Histoplasma Fever, chest pain, shortness of breath, cough, and/or hemoptysis Exposure history and culture results

9. Physical examination Common signs include BMI below 18.5 /Z score of -1 and above Fever > 37.5 Tachypnea (rapid breathing), Wasting, Pallor Signs of respiratory distress may be present Respiratory system Bronchial breath sounds, crepitation on auscultation Dullness on chest percussion, Reduced air entry, Systemic examination is key in the identification of extrapulmonary disease. These individuals may not have respiratory symptom

10. Imaging X-ray A key tool in TB screening, in clinical diagnosis of TB, and follow up in some cases CT scan - where available/ accessible MRI Ultrasound Useful in the evaluation of EPTB presenting with fluid accumulation i.e. pleural, pericardial effusions, joint swellings Maybe used in children- evaluation of nodal involvement, fluid accumulation

11. Chest X-ray (CXR) Screening tool for TB Diagnostic aid of active Pulmonary TB and some forms of EPTB Used to differentiate latent TB vs active TB based on the radiographic findings To characterize radiographic abnormalities so as to exclude other differentials for appropriate referral and management Useful in the follow up treatment response based on clinical status For patients who are not improving in the initial phase of treatment or patients who worsen after initially improving clinically. Detection of complications of active TB disease and post TB sequelae. Baseline CXR examination to support comparative evaluation during treatment and follow up of patients

12. Investigations of TB Investigation Target Purpose 1.GeneXpert and GeneXpert ultra Preferred test of choice diagnosis of TB for all presumptive TB cases For diagnosis of TB and detection RR TB 2.Smear microscopy (Fluorescent and Light microscopy) All presumptive Pulmonary TB where GeneXpert is not available (a second sample should be sent for geneXpert testing) All DS TB and DR TB patients for treatment follow up. Detect TB disease. For diagnosis of TB as an add-on test to GeneXpert/ GeneXpert ultra Monitoring of bacteriologically confirmed TB patients on treatment at months 2/3, 5 and 6 and in patients with pulmonary DR TB 3. Chest X-ray Preferred for all presumptive pulmonary and some forms of extra-pulmonary TB where accessible and affordable A screening tool to identify those at high risk of TB disease. Supports TB diagnosis especially in children and when sputum for AFB/GeneXpert is negative or not applicable

13. Negative bacteriology tests do not exclude TB disease All attempts must be made to make a bacteriological diagnosis of PTB in adults. 4. Histology All presumptive EPTB where feasible Tissue diagnosis in suspected EPTB e.g. TB adenitis through identification of caseating granulomas 5. Culture All presumptive EPTB cases, individuals with poor response, patients presumed to have DR TB and those at high risk for DR TB Diagnosis EPTB and DR TB May also diagnose PTB in patients with paucibacillary disease 6. Lateral flow urine lipoarabinomannan assay (LF-LAM) HIV infected patients with severe illness or advanced disease All hospitalized PLHA For diagnosis of TB as an add-on test to GeneXpert/ GeneXpert ultra It is an add-on test to GeneXpert testing to increase diagnostic yield of TB testing in severely immunocompromised PLHA.

14. Diagnosis of EPTB Diagnosis of EPTB requires a high index of suspicion Common in children and in immunocompromised individuals TB can affect any part of the body except the enamel of teeth, hair and nails Yield for MTBC is generally low in extrapulmonary samples Testing methods with high sensitivity are preferred for confirmation of detection and DST Culture Genexpert testing where feasible Extrapulmonary samples should be carefully handled and expedited for testing to increase yield

15. TB adenitis Presentation Is the commonest form of extra-pulmonary TB Most common site is the cervical area Common among PLHIV Usually unilateral • • Painless swelling – initially discrete then matted Fistula and sinus formation Aspirate node for geneXpert and culture Node biopsy for both histology and culture Investigation Aspirate node for AFB (while awaiting geneXpert results) GeneXpert/geneXpert ultra and culture and DST Node biopsy for both histology and culture

16. Pleural TB with effusion Presentation Local chest symptoms that include chest pain, Shortness of breath Cough and systemic symptoms including fever and night sweats ““Stony” dullness on percussion Reduced breath sounds on the side of the effusion Common among PLHIV as compared to those who are HIV negative Work up CXR Blunting of the costophrenic angle Pleural aspirate(with availability of expertise) especially in persons aged above 40 years Yield for TB is generally low Pleural biopsy Culture Histopathological examination

17. Tuberculous Peritonitis and Ascites Culture of ascitic fluid and/or Peritoneal biopsy specimens HPE - caseating granulomata peritoneal biopsy specimens CT abdomen Ultrasound Laparascopy Presentation Presentation usually vague and non specific Clinical index of suspicion is key Constitutional symptoms - fever, weight loss GI symptoms Abdominal pain Constipation or diarrhea Abdominal mass(es) Signs and symptoms of peritonitis

18. TB meningitis Presentation Challenging to diagnose and requires a very high index of clinical suspicion Subacute presentation - several days to several months Common among immunocompromised individuals typical symptoms and signs of meningitis including headache, fever, and stiff neck, although meningeal signs may be absent in the early stage High morbidity and mortality This disease presents with: prodromal phase - mild headache, fever, malaise meningitic phase - headache, vomiting, confusion, meningismus paralytic phase - stupor, coma, seizures, hemiparesis Work up Examination of cerebrospinal fluid (CSF) obtained following a lumbar puncture Routine analysis - Microscopy and biochemistry of CSF Lymphocytic pleiocytosis Reduced glucose level Elevated protein levels >100mg/dl AFB GeneXpert Culture and DST NB Yield for TB is typically relatively low CT Scan (with contract) of the brain which shows Meningeal enhancement, basal meningitis, tuberculomas infarcts and development of hydrocephalus. MRI

19. TB encephalitis including Tuberculoma Presentation The clinical presentation is similar to that of other space occupying brain lesions and includes: • Headaches. • Vomiting. • Convulsions. • Limb weakness. Cranial nerve palsies. Work up • Brain CT scans are useful in demonstrating lesions such as tuberculomas or cerebral infarcts. • MRI with contrast and spectroscopy is superior in the diagnosis of encephalitis, tuberculoma and spinal TB . Often it is difficult to confirm the diagnosis of brain TB and most patients are treated on an empiric basis.

20. TB pericarditis Presentation Tuberculous pericarditis is increasingly becoming common in the HIV era and it may present with a variety of symptoms including: · Shortness of breath (the most common symptom). · Chest pain. · Cough. · Leg swelling. · Fever. · Usually has a high pulse rate (tachycardia). May have a low blood pressure, impalpable apex beat, quiet heart sounds and signs of heart failure like a large liver, ascites and leg edema. Work up · A chest x-ray is always required and usually shows a large globular heart . · Where feasible patients suspected to have a pericardial effusion should be referred to a heart specialist for confirmation of the diagnosis using echocardiography. A pericardial tap for diagnostic purpose is rarely required but may be life saving if there are signs of cardiac compression (tamponade). This procedure must be done by experienced health care workers (cardiologists) only.

21. Osteoarticular TB Presentation· Mainly affects the large bones, weight joints e.g hip and the spine Symptoms Common - weight loss, fever Swelling, deformities, pain The spine is affected in many instances with a characteristic ‘gibbus’ deformity of the spine. Work up Imaging - dependent on site Biopsy HPE Culture and DST Aspiration Microscopy for AFB GeneXpert/ultra Culture and DST

22. TB skin Presentation · Lupus vulgaris: Persistent and progressive form of cutaneous TB. It occurs as small sharply defined reddish-brown lesions with a gelatinous consistency (called apple jelly nodules). · Untreated, lesions persist for years, leading to disfigurement · Scrofuloderma: Skin lesions result from direct extension of underlying TB infection of lymph nodes, bone or joints. Often associated with TB of the lungs. Firm, painless lesions that eventually ulcerate with a granular base. May heal even without treatment but this takes years and leaves unsightly scars. Work up Skin biopsy Typical tubercles are caseating epithelioid granulomas that contain acid-fast bacilli. These are detected by tissue staining Culture

23. Treatment preparation

24. Treatment preparation 1/2 Initiation of treatment and follow up during treatment Detailed review clinical presentation and diagnosis Review previous Tb treatment, comorbidities, current medication To avoid misdiagnosis or missed opportunities for diagnosis of EPTB and DDx Patient education, counselling (including adherence counselling Nutritional assessment, diagnosis and management Baseline CXR whenever possible Line listing of all contacts, contact invitation/ tracing and management Document in the contact/TPT register

25. Treatment preparation 2/2 Screen for mental illness PHQ 9 tool Screen for substance abuse and alcohol use CAGE AID tool CRAFFT tool for adolescents (12-21 years) Create linkages with other relevant health services as needed E.g linkages with other ongoing clinical visits for patients convenience. IPC issues are key for patients with BC TB to minimise transmission to other vulnerable populations ege PLHIV, diabetics, children etc Patients with DR TB require additional work up Refer to the DR TB module on treatment preparation

26. Treatment

27. Goals of TB treatment To cure the patient and restore quality of life and productivity To prevent death from active TB or its complications To prevent relapse of TB To reduce transmission of TB to others To prevent the development and transmission of drug resistance

28. Fundamentals of TB treatment 1/2 Use of combinations of drugs in a regimen (Never monotherapy) Use of fixed drug combinations (FDCs) At least 4 effective drugs in the intensive phase and 2-3 effective drugs in the continuation phase Never use monotherapy Inadvertent monotherapy may occur e.g. IPT administration in a person with undiagnosed TB, continuation phase for DS TB with undetected resistance NEVER add a single drug to a failing regimen Long-term treatment Allow action on all bacillary populations Combination of bactericidal and sterilizing drugs

29. Fundamentals of TB treatment 2/2 The concept of two-phase therapy Intensive and continuation phase Initial/intensive phase – bactericidal - reduces bacillary load Maintenance/Continuation phase – sterilization – prevents relapse Compliance is key DOT Dosage should always be based on weight ie weight bands Follow up for response to therapy BC TB – smear and /or culture and clinical response Clinically diagnosed TB – clinical response

30. Treatment regimens for DS TB TB type Intensive phase Continuation phase All forms of TB except TB Meningitis and osteoarticular TB. 2 RHZE 4 RH TB Meningitis and osteo-articular TB 2 RHZE 10 RH

31. Dosages FDC Dosages Formulation 25-39 kg 40-54 kg 55 - 69 kg Over 70 Kg Rifampicin 150 mg + Isoniazid 75 mg + Pyrazinamide 400 mg + Ethambutol 275 mg 4-FDC tablet RHZE 2 3 4 5 Rifampicin 150mg + Isoniazid 75mg 2-FDC tablet RH 2 3 4 5

32. Treatment - points to remember Monthly monitoring of weight should be done and recorded Dosage should adjusted accordingly No trial of therapy should be done to minimize the emergence of drug resistance For children or adolescents above 30kg do not give RH 60/60 but treat as adults All patients on anti-TBs should also receive daily pyridoxine Reduces the risk of developing peripheral neuropathy. Lack of pyridoxine should not stop TB therapy

33. Pyridoxine dosage Weight (kg) Dose of pyridoxine (available in both 25mg and 50mg tablets) 1-13.9 kg 12.5mg 14-25 kg 25mg >25 kg 50mg

34. Special considerations in TB treatment

35. Hospitalization Indications: 1) Severe forms of PTB and EPTB (e.g. TB meningitis and pleural effusion) 2) Severe malnutrition 3) Severe pneumonia 4) Other comorbidities e.g. severe anemia, severe diarrhea, etc 5) Court ordered patients to ensure adherence 6) Severe adverse reactions such as hepatotoxicity, severe cutaneous reactions

36. Steroid therapy Corticosteroids improve the morbidity and mortality outcomes in: 1) TB meningitis 2) TB pericarditis 3) TB Immune Reconstitution Inflammatory Syndrome in PLHIV For TB meningitis, dexamethasone in the dose of 0.4 mg/kg/day is recommended in adults (>14 years) in conjugation with antitubercular drugs. The dose should be tapered over 6–8 weeks. In other conditions, Prednisolone is the preferred corticosteroid used. DOSAGE of Prednisone Weeks 1-4 Weeks 5-6 Week 7 Adult and Children>30kg 1mg/kg (max 60mg) 0.5mg/kg 0.25mg/kg Children < 30kg 1-2mg/kg (max 60mg) 0.5-1mg/kg 0.25-0.5 mg/kg

37. Patient follow up

38. Patient follow up Key component of TB care Monitor response Bacteriologic response for BC TB cases - Smear microscopy and DST for high risk groups and those who fail to convert Clinical improvement - weight monthly, resolution of symptoms Radiologic monitoring may be warranted in individuals with extensive pulmonary disease ADRs Adherence Clinically diagnosed and EPTB cases require clinical follow up for improvement Alternative DDx and evaluation for possible comorbidities is key to prevent misdiagnosis and missed diagnoses Scheduled visits at months 2/3, 5 and 6 For patients who are smear negative, continue treatment. Treat other comorbidities as needed For smear positive patients, see the next slides

39. Follow up of patients who remain smear positive at months 2/3 Evaluate for adherence , and other causes of delayed conversion Request for all the following drug susceptibility tests (DST) ; GeneXpert, FL LPA and SL LPA. Culture and FL and SL DST Continue with RHZE for one more month, or longer if DST results not received by then Adjust treatment regimen based on DST results Repeat smear microscopy at end of month 3. If smear positive continue with RHZE and review DST results and inform the SCTLC immediately Do not proceed to the continuation phase (RH) without a DST result confirming susceptibility to RH (rifampicin and Isoniazid)

40. Follow up of patients who remain smear positive at months 5/6 Declare treatment failure and stop anti-TB treatment Review should be conducted by the sub county and county TB clinical review teams Evaluate for adherence, other causes of delayed conversion and treatment failure Request for GeneXpert, First Line(FL) LPA and Second Line(SL) LPA . Culture and FL and SL DST Review DST results and re-initiate treatment based on DST results and other clinical findings

41. Causes of delayed conversion Smear status at the end of the intensive phase is a poor predictor of which new patients will relapse. However, detection of a positive sputum smear remains important as a trigger for the patient assessment as well as for additional drug susceptibility tests

42. Management of treatment interruption If a patient misses a clinic appointment, they should be contacted within a day after missing treatment during the initial phase, and within a week during the continuation phase. The patient can be traced using the locating information previously obtained on enrolment. Steps to take for treatment interruption include: 1. Actively trace patients back from locator information in register (phone call, home visit) 2. Establish the causes for interruption of treatment 3. Address the problem or concerns of the patients 4. Educate and counsel the patients 5. Collect sputum for GenXpert to rule out

43. Stepwise management of treatment interruption

44. Stepwise management of treatment interruption