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1. Tuberculosis Presenter: Kogilavani Mani ( Kogi )

2. Epidemiology In Malaysia, Sabah has recorded the highest number of TB cases followed by Selangor in the year of 20 23 In the year 202 3 , a total 5 , 814 cases of tuberculosis were reported in Sabah , followed by Selangor 5,631 cases and Sarawak with 3,177 cases. The district with the highest TB cases was Kota Kinabalu with 793 cases followed by Sandakan 485 cases, Tawau 445 cases, Lahad Datu 353 cases, Semporna 334 cases and Keningau 277 cases. The other district only reported less than 200 cases per year. Source: Sabah Handbook on Management of TB

3. Introduction Etiology Mycobacterium tuberculosis Mode of transmission inhalation of infected aerosolized droplets. " It mainly affects the lungs, making pulmonary disease the most common presentation " " Tuberculosis can affect every organ in the body except nail, hair and teeth " Tuberculosis

4. Approach to patient suspected with TB

5. Presentation Extrapulmonary symptoms GIT :Abd. pain, diarrhoea, bloating CNS : Headache, focal neurology deficit CVS : chest pain, failure symptoms Bone/Joint: swellings, fractures, discharging sinus. Larynx: hoarseness of voice, odynophagia, dysphagia Constutional symptoms 1.Prolonged Fever Low grade fever 2. Night sweats 3. Loss of weight and loss of appetite Risk factors Any h/o close contact with PTB patients High risk behaviour : Subtance Abusers, h/o multiple partners Active smokers Overcrowded conditions: prison, shelters, immigrants R espiratory symptoms: Prolong cough Chest pain SOB Hemoptysis

6. Examination Physical examination findings associated with TB depend on the organs involved. General condition: Cachexic, lethargic looking, tachypneic Pulmonary TB Palpation : Reduced chest expansion, increased vocal fremitus Percussion : Dull Auscultation : Bronchial breath, Increased vocal resonance Signs of extrapulmonary TB Differ according to the organs involved

7. What is a ghon focus? A Ghon focus is  a primary lesion usually subpleural , often in the mid to lower zones, caused by Mycobacterium bacilli (tuberculosis) developed in the lung of a nonimmune host (usually a child) . It is named for Anton Ghon (1866–1936), an Austrian pathologist.  Approximately three weeks after the initial infection, more specific immune cells (e.g.,  T cells, B cells, and Neutrophils ) surround the site of TB infection, creating a wall of immune cells known as a granuloma, which isolates the bacteria and prevents it from spreading. The tissue inside the granuloma then dies during a process referred to as caseous necrosis, or cheese-like necrosis. This necrotic area is known as a Ghon focus. TB infection can also spread to nearby hilar lymph nodes, either carried through the lymph or by direct extension of the Ghon focus. Together, the caseating tissue and associated lymph node involvement make up the characteristic “ Ghon complex.” 

8. Sometimes, the Ghon complex can present similarly to the “ Ranke complex,” which is a later manifestation of the Ghon complex that forms when the granuloma undergoes fibrosis, and often calcification. On chest X-ray, the Ranke complex is characterized by the presence of a calcified Ghon lesion along with same side calcified mediastinal lymph nodes.

9. The usual location for Ghon focus is the apical segment of right lower lobe. • Ghon complex comprising Ghon focus and right hilar lymphadenopathy plus pleural effusion.

10. The combination of late fibrocalcific lesions of the lung and lymph node which evolved from the Ghon complex is referred to as the “Ranke complex” Ranke Complex. There is a combination of a calcified peripheral granuloma (black arrow) and a calcified hilar lymph node (white arrow) on the same side. Several other, small calcified granulomas are seen in the right mid-lung field.

11. Parenchymal opacities – heterogeneous opacities most commonly in apical and posterior segmental upper lobes and the superior segment of the lower lobes. Cavitation and Air-fluid levels Bronchogenic spread Chest X-ray of our patient at the time of admission

12. T y p I c a l fe a tu r e s O f p r I m a r y P T B consolidation of the upper zone with ipsilateral hilar enlargement due to lymphadenopathy

13. GRADING OF PULMONARY TUBERCULOSIS SEVERITY BASED ON C H E S T R A D I O G R A PH I N A DU L T S ( 1 / 3) Minimal M i n i m a l l e si o n s c on f i n ed t o a s m a l l p a r t o f one o f bo t h l u ng s t o ta l e x t e n t o f t h e l e si on s s h o u l d no t e x c e e d t h e v o l u m e o f t h e l u n g o n on e side.

14. GRADING OF PULMONARY TUBERCULOSIS SEVERITY BASED ON C H E S T R A D I O G R A PH I N A DU L T S ( 2 /3) Moderately Advanced O n e o f b o t h l u ng s m a y b e i n v o l v e d b u t t h e total extent of the lesions should not e x ce ed t h e f o ll o w i n g li m i t s : D i sse m i n a t e d l e si o n s o f m i n i m a l t o m od e r a t e d e n s i t y no t e x c e e d i n g t h e t o t a l v o l u m e o f on e l u n g o f t h e e q u i v a l e n t i n bo t h l u ng s d e n s e a n d c on f l u e n c e l e si on s no t e x c e e d i n g on e t h ir d o f t h e v o l u m e o f o ne l u n g T o t a l d i a m e t e r o f c a v i t a t i on s , i f p r e s e n t , m u s t b e < 4 c m .

15. GRADING OF PULMONARY TUBERCULOSIS SEVERITY BASED ON C H E S T R A D I O G R A PH I N A DU L T S ( 3/3) Far Advanced L e s i o n s a re m o r e e x t e n s i v e t h a n mode r ately advanced

16. CXR Example of patient’s CXR

17. Sputum AFB Example of lab result Microscopic evaluation of sputum for acid-fast bacilli begins with making a smear

18. What if the AFB is Negative? Always ensure satisfactory specimen

19. MTB GeneXpert Able to simultaneously detect MTBC and Rifampicin resistance Sputum should be sent for MTB GeneXpert if smear negative PTB is suspected. In 2020, WHO recommended that this test be used as the first line TB screening test, however this is not feasible as yet in Sabah due to steep testing costs .

20. MTB GeneXpert

21. Smear negative AFB

22. Investigations PTB Specific Investigations Other investigations Investigations for Extra-PTB Sputum AFB - x1, x2, x3 Mycobacterial culture and sensitivity * Taken at initiation of TB treatment * To confirm presence of Mycobacterium Tuberculosis * To test for drug sensitivity LTAT for culture is 14 days while LTAT sensitivity is 42 days to 68 days MTB GeneXpert Sputum LPA ( Line Probe Assay ) - is another molecular method and relatively fast in determining Isoniazid and Rifampicin resistant - Indication: a. Persistant smear positive despite after 2month of effective regime b. Prior to MDR regime initiation (to determine mutation ) c. Newly diagnose PTB smear positive patient with positive contact with Isoniazid resistant index. Imaging – CXR Blood Baseline FBC, RP, LFT ,CRP,ESR TRO immunocompromised state Infective screening FBS Urine - UPT ( all female childbearing ages ) 1. CNS * Contrasted CT brain * Lumbar puncture - MTB GeneXpert - AFB - MTB C&S 2. Spine * CT/MRI Spine * Tissue for HPE MTB C+S * Pus - AFB - MTB C+S - MTB GeneXpert 3. Pericardium * Echocardiography * Pericardial tapping - AFB - MTB C+S - MTB GeneXpert 4. Abdomen ( Liver, Gut, Peritoneum ) * Ultrasound Abdomen * CECT Abdomen if needed * Colonoscopy * Tissues for HPE & MTB C+S 5. Lymph node * Lymph node FNAC and/or biopsy - HPE & MTB C+S 6. Pleural * Pleural fluid ADA * MTB C+S * AFB

23. Treatment

24. Treatment for new case Six-month regimen consisting of two months of daily EHRZ* (2EHRZ) followed by four months of daily HR* (4HR) is recommended for newly-diagnosed PTB Pyridoxine 10 mg OD is also prescribed to prevent peripheral neuropathy caused by Isoniazid

25. Treatment for new case After measuring latest body weight, attending clinician should round ATT dosage to nearest available preparation (highest range is preferred for H & R)

26. Refer to Opthal Clinic for Eye Assessment Ethambutol ADR: Optic neuritis - decrease in visual acuity, red- green colour blindness, blurring and central scotoma. Snellen’s Chart Ishihara

27. Duration of ATT will depend on severity or site of infection. All EPTB cases in Sabah should be referred to Infectious Disease (ID) team for optimum regime & duration of treatment.

28. Steroid is required for TB meningitis and TB pericarditis. It can improve symptom and survival

29. TB notification form

30. So until when do we keep the patient? By right, we can allow discharge and continue follow up in JPL , if: 1. - Patient is clinically well - Sputum smear conversion * Sputum AFB is repeated @ 2 weeks after ATT initiation * Indicating response to ATT * Reduces risk of transmission 2. * If patient has an isolated room in his/her house * Clinically well

31. Directly observe therapy (DOT) Every clinician managing TB should ensure all TB patient that on ATT treatment need to undergo DOT to optimised management of TB.

32. Follow up

33. Problems During Follow Up Common problems encountered in managing TB are: • Adverse drug reaction: -Drug-induced liver injury(DILI) - Drug-induced rash(DIR) - Other common adverse drug reactions(ADR) • Delay conversion • Treatment interruption

34. Drug Induced Liver Injury ( DILI ) The most important aspect of DILI management is that the clinician should know when to stop and how to rechallenge. The most common drug causing transaminitis are as below: • Pyrazinamide • Isoniazid • Rifampicin Cases should be divided into symptom and/or severity of transaminitis . Healthcare providers should be aware that the initial presentation of DILI could be as mild as: Abdominal pain Nausea Vomiting Lethargy Jaundice will usually increases later as severity increase.

35. Approach to DILI

36. Common Adverse Drug Reaction

37. THANK YOU

38. Resources Adigun R, Singh R. Tuberculosis. [Updated 2023 May 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441916/ Das S, Das D, Bhuyan UT, Saikia N. Head and Neck Tuberculosis: Scenario in a Tertiary Care Hospital of North Eastern India. J Clin Diagn Res. 2016 Jan;10(1):MC04-7. doi: 10.7860/JCDR/2016/17171.7076. Epub 2016 Jan 1. PMID: 26894099; PMCID: PMC4740627. Sabah Handbook on Management of Tuberculosis, 2021 CPG Management of Tuberculosis, 4th Edition