MDR-TB Consultation

1. MDR-TB Consultation ALERT Center/Hospital/training division Mulugeta Tsegaye (MD, Consultant Internist) Daniel Azmeraw (MD, MPH, Internist, Internal medicine case team manager)

2. Outline • Introduction • Case study • Pitfall of Hx and PE • Pitfall of Laboratory Dx • Problem List • Pre XDR-TB Mx • Mx of IPF • Mx of Pul. HTN • Mx of corpulmonale • Mx of HIV • Mx of sever malnutrition • Recommendations

3. A case summery of a pre-XDR patient • identification • NAME – YIBELTAL AMARA • AGE- 14 • ADDRSS- N/ GONDAR, BELESSA • STUDENT • DIAGNOSIS • P1. Stage T3 RVI on (AZT + 3TC + NVP) • P2. Disseminated RR TB to (lung, joint) with treatment failuremoved to pre- XDR • P3. Cor-Pulmonal 2o post TB fibrosis

4. history and physical examination • Known RVI patient on AZT + 3TC + NVP for the past 07 years • Unknown base line CD4 count but current CD4 count of 293, • Viral load of 156, • DXeD with disseminated RR TB 08 month back and was started on 2nd line anti TB( LFX + CM + PTO + CS +Z + Vit B6)

5. history and physical examination • After he presented with productive cough of 02 month duration with associated high grade intermittent fever, with night sweeting, loss of appetite, and unquantified significant weight loss, also he was complaining left leg swelling with associated limitation of movement, • For the above complaint he was investigated with sputum gen xpert and CXR knee x-ray • Dxed to be RR Plu. TB and • Started on 2nd line anti TB and he was adherent to his medication.

6. history and physical examination • Three months back he was admitted for the complaint of shortness of breath at ordinary activities, with associated easy fatigability, and bilateral leg swelling, • But no history of orthopnea, PND, and • Started on lasix40 mg po BID and intermittent INO2. • He had previous his of TB treatment 02 times after he was diagnosed with chestx-ray and completed treatment twice,

7. Physical EXAMINNATION • GA • Chronically sick looking • Vital sign • BP; PR-98bpm , RR- 24 , T0-36.5, SO2 - 86%-88% • Wt-21KG Ht-27cm BMI=13.02 • HEENT; pink conjunctiva and NIS • LGS; • No LAP’S • CHEST; • Symmetrical chest expansion, • ↓air entry over the right lower 1/3rd of the lung field • Coarse crepitation over the left lower lung field, no other findings

8. Physical EXAMINNATION • CVS • Distended neck vein with raised JVP • Active precordium • Murmur of TR, with accentuated P2 • Abdominal; • Symmetrical abdomen which moves with respiration • Right upper quadrant tenderness, but no palpable organomegally • No sign of fluid collection

9. Physical EXAMINNATION • MSS; • No edema, there is deformity over the right knee joint • IS; • No pallor, • CNS; • Conscious and oriented

10. Pitfall of Hx and PE • Place of residence • Contact with birds, non draining water, • Hx of employment of contact with chemicals, mmining materials, coal mining • Farming history • Family history of similar illness • Contact tracing • Treatment history for PCP , fungal infection, viral infection, HSP • Drug history • Nutritional history

11. history and physical examination • MUAC • Thyroid gland, parotid gland • GUS- secondary sexual characteristics-hypopitutarisim (growth failure, poor nutrition) • MSS- incomplete but positive findings • Skin lesions, axillary and pubic hair distribution • CNS- complete examination with MMS

12. LABORATORY INVESTIGATION

13. LABORATORY INVESTIGATION CBC (march 19/ 2018) OFT (MARCH 20/ 2018)

14. LABORATORY INVESTIGATION • Echocardiography -march 14/ 2018 • Dilatation of the right-side chamber (RA= 6.1cm RV= 5.0 cm) with sever TR • The pulmonary artery is dilated (3.7) • Normal left ventricular chamber…. • →right side chamber enlargement with sever TR + Pulmonary artery hypertension

15. LABORATORY INVESTIGATION • Chest x-ray -march 14/ 2018 • Cardiomegaly + plu. HTN + Old fibrotic changes

16. Pitfall of LABORATORY INVESTIGATION • LP-fungal infection • ECG • TSH • ANA, anti-GBM, ANCA • PFT (Spirometry, Dco, ABG) • Precipitine antigen test (hypersensitivity Pnumonia)

17. Pitfall of LABORATORY INVESTIGATION • HRCT-chest ( IPF, PTE, other causes, grading of lung damage) • Chest and abdominal U/S • FBS • BAL • Bronchoscopy

18. Diagnosis • Stage IV RVI with Pre-XDR TB+ Corpulonalea 2nd ??Pul. HTN??2nd ??IPF??2nd Old TB + sever malnutrition+ r/o ART treatment failure.

19. List of problems • Stage IV RVI • Pre XDR (Quinolone resistance) TB • Pulmonary hypertension with right sided heart failure ( Cor pulmonale) secondary to fibrosis ( from repeated tuberculosis and unsuccessful therapy for the disease due to drug resistant strain of MTB) • Cor pulmonale 2nd to sever pul. HTN 2nd to Pulmonary fibrosis 2nd to ? Repeated Tb infection, 2nd to ????( IPF) 2nd ???Environmental exposure, connective tissue disorder, R/O thyropulmonary disease • Cor pulmonale 2nd to sever pul. HTN 2 nd to ????Idiopathic pulmonary HTN 2nd to HIV • Sever malnutrition 2nd ????chronic illness, poor nutrition

20. List of problems • Incomplete history • Incomplete physical examination • Incomplete investigation

21. Management approach • Particularly alarming from public health point of view. • As can be seen from the bacteriologic follow-up smear and culture reverted to positive on the third and fourth month of treatment. • This shows that the strain was resistant for quinolones from the outset. • The fact that this strain was circulating in the community clicks an alarm. • The use of both second line and first line DST in selected cases at the start of treatment should be something the program and clinicians think about.

22. Management approach • As for the next direct management of this patient the recommended regimen should be the following . • Quoting the 6th edition of the national guideline 2017 • “In case of fluoroquinolone resistance neither Levofloxacin nor Moxifloxacin will be counted as one of the drugs with ‘certain effectiveness”.

23. Management approach • Drugs from agents from groups C, D2 or D3 are added when resistance to quinolones is confirmed using either SL-LPA or phenotypic DST. • Note that the off-label use of Bdq or Dlm for extended period beyond six month is only considered if the regimen in the continuation phase is considered not adequate and in consultation with the national/regional clinical review committee.

24. Suggested regimen

25. Management approach • Choice on Bedaquiline Vs Delamanide • As the patient is RVI += • Delamanide • Recommended coz of fewer drug-drug interaction.

26. Management approach • Surgical resection should be considered

27. Managing the cor-pulmonale • Mainstay of therapy • Oxygen therapy • ↓ hypoxia induced vasoconstriction • Diuretics (Frusemide) and

28. Treatment of cor pulmonale • Three major physiological goals: • Reduction of right ventricular afterload (ie, reduction of the pulmonary artery pressure), • Decrease of right ventricular pressure, and • Improvement of right ventricular contractility.

29. Specific Rx for IPF • IMMUNSUPPRESSANT ( TRAIL OF GLUCOCORTICOID 1 mg/kg fro 8-12 weeks based on response • Cytotoxic drugs • Cyclophosphamide • Cyclosporine • Azathioprine

30. Specific Rx for Pul. HTN • CCB, phosphodiesterase inhibitors, endothelin antagonist, prostaglandin E analogues • Egg and Hen theory • Pulmonary rehabilitation

31. Managing the cor-pulmonale • Removing the involved lobe of the lung surgically is another option in unilateral pulmonary fibrosis provided the other lobe is not affected and can maintain acceptable level of respiratory function. • Other therapeutic options are targeting blood PH. • This option is also popular in patients with IPAH. • For this particular patient diuresis and oxygen is recommended. • The surgical option should be explored in consultation with pulmonologists.

32. The HIV infection • The immunologic status (Even if the baseline CD4 is not known) and virologic suppression of the virus appears to be reasonable. • So the ART regimen he is taking can be continued without modification. • But he should be closely followed with CD4 and viral load for treatment failure as there is detectable virus in his serum and considering his long treatment period. • Treatment failure probability and DST for antiretroviral drugs

33. Management approach • N.B. To analyze the case management fully the following bits of information could be of great assistance • Pictures of the CXR serially taken to comment on the extent of pulmonary involvement and the severity of fibrosis. The XRAY could be also of use to consider the benefit of surgery for this particular patient. • Surface 12 lead ECG of the patient is also important to reinforce the diagnosis of cor-pulmonale and for the subsequent initiation of new drug regimen that may include the use of new drugs like delamanide and bedaquiline.

34. Management approach…Malnutrition • Sever malnutrition • Ready to Use Therapeutic Foods (RUTF) or Plumpy nut* • Duration as per the national guideline until graduation.

35. Recommendations • Complete history • Complete physical examinations • Comprehensive laboratory tests

36. Recommendations • Complete

37. Recommendations • Prednisolone trial • CCB trail • Oxygen supplement • Pulmonary rehabilitation • Lung reduction surgery

38. Recommendations • DST for antiretroviral therapy • Close follow up for • ADR • Drug-drug interaction

39. Thank you