1. Unit 10 Treating the Dually Infected Patient: B Family Case Botswana National Tuberculosis Programme Manual Training for Medical Officers

2. Slide 2 Unit 10: Case Studies B Family Case: Question 1 Mr. B is on TB retreatment and ART Mr. B returns with nausea, vomiting, and jaundice What do you do for Mr. B?

3. Slide 3 Unit 10: Case Studies B Family Case: Answer 1 Take a detailed history Do a physical examination Make sure to assess Mr. B’s liver Take blood for liver function, electrolytes, full blood count Bilirubin (100), AST (400 range), ALT (500 range) Admit Mr. B to the hospital for observation Stop all TB and HIV medications, but maintain cotrimoxazole

4. Slide 4 Unit 10: Case Studies B Family Case: Question 2 1 week later, Mr. B’s LFTs have decreased to less than 2 x ULN What do you do for Mr. B now?

5. Slide 5 Unit 10: Case Studies B Family Case: Answer 2 Reintroduce TB drugs Monitor liver function tests

6. Slide 6 Unit 10: Case Studies B Family Case: Question 3 After a 16 day re-introduction, the patient’s LFTs remain < 2x ULN and Mr. B is without jaundice 1.When do you consider starting ART again? 2.Which drugs should Mr. B take?

7. Slide 7 Unit 10: Case Studies B Family Case: Answer 3 1.2-4 weeks after re-starting full doses of anti- tuberculosis drugs 2.Medications Alluvia, 2 tabs BD Ritonavir, 3 capsules BD Combivir, 1 tab BD * Alluvia is now available in Botswana – it is a tablet form of Kaletra and does not need to be refrigerated

8. Slide 8 Unit 10: Case Studies B Family Case: Question 5 Why should Mr. B take Alluvia + Ritonvir instead of restarting EFV?

9. Slide 9 Unit 10: Case Studies B Family Case: Answer 5 EFV can cause heptatotoxicity Since Mr. B is tolerating the ATT, you assume it was the efavirenz that caused the deviation in liver function and jaundice

10. Unit 10 Treating the Dually Infected Patient: Case Botswana National Tuberculosis Programme Manual Training for Medical Officers

11. Slide 11 Unit 10: Case Studies Additional Case A 45 year old female named TT with fever for 4 weeks, cough with bloody sputum, sweats and weight loss of 7 kg Sputum is AFB+ Her HIV test is positive and CD4 is 20 cell/cu mm Chest X-ray shows right paratracheal adenopathy

12. Slide 12 Unit 10: Case Studies Additional Case: Question 1 1.What questions do you ask her? 2.What medications do you start her on?

13. Slide 13 Unit 10: Case Studies Additional Case: Answer 1 1.Ask her if she is still menstruating TT reports that her menses stopped at 43 years of age 2.Start patient on rifampicin, isoniazid, pyrazinamide and ethambutol plus cotrimoxazole

14. Slide 14 Unit 10: Case Studies Additional Case: Question 2 TT is started on a four drug TB therapy and is discharged She returns after 1 month Her fevers, night sweats and cough have stopped and she has gained 5kg She is tolerating the TB drugs TB therapy is continued She is started on ARVs including zidovudine, lamivudine and efavirenz Why is she taking efavirenz instead of nevirapine? X-ray shows improvement

15. Slide 15 Unit 10: Case Studies Additional Case: Answer 2 TT is taking efavirenz instead of nevirapine because she is beyond child bearing age and because efavirenz is the preferred NNRTI for use in patients taking rifampin

16. Slide 16 Unit 10: Case Studies Additional Case: Question 3 She comes back to your facility 2 weeks after starting ARVs She says that her fever, cough and night sweats have come back She has taken her ARTs as prescribed, but thinks they are making her more sick and she would like to stop them 1.What other information do you want from her history? 2.How would you assess her?

17. Slide 17 Unit 10: Case Studies Additional Case: Answer 3 1.You want to know whether or not she was adherent to all her medications 2.Assessing TT Check for other signs/symptoms: nausea, vomiting and diarrhoea, which may indicate other infections or malabsorption Check blood pressure, heart rate, temperature, respiratory rate and oxygen saturation Perform labs: sputum smear for AFB, sputum culture, FBC, liver tests, CD4 count, viral load Perform a chest x-ray

18. Slide 18 Unit 10: Case Studies Additional Case: Question 4 1.What is your differential diagnosis? 2.What do you look for on physical exam?

19. Slide 19 Unit 10: Case Studies Additional Case: Answer 4 (1) 1.Differential diagnosis TB IRIS Drug-resistant TB Failure of TB therapy due to poor adherence or malabsorption of medications Bacterial pneumonia PCP Drug toxicity

20. Slide 20 Unit 10: Case Studies Additional Case: Answer 4 (2) 2.Physical examination Close evaluation of the chest Listen for adventitious sounds, symmetrical excursion Check for enlarged lymph nodes Assess for body swelling (oedema) Assess for abdominal distention Asses for jaundice Complete neurologic exam

21. Slide 21 Unit 10: Case Studies Additional Case: Question 5 (1) TT reports excellent adherence and denies nausea, vomiting or diarrhoea Oxygen saturation is 96% on room air Heart rate, respiratory rate and other vital signs are normal Remainder of physical exam is normal Sputum smear negative Diffuse bilateral infiltrates

22. Slide 22 Unit 10: Case Studies Additional Case: Question 5 (2) 1.What condition(s) do you suspect now? 2.What is your management plan now?

23. Slide 23 Unit 10: Case Studies Additional Case: Answer 5 1.Narrowed differential diagnosis TB IRIS PCP Bacterial pneumonia 2.Management Advise her to continue ART and the TB continuation regimen Educate her, using a caring, respectful attitude Ask questions and listen Ensure she understands the benefit of remaining on both treatments Encouragement Schedule her to come back in 1-2 weeks, or sooner if she gets worse

24. Slide 24 Unit 10: Case Studies Additional Case: Question 6 2 weeks later her symptoms are worse Sputum culture from last visit shows no growth to date Sputum smear is AFB negative Respiratory rate is 28 Oxygen saturation is 90% on room air Crackles heard bilaterally What is your diagnosis? X-ray shows no improvement

25. Slide 25 Unit 10: Case Studies Additional Case: Answer 6 TB IRIS: Occurs in 10-40% of patients The immune system is likely reacting to dead mycobacteria in the system The inflammation is worsening as her immune system reconstitutes itself on ART Risk factors Starting ARVs within 6 weeks of TB treatment Disseminated, extra-pulmonary disease Low baseline CD4 count Rise in CD4 % Fall in viral load High bacillary burden Source: www.who.int/entity/tb/events/tbiris.ppt

26. Slide 26 Unit 10: Case Studies Additional Case: Question 7 How do you manage TT now?

27. Slide 27 Unit 10: Case Studies Additional Case: Answer 7 Admit her to hospital Give oxygen FBC, chemistry panel Administer corticosteroids to reduce inflammation If she continues to worsen despite steroid treatment: Stop ART until she has clinically improved (resolution of chest x- ray, respiratory distress) Restart ART once clinically stable Continue TB treatment regimen throughout If a culture turns positive: Suspect drug resistance Do sensitivity testing

28. Slide 28 Unit 10: Case Studies Additional Case: Question 8 1 week later, TT remains on ART and TB treatment + steroids T.T. reports feeling much better Lungs sound normal Sputum culture is still negative Chest x-ray shows improvement How long should steroids be continued?

29. Slide 29 Unit 10: Case Studies Additional Case: Answer 8 Consider a 4 week taper May need to restart if IRIS recurs