Introduction to the diagnosis and management of common opportunistic infections (Ols)

1. Introduction to the diagnosis and management of common opportunisticinfections (Ols) Module 4 Sub module OIs

2. Pneumocystis carinii pneumonia (PCP) Penicilliosis Recurrent pneumonia Cryptococcus Toxoplasmosis Oesophageal candidasis Mycobacterium Avium Complex (MAC) Cytomegalovirus (CMV) Opportunistic Infections

3. Natural course & common clinical manifestations

4. Common opportunistic infections

5. The most common opportunistic infections Division Epidemiology, Department of Communicable Diseases Control, MOPH, Thailand

6. Pneumocystis Carinii Pneumonia (PCP) • Organism • Pneumocystis Carinii • Very common • CD4 count < 200 cells • Absolute lymphocyte count <1200

7. Differentiation of bacterial pneumonia & PCP

8. PCP Bacterial pneumonia

9. Pneumocystis carinii pneumonia

10. PCP • Diagnosis • Frequently clinical • Typical symptoms • Response to treatment • Microscopic demonstration of P. carinii in lung secretions/tissue • Culture unavailable

11. PCP • Diagnosis • special methods to obtain specimens are necessary • Induced sputum/B.A.L./Biopsy • DDX: • MTB, bacterial pneumonia, fungal pneumonia, lymphoma, KS

12. PCP • Treatment • Trimethoprim-Sulfamethoxazole • drug of choice (iv 15 mg/kg/day or oral 2 DS tablets tid) • 3 weeks recommended • Allergy to TMP-SMX • Corticosteroidsif severely hypoxic

13. PCP • Alternative treatment for allergic patients • (all for 21 days) • pentamidine • dapsone + trimethoprim • clindamycin + primaquine • atovaquone • less effective

14. PCP • Prognosis: • 100% fatal untreated • Level of hypoxaemia best predicts outcome • Secondary Prophylaxis • co-trimoxazole 1-2 tabs daily • Dapsone 100 mg daily • aerosilized pentamidine 300 mg monthly

15. Penicilliosis • Organism: Penicillium marneffei • Endemic area: • SE Asia (Northern Thailand, Southern China, Vietnam, Indonesia, Hong Kong) • 3rd most common OI in Northern Thailand • CD4 count < 100 cells

16. Penicilliosis • Clinical symptoms: • Fever (99%) • papulo-necrotic skin lesions (71%) • weight loss (76%) • anaemia (77%) • lymphadenopathy (58%) • hepatomegaly (51%) • productive cough • lung disease

17. Penicilliosis • Diagnosis • Presumptive:microscopy on smear • Definitive: culture • DDx: • other disseminated mycobacterial or fungal disease

18. Penicilliosis

19. Penicilliosis

20. Penicilliosis • Treatment: • amphotericin B IV for 6-8 weeks • amphotericin IV for 2 weeks + itraconazole 400 mg orally daily for 10 weeks • In mild cases: • Itraconazole 400 mg orally daily for 8 weeks

21. Penicilliosis • Prognosis: • high mortality in patients with delayed diagnosis/treatment. • Secondary prophylaxis • Itraconazole 200 mg orally daily for life • > 50% relapse at 1 year without secondary prophylaxis • Primary prophylaxis - not routinely indicated

22. Recurrent Pneumonia • Definition > 1 episode of pneumonia in 12 months • Epidemiology • common in HIV infected patients • S. pneumoniae and H. influenzae at least 20 times more common in HIV • Pneumococcal bacteraemia rate 100 times higher in AIDS v. non-AIDS • Clinical • clinical presentation same as for non-HIV

23. Organism S. pneumoniaeH. influenzae S. aureusenteric gram neg rods M.TB Rhodococcus equi Nocardia asteroides Stage of HIV Infection early and late late early and late late late Recurrent Pneumonia

24. Recurrent Pneumonia

25. RUL infiltrate caused by Nocardia

26. RUL infiltrate of TB

27. TB with cavitation

28. Disseminated candidiasis

29. Recurrent Pneumonia • Diagnosis • clinical evaluation, sputum smear/culture, CXR, blood culture • Treatment • as per local guidelines for pneumonia in non HIV • Prevention • Co-trimoxazole prophylaxis protects against recurrent pneumonia • Improve immune function with HAART

30. Cryptococcosis • Clinical features • fever • headache • signs of meningism & photophobia • malaise, nausea and vomiting • alteration of mental status

31. Cryptococcosis • Diagnosis • Lumbar puncture - India ink staining • Cryptococcal antigen, and culture • Cryptococcal Ag highly sensitive and specific (CSF and blood)Titre > 1:8 presumptive evidence of infection • Differential Diagnosis • pyogenic meningitis, TB meningitis, toxoplasmosis, neurosyphillis

32. Encapsulated yeast of Cryptococcus neoformans in CSF India ink preparation

33. Cryptococcosis

34. Cryptococcosis

35. Cryptococcosis • Treatment of Cryptococcal Meningitis • Induction phase • amphotericin B iv daily for 14 days • consider adding 5-flucytosine (5-FC) • Consolidation phase • fluconazole 400 mg po daily for 8 week

36. Cryptococcosis • Prognosis • mortality rates as high as 30% despite therapy • Secondary Prophylaxis • fluconazole 200-400 mg daily • itraconazole 100-200 mg po bid (less effective than fluconazole)

37. Toxoplasmosis • Organism:Toxoplasma gondii • Epidemiology: • Cats the definitive hosts • Ingestion of faecally contaminated material • Ingestion of undercooked meat • CD4 count < 100

38. Toxoplasmosis • Clinical Features: • encephalitis the most common manifestation (90%) • fever (70%), headaches (60%), focal neurological signs, reduced consciousness (40%), seizures (30%) • Constellation of fever, headache, and neurological deficit is classic • chorio-retinitis • pneumonitis • disseminated disease

39. Toxoplasmosis • Diagnosis • positive serology with typical syndrome • suggestive CT/MRI scan: • multiple, bilateral cerebral lesions; hypodense with ring enhancement • Differential diagnosis • CNS lymphoma, tuberculoma, fungal abscess, cryptococcosis, PML

40. Toxoplasmosis

41. Toxoplasmosis

42. Toxoplasmosis- Response to therapy

43. Toxoplasmosis • Treatment • Empirical therapy reasonable as trial, at least for 2 weeks • Pyrimethamine plus folinic acidplus either sulfadiazineor clindamycin • 6 weeks therapy at least, or until 3 weeks after complete scan resolution • Corticosteroids for raised intracranial pressure

44. Toxoplasmosis • Secondary Prophylaxis • Essentialbecause latent (cyst) phase cannot be erdicated • Pyrimethamine plus folinic acid plus sulfadiazine (or clindamycin) • relapse occurs in 20-30% of patients despite maintenance therapy • Improve immunity with HAART

45. Oesophageal Candidiasis • Organism:Candida yeast • CD4 count < 200 • Clinical symptoms • dysphagia, retrosternal pain • oral thrush in 50-90% • endoscopy • ulceration • plaques

46. Oesophageal Candidiasis

47. Oesophogeal Candidiasis • Diagnosis • oral thrush and dysphagia sufficient • consider endoscopy if • symptoms without oral thrush • failure of empirical antifungal therapy • Treatment • Fluconazole 200-400 mg /day until resolved • Long term suppressive therapy if recurrent

48. Mycobacterium Avium Complex (MAC) • Organism: M.avium/M. intracellulare • CD4 count: < 100 cells • Clinical symptoms • fever & night sweats • anorexia & weight loss • Nausea & abdominal pain & diarrhoea • lymphadenopathy • hepatosplenomegaly • anaemia

49. MAC • Diagnosis; • Blood cultures • 2 blood cultures will detect 95% of cases • microscopy and culture of bone marrow, lymph nodes • DDx: • MTB, disseminated fungal disease, malignancy

50. MAC Treatment • Option 1 • clarithromycin + ethambutol • Option 2 • clarithromycin + ethambutol + rifabutin • Option 3  • HAART