1. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions

2. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Learning Objectives Use empirical antibiotics for respiratory conditions Evaluate the specific cause of respiratory conditions when empirical antibiotics are not successful Describe appropriate use of sputum gram stains, direct microscopy for acid fast bacilli (AFB) and chest x-rays Explain specific therapy for HIV- related respiratory conditions Unit 7: Respiratory Conditions, Slide 2

3. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Respiratory Condition:Case History Angula, a 33 year old HIV positive man, presents today with 1 week of nonproductive cough and fevers. The symptoms have been gradually worsening. He feels short of breath with exertion, but not at rest. Angula had a CD4 count of 35 three months ago. He recently completed his pre-HAART assessment and counselling and was going to start ART in a few weeks. Unit 7: Respiratory Conditions, Slide 3

4. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Angula has been feeling generally weak for the past year and had to quit his job 6 months ago. His only opportunistic infection was a case of herpes zoster 3 months ago. He was prescribed Cotrimoxazole for PCP prophylaxis 3 month ago but it gave him a rash so he stopped it. Respiratory Condition: Case History (2) Unit 7: Respiratory Conditions, Slide 4

5. Training on Clinical Care of HIV, AIDS and Opportunistic Infections On exam, Angula has a Temperature of 39°C, BP 110/70, Pulse 90, RR 24. He appears thin, but not emaciated. He appears calm and comfortable. Chest exam shows deep inspirations but no retractions, there are diffuse crackles. The exam is otherwise normal. Respiratory Condition: Case Exam Unit 7: Respiratory Conditions, Slide 5

6. Training on Clinical Care of HIV, AIDS and Opportunistic Infections First, Assess the Severity of the Illness Severe Dyspnea Subjective At rest or minimal exertion Respiratory Distress Objective RR > 30 Hypoxemia Tachycardia Signs of ventilatory effort Unit 7: Respiratory Conditions, Slide 6

7. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Consider the Differential Diagnosis Bacterial Infection Bacteria, TB, Mycobacteria other than TB (MOTT) Fungal Infection Pneumocystis (PCP) Cryptococcus, Histoplasmosis, Aspergillus Viral Infection Varicella, Cytomegalovirus Malignancy Kaposi’s Sarcoma, Lymphoma Unit 7: Respiratory Conditions, Slide 7

8. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Effect of CD4 on Differential Any CD4 Count Bacterial pneumonia (Pneumococcus, Hemophilus, Staphylococcus), ‘atypical’ pneumonia (Mycoplasma, Chlamydia), TB CD4 < 200 PCP, KS, Lymphoma CD4 < 100 Cryptococcus, Histoplasma, Mycobacterium kansasii (MOTT) CD4 < 50 Mycobacterium avium complex (MOTT), Cytomegalovirus, Aspergillus Unit 7: Respiratory Conditions, Slide 8

9. Training on Clinical Care of HIV, AIDS and Opportunistic Infections General Approach to Hospital Evaluation Assess hydration and need for oxygen History and physical exam Make/confirm diagnosis assess immune status FBC Sputum for MCS Microscopy, culture, sensitivity For chronic cough: 3 sputum specimens for AFB If not done previously: HIV test Unit 7: Respiratory Conditions, Slide 9

10. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Hospital Evaluation As indicated in patients severely ill: Chest x-ray Creatinine ALT Bilirubin Blood culture CD4 count (if not done previously) Unit 7: Respiratory Conditions, Slide 10

11. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Bacterial Pneumonia Common at all CD4 counts Often purulent sputum, pleuritic chest pain, focal abnormalities on chest exam, increased WBC Usual pathogens may be seen on MCS (gram stain): Streptococcus pneumoniae Hemophilus influenza Staphylococcal aureus Klebsiella pneumoniae or another gram negative organism Unit 7: Respiratory Conditions, Slide 11

12. Bacterial Pneumonia (2) Left lower lobe+ RML infiltrates+ air bronchogram Volume loss causes raised left hemi-diaphragm Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions, Slide 12

13. Streptococcus pneumoniae Gram stain: Polys and gram- positive diplococci Treatment: IV - penicillin PO - amoxycillin 250-500 mg tds or doxycycline 100 mg bd Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions, Slide 13

14. Hemophilus influenza Gram-negative diplococci Treatment: IV - ampicillin, cefuroxime, or ceftriaxone Depends on availability and cost PO – amoxycillin, azithromycin or doxycycline Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions, Slide 14

15. Staphylococcus aureus Gram positive cocci in clusters Treatment: IV – cloxacillin, cefuroxime, ceftriaxone, cephalothin PO – cloxacillin or clindamycin Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions, Slide 15

16. Pseudomonas aerogenosa Gram negative bacilli Treatment: IV – pipiracillin/tazoba ctam, ciprofloxacin or gentamicin depending on the culture sensitivity Training on Clinical Care of HIV, AIDS and Opportunistic Infections Unit 7: Respiratory Conditions, Slide 16

17. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Atypical Pneumonia May be milder than classical bacterial pneumonia More common in younger patients Less common among AIDS patients than bacterial pneumonia No organism seen on gram stain Pathogens: Mycoplasma Chlamydia Legionella (this may be severe) Treatment: Azithromycin, doxycycline, erythromycin Ciprofloxacin may also be used for legionella Unit 7: Respiratory Conditions, Slide 17

18. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Empiric Outpatient Therapy for Bacterial/Atypical Pneumonia Amoxycillin 250-500 mg tds S. pneumonia and H. influenza Doxycycline 100 mg bd (Tetracycline 500 mg od) Above plus Staph and atypical pneumonia organisms Azithromycin 500 mg od (3d) Erythromycin 500 mg qid Like tetracycline, but doesn’t include H. influenza Unit 7: Respiratory Conditions, Slide 18

19. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Empiric Inpatient Therapy for Severe Bacterial Pneumonia IV Penicillin plus gentamicin OR IV Cefuroxime plus azithromycin / erythromycin OR IV Ampicillin plus doxycyline Adequate initial therapy for most Pneumococcus, Haemophilus, Staphylococus, and many gram-negative organisms Azithromycin, erythromycin and doxycyline treat mycoplasma, chlamydia Therapy should be adjusted if a specific diagnosis is made Unit 7: Respiratory Conditions, Slide 19

20. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Pulmonary TB Chronic cough, fever, sweats, weight loss are typical Must send sputum for direct microscopy if cough persisted ≥ 3 weeks Do not house TB suspects with general medical patients Many general medical patients have HIV and can very easily catch a new TB infection Unit 7: Respiratory Conditions, Slide 20

21. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Pulmonary TB (2) Occurs at all CD4 counts Classic pulmonary TB at higher CD4 counts Atypical at lower CD4 counts Sputum smear negative Lack of pulmonary cavity Pleural effusion Hilar or mediastinal adenopathy Lower lobe infiltrates Unit 7: Respiratory Conditions, Slide 21

22. Pulmonary TB (3) Perform CXR if sputum smears are negative in TB suspect Training on Clinical Care of HIV, AIDS and Opportunistic Infections Source: International Union Against Tuberculosis and Lung Disease (IUATLD) www.tbrieder.orgwww.tbrieder.org Unit 7: Respiratory Conditions, Slide 22

23. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Treatment of PTB Follow National Guidelines New case, smear positive or smear negative PTB 2 HRZE / 4 HR Directly observed therapy in hospital Arrange for directly observed therapy on discharge and follow-up sputum exams at 2 and 5 months Recommend HIV test if not previously performed Unit 7: Respiratory Conditions, Slide 23

24. Training on Clinical Care of HIV, AIDS and Opportunistic Infections When to Start HAART in TB Patients CD4 > 350 May not require HAART. Re-evaluate after completion of TB treatment CD4 200 – 350 If patient is eligible for HAART, then start HAART after TB treatment is completed CD4 < 200 Start HAART after completing 2 month initial phase of TB treatment Delay is to minimize pill burden, reduce toxicity, and avoid immune response syndrome Unit 7: Respiratory Conditions, Slide 24

25. Training on Clinical Care of HIV, AIDS and Opportunistic Infections HAART Selection with TB Main issue is rifampicin drug interactions Dramatically reduces drug levels of nevirapine and most protease inhibitors Small decrease in efavirenz levels, no dose adjustment needed NRTI levels not affected Unit 7: Respiratory Conditions, Slide 25

26. Training on Clinical Care of HIV, AIDS and Opportunistic Infections HAART Selection with TB (2) First-line per Namibian Guidelines: d4T/3TC/EFV When patient discontinues Rifampicin, can switch EFV to NVP if desired Unit 7: Respiratory Conditions, Slide 26

27. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Pneumocystis Pneumonia (PCP) Causative organism now known as Pneumocystis jiroveci Usually progresses over several weeks Dyspnea Non-productive cough Fever, fatigue, weight loss No pleuritic pain May have vague substernal discomfort Unit 7: Respiratory Conditions, Slide 27

28. Training on Clinical Care of HIV, AIDS and Opportunistic Infections PCP (2) Occurs at CD4 count < 200 Dyspnea may be obvious or subtle Worsens with exercise, walking, speaking Lung sounds may be normal No organisms on sputum gram stain or AFB stain Probably more common than we diagnose Unit 7: Respiratory Conditions, Slide 28

29. Training on Clinical Care of HIV, AIDS and Opportunistic Infections PCP (3) Unit 7: Respiratory Conditions, Slide 29

30. Training on Clinical Care of HIV, AIDS and Opportunistic Infections PCP Diagnosis Consider diagnosis when bacterial pneumonia and TB are not present, especially if CD4 < 200 or patient has signs of immunodeficiency Oral candidiasis or oral hairy leukoplakia Special sputum stains and bronchoscopy to prove diagnosis not available in Namibia Unit 7: Respiratory Conditions, Slide 30

31. Training on Clinical Care of HIV, AIDS and Opportunistic Infections PCP Treatment Cotrimoxazole 80/400mg, 4 tabs q8hrs for 21 days IV dose: TMP 15mg/kg, SMX 75mg/kg divided 6-8 hourly Add prednisone only for severe dyspnea pO 2 < 70 O 2 saturation < 92% Prednisone dose 40 mg bd x 5 days then 40 mg daily x 5 days then 20 mg daily for 11 days Unit 7: Respiratory Conditions, Slide 31

32. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Respiratory Condition: PCP Treatment If Cotrimoxazole allergy was not severe: Consider rapid desensitization If Cotrimoxazole allergy was severe: Dapsone 100mg po daily plus Trimethoprim 5mg/kg po tds for 21 days (not currently available) Unit 7: Respiratory Conditions, Slide 32

33. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Rapid Cotrimoxazole Densensitisation HourDose (mg) 00.004/0.02 10.04/0.2 20.4/2 34/20 440/200 5160/800 Respiratory Condition: PCP Treatment (2) See Handout 7.1 Successful in 86% of HIV+ Patients. Source: Gluckstein and Ruskin, CID. 1995; 20:849 Slide 33

34. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Fungal Pneumonia May present like TB: Chronic cough, fever, night sweats, weight loss Chest xray may show focal abnormalities, diffuse infiltrates, miliary pattern, rarely cavities Sputum smears for AFB negative No response to TB therapy Unit 7: Respiratory Conditions, Slide 34

35. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Cryptococcal Pneumonia Other than PCP, most common Lung is portal of entry for organism May occur before, during, or after meningitis In absence of meningitis, difficult to diagnose Blood culture may be positive Serum cryptococcal antigen is usually positive Sputum fungal culture or lung biopsy would demonstrate organism Unit 7: Respiratory Conditions, Slide 35

36. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Cryptococcal Pneumonia (2) Treat like cryptococcal meningitis Amphotericin B x 2 weeks if available Fluconazole 400 mg daily 8-10 weeks Fluconazole 200 mg daily for life long suppressive therapy Unit 7: Respiratory Conditions, Slide 36

37. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Histoplasma Pneumonia Histoplasma capsulatum is present worldwide H. capsulatum var. dubosii is present in sub- Saharan Africa AIDS patients get disseminated infection presenting like disseminated TB Hepatosplenomegaly Typical skin lesions and oral ulcers Case reports in AIDS patients from Congo, Kenya, South Africa, Zimbabwe Unit 7: Respiratory Conditions, Slide 37

38. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Fungal Pneumonia Unit 7: Respiratory Conditions, Slide 38

39. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Oral ulcer of Histoplasmosis Unit 7: Respiratory Conditions, Slide 39

40. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Haematology Lab Finds the Pathogen Wright-stained peripheral blood smear shows intracellular Histoplasma organisms Unit 7: Respiratory Conditions, Slide 40

41. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Treatment of Histoplasmosis If severely ill, best to start with 1-2 weeks of Amphotericin, followed by Itraconazole 200 mg bd for 10-12 weeks, followed by Lifetime suppression with itraconazole 200 mg daily Alternative Ketoconazole 200 mg bd with food or orange juice Fluconazole is not effective Unit 7: Respiratory Conditions, Slide 41

42. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Aspergillus Causes severe necrotizing pneumonia Associated with low CD4 count and low WBC May cause pleural-based wedge shaped infiltrates and/or cavities anywhere in lung Treated with high dose amphotericin for weeks to months Unit 7: Respiratory Conditions, Slide 42

43. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Opportunistic Viral Pneumonia Herpes simplex may occur with HSV disease at other sites Acyclovir 800 mg 5x daily Varicella occurs during primary chicken pox or with disseminated zoster Acyclovir 800 mg 5x daily CMV pneumonia may occur with retinal or GI disease Ganciclovir IV Unit 7: Respiratory Conditions, Slide 43

44. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Kaposi’s Sarcoma Lung disease represents visceral spread Skin lesions and often oral lesions precede lung lesions Treatment of fit patients: HAART Palliative chemotherapy Unfit patients Symptomatic treatment Unit 7: Respiratory Conditions, Slide 44

45. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Kaposi’s Sarcoma Unit 7: Respiratory Conditions, Slide 45

46. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Chest CT Scan: KS nodules in Lung Unit 7: Respiratory Conditions, Slide 46

47. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Lymphoma Can cause Hilar adenopathy Pleural and pericardial effusions Focal or diffuse lung infiltrates Tissue diagnosis required if chemotherapy is considered Unit 7: Respiratory Conditions, Slide 47

48. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Pulmonary Case Angula was admitted for evaluation WBC was 2700 Sputum gram stain and AFB stains: no organisms CXR: diffuse interstitial infiltrates Did not improve on empiric penicllin and gentamicin Received cotrimoxazole desensitization and responded to 21 day course Unit 7: Respiratory Conditions, Slide 48

49. Training on Clinical Care of HIV, AIDS and Opportunistic Infections CXR Patterns Focal InfiltratesDiffuse Infiltrates Bacterial Atypical MTB PCP MTB Fungal Viral Hilar NodesCavities MTB, MOTT Fungal Lymphoma MTB, MOTT Bacterial Fungal Nodules/MassesNormal MTB Fungal KS, Lymphoma PCP MTB Slide 49

50. Training on Clinical Care of HIV, AIDS and Opportunistic Infections Key Points 1.First assess for respiratory distress 2.Treat empirically if signs/symptoms NOT severe 3.If not responding get AFB sputum exams 4.If severe or not responding get chest x-ray and sputums 5.Although TB is the most common opportunistic infection, consider other treatable conditions as well Unit 7: Respiratory Conditions, Slide 50