肺結核合併愛滋病治療

1. 肺結核合併愛滋病治療 台北榮民總醫院 感染科 國立陽明大學愛滋病預防及研究中心 王永衛 醫師

2. Worldwide Adult Prevalence of HIV Infection • HIV-infected Persons • Total: 18386 (in 2009) • AIDS: 5811 • Deaths: 2418 • On ART 5000 (33%) 1,000,000 -1,200,000 HIV-infected individuals in USA, 2007, 57% on ART TAIWAN 0.08 % (0.03-0.14) 目前愛滋病毒感染存活人數:4000萬人 每年新感染HIV人數:500萬人 每年愛滋病患死亡人數:300萬人 Synovate Healthcare U.S. HIV Monitor Q2, 2007; Centers for Disease Control and Prevention (CDC) : http://www.cdc.gov ; Taiwan Center for Disease Control (2009 report)

3. Natural History of HIV Infection Primaryinfection 1200 1100 1000 900 800 700 600 500 400 300 200 100 0 Death Possible acute HIV syndrome Wide dissemination of virus Seeding of lymphoid organs Opportunisticdiseases 1:512 1:256 1:128 1:64 1:32 1:16 1.8 1.4 1.2 0 ) Clinical latency Constitutionalsymptoms CD4 T Cells/mm3 ) ( Plasma Viremia Titer ( 6 3 9 10 1 6 7 8 9 12 11 0 2 5 4 3 Weeks Years

4. FungiPneumocystis cariniiPenicillium marneffeiCryptococcus neoformansAspergillus fumigatusHistoplasma capsulatum ProtozoaToxoplasma gondiiCryptosporidium spp. Virus CMVHSVAdenovirusHIV BacteriaMycobacterium tuberculosisMACM. kansasiiNocardia asteroidesStreptococcus pneumoniaeStaphylococus aureusLegionella pneumophilia Rhodococcus equiHemophilus influenzae Lymphocytic interstitial pneumonitis Pulmonary Complications of HIV Infection

5. Tuberculosis

6. 結核病~三千年歷史的古老疾病埃及時代 西元前 3700-1000年

7. 誰是肺結核病人? 魯迅 李叔同 林徽音 林黛玉 身邊隨時都有機會接觸病人，與其排斥逃避，不如主動關懷，幫助病人好好治療。

8. Robert Koch

9. 結核病防治 • 全球每年約有300萬人死於結核病，約300萬人死於愛滋病，其中愛滋病人死於結核病約佔1/3。 • 全球約有1/3 人口已受結核菌感染，每年約有 800 萬人新發生結核病，其中台灣約佔 15,000人。

10. 何謂結核病（TB tuberculosis）？ • 慢性傳染性疾病 • 由結核分枝桿菌（結核桿菌）所引起的 • 由飛沫（空氣）傳染 • 病情進展緩慢，早期症狀不明顯 • 人體之任何器官都可能得結核病，以肺部居多

11. 認識結核桿菌（tubercle bacillus） • 嗜氧菌、抗酸菌，喜潮濕、陰暗處 • 長約1 ～ 10μm〈微米〉，寬約0.2～0.6 μm，生長期約 4～8 週 • 最適宜之生存溫度是37℃ • 怕熱、怕火，100℃，5分鐘；65℃，15分鐘即可殺菌 • 怕陽光；紫外線照射迅速死亡

12. 認識結核桿菌（tubercle bacillus）

13. HIV prevalence in adults, and TB notification rates, for Kisumu, Kenya Nat Rev Immunol 2005;5:819-26.

14. TB-HIV co-infection in Taiwan • HIV帶原者中有5.6%曾罹患結核病 • 2006年確診結核病與HIV資料庫進行勾稽 • HIV(+) / TB 的比率為 0.71%（112人） • Prevalence of HIV in adult TB patients (15–49yrs) is 2.03% in 2006

15. Clinical manifestation in AIDS with disseminated mycobacterial infection in NTUH • S/S DTB (22) DMAC (15) • Fever 21 (95.5) 14 (93.3) • Night sweating 15 (68.2) 4 (26.7) • BW loss 10 (45.5) 11 (73.3) • Diarrhea 5 (22.7) 7 (46.7) • LNP 15 (68.2) 1 (6.7) • Hepatosplenomegaly 3 (13.3) 6 (40) • Splenomegaly 2 (9.1) 7 (46.7) AIDS 1998;12:1301-7

16. CXR findingTB in HIV infected patients • CD4>200 CD4 <200Upper lobes involvement Lower lobe pneumonia Cavity Hilar or mediastinal LNP Miliary TB Normal • Normal CXR 8-20%

17. 28 Y/O MSMProductive cough for 1 months, BW lossCD4 38 HIV virus load 460000Sputum AFS (-), Lung biopsy: granulomatous inflammation, Caseous necrosis, Multinuclear giant cell 20060404 20060928

18. TB

21. TB empyema

22. Pulmonary TB with TB lymphadenitis 42 y/o MSM Intermittent fever, night sweating for 2 months CD4 215 CD8 1175 HIV virus load 486000 LN aspirate AFS (+) Sputum TB culture : MTB

23. Extra-pulmonary tuberculosis

24. PJP and TB

25. 38 y/o MSMDOE for 2 weeks, BW loss 11 KgCD4 64 CD8 345 HIV virus load 67300 WBC 2840, Sputum TB culture: MTB, Blood culture: Salmonella choleraesuis 20060214 20060207

26. Diagnosis HIV infection with TB • Specimen Microscopy % Culture % • Sputum 40-67 74-95 • BronchoscopyBronchoalveolar larvage 7-20 52-89Transbronchial biopsy 10-39 42-85 • Urine 22 45-77 • Blood 26-64 • Lymph nodes 37-90 40-95 • Bone marrow 18-52 25-67 • CSF 0-27 • Pleural specimenPleural fluid 3-6Pleural biopsy 52-55 Textbook of AIDS Medicine 1999; Chapter16

27. Comparison of HIV Disease Progression in TBTC Study 23 vs. CPCRA 019/ACTG 222 CPCRA/ACTG 1993-1995 86 0 20% 38.9% TBTC 23 1999-2002 90 80% 4.5% 15.7% Years of enrollment Baseline CD4 cell count Use of HAART during TB treatment Death within 1 year of start of TB therapy Death or new OI within 1 year of start of TB therapy

28. Overlapping Side Effect Profiles of First-line Antituberculosis Drugs and Antiretroviral Drugs Side effect Possible causes Antituberculosis drugs Antiretroviral drugs NVP, EFZ, ABC ZDV, RTV, AMP, IDV NVP, PIs, Immune reconstitution ZDV Skin rash Nausea, vomiting Hepatitis Leukopenia, anemia PZA, RIF, INH PZA, RIF, RBT, INH PZA, RIF, RBT, INH RBT, RIF

29. IRS response to pathogens • Mycobacterium tuberculosis (TB) • Mycobacterium avium complex (MAC) • Cytomegalovirus (CMV), • Cryptococcus • Pneumocystis • Toxoplasma • Hepatitis B • Varicella zoster virus.

30. Clinical Diseases and NTM in Humans • Clinical Disease NTM • Pulmonary MACM. kansasiiM. chelonaeM. xenopi • Lymphadenitis MACM. scrofulaceum • Cutaneous M. marinumM. fortuitumM. chelonaeM. ulcerans • DisseminatedMAC M. genovense M. kansasii M. chelonae M. haemophilum M. malmoense Textbook of AIDS Medicine 1999

31. Mycobacteriual species causing Disseminated NTM infection in AIDS patients • Species Number (%) • MAC 1906 (96.1) • M. kansasii 57 (2.9) • M. gordonae 11 (0.6) • M. fortuitum 5 (0.3) • M. chelonae 5 (0.3) Am Rev Respir Dis 1989;139:4-7

32. GeneralizedFeverFatigueWeight lossPancytopenia GastrointestinalChronic diarrheaAbdominal painChronic malnutritionPeriportal LNPExtrabiliary obstructive jaundice Clinical Syndromes of Disseminated MAC in AIDS

33. MAC pneumonia