Chronic Pneumonias, Lung Infections in Immunosupresssion and T.B

1. Chronic Pneumonias, Lung Infections in Immunosupresssion and T.B

2. Chronic Pneumonias • Localized lesion in the immunocompetent patient, with or without regional lymph node involvement. • Disseminated disease may occur in the immunocompromised. • Granulomatousinflamatory diseases caused by ,Mycobacterium tuberculosis or the fungi(Histoplasma,Coccidiodes and Blastomycoses.)

3. Chronic Pneumonias • The three fungi discussed causes granulomatous disease resembling T.B. • The organisms are also thermally dimorphic existing in hyphae form at environmental temperature and as yeasts at body temperature.

4. Chronic Pneumonias • Each fungus is geographic in the pattern of disease among immunocompetentindividuals.Hence, • Histoplasma: The Ohio and Mississippi rivers and in the Caribbean. • Blastomyces: The central and southeastern United States • Coccidioides: The Southwest and Far West of the United States and in Mexico .

5. Histoplasmosis • Pathogenesis not fully understood. • Macrophages are the major target of infection. • Histoplasmacapsulatum infection . • Acquired by inhalation of dust particles from soil contaminated with bird or bat droppings that contain small spores (microconidia), the infectious form of the fungus. • Similar clinical picture to tuberculosis: • self-limited , latent primary pulmonary involvement, ( coin lesion on X-Ray) • Chronic, progressive, secondary lung disease, which is localized to the lung apices and causes cough, fever, and night sweats;

6. Histoplasmosis

7. Histoplasmosis • Localized lesions in extrapulmonary sites, including mediastinum, adrenals, liver, or meninges; • Disseminated disease in immunocompromised patients. • Diagnosis: antigen testing, fungal culture.

8. Blastomycosis Blastomycesdermatitidis • is a soil-inhabiting, dimorphic fungus . • central and southeastern United States, Canada, Mexico, the Middle East, Africa, and India. Three clinical forms: • pulmonary blastomycosis, • disseminated blastomycosis • primary cutaneous form that results from direct inoculation of organisms into the skin (rare)

9. Blastomycosis • Morphology: • Round yeast cell that divides by broad based budding • Thick, double contour cell wall and multiple nuclei.

10. Thick walled ,budding yeast cellsBlastomycosis

11. Thick walled ,budding yeast cellsBlastomycosis

12. Coccidioidomycosis • Up to 80% of the population of endemic areas(south western U.S and west U.S)have a positive skin test(delayed hypersensitivity reaction. • Infective arthroconidia block fusion of the phagosome and lysosome and so resist intracellular killing. • Most are asymptomatic, • 10% of people have lung lesions, fever, cough, and pleuritic pains, accompanied by erythemanodosum or erythemamultiforme (the San Joaquin Valley fever complex). • Less than 1% of people develop disseminated C. immitis infection, which frequently involves the skin and meninges.

13. Lung infection in immunosuppression • The CD4+ T-cell count can define the risk of infection with specific organisms. • In general: • CD4+ counts >200 cells/mm3: bacterial and T.B • CD4+ counts <200 cells/mm3 Pneumocystis pneumonia CD4+ counts <50 cells/mm3 cytomegalovirus and Mycobacterium avium complex infections .

14. Pulmonary T.B

15. It is caused by Mycobacterium tuberculosis (MTB), which causes a chronic granulomatous disease- undergoes caseous necrosis There is worldwide prevalence and it remains as the leading cause of death in impoverished nations. Recent resurgence due to HIV TUBerculosis

16. Infection with MTB leads to delayed hypersensitivity. This is detected by the Mantoux test. Mantoux Test- 0.1 ml is injected subcutaneously into the skin and 48-72 hours later, an induration of at least 5mm will appear . A positive tuberculin test indicates cell mediated hypersensitivity to the tubercular antigen NOTE: the test does not differentiate between active disease or infection. The test indicates exposure only. Tuberculosis

17. Pathogenesis: Mycobacterium tuberculosis infects the lung, and is distributed systemically within macrophages and survives intracellularly. Inhibition of phagosome-lysosome fusion and resistance to lysosomal enzymes have both been suggested to play a role. Cell-mediated immunity develops which causes infiltration of macrophages and lymphocytes with development of a granuloma (tubercles). Tuberculosis

18. Pathogenesis of primary pulmonary tuberculosis Early phase (<3 weeks) -bacillary proliferation within the pulmonary alveolar macrophages -this results in bacteremia and seeding - clinically the patient is asymptomatic or flu like illness may be present Late phase (>3 weeks) - cell mediated immunity develops -CD4 T cells secrete IFN- gamma –which activates macrophages -activated macrophages release mediators  recruit monocytesdifferentiates into epitheloid cells Note: reactivation or re-exposure results in a an increased response, with more tissue necrosis Tuberculosis con’t

19. Primary tuberculosis- refers to the disease that develops in an unsensitized, unexposed individual Inhaled bacilli get lodged in the lower part of the upper lobe or upper part of the lower lobe . This leads to a 1 -2 cm area of consolidation – known as the ghon focus, which undergoes caseous necrosis Ghon focus + hilar lymph nodes = Ghon complex Hematogeneous and lymphatic spread occurs to other parts of the body The ghon focus undergoes progressive fibrosis Pathogenesis

20. Progressive primary tuberculosis the disease may develop without interruption (HIV ,patient on long term steroids) immunosuppression prevents CD4 T cell mediated response that would normally contain the focus – caseatinggranulomas would be absent. dissemination leads to tuberculous meningitis or miliarytuberculosis clinically- it would appear as pneumonia. with or without Pleural effusion . Tuberculosis

21. Secondary tuberculosis -this occurs in a patient who has been previously sensitized -this usually appears many decades after the reactivation of dormant primary lesion i.e. in cases of weakened defenses -it may also result from reinfection -it is localized in the apex of the lung, due to pre-existing hypersensitivity -cavitation may lead to dissemination- sputum samples will contain the bacilli. Note: cavitation occurs readily in secondary disease. -if treatment proves inadequate, the infection will spread into the neighbouring structures or via dissemination through lymphatics or the vascular system Tuberculosis

22. Miliary spread Into the pulmonary system: Enter through the lymphatic system, which drain to the right side of the heart enter pulmonary circulation. Multiple lesions or foci will be seen throughout the lungs Progressive pulmonary TB – pleural effusions , empyema etc. Systemic miliary TB – when infective foci enters left side of heart to reach circulation- this can seed to other parts of the body i.e. liver, bone, spleen, meninges, kidneys, fallopian tubes, etc. Tuberculosis con't

23. Clinical findings of secondary TB Localized: asymptomatic Systemic: low grade fever, night sweats Progressive pulmonary: sputum – mucoid followed by purulent or hemoptysis may be present With cavitation present: sputum contains tubercle bacillli Tuberculous meningitis: headache and focal neurologic deficit Diagnosis: Sputum samples of acid fast bacilli PCR Culture- gold standard CXR- consolidation or cavitation in the apices of the lung Tuberculosis con't

25. Primary TB-CXR This CXR shows extensive right paratracheallymphadenopathy and poorly defined right upper lobe consolidation.

26. Miliary TB This CXR has a miliary pattern of involvement (M) The arrow points at a cavity in the upper lobe

27. Pulmonary TB Microscopically, the characteristic lesion in tuberculosis is the tuberculousgranuloma.

28. Pulmonary TB-M/E Higher magnification of a tuberculousgranuloma

29. Pulmonary TB -gross Here is the gross appearance of a lung with tuberculosis. Scattered tan granulomas are present, mostly in the upper lung fields. Some of the larger granulomas have central caseation.

30. Miliary TB -Gross This is a "miliary" pattern of granulomas because there are a multitude of small tan granulomas, about 2 to 4 mm in size, scattered throughout the lung parenchyma. The miliary pattern gets its name from the resemblence of the granulomas to millet seeds.