1. Pneumonia 2

2. Classification of Pneumonia:  Acute Pneumonia:  Community acquired: o Person to person Classical bacterial pneumonia Atypical bacterial pneumonia Viral pneumonia o Animal, or Environmental Exposure.  Nosocomial acquired.  Chronic Pneumonia.

3.  Animal, or Environmental Exposure: o Legionellosis. o Tularemia. o Plague. o Q fever. o Anthrax.

4. Legionnaires' disease ( legionellosis) History:  Legionnaires' disease was diagnosed for the first time in 1976 in Philadelphia among attendees of a Legionnaires' convention held in a hotel, 182 attendees contracted the disease and 29 of them died.  It had caused several outbreaks. The last one was in November 12 2014 in Portugal, 302 people have been hospitalized and 7 died.

5. Causative agent: Legionella pneumophila. Microscopy: - Gram’s negative rod in nature, coccobacilli in clinical specimens. - Facultative intracellular parasites. - Rods are motile by monotrichous flagella. Transmission: o Inhalation of contaminated water aerosols from showers, humidifiers, air condition…..It lives inside the free living protozoa. o No person to person transmission. o It had caused several outbreaks as well as sporadic cases and nosocomial infections.

6. N Pathogenesis: - Engulfment by alveolar macrophages. - Inhibition of phagosome-lysosome fusion. - Replication inside the microphages until it ruptures. - Monocytic and neutrophils infiltration of alveoli; TNF-α, and INF-γ production. - Alveolitis (consolidation) and micro-abscess and cavity formation. - Bronchi are not affected.

8. N Laboratory diagnosis: -Staining of specimens (sputum, bronchial aspirate) by gram stain and Giemsa stain. -Cultured on buffered charcoal yeast extract agar (BCYE; Enriched media: cysteine, iron) for 3- 5 days. -Rapid identification: Immunofluorescent microscopy. PCR.

9. N Pneumonic Tularemia (granulomatous infection): Causative agent: Francisella tularensis. Gram negative capsulated coccobacilli with. Facultative intracellular parasite. Obligate aerobic bacteria. Transmission: from animals (rabbit, birds) to man (zoonosis).Highly infectious. Arthropods bite; vector (ticks, mites). Skin penetration; handling infected animal tissues. Inhalation of infectious aerosols. No person – person transmission.

10. N Pathogenesis and clinical presentation:

11. N Clinical presentations: Ulceroglandular tularemia: (the most common presentation). Infection of skin macrophage; ulcerative papule at the site of bite or entry; transmitted to regional lymph nodes; lymphadenitis. Hematogenous dissemination: to the lungs. liver, spleen, bone marrow. Pneumonic tularemia: By inhalation or blood dissemination. Infection of alveolar macrophage; granuloma in the lung.

12. Laboratory Diagnosis: Cultured on buffered charcoal yeast extract agar (BCYE) (Enriched media: cysteine, iron).

13. N Pneumonic Plague Causative agent: Yersinia pestis.  Gram negative coccobacilli.  In sputum: Gram negative bipolar-stained (safety pin appearance). Virulence factors: o Capsular antiphagocytic antigens: F1, V, and W. o Lipopolysaccharide (LPS) endotoxin. o Plasminogen activator: degrades fibrin. Transmission: Vector-borne: insect bite (fleas) from rats. Skin penetration. Person-to-person: inhalation of droplets.

15. N Infective dose: 100-500 cells. Incubation: 2-8 days. Three clinical presentations: Primary: Bubonic plague: Swollen tender regional lymph node (buboes); lymphadenitis (hemorrhagic necrosis). Septicemic plague: DIC, purpura and ecchymosis. Pneumonic plague: (Bronchopneumonia): o Primary: Inhalation of droplets. o Secondary: Hematogenous spread.

17. N Black death: ischemic lesion + cyanosis Treatment of Plague: Pneumonic plague should be treated within 24 hours of appearance of symptoms, (mortality rate approaches100%).

18. Inhalation anthrax: Wool sorter's disease: Causative agent: Bacillus anthracis Gram positive aerobic spore-forming bacilli. Transmission: inhalation of spores. Clinical presentation of inhalation anthrax:  Inhalation anthrax; hemorrhagic mediastinal lymphadenitis: not a true pneumonia: alveolar macrophages transfer the spores to the mediastinal and peribronchial lymph nodes.  Anthrax meningitis; in 50% of inhalation cases; extensive hemorrhage in the leptomeninges; dark- red appearance on autopsy “Cardinal’s cap”.

19. Treatment: -Only if multiple intravenous antibiotics and passive vaccine administered prophylactically after spore exposure.

20. Hospital-acquired Pneumonia (Nosocomial)

21. Nosocomial pneumonia: pneumonia acquired during or after hospitalization (at least 72 hour after admission) Who are at Risk? Patients on mechanical ventilation (ICU). Immunocompromised patients. Other factors: malnutrition, heart and lung diseases. Causative agents: Aspiration of oropharyngeal and GIT flora & hospital bacteria: methicillin resistant S. aureus (MRSA), Pseudomonas, Enterobacter, Klebsiella, Serratia, VRE and Acinetobacter (person-to person).

22. Chronic Pneumonias (coccidioidomycosis, histoplasmosis)

23. Chronic granulomatous pneumonia: o Bacterial granulomatous pneumonia Mycobacterium tuberculosis. Acid-fast bacilli (Mycolic acid waxy capsule). Cultured on Lowenstein-Jensen agar. Stained by Z.N stain. Fungal granulomatous pneumonia: Endemic in America. Coccidioidomycosis. Histoplasmosis. Blastomycosis. Paracoccidioidomycosis

24. Coccidioidomycosis: Caused by dimorphic fungi :Coccidioides immitis. In the environment; they are molds with hyphae and arthroconidia (the infective stage). In the tissues, a large structure called spherule filled with endospores (the diagnostic stage). Pathogenesis and tissue damage: -Arthroconidia engulfment by alveolar macrophage; spherule. -T cell mediated immunity and macrophage activation.

25. N Clinical presentations: o Asymptomatic or mild flu like illness. o Acute pulmonary infection; fever, dry cough and chest pain (self-limited illness). o Chronic pulmonary infection with cavitation; in a small number of people. o Chronic meningitis. o Disseminated infection: in cell-mediated immune deficiencies (e.g. AIDS): cutaneous or systemic infection.

27. Histoplasmosis: Causative agent: the dimorphic fungus Histoplasma capsulatum (non-capsulated). Pathogenesis and tissue damage: -Inhalation of microconidia (infective stage); engulfed by alveolar macrophage. -Transferred into yeast form (diagnostic) that modulate the phago-lysosomal pH. -T cell mediated immunity; killing of yeast by macrophage; Granuloma formation.

28. N Depending on pathogenic dose and T-cell mediated response: Patchy pneumonitis. Mediastinal lymphadenopathy Chronic cavitary pulmonary histoplasmosis, in patients with chronic obstructive pulmonary disease (COPD). Acute disseminated histoplasmosis: in immunocompromised: hepatosplenomegaly, mucus membrane ulcers, sepsis, and DIC.

29. N Diagnosis: Microbiology Lab: Histology Lab: Tuberculate macroconidia. Macrophage with yeast cells.

30. Fungal Pneumonia in AIDS patients B - Cryptococcosis A - Pneumocystis pneumonia: (The most common). -Caused by Pneumocystis jiroveci (P.carinii). -Yeast lacking ergosterol in cell membrane and so can not be treated by amphotericin. -Encysted forms infects alveoli; exudate; blocks gas exchange. -Treatment: Sulfamethoxazole and trimethoprim. Cysts of Pneumocystis carinii ; Sliver stain.

31. N B- Cryptococcosis: Causative agents: Cryptococcus neoformans. -Yeast transmitted to man from birds (pigeon). Capsulated microbe. -Pneumonia and meningitis in Immunocompromised host. The Budding capsulated yeast Cryptococcus neoformans as shown in India ink wet mount.