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Immunocompromised hosts
General principles
-Can get pneumonia from "normal" pathogens: CAP, atypical, aspiration, nosocomial...
- Predisposed to severe infections with "normal":
- -lack of Ig: encapsulated organisms
- -complement deficiency: Neisseria species
- Opportunistic: organisms don't usually infect people with intact immune system
- -Disease is quicker, more severe
- -emperic treatment often needed
- Common immunodeficiencies:
- -Granulocytopenia
- -T cell dysfunction
- -Chemotherapy and steroids
- -Injuries to mucosal barriers
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Pneumonia
agranulocytosis or Ig deficiency
- Presentation: (acute)
- -fever
- -hypotension
- -infiltrates on CxR
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Pneumonia
T cell defects
- Presentation: slower progression (over days)
- -progressive cough
- -fever (later)
- -SOB (later)
- -extrapulmonary manifestations
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Pneumonia
Major pathogens in immunocompromised
- Pneumocystis
- Cryptococcus
- Aspergillus
- Viruses
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Pneumocystis
History, pathophys, epidemiology
- History:
- -pre 1988, very few cases
- -HIV (pre-HART): most common CAP leading to admission; "Pneumocystis carinii = PCP"
- -P. carinii found to only infect cats; Pneumocystis jirovecii is human pathogen (still called PCP)
- -Now, infrequent (due to antiretrovirals and prophylaxis)
- EM:
 - -No reliable in vitro culture system
- -Major surface gycoprotein (MSG) undergoes antigenic variation to evade host immunity
- -MSG may also inhibit surfactant production
- -multiple strainss exist
- Pathogenesis:
- -airborne transmission
- -trophic form attaches to type 1 pneumocytes
- -organism can lay dormant for years without causing overt disease
- -CD4 cells play central role in host defense (macrophages and Abs play small role)
- -Organism proliferates, fills alveolar space (foamy eosinophilic exudate)
- Epidemiology:
- -initially thought to be reactivation: children generally have + antibodies by age 4
- -Reinfection also occurs
- -AIDs infection corolates with CD4 count <200 cells/mm3
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Pneumocystis
Presentation, labs, dx, Tx
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Cryptococcus
yeast
Pathogen, epidemiology, pathogenesis
- Pathogen:
- -round, encapsulated yeast
- -reproduction: simple, narrow-based budding
- -Serotypes:
- -C. neoformans
- -C. gattii
- -Can culture from blood on solid media (48-72h):
- -produce urease
- -Makes black pigment (melanin) on niger seed agar
- C. neoformans: (serotypes A, D, and AD)
- -soil rich in bird droppings (pigeons)
- C. gattii: (serotypes B and C)
- -eucalyptus trees
- Epidemiolgy:
- -normal host: usually asymptomatic
- -most children have Ab before age 10
- -Immunocompromised: serious, progressive and disseminated disease
- -Dogs and cats also infected
- Pathogenesis:
- -Polysaccharide capsule upregulates in vivo
 - Function:
- 1. inhibits phagocytosis
- 2. depletes complement
- 3. inhibits antibody formation
- 4. dysregulated cytokines
- 5. interferes with antigen presentation
- -Melanin is also a virulence factor: antioxidant
- -Grows well at body temp; inhibited growth at higher temps
- -Macrophages and CMI important in limiting growth
- -Pathology variable (depending on host): absense of inflammatory rxn --> intense granulomatous inflammation
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Cryptococcus
Presentation, dx, Tx
- Presentation:
- -ranges from asymptomatic to severe cough, SOB and chest pain
- -not much fever
- -Nl host: nodular infiltrates, nodules later calcify
- -Mass like lesions, hilar adenopathy, cavitation
- -Disseminates to CNS, bond, skin, prostate, eye
- CxR:
 - Dx:
- -Stains (India Ink, H&E, GMS)
- -Culture from sputum or BAL
- -Serology: Cryptococcal antigen

- Tx:
- -Isolated pulmonary infection: fluconazole
- -CNS: Amphotericin + 5FC
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Invasive mold infections
- -Common in pts with AML, BMT
- -Severe neutropenia present in 96% of cases before onset
 - Aspergillus is most common; others
- -Scedosporium
- -Mucorales (zygomycetes) - diabetes pts
- -Dematiaceous fungi
- -Fusarium
- Epidemiology:
- -Incidence varies by location, 1-13% per year
- Risk factors:
- -Iron overload, multiple blood transfusions (Macrophages busy consuming iron)
- -CMV infection
- -Graft vs Host disease
- Immune response: need both to contain infection
- -Macrophages (and polys) - steroids inhibit macrophages
- -Th1 cells
- Pathology:
- -Tissue invasion, vessels... leading to infarct
- -Hematogenous spread
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Invasive mold infections
presentation, Dx, Tx
- Clinical presentation:
- -progressive dry cough
- -dyspnea
- -pleuritic chest pain
- -fever (despite broad coverage with Abx)
- -pulmonary infiltrates:

- Dx:
- -Biopsy and culture, but biopsy often difficult
- -Galactomannan testing for Aspergillus from serum (sensitivity 71%, specificity89%) or BAL (sensitivity 58%, specificity 96%)
- -1,3‐beta‐D‐glucan is common in cell wall of many molds, but not specific
- CT: suggestive of IMI, but should be confirmed with CT guided biopsy
- -Nodules 1 cm or greater
- -Halo sign (aspergillus) (top) or reverse halo sign (mucorales)
- -Air crescent sign (bottom)
- -Cavities

- Tx:
- -Mortality high
- -Prophylaxis now standard
- Etiologic diagnosis important:
- –Aspergillus: Voriconazole, Amphotericin, Echinocandins
- –Mucorales: Amphotericin, Posaconazole
- –Scedosporium: Voriconazole for apiospermum, prolificans resistant to all
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Aspergillus
- -Causes allergic reaction in the airways (Allergic Bronchopulmonary Aspergillosis - ABPA)
- -Causes cavitary and disseminated disease
- -Most infectious is A. fumigatus
- -Septate hyphae with branching at acute angles, distinguished by their "fruiting heads":

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Cytomegalovirus
CMV
- -Often present in immunosuppressed (but not always causing disease)
- -30-50% of adults have CMV antibody; CMV persists in latent state
- -In HIV, can be recovered from lung, not usually alone: Tx not indicated
- -Transplant: CMV has predilection for the organ transplanted
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CMV Pneumonitis
- lung transplant patients:
- -disease in first 3 months after transplant (if not on prophylaxis); or 3 months following cessation of prophylaxis
- -may mimic rejection
- -increases the risk for rejection
- Primary: seronegative recipient given seropositive donor
- -disease from primary is worse than reactivation
- -involves multi organ systems
- Radiograph: patchy or diffuse ground glass opacities, patchy consolidations, small nodular opacities
- -less common: thickened bronchovascular bundles, tree-in-bud airway pattern, reticular opacities, small pleural effusions

- Dx: tests detect viral replication/antigens
- -Viral load assay of blood or BAL
- -CMV pp65 antigenemia
- -Shell-vial cultures
- Histopathology is the gold standard:

- Tx:
- -IV ganciclovir
- -Oral valganciclovir
- -Foscarnet for ganciclovir resistance
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