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Invasive Aspergillosis caused by Aspergillus fumigatus


Follow either myeloid or lymphoid lineage. Differentiate into other cells ... Compost vegetation, wood chip piles, moldy hay, and soil. Grows best between 20 and 50 C ... – PowerPoint PPT presentation

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Title: Invasive Aspergillosis caused by Aspergillus fumigatus

Invasive Aspergillosis caused by Aspergillus
  • Presented by
  • Heidi Quackenbush

Hematopoietic Stem Cells
  • Abbreviated HSC
  • Arise in bone marrow
  • Self-renewing
  • Follow either myeloid or lymphoid lineage
  • Differentiate into other cells
  • Dendritic cells, Platelets, NK cells and more

HSC lineages
  • Hematopoiesis follows many lineages
  • Myeloid
  • Lymphoid

HSC Transplantation
  • Indications for HSC transplantation
  • Leukemias
  • Lymphomas
  • Plasma cell disorders
  • Solid tumors
  • Acquired bone marrow disorders
  • Congenital disorders
  • Auto-immune diseases

Invasive Aspergillosis
  • 357 increase in death rates in United States
    from 1980 to 1997
  • Pulmonary fungal infection
  • Common etiological agents
  • A. fumigatus
  • A. flavus
  • A. fumigatus is found in
  • Compost vegetation, wood chip piles, moldy hay,
    and soil
  • Grows best between 20 and 50C

Aspergilli spp.
  • Fungi
  • Thick, polysaccharide walls
  • Aiding in resistance to available penicillin
  • Live in aerobic environments
  • single- or multi-cellular
  • Respiratory pathogens
  • Conidia (fungal spores)
  • Indoor and outdoor air
  • Transmission
  • Airborne spores, nosocomial and cutaneous

Pathogenicity of A. fumigatus
  • Disturbs balance in Th1/Th2
  • Th1 cell-med, intracellular
  • Th2 Ab-med, but fungi are euks, like host cells
  • Induces Th2, causing invasive aspergillosis
  • Manifestations
  • Immunocompromised host
  • Fever, cough and chest pain
  • Invasive pulmonary infection, spread to other
  • Immunocompetent host
  • Similar symptoms, but localized pulmonary
    infection, no spreading

Invasive Aspergillosis associated with HSC
  • Risk factors following HSC transplant
  • Individuals with underlying disease are
    susceptible to IA
  • Aplastic anemia, multiple myeloma
  • Another factor, age at time of transplant
  • Increased risk in older patients,
  • T-cell depletion or CD34 selection
  • Protective Th1, IFN-gamma, IL-12
  • Progression IL-4, IL-10, CD4 Th2

Categories of Infection
  • Three categories
  • Allergic bronchopulmonary hypersensitivity
  • A. fumigatus present in the lung tissue
  • Disseminated disease
  • Also associated with presence of pathogen in the
  • Aspergilloma
  • Mass of entangled hyphae
  • Pre-existing lung cavities
  • Can spread from lungs to blood vessels
  • Thrombosis and possible infarction

Host Defenses
  • Dendritic cells
  • Transport conidia and hyphae from airways to
    draining lymph nodes
  • Initiates Th responses to the fungus
  • Macrophages
  • Resting alveolar macrophages
  • Phagocytosis and killing of conidia
  • Non-oxidative mechanisms
  • Induction of IL-12 production, Th1 cells
  • T-cells, possibility, mentioned previously

Host Defenses (cont.)
  • Neutrophils
  • Attack developing hyphae
  • Oxygen-dependent mechanisms
  • Induces production of
  • IL-4 T/B cell proliferation and Macrophage
  • IL-10 inhibition of Th1 cytokine production
  • NK cells
  • Chemokine-mediated recruitment
  • MCP-1 monocyte chemotactic protein-1
  • CCL-2 CC chemokine ligand-2
  • Neutralization caused reduced NK recruitment to
  • Defects in NK cells, predisposition to IA
  • Antibody-mediated depletion of NK cells
  • Impaired defense against the infection

Diagnosis and Treatment
  • Techniques for diagnosis
  • Microscopic observation
  • Cultured specimens
  • Skin tests
  • Still many cases undetected and untreated
  • Treatment suggestions
  • Increased number of NK cells
  • Antifungal drugs
  • Amphotericin B, Fluconazole
  • Collateral damage, fungi are also eukaryotic, low
    in selective toxicity

Treatment-new option
  • Pentraxin 3 (PTX3)
  • Alone or with other antifungals
  • Activates complement, classical pathway, binds
  • Promotes phagocytosis
  • Unidentified cell receptor
  • New developments extremely important
  • Limited use of amphotericin B, nephrotoxicity
  • Inevitable resistance, antibiotics in general

Prevention Strategies
  • HSCT patients
  • Ventilation, hospital construction, equipment,
    plants, play areas and toys, skin and oral care
  • Nosocomial Aspergillus infection
  • Associated with dissemination of spores, hospital
    visitors and hand hygiene
  • Isolation Protective (single room) and Source
    (separate building)
  • Also use with HEPA filters and controlled

Conclusion and Questions
  • Many benefits to transplants and preventative
  • Opportunistic eukaryotic pathogens
  • Importance of cleanliness and awareness of
    surrounding environment
  • Questions??

  • Bozza, Silvia, et al. Dendritic cells transport
    conidia and hyphae of Aspergillus funmigatus
    from the airways to the draining lymph nodes and
    initiate disparate Th responses to the fungus.
    The Journal of Immunnology 168 (2002) 1362-71.
  • Dykewicz, Clare A. Hospital Infection Control in
    Hematopoietic Stem Cell Transplant Recipients.
    Emerging Infectious Diseases 7 (2001) 263-267.
  • Gaziano, Roberta et al. Anti-Aspergillus
    fumigatus Efficacy of Pentraxin 3 Alone and in
    Combination with Antifungals. Antimicrobial
    Agents and Chemotherapy 48 (2004) 4414-21.
  • Goldsby, Richard, et al. Immunology Fifth
    Edition. New York W.H. Freeman and Company,
  • Jansen, Jan et al. Transplantation of
    hematopoietic stem cells from the peripheral
    blood. J. Cell. Mol. Med. 9 (2005) 37-50.
  • Maier, Raina M., Ian L. Pepper and Charles P.
    Gerba. Environmental Microbiology. San Diego
    Elsevier, 2000.
  • Marr, Kieren A., et al. Invasive aspergillosis
    in allogenic stem cell transplant recipients
    changes in epidemiology and risk factors. Blood
    100 (2002) 4358-66.
  • McCance, Kathryn L. and Sue E. Huether.
    Pathophysiology The Biologic Basis For Disease
    in Adults Children. St. Louis Mosby, Inc.,
  • Mims, Cedric, et al. Medical Microbiology Third
    Edition. Spain Mosby-Year Book Europe Ltd.,
  • Morrison, Brad E. et al. Chemokine-mediated
    recruitment of NK cells is a critical host
    defense mechanism in invasive aspergillosis. The
    Journal of Clinical Investigation 112 (2003)
  • Panackal, Anil A., et al. Aspergillus ustus
    Infections among Transplant Recipients. Emerging
    Infectious Diseases 12 (2006) 403-8.