Page 434 - Clinical Immunology_ Principles and Practice ( PDFDrive )

414 ParT ThrEE Host Defenses to Infectious Agents

Immunotherapy for Immunotherapy Cancer and
autoimmune for HIV / AIDS chemotherapy
diseases cancer

Parenteral Intensive
nutrition care unit
treatment
Catheterization Immunosuppressive
therapy
Neonates
and elderly Broad-spectrum
antibiotics
Organ/bone marrow Invasive
transplant fungal
infections Surgery

Hematologic Inherited
malignancy immunodeficiencies
FIG 29.1 Major risk factors for developing invasive fungal infections. (Adapted from Karkowska-
Kuleta J, Kozik A. Cell wall proteome of pathogenic fungi. Acta Biochim Pol 2015; 62: 339–51.)

CLINICALLY RELEVANT FUNGAL ORGANISMS Candida albicans
Candida species are ubiquitous commensal fungi that normally
Although it is estimated that there are in excess of 5 million colonize human mucosa and skin. There are over 165 species of
distinct species of fungi, only a handful are considered sig- Candida, but only a few are known to cause human disease. C.
nificant to human health: Aspergillus spp., Candida spp., and albicans accounts for the majority of infections, followed by C.
Cryptococcus spp. cause the majority of IFIs in the United States glabrata. Less frequently, C. parapsilosis, C. tropicalis, C. krusei,
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and Europe. Invasive infections caused by these pathogens and others cause invasive candidiasis. In immunocompromised
in immunocompromised patients are serious and often life individuals, Candida can become pathogenic and infect host
threatening. tissues. For example, Candida is commonly associated with skin
infections, as well as oral and vaginal thrush. However, Candida
Aspergillus fumigatus can become invasive (invasive candidiasis), entering the blood-
Aspergillus fumigatus is a ubiquitous airborne mold found in soil, stream (candidemia) and other organs (e.g., bladder/kidneys,
air, food, and decaying organic material. Humans routinely inhale liver, spleen, gut, etc.), resulting in a life-threatening infection.
A. fumigatus conidia, but the microorganism is rapidly eliminated Despite the availability of antifungal therapy, the crude mortality
by the innate immune system in immunocompetent individuals. rate for candidemia exceeds 50%, indicating that the immune
In immunocompromised patients, A. fumigatus can cause IA, a system is a necessary partner for successful treatment of this
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severe and usually fatal infection. It is estimated that IA occurs in infection. Every year, it is estimated that invasive candidiasis
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200 000 patients annually. In cases of widespread infection, IA affects 250 000 people worldwide and causes more than 50 000
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mortality rates approach 90%, with favorable responses to anti- deaths. As with other opportunistic fungal infections, patients
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fungal therapy observed in <30% of patients. In particular, IA on immunosuppressive regimens (i.e., transplant recipients) and
has emerged as a significant cause of mortality among patients patients with hematological cancers are at high risk for invasive
who have undergone hematopoietic stem cell transplantation and candidiasis. Other major risk factors include recent surgery,
solid organ transplantations. Advanced age, respiratory viruses, broad-spectrum antibiotic therapy, and central vascular catheters.
graft-versus-host disease (GvHD), prolonged glucocorticosteroid Disruptions to the balance of C. albicans in the gut are associated
use, cytomegalovirus (CMV) infection, and iron overload are also with increasing severity of Crohn disease and ulcerative colitis
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common risk factors for IA. Given that A. fumigatus spores are (UC). Moreover, disseminated candidiasis may originate in the
inhaled, IA most frequently manifests as an invasive pulmonary gut.
disease, but the pathogen can enter the bloodstream and infect
multiple organs. Less frequently, IA affects skin, sinuses, and the Cryptococcus neoformans
central nervous system (CNS). Clinical characteristics of IA vary, During the 1980s to the 1990s, cryptococcosis emerged as a
depending on the organ(s) affected. major cause of morbidity and mortality among persons with
Aspergillus can cause a condition called chronic pulmonary HIV/AIDS. The majority of cryptococcosis cases are caused by
aspergillosis (CPA), which causes progressive destruction of lung C. neoformans, a fungus that is widely distributed in soil. The
tissue. CPA is most common in patients with underlying lung major route of exposure to C. neoformans is inhalation of airborne
disease (e.g., asthma) and affects 3 million people worldwide. organisms into the lungs. In healthy individuals, the immune
CPA is estimated to have 15% mortality, often as a result of a system is effective at clearing the pathogen, but in immuno-
massive pulmonary hemorrhage within the first 6 months of compromised individuals (especially those with HIV/AIDS),
diagnosis. 4 C. neoformans can cause an IFI. Interestingly, C. neoformans