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Micrograph of dark purple circles on a light purple background.
A light micrograph of a smear containing Pneumocystis jirovecii (dark purple cells) obtained from human lung tissue and stained with toluidine blue. (credit: Centers for Disease Control and Prevention)

Cryptococcosis

Infection by the encapsulated yeast Cryptococcus neoformans causes cryptococcosis . This fungus is ubiquitous in the soil and can be isolated from bird feces. Immunocompromised people are infected by inhaling basidiospores found in aerosols. The thick polysaccharide capsule surrounding these microbes enables them to avoid clearance by the alveolar macrophage. Initial symptoms of infection include fever, fatigue, and a dry cough. In immunocompromised patients, pulmonary infections often disseminate to the brain. The resulting meningitis produces headaches, sensitivity to light, and confusion. Left untreated, such infections are often fatal.

Cryptococcus infections are often diagnosed based on microscopic examination of lung tissues or cerebrospinal fluids. India ink preparations ( [link] ) can be used to visualize the extensive capsules that surround the yeast cells. Serological tests are also available to confirm the diagnosis. Amphotericin B, in combination with flucytosine , is typically used for the initial treatment of pulmonary infections. Amphotericin B is a broad-spectrum antifungal drug that targets fungal cell membranes. It can also adversely impact host cells and produce side effects. For this reason, clinicians must carefully balance the risks and benefits of treatments in these patients. Because it is difficult to eradicate cryptococcal infections, patients usually need to take fluconazole for up to 6 months after treatment with amphotericin B and flucytosine to clear the fungus. Cryptococcal infections are more common in immunocompromised people, such as those with AIDS. These patients typically require life-long suppressive therapy to control this fungal infection.

a) A micrograph with dark circles (some attached to form a figure 8) on a green background. The dark cells are labeled Cryptococcus. The figure 8 cells are labeled budding cells. b) a negative stain micrograph of cryptococcus neoformans is shown. It appears as green spots on a brown background.
(a) The micrograph shows stained budding Cryptococcus yeast cells from the lungs of a patient with AIDS. (b) The large capsule of Cryptococcus neoformans is visible in this negative stain micrograph. (credit a, b: modification of work by Centers for Disease Control and Prevention)
  • What populations are most at risk for developing Pneumocystis pneumonia or cryptococcosis?
  • Why are these infections fatal if left untreated?

Fungal diseases of the respiratory tract

Most respiratory mycoses are caused by fungi that inhabit the environment. Such infections are generally transmitted via inhalation of fungal spores and cannot be transmitted between humans. In addition, healthy people are generally not susceptible to infection even when exposed; the fungi are only virulent enough to establish infection in patients with HIV, AIDS, or another condition that compromises the immune defenses. [link] summarizes the features of important respiratory mycoses.

Table titled: Fungal Infections of the Respiratory Tract. Columns: Disease, Pathogen, Signs and Symptoms, Diagnostic Tests, Antimicrobial Drugs. Aspergillosis; Aspergillus fumigatus; Shortness of breath, wheezing, coughing, runny nose, headaches; formation of aspergillomas causing severe pneumonia and pulmonary or brain hemorrhages; can be fatal; Chest radiograph, skin test, microscopic observation of sputum samples; Itraconazole, voriconazole. Blastomycosis; Blastomyces dermatitidis; Fever, chills, cough, headache, fatigue, chest pain, body aches; in disseminated infections, chronic, crusted lesions on face and hands with permanent scarring; can be fatal; Microscopic observation of sputum samples; urine antigen test; EIA; Amphotericin B, ketoconazole; Coccidioidomycosis (Valley fever); Coccidioides immitis; Granulomatous lesions on face and nose; may spread to organs or brain, causing fatal meningitis; Culture (in BSL-3 lab only), serological antibody tests; Amphotericin B. Cryptococcosis; Cryptococcus neoformans; Fever, cough, shortness of breath; can cause fatal meningitis if disseminated to brain; Microscopic examination of lung tissue or cerebrospinal fluid; Amphotericin B, fluconazole, flucytosine. Histoplasmosis; Histoplasma capsulatum; Fever, headache, weakness, chest pain, lesions on lungs; Chest radiograph, culture, direct fluorescence antibody staining, complement fixation assay, histoplasmin sensitivity test Amphotericin B, ketoconazole, itraconazole. Mucormycosis; Rhizopus arrhizus, other Rhizopus spp., Mucor spp.; Headache, fever, facial swelling, congestion, black lesions in oral cavity, cough, chest pain, shortness of breath; often fatal; Microscopic examination of tissue biopsy specimens; Amphotericin B. Pneumocystis pneumonia (PCP); Pneumocystis jirovecii Fever, cough, shortness of breath; can be fatal if untreated Microscopic examination of lung tissue and fluid, PCR; Trimethoprim-sulfamethoxazole.

Key concepts and summary

  • Fungal pathogens rarely cause respiratory disease in healthy individuals, but inhalation of fungal spores can cause severe pneumonia and systemic infections in immunocompromised patients.
  • Antifungal drugs like amphotericin B can control most fungal respiratory infections.
  • Histoplasmosis is caused by a mold that grows in soil rich in bird or bat droppings. Few exposed individuals become sick, but vulnerable individuals are susceptible. The yeast-like infectious cells grow inside phagocytes.
  • Coccidioidomycosis is also acquired from soil and, in some individuals, will cause lesions on the face. Extreme cases may infect other organs, causing death.
  • Blastomycosis , a rare disease caused by a soil fungus, typically produces a mild lung infection but can become disseminated in the immunocompromised. Systemic cases are fatal if untreated.
  • Mucormycosis is a rare disease, caused by fungi of the order Mucorales. It primarily affects immunocompromised people. Infection involves growth of the hyphae into infected tissues and can lead to death in some cases.
  • Aspergillosis , caused by the common soil fungus Aspergillus , infects immunocompromised people. Hyphal balls may impede lung function and hyphal growth into tissues can cause damage. Disseminated forms can lead to death.
  • Pneumocystis pneumonia is caused by the fungus P. jirovecii . The disease is found in patients with AIDS and other immunocompromised individuals. Sulfa drug treatments have side effects, but untreated cases may be fatal.
  • Cryptococcosis is caused by Cryptococcus neoformans . Lung infections may move to the brain, causing meningitis, which can be fatal.

Fill in the blank

In coccidioidomycosis, _______ containing many endospores form in the lungs.

spherules

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In cryptococcosis, the main fungal virulence factor is the _______, which helps the pathogen avoid phagocytosis.

capsule

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In some mycoses, fungal balls called _______ form in the lungs

aspergillomas

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Most US cases of coccidioidomycosis occur in _______.

the desert southwest

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Coccidioidomycosis may develop when Coccidioides immitis _______ are inhaled.

arthrospores

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Short answer

Which pulmonary fungal infection is most likely to be confused with tuberculosis? How can we discriminate between these two types of infection?

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Compare and contrast aspergillosis and mucormycosis.

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Questions & Answers

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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