Opportunistic Mycoses: Mucormycosis & Aspergillosis

• Opportunistic mycoses are fungal infections that primarily affect individuals with weakened immune systems.

Mucormycosis

• Mucormycosis is commonly caused by Mucor and Rhizopus species.
• Less common causes include Apophysomyces and Rhizomucor species.
• These fungi are saprophytic, non-dimorphic, and characterized by aseptate hyphae.

Risk Factors

• Diabetes, especially with ketoacidosis
• Burn injuries
• Bone marrow transplants
• Leukemia

Pathogenesis & Clinical Symptoms

• Rhinocerebral mucormycosis is a severe form that can be fatal within a week.
• It particularly affects diabetic patients where mold spores in the sinuses form hyphae that invade brain blood vessels.
• Infection starts in the nasal mucosa or sinuses and progresses to the orbits, palate, and brain.

Treatment

• High-dose amphotericin B
• Surgical removal of necrotic tissue
• Correction of the underlying predisposing condition

Aspergillosis

• Aspergillosis is mainly caused by Aspergillus fumigatus, among other Aspergillus species.
• Aspergillus species are filamentous molds and are not dimorphic.

Morphology & Source of Infection

• These are ubiquitous molds that grow as filamentous forms and produce conidiospores.

Clinical Symptoms

• Cause infections of the skin, sinuses, eyes, and ears.
• Can cause fungus balls in the lungs and allergic bronchopulmonary aspergillosis.

Forms of Disease

• Fungal sinusitis is most commonly caused by Aspergillus.
• Acute invasive aspergillosis is a severe, often fatal form originating in the lungs, which can spread to the brain, gastrointestinal tract, and other organs.
• Aspergilloma (fungus ball) is a non-invasive lung infection where hyphal tissue masses form in pre-existing lung cavities, such as those from tuberculosis.
  • It appears as a radiodense structure on chest X-rays that shifts with patient movement.
• Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus in the bronchi.

Diagnosis

• Definitive diagnosis involves detecting hyphae in tissue and isolating the organism from clinical samples.
• Aspergillus hyphae are septate and branch at 45-degree angles.
• Colonies grown in culture display radiating chains of conidia.
• ABPA patients have high IgE levels specific for Aspergillus antigens and prominent eosinophilia.

Treatment

• Amphotericin B
• Surgical removal of fungal masses or infected tissues
• Transmitted by airborne asexual sporangiospores.

Imaging & Microscopy

• CT scans of the head show involvement of the paranasal sinuses and periorbital soft tissue.
• PAS stain of periorbital tissue demonstrates irregular, broad hyphae with right-angle branching.
• Rhizoids of Rhizopus species are visible on staining of blood vessels.
• These organisms reside in dust, soil, and decomposing organic matter.
• Hospital outbreaks affecting immunocompromised patients have been linked to dust from nearby construction work.
• Common among immunocompromised and neutropenic patients

Cryptococcosis

• Cryptococcus neoformans, a yeast, causes cryptococcal meningitis.
• It is the most common life-threatening basidiomycete fungal disease globally.
• Not dimorphic

Properties

• Oval budding yeast surrounded by a wide polysaccharide capsule
• Forms a narrow-based bud
• Abundant in soil containing bird droppings

Susceptible Populations

• Commonly affects patients with reduced cell-mediated immunity, especially those with AIDS.
• HIV-related cryptococcosis is the second most common fungal infection after candidiasis.
• Cryptococcal meningitis is an AIDS-defining condition.

Transmission

• By inhalation of the organism
• No human-to-human transmission

Clinical Features

• Mild, subclinical lung infection is the most common form.
• In immunocompromised patients, it often spreads to the brain, causing cryptococcal meningitis with fatal consequences.
• Can trigger immune reconstitution inflammatory syndrome (IRIS) upon antiretroviral therapy due to increased CD4 count.

Diagnosis

• In spinal fluid mixed with India ink, the yeast cell is seen surrounded by a wide, unstained capsule.
• Mucicarmine stain can be used for Cryptococcus neoformans in lung tissue.
• Periodic acid-Schiff (PAS) and methenamine silver stains are other useful stains.

Treatment

• Amphotericin B
• Flucytosine
• The treatment regimen depends on the stage of the disease, site of infection, and patient’s immune status.

Pneumocystis Pneumonia (PCP)

• Pneumocystis jirovecii pneumonia is caused by a disc-shaped yeast-like fungus.
• Previously known as Pneumocystis carinii.
• Classified as a yeast based on molecular analysis but has some protozoan characteristics.
• Considered the most common AIDS-defining opportunistic infection

Transmission

• Ubiquitous in nature
• Acquired through inhalation of airborne organisms into the lungs
• Not transmitted person to person
• Disease in immunodeficient patients results from reactivation of pre-existing dormant cells in the lungs.
• Most immunocompetent individuals have asymptomatic infections.

Pathogenesis

• Encysted forms of Pneumocystis jirovecii induce alveolar inflammation, leading to exudate production that blocks gas exchange, causing dyspnea.

Clinical Symptoms

• Fever
• Nonproductive cough
• Dyspnea
• If left untreated, mortality is approximately 100%.

Diagnosis

• Based on microscopic examination of cysts in lung tissue biopsy or washings.
• Lactic acid dehydrogenase (LDH) levels are generally elevated (>220 U/L) in patients with PCP.
• PCP infection is confined to the lungs, resulting in pneumonia.
• Chest X-ray shows a characteristic patchy or ground-glass appearance, sparing the lower lobes.
• Bilateral rales are heard on auscultation.

Treatment

• First-line treatment is trimethoprim-sulfamethoxazole (for both treatment and prophylaxis).
• Other antifungal drugs are not effective as ergosterol is absent in the cell wall.
• Common opportunistic disease in individuals infected with HIV with reduced CD4+ cells