Opportunistic Mycoses & Mucormycosis

Opportunistic Mycoses

• Fungi that infect immunocompromised individuals cause opportunistic mycoses.

Mucormycosis

• Mucormycosis is most often caused by Rhizopus species, and less often by Apophysomyces and Rhizomucor species.
• These species are saprophytic and non-dimorphic, possessing aseptate hyphae. They are transmitted via airborne asexual spores.
• Spores are abundant in rotten fruit and old bread.

Risk Factors for Mucormycosis

• Mucormycosis is primarily found in individuals with:
  • Diabetes, especially with ketoacidosis
  • Burn injuries
  • Bone marrow transplants
  • Leukemia

Pathogenesis and Clinical Symptoms of Mucormycosis

• Rhinocerebral mucormycosis is a common and potentially fatal form, with death possible within a week.
• Diabetic patients are particularly susceptible to rhinocerebral mucormycosis.
• Mold spores germinate in the sinuses, forming hyphae and invade blood vessels that supply the brain.
• The infection begins in the nasal mucosa or sinuses and can progress to the orbits, palate, and brain.
• Diagnosis is often made post-mortem due to the aggressive nature of the disease.

Diagnosis and Treatment of Mucormycosis

• Treatment involves high-dose amphotericin B, surgical removal of necrotic tissue, and correction of predisposing conditions.
• CT scans of the head reveal involvement of the paranasal sinuses and periorbital soft tissue.
• Periodic acid-Schiff (PAS) stain of periorbital tissue demonstrates typical irregular, broad hyphae with right-angle branching.
• Staining of blood vessels shows rhizoids of Rhizopus species.

Aspergillosis

• Aspergillosis is primarily caused by Aspergillus fumigatus, among several Aspergillus species.
• Aspergillus species are filamentous molds and produce numerous conidia (spores).
• They reside in dust, soil, and decomposing organic matter, also found in dust from construction work.

Pathogenesis and Clinical Symptoms of Aspergillosis

• Aspergillus fumigatus can infect:
  • Sinuses
  • Eyes
  • Ears
  • Lungs

Forms of Aspergillosis

• Fungal sinusitis is commonly caused by Aspergillus.
• Acute invasive aspergillosis is a severe and often fatal form originating in the lungs, which can spread to the brain, gastrointestinal tract, and other organs.
• Aspergilloma is a non-invasive lung infection where a mass of hyphal tissue forms in pre-existing lung cavities.
  • Seen on chest X-rays, shifting with patient movement.
• Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus in the bronchi.

Diagnosis and Treatment of Aspergillosis

• Definitive diagnosis is achieved through detection of hyphae in tissue and isolation of the organism via clinical samples.
• Aspergillus hyphae are septate and form V-shaped branches at 45-degree angles.
• Colonies show radiating chains of conidia.
• ABPA patients will have elevated IgE levels specific for Aspergillus antigens and prominent eosinophilia.
• Treatment includes amphotericin B and surgical removal of fungal masses or infected tissues.

Cryptococcus neoformans

• The yeast Cryptococcus neoformans causes cryptococcal meningitis.
• This is the most common life-threatening basidiomycete fungal disease worldwide. Cryptococcus neoformans is not dimorphic.
• Cryptococcus neoformans is an oval budding yeast surrounded by a wide polysaccharide capsule.
• It forms a narrow-based bud, unlike Blastomyces, which forms a broad-based bud.
• This yeast is abundant in soil containing pigeon droppings.

Pathogenesis and Clinical Symptoms of Cryptococcus neoformans

• Disease caused by Cryptococcus neoformans mainly occurs in 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 of Cryptococcus neoformans

• Human infection results from inhalation of the organism.
• There is no human-to-human transmission.

Clinical Features of Cryptococcus neoformans

• The most common form of cryptococcosis is a mild, subclinical lung infection.
• In immunocompromised patients, infection often spreads to the brain, causing meningitis with fatal consequences.

Diagnosis of Cryptococcus neoformans

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

Treatment of Cryptococcus neoformans

• Antifungal drugs used include amphotericin B and flucytosine.
• The treatment regimen depends on the stage of the disease, site of infection, and the patient’s immune status.

Pneumocystis jirovecii

• Pneumocystis jirovecii pneumonia is caused by a yeast-like fungus.
• It was previously called Pneumocystis carinii.
• It is classified as a yeast based on molecular analysis, but shares protozoan characteristics.
• This is one of the most common opportunistic diseases in individuals infected with HIV.

Transmission of Pneumocystis jirovecii

• This fungus is ubiquitous in nature.
• It is acquired via inhalation of airborne organisms into the lungs.
• There is no person-to-person transmission.
• Disease in immunodeficient patients results from reactivation of pre-existing dormant cells in the lungs.
• Infections are mostly asymptomatic in immunocompetent individuals.

Pathogenesis of Pneumocystis jirovecii

• The ascus forms of Pneumocystis jirovecii induce alveolar inflammation.
• This leads to the production of an exudate that blocks gas exchange, causing dyspnea.

Clinical Symptoms of Pneumocystis jirovecii

• Pneumocystis pneumonia (PCP) includes:
  • Fever
  • Nonproductive cough
  • Dyspnea
• Untreated, mortality is approximately 100%.

Diagnosis of Pneumocystis jirovecii

• Diagnosis is based on microscopic examination of lung tissue biopsy or washings.
• Bilateral rales are heard on auscultation.
• Chest X-ray shows a ground-glass pattern.

Treatment of Pneumocystis jirovecii

• Most effective therapy is sulfamethoxazole and trimethoprim.
• This can also be used for prophylaxis.
• Other antifungal drugs are ineffective due to the absence of ergosterol in the cell wall.