OPPORTUNISTIC MYCOSES

General Introduction
Opportunistic mycoses are fungal infections that occur primarily in
immunocompromised individuals. These infections have become more
prevalent with the rise of conditions such as HIV/AIDS, cancer treatments,
and organ transplants. Historically, the recognition of these infections has
paralleled advancements in medical treatments that compromise the
immune system.

Mycological Classification of Opportunistic Mycoses

Opportunistic mycoses are caused by a variety of fungi, which can be

classified into several groups:

- Aspergillosis: Caused by Aspergillus species.

- Candidiasis: Caused by Candida species.
- Cryptococcosis: Caused by Cryptococcus species.
- Mucormycosis: Caused by Mucorales fungi.
- Pneumocystis pneumonia: Caused by Pneumocystis jirovecii.

I. Aspergillosis
1. Introduction and History

Aspergillosis is an infection caused by Aspergillus species, commonly

found in the environment, particularly in soil, decaying vegetation, and
dust. The disease primarily affects immunocompromised individuals, such
as those undergoing chemotherapy, organ transplants, or with chronic
granulomatous disease. The first documented case of aspergillosis dates
back to the early 19th century, but it became more prominent with the
advent of modern immunosuppressive therapies.

2. Mycological Classification

Aspergillus is a genus of molds consisting of several species, with the most

common pathogenic ones being:

Aspergillus fumigatus

Aspergillus flavus

Aspergillus niger

Aspergillus terreus

These species are classified based on their morphological characteristics

and genetic sequencing.

3. Clinical Manifestation
Aspergillosis can present in various forms depending on the site of
infection:

Allergic Bronchopulmonary Aspergillosis (ABPA): Characterized by

asthma-like symptoms, wheezing, and pulmonary infiltrates.

Chronic Pulmonary Aspergillosis (CPA): Symptoms include chronic

cough, hemoptysis, and weight loss.

Invasive Aspergillosis: Affects immunocompromised patients, leading to

fever, chest pain, and respiratory distress. It can disseminate to other
organs, causing severe complications.

4. Pathophysiology

Inhaled Aspergillus spores (conidia) reach the alveoli, where they can
germinate and form hyphae. In immunocompetent individuals, these
spores are cleared by the immune system. However, in
immunocompromised patients, the spores can evade the immune
response, leading to tissue invasion and necrosis. The hyphae can invade
blood vessels, causing thrombosis and dissemination to other organs.

5. Laboratory Diagnosis

Microscopy and Culture: Sputum, bronchoalveolar lavage, or tissue

biopsy samples are examined under a microscope and cultured to identify
Aspergillus species.

Galactomannan Antigen Test: Detects Aspergillus antigens in blood or

bronchoalveolar lavage fluid.

PCR: Used to detect Aspergillus DNA in clinical samples.

Histopathology: Tissue biopsy showing septate hyphae with acute-angle

branching is indicative of Aspergillus infection.

6. Treatment of Aspergillosis

Invasive Aspergillosis

Voriconazole: The first-line treatment for invasive aspergillosis. It has

shown superior efficacy compared to deoxycholate amphotericin B (D-
AMB) in clinical trials.

Liposomal Amphotericin B (L-AMB): An alternative primary therapy,

especially for patients who cannot tolerate voriconazole.

Salvage Therapy: Includes lipid formulations of amphotericin (LFAB),

posaconazole, itraconazole, caspofungin, or micafungin.

Chronic Pulmonary Aspergillosis (CPA)

Itraconazole: Often used for long-term management of CPA.

Voriconazole: Another option for chronic cases.

Surgical Intervention: May be necessary to remove fungal masses or

necrotic tissue.

Allergic Bronchopulmonary Aspergillosis (ABPA)

Corticosteroids: To reduce inflammation and immune response.

Itraconazole: Used to reduce fungal load and prevent exacerbations.

7. Prevention and Control

Environmental Control

HEPA Filters: Use in high-risk areas to reduce exposure to Aspergillus

spores.

Avoiding Construction Sites: Immunocompromised individuals should

avoid areas with high levels of dust and mold spores.

Prophylactic Antifungals

Voriconazole or Posaconazole: Administered to high-risk patients, such

as those undergoing bone marrow transplants or with prolonged
neutropenia.

Monitoring and Early Detection

Regular Screening: For Aspergillus antigens in immunocompromised

patients to detect infections early.

II. Candidiasis
1. Introduction and History

Candidiasis is an infection caused by Candida species, which are yeast-like

fungi. Candida is part of the normal flora of the skin, mouth, gut, and
vagina but can cause infections when the host’s immune system is
compromised or the normal flora is disrupted. The most common species
causing infection is Candida albicans. The recognition of Candida as a
pathogen dates back to the early 20th century, with increased incidence
noted in patients with HIV/AIDS and those undergoing immunosuppressive
therapies.

2. Mycological Classification

Candida species are classified based on their morphological and genetic

characteristics. The most common pathogenic species include:
Candida albicans

Candida glabrata

Candida parapsilosis

Candida tropicalis

Candida krusei

These species can be identified through culture and molecular techniques.

3. Clinical Manifestation

Candidiasis can present in various forms depending on the site of

infection:

Oral Candidiasis (Thrush): White patches on the tongue, inner cheeks,

and throat.

Esophageal Candidiasis: Painful swallowing and retrosternal pain.

Vulvovaginal Candidiasis: Itching, discharge, and discomfort.

Invasive Candidiasis: Fever, chills, and sepsis, particularly in

hospitalized patients.

4. Pathophysiology

Candida species can adhere to and invade mucosal surfaces, forming

biofilms that protect them from the host immune response and antifungal
treatments. In immunocompromised individuals, Candida can disseminate
through the bloodstream, leading to systemic infections. The ability of
Candida to switch between yeast and hyphal forms is crucial for its
pathogenicity.

5. Laboratory Diagnosis

Microscopy and Culture: Samples from infected sites are examined

under a microscope and cultured to identify Candida species.

PCR: Used to detect Candida DNA in clinical samples.

Beta-D-Glucan Assay: Detects fungal cell wall components in the blood,

indicative of invasive candidiasis.

Germ Tube Test: Used to identify Candida albicans by its ability to form
germ tubes in serum.

6. Treatments

Fluconazole: Commonly used for mucosal and systemic candidiasis.

Echinocandins: Such as caspofungin, used for invasive candidiasis.

Amphotericin B: Used for severe or resistant infections.

Topical Antifungals: Such as clotrimazole for oral and vulvovaginal

candidiasis.

7. Prevention and Control

Good Hygiene: Regular handwashing and oral care.

Antifungal Prophylaxis: In high-risk patients, such as those undergoing

chemotherapy or organ transplants.

Minimizing Invasive Procedures: Reducing the use of catheters and

other invasive devices.

Diet and Lifestyle: Maintaining a balanced diet and avoiding excessive

use of antibiotics.

III. Cryptococcosis
1. Introduction and History

Cryptococcosis is an infection caused by the encapsulated yeast

Cryptococcus neoformans and Cryptococcus gattii. These fungi are found
in soil contaminated with bird droppings and in decaying wood.
Cryptococcosis primarily affects immunocompromised individuals, such as
those with HIV/AIDS, but can also occur in immunocompetent hosts. The
disease was first described in the late 19th century, with significant
advancements in understanding its pathogenesis and treatment occurring
in the 20th century.

2. Mycological Classification

Cryptococcus species are classified based on their morphological

characteristics and genetic sequencing. The main pathogenic species are:

Cryptococcus neoformans: Commonly affects immunocompromised

individuals.

Cryptococcus gattii: More likely to infect immunocompetent individuals

and is associated with eucalyptus trees.

3. Clinical Manifestation

Cryptococcosis can present in various forms depending on the site of

infection:

Pulmonary Cryptococcosis: Symptoms include cough, chest pain, and

shortness of breath.

Cryptococcal Meningitis: The most severe form, presenting with

headache, fever, neck stiffness, and altered mental status.

Cutaneous Cryptococcosis: Skin lesions that can resemble molluscum

contagiosum or cellulitis.
 4. Pathophysiology

Cryptococcus species are inhaled into the lungs, where they can cause
localized infection or disseminate to other parts of the body. The yeast’s
polysaccharide capsule is a major virulence factor, helping it evade the
host immune response. In immunocompromised individuals, the fungus
can cross the blood-brain barrier, leading to meningitis. The ability to
survive and replicate within macrophages also contributes to its
pathogenicity.

5. Laboratory Diagnosis
India Ink Staining: Used to visualize the encapsulated yeast in
cerebrospinal fluid (CSF).

Cryptococcal Antigen Test: Detects cryptococcal polysaccharide antigen

in blood or CSF.

Culture: Samples from CSF, blood, or respiratory secretions are cultured

to identify Cryptococcus species.

Histopathology: Tissue biopsy showing encapsulated yeast cells.

6. Treatments

Amphotericin B and Flucytosine: The initial treatment for cryptococcal

meningitis.

Fluconazole: Used for consolidation and maintenance therapy after initial

treatment.

Liposomal Amphotericin B: An alternative for patients who cannot

tolerate conventional amphotericin B.

7. Prevention and Control

Avoiding Exposure: Immunocompromised individuals should avoid areas

contaminated with bird droppings.

Antifungal Prophylaxis: In high-risk patients, such as those with

advanced HIV/AIDS.

Early Detection and Treatment: Regular screening for cryptococcal

antigen in high-risk populations.

IV. Mucormycosis
1. Introduction and History

Mucormycosis, also known as zygomycosis, is a serious fungal infection

caused by a group of molds called Mucorales. These fungi are ubiquitous
in the environment, particularly in soil and decaying organic matter.
Mucormycosis primarily affects immunocompromised individuals, such as
those with uncontrolled diabetes, hematologic malignancies, or those
undergoing organ transplants. The disease was first described in the late
19th century, with significant outbreaks noted during the COVID-19
pandemic among patients with severe COVID-19 and diabetes.

2. Mycological Classification

Mucorales is an order of fungi within the class Zygomycetes. The most

common genera causing mucormycosis include:

Rhizopus
Mucor

Rhizomucor

Lichtheimia (formerly Absidia)

Cunninghamella

These fungi are identified based on their morphological characteristics and

genetic sequencing.

3. Clinical Manifestation

Mucormycosis can present in various forms depending on the site of

infection:

Rhinocerebral Mucormycosis: Involves the sinuses and brain,

presenting with facial pain, nasal congestion, black lesions on the nasal
bridge or upper inside of the mouth, and fever.

Pulmonary Mucormycosis: Symptoms include fever, cough, chest pain,

and shortness of breath.

Cutaneous Mucormycosis: Presents with necrotic skin lesions, often

following trauma or surgery.

Gastrointestinal Mucormycosis: Symptoms include abdominal pain,

gastrointestinal bleeding, and perforation.

Disseminated Mucormycosis: Occurs when the infection spreads to

other organs, such as the brain, spleen, and heart.

4. Pathophysiology

Mucorales spores are inhaled or enter the body through skin breaks. In
immunocompromised individuals, the spores germinate and form hyphae
that invade blood vessels, causing thrombosis and tissue necrosis. The
fungi’s ability to invade blood vessels is a key factor in its pathogenesis,
leading to rapid tissue destruction and dissemination to other organs.
 5. Laboratory Diagnosis

Microscopy and Culture: Tissue biopsy samples are examined under a

microscope and cultured to identify Mucorales species.

Histopathology: Tissue biopsy showing broad, non-septate hyphae with

right-angle branching is indicative of mucormycosis.

PCR: Used to detect Mucorales DNA in clinical samples.

Imaging: CT or MRI scans can help identify the extent of infection,

particularly in rhinocerebral and pulmonary mucormycosis.

6. Treatments

Amphotericin B: The first-line treatment for mucormycosis.

Posaconazole and Isavuconazole: Used as alternative or adjunctive

therapies.

Surgical Debridement: Essential to remove necrotic tissue and reduce

fungal load.

Management of Underlying Conditions: Controlling diabetes and

reducing immunosuppression when possible.

7. Prevention and Control

Environmental Control: Reducing exposure to soil and decaying organic
matter, particularly for immunocompromised individuals.

Good Hygiene: Regular handwashing and wound care.

Antifungal Prophylaxis: In high-risk patients, such as those undergoing

hematopoietic stem cell transplants.

Early Detection and Treatment: Prompt recognition and treatment of

mucormycosis in high-risk patients.mycoses-uncommon-types.

V. Pneumocystis Pneumonia (PCP)

1. Introduction and History
Pneumocystis pneumonia (PCP) is a serious infection caused by the fungus Pneumocystis
jirovecii. This organism was previously classified as a protozoan but is now recognized as a
fungus. PCP primarily affects immunocompromised individuals, such as those with
HIV/AIDS, cancer, or those undergoing immunosuppressive treatments. The disease was first
described in the early 20th century, with significant outbreaks occurring among malnourished
infants and later among HIV/AIDS patients in the 1980s.
2. Mycological Classification
Pneumocystis jirovecii is classified within the fungal kingdom, although it has unique
characteristics that differentiate it from other fungi. It does not grow in standard fungal
cultures and requires specialized staining techniques for identification.
3. Clinical Manifestation
PCP typically presents with respiratory symptoms, including:
Fever
Dry Cough
Shortness of Breath
Fatigue
Chest Discomfort
In severe cases, it can lead to respiratory failure and death if not promptly treated.
4. Pathophysiology
Pneumocystis jirovecii is inhaled into the lungs, where it attaches to the alveolar epithelial
cells. The fungus proliferates within the alveoli, causing inflammation and damage to the
alveolar-capillary barrier. This leads to impaired gas exchange and hypoxemia. The host
immune response, particularly in immunocompromised individuals, is insufficient to clear the
infection, resulting in persistent and progressive lung damage.
 5. Laboratory Diagnosis
Microscopy: Sputum, bronchoalveolar lavage (BAL) fluid, or lung biopsy samples are
stained with special stains (e.g., Giemsa, Gomori methenamine silver) to visualize
Pneumocystis organisms.
PCR: Used to detect Pneumocystis DNA in clinical samples.
Beta-D-Glucan Assay: Detects fungal cell wall components in the blood, indicative of PCP.
Chest X-ray or CT Scan: Imaging studies often show diffuse bilateral interstitial infiltrates,
which are characteristic of PCP.
6. Treatments
Trimethoprim-Sulfamethoxazole (TMP-SMX): The first-line treatment for PCP.
Pentamidine: An alternative for patients who cannot tolerate TMP-SMX.
Corticosteroids: Used in severe cases to reduce inflammation and improve oxygenation.
Adjunctive Oxygen Therapy: May be necessary for patients with significant hypoxemia.
7. Prevention and Control
Prophylactic TMP-SMX: Administered to high-risk patients, such as those with HIV/AIDS
with low CD4 counts or those undergoing immunosuppressive treatments.
Regular Monitoring: For early detection and treatment of PCP in high-risk populations.
Good Hygiene and Infection Control Practices: To reduce the risk of exposure and
transmission.
Conclusion
Opportunistic mycoses are a significant concern in immunocompromised individuals, leading
to severe infections that can be challenging to diagnose and treat. These infections, caused by
various fungal species such as Aspergillus, Candida, Cryptococcus, Mucorales, and
Pneumocystis jirovecii, highlight the importance of understanding their pathophysiology,
clinical manifestations, and appropriate management strategies.
Summary :
Aspergillosis : Primarily affects the lungs but can disseminate in immunocompromised
patients. Early diagnosis and treatment with antifungals like voriconazole are crucial.
Candidiasis : Can range from superficial infections to life-threatening systemic infections.
Management includes antifungals such as fluconazole and echinocandins.
Cryptococcosis : Often presents as meningitis in immunocompromised individuals.
Treatment involves amphotericin B and flucytosine, followed by fluconazole.
Mucormycosis : A rapidly progressing infection requiring prompt surgical intervention and
antifungal therapy with amphotericin B.
Pneumocystis Pneumonia (PCP) : A common cause of pneumonia in HIV/AIDS patients,
treated with TMP-SMX and corticosteroids in severe cases.