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Fungal infections. Lobna AL Juffali,Msc. Introduction. Primary or “pathogenic” fungi that can cause disease in both healthy and immunocompromised individuals Histoplasmosis Coccidioidomycosis cryptococcosis Blastomycosis , paracoccidioidomycosis , sporotrichosis ,. Introduction.
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Fungal infections Lobna AL Juffali,Msc
Introduction Primary or “pathogenic” fungi that can cause disease in both healthy and immunocompromised individuals • Histoplasmosis • Coccidioidomycosis • cryptococcosis • Blastomycosis, • paracoccidioidomycosis, • sporotrichosis,
Introduction Fungi found only in immunocompromised host such as • Candida albicans, • Aspergillus spp., • Trichosporon, • Torulopsis • (Candida) glabrata, Fusarium, Alternaria, and Mucor
Factors that increase the risk of Fungal infections • Organ and bone marrow transplantation, • Cytotoxic chemotherapy, • The widespread use of indwelling IV catheters • The increased use of potent, broad-spectrum antimicrobial agents
HISTOPLASMOSIS • Histoplasmosis is caused by inhalation of dust-borne microconidia of the dimorphic fungus Histoplasmacapsulatum. • In the United States, most disease is localized along the Ohio and Mississippi river valleys.
Treatment • Asymptomatic or mildly ill patients and patients with sarcoid-like disease generally do not benefit from antifungal therapy. • Therapy may be helpful in symptomatic patients whose conditions have not improved during the first month of infection.
Treatment • Patients with mild, self-limited disease, chronic disseminated disease, or chronic pulmonary histoplasmosis who have no underlying immunosuppression can usually be treated with either oral ketoconazole or IV amphotericin B.
Traetment in AIDs Patients • Intensive 12-week primary (induction and consolidation therapy) • Amphotericin B should be administered in patients who require hospitalization. • Itraconazole 200 mg twice daily may be used to complete a 12-week course or for a full 12-week course in patients who do not require hospitalization • followed by lifelong suppressive (maintenance) therapy with itraconazole.
Treatment • Once the initial course of therapy for histoplasmosis is completed, lifelong suppressive therapy with oral azoles or amphotericin B (1 to 1.5 mg/kg weekly or biweekly) is recommended, because of the frequent recurrence of infection. • Relapse rates in AIDS patients not receiving preventive maintenance are 50% to 90%.
Blastomycosis • North American blastomycosis is a systemic fungal infection caused by Blastomycesdermatitidis. • Pulmonary disease probably occurs by inhalation conidia, which convert to the yeast forms in the lungs. • It may be acute or chronic and can mimic infection with tuberculosis, pyogenic bacteria, other fungi, or malignancy.
Blastomycosis • Blastomycosis can disseminate to virtually every other body organ, including skin, bones, and joints, or the genitourinary tract, without any evidence of pulmonary disease.
Clinical Presentation and Diagnosis • Acute pulmonary blastomycosis is generally an asymptomatic or self-limited disease characterized by fever, shaking chills, and a productive, purulent cough, with or without hemoptysis in immunocompetent individuals. • Sporadic pulmonary blastomycosis may present as a more chronic or subacute disease, with low-grade fever, night sweats, weight loss, and a productive cough resembling that of tuberculosis rather than bacterial pneumonia. • Chronic pulmonary blastomycosis is characterized by fever, malaise, weight loss, night sweats, and cough.
Diagnosis • direct microscopic visualization of the large, multinucleated yeast with single, broad-based buds in sputum or other respiratory specimens, following digestion of cells and debris with 10% potassium hydroxide. • Histopathologic examination of tissue biopsies and culture of secretions should be used to identify B. dermatitidis.
Treatment • All immunocompromised patients and patients with progressive disease or with extrapulmonary disease should be treated with antifungals.
Cryptococcosis • Cryptococcosis is a noncontagious, systemic mycotic infection caused by the ubiquitous encapsulated soil yeast Cryptococcus neoformans.
Clinical Presentation • Primary cryptococcosis in humans almost always occurs in the lungs. • Symptomatic infections are usually manifested by cough, rales, and shortness of breath that generally resolve spontaneously. • Disease may remain localized in the lungs or disseminate to other tissues, particularly the CNS, although the skin can also be affected.
Clinical presentation • In the non-AIDS patient, the symptoms of cryptococcal meningitis are nonspecific. Headache, fever, nausea, vomiting, mental status changes, and neck stiffness are generally observed. • In AIDS patients, fever and headache are common, but meningismus and photophobia are much less common than in non-AIDS patients.
Diagnosis • latex agglutination. C. • India ink smear of CSF and cultured in more than 96% of patients. • CSF • reveals an elevated opening pressure • CSF pleocytosis (usually lymphocytes), • leukocytosis, • a decreased CSF glucose, • an elevated CSF protein, • a positive cryptococcal antigen.
Treatment • For asymptomatic, immunocompetent persons with isolated pulmonary disease and no evidence of CNS disease, careful observation may be warranted. • With symptomatic infection, fluconazole or amphotericin B is warranted.
Treatment Cryptococcal meningitis • amphotericin B with flucytosine for 6 weeks • An alternative is amphotericin B for 2 weeks followed by fluconazole for an additional 8 to 10 weeks. • Suppressive therapy with fluconazole 200 mg/day for 6 to 12 months is optional.
HEMATOGENOUS CANDIDIASIS • Hematogenouscandidiasis describes the clinical circumstances in which hematogenous seeding to deep organs such as the eye, brain, heart, and kidney occurs • Candida is generally acquired via the GI tract, although organisms may also enter the bloodstream via indwelling IV catheters. • Immunosuppressed Patients are at high risk for invasive fungal infections
Clinical presentation • Three distinct presentations of disseminated C. albicans have been recognized: (1) the acute onset of fever, tachycardia, tachypnea, and occasionally chills or hypotension (similar to bacterial sepsis); (2) intermittent fevers; (3) progressive deterioration with or without fever; (4) hepatospleniccandidiasis manifested only as fever while the patient is neutropenic.
Treatment • Amphotericin B may be switched to fluconazole (IV or oral) for completion of therapy. • Azoles and deoxycholateamphotericin B are similarly effective; however, fewer adverse effects are observed with azoles. • Echinocandins are at least as effective as amphotericin B or fluconazole in nonneutropenic adult patients with candidemia. • In patients with an intact immune system, removal of all existing central venous catheters should be considered.
ASPERGILLUS INFECTIONS • Of more than 300 species of Aspergillus, three are most commonly pathogenic: A. fumigatus, A. flavus, and A. niger. • Aspergillosis is generally acquired by inhalation of airborne conidia that are small enough (2.5 to 3 mm) to reach the alveoli or the paranasal sinuses. • Superficial Infection Superficial or locally invasive infections of the ear, skin, or appendages can often be managed with topical antifungal therapy.
Allergic BronchopulmonaryAspergillosis • Allergic manifestations of Aspergillus range in severity from mild asthma to allergic bronchopulmonaryaspergillosis • characterized by severe asthma with wheezing, fever, malaise, weight loss, chest pain, and a cough productive of blood-streaked sputum.
treatment of Allergic BronchopulmonaryAspergillosis • Therapy is aimed at minimizing the quantity of antigenic material released in the tracheobronchial tree. • Antifungal therapy is generally not indicated in the management of allergic manifestations of aspergillosis, • Itraconazole 200 mg twice daily for 16 weeks resulted in reduced corticosteroid dose and improvement in exercise tolerance and pulmonary function
Aspergilloma • In the nonimmunocompromised host, Aspergillus infections of the sinuses • most commonly occur as saprophytic colonization (aspergillomas, or fungus balls)
Treatment • removal of the aspergilloma. • Therapy with glucocorticoids and surgery is generally successful. • Although IV amphotericin B is generally not useful in eradicating aspergillomas, intracavitary instillation of amphotericin B has been employed successfully in a limited number of patients.
Invasive Aspergillosis • Patients often present with classic signs and symptoms of acute pulmonary embolus: pleuritic chest pain, fever, hemoptysis, a friction rub, and a wedge-shaped infiltrate on chest radiographs. • Demonstration of Aspergillus by repeated culture and microscopic examination of tissue provides the most firm diagnosis. • In the immunocompromised host, aspergillosis is characterized by vascular invasion leading to thrombosis, infarction, and necrosis of tissue
Antifungal therapy should be instituted in any of the following conditions • persistent fever or progressive sinusitis unresponsive to antimicrobial therapy; (2) an eschar over the nose, sinuses, or palate; (3) the presence of characteristic radiographic findings, including wedge-shaped infarcts, nodular densities, or new cavitary lesions; or (4) any clinical manifestation suggestive of orbital or cavernous sinus disease or an acute vascular event associated with fever.
Treatment • Voriconazole is the drug of choice for primary therapy of most patients • amphotericin B second line • The lipid-based formulations may be preferred as initial therapy in patients with marginal renal function or in patients receiving other nephrotoxic drugs. • The optimal duration of treatment is unknown. • Caspofungin is indicated for treatment of invasive aspergillosis in patientswho are refractory to or intolerant of other therapies such as amphotericin B.