Clinical Mycology Lec 5 - Copy PDF

Lec (4) ASPERGILLOSIS Dr. Wifag Rabih Aspergillosis Aspergillosis is a spectrum of diseases of humans and animals caused by members of the genus Aspergillus. The symptoms – fever, a cough, chest pain, or breathlessness occur in many other illnesses so diagnosis can be hard. Usually, only patients wi...

Lec (4) ASPERGILLOSIS Dr. Wifag Rabih Aspergillosis Aspergillosis is a spectrum of diseases of humans and animals caused by members of the genus Aspergillus. The symptoms – fever, a cough, chest pain, or breathlessness occur in many other illnesses so diagnosis can be hard. Usually, only patients with already weakened immune systems or who suffer from other lung conditions are susceptible. Similar to Candida they rarely infect a normal host. They can even grow in disinfectant. There are more than one hundred species of aspergilli. The most common etiologic agents of aspergillosis : Aspergillus fumigatus A. niger A. flavus Aspergillus Conidia Conidiogenous cells (phialides) Supporting cell (branch or metulae) Swollen apex of conidiophore (vesicle) Conidiophore Basal part of conidiophore (foot cell) The genus Aspergillus - importance to humanity on the negative side: cause invasive and allergic disease in humans and other animals: A. fumigatus cause plant and food spoilage and produce mycotoxins: A. flavus and A. parasiticus The genus Aspergillus - importance to humanity on the positive side: well-established model organism in cell biology and genetics: A. nidulans food production: enzymes and organic acids: A. niger East Asian foods: A. oryzae and A. sojae pharmaceuticals: lovastatin: A. terreus fumagillin: A. fumigatus Immunosuppression and infection Inhalation of aspergillus spores is a common daily occurrence. A healthy immune system would normally remove the spores and no symptoms or infection would occur. In individuals whose immune system may be suppressed either because of illness eg AIDS, cancer patients or drugs, spores may germinate and resulting tissue or systemic aspergillus invasion can result. Individuals with allergies such as asthma, can also be vulnerable to aspergillus disease. Sources of Infection? ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Aspergillus species are found in : Soil Air; spores may be inhaled Water / storage tanks in hospitals etc Food Compost and decaying vegetation Fire proofing materials Bedding, pillows Ventilation and air conditioning systems Computer fans Aspergillosis These disease include: (1) Mycotoxicosis due to ingestion of contaminated foods A. flavus and A. parasiticus (2) Allergy to the presence of conidia of the organism Aspergillus fumigatus and Aspergillus clavatus. (3) Colonization without extension in preformed cavities 4) Invasive, Inflammatory, granulomatous, necrotizing disease of lungs, and other organs; Aspergillus fumigatus and Aspergillus flavus. (5) Systemic and fatal disseminated disease. (rarely ) Aspergillus Life-cycle Spores inhaled Mass of hyphae (plateau phase) Germination Hyphal elongation and branching Pulmonary aspergillosis There are three clinical types of pulmonary aspergillosis: Allergic - hypersensitivity to the organism. Symptoms may vary from mild respiratory distress to alveolar fibrosis. Aggressive tissue invasion. Primarily a pulmonary disease, but the aspergilli may disseminate to any organ. They may cause endocarditis, osteomyelitis, otomycosis and cutaneous lesions. Fungus ball or Pulmonary Aspergilloma which is characteristically seen in the old cavities of TB patients. This is easily recognized by x-ray, because the lesion (actually a colony of mold growing in the cavity) is shaped like a half-moon (semi-lunar growth). The patients may cough up the fungus elements because the organism frequently invades the bronchus. Chains of conidia can sometimes be seen in the sputum. Spergillosis affect different groups of people. Allergic bronchopulmonary aspergillosis (ABPA) most often occurs in people who have cystic fibrosis or asthma. Aspergillomas usually affects people who have other lung diseases like tuberculosis. Also called a “fungus ball.” Chronic pulmonary aspergillosis typically occurs in people who have other lung diseases, including tuberculosis, chronic obstructive pulmonary disease (COPD) Invasive aspergillosis affects people who have weakened immune systems, such as people who have had a stem cell transplant or organ transplant, are getting chemotherapy for cancer, or are taking high doses of corticosteroids. Laboratory diagnosis A tissue biopsy, respiratory secretion (sputum) For microscope, or fungal culture. A blood test can help diagnose invasive aspergillosis early in people who have severely weakened immune systems. Culture: Aspergilli require 1-3 weeks for growth. Histopathology: The septate hyphae are wide and form dichotomous branching, i.e., a single hypha branch into two even hyphae, and then the mycelium continues Serology: There is an excellent serological test for aspergillosis which is an Immunodiffusion test ( ELISA). i.e., tissue invasion.( detection of IgG and IgE). Polymerase chain reaction PCR Imaging test ( A chest X-ray, CT scan) Asergillosis A. niger A.fugimatus Gomori methenamine silver (GMS) stained tissue section of lung showing dichotomously branched, septate hyphae of Aspergillus fumigatus Treatment for Aspergillosis Oral corticosteroid drugs: Solid or liquid oral medications may be prescribed to treat allergic bronchopulmonary aspergillosis. (prednisone, prednisolone, and methylprednisolone) Antifungal drugs: These medications are generally used to treat invasive pulmonary aspergillosis. Voriconazole is currently the drug of choice because it causes fewer side effects and appears to be more effective than other medications. Amphotericin B or itraconazole. Caspofungin is sometimes used in cases where the infection is resistant to other antifungals. Surgery: Surgery may be necessary in cases when aspergillomas are present and cause serious problems, such as excessive bleeding. Antifungal medications are usually not effective against aspergillomas, so surgery is recommended. Embolization may be an option to block blood flow to the artery supplying blood to the lung cavity where the fungus ball is located. This will stop the bleeding, but it may recur later. Cryptococcosis Cryptococcosis Chronic , sub acute to acute pulmonary, systemic or meningitic disease, initiated by the inhalation of the fungus C. neoformans the major pathogenic member of the genus. (An encapsulated yeast) Primary pulmonary infections have no diagnostic symptoms and are usually subclinical. On dissemination, the fungus usually shows spreading to the central nervous system, however skin, bones and other visceral organs may also become involved. Cryptococcosis ◦ Found worldwide in soil contaminated by bird droppings (chickens and pigeons), roosting sites, and rotting vegetation ◦ Cryptococcus can be found in the pigeon GI tract ◦ Infection via ingestion of contaminated vegetation Increasing proportions of patients have an underlying immune deficiency. ◦ HIV/AIDS ◦ CD 4 < 200 ◦ Prolonged steroid therapy ◦ Organ transplantation and Malignancy Life cycle of C.neofromans Pathogenesis Enters through lungs - inhalation of Basidiospores of C.neoformans. Can infect normal humans Enters deep into the lungs, Men acquire more infections, and women are less infected. Self-limiting in most cases, Pulmonary infections can occur. Present as discrete nodules – Cryptococcoma. Abnormalities of T lymphocyte function. In AIDS 3- 20% develop Cryptococcosis. Treatment reduces the morbidity and cure in non-immune suppressed expected. Can mimic Tuberculosis Clinical Manifestations Pulmonary cryptococcosis ◦ Asymptomatic carriage may occur in healthy people as well as those with chronic lung disease CNS disease ◦ Meningitis (85%), meningoencephalitis, cryptococcoma ◦ Generally symptoms are more insidious and of longer duration in the nonimmunosuppressed Cutaneous cryptococcosis ◦ Ulcerated or nodular lesions – usually portend poor prognosis in disseminated disease ◦ cellulitis Bone and joint disease, Ocular cryptococcosis and Genitourinary disease Laboratory diagnosis 1. Direct microscopic examination of sputum and CSF after staining with India ink, reveals a large gelatinous capsule around budding yeast cells. 2. Culture on SDA without acidione , at 20-37 shows mucoid colonies. Creamy, white, yellow Brown colored which are identified by India ink staining. 3. A simple urease test helps in confirming the isolate. 4. Capsular antigens are detected in CSF by using anticapsular antibodies in a latex agglutination test. 5. Antibodies are detected in patient’s sera Treatment CNS disease is uniformly fatal Immunocompromised patients need long-term suppressive therapy unless their immune status substantially recovers ◦ Amphotericin B 0.5-0.7 mg/kg/d + flucytosine 100-150 mg/kg/d for 6 weeks followed by fluconazole 400 mg/d for 3-6 months In HIV/AIDS most switch early to oral therapy, or use high-dose oral fluconazole from the outset if the mild disease Fungal Infections in Immunosuppressed Patients Fungal infections are important causes of morbidity and mortality in humans. Some fungal infections are endemic, caused by fungi that are present in the environment and whose spores enter humans. Other fungal infections are said to be opportunistic because the causative agents cause mild or no disease in healthy individuals but may infect and cause severe disease in immunodeficient persons. The human airway is continuously open to the nonsterile environment where fungal spores have the potential to reach lung tissue and produce disease. In the immunocompromised host, many fungi, including species of fungi typically considered nonpathogenic, have the potential to cause serious morbidity and mortality. Over the last several decades the advent of the human immunodeficiency virus (HIV) epidemic and the increasing use of immunosuppressive drugs for serious medical conditions have increased the number of persons who are severely immunocompromised. In addition, the range and diversity of fungi that cause disease have broadened. more aggressive cancer and post-transplantation chemotherapy and the use of antibiotics, cytotoxins, immunosuppressives, and corticosteroids. That results in lowered resistance of the host allowing fungi to invade tissues and produce pathological changes that can cause death. Common invasive pulmonary mycoses in HIV patients: Cryptococcosis, Pneumocystis, pneumonia-histoplasmosis, Blastomycosis, coccidioidomycosis, and Aspergillosis Candida and Aspergillus species continue to be the fungal pathogens that most frequently cause invasive fungal disease in immunocompromised persons. Worldwide deaths from Candida, Aspergillus, Pneumocystis, and Cryptococcus infections are estimated to exceed 1.4 million annually with individual patient mortality rates in excess of 30%.overall, infections due to previously uncommon hyaline and dematiaceous filamentous fungi are being reported with increasing frequency. Infections caused by opportunistic fungal infections continue to be associated with high morbidity, high mortality, and poor patient outcomes. The principal mediators of innate immunity against fungi are neutrophils and macrophages. Patients with neutropenia are extremely susceptible to opportunistic fungal infections. Candida infections often start at mucosal surfaces, and cell-mediated immunity is believed to prevent spread of the fungi into tissues. T helper cell (CD4) responses are protective in intracellular fungal infections, such as histoplasmosis, but these responses may elicit granulomatous inflammation, which is an important cause of host tissue injury in these infections. Improved diagnostic methods have been developed for an early diagnostic of opportunistic mycosis in order to control the disease and save more lives. An 8-year-old Immunocompromised Boy With Disseminated Fungal Infection Oral Thrush and HIV THANK YOU