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Transcript of Systemic Mycoses.
Raed Alharbi Systemic Mycoses Objectives -Background of Systemic Mycoses.
-Blastomyces dermatitidis (Blastomycosis).
-Paracoccidioides brasiliensis (Paracoccidiodomycosis).
-Histoplasma capsulatum (Histoplasmosis).
-Questions for the class (case study). Systemic mycoses refer to fungal infections affecting the internal organs.
The fungi have the ability to enter the body through the lungs, the gut, the paranasal sinuses or the skin. Systemic Mycoses Most infections tend to originate in the respiratory tract and the fungi can then spread through the bloodstream to multiple organs including the skin, often causing multiple organs to fail and eventually resulting in the death of the patient. Systemic Mycoses Patients who are immunocompromised are more predisposed to systemic mycoses, but these infections can also develop in otherwise healthy patients.
While potentially life threatening, most infections tend to go unrecognized, and occur as asymptomatic or sub-clinical infections.
Of those that manifest symptoms, most occur as mild or acute self limiting disease. Only in rare situations, does disseminated, invasive, and progressive infection occur. Systemic Mycoses Causative agents:
Coccidioides Systemic Mycoses Causative agent of Blastomycosis Blastomyces dermatitidis -At 25C on Sabouraud’s dextrose agar (4days)
A fluffy white cob-web aerial mycelium and glabrous, tan, non-sporulating colonies
-At 37C on blood agar (5days)
Colonies are wrinkled and folded, glabrous and white prickly yeast like
Hyaline, ovoid to pyriform, one celled,
smooth walled conidia (2-10um) Parasitic Phase large, broad-base, unipolar budding yeast-like Brain heart infusion agar with 10% sheep blood, gentamycin, and chloramphenicol At 25C° Saprobic
Phase Macro Micro Morphology -A systemic fungal infection.
-1894- first described by Gilchrist in USA.
-Common infections among dogs in endemic area.
-Caused by inhalation of aerosolized conidia from moist soil.
-Half of people how are infected will show symptoms.
-Symptoms appear from 3 to 15 weeks after exposure Blastomycosis 1- Blastomyces dermatitidis exists as mold with septate aerial hyphae. The hyphae produce conidial spores
2- These spores are either inhaled, or inoculated into the skin
3- The warmer temperature (37C) inside the host signals a transformation
4- formation of broad-based budding yeast. The yeast may continue to colonize the lungs or disseminate in the bloodstream
5- other parts of the body, such as the skin, bones and joints, organs, and central nervous system may be effected -Flu like symptoms
fever, chills, cough, muscle aches, joint pain, and chest pain.
resembling bacterial pneumonia
high fever, productive cough and pleuritic chest pain.
Mimic tuberculosis and lung cancer. Signs & Symptoms Direct microscopy
Yeasts, 8-20 micrometers in size, with single, broad-based buds, double refractile walls, and multiple nuclei.
-The yeast forms are visualized with a periodic acid-Schiff (PAS) stain
showed an oval conidia borne laterally on branching hyphae Diagnosis Antifungal medicine
-Itraconazole (drugs of choice)
-Posaconazole Treatment -Dimorphic fungal pathogen.
Found in soil with organic debris (rotting woods and animals droplet)
-Found in the mid-West and North of USA.
Endemic in Ohio and Mississippi River Valley region.
-Causative agent of Blastomycosis.
-In nature (25C°)
-In Human body (37C°)
-Yeast. 15-20 micron Blastomyces dermatitidis Paracoccidioides brasiliensis -Kingdom: Fungi
-Only one species in the Paracoccidioides genus, however there are several genetically isolated cultures.
-Also called: Brazilian blastomycosis, South American blastomycosis, Lutz-Splendore-de Almeida disease and Paracoccidioidal granuloma Taxonomy Cultured on SABHI (Sabouraud Dextrose with Brain Heart Infusion Agar)
-At room temperature (20-26oC), colonies are filamentous, slow growing, leathery, flat to wrinkled, woolly, cottony or glabrous to velvety. The colony matures and its diameter reaches 1 to 2 cm in 2 to 3 weeks. The front color is white cream, tan or brown and the reverse color is yellowish brown to brown.
-At 37oC (SABHI with blood), colonies are waxy, wrinkled, heaped or folded and cream to tan in color.
-Mold to yeast conversion usually occurs in 3 to 7 days Macroscopic -Thermally dimorphic, mold at 25oC and yeast at 37oC.
-Molds (25oC) - hyphae display intercalary and terminal chlamydoconidia from room temperature tease mounts. Arthroconidia may form.
-Yeasts (37oC) – large, thick walled, multiple budding yeast cells with narrow necks where the daughter cells attach. (Ship’s wheel) Microscopic Paracoccidioides brasiliensis is the agent of systemic mycosis called paracoccidioidomycosis.
-Wide spectrum of the disease; varying from asymptomatic infection to sub-clinical, symptomatic or chronic infection
-Pulmonary paracoccidioidomycosis - acute and chronic, lesions are similar to tuberculosis
-Mucocutaneous paracoccidioidomycosis -– ulcerated lesions of the gums, tongue, lips or palate
-Perforations of the palate and nasal septum can occur.
-Lymphonodular paracoccidioidomycosis -– cervical and submandibular chains and may progress to abscesses on the lymph nodes with draining sinuses.
-Visceral paracoccidioidomycosis –- lesions of the small or large intestine, hepatic (liver) lesions, adrenal gland destruction, osteomyelitis (bone infection), arthritis, endophthalmitis (inflammation of the internal components of the eye) and meningoencephalitis (inflammation of the meninges and brain) or focal cerebral lesions Pathogenicity -Diagnosis is difficult as it possibly has a long latent period.
-Transmission is thought to be mainly by inhalation of the conidia.
-Transmission of chewing on or consuming contaminated vegetable matter occurs less frequently.
-Death can occur from disseminated disease or malnourishment from inability to eat, within 2-3 years Pathogenicity cont. -Specimens for culture and direct microscopy- skin scrapings, sputum and bronchial washings, cerebrospinal fluid, pleural fluid and blood, bone marrow, and tissue biopsies from various visceral organs.
-Skin scrapings should be examined using 10% KOH and Parker ink or calcofluor white mounts.
-Exudates and body fluids should be centrifuged and the sediment examined using either 10% KOH and Parker ink or calcofluor white mounts.
-Tissue sections should be stained using PAS digest, Grocott's methenamine silver (GMS) or Gram stain Diagnosis -Culture
-Clinical specimens should be inoculated onto primary isolation media SABHI (Sabouraud's dextrose agar and Brain Heart Infusion Agar supplemented with 5% sheep blood) Diagnosis cont. -Primarily trimethoprim plus sulfamethexazole.
-Oral itraconazole (Sporonox) is the drug of choice as it is relatively inexpensive and available in the endemic areas.
-Intravenous amphotericin B is used for severe cases. Treatment -Paracoccidioides has been isolated from soil and from the digestive tract of some animals (guinea pig, porcupine, raccoon and armadillos), but its natural habitat is unknown.
-Epidemiology is not fully understood.
-Almost exclusively found in Central and South America, primarily Argentina, Brazil, Venezuela, Peru and Columbia. Geographic distribution
S1, PS2, PS3 and Pb01-like represent genetically isolated clusters Intracellular mycotic infection
Caused by inhalation of airborne spores from soil contaminated with bird or bat dung, direct inoculation (mucocutaneous) or from organ transplant
Worst cases seen among immunosuppressed, children less than 2, elderly and people exposed to very large inoculum
Most common in central Mississippi, southern and Ohio river valleys. Also found in Africa Histoplasmosis Histoplasma capsulatum Dimorphic fungi
Primary cause of histoplasmosis
Two forms- var. duboisii, and var. capsulatum -Intracellular mycotic infection.
-Caused by inhalation of airborne spores from soil contaminated with bird or bat dung, direct inoculation (mucocutaneous) or from organ transplant.
-Worst cases seen among immunosuppressed, children less than 2, elderly and people exposed to very large inoculum.
-Most common in central Mississippi, southern and Ohio river valleys. Also found in Africa Histoplasmosis -Disease can vary from acute benign pulmonary infection to a chronic pulmonary or fatal disseminated disease.
-Lungs primarily involved but also reticuloendothelial system (RES) in disseminated cases.
-Chronic Pulmonary- Radiologic presentations include a Ghon complex suggestive of tuberculosis, histoplasmoma, and cavitary disease.
-Disseminated – Specific to organs Pathogenicity and Clinical presentation Tissue Sections Gomori Methen-amine Silver (GMS) stain Hematoxylin and eosin tissue section -Treatment varies by which form of histoplasmosis acquired.
-Acute pulmonary- Amphotericin B +/- corticosteroids, follow by Itraconazole for a total of 6-12 weeks of therapy.
-Chronic pulmonary- Amphotericin B followed by Itraconazole for a total of 12-24 months.
-Disseminated in AIDS patients- Amphotericin B followed by Itraconazole for life.
-Disseminated in non-AIDS patients- Amphotericin B followed by Itraconazole for a total of 12 weeks Treatment -25oC – Slow growing and granular to cottony.
-Front- Color is white initially and usually becomes buff brown.
-Reverse- A yellow or yellowish orange color may be observed
37oC – Slow growing, creamy and moist. Macroscopic features -25oC – Hyphae are septate and hyaline.
-Produce hyphae-like conidiophores which arise at right angles to the parent hyphae.
-Macro and micro conidia are present.
-Macro- Thick walled, round, unicellular, hyaline, large and often have fingerlike projections.
-Micro- Unicellular, hyaline and round, w/smooth or rough wall.
-37oC – Budding yeast are narrow-based, ovoid and roughly 2-4 µm in var. capsulatum, and 12-15 µm in var. duboisii Microscopic features Coccidioides -There are two species of the genus Coccidioides;
-Coccidioides sp are identical in their morphology features but different genetically.
-Coccidioides immitis/posadasii is usually seen in the soil at warm and dry areas with low rain fall and high summer temperatures.
-The causative agents of the disease Coccidioidomycosis (Valley Fever).
-In 1890s, the first cases of Valley Fever were recognized.
-Coccidioides species were recognized in 1937. -Macroscopic Features
Colonies grow fast.
On Sabouraud’s dextrose agar ;
-Grayish Later White and cottony aerial mycelium.
-With age, colonies turn to brown color. Coccidioides- Morphology -Microscopic Features
-Barrel-shaped. Coccidioides- Morphology -Microscopic Feature
-Filled with endospores Coccidioides- Morphology Spherule phase (tissue phase) Mycelial phase Life cycle of Coccidioides The initial infection of Valley Fever may appear as an acute pulmonary infection. Coccidioidomycosis (Valley fever) -Five major clinical manifestations are associated with coccidioidomycosis;
1- Acute pneumonia.
-This manifestation is included as one of the community-acquired pneumonias.
- Several cutaneous abnormalities such as erythema multiform, toxic erythema, and erythema nodosum may occur. Clinical Manifestations 2- Chronic progressive pneumonia
-Occurs when the acute pneumonia patients still have the disease for more than 3 months.
-Symptoms : production of sputum, insistent coughing, weight loss, and hemoptysis.
3- Pulmonary nodules and cavities
-Nodules or cavities may develop alone after infiltrates of the initial coccidioidal pneumonia resolve.
-Diagnosis can be done by using a serologic test, which shows positive results in 30% to 60% of the coccidioidal infection cases. Cont. 4- Disseminated coccidioidomycosis
-This disease is systemic in that it can reach several sites in the body such as, lymph nodes, bones, joints, and the skin.
-Meningitis is commonly associated with the disseminated disease. Cont. 5-Meningitis
-meningitis is the worst clinical manifestation of coccidioidomycosis.
-Meningitis due to coccidioidomycosis always leads to changes in the mental status of the patients, and leads to cranial nerve deficits.
-Serologic testing is very important especially for meningitis patients in the endemic regions. Cont. -Coccidioidal spherules can be identified through cytology or biopsy.
-The presence of the spherules is an indication of coccidioidal infection.
-Body fluid can be cultured and tested for the presence of Coccidioides species.
-positive culture with Coccidioides spp. is an indication of coccidioidal infection.
-Serologic testing is a very useful method because of its sensitivity and specificity.
-It is a very helpful method for doctors in evaluating the disease progression and improvement. Diagnosis -Endemic areas
-Southwest the United State (Arizona & California).
Approximately 150,000 Coccidioidial infections each year in the United States.
- 60% of the reported cases in the U.S. are in Arizona.
-South America (Argentina & Paraguay). Epidemiology -Treatment
-Infected people who show no severe Valley Fever symptoms may not need any medications.
-There are many antifungal agents for treating coccidioidomycosis.
- Risk groups should avoid any contact with dust particularly if they have skin injuries.
-Wearing masks and using air quality measures are very important during dust conditions in the endemic regions.
-Unfortunately, an effective vaccine for coccidioidomycosis has not been developed yet. Treatment & Prevention Coccidioides Histoplasma Paracoccidioides Blastomyces Systemic Mycoses Case study -Case History: A 59 year old man from Alberta, Canada reported a 3 month history of anorexia, generalized muscle weakness, a 20kg (44lds) weight loss, painful oral ulcers, progressive shortness of breath and a non-productive cough. He worked in Brazil and Argentina for approximately 8 years.
-His medical history included alcohol abuse, a chronic cigarette habit and a surgically repaired stomach ulcer.
-Symptoms: ulcerative lesion on the nose, red bumps on the skin, infiltrative lesion on the tongue and shortness of breath. Case study # 1 Direct Microscopy
After being cultured at 25℃ for 7 days and 35 for 3 days on BHIA.
What is your identification? Diagnosis is:
Paracoccidioides brasiliensis -Case History: A 34-year-old female presented with an ulcerating lesion on the face. She had a six month travel history which included visits to the USA, Mexico and Argentina. Skin scrapings showed the presence of fungal elements and the culture grew the fungus shown below.
Direct Microscopy : (KOH stain) Microscopy: Case Study # 2 Culture:
What is your identification? Case Study # 2 Diagnosis is :
Coccidioides posadasii -Case History: A 24-year-old previously healthy man from Tanzania presented with dry cough, fatigue, skin lesions, a 14 kg weight loss and fever.
-He was treated empirically for a community-acquired pneumonia.
-After two courses of antibiotic treatment he did not improve clinically.
-He had a worsening chest radiograph showing a large unilateral pleural effusion.
-A plain chest radiograph showed a moderate-sized right pleural effusion Case Study # 3 -Presumptive diagnosis was made by direct histological visualization of a characteristic yeast with broad-based budding.
-A periodic acid-Schiff stain confirmed the presence of large fungal spores.
What is your identification? Diagnosis is :
Blastomyces dermatitidis Case History: A 32 year-old immigrant from Conakry, Guinea was admitted to a regional hospital, upon his arrival in Switzerland.
-Report of original case of Disseminated histoplasmosis (DH).
-Upon extensive antifungal treatment and nonsteroidal anti-inflammatory drugs, the patient recovered.
-Symptoms: 4-month history of fever, night sweats, productive cough, weight loss, and multiple cervical lymphadenopathies.
-Lab investigations showed a positive HIV-1 test.
-PCR results were negative for Mycobacterium tuberculosis. Case Study # 4 Silver-stained
What is your identification? Diagnosis is :
Histoplasma capsulatum Thank you Morphology