Case 1 introduction
Diagnosis Diagnosis of allergic aspergillosis is usually made clinically, although these patients may have positive respiratory cultures
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Diagnosis Diagnosis of allergic aspergillosis is usually made clinically, although these patients may have positive respiratory cultures for Aspergillus. Patients typically have a long-standing history of asthma with a history of infiltrates on chest x-ray. Other diagnostic criteria include presence of specific antibody to Aspergillus as well as elevated levels of IgE in the serum and peripheral blood eosinophils. The lack of systemic symptoms helps differentiate ABPA from Aspergillus pneumonia or disseminated disease. Diagnosis of disseminated disease is by culture of the organism from a normally sterile site and/or demonstration of hyphae invading blood vessels in a tissue biopsy. Disseminated disease can also be presumptively diagnosed by presence of antibody or galactomannan antigen in the patient's serum. Fungal hyphae can be seen on direct smear using KOH or calcofluor white, which is a more sensitive fluorescent stain. Aspergillus hyphae can be identified by their frequent septae, and branching at regular intervals at a 45 angle (Figure 39-1); however, these characteristics are not specific or diagnostic for Aspergillus. Definitive diagnosis would be made by microscopic observation of the fungus after culture of the organism. Aspergillus species can be cultured from sputum or bronchoalveolar lavages of infected patients. The fungus grows rapidly on most laboratory media including blood agar, although a more selective media such as Sabouraud agar is commonly used to culture fungus. Growth is enhanced by incubation at room temperature versus 35C. Visualization of the characteristic structure with a conidiophore, a vesicle to which the phialides are attached would confirm the diagnosis of Aspergillus. Although speciation can be preliminarily made by the color of the front and reverse of the colony on Sabouraud dextrose agar and their microscopic features, A. fumigatus is differentiated from the others by growth at a temperature at or above 50C. Figure 39-1. Aspergillus fumigatus. Frequent septa with branching pattern is charac teristic Treatment and Prevention Treatment of ABPA is usually not warranted; however because this is a hypersensitivity reaction, systemic corticosteroids are effective treatment, whereas inhaled corticosteroids are not. Therapy for invasive aspergillosis is with amphotericin B, itraconazole, or voriconazole. Antifungal agents may be used for prophylaxis of patients who are severely immunocompromised to prevent disseminated disease, particularly bone marrow transplant patients. These patients should also be protected from exposure to the organism by use of air filters. COMPREHENSION QUESTIONS [39.1] A biopsy of an infected lung from a 76-year-old woman who suffered a third-degree burn 2 months ago revealed uniform hyphae with regularly spaced septation and a parallel arrangement. No yeast cells were observed. Which of the following is the most probable diagnosis? A. Actinomycosis B. Aspergillosis C. Blastomycosis D. Cryptococcosis E. Zygomycosis [39.2] Which of the following is the probable source of infection in aspergillosis in the patient [39.1]? 1. Contact with an infected animal 2. Implantation 3. Ingestion 4. Inhalation 5. Water used in preparing lemonade [39.3] An examination of sputum for a suspected case of fungal infection may reveal hyphae in which of the following? A. Aspergillosis B. Cryptococcosis C. Histoplasmosis D. Paracoccidioidomycosis E. Sporotrichosis ANSWERS [39.1] B. Aspergillosis is a spectrum of diseases that may be caused by a number of Aspergillus species. These species are widespread in nature. Aspergillus species grow rapidly in vivo and in vitro and bear long conidiophores with terminal vesicles on which phialides produce chains of conidia. In healthy individuals, alveolar macrophages are able to phagocytize and destroy the conidia. Macrophages from immunocompromised patients have a diminished ability to do this. In the lung, conidia swell and germinate to produce hyphae that have a tendency to invade preexisting cavities (abnormal pulmonary space as a result of tuberculosis, sarcoidosis, or emphysema). Sputum and lung tissue specimens produce colonies which are hyaline, septate and uniform in width. Blastomyces and Cryptococcus from yeast cells, while Zygomycoses species have hyphae that are sparsely septate. Actinomyces may be considered a branching bacterium. [39.2] B. Aspergillosis is a spectrum of diseases that may be caused by a number of Aspergillus species. These species are widespread in nature. Aspergillus species grow rapidly in vivo and in vitro and bear long conidiophores with terminal vesicles on which phialides produce chains of conidia. In healthy individuals, alveolar macrophages are able to phagocytize and destroy the conidia. Macrophages from immunocompromised patients have a diminished ability to do this. In the lung, conidia swell and germinate to produce hyphae that have a tendency to invade preexisting cavities (abnormal pulmonary space as a result of tuberculosis, sarcoidosis, or emphysema). Sputum and lung tissue specimens produce colonies which are hyaline, septate and uniform in width. Blastomyces and Cryptococcus from yeast cells, while Zygomycoses species have hyphae that are sparsely septate. Actinomyces may be considered a branching bacterium. [39.3] A. Cryptococcosis, histoplasmosis, paracoccidioidomycosis and sporotrichosis are all caused by dimorphic fungi. At 37C, the yeast form predominates. Aspergillosis, on the other hand, is caused by an organism that produces only hyphae (no-yeast component). CASE 40 INTRODUCTION A 52-year-old man presents to the office for the evaluation of a cough and fever. He has had these symptoms for about a week. He has also noted a sharp chest pain that is worse when he coughs or takes a deep breath. He has had some associated fatigue, headaches, achy joints, and sweatiness at night. He has been using an over-the-counter flu medication, which helps to reduce the cough, but he wanted to be checked because his symptoms are lingering. He has no history of pulmonary diseases and has never smoked cigarettes. He has had no exposure to ill contacts. His only recent travel was a weeklong golf vacation to Phoenix, which he took 3 weeks ago. On examination, he is comfortable appearing and in no respiratory distress. His temperature is 37.7C (99.9F), and his vital signs are otherwise normal. His pulmonary examination is notable for some faint expiratory wheezing and crackles in the left upper lung field. The remainder of his physical examination is unremarkable. A chest x-ray shows hilar adenopathy. A CBC shows a normal total white blood cell count but with a high percentage of circulating eosinophils. Microscopic examination of a fresh sputum sample treated with KOH reveals numerous spherules. What organism is the likely cause of this patient's symptoms? For this organism, how do spherules form and what is their role in propagating infection? ANSWERS TO CASE 40: Blastomycosis, Coccidiodomycosis, and Histoplasmosis Organism most likely to cause his symptoms: Coccidioides immitis. How do spherules form and what is their role in propagating infection: Inhaled arthroconidia lose their hydrophobic outer wall and remodel into spherical cells, or spherules. Nuclear division and cell multiplication occur and multiple septae develop within the circular cell, dividing it into endospore-containing compartments. The external wall of the spherule thins as growth occurs and then ruptures, releasing multiple spores and propagating the infection. Summary: A 52-year-old man who recently traveled to Phoenix complains of a cough, fatigue, and night sweats. A chest x-ray shows hilar adenopathy. The sputum reveals numerous spherules. CLINICAL CORRELATION Introduction C. immitis is a dimorphic fungus endemic in the western hemisphere. It is typically found in semiarid climates within the north and south 40 latitudes. Common endemic regions in the United States include the San Joaquin Valley, southern Arizona, and southwestern Texas. Transmission occurs by inhalation of the arthroconidia from the soil. The arthroconidia are taken into the bronchioles, where they form a spherule. When symptoms do occur, they usually start 1-3 weeks after exposure and typically include cough, fever, and fatigue. Chest pain, dyspnea, arthralgias, and skin rashes may occur as well. Most infections are self-limited, but it can take several weeks to months for symptomatic resolution. A small percentage of infections result in progressive pulmonary disease or chronic pulmonary complications, and an even smaller percentage may result in dissemination outside of the lung the most common site being the skin. Other areas of dissemination include the bones, joints, and the central nervous system (CNS). Most patients who develop disseminated disease have an underlying risk factor of severe immunosuppression, including those infected with HIV. Approach to the Suspected Coccidoides Patient Definitions Dyspnea: Shortness of breath or difficulty breathing. Dimorphic fungi: Fungi that grow as a mold at room temperature and in the environment and as yeast at 35C or in the body. Arthroconidia: Barrel-shaped structures that are the mold and infectious form of C. immitis. Objectives 1. Know the morphology, growth, and reproductive characteristics of C. immitis. 2. Know the sources of infection, modes of transmission, and clinical diseases associated with C. immitis infection. Discussion Characteristics of Coccidioides Species Coccidioides is one of several systemic and dimorphic fungi. Histoplasma capsulatum, Blastomyces dermatitidis, and Paracoccidioides braziliensis are the others. Cryptococcus neoformans is also a systemic fungus but is not dimorphic. Sporothrix schenckii is dimorphic but not usually systemic. These fungi are commonly found in the environment in differing parts of the world and are transmitted by the aerosol route. In the majority of cases, fungi are inhaled into the lungs, and disease is unrecognized because patients remain asymptomatic. C. immitis grows in the soil as mycelia by apical extension. Maturation results in the development of arthroconidia, which have a hydrophobic outer layer and can remain viable for a long period of time. They form fragile attachments to adjacent cells that are easily broken. Physical trauma, even a mild wind, can break these attachments and result in airborne dissemination of arthroconidia. If inhaled, the arthroconidia can deposit in the lung, where they lose their hydrophobic outer wall. The cell remodels into a spherical form known as a spherule. Within the spherule, cells multiply and septae form that divide the spherule into multiple compartments. These compartments contain endospores that are released as the spherule grows and eventually ruptures. The endospores are capable of generating new spherules or reverting to mycelial growth if removed from the site of an infection. Spherule growth and rupture result in a host inflammatory response that includes the action of neutrophils and eosinophils. T lymphocytes also play an important role in the control of C. immitis infection. Most infections with this organism are asymptomatic or cause mild, nonspecific upper respiratory symptoms that are not diagnosed. Diagnosis Initial preliminary diagnosis is made by consistent clinical symptoms in a patient with recent travel to a Coccidioides endemic area of the country. Definitive diagnosis is made by direct observation of spherules with subsequent culture of the organism in a specimen, usually of respiratory origin. Direct examination can be made using either KOH or calcofluor white stains. Coccidioides immitis is a dimorphic fungus that forms spherules in the patient (35C) and arthroconidia in the environment (room temperature). The arthroconidia are the infectious form and can be transmitted in the laboratory if proper biosafety precautions are not adhered to. C. immitis grows rapidly (within 1 week) on routine laboratory media. Colonies appear as a white fluffy mold, whose appearance is indistinguishable from the other dimorphic fungi, including Histoplasma capsulatum and Blastomyces dermatitidis. C. immitis can be specifically identified by immunodiffusion of extracted C. immitis antigen and commercially prepared antibody or by DNA probes specific for C. immitis RNA. In cases in which culture is not possible, or negative, serology or skin testing may be helpful for diagnosis. The disadvantage of both is that a positive conversion may last for life and make diagnosis of a current infection difficult.
Treatment is not usually provided to patients with uncomplicated respiratory disease without risk factors for dissemination. Patients with complicated disease are treated with either an azole or amphotericin B. COMPREHENSION QUESTIONS [40.1] A 35-year-old man is HIV antibody-positive and has a CD4 count of 50 cells/mm3 (normal: 500-1000 cells/mm3). He has had a fever of 38.3C (101F) for a few weeks and "feels tired all the time." He has no other symptoms, and findings on physical examination are normal. Complete blood count (CBC), urinalysis, and chest x-ray are normal. A bone marrow biopsy reveals granulomas, and a culture grows an organism that is a budding yeast at 37C, but produces hyphae and tuberculated chlamydospores at 25C. Of the following, which is the most likely cause? A. Aspergillus fumigatus B. Coccidioides immitis C. Cryptococcus neoformans D. Histoplasma capsulatum E. Mucor species [40.2] A 4-year-old girl who lives in Bakersfield, CA, has had a low-grade fever. Skin tests performed for the first time give the following results: Tuberculin (PPD)
The test results suggest that the patient: A. Has been exposed to Coccidioides immitis. B. Has been immunized against Coccidioides immitis. C. Has had scarlet fever. D. Has IgG antibody to Mycobacterium tuberculosis. E. Lacks immunity to Corynebacterium diphtheriae. [40.3] A 50-year-old immunocompromised woman is diagnosed as having meningitis. A latex agglutination test on the spinal fluid for capsular polysaccharide antigen is positive. Of the following organisms, which one is the most likely cause? A. Aspergillus fumigatus B. Cryptococcus neoformans C. Histoplasma capsulatum D. Nocardia asteroides E. Toxoplasma gondii [40.4] Which of the following is the most common portal of entry in Blastomyces dermatitidis infection? A. Genitourinary tract B. Lymphatic system C. Mouth D. Respiratory tract E. Skin ANSWERS [40.1] D. An HIV-positive individual may have normal immune capacity as measured by laboratory parameters, but still be more at risk for opportunistic organisms. Respiratory infections may be caused by fungi, bacteria, or viruses. As a result, laboratory results may be crucial in determining the exact organism causing an infection. In this case, the bone marrow biopsy revealed a budding yeast form at 37C, but hyphae and tuberculated chlamydospores at room temperature (25C). In disseminated histoplasmosis, bone marrow cultures are often positive. Tuberculate macroconidia are characteristic for H. capsulatum's mycelial form. [40.2] A. The Dick and Schick tests are related to streptococcal infections, specifically scarlet fever. The young girl has been exposed to a Mycobacterium, most likely M. tuberculosis, but the positive reaction observed is based on a cellular immune reaction, not one mediated by antibodies. The location is a region where coccidioides is endemic and should be one of the suspected pathogens to be considered. No vaccine is available for C. immitis. Therefore, a positive coccidioidin test indicates that the young girl has been exposed to the agent and has developed a cellular immune reaction in response. [40.3] B. Cryptococcus neoformans is a yeast characterized by a thick polysaccharide capsule. It occurs worldwide in nature and in very large numbers in pigeon feces. Cryptococcus infection is usually associated with immunosuppression. Tests for capsular antigen can be performed on cerebrospinal fluid and serum. The latex agglutination test for cryptococcal antigen is positive in 90 percent of patients with cryptococcal meningitis. With effective treatment (amphotericin B and possibly flucytosine), the antigen titer usually drops except for AIDS patients. [40.4] D. Blastomyces dermatitidis grows as a mold culture, producing septate hyphae and conidia. In a host, it converts to a large, singly budding yeast cell. It is endemic in North America. Human infection is initiated in the lungs. Diagnosis may be difficult because no skin or serologic tests exist. Chronic pneumonia is a common presentation. Sputum, pus, exudates, urine, and lung biopsy material can be examined microscopically, looking for thick walled yeast cells with broadly attached buds. It may also be cultured.
A 28-year-old woman presents to the office complaining of 2-days of itchy vaginal discharge. One week ago you saw and treated her for a urinary tract infection (UTI) with sulfamethoxazole and trimethoprim (SMX-TMP). She completed her medication as ordered and developed the vaginal discharge shortly thereafter. She denies abdominal pain, and her dysuria has resolved. She is not currently taking any medications. On examination, she is comfortable appearing and has normal vital signs. Her general physical examination is normal. A pelvic examination reveals a thick, curd-like, white discharge in her vagina that is adherent to the vaginal sidewalls. There is no cervical discharge or cervical motion tenderness, and bimanual examination of the uterus and adnexa is normal. What is the most likely cause of these symptoms? What are the most likely reservoirs of this organism in this patient? ANSWERS TO CASE 41: Candida Most likely etiologic organism: Candida albicans. Most likely reservoirs of infection: Gastrointestinal (GI) and vaginal colonization.
Most Candida infections come from the host's endogenous flora. Both humoral and cell-mediated immune functions play a role in defense against Candida infections. Those with impaired or suppressed immunity are predisposed to more severe or diffuse disease. Neutropenic persons, such as those on chemotherapy or posttransplant patients, are at risk for severe disease, which disseminates in the blood stream. In contrast, AIDS patients often develop oral, pharyngeal, or esophageal candidiasis but rarely disseminated disease. Intact skin also plays a key role in preventing cutaneous infections, because breaks in the skin of even healthy hosts may result in Candida skin infections. The use of antibiotics is probably the most significant predisposing factor for the development of Candida infections. Antibiotics that suppress the growth of the normal host bacterial flora can allow Candida to proliferate. This is a frequent contributing cause of the development of vaginal candidiasis in women and Candida diaper dermatitis in infants. Candida is the cause of a wide range of infections from oral lesions (thrush) to disseminated disease including endocarditis and meningitis. Candida albicans is the most common cause of vaginitis. Predisposing factors include diabetes, previous antimicrobial use, pregnancy, and use of oral contraceptives. Although the pathogenesis and the virulence mechanisms of Candida infection is unclear, the presence of pseudohyphae seems to indicate active disease versus colonization. Pseudohyphae are able to adhere to epithelial cells, then the blastoconidia. Approach to the Suspected Candida Patient Definitions Neutropenia: A decrease in the number of neutrophils circulating in the blood to less than 2.0109/L, with significant neutropenia being less than 0.5109/L. Thrush: Form of oral candidiasis in which a membrane forms in the oral cavity consisting of Candida, desquamated cells and white blood cells and debris. The appearance is of a creamy white, curd-like exudative plaque on the tongue and in the mouth. Objectives 1. Know the morphology, reservoirs, and reproduction of Candida species. 2. Know the clinical syndromes, risk factors, and routes of transmission of diseases associated with Candida infection. Discussion Characteristics of Candida Candida are yeasts that exist as both sexual and asexual forms, reproduce by budding and form blastospores, which are small, thin-walled ovoid cells. Blastospores, pseudohyphae may be seen on examination of clinical specimens. There are over 150 species of Candida, nine of which appear to cause disease in humans. C. albicans is the most common cause of human candidiasis. It can be found in soil and on inanimate objects and foods. It is also found in the normal flora of the human GI tract, vagina, and skin. Diagnosis Diagnosis of vaginitis is made by a combination of physical examination and testing the vaginal exudate. Ruling out other causes of vaginitis may be aided by determining the pH of the exudates as well as stain and culture of the material. Yeast cells are larger than bacteria and can be visualized easily by direct wet preparation of the exudates with KOH. Candida will grow with 24-48 hours on most routine laboratory media; however, Sabouraud dextrose agar can be used to inhibit the normal flora bacteria in cultures for mucosal candidiasis. Candida colonies are smooth and creamy, although some species may be dry and can be identified as yeast by a wet preparation. Candida species produce round or oval blastoconidia, and some species also produce pseudohyphae (chains of elongated blastoconidia), as in Figure 41-1. Preliminary differentiation of Candida albicans from the other Candida species can be made by observation of the presence of a germ tube. Candida albicans will make a germ tube after several hours incubation in the presence of serum. Candida albicans can also be differentiated from other yeast based on their microscopic morphology on corn meal agar. C. albicans produce chlamydospores, large rounded structures in the middle of the pseudohyphae. Yeast that are germ tube-negative can be further identified by assimilation of different substrates. Several commercial kits are available that identify Candida to the species level. Download 0.69 Mb. Share with your friends:
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