6 Infections Due to the Dimorphic Fungi T.S. HARRISON l and S.M. LEVITZ l CONTENTS VII. Infections Caused by Penicillium marneffei .. 142 A. Mycology ............................. 142 I. Introduction ........................... 125 B. Epidemiology and Ecology .............. 142 II. Coccidioidomycosis ..................... 125 C. Clinical Manifestations .................. 142 A. Mycology ............................. 126 D. Diagnosis ............................. 143 B. Epidemiology and Ecology .............. 126 E. Treatment ............................. 143 C. Clinical Manifestations .................. 127 VIII. Conclusions ........................... 143 1. Primary Coccidioidomycosis ........... 127 References ............................ 144 2. Disseminated Disease ................ 128 3. Coccidioidomycosis in HIV Infection ... 128 D. Diagnosis ............................. 128 E. Therapy and Prevention ................. 129 III. Histoplasmosis ......................... 130 I. Introduction A. Mycology ............................. 130 B. Epidemiology and Ecology .............. 131 C. Clinical Manifestations .................. 131 1. Primary and Thoracic Disease ......... 131 The thermally dimorphic fungi grow as molds in 2. Disseminated Disease ................ 132 the natural environment or in the laboratory at 3. Histoplasmosis in HIV Infection ....... 133 25-30 DC, and as yeasts or spherules in tissue or D. Diagnosis ............................. 133 when incubated on enriched media at 37 DC. E. Treatment ............................. 133 IV. Blastomycosis .......................... 134 They include the agents of the endemic systemic A. Mycology ............................. 134 mycoses prevalent in the Western Hemisphere, B. Epidemiology and Ecology .............. 135 i.e., Coccidioides immitis, Histoplasma cap­ C. Clinical Manifestations .................. 135 sulatum, Blastomyces dermatitidis, and Par­ 1. Primary and Pulmonary Disease ....... 135 2. Extrapulmonary Disease .............. 136 acoccidioides brasiliensis. Also discussed here are 3. Blastomycosis in HIV Infection ........ 136 Sporothrix schenckii, which occurs worldwide and D. Diagnosis ............................. 136 usually causes cutaneous rather than systemic E. Treatment ............................. 137 disease, and Penicillium marneffei, a recently V. Paracoccidioidomycosis ................. 137 A. Mycology ............................. 137 recognized cause of systemic mycosis in Southeast B. Epidemiology and Ecology .............. 138 Asia. In recent years, these fungi have become an C. Clinical Manifestations .................. 138 increasing problem due to rising populations in 1. Childhood Disease ................... 138 2. Adult Disease ....................... 139 the endemic areas, more travel, and an increasing 3. Paracoccidioidomycosis in HIV Infection 139 number of immunocompromised patients D. Diagnosis ............................. 139 (especially those with AIDS). Because of space E. Treatment ............................. 139 limitations we have tried to emphasize more VI. Sporotrichosis .......................... 140 A. Mycology ............................. 140 recent developments in the ecology, epidemiology, B. Epidemiology and Ecology .............. 140 and clinical aspects of these mycoses. Pathogenesis C. Clinical Manifestations .................. 141 and host defense are reviewed in other chapters 1. Cutaneous Sporotrichosis ............. 141 (Chaps. 1,3,4, this Vol.). 2. Systemic Sporotrichosis ............... 141 D. Diagnosis ............................. 141 E. Treatment ............................. 141 II. Coccidioidomycosis 1 Section of Infectious Diseases, Evans Memorial Department of Clinical Research and Department of The first case of disseminated coccidioidomycosis Medicine, Boston University School of Medicine, Boston was reported in 1892 in Argentina. By 1900 MA 02118, USA Ophiils described the causative organism as a The Mycota VI Human and Animal Relationships Howard/Miller (Eds.) © Springer-Verlag Berlin Heidelberg 1996 126 T.S. Harrison and S.M. Levitz dimorphic fungus. In the 1930s Dickson and the presence of particular plants (e.g., creosote Gifford recognized the milder self-limiting forms bush, cacti, and yuccas) and animals (Drutz and of primary pulmonary infection. Charles Smith Catanzaro 1978). The highest prevalences are in and his coworkers (1946) defined much of the southern Arizona around Phoenix and Tucson, in epidemiology of the infection in studies during the San Joaquin Valley in southern California, World War II at military installations in the San and in Texas along the Rio Grande around EI Joaquin Valley. The first effective treatment, Paso. Parts of southern Nevada, Utah, and New amphotericin B, was introduced in 1957; and Mexico are also endemic. In Mexico the main from the 1970s azoles also became available. areas are in the north and west along the border with the USA, the Pacific coast, and a more central region. There are smaller endemic areas A. Mycology in Honduras and Guatemala. In South America the highest incidence occurs in northwest Coccidioides immitis is classified with imperfect Venezuela. Endemic disease has also been re­ fungi or deuteromycetes, as no sexual state has ported in the adjacent areas of Columbia, and in yet been described (Kwon-Chung and Bennett Paraguay, Bolivia, and Argentina. Interestingly, 1992). However, analysis of rONA sequence data endemic foci have also been found outside the suggests a close relationship with other dimorphic Lower Sonoran Life Zone, e.g., in the Pacific fungi of medical importance, such as Blastomyces beach area of San Diego, in a woodland area of dermatitidis and Histoplasma capsulatum, whose northern California, and in two tropical areas of sexual forms place them in the Ascomycotina. As Mexico. Within endemic areas, the occurrence of a saprophyte in soil or on agar, C. immitis pro­ C. immitis in the soil is very patchy. The reasons duces septate hyphae. Arthroconidia are formed for this are not fully understood. Soil around by alternate cells which swell and lay down an rodent burrows more often yields fungus. The inner wall, while the intervening cells degenerate. high salinity and alkalinity of most positive When disturbed, the hardy arthroconidia are soils may inhibit the growth of competing released into the air. They may germinate to microorganisms. produce hyphae, but if inhaled by man or a range Within endemic areas, the risk of infection is of animals they enlarge to become multinucleate clearly increased by work outdoors under dusty spherules up to 80.um in diameter within the host conditions. Outbreaks can occur during construc­ tissues. By successive cycles of cleavage, endo­ tion and archeological digs. Larger epidemics spores 2-5.um in diameter with single nuclei are may result from climatic factors. In December formed and released when the spherule wall rup­ 1977, high winds scoured the topsoil from the tures. In the susceptible host, each endospore can southern San Joaquin Valley and deposited dust then form a new spherule. In the laboratory, up to 700 km to the north, well outside the usual conversion to the parasitic form is favored by endemic area. In the first 16 weeks of 1978, 550 increased CO2 tension and a temperature between cases of coccidioidomycosis were reported in 34 and 40°C. Up to one quarter of isolates show California compared to a maximum of 175 in the variations in the color, texture, or form of the same period over the previous 10 years (Flynn et mycelial colonies, or in the pattern of conidiation, al. 1979). From September to December 1991, which can lead to delays in identification. Atypical and again in the latter half of 1992, there was isolates may have differing degrees of virulence in a dramatic increase in the number of cases of mice, but there is no evidence for any clinical coccidioidomycosis in the southern San Joaquin correlation in man. In addition, there is no Valley (Einstein and Johnson 1993). After a pro­ evidence for any significant antigenic variation longed drought, significant rainfall in March 1991 between strains. and in February and March 1992 may have led to mycelial growth and the germination of arth­ roconidia which were dispersed in the subsequent B. Epidemiology and Ecology dry months. In southern California in a normal year, there is not usually such a marked seasonal In the USA the endemic areas largely correspond variation in incidence, but studies from Arizona with the Lower Sonoran Life Zone, characterized have also found an increased incidence in the by an arid climate with short rainy seasons and second half of the year (Kerrick et al. 1985). Dimorphic Fungal Infections 127 Outside the endemic region, cases most often C. Clinical Manifestations result from travel, which may only have been brief within an endemic area. Very rarely fomites 1. Primary Coccidioidomycosis (e.g., cotton and clothes) have led to infections outside the endemic area. Infrequent cases Symptomatic disease occurs in about 40% of those acquired by direct cutaneous inoculation have infected, within 1 to 4 weeks after exposure. The also been described. Under normal circumstances, common manifestations are cough (which is person to person spread does not occur, although usually dry), fever, headache, chest pain (which in one case report, medical staff were infected may be pleuritic), malaise, and myalgia. A fine from arthroconidia produced by a mycelium which erythematous macular rash in