History and Epidemiology

Histoplasma capsulatum is a dimorphic fungus primarily acquired via respiratory exposure that is responsible for approximately 500,000 infections annually in the United States, which makes it the most prevalent cause of fungal pulmonary disease. Similarly, these calculations also indicate that nearly 50 million North American residents are latently infected with the fungus. The fungus is endemic worldwide, although there are areas with a high incidence of disease. The Ohio and Mississippi River Valleys in the United States are a highly endemic region and skin testing has shown that up to 90% of adults in these regions have been exposed to the fungus. High endemicity areas are also present in Latin America, particularly within Brazil, Venezuela, Ecuador, Paraguay, Uruguay, and Argentina. For example, the prevalence in Midwestern and Southeastern portions of Brazil has been reported as approximately 63% and 93%, respectively.

The most recent data on rates of clinically significant disease in the United States are from an extraction of data from the Nationwide Inpatient Sample, a database of diagnostic codes of diseases, for the year 2002. This methodology likely underestimates the incidence of hospitalizations for histoplasmosis or other endemic mycoses due to diagnostic difficulties and incomplete coding. Nevertheless, in 2002, there were 3259 adults (60% male, 40% female) and 111 children (42% male, 58% female) hospitalized with histoplasmosis. The majority of patients were not known to have an underlying immunodeficiency, with only 14% of adults having an immune defect while 32% of children were considered immunocompromised. In-hospital mortality rates were 8% and 5% for adults and children, respectively. Hence, there are approximately 270 deaths due to H. capsulatum annually in the United States. For comparison, in 2009 (the most current complete U.S. death statistics), 529 deaths were due to tuberculosis (405 due to respiratory tuberculosis), 99 due to meningococcal infection, 26 due to salmonellosis, and 3 due to malaria.

The genus Histoplasma was designated in 1906 by Samuel Darling who described the fungus in the lungs, liver, spleen, and lymph nodes of a carpenter from Martinique working on the Panama canal. Darling incorrectly characterized the 1- to 4-µm intracellular ovoid yeast as protozoa, similar to Leishmania sp . Subsequent to the identification of H. capsulatum by Darling, several varieties of Histoplasma were identified, with distinct geographic or host niches. More recently, analysis of sequence diversity of four protein-coding genes of H. capsulatum revealed that the different varieties of Histoplasma are not phylogenetically distinct and that H. capsulatum comprises seven phylogenetic species, which radiated rapidly from a single ancestor between 3 million and 13 million years ago.

Pathogenesis

H. capsulatum exists in either a filamentous or yeast form, depending mainly on temperature and nutritional conditions. In the environment and at ambient temperatures, H. capsulatum is mycelial. This saprophytic mold grows particularly well in soils enriched with organic nitrogen sources, such as areas contaminated with bird or bat droppings. Hyphal elements are 1.25 to 2 µm in diameter and produce two types of spores called conidia: thick walled macroconidia (8- to 15-µm diameter) and microconidia (2- to 5-µm diameter). Both conidial forms are produced singly at the tips of narrow, short conidiophores that branch at right angles to vegetative hyphae. The microconidia are the purported infectious particle, in that their size is most effective for aerosolization and subsequent inhalation and deposition into distal lung structures. Environmental disturbances, especially construction or tree removal, are highly associated with aerosolization of H. capsulatum. At 37°C or in human tissues, the yeast form is the predominant morphology. Yeast cells have thin walls and are oval with diameters from 2 to 5 µm. The cells reproduce by polar budding with a narrow bridge between the mother and daughter cells. Rarely, it is possible to find both yeast and mycelial forms in lung tissues as well as on endovascular devices.

Histoplasmosis is initiated by inhalation and deposition of microconidia within alveoli. This event is followed by conversion of microconidia to the yeast form, which begins within several hours to a few days. Morphogenesis is initiated by the shift in temperature and availability of nutrients. Notably, despite the species name, the cells lack a capsule. During primary infection, the yeast cells are phagocytosed into the endosomal compartment of phagocytes and these infected host cells then migrate to hilar and mediastinal lymph nodes and subsequently disseminate hematogenously, distributing the fungus into diverse tissues. In fact, autopsy studies have found that approximately 70% of individuals with history of histoplasmosis have splenic granulomas. The incubation period for disease manifestations is typically 8 to 17 days, although heavy exposure may result in disease in as little as 3 days.

It is understood that effective control of histoplasmosis requires activation of cellular immunity in concert with innate responses, because the absence of intact immunity leads to disseminated, progressive disease. Additionally, impairment of cellular immunity in latently infected individuals can result in the reactivation of previously controlled foci of infection. Although significantly less common in the current era of effective antiretroviral medications, individuals with acquired immunodeficiency syndrome (AIDS) are at high risk for reactivation disease (see Chapter 90 ). Histoplasmosis also reactivates in patients receiving anti­cytokine therapies. Reactivation disease has also been documented in liver transplant recipients with disease originating from latent infections in the transplanted organs, and disease is associated with a high incidence of graft loss and mortality.

Neutrophils are considered primary responders to H. capsulatum in the lung ; however, the majority of yeast are found within immature dendritic cells on the first day after experimental pulmonary infection of mice. In the same murine model, neutrophils predominate for several days thereafter. Human neutrophils effectively inhibit the fungus, and azurophilic granules are responsible for this fungistatic effect. Resident and inflammatory macrophages contain significant numbers of yeast cells by 3 days after experimental infection and yeast cells are primarily in inflammatory macrophages by the end of the first week. Although experimental systems have shown that murine dendritic cells and macrophages fail to control replication and facilitate dissemination, human dendritic cells and macrophages, especially activated macrophages, can efficiently kill H. capsulatum yeast cells. Moreover, human dendritic cells can inhibit conidial germination, which can modify subsequent disease progression by presenting fungal antigen to CD8 ⁺ T cells. Several experimental studies have suggested that CD8 ⁺ T cells are instrumental in initial clearance of H. capsulatum yeast cells, whereas CD 4 ⁺ T cells are required for survival. The role of antibody in histoplasmosis is controversial, although monoclonal antibodies have been shown to modify the pathogenesis of disease. Consistent with a key role for B cells in histoplasmosis is the finding that depletion of B cells significantly enhances the severity of disease.

Among the many innate elements engaged in augmentation of protective immunity to H. capsulatum are several cytokines, including interleukin-12, tumor necrosis factor (TNF)-α, granulocyte macrophage colony-stimulating factor, and interferon-γ. The ability of lymphocytes and phagocytes to produce these cytokines constitutes a major effector mechanism of host resistance. The critical role of TNF is underscored, as described earlier, by the association of inhibition of this cytokine and the development of severe histoplasmosis. The lack of TNF is thought to diminish control of intracellular growth of the fungi and leads to dysregulation of granulomas containing H. capsulatum yeast cells and/or an inability to form new granulomas. In the setting of intact immunity, granuloma formation can be caseating and indistinguishable from that caused by Mycobacterium tuberculosis . As in tuberculosis, healing of granulomas can also result in calcification of lesions, especially in lymph nodes and in the liver and spleen.

Clinical Manifestations

The severity of histoplasmosis is closely linked to the number of spores inhaled, the virulence of the infecting strain, and the immunologic status of the exposed individual. The most common presentation is pneumonia, although the disease may involve virtually any tissue and can manifest as a fulminant life-threatening disseminated sepsis. Low inoculum infection results in development of self-limiting disease in 1% of individuals, while 99% have subclinical infection. In contrast, high inoculum infection leads to symptomatic disease in 50% to 100% of exposures. Therefore, infection usually results in a mild, often asymptomatic respiratory illness, but may progress to life-threatening systemic disease, particularly in immunocompromised individuals. In the setting of HIV infection, disseminated histoplasmosis has been considered an AIDS-defining illness, although the prevalence of histoplasmosis in individuals with HIV has diminished with currently available antiretroviral regimens.

Acute Histoplasmosis

As noted, the most common outcome after exposure to H. capsulatum is an asymptomatic infection. However, 1 to 3 weeks after acquisition, acute disease can manifest. Symptomatic histoplasmosis typically presents as a flulike illness with the rapid onset of fever, chills, headache, myalgia, nonproductive cough, and chest pain. Chest radiographs are generally unrevealing, although mediastinal lymphadenopathy with ( Fig. 37-2A ) or without opacities may be present. However, approximately 1 in 2,000 adults will develop acute progressive pneumonia, associated with a heavy exposure to H. capsulatum . In acute disease, approximately 10% of patients have rheumatologic symptoms, such as arthritis or severe arthralgia accompanied by erythema nodosum. Additionally, pericarditis can develop in approximately 10% of patients with acute disease, although pericarditis is typically a late manifestation after the resolution of pulmonary symptoms. Uncommonly, lymph node enlargement may cause compression of mediastinal structures. Although resolution is typical, surgical decompression may be required to alleviate esophageal compression or endovascular stenting may be needed to prevent superior vena caval occlusion. Mediastinal fibrosis ( eFig. 37-1 ) is a rare postinfectious complication that is perceived to be due to an abnormal inflammatory response to residual H. capsulatum antigens; this disease is more common in individuals with an HLA-A2 allele. Steroids or antifungal agents are not useful in mediastinal fibrosis and surgery has not proven to be particularly effective, although endovascular stenting has been reported to alleviate vascular complications. The majority of patients with acute pulmonary histoplasmosis recover over several weeks without sequelae, although occasional patients complain of fatigue persisting for months. Subsequent radiographs may appear normal or demonstrate a single calcified ( eFig. 37-2 ) or noncalcified nodule or “coin” lesion, or a miliary pattern of calcified granulomas indistinguishable from that found in certain tuberculosis patients ( Fig. 37-3 ). The miliary appearance is more common in disease associated with a high inoculum exposure. Although it is well recognized that pulmonary coin lesions can be sequelae of histoplasmosis, surgical resections continue due to suspicion of neoplasm. Positron emission tomography may be of limited value, because they can display enhanced uptake in histoplasmosis nodules.

Acute histoplasmosis.

A, Frontal chest radiograph in a patient with acute histoplasmosis shows numerous bilateral small nodules ( arrowheads ) and right paratracheal lymphadenopathy ( arrow ). B, Photomicrograph of bone marrow biopsy specimen shows abundant small yeast in macrophages. There were no well-formed granulomas. (Wright stain; original magnification ×450.)

( A, Courtesy Michael Gotway, MD.)

Multiple calcified pulmonary granulomas due to histoplasmosis.

Frontal chest radiograph shows numerous small calcified nodules ( arrows ) bilaterally due to previous disseminated histoplasmosis.

(Courtesy Michael Gotway, MD.)

Chronic Pulmonary Histoplasmosis

Chronic respiratory illness can develop in individuals with long-standing lung diseases, particularly emphysema or chronic obstructive lung disease, who acquire H. capsulatum. The disease can manifest after acute infection or due to reactivation of previously latent infection. Chronic histoplasmosis is characterized by indolent, progressive lung opacities, fibrosis, and cavitation ( Fig. 37-4 ). The majority of patients present with complaints of fever, weight loss, increasingly severe cough, and dyspnea, a presentation clinically and radiographically similar to that of cavitary tuberculosis. Without therapy, the disease progresses in approximately 50% of affected individuals.

Chronic histoplasmosis.

Axial chest CT (A–D) shows upper lobe bronchovascular thickening with architectural distortion and areas of consolidation ( arrowheads , B ). Small nodules ( single arrow , D ) are also present. A cavity ( double arrows , A ) is present within the right upper lobe. The appearance closely resembles postprimary tuberculosis.

(Courtesy Michael Gotway, MD.)

Diagnosis

The “gold standard” for diagnosis is culture of H. capsulatum ; however, this process takes a minimum of 1 week and growth may not be detected for approximately 1 month. Moreover, H. capsulatum is cultured from respiratory samples in fewer than 50% of patients with acute pulmonary histoplasmosis. In contrast, cultures are positive in 65% to 85% of patients with chronic pulmonary histoplasmosis. These data are complicated by the fact that studies have not critically examined the relative worth of different respiratory samples, although bronchoscopy with biopsy may provide the most effective testing mechanism because it can allow rapid visualization of the fungus in the tissue (see Fig. 37-2B ). Direct observation of the fungus in respiratory secretions has high specificity but low sensitivity, and may be difficult because the fungus is located within macrophages. In disseminated disease, the fungus is usually detectable in bone marrow aspirates and can even be identified in peripheral blood, especially in buffy coats.

In the absence of positive cultures, serologic techniques such as immunodiffusion, complement fixation, enzyme immunoassay, and radioimmunoassay have been used to provide immunologic evidence of H. capsulatum infection. These serologic tests for the detection of either antibodies and/or antigen in clinical specimens (e.g., serum or urine) offer a rapid alternative method for the diagnosis of histoplasmosis (see Chapter 17 ). Although promising, polymerase chain reaction or mass spectroscopy methodologies for detecting H. capsulatum are not yet developed for routine use. Skin testing with H. capsulatum antigens is not recommended for purposes other than epidemiologic studies.

In the United States, histoplasmosis is commonly diagnosed by antigen detection. H. capsulatum polysaccharide antigen can be detected by enzyme-linked immunosorbent assay (ELISA) in the urine of 92% of patients with disseminated histoplasmosis, 83% with acute disease, and 88% with chronic pulmonary histoplasmosis. Additionally, antigen can frequently be detected in the serum of patients with disseminated disease, suggesting that testing of both urine and blood will increase the sensitivity of testing. Testing of bronchoalveolar lavage fluid or cerebrospinal fluid can lead to the diagnosis of pulmonary or meningeal histoplasmosis, respectively. The assay is useful for following response to therapy and evaluating for disease relapse. The current Infectious Diseases Society of America (IDSA) guidelines recommend following antigen levels during and after treatment of histoplasmosis. However, existing antigen assays may also detect related antigens from other endemic fungi, indicating that their interpretation must be undertaken in the context of other diagnostic information.

At present, the aforementioned tests are costly and impractical for use in less economically developed countries. A mainstay of diagnosis in many regions is an immunodiffusion test for detection of H and M precipitin bands utilizing histoplasmin (HMIN) as the antigen; HMIN is a well characterized antigen secreted by H. capsulatum mycelia and yeast. The H antigen is a β-glucosidase and the M antigen is a catalase. Antibodies to these antigens can be detected by approximately 1 month after infection. The M band is detectable in approximately 75% of patients and can persist for years, whereas antibodies to the H antigen can be identified in less than 25% of patients and are undetectable after 6 months. Complement fixation tests use both HMIN and intact yeast cells, and this reaction becomes positive by approximately 3 weeks of disease and can persist for months to years. A titer of 32 or greater is strongly suggestive of acute disease, although a titer of 8 in a patient with a high suspicion of histoplasmosis is consistent with disease. Titers are nondiagnostic in approximately 30% of patients with acute histoplasmosis and in 50% with disseminated disease. Most laboratories perform both the immunodiffusion and complement fixation tests concurrently to increase sensitivity. In immunocompromised patients with histoplasmosis, specific antibodies to the disease cannot be routinely detected, making these tests less sensitive in this population.

ELISA assays for the detection of antibodies in sera using HMIN have been established. ELISAs using HMIN compared to deglycosylated HMIN have sensitivities and specificities of 57% and 93% versus 92% and 96%, respectively. Treatment of purified HMIN with metaperiodate may further improve the utility of ELISA.

Treatment

Detailed information on antifungal drugs and their characteristics and uses is available in Chapter 38 .

Comprehensive treatment recommendations for histoplasmosis have been made by the American Thoracic Society in 2011 and the IDSA in 2007. The majority of indi­viduals who acquire H. capsulatum are either asymptomatic or have a mild, self-limited flulike illness. Unless the patient is immunocompromised, there is no need for urgent administration of antimycotics under these circumstances.

History and Epidemiology

Coccidioidomycosis is a primary pulmonary infection caused by two species of Coccidioides , C. posadasii and C. immitis , which are endemic to the Central Valley of California, southwestern United States, and Central and South America where there are arid to semiarid life zones. The association of Coccidioides with human disease was first made by observing symptoms traditionally associated with “Valley fever” in a medical student exposed to a culture of the fungus in a laboratory. In the United States, it is estimated that approximately 150,000 persons are infected annually and that approximately 50,000 of these develop symptomatic disease. California and Arizona actively track cases of coccidioidomycosis and both states have reported significant increases in disease rates over the past decade, with Arizona having the most cases. In 2009, there were 10,233 laboratory-confirmed cases of coccidioidomycosis (155/100,000 population) reported in Arizona. Data from 2011 in California indicates that Coccidioides caused 5 hospitalizations/100,000 population. It is also estimated that these fungi are responsible for approximately 2200 hospital admissions in the United States with an in-hospital mortality rate of 6% to 8%.

Acquisition of the fungus is associated with disturbances of the soil. Purportedly, hyphae grow in moist soil and viable arthroconidia exist for protracted periods during dry periods. The fungus is thought to grow to a depth of approximately 8 inches. Arthroconidia are frequently aerosolized due to agriculture, excavation, or construction; individuals participating in these activities are at high risk for coccidioidomycosis in endemic regions. Additionally, soldiers marching behind tanks or other vehicles are at significant risk for inhalation of arthroconidia. Especially valuable insight into the epidemiology of coccidioidomycosis was obtained following an earthquake that caused landslides in a mountain range and dispersal of large dust clouds to a nearby community in Southern California in 1994. As an isolated exposure, limited in space and time, the transient dispersal of dust containing Coccidioides arthrospores revealed a clear dose dependence between exposure and disease rate (disease was highest in those closest to the source of dust clouds and that spent the longest time in dust clouds). In addition, when adjusted for exposure dose, symptomatic disease was more frequent in those older than 40 years of age. Individuals with advanced HIV infection or patients on corticosteroids or other immunosuppressants are at increased risk for severe disease. Disseminated disease is also more likely in women in their third trimester of pregnancy and may be more likely in individuals of Filipino or African descent.

Disease is indistinguishable between the two species of Coccidioides. The two species were separated due to careful phylogenic studies demonstrating divergence between the historically well described species C. immitis and the newer named species, C. posadasii. There are certain phenotypic differences, such as differential growth rates under stress conditions, but they are morphologically indistinguishable and routine laboratory testing does not separate the species. Initially, C. immitis was defined as limited to the San Joaquin Valley in California whereas C. posadasii was present diffusely throughout the endemic regions detailed for the fungus; more recent data suggest that there is significant overlap in the distribution of the two species.

Coccidioidomycosis was first described in 1892 by Alejandro Posadas in an Argentinian soldier. The organism was initially thought to be a protozoan of the order Coccidia, leading to its name. Coccidioides was not confirmed as a fungus until 1900.

Pathogenesis

The specialized spores, arthroconidia, arise from hypha and form chains of cells. The arthroconidia are 2 to 4 µm × 5 to 6 µm ovoid cells, and the chain usually consists of an intact multinucleate arthroconidia alternating with a degenerated cell. The thinner wall of the degenerated cell is readily disrupted when the chain is disturbed, such as during a wind storm, landslide, or construction, and individual or small collections of arthroconidia can then be aerosolized and subsequently inhaled. The arthroconidia undergo morphogenesis in humans or under specialized laboratory conditions at 37°C into a unique structure, a spherule. An arthroconidia converts to a spherule over approximately 2 to 4 days with the arthroconidia first developing into a round cell. Then, the spherule forms by successive growth and segmentation into an oval structure of 20 to 150 µm in diameter that contains dozens to hundreds of 2- to 4-µm endospores ( Fig. 37-5E ). Rupture of mature spherules leads to the release of endospores that, in the absence of effective host immunity, can develop locally into spherules or disseminate through hematogenous or lymphatic routes to cause disease in other tissues. Notably, arthroconidia and septate hyphae can be identified in some patients with chronic disease, especially those with diabetes, in whom there is low oxygen tension and tissue necrosis.

Disseminated coccidioidomycosis in an immunosuppressed patient.

A, Frontal chest radiograph shows numerous, randomly disseminated nodules bilaterally consistent with a miliary pattern. B, Chest CT shown in lung windows confirms the miliary pattern. Axial chest CT shown in soft tissue ( C ) and bone (D) windows demonstrates bilateral paraspinous masses ( arrows ) associated with vertebral body destruction. The CT image shown in bone windows (D) reveals the vertebral body destruction ( arrow ) to advantage. E, Photomicrograph shows characteristic giant spherule of coccidioidomycosis in a lung biopsy. (Hematoxylin and eosin stain; original magnification ×450.)

(Courtesy Michael Gotway, MD.)

Coccidioides cause disease in immunocompetent or immunocompromised individuals, with disease severity typically being worse in immunodeficient patients. Initial host responses to arthroconidia include influxes of both macrophages and neutrophils. Neutrophils may stimulate arthroconidia to convert into spherules, yet they can impede morphogenesis after the development of antibody responses. The oxidative burst is effective against arthroconidia and immature, but not mature, spherules. Additionally, after conversion to a spherule, the sheer size of this form precludes its phagocytosis by neutrophils or macrophages. In tissues, organized necrotizing granulomatous inflammation predominates, with T and B lymphocytes present at the margins of the lesions.

T lymphocyte responses are critical for protection against Coccidioides : Th1 responses are protective, whereas Th2 responses are less effective and may drive adverse outcomes. Consistent with this, lymphocyte secretion of interferon-γ is associated with resistance, whereas interleukin-4 is associated with susceptibility. The roles of other T-helper lymphocyte subsets in human immunity to Coccidioides is not yet known. Consistent with the importance of CD4 ⁺ T lymphocytes, severe disease is more common in patients with advanced HIV infection.

Individuals with prior symptomatic infection are generally protected against reinfection with either species of Coccidioides . However, waning immunity, such as in advanced HIV infection, or treatment with immunosuppressants can lead to reactivation of latent lesions or abolish protection against reinfection.

Clinical Manifestations

Disease manifestations can range from asymptomatic acquisition to pneumonia, cavitary pulmonary disease, or disseminated infection that can involve skin, bone, central nervous system, and visceral organs. Of individuals infected with Coccidioides , 60% to 80% are either asymptomatic or have mild respiratory symptoms. However, 15% to 35% of individuals develop respiratory symptoms, 1 to 4 weeks after inhalation of the arthroconidia. Although the majority of these cases resolve without sequelae, approximately 5% develop persistent or progressive pulmonary disease ( eFig. 37-5 ). Furthermore, approximately 1% to 5% will have disseminated disease, which is more common in pregnant women, people of African descent, and immunocompromised individuals (see Fig. 37-5 ).

Pulmonary Coccidioidomycosis (Valley Fever or Primary Coccidioidal Infection)

Primary symptomatic infection is typically a subacute pulmonary disease. The initial symptoms resemble influenza, with fever, cough, dyspnea, fatigue, headaches, myalgias, and arthralgias. Patients whose disease progresses to pneumonia typically have segmental or lobar disease, and mediastinal and/or hilar lymphadenopathy is characteristic ( eFig. 37-6 ). In areas with high endemicity, approximately 15% to 30% of cases of community-acquired pneumonia may be due to Coccidioides . Dermatologic immunologic manifestations such as erythema nodosum or erythema multiforme are associated with a favorable host response to the fungus. Pleural effusions complicate approximately 5% to 15% of cases, although the presence of an effusion does not correspond to increased severity of disease. The pleural fluid can be either transudative or exudative, and lymphocytes and eosinophils predominate. Coccidioidal empyema may develop, requiring aggressive interventions ( Fig. 37-6A ).

Coccidioidomycosis peripheral cavity with rupture into pleural space and empyema and bronchopleural fistula.

A, Frontal chest radiograph shows a large left hydropneumothorax; note air-fluid level. The patient was treated with extended tube thoracostomy, antifungal therapy, and eventually video-assisted thoracoscopic pleural space débridement. Coccidioides spherules were recovered from the left pleural space. B, One year later, the chest CT shows a uniformly thin-walled, peripheral cavity ( arrow ) characteristic of Coccidioides immitis pulmonary infection.

(Courtesy Michael Gotway, MD.)

Diagnosis

The gold standard for diagnosis remains isolation of Coccidioides from infected tissues; however, patients frequently do not produce sputum and the cultures take a minimum of a week to detect growth and more frequently take several weeks. Direct examination of sputum is not sensitive. Cultures are most often used in hospitalized patients.

The most commonly used diagnostic tests depend on serologic assays for the presence of antibodies to Coccidioides antigens. However, antibody responses may lag behind clinical symptoms, especially in immunocompromised individuals. Hence, negative antibody testing in such patients does not exclude infection with Coccidioides . The immunodiffusion assays for IgM and IgG antibodies are commonly used, because they provide the greatest specificity. A commercial enzyme-linked immunoassay can detect IgM and IgG antibodies to Coccidioides and is more sensitive but less specific than the immunodiffusion assay. A complement fixation method that detects IgG antibodies to Coccidioides chitinase is also used in many laboratories. Either immunodiffusion or complement fixation assays can be used to monitor responses to treatment. Molecular methodologies have not yet been validated for Coccidioides . Additional information on serologic and other diagnostic testing for coccidioidomycosis is available in Chapter 17 .

Treatment

Comprehensive treatment recommendations for coccidioidomycosis have been made by the American Thoracic Society in 2011 and the IDSA in 2005. An update in recommendations is currently in progress by the IDSA and is projected to be available by Spring 2015.