Coccidioides Species Research Articles

Coccidioidomycosis in a cat imported from the USA to Portugal

COCCIDIOIDOMYCOSIS is a mycotic infection caused by the dimorphic fungus Coccidioides species ( C immitis and C posadasii ) that affects both human beings and domestic animals (Gross and others...

The Utility of Fine Needle Aspiration for Diagnosis of Extrapulmonary Coccidioidomycosis: A Case Report and Discussion

Coccidioidomycosis typically presents as pneumonia, but rarely manifests as extrapulmonary disease. We describe a case of coccidioidal infection that presented as a neck mass and was diagnosed by fine needle aspiration (FNA). Initial clinical suspicion was for mycobacterial infection. Several modalities are available for the detection of Coccidioides species, but culture has been the mainstay of diagnosis. FNA provides a relatively noninvasive and effective modality for tissue-based diagnosis based on characteristic histological findings. It allows the additional advantage of early on-site identification, allowing for triage of the specimen, notification of laboratory staff and prompt initiation of treatment. The case herein described is intended to demonstrate an atypical presentation of extrapulmonary coccidioidomycosis and highlight the utility of FNA for diagnosis of such lesions. Clinicians should be aware of the unique advantages of FNA for evaluation of lesions of infectious etiology.

Abdominal and Pelvic Coccidioidomycosis

Coccidioidomycosis is a fungal infection endemic to the Southwestern United States that has a clinical presentation resembling community-acquired pneumonia. Disease occurs after inhalation of airborne arthroconidia. Dissemination to a variety of organ systems via hematogenous spread from a primary pulmonary focus may then occur. Coccidioidomycosis rarely involves the abdominal cavity. The authors review the spectrum of abdominal and pelvic presentations of coccidioidomycosis and report 6 unusual cases, including acute appendicitis, hepatitis and adnexal masses. Pathologists played a critical role in the diagnosis of these presentations by recognizing spherules in tissue. In only 2 of the cases were Coccidioides species cultured.

Fungal Infection from Sweeping in the Wrong Place

A 43-year-old man presented with fever, malaise, a nonproductive cough, and skin lesions near the left eyelid and eyebrow (Panel A) and left antecubital fossa (Panel B). The symptoms had developed during the course of several weeks. The patient underwent a biopsy of the facial lesion. Histopathological analysis of the biopsy specimen revealed changes characteristic of coccidioidal infection, including granulomatous inflammation and spherules containing endospores (Panel C, arrow; hematoxylin and eosin). Antibodies to coccidioides species were present in his serum. Although the patient had no history of travel to an area where coccidioidomycosis is endemic, he worked as a driver . . .

Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi

BackgroundMillions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans.Results97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales (Coccidioides species) and the mould Aspergillus fumigatus. The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species.ConclusionsOur results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens.

Coccidioidomycosis in Liver Transplant Recipients in an Endemic Area

Coccidioidomycosis is an infection caused by Coccidioides species, which are endemic for the Southwestern United States and parts of Central America and South America. Most infected individuals are asymptomatic or have mild-to-moderate respiratory illness. Coccidioidomycosis is more severe in patients with depressed cellular immunity, such as organ transplant recipients. We retrospectively reviewed charts of 391 liver transplant recipients (mean follow-up, 38.7 months; range, 2-105 months). Before transplantation, 12 patients had a history of coccidioidomycosis and 13 patients had asymptomatic seropositivity. Of these 25 patients, 23 had no active coccidioidomycosis posttransplantation and 2 had reactivated infection. One of 5 patients with indeterminate serology before transplantation died of disseminated coccidioidomycosis shortly after transplantation. De novo coccidioidomycosis developed in 12 patients (3%) who had no evidence of coccidioidomycosis pretransplantation. Of 15 total episodes of posttransplantation coccidioidomycosis, 10 (66%) occurred during the first year. Dissemination was noted in 33% of active coccidioidomycosis after transplantation; two patients (13%) died of coccidioidomycosis. Because most coccidioidal infections occurred in the first posttransplantation year despite targeted antifungal prophylaxis, we recommend a new strategy of universal antifungal prophylaxis for 6-12 months for liver transplant recipients who reside in the endemic area.

Successful kidney transplantation after coccidioidal meningitis

Coccidioidomycosis is a fungal infection primarily found in residents or visitors to geographic areas where Coccidioides species are endemic, including the southwestern United States, northwestern Mexico, and certain areas of Central and South America. The infection rarely disseminates, but certain populations are at higher risk of dissemination. One population at high risk of disseminated disease is solid organ transplant recipients. At our transplant center in Arizona, patients with proven coccidioidal infection before transplantation undergo thorough counseling about the risks of dissemination and possible death from coccidioidomycosis subsequent to the use of immunosuppressive medications after transplantation. Currently, patients with coccidioidal infection before transplantation are maintained on lifelong infection suppression with triazole therapy. We present the first successful case of a kidney transplant in a patient after treatment for coccidioidal meningitis without post-transplant reactivation of the coccidioidal infection.

Coccidioidomycosis in Lung Transplant Recipients in an Endemic Area

PURPOSE: Coccidioides species commonly cause pneumonia in endemic areas. In immunosuppressed patients, the risk of severe disease increases. Incidence of infection in solid organ transplant recipients has been reported as 1-2%.¹ The burden of disease in lung transplant recipients is unknown.

Disseminated primary coccidioidomycosis of the chest wall

FIGURE 1. High-powered micrograph of Coccidioides species spherule in skeletal muscle tissue (circle). Pulmonary coccidioidomycosis, or valley fever, is a diagnosis with increasing incidence in the western United States. Although coccidioidomycosis is an infectious disease classically described to be endemic to the southwestern United States, the first cases were indentified in central California. One defined population that has been especially subject to this disease is residents of the greater Sacramento counties in California, with 0.1 to 5.0 cases per 100,000 population from 2001 to 2008. Coccidioidomycosis spreads through inhalation of aerosolized mold or arthroconidia. Although pulmonary (acute pneumonia, chronic progressive pneumonia, and pulmonary nodules) and certain extrapulmonary (nonmeningeal and meningitis) manifestations of coccidioidomycosis infection are well described, treatment of disseminated coccidioidomycosis presenting as chest wall disease is not. In this report we present 2 cases that illustrate the clinical presentation and treatment strategy of disseminated coccidioidomycosis infection of the chest wall.

TaqMan Real-Time PCR Assay forCoccidioides

Sir: I read the recent publication by Sheff et al. with great interest [1]. These authors concluded that their new TaqMan real-time PCR assay would provide a rapid and accurate method for the differentiation of the Coccidioides species [1]. While I agree that this new diagnostic tool can provide accurate results, there remain questions as to whether it is rapid and cost effective. Real time PCR might provide faster results than basic mycological identifi cation procedures, but its use is associated with higher costs. The expenses associated with Sheff et al.’s assay must include the costs of the instrumentation and reagents needed for this complex

Endemic Fungal Infections in Solid Organ Transplant Recipients

Endemic Fungal Infections in Solid Organ Transplant Recipients

Coccidioidal meningitis and brain abscesses

Coccidioides species are the most common etiologic agents of chronic meningitis in regions endemic for coccidioidomycosis. Occasionally, even short-term travel to endemic regions results in the acquisition of meningeal disease, so awareness of this complication of coccidioidomycosis is important even in nonendemic areas. The prognosis depends on the early recognition and treatment of the disease, so it is important to be familiar with the varied clinical manifestations, risk factors associated with meningeal involvement, diagnostic challenges, and therapeutic modalities. We performed a retrospective analysis of 71 cases with coccidioidomycosis involving the CNS seen from 1996 to 2007 at a referral medical center in southern Arizona. The only presenting symptom found in the majority of patients was headache. Those who were immunocompromised (most commonly HIV/AIDS and chronic steroid therapy) were at increased risk, but diabetics were not at increased risk. There was a preponderance of males (2:1) and people of Hispanic, African, and Asian (especially Pacific Isles) background. CSF anticoccidioidal antibody and culture were frequently negative on presentation, but in these cases, the serum antibody test was usually positive. Imaging studies were helpful in two thirds of cases, most commonly demonstrating basilar meningitis or hydrocephalus, which frequently required ventriculoperitoneal shunting. Most were treated with fluconazole, and prognosis was good for most of those who remained on treatment. Coccidioidal meningitis remains a diagnostic challenge, but the diagnosis can usually be made successfully when coccidioidal serum and CSF antibodies and cultures are combined with appropriate imaging studies.

Surgery for Pulmonary Coccidioidomycosis: A 10-Year Experience

Coccidioidomycosis results from infection with Coccidioides species endemic to the southwestern United States. The mobile US population has resulted in incremental cases being found throughout the world. The fungal infection can result in pulmonary sequelae, including nodules, cavities, and complications requiring treatment by the thoracic surgeon. A retrospective chart review was conducted of 1,496 patients with coccidioidomycosis treated at our institution (January 1998 to December 2008) to identify those requiring surgery. Of the 1,496 patients, 86 (6%; mean age, 58 years [range, 18 to 81], 48 women) underwent operations. Radiographs revealed 59 nodules, 18 cavities, 2 infiltrates, and 7 complications of disease (e.g., effusion, pneumothorax, and empyema). Of the 86 patients, 40% underwent resection for persistent symptoms or disease progression despite adequate antifungal therapy. One third of the operations were performed by video-assisted thoracoscopic surgery. Morbidity, 21% (18 patients), and in-hospital mortality, 2% (2 patients), were greater after resection for cavitary lesions with resultant complications versus for nodular disease: 41% versus 12% (p < or = 0.002) and 8% versus 0% (p < 0.005). Prolonged air leaks or bronchopleural fistulas were the most common complications (13 patients). Postoperative antifungal therapy was administered to 42% of patients (89% of cavitary and complicated). There were no cases of recurrence at follow-up (mean, 24 months). Surgical intervention was indicated for only a few patients, most commonly for diagnostic dilemmas involving nodular disease, symptomatic nonresponsive cavitary disease, or complications. Prolonged air leaks were the main cause of morbidity. Resection should result in symptom resolution and long-term freedom from recurrence.

Cerebral coccidioidomycosis after renal transplantation in a non-endemic area

Coccidioidomycosis is a fungal infection caused by Coccidioides species endemic to the desert south western United States. In healthy people, manifestations range mainly from asymptomatic to mild influenza-like syndrome. In immunosuppressed patients, extrapulmonary dissemination is common. We report the case of a patient with a parenchymal central nervous system lesion. This presentation is considered very rare. The highest risk of infection after solid organ transplantation occurs during the first year. Risk factors include treatment of acute rejection. In the reported case, the infection was probably donor-derived, as our patient had no history of traveling to endemic areas. Mortality is high among transplanted recipients with coccidioidomycosis, particularly those with disseminated infection.

Expert Opinion: What To Do When There IsCoccidioidesExposure in a Laboratory

Inadvertent exposure to Coccidioides species by laboratory staff and others as a result of a mishap is not an uncommon cause of infection in clinical microbiology laboratories. These types of infection may occur in laboratories outside the endemic areas, because the etiologic agent is unexpected in the submitted specimens and because personnel may be unfamiliar with the hazards of dealing with Coccidioides species in the laboratory. Coccidioidal infections are often difficult to treat, and outcomes can be poor. Here, we emphasize prevention and an approach to a laboratory accident that minimizes the risk of exposure to laboratory staff and staff in adjacent areas. On the basis of an artificially large exposure to arthroconidia that may occur as a result of a laboratory accident, a conservative approach of close observation and early treatment of exposed staff is discussed.

Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives

While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.

The Spectrum and Presentation of Disseminated Coccidioidomycosis

Purpose Extrapulmonary dissemination of Coccidioides species is associated with significant morbidity and mortality. The clinical manifestations vary widely according to the host, the severity of illness, and location of dissemination. The morbidity and mortality can be reduced by early recognition and treatment, which in turn depends on understanding the spectrum and presentation of disease. Methods We performed a retrospective analysis of 150 cases with extrapulmonary nonmeningeal disease seen from 1996 to 2007 at a referral medical center in an endemic region. Results Hematogenous dissemination was associated with high mortality and occurred primarily in immunocompromised patients, but only 30% of patients with more limited forms of dissemination were immunocompromised. In keeping with prior studies, there was a preponderance of males (nearly 2:1) and people of African or Asian (especially Pacific Islanders) descent. In contrast, Hispanics and diabetics were not at increased risk. Serology was frequently negative in immunocompromised patients, but the diagnosis could be established by isolation of the organism in culture, or in histologic or cytologic specimens. Conclusions Although coccidioidomycosis is a great imitator, the diagnosis can usually be made readily if a high level of suspicion is maintained and appropriate diagnostic testing is performed. In most patients, that will include serologic testing in addition to cultures and histology or cytology of appropriate samples.

Molecular phylogeny of animal pathogen Lacazia loboi inferred from rDNA and DNA coding sequences

Lacazia loboi is a geographically restricted, uncultivated fungal pathogen of humans and dolphins. Previous investigations using 18S small unit rDNA, chitin synthase 2 and gp43 DNA sequences positioned L. loboi as a close relative of Paracoccidioides brasiliensis. However, given the few individuals of L. loboi studied and the high degree of genetic variation observed in P. brasiliensis, the existence of L. loboi as an independent species has been questioned. To investigate the phylogenetic position of this species, we conducted a phylogenetic analysis using 20 L. loboi collections ( L. loboi was obtained from proven cases of lacaziosis and 14 collections were maintained in mice, the others were analyzed from DNA taken directly from infected human tissue.). L. loboi DNA sequence was compared to that from 17 P. brasiliensis strains that represented the known variation in this species, and outgroup taxa in the Onygenales ( Ajellomyces and Coccidioides species). Our analyses used DNA sequence from ITS rRNA, and partial coding sequences of chitin synthase 4, ADP-ribosylation factor, and gp43. Nucleotide variation among strains of L. loboi was minor but numerous nucleotide mismatches and multiple gaps were found for these gene regions among members in the Ajellomycetaceae, including P. brasiliensis. Phylogenies inferred using neighbor-joining, maximum parsimony and Bayesian analyses showed no significant conflict and depicted L. loboi as a well-supported, monophyletic group that was sister to the Paracoccidioides clade. These results argue for maintaining L. loboi as a taxon independent from Paracoccidioides within the Ajellomycetaceae.

Factors and Outcomes Associated with the Decision to Treat Primary Pulmonary Coccidioidomycosis

Studies that assess the value of initiating oral antifungal therapy to treat primary pulmonary coccidioidomycosis have not been published previously. Prospectively collected observational data were analyzed from patients with primary pulmonary coccidioidomycosis who attended a single clinic devoted to the management of coccidioidomycosis that is located in a region of coccidioidal endemicity. Fifty-four of 105 patients with primary pulmonary coccidioidomycosis were prescribed antifungal therapy, whereas 51 were not. No statistically significant differences were found between the 2 groups with regard to age, ethnicity, sex, or the presence or type of underlying diseases (for all, P > .100). Treated patients had a higher total clinical score (P = .001), had a higher symptom score (P = .049), and were more likely to have a culture of sputum that was positive for Coccidioides species (P = .048), compared with patients who were not prescribed therapy. There was prospective in-clinic follow-up for 43 patients, for a median duration of 286 days (range, 35-1124 days). The health of all 16 patients who were not treated improved after a median of 217 days, and no patients developed complications during follow-up. However, 2 of 20 patients who were treated but whose therapy was subsequently stopped developed disseminated disease. The rate of clinical improvement was similar in treated and untreated patients (P = .899). A retrospective follow-up of 58 of the remaining 62 patients identified 6 additional patients with complications, all from the group that was initially treated but whose therapy was subsequently discontinued. Approximately one-half of patients with primary pulmonary coccidioidomycosis were prescribed antifungal therapy on the basis of clinical severity. Complications were seen only among patients in the group that was prescribed therapy but whose treatment was discontinued.

Coccidioidomycosis in Elderly Persons

Coccidioidomycosis is a fungal infection acquired via inhalation of airborne fungal arthrospores of Coccidioides species in regions of endemicity in the deserts of the southwestern United States and northern Mexico. In recent years, the incidence of coccidioidomycosis has increased in areas of endemicity, and previous studies have found the highest incidence of coccidioidal infection in Arizona among persons in older age groups. We conducted a retrospective review of data for all patients with coccidioidomycosis who were treated at our institution that compared clinical manifestations of coccidioidomycosis in patients aged >or=60 years with those in patients aged <60 years. We compared 210 patients aged >or=60 years with 186 patients aged <60 years. No significant differences were observed with regard to manifestations of coccidioidomycosis, even after adjustment for comorbid conditions, excluding immunosuppression. Regardless of age, when coccidioidal illnesses in immunosuppressed patients were compared with those in nonimmunosuppressed patients, immunosuppressed patients were significantly more likely to have extrapulmonary dissemination of infection, to require hospitalization, and to have progressive infection or to die of coccidioidomycosis. Univariate logistic regression identified immunosuppression as the only marker that increased risk of extrapulmonary dissemination of infection (odds ratio, 2.13;P=.05), hospitalization (odds ratio, 2.68; P<.001), and death (odds ratio, 8.39; P<.001). Multivariate analysis revealed that neither age nor an interaction of age and immunosuppression had a significant impact on coccidioidal manifestations. Coccidioidomycosis is a serious illness in all patients, but its different manifestations in older-aged persons, compared with those in younger-aged persons, may be related to immunosuppression rather than age alone.