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PubMed2006

A recombinant aspartyl protease of Coccidioides posadasii induces protection against pulmonary coccidioidomycosis in mice.

Coccidioidomycosis is a respiratory disease of humans caused by the desert soil-borne fungal pathogens Coccidioides spp. Recurrent epidemics of this mycosis in the southwestern United States have contributed significantly to escalated health care costs. Clinical and experimental studies indicate that prior symptomatic coccidioidomycosis induces immunity against subsequent infection, and activation of T cells is essential for containment of the pathogen and its clearance from host tissue. Development of a human vaccine against coccidioidomycosis has focused on recombinant T-cell-reactive antigens which elicit a durable protective immune response against pulmonary infection in mice. In this study we fractionated a protective multicomponent parasitic cell wall extract in an attempt to identify T-cell antigens. Immunoblots of electrophoretic separations of this extract identified patient seroreactive proteins which were subsequently excised from two-dimensional polyacrylamide gel electrophoresis gels, trypsin digested, and sequenced by tandem mass spectrometry. The full-length gene which encodes a dominant protein in the immunoblot was identified using established methods of bioinformatics. The gene was cloned and expressed, and the recombinant protein was shown to stimulate immune T cells in vitro. The deduced protein was predicted to contain epitopes that bind to human major histocompatibility complex class II molecules using a TEPITOPE-based algorithm. Synthetic peptides corresponding to the predicted T-cell epitopes induced gamma interferon production by immune T lymphocytes. The T-cell-reactive antigen, which is homologous to secreted fungal aspartyl proteases, protected mice against pulmonary infection with Coccidioides posadasii. We argue that this immunoproteomic/bioinformatic approach to the identification of candidate vaccines against coccidioidomycosis is both efficient and productive.

Amino Acid Sequence↗

PubMed1983

Antigenemia detected in human coccidioidomycosis.

To advance the serological diagnosis of coccidioidomycosis, a radioimmunoassay was developed to detect an antigen of Coccidioides immitis and evaluated with serum samples from patients and controls. The assay antigen was fractionated from a culture filtrate of C. immitis cells by Sephacryl S300 gel chromatography. The assay used preliminary acid-heat extraction to dissociate serum-bound antigen and staphylococcal protein A as an absorbent. Antigenemia was detected in five (56%) of nine patients with coccidioidomycosis. Three of four negative tests occurred with sera from patients who had already received antifungal chemotherapy. Antigenemia was not detected in 106 control patients and normal donors. One false-positive reaction was observed in a patient with histoplasmosis. In all nine patients with active coccidioidomycosis, anti-C. immitis antibodies were detected during the initial evaluation or in the follow-up. In summary, an immunoassay for C. immitis antigenemia was developed; antigenemia was detected in five (56%) of nine patients with active coccidioidomycosis and a positive test indicated active or persistent disease.

Adult↗

PubMed2004

Seroincidence of Coccidioidomycosis during military desert training exercises.

Coccidioidomycosis is a common fungal infection acquired in the southwestern United States. This is the first study in over 2 decades to determine the seroincidence of Coccidioides immitis infections among U.S. military members performing training exercises in an area of endemicity. Only 8% of participants were aware of coccidioidomycosis, despite the majority having visited or lived previously in an area of endemicity. One (0.6%) of the 178 participants developed "definite" serologic evidence of infection over a 5-week training period; four (2.3%) additional patients developed "possible" coccidioidomycosis infections. None had complicated disease. The calculated annual incidence ranged from 6 to 32%. This study suggests that the risk of serious coccidioidomycosis is low among military personnel during desert training exercises; however, disease incidence may vary depending on specific activities and geographic factors. Due to the potential morbidity and mortality of this infection, preventative strategies, including vaccine development, are advocated.

Adolescent↗

PubMed1976

In vivo and in vitro cell-mediated responses in coccidioidomycosis. I. Immumologic responses of persons with primary, asymptomatic infections.

Chest roentgenograms of 58 children who were skin test positive to coccidioidin and resided in an area endemic for coccidioidomycosis revealed that 34 per cent had roentgenographic evidence of an inflammatory process, 14 per cent showed calcific densities, and 52 per cent showed no evidence of infection. The in vitro lymphocyte responses of children who had evidence of an inflammatory process (Group I) were compared with those of children who had calcific densities (Group II); those of children who were coccidioidin skin test negative and had normal chest roentgenograms (Group III); and those of patients who had active coccidioidomycosis (Group IV). The mean lymphocyte transformation responses (expressed as cpm times 10-(4)) of Groups I, II, III, and IV to a coccidioides antigen were 16.8, 19.5, 4.2, and 7.0, respectively. The mean migration inhibitory factor responses of these groups were 22.4, 20.0, 1.2, and 4.0 per cent, respectively. Thus, the over-all responses of children in Groups I and II were comparable to each other, whereas the responses of patients in Group IV were depressed to the extent that they were indistinguishable from those of coccidioidin skin test-negative donors in Group III. Follow-up chest roentgenograms taken 3 months after the immunologic assays were performed revealed that the one subject in Group I who had been nonresponsive in the lymphocyte assays had now stabilized his infection, as evidenced by calcifications. In contrast, the 2 subjects in Group I who had yet to stabilize their infection had exhibited strong in vitro lymphocyte responses. These findings suggest that primary, asymptomatic coccidioidomycosis is not associated with an immunologically nonresponsive state. However, patients with active, progressive coccidioidomycosis do have a depressed immunologic response to coccidioides antigens.

Adolescent↗

PubMed1981

Flexible fiberoptic bronchoscopy for diagnosing pulmonary coccidioidomycosis.

To assess the diagnostic yield of flexible fiberoptic bronchoscopy (FFB), we reviewed records of 30 patients who had (1) cultural and/or histologic evidence of coccidioidomycosis, (2) abnormal chest roentgenograms, and (3) undergone FFB. Each patient underwent a complete examination including sputum collection for smears and culture. As additional diagnostic information was needed, FFB was performed in all patients, followed by percutaneous needle aspiration in 4 patients and thoracotomy in 10. Prebronchoscopy sputum cultures yielded Coccidioides immitis in 6 of 30 patients (20%). Bronchoscopy provided specimens diagnostic of coccidioidomycosis in 16 of 30 patients (53%), and in 10 of 30 (33%), FFB was the first procedure of the examination to produce a diagnostic specimen. The diagnosis was first obtained by needle aspiration in 1 of 30 (3%), by extrathoracic specimens in 3 of 30 (10%), and by thoracotomy in 10 of 30 (33%). All 8 patients with a solitary pulmonary nodule (SPN) had nondiagnostic FFB and comprised the majority of patients not diagnosed until thoracotomy was performed. When patients with a SPN were excluded, 20 of 29 (69%) FFB procedures documented coccidioidal infection. Seven of 22 (32%) prebronchoscopy sputum collections compared with 17 of 29 (59%) FFB procedures produced positive cultures for C. immitis. One of 22 (5%) prebronchoscopy sputum collections, compared with smears and biopsies from 8 of 29 (28%) FFB procedures, produced immediate microscopic evidence of coccidioidomycosis. Coexisting pulmonary pathologic findings in 4 patients were uncovered by FFB. Except in patients with a SPN, FFB is a valuable procedure for documenting pulmonary coccidioidomycosis when sputum specimens are nondiagnostic.

Biopsy, Needle↗

PubMed1991

Itraconazole in the treatment of coccidioidomycosis.

Sixteen patients with coccidioidomycosis were treated with itraconazole for one year. Sixteen suffered from pulmonary coccidioidomycosis, two of them had associated mediastinal lesions, and one suffered from skin coccidioidomycosis. The daily dose used was 400 mg during the one-year period. Patients were clinically evaluated every month and tested for mycosis every three months. All patients except for one showed negative cultures on the third month after treatment began. Effectiveness achieved was excellent in eight patients (50 percent); a very good response was found in seven patients (44 percent); no response was seen in one patient (6 percent). There were four (25 percent) relapses and one dropout. Side effects seen were high blood pressure (19 percent) and lower limb edema (6 percent), which was temporary and at no time required discontinuing the drug therapy. We believe that itraconazole is an effective drug to treat coccidioidomycosis with a wide safety margin. It is well tolerated, and the incidence of relapses was low.

Adult↗

PubMed2001

Clinical presentation, radiological findings, and treatment results of coccidioidomycosis involving the spine: report on 23 cases.

OBJECT: This study was conducted to review the presentation and management of patients with coccidioidomycosis involving the spine. METHODS: The authors reviewed 23 cases of spinal coccidioidomycosis treated at their institutions. There were 20 males and three females who ranged in age from 9 to 62 years. Non-Caucasian individuals were disproportionately represented. Spinal disease was the first manifestation of disseminated coccidioidomycosis in 10 cases. Thirteen patients with meningitis, soft-tissue involvement, or pulmonary involvement developed new spinal lesions despite undergoing continued systemic therapy with amphotericin and/or fluconazole. In all patients computerized tomography and magnetic resonance imaging studies demonstrated preferential involvement of the disc spaces, vertebral bodies, and pedicles with extensive paravertebral phlegmons and retropharyngeal, mediastinal, or psoas abscesses. Despite the significant imaging findings, only four patients presented with a significant neurological deficit. Local pain or radiculopathy was the most common complaint. Twenty patients underwent invasive therapy. In five patients with prominent psoas abscesses and disc space disease, drainage was performed after inserting a percutaneous catheter. Progressive bone destruction necessitated debridement and fusion in one of these patients, and two others had poor outcomes after receiving antifungal therapy alone. Initially 15 patients underwent debridement and fusion in which instrumentation (10 cases) or bone graft alone was used (five cases). One patient worsened neurologically after surgery, and another patient required reoperation for a failed fusion and to correct progressive kyphosis. Four of the 23 patients died of complications related to fungemia. Most of the 15 surviving patients have required long-term antifungal therapy for spinal and extraspinal foci. CONCLUSIONS: Spinal coccidioidomycosis can be an aggressive disease process. Systemic antifungal therapy fails to prevent de novo spinal involvement and is usually insufficient treatment for established spinal disease.

Adolescent↗

PubMedDate not supplied

Coccidioidomycosis: a reemerging infectious disease.

Coccidioides immitis, the primary pathogenic fungus that causes coccidioidomycosis, is most commonly found in the deserts of the southwestern United States and Central and South America. During the early 1990s, the incidence of coccidioidomycosis in California increased dramatically. Even though most infections are subclinical or self-limited, the outbreak is estimated to have cost more than $66 million in direct medical expenses and time lost from work in Kern County, California, alone. In addition to the financial loss, this pathogen causes serious and life-threatening disseminated infections, especially among the immunosuppressed, including AIDS patients. This article discusses factors that may be responsible for the increased incidence of coccidioidomycosis (e.g., climatic and demographic changes and the clinical problems of coccidioidomycosis in the immunocompromised) and new approaches to therapy and prevention.

Antifungal Agents↗

PubMedDate not supplied

Coccidioidomycosis in New York State.

Coccidioidomycosis, a systemic fungal disease caused by Coccidioides immitis, is endemic in the southwestern United States and in parts of Mexico and Central and South America. Only sporadic cases have been reported in areas (including New York) where the disease is not endemic. We used hospital discharge records and state mycology laboratory data to investigate the characteristics of C. immitis infections among New York State residents. From 1992 to 1997, 161 persons had hospital discharge diagnoses of coccidioidomycosis (ICD9 Code 114.0 - 114.5, 114.9). From 1989 to 1997, 49 cultures from patients were confirmed as C. immitis; 26 of these patients had traveled to disease-endemic areas. Fourteen of 16 isolates had multilocus genotypes similar to those of Arizona isolates, which corroborates the travel-related acquisition of the disease. Our results indicate that coccidioidomycosis may be more common in New York residents than previously recognized. Increased awareness among health-care providers should improve timely diagnosis of coccidioidomycosis and prevention of associated illnesses and deaths among patients in nondisease-endemic areas.

Adult↗

PubMed1999

Delayed-type hypersensitivity, in vitro T-cell responsiveness and risk of active coccidioidomycosis among HIV-infected patients living in the coccidioidal endemic area.

The prognostic importance of specific and general tests of immune function were examined among a cohort of 170 subjects infected with human immunodeficiency virus type-1 (HIV), living in an area endemic for the fungal infection coccidioidomycosis. Using the proportional hazards model and multivariate analysis, lack of expression of coccidioidal delayed-type hypersensitivity (DTH) was found to be dependent on anergy in response to the non-coccidioidal antigens mumps, Trichophyton and Candida (relative hazard 4.2, 95% CI 1.8-9.8, P=0.001). Among subjects with CD4 lymphocyte counts >/=250 microl-1 on entry into the study, the in vitro lymphocyte transformation (LT) response to the coccidioidal antigen toluene spherule lysate was 4967+/-1652 (mean counts per minute (c.p.m.)+/-SEM) in subjects with coccidioidal DTH compared with 136+/-222 in those with negative DTH (P<0.001). However, amongst those whose CD4 count was <250 microl-1, LT responses were low and there was no significant difference based on coccidioidal DTH (P=0.965). Using the proportional hazards model and multivariate analysis, only a CD4 count <250 microl-1 was prognostically associated with the development of either active coccidioidomycosis or AIDS. These data indicate that immunodeficiency, particularly a CD4 lymphocyte count <250 microl-1, is the most important factor in the lack of expression of specific immunity to coccidioidomycosis and in the development of active coccidioidomycosis among HIV-infected individuals living in the coccidioidal endemic area.

Arizona↗

PubMed1975

Female genital coccidioidomycosis.

Three cases of coccidioidomycosis of the female genital tract are reviewed. The diagnosis was made by laparotomy in 2 patients who presented with tender adnexal masses, and by endometrical curettage in a third patient with disseminated coccidioidomycosis. Hysterectomies were performed in all 3 patients; 1 had a bilateral salpingo-oophorectomy and the others a bilteral salpingectomy and unilateral oophorectomy. Two patients received chemotherapy with amphotericin B. One patient died 4 years after her operation from disseminated and meningeal coccidioidomycosis. In a female patient who has resided in an endemic region and who presents with pelvic pain of obscure origin, unexplained infertility, a menstrual disorder, or a chronic, refractory pelvic inflammatory disease, genital coccidioidomycosis should be considered in the differential diagnosis.

Adolescent↗

PubMed2004

[A clinical and pathological study of coccidioidomycosis and pregnancy in four Mexican women].

BACKGROUND: In northeastern Mexican population prevalence of positive cutaneous reaction to coccidioidin varies from 30 to 49%. Pregnancy is a risk factor for disseminated coccidioidomycosis. OBJECTIVES: 1) To describe the clinical spectrum of coccidioidomycosis in four women who acquired the disease during pregnancy or puerperium. 2) To discuss the autopsy findings. 3) To review the medical literature. MATERIAL AND METHODS: From 1983 to 2000, files of the Pathology Department of a reference tertiary hospital in northeastern Mexico were reviewed. Four cases of 4,598 autopsies corresponded to pregnant women with coccidioidomycosis. Clinical and autopsy charts, and the histological material were studied. RESULTS: Clinical spectrum included a septicemia case with fetal lost, an atypical pneumonia, a chronic meningitis with neuropsychiatric alterations and a patient with hypertensive pregnancy disease with secondary renal insufficiency and repeated episodes of pneumonia. All patients at autopsy showed multiple granulomas with abundant mycotic spherules. Lung involvement included bilateral 2-10 mm nodules. CONCLUSION: In pregnant women of endemic areas or who had traveled to these zones during pregnancy, coccidioidomycosis should be considered in the differential diagnosis of febrile syndrome with pneumonia, specially if it is accompanied of bilateral nodular infiltrates in lung, with or without erythema nodosum or meningitis.

Adult↗

PubMed2006

Guillain-Barré syndrome in an immunocompromised patient and coccidioidomycosis infection.

A 70-year-old man was referred for evaluation of a 2-week history of numbness and progressive weakness in his lower and upper extremities and subsequently diagnosed with Guillain-Barré syndrome. The patient had been taking mycophenolate mofetil 500 mg twice daily and tacrolimus 6 mg daily for immunosuppression following a kidney transplant 2 years earlier. However, 5 weeks prior to presentation he had been diagnosed with pneumonia due to coccidioidomycosis and his tacrolimus dose was reduced to 1 mg daily to prevent a drug interaction with fluconazole, which was prescribed to treat the coccidioidomycosis infection. The authors surmise that the reduced tacrolimus dose, coupled with a relatively low maintenance dose of mycophenolate mofetil, left the patient less immunosuppressed and therefore able to mount an immune response to the coccidioidomycosis infection, resulting in Guillain-Barré syndrome. This is the first known report of an association between coccidioidomycosis infection and Guillain-Barré syndrome.

Aged↗

PubMed1990

A fatal case of disseminated coccidioidomycosis in Louisiana.

We are reporting a fatal case of coccidioidomycosis, which is an uncommon mycotic infection in Louisiana. The patient was a 21-year-old, apparently immunocompetent, pregnant black woman who had fever of unknown origin for 6 weeks. She had recently moved from Arizona. Despite her progressively worsening condition, the patient delivered a baby girl who has been doing well. An exhaustive workup and a laparotomy failed to lead to the diagnosis. The diagnosis was established by trans-bronchial biopsy a day before her death. At autopsy, disseminated coccidioidomycosis was observed. A review of the mycology records of Charity Hospital of New Orleans revealed this to be the second case of coccidioidomycosis in 20 years. Coccidioidomycosis should be considered in the differential diagnosis of fever of unknown origin in Louisianians who have lived in endemic areas, especially in pregnant patients, who are at an increased risk of disseminated infection.

Adult↗

PubMed1973

Coccidioidomycosis in Northern California. An outbreak among archeology students near Red Bluff.

An outbreak of coccidioidomycosis occurred among 39 archeology students in the summer of 1972. The students excavated Indian ruins near Red Bluff in Tehama County, California, 20 miles north of the previously recognized northernmost limit of endemicity. At least 17 persons contracted an illness clinically compatible with a diagnosis of coccidioidomycosis. Coccidioidomycosis was documented by skin test conversion as well as by specific serologic reactions. Coccidioides immitis was also isolated from two soil samples taken at the excavation site. In light of its ecological requirements, it is doubtful that C. immitis will be recovered much farther north than Red Bluff. The occupational hazard of coccidioidomycosis to archeologists and others employed in known endemic areas remains a substantial threat to health.

Adolescent↗

PubMed1982

Coccidioidomycosis in renal replacement therapy.

The potential risk of coccidioidomycosis has led to concern about the advisability of maintaining renal transplantation programs in endemic areas. We reviewed the charts of 721 patients undergoing dialysis and 260 renal transplant recipients in Arizona to determine the incidence, risk factors, and clinical course of coccidioidomycosis in these immunosuppressed populations. Symptomatic infection occurred in six (0.83%) patients undergoing dialysis and 18 (6.9%) transplant recipients. Male sex and blood type B predisposed to dissemination. Urine cultures for fungus were important diagnosis aids. Four of six patients with infection limited to the thorax and five of 18 patients with dissemination remained alive after seven months to 7 1/2 years. Although the rate of dissemination (75%) and mortality (63%) from coccidioidomycosis were high, the incidence of infection was low and does not preclude renal transplantation in Arizona. Those who have received transplants elsewhere should be advised not to move or to visit areas endemic for coccidioidomycosis.

ABO Blood-Group System↗

PubMedDate not supplied

Primary diagnosis of disseminated coccidioidomycosis by fine needle aspiration of a neck mass. A case report.

Coccidioidomycosis is a pulmonary fungal infection endemic to the southwestern United States and northern Mexico. Disseminated coccidioidomycosis occurs in 0.1-0.5% of cases and is a life-threatening condition. We report a case of disseminated coccidioidomycosis in an immunocompetent black male with cutaneous lesions, a flocculent neck mass, bilateral hilar adenopathy, persistent fever, night sweats and malaise. The clinical suspicion was lymphoma with cutaneous involvement. Fine needle aspiration (FNA) of the neck mass provided the primary diagnosis of coccidioidomycosis. It was confirmed by culture of FNA-obtained fluid and a subsequent biopsy of a cutaneous lesion. As shown in this case, FNA of soft tissue masses may provide rapid identification of the responsible organism and allow early initiation of therapy for this potentially life-threatening infection.

Adult↗

PubMed1994

Update: coccidioidomycosis--California, 1991-1993.

Coccidioidomycosis is an infection caused by the fungus Coccidioides immitis, which resides in the soil in some areas of Arizona, California, Nevada, New Mexico, Texas, and Utah. Infection can occur when airborne, infective arthroconidia are inhaled. Symptomatic coccidioidomycosis, which occurs in approximately 40% of all infections, has a wide clinical spectrum, including mild influenza-like illness, severe pneumonia, and disseminated disease. Beginning in 1991, the number of cases of coccidioidomycosis reported annually to the California Department of Health Services (CDHS) increased dramatically (1) (Figure 1). This report summarizes the occurrence of coccidioidomycosis in California during 1991-1993.

California↗