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PubMed2000

A major cell surface antigen of Coccidioides immitis which elicits both humoral and cellular immune responses.

Multinucleate parasitic cells (spherules) of Coccidioides immitis isolates produce a membranous outer wall component (SOW) in vitro which has been reported to be reactive with antibody from patients with coccidioidal infection, elicits a potent proliferative response of murine immune T cells, and has immunoprotective capacity in a murine model of coccidioidomycosis. To identify the antigenic components of SOW, the crude wall material was first subjected to Triton X-114 extraction, and a water-soluble fraction derived from this treatment was examined for protein composition and reactivity in humoral and cellular immunoassays. Protein electrophoresis revealed that the aqueous fraction of three different isolates of C. immitis each contained one or two major glycoproteins (SOWgps), distinguished by their molecular sizes, which ranged from 58 to 82 kDa. The SOWgps, however, showed identical N-terminal amino acid sequences, and each was recognized by sera from patients with C. immitis infection. Antibody raised against the purified 58-kDa glycoprotein (SOWgp58) of the Silveira isolate was used for Western blot and immunolocalization analyses. Expression of SOWgp was shown to be parasitic phase specific, and the antigen was localized to the membranous SOW. The water-soluble fraction of SOW and the purified SOWgp58 were tested for the ability to stimulate proliferation of human peripheral monocytic cells (PBMC). The latter were obtained from healthy volunteers with positive skin test reaction to spherulin, a parasitic-phase antigen of C. immitis, and from volunteers who showed no skin test reaction to the same antigen. The SOW preparations stimulated proliferation of PBMC from skin test-positive but not skin test-negative donors, and the activated cells secreted gamma interferon, which is indicative of a T helper 1 pathway of immune response. Results of this study suggest that SOWgp is a major parasitic cell surface-expressed antigen that elicits both humoral and cellular immune responses in patients with coccidioidal infection.

Amino Acid Sequence↗
PubMed2005

A metalloproteinase of Coccidioides posadasii contributes to evasion of host detection.

Coccidioides posadasii is a fungal respiratory pathogen of humans that can cause disease in immunocompetent individuals. Coccidioidomycosis ranges from a mild to a severe infection. It is frequently characterized either as a persistent disease that requires months to resolve or as an essentially asymptomatic infection that can reactivate several years after the original insult. In this report we describe a mechanism by which the pathogen evades host detection during the pivotal reproductive (endosporulation) phase of the parasitic cycle. A metalloproteinase (Mep1) secreted during endospore differentiation digests an immunodominant cell surface antigen (SOWgp) and prevents host recognition of endospores during the phase of development when these fungal cells are most vulnerable to phagocytic cell defenses. C57BL/6 mice were immunized with recombinant SOWgp and then challenged with a mutant strain of C. posadasii in which the MEP1 gene was disrupted. The animals showed a significant increase in percent survival compared to SOWgp-immune mice challenged with the parental strain. To explain these results, we proposed that retention of SOWgp on the surfaces of endospores of the mutant strain in the presence of high titers of antibody to the immunodominant antigen contributes to opsonization, increased phagocytosis, and killing of the fungal cells. In vitro studies of the interaction between a murine alveolar macrophage cell line and parasitic cells coated with SOWgp showed that the addition of anti-SOWgp antibody could enhance phagocytosis and killing of Coccidioides. We suggest that Mep1 plays a pivotal role as a pathogenicity determinant during coccidioidal infections and contributes to the ability of the pathogen to persist within the mammalian host.

Animals↗
PubMed1962

Pathogenesis of Coccidioides immitis in monkeys.

Converse, J. L. (U. S. Army Chemical Corps, Fort Detrick, Frederick, Md.), E. P. Lowe, M. W. Castleberry, G. P. Blundell, and A. R. Besemer. Pathogenesis of Coccidioides immitis in monkeys. J. Bacteriol. 83:871-878. 1962.-Respiratory exposure to arthrospores from the submerged growth of Coccidioides immitis, strain Cash, in liquid medium resulted in similar pathogenesis in monkeys to that of strain Silveira arthrospores harvested from solid medium. Infectivity of 100% was noted with doses of 50 to 10,000 arthrospores. The disease was characterized by loss of appetite and weight, malaise, and extreme respiratory distress accompanied by coughing, with the immediate cause of death being acute coccidioidal pneumonia. The pathological picture was one of extensive, progressive, destructive pulmonary disease in the higher dose levels and few, small, self-contained, fibrous lesions, with little destruction of lung tissue, in the low doses. This was correlated in general with the findings of serial X rays and serological tests. The presence of the parasitic phase (spherule and endospore) of the organism was noted in large numbers within the pulmonary lesions and bronchial exudates and was substantiated by cultural methods. Occasionally, hyphal elements of the saprophytic growth phase were noted around the periphery of residual cavitated areas of the lungs.

Animals↗
PubMed1966

Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis.

Kong, Yi-chi M. (University of California, Berkeley), D. C. Savage, and Leighton N. L. Kong. Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J. Bacteriol. 91:876-883. 1966.-A delayed hypersensitivity reaction to spherule and mycelial extracts of Coccidioides immitis was elicited in the footpads of mice vaccinated with killed spherules. Emulsification of the spherules with Freund's adjuvants was unnecessary, but a high concentration of antigen was required to elicit the reaction. Injection of the extracts produced, initially, a swelling which subsided within 4 hr, and then induration, which began at 6 to 8 hr and reached a maximum at 24 hr. The time course of the reaction corresponded to that of the tuberculin reaction in BCG-vaccinated mice. The histological response to coccidioidal extracts was characterized by the early infiltration of both polymorphonuclear and mononuclear cells, and the subsequent predominance of mononuclear cells at 24 to 48 hr. By 72 hr, the mononuclear cells comprised >90% of the cellular infiltrate. Animals infected intranasally with arthrospores (1 to 5 ld(50)) reacted negatively before and during the crisis period; thereafter (by 28 to 31 days after infection), up to 50% of the survivors showed a delayed reaction.

Animals↗
PubMed1976

Acute coccidioidal pleural effusion.

Acute coccidioidal pleural effusions were studied in 28 patients. Coccidioidal pleural effusion appeared to be secondary to direct spread of contigous parenchymal infection, rather than to hematogenous dissemination, in more than 90 per cent of these patients. Only 2 of 28 patients had the concomitant development of disseminated infection, and both patients possessed factors known to predispose to dissemination. Because of the excellent prognosis in most patients, therapy in patients with coccidioidal pleural effusion should be expectant. This is true even when substantial increases occur in complement fixation titers; such elevations were frequent in this series. Cultures of pleural biopsy specimens were the most rewarding cultural source in this series, being positive in all 8 patients in whom such biopsy specimens were cultured. Dermal hypersensitivity, including erythema nodosum and erythema multiforme, was commin in patients whose clinical course was uncomplicated.

Adolescent↗
PubMedDate not supplied

[Coccidioides immitis: primary infection of the central nervous system. Case report and literature review].

A case of primary coccidiodal meningitis without pulmonary, osseous or dermic affection due to Coccidioides immitis in a 27 years old male patient with hypertensive brain of one month of evolution, was reported. The patient was resident of Northern California, and he was previously healthy. The cerebrospinal fluid (CSF) showed a glucose of 22 mg/dL, proteins 62 mg/dL, white blood cells 100/mm3 (97% PMN, 3% MN). CT SCAN showed bilateral ventricular dilatation. Diagnosis of coccidioidal meningitis was made based on antibodies against anticoccidioides (IgM 6.8 mg/dL and IgG 4.9 mg/dL, normal < 2 mg/dL) and growth of Coccidioides immitis. The chest radiograph was normal and the detection of antibodies against human immunodeficiency virus was negative. A VP shunt was placed and the patient was treated with intravenous amphotericin B and intratecal amphotericin B through on Ommaya reservoir. Even with antifungal treatment the patient deteriorated neurologically after an initial transient improvement, he died two weeks later in his hometown.

Adult↗
PubMed1979

Chronic progressive coccidioidal pneumonitis. Report of six cases with clinical, roentgenographic, serologic, and therapeutic features.

Chronic progressive coccidioidal pneumonitis (CPCP) is an uncommon sequela of acute pulmonary coccidiodomycosis. Six recent patients with CPCP are described, most of whom were previously healthy. The clinical presentation was indolent, resulting in long diagnostic delays. Serial chest roentgenograms showed progressive pulmonary infiltration and sputum cultures were persistently positive for Coccidioides immitis. Serum complement fixation (CF) antibody titers were high, with five of six patients having titers greater than or equal to 1:16. No patients had evidence of extrapulmonary coccidioidal spread at time of diagnosis of CPCP, although hematogenous dissemination occurred later in one patient. Five patients received amphotericin B intravenously (greater than or equal to 30 mg/kg total), resulting in rapid clinical and mycologic cure, decline in CF titers, and roentgenographic improvement or stabilization. However, two of these five patients suffered permanent physiologic impairment. One patient refused therapy and remains clinically symptomatic, with chronic positivity of sputum cultures for C immitis and high CF titers.

Adult↗
PubMed2005

Central Nervous System Coccidioides immitis Infections.

Coccidioidal meningitis occurs in healthy individuals and patients with AIDS or other immunosuppressive illnesses. The central nervous system infection results when Coccidioides immitis disseminates from a primary lung infection via a fungemia to reach the meninges. Cases develop primarily in individuals living in or traveling to the Lower Sonoran Life Zone of Southwest United States. Most cases begin as subacute granulomatous meningitis with occasional patients developing brain abscesses. Diagnosis may be challenging because C. immitis is isolated from cerebrospinal fluid in less than 50% of patients. However, a cerebrospinal fluid complement fixation test for IgG antibody to C. immitis has high sensitivity and specificity. Currently, optimal treatment is unclear. Standard therapy has been with life-long oral fluconazole or intrathecal amphotericin B followed by prolonged oral fluconazole. Liposomal amphotericin B given intravenously seems promising as an initial treatment as it has much higher brain penetration, less nephrotoxicity, and less severe infusion-related adverse effects than conventional amphotericin B. However, current comparative studies for efficacy of liposomal amphotericin B in coccidioidal meningitis are lacking.

Journal Article↗
PubMed2001

Vasculitic complications associated with coccidioidal meningitis.

Vasculitis complicating coccidioidal meningitis is becoming increasingly recognized. At this time, predisposing clinical features have not been elucidated. Histologically, 2 types of vascular inflammation have been described. The first is a transmural inflammatory process of the intracranial blood vessels that occurs early in the course of disease. Encroachment of the vessel lumen may result in thrombosis. The second process occurs with chronic disease and is associated with intimal thickening and luminal occlusion with little inflammation. Numerous substances, including metalloproteinases, cytokines such as tumor necrosis factor (TNF)-alpha, and an elastase, have been postulated as putative virulence factors. Recently, a rabbit model has been developed that appears to closely mimic human disease. By using this model, a parallel between coccidioidal vasculitis and temporal arteritis has been developed. Currently, there are no established therapies for coccidioidal vasculitis. The use of corticosteroids is controversial. Of interest are agents that may block the pathologic process, such as omega-3 oils, and pentoxyfylline.

Animals↗
PubMed1987

Multiple intracranial aneurysms due to Coccidioides immitis infection. Case report.

True mycotic (fungal) aneurysms are distinctly uncommon. The case of a young woman with multiple intracranial aneurysms of Coccidioides immitis origin is presented. Coccidioides immitis organisms are not uncommon central nervous system pathogens and usually cause basilar meningitis and hydrocephalus. There are no previous reports of a coccidioidal mycotic aneurysm. The management of intracranial coccidioidomycosis and fungal aneurysms is reviewed.

Adult↗
PubMed1990

Itraconazole therapy for chronic coccidioidal meningitis.

STUDY OBJECTIVE: To assess the efficacy of orally administered itraconazole in the treatment of coccidioidal meningitis. DESIGN: Prospective, nonrandomized open trial. SETTING: Multicenter trial at an urban county hospital, a university referral center, and referring institutions. PATIENTS: Ten patients with culture or serologic evidence of coccidioidal meningitis refractory to standard therapy. Patients receiving other systemic antifungal therapy were excluded. INTERVENTION: Itraconazole was administered orally at doses of 300 to 400 mg/d for a median duration of 10 months. Disease activity and drug efficacy were evaluated at initiation of therapy and at the most recent follow-up using a standardized scoring system. MEASUREMENTS AND MAIN RESULTS: Eight of ten patients are evaluable. Of five patients receiving itraconazole as sole therapy, four have responded. All three patients receiving intrathecal amphotericin B have had that therapy discontinued and have no evidence of active disease in the absence of intrathecal therapy. Toxicity has been minimal; one patient had mild nausea. CONCLUSIONS: Itraconazole shows impressive activity in this series of patients with refractory coccidioidal meningitis. Itraconazole in this and other fungal meningitides should be evaluated further.

Adolescent↗
PubMed1993

Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group.

OBJECTIVE: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis. DESIGN: Uncontrolled clinical trial. SETTING: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization. PATIENTS: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV). INTERVENTION: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited. MEASUREMENTS: Predefined assessment of infection-related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response. RESULTS: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced. CONCLUSION: Fluconazole therapy is often effective in suppressing coccidioidal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1999

MR imaging of acute coccidioidal meningitis.

BACKGROUND AND PURPOSE: Our purpose was to describe the MR imaging findings in patients with acute coccidioidal meningitis. METHODS: Fourteen patients (11 men, three women; 22-78 years old; mean age, 47 years) with coccidioidal meningitis underwent neuroimaging within 2 months of diagnosis. Thirteen patients had MR imaging and one had an initial CT study with a follow-up MR examination 5 months later. Initial and follow-up MR images were evaluated for the presence of ventricular dilatation, signal abnormalities, enhancement characteristics, sites of involvement, and evidence of white matter or cortical infarction. The patterns of enhancement were characterized as focal or diffuse. Pathologic specimens were reviewed in two patients. RESULTS: Ten of the 14 images obtained at the time of initial diagnosis showed evidence of meningitis. All of the initially abnormal studies showed enhancement in the basal cisterns, sylvian fissures, or pericallosal region. Subsequent studies, which were available for three of the four patients with normal findings initially, all eventually became abnormal, with focal enhancement seen on the initial abnormal examination. Other abnormalities seen at presentation included ventricular dilatation (six patients) and deep infarcts (four patients). Pathologic specimens in two patients showed focal collections of the organism corresponding to the areas of intense enhancement on MR images. CONCLUSION: Early in its disease course, coccidioidal meningitis may show areas of focal enhancement in the basal cisterns, which may progress to diffuse disease. Pathologically, the areas of enhancement represent focal collections of the organism. Deep infarcts and communicating hydrocephalus are associated findings.

Acute Disease↗
PubMed1975

Coccidioidal synovitis of the knee.

Four patients are described with documented coccicioidal synovitis of the knee joint. In two of them, no previous diagnosis of coccidioidomycosis had been made prior to diagnosis of coccidioidal synovitis. The other two had active disease after courses of amphotericin B administered both parenterally and intra-articularly for disseminated coccidioidomycosis and coccidioidal synovitis. After synovectomy and limited parenteral amphotericin B therapy, none of the four patients whos evidence of active synovial infection two to seven years later. Synovectomy appears to be an important aspect of the optimal therapy of coccidioidal synovitis of the knee, and when performed, the parenteral dosage of amphotericin B can be limited. Intra-articularly administered amphotericin B is also advocated when possible.

Adult↗
PubMed1986

Experience with needle biopsy for coccidioidal lung nodules.

Three hundred forty-eight patients with solitary pulmonary nodules underwent needle biopsy of the lung in an endemic area for coccidioidomycosis. The purposes of the study were to establish the value of smears and cultures from needle biopsy specimens in the diagnosis of solitary coccidioidal granuloma and to determine how the final diagnosis was established for patients without a clear-cut diagnosis after initial biopsy. Spherules of Coccidioides immitis were initially identified in 49 of the 96 patients with coccidioidomas. Only three of 35 cultures from biopsy-proved coccidioidal lesions were positive (8.6% yield); nevertheless, cultures were cost-effective in nondiagnostic cases. Thoracotomy should be delayed until the results of cultures are known if findings of skin tests, serologic studies, and roentgenography make a benign diagnosis plausible.

Adult↗
PubMed1981

Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature.

Clinical and laboratory features of 31 patients with coccidioidal meningitis seen from January 1964 through December 1976 with follow-up through 1979 are reported and data on 114 patients from the literature reviewed. History of exposure to C. immitis, a wide age range, and, in about one third, underlying conditions are noteworthy. Dissemination to the meninges usually occurs within the first few months although diagnosis is frequently delayed. Presenting symptoms and signs of coccidioidal meningitis are varied but signs of chronic meningitis or suggestion of hydrocephalus are prominent. Evidence of acute infection is unusual even with widespread disease. Diagnosis is usually made by demonstration of coccidioidal CF antibodies in the CSF although they are not found in all patients. Some show other direct evidence of C. immitis. Special diagnostic techniques such as CAT scanning for evidence of basilar meningitis or hydrocephalus are valuable. Amphotericin B remains the drug of choice despite the need for long-term therapy and the problems with intrathecal administration. Reservoirs are only occasionally useful but shunts are frequently lifesaving despite complications. Factors associated with a bad prognosis are hydrocephalus, non-Caucasian race, or presence of an underlying disease.

Adolescent↗
PubMed1998

Granulomatous meningitis caused by Coccidioides immitis in a dog.

Granulomatous meningitis attributable to Coccidioides immitis was diagnosed on postmortem examination in a 4-year-old Border Collie. Clinical signs included CNS disease, aspiration pneumonia secondary to a megaesophagus, and otitis externa. Central nervous system signs included central vestibular and cranial nerve dysfunction. Cerebellar and medullary infiltrates seen on histologic examination affected cranial nerves VIII, IX, and X. Despite extensive diagnostics, diagnosis was not made antemortem. Analysis of CSF suggested suppurative meningitis, but bacteriologic culture results were negative. Coccidioides endospores were identified on reexamination of brain tissue. The clinical course of disease and rate of Coccidioides immitis infection is variable. Causative agents of granulomatous or inflammatory CNS disease may include fungal infection more often than is currently suspected.

Animals↗