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PubMed1981

In vitro assays of cellular immunity in progressive coccidioidomycosis: evaluation of suppression with parasitic-phase antigen.

Patients with progressive coccidioidomycosis commonly have depressed cell-mediated immune responses to coccidioidal antigens. We studied in vitro lymphocyte transformation in response to spherulin, as extract of the parasitic phase of Coccidioides immitis, and the nonspecific mitogen phytohemagglutinin in patients with progressive disseminated coccidioidomycosis who were anergic to spherulin and in healthy skin test-positive and skin test-negative control subjects. Lymphocyte responses to phytohemagglutinin were indistinguishable for all three groups. When assayed in pooled blood group AB serum, lymphocyte responses to spherulin were identical for patients and skin test-positive control subjects; however, the patients' responses to spherulin were depressed in autologous serum. Prolonged incubation of cells in vitro did not restore the hyporesponsiveness. Serial studies of the patients revealed a trend toward restoration of the lymphocyte response during therapy. Preliminary experiments suggest that, although there were no intrinsic cell defects in these patients with coccidioidomycosis, there may be specificity of patient cells to be suppressed by serum. A prospective study of the incidence of depression of lymphocyte responsiveness in autologous serum revealed that this occurs in a minority of patients with negative spherulin skin tests, is rare in patients with positive skin tests, and appears to be associated with clinical deterioration.

Adult↗

PubMed1985

Coccidioidomycosis at a university health service.

At a single university health service within an endemic area, 172 cases of coccidioidomycosis were retrospectively identified by fungal cultures, serologic studies, or intercurrent skin test conversions. The average annual incidence of symptomatic infection was 0.43% for susceptible students. Peak case rates occurred in November and June (11 cases/10,000 clinic visits) and were 1.5 to 6 times greater than in other months. Although mononucleosis was diagnosed approximately twice as frequently as coccidioidomycosis, coccidioidal infections required 74% more visits per patient and over 3 times longer clinical supervision than did mononucleosis. Although only 2 patients disseminated, diagnosis and management of patients with coccidioidomycosis constituted more than 2% of our clinic's visits, for an estimated annual cost of more than $34,000. Because our patient population is young and otherwise healthy, our estimates of the impact of primary coccidioidal infection may underestimate that on civilian public health as a whole.

Adult↗

PubMed1985

Acute respiratory failure caused by primary pulmonary coccidioidomycosis. Two case reports and a review of the literature.

Acute respiratory failure caused by infection with Coccidioides immitis is a rare, usually fatal, event. We report 2 patients who survived acute respiratory failure caused by primary pulmonary coccidioidomycosis. We attribute the severity of illness to a large inoculum of organisms. Their treatment included antifungal therapy with amphotericin B and diuresis to decrease noncardiogenic pulmonary edema. Coccidioidomycosis causing respiratory failure may be more frequent than currently clinically appreciated and may result from primary pulmonary coccidioidomycosis, miliary pulmonary disease, or as part of the multisystem organ failure seen in fungemic patients.

Adult↗

PubMed2026

Th2 skewing in patients with disseminated coccidioidomycosis.

BACKGROUNDDisseminated coccidioidomycosis (DCM) is an often fatal and otherwise intractable condition requiring lifelong antifungal treatment. We have previously shown that a deranged polarization of CD4+ T cells toward a Th2 phenotype can exist in the context of DCM. Here, we studied a large population to determine the frequency of abnormal Th2 skewing of CD4+ T cells in patients with coccidioidomycosis and to identify underlying genetic mechanisms supporting this phenotype.METHODSWe collected PBMCs from 204 patients with coccidioidomycosis, including 96 patients with disseminated disease. We measured immune phenotypes and cytokine production by CD4+ T cells from patients and healthy controls, and comparisons between groups were made based on disease severity and demographics. Whole-genome sequencing was conducted on 180 individuals who also had cytokine profiling.RESULTSWe found that approximately 25% of patients with DCM had a CD4+ T cell compartment that was abnormally skewed toward a Th2 phenotype, and Th2 skewing was highly correlated with male sex. Coculture of T cells with the IL-4R/IL-13R-blocking antibody dupilumab reduced Th2 skewing. Sequencing revealed rare variants in genes involved in the IL-12/IFN-γ axis in several Th2-skewed patients, and we validated one such variant in IFNGR1 as hypomorphic.CONCLUSIONPatients with DCM, especially males, should be screened for Th2 skewing of CD4+ T cells. Patients with Th2 skewing should be additionally screened for genetic defects in the IL-12/IFN-γ axis. Our findings give a mechanistic rationale for blockade of IL-4R in Th2-skewed patients with refractory coccidioidomycosis.FUNDINGNational Institute of Allergy and Infectious Diseases/NIH grants R21 AI149654 and U19 AI166059 and University of California Office of the President grant VFR-19-633386.

Humans↗

PubMed1980

Circulating immune complexes in coccidioidomycosis. Detection and characterization.

Sera of 22 patients with active and 13 with inactive coccidioidomycosis, as well as 15 healthy subjects who were skin-test positive to coccidioidin and 39 healthy subjects who were coccidioidin skin-test negative, were assayed for immune complexes. Circulating immune complexes were measured by the Clq-binding assay, the Clq-solid phase assay, the monoclonal rheumatoid factor inhibition assay, and the monoclonal rheumatoid factor solid phase assay. An increased concentration of circulating immune complexes was detected in 73% of those with active disease by at least one assay compared with 13% of the healthy controls. Significantly increased levels of immune complexes were detected in sera of patients with active coccidioidomycosis by the Clq-binding assay (P < 0.001), the Clq-solid phase assay (P < 0.001), the monoclonal rheumatoid factor inhibition assay (P < 0.005), and the monoclonal rheumatoid solid phase assay (P < 0.05) compared with the results obtained in the 54 healthy subjects. In contrast, those with inactive disease did not show significantly increased concentrations of circulating immune complexes. Sucrose density gradient ultracentrifugation of patients' sera established that the immune complexes were of intermediate size, sedimenting between the 6.6S and 19S markers. Immune complexes were shown to contain both coccidioidin antigen and anticoccidioidin antibody. In addition, a radioimmunoassay was developed to quantitate coccidioidin antigen-containing immune complexes. The latter assay proved highly sensitive in detecting immune complexes in patients with active coccidioidomycosis.

Antibodies, Fungal↗

PubMed2005

Climate factors influencing coccidioidomycosis seasonality and outbreaks.

Although broad links between climatic factors and coccidioidomycosis have been established, the identification of simple and robust relationships linking climatic controls to seasonal timing and outbreaks of the disease has remained elusive. Using an adaptive data-oriented method for estimating date of exposure, in this article I analyze hypotheses linking climate and dust to fungal growth and dispersion, and evaluate their respective roles for Pima County, Arizona. Results confirm a strong bimodal disease seasonality that was suspected but not previously seen in reported data. Dispersion-related conditions are important predictors of coccidioidomycosis incidence during fall, winter, and the arid foresummer. However, precipitation during the normally arid foresummer 1.5-2 years before the season of exposure is the dominant predictor of the disease in all seasons, accounting for half of the overall variance. Cross-validated models combining antecedent and concurrent conditions explain 80% of the variance in coccidioidomycosis incidence. .

Arizona↗

PubMed1983

Amphotericin B in the treatment of coccidioidomycosis.

In the 25 years since its introduction, amphotericin B has demonstrated clear value in the management of coccidioidomycosis. However, its effectiveness is less certain than in diseases due to other fungal aetiological agents, even when the loci of infection and in vitro drug susceptibilities are identical. The refractoriness of coccidioidomycosis may relate to the unique ability of each Coccidioides immitis spherule to release hundreds of endospores, thus maximally challenging host defence mechanisms. Amphotericin B is most likely to be effective where there is evidence of intact cell-mediated immunity against C. immitis (i.e. positive coccidioidin or spherulin skin test; low titre of complement fixing antibody), and structural damage to tissues. When bones and joints are involved, as is frequently the case, adjunctive surgical management is generally required. Patients with structural lung disease (i.e. cysts and/or cavities) show variable, often minimal, response to treatment. Amphotericin B has transformed coccidioidal meningitis from a routinely fatal disease to one where prolonged survival is possible. However, the drug must be given by the intrathecal route, and for periods of years, before the possibility of cure can be considered. Relapses of bone, joint and meningeal coccidioidomycosis are common and should be anticipated, especially in patients with impaired immunity.

Amphotericin B↗

PubMed1983

Ketoconazole in the treatment of coccidioidomycosis.

Ketoconazole is the newest antifungal agent evaluated for efficacy in the treatment of coccidioidomycosis and the only one used by oral administration. The inhibition of Coccidioides immitis observed by in vitro susceptibility testing has been corroborated in murine studies in which ketoconazole therapy has led to survival in otherwise lethally infected animals. In man, absorption of ketoconazole from the gastrointestinal tract is generally favourable. However, there is considerable variation between patients in achieved serum concentrations, the causes of which may be multiple and as yet are incompletely understood. All completed studies of ketoconazole treatment of human coccidioidomycosis have been non-comparative in design. Entry criteria have selected patients that would have been treated otherwise with another antifungal agent. Dosages were usually 200 or 400 mg/day and treatment was continued for many months. Soft tissue infections improved more frequently and after less ketoconazole than did pulmonary or skeletal infections. No effect on coccidioidal meningitis has been found at these dosages. In skeletal infections, symptoms, physical findings and coccidioidal antibody levels commonly improved, but radiographs of skeletal lesions frequently did not change. Repeat culture of treated lesions, even those that had improved, often continued to grow C. immitis. Relapses after stopping ketoconazole have occurred in a significant number of patients. Untoward effects were usually manageable without discontinuing therapy. Ketoconazole appears to be of use in the treatment of progressive forms of coccidioidomycosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1987

Coccidioidomycosis in renal dialysis and transplant patients: radiologic findings in 30 patients.

Asymptomatic primary coccidioidal infection is common. After the initial infection is contained, the organism can remain dormant in the body for years. Immunosuppression related to renal transplantation or dialysis may reactivate dormant disease. Thus, symptomatic disease may be seen in those with no known history of previous coccidioidomycosis who have visited endemic areas only briefly. To determine if coccidioidomycosis produces characteristic radiographic findings in renal transplant and dialysis patients, we reviewed the records and radiographs of all patients in either of these two categories who are known to have developed active coccidioidal infection in southern Arizona since 1965. Thirty patients (12 undergoing dialysis and 18 transplant recipients) were identified. We conclude that the radiographic manifestations of pulmonary coccidioidomycosis in renal transplant and dialysis patients are highly variable. Interstitial and alveolar patterns of disease are equally likely to occur. Extrathoracic infection without evidence of pulmonary disease occurred in 11 patients (37%), but was radiographically demonstrable only as septic arthritis or perinephric abscess.

Coccidioidomycosis↗

PubMedDate not supplied

Influence of host genetics on the severity of coccidioidomycosis.

Coccidioidomycosis, a mild flulike illness in approximately 40% of infected persons, progresses to severe pulmonary or disseminated disease in 1% to 10% of symptomatic cases. We examined host genetic influences on disease severity among class II HLA loci and the ABO blood group. Participants included African-American, Caucasian, and Hispanic persons with mild or severe disseminated coccidioidomycosis from Kern County, California. Among Hispanics, predisposition to symptomatic disease and severe disseminated disease is associated with blood types A and B, respectively. The HLA class II DRB1*1301 allele marks a pre-disposition to severe disseminated disease in each of the three groups. Reduced risk for severe disease is associated with DRB1*0301-DQB1*0201 among Caucasians and Hispanics and with DRB1*1501-DQB1*0602 among African-Americans. These data support the hypothesis that host genes, in particular HLA class II and the ABO blood group, influence susceptibility to severe coccidioidomycosis.

ABO Blood-Group System↗

PubMed2004

Coccidioidomycosis among workers at an archeological site, northeastern Utah.

In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9-12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, which extends northward its known geographic distribution in Utah by approximately 200 miles.

Adolescent↗

PubMed1999

The first imported case of pulmonary coccidioidomycosis in Korea.

Coccidioidomycosis is an endemic disease found in the southwestern part of North America. Travellers who visit the endemic area may carry the infection. We report a case of pulmonary coccidioidomycosis in a 74-year-old woman. She was healthy before visiting Arizona, U.S.A twice. After returning home, she began to complain of intermittent dry coughing. The symptom was mild, however, and she was treated symptomatically. Later a chest radiograph, which was taken 4 years after the onset of the symptom, showed a solitary pulmonary nodule in the right upper lobe. By percutaneous needle aspiration, a few clusters of atypical cells were noted in the necrotic background. A right upper and middle lobectomy was done. A 1.5 x 1.5 x 1.2 cm sized tan nodule was present in otherwise normal lung parenchyma. Microscopically, the nodule consisted of aggregates of multiple solid granulomas inside of which was mostly necrotic. Neutrophils and nuclear debris were scattered along the periphery of the necrotic foci. Numerous multinucleated giant cells were associated with the granulomas. In the necrotic area, mature spherules of Coccidioides immitis, which were 30-100 microm in diameter, were present. They contained numerous endospores which ranged from 5 to 15 microm and were also noted in multinucleated giant cells. The diagnosis of coccidioidomycosis was made. She is doing well after the resection.

Aged↗

PubMed1998

Risk factors for primary pulmonary coccidioidomycosis hospitalizations among United States Navy and Marine Corps personnel, 1981-1994.

Recent coccidioidomycosis outbreaks among military personnel have alarmed public health officials. We used computerized hospitalization records to identify risk factors for coccidioidomycosis hospitalizations among active-duty United States Navy and Marine Corps personnel for the years 1981 to 1994. Primary pulmonary disease was the most common form of disease, accounting for 82 (73%) of the 113 first admissions. Crude annual rates of primary pulmonary disease increased markedly in 1992 and 1993 in concert with an epidemic in the United States. Demographic data from the pulmonary admissions were combined with that of a 2% random sample of the entire Navy and Marine Corps population for multivariate risk factor modeling. Persons from junior paygrades, older age groups, and those reporting a race/ethnicity other than Caucasian or Hispanic were most likely to be hospitalized with this disease. These risk factor data should be considered in designing coccidioidomycosis surveillance and prevention programs.

Adolescent↗

PubMed2002

Disseminated coccidioidomycosis discovered during routine skin cancer screening.

A 78-year-old white man presented for routine dermatologic examination. A 4x4-mm erythematous papule was noted on the left upper back. It was asymptomatic and previously unnoticed by the patient. The results of a shave biopsy revealed a large spherule with granular cytoplasm diagnostic of coccidioidomycosis. Chest x-ray revealed a 1.8-cm right upper lobe mass. The complement fixation antibody titer for cocci was 1:128. The patient was treated for disseminated coccidioidomycosis with oral fluconazole. The epidemiology, diagnosis, and management of coccidioidomycosis are discussed.

Aged↗

PubMed1956

Cortisone in coccidioidomycosis.

Cortisone administered orally, in low dosages for brief periods, promptly suppressed the allergic manifestations accompanying primary pulmonary coccidioidomycosis in 19 cases. There was no interference with the coccidioidin skin test reaction or with the usual serologic pattern. Dissemination of the disease as a sequel to the administration of cortisone and/or corticotropin has not been reported. A survey of physicians and of the known instances of disseminated coccidioidomycosis in Kern County failed to reveal any such episode. In none of the cases in which the authors gave cortisone in the presence of coccidioidomycosis was there any complication or undesirable sequel-specifically, no subsequent dissemination of the disease. The data presented are not to be interpreted as a therapeutic recommendation, but as a contribution to the information available concerning the effects of these drugs in infectious diseases.

Coccidioidomycosis↗

PubMed1951

Coccidioidomycosis as a complication of pregnancy.

Records of 33 cases of coccidioidomycosis occurring during pregnancy were reviewed. In this group the incidence of dissemination of the disease was considerably greater than the reported incidence of dissemination in all cases of coccidioidomycosis. The incidence of dissemination was higher in the patients who contracted coccidioidomycosis late in pregnancy than it was in those in whom onset of the disease occurred earlier in gestation; but dissemination occurred in all Negro patients in the group, regardless of the time of onset during pregnancy. The chief complicating effect when onset was in the first trimester of pregnancy was a tendency to abortion. In cases in which onset was in the third trimester, the incidence of premature labor was extremely high. There was no evidence of congenital infection in any of the babies, but in one case invasion of the placenta by coccidioidal spherules was observed.

Abortion, Induced↗

PubMed1991

Disseminated coccidioidomycosis with lung, skin and lymph node involvement: report of a case.

Coccidioidomycosis is a deep mycotic infection endemic to the southwestern United States. Although it has also been reported to occur in nonendemic areas, it has rarely been reported in Taiwan. We report a case of disseminated coccidioidomycosis which is the first such case reported on this island. The 28-year-old male patient developed a nonproductive cough and fever while travelling in Arizona. Chest roentgenogram revealed infiltration of the right lower lung field and enlargement of the right paratracheal lymph nodes. The titer for the complement fixation test for coccidioidin was 1:32. The patient was treated with ketoconazole for 3 months with good clinical response. However, submandibular lymphadenopathy and a macular skin lesion were noted one month after discontinuation of treatment. During hospitalization, both pathologic findings from a submandibular lymph node and a scratching smear of the skin lesion contained Coccidioides immites. The patient was put on ketoconazole again for another 6 months. Lesions on chest film were resolved and the coccidioidin complement fixation titer was gradually reduced. The patient received regular follow-up and no evidence of relapse has been seen. In this report, clinical manifestations, diagnostic methods and recent advances in the treatment of coccidioidomycosis are discussed. Because of increasing intercontinental travel and the increasing usage of immunosuppressive agents, we expect that more cases will be found in Taiwan. Keeping this disease in mind when making a differential diagnosis is the best way to make an accurate diagnosis.

Adult↗

PubMed1991

[A case of pulmonary coccidioidomycosis].

A 55-year-old Japanese woman was admitted to our hospital, complaining of flu-like symptoms and left-sided chest pain. Her chest X-ray films revealed a solitary coin lesion in the left middle lung field. She had traveled to California and Arizona 3 months before being taken ill. Because of negative result in sputum cytology and trans-bronchial lung biopsy examination, open lung biopsy and wedge resection was performed. Histological examination revealed endosporulating spherules in a caseous lesion of the epithelioid granulomas, and fungal cultures demonstrated barrel-shaped arthropores. Pulmonary coccidioidomycosis was diagnosed. Coccidioidomycosis is a rare fungal disease found in certain endemic areas in the southwestern region of the United States. She had been infected during her travels in America, and this is the second case in Japan who had taken surgical intervention for pulmonary coccidioidomycosis.

Coccidioidomycosis↗