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Biomedical subjects

D Pappagianis

Publications and source records attributed to D Pappagianis.

At least 37 records · Page 2Linked to original sources
PubMed1997

A coccidioidomycosis outbreak following the Northridge, Calif, earthquake.

OBJECTIVE: To describe a coccidioidomycosis outbreak in Ventura County following the January 1994 earthquake, centered in Northridge, Calif, and to identify factors that increased the risk for acquiring acute coccidioidomycosis infection. DESIGN: Epidemic investigation, population-based skin test survey, and case-control study. SETTING: Ventura County, California. RESULTS: In Ventura County, between January 24 and March 15, 1994, 203 outbreak-associated coccidioidomycosis cases, including 3 fatalities, were identified (attack rate [AR], 30 cases per 100,000 population). The majority of cases (56%) and the highest AR (114 per 100,000 population) occurred in the town of Simi Valley, a community located at the base of a mountain range that experienced numerous landslides associated with the earthquake. Disease onset for cases peaked 2 weeks after the earthquake. The AR was 2.8 times greater for persons 40 years of age and older than for younger persons (relative risk, 2.8; 95% confidence interval [CI], 2.1-3.7; P<.001). Environmental data indicated that large dust clouds, generated by landslides following the earthquake and strong aftershocks in the Santa Susana Mountains north of Simi Valley, were dispersed into nearby valleys by northeast winds. Simi Valley case-control study data indicated that physically being in a dust cloud (odds ratio, 3.0; 95% CI, 1.6-5.4; P<.001) and time spent in a dust cloud (P<.001) significantly increased the risk for being diagnosed with acute coccidioidomycosis. CONCLUSIONS: Both the location and timing of cases strongly suggest that the coccidioidomycosis outbreak in Ventura County was caused when arthrospores were spread in dust clouds generated by the earthquake. This is the first report of a coccidioidomycosis outbreak following an earthquake. Public and physician awareness, especially in endemic areas following similar dust cloud-generating events, may result in prevention and early recognition of acute coccidioidomycosis.

Acute Disease↗
PubMed1996

Cerebrospinal fluid antibodies detected by ELISA against a 33-kDa antigen from spherules of Coccidioides immitis in patients with coccidioidal meningitis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

Antibodies against a 33-kDa antigen from Coccidioides immitis were detected by ELISA in patients' cerebrospinal fluid (CSF). Anti-33-kDa antibodies were detected at dilutions > 1:80 in only 1 (1.4%) of 73 patients without coccidioidal meningitis but in 74 (71.8%) of 103 with meningitis. Anti-33-kDa antibodies were detected in 53 (91.4%) of 58 patients whose anti-coccidioidal complement-fixing (CF) antibodies were detectable and in 21 (46.7%) of 45 patients whose CSF was negative by CF test (positive predictive value, 99%; negative predictive value, 71%; sensitivity, 72%; specificity, 99%). Anti-33-kDa antibodies, among which IgG1 was the dominant subclass, increased when infections worsened and decreased when patients' conditions improved. Antibody concentration appeared to be independent of most baseline findings, although only 1 of 5 patients coinfected with human immunodeficiency virus had initially detectable antibodies. Measurement of anti-33-kDa antibodies is a sensitive indicator of coccidioidal meningitis and of its clinical course.

Antibodies, Fungal↗
PubMed1996

Cloning and expression of the complement fixation antigen-chitinase of Coccidioides immitis.

A chitinase had been isolated from the culture filtrates of Coccidioides immitis endosporulating spherules and from hyphae and shown to be the coccidioidal complement fixation (CF) and immunodiffusion-CF antigen. In the present study, we made use of our previously determined amino-terminal (N-terminal) sequence of the CF-chitinase to design degenerate oligonucleotide primers and to amplify and sequence a PCR product that coded for the N-terminal portion of the CF-chitinase. The PCR product was used as a hybridization probe to screen a developing spherule-(lambda)ZAP cDNA library, and three hybridizing clones were selected. These clones were converted into their pBluescript expression plasmid form in Escherichia coli and induced to express their recombinant proteins. Lysate from only one clone, pCTS 4-2A, yielded an enzymatically functional CF-chitinase and a line of identity with control immunodiffusion-CF-positive antigen. The pCTS 4-2A insert was sequenced and found to contain a deduced open reading frame coding for a 427-amino-acid polypeptide with an approximate molecular weight of 47 kDa. When purified by a chitin adsorption-desorption method, the recombinant protein exhibited virtually identical characteristics to those of the original C. immitis CF-chitinase. Nondenaturing gels of the pCTS 4-2A E. coli lysates and the purified C. immitis and recombinant CF-chitinase revealed proteins that had chitinase activity and similar relative electrophoretic mobilities. The appearance and relative levels of hybridizing RNA from the developing spherules-endospores (SEs) and hyphae correlated with the appearance or presence and level of CF-chitinase enzyme activity found in SEs culture filtrate and in cellular extracts of developing SE and hyphae. Thus, a functional recombinant CF-chitinase antigen was produced in E. coli and was used in serological diagnostic applications. These results also suggest a functional role for this chitinase in SE development and maturation.

Amino Acid Sequence↗
PubMed1996

Use of a recombinant Coccidioides immitis complement fixation antigen-chitinase in conventional serological assays.

The coccidioidal complement fixation (CF) antigen has been cloned previously, and the fusion protein has been expressed in Escherichia coli. The recombinant CF (rCF) antigen was affinity purified by adsorption-desorption to chitin, and its reactivity was studied by using sera containing coccidioidal antibodies. The affinity-purified rCF antigen formed a line of identity with an immunodiffusion (ID) CF reference antigen (coccidioidin) derived from mycelial-phase Coccidioides immitis and was reactive with human, canine, and equine sera containing coccidioidal antibody. The affinity-purified rCF antigen yielded no detectable reaction with Blastomyces of Histoplasma antiserum by ID. The affinity-purified rCF antigen fixed complement with positive human sera and, even when used at lower concentrations, yielded titers comparable to those obtained with the coccidioidin. The reactivity of the affinity-purified rCF antigen was further evaluated by enzyme immunoassay, in which it manifested good sensitivity (96.9%) and specificity (100%) when evaluated with 43 human patients' sera. Thus, the affinity-purified rCF antigen has yielded reactions comparable to those of crude coccidioidal antigens in conventional CF, IDCF, and enzyme immunoassay.

Animals↗
PubMed1995

Comparative evaluation of commercial Premier EIA and microimmunodiffusion and complement fixation tests for Coccidioides immitis antibodies.

A total of 409 serum and cerebrospinal fluid specimens from human subjects with proven coccidioidomycosis, with other infections, or with no apparent illness were tested for antibodies to Coccidioides immitis by the Premier EIA (Meridian Diagnostics, Inc., Cincinnati, Ohio), which tests for immunoglobulin G (IgG) and IgM responses to coccidioidal antigens, and by the conventional complement fixation (CF) or immunodiffusion (ID) assays for antibodies corresponding to those detected by the tube precipitin (TP) or CF tests. Of the 409 specimens, 47 were from persons with confirmed coccidioidomycosis and all were positive for C. immitis antibodies in IDCF tests and enzyme immunoassays (EIAs) for both IgG and IgM. The EIA for detecting both IgG and IgM antibodies proved to be sensitive for detecting coccidioidomycosis case sera positive by the IDCF, IDTP, and CF tests. Maximal sensitivity for diagnosing coccidioidomycosis is dependent upon detection of both IgG and IgM antibodies in the EIA. The EIA, however, was not absolutely specific, since some sera from patients with confirmed blastomycosis and some from patients with noncoccidioidal disease produced false-positive reactions.

Antibodies, Fungal↗
PubMed1994

Dematiaceous--a mycologic misnomer?

The term dematiaceous has been used to describe dark fungi. However, the historic and etymologic derivation suggest that the concept of dark coloration attached to the root demat... is epistemologically incorrect.

Color↗
PubMed1994

Marked increase in cases of coccidioidomycosis in California: 1991, 1992, and 1993.

Coccidioidomycosis is endemic in California. In an 11-year period from the beginning of 1980 to the end of 1990, an average of approximately 400-500 cases per year were reported to the California State Department of Health Services (CSDHS). In 1990, 441 cases were reported. However, a striking increase in the number of cases was noted in 1991, 1992, and 1993, particularly in the southern San Joaquin Valley counties of Kern and Tulare. In 1992, striking increases were noted in other counties as well. In California there were 1,200 and 4,541 new cases in 1991 and 1992, respectively, that were reported to the CSDHS. The usual rate (5%-7%) of metapulmonary dissemination was noted in these outbreaks, and cases resembling acute adult respiratory distress syndrome that had been noted infrequently in previous outbreaks were conspicuous among the 1991 and 1992 cases. Factors thought to contribute to the extraordinary increases in coccidioidomycosis were a drought of 5 to 6 years' duration; abundant rain in March 1991 and February-March 1992; construction of new buildings; and arrival of new, susceptible individuals to the areas of endemicity.

California↗
PubMed1994

Characterization of Coccidioides immitis isolates by restriction fragment length polymorphisms.

The marked increase in the number of cases of coccidioidomycosis in California in 1992 led to a study of isolates from various patients and environmental sources by restriction fragment length polymorphism (RFLP) analysis. Of 15 different isolates, most of the isolates (13 of 15) from California and 1 from Venezuela yielded one main RFLP pattern with evidence of two subgroups. The other two isolates (both from patients in the San Joaquin Valley of California) yielded a different RFLP pattern.

Animals↗
PubMed1993

Coccidioidomycosis and pregnancy.

Pregnant women with respiratory symptoms of pleuritic pain and productive cough should undergo evaluation for coccidioidomycosis. This should include a history of travel or residency in endemic areas and careful assessment for toxic erythema, erythema nodosum, or erythema multiforme. To confirm a diagnosis of this disease, a sputum culture, wet mount, and serological tests should be performed. The risk of dissemination, which is highest in the second and third trimesters, can be estimated by a complement-fixation titer. In disseminated cases aggressive treatment with amphotericin B has improved the previously reported high maternal and neonatal mortality rate. Fortunately, case reports do not indicate that transplacental spread occurs. Reactivation or exacerbation of a chronic low-grade infection during pregnancy may occur in patients treated for prior disseminated disease (32, 34). Interestingly, both of the reported cases of reactivation or exacerbation occurred in insulin-dependent diabetics.

Adult↗
PubMed1993

Amino-terminal sequence analysis of the Coccidioides immitis chitinase/immunodiffusion-complement fixation protein.

A chitinase isolated from Coccidioides immitis was subjected to amino-terminal protein sequence analysis. The resulting 18-amino-acid sequence was compared with the previously reported amino acid sequence of coccidioidal immunodiffusion-complement fixation (IDCF) antigen. From the homology of the two sequences, the results support the identification of the IDCF antigen with a chitinase.

Amino Acid Sequence↗
PubMed1993

Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans. The Valley Fever Vaccine Study Group.

A vaccine consisting of formaldehyde-killed spherules of Coccidioides immitis, previously shown to provide protection against development of lethal coccidioidomycosis in laboratory animals, was evaluated in humans. This double blind "Phase 3" study, conducted during the period 1980 to 1985, involved 2,867 healthy subjects with no history of coccidioidomycosis and negative skin tests. Randomized into vaccine (n = 1,436) or placebo (n = 1,431) groups, the former received three intramuscular injections of 1.75 mg (dry weight) of spherules, the latter received three injections of sterile 0.85% NaCl solution. Compatible clinical presentation with cultural or serologic findings permitted detection of coccidioidomycosis. Of those receiving vaccine, nine developed coccidioidomycosis and nine additional were suspected of having the disease. Of the group receiving placebo, 12 developed coccidioidomycosis, and 13 additional were suspected of having the disease. All cases and suspected cases were mild. Under the conditions of this study, a slight but statistically insignificant reduction in the incidence of coccidioidomycosis was noted in the vaccinated group compared with that in the placebo group, and there was no discernible difference in severity of disease between these groups.

Adolescent↗
PubMed1993

Coccidioidomycosis.

Coccidioidomycosis is usually acquired by inhalation of Coccidioides immitis in certain areas of the Western Hemisphere. However, the disease may occur far away in individuals who have visited or lived in, then departed from, the endemic areas. The disease which can affect normal and immunocompromised individuals, has many manifestations resembling those of many diseases. The diagnosis is usually not difficult and can be accomplished by histopathological, cultural, and serological methods. Therapy can be surgical and/or medical. The latter can make use of parenteral amphotericin B and its lipid-complex, or the azoles ketoconazole, fluconazole, and itraconazole. However coccidioidal meningitis, coccidioidal arthritis, and acute coccidioidal respiratory insufficiency pose significant challenges to the available therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Coccidioidomycosis in llamas in the United States: 19 cases (1981-1989).

Coccidioidomycosis was diagnosed in 19 llamas (California, 9; Arizona, 10). All but 1 had a disseminated form, with pyogranulomas principally in the lungs, thoracic lymph nodes, liver, and kidneys. However, lesions were found in tissue specimens from most organ systems. Antemortem diagnosis was based on radiographic evaluation of the lungs, serologic testing, or presence of spherules of Coccidioides immitis in pyogranuloma aspirates, skin scrapings, or biopsy specimens. Animals residing in endemic areas of southwestern United States are at risk, and llamas appear to be highly susceptible to developing disseminated forms of coccidioidomycosis.

Animals↗
PubMed1992

Coccidioidomycosis in horses: 15 cases (1975-1984).

Fifteen confirmed cases of equine coccidioidomycosis that originated in California and Arizona were studied retrospectively. Age, breed, and sex varied among affected horses. The most common historical problems were chronic weight loss (53% of cases) and persistent cough (33% of cases). The most frequent physical examination abnormalities were related to the respiratory tract (60% of cases). In 27% of cases, horses had signs of musculoskeletal pain. Horses consistently had hyperproteinemia, hyperfibrinogenemia, leukocytosis, and neutrophilia. An antemortem etiologic diagnosis was made for 11 (73%) horses, all of which had positive serologic tests for coccidioidomycosis. Of the seropositive horses, 5 (46%) also had positive cultures for Coccidioides immitis. One horse died naturally. The other 14 were euthanatized. Prolonged treatment with specific antifungal agents was attempted in 4 horses without apparent benefit. Postmortem abnormalities included pulmonary parenchymal lesions (64% of cases), thoracic lymphadenopathy (57% of cases), hepatic parenchymal involvement (43% of cases), and osteomyelitis (29% of cases). The lesions were granulomatous or pyogranulomatous and C immitis was observed microscopically in 83% of cases.

Amphotericin B↗
PubMed1992

Evaluation of new antifungal drugs for the treatment of systemic fungal infections. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines are applicable to all fungal pathogens that produce systemic infections in humans. Specific examples are provided whenever they might clarify special issues. Systemic fungal infections usually are divided into two broad categories: endemic systemic fungal diseases, which occur classically in healthy hosts, and opportunistic fungal diseases, which occur almost exclusively in patients with impaired host defenses. Both the increasing frequency of disseminated histoplasmosis and coccidioidomycosis in patients with AIDS and the occurrence of candidemia due to vascular-line infections have begun to blur this distinction. The fungi included in these guidelines are Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Candida species, Cryptococcus neoformans, Aspergillus species, and Sporothrix schenckii. Diagnosis of infections caused by these fungi should be based on culture of infected body fluids or tissues whenever possible. Cryptococcal and coccidioidal meningitis are exceptions. Amphotericin B remains the standard comparative agent for most new agents. Further studies of the efficacy of new oral agents used alone or after a hospital course of amphotericin B are needed. The agents currently available are usually inadequate for eradication of fungal infections in patients with AIDS, who may need prolonged treatment. Final assessment for these patients may need to be classified as clinical cure with presumed microbiologic persistence.

Antifungal Agents↗
PubMed1992

Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations.

Twelve patients receiving therapy with an azole agent (ketoconazole, itraconazole, and/or fluconazole) for systemic mycoses experienced drug interactions with rifampin, phenytoin, and/or carbamazepine resulting in substantial decreases in azole concentrations in serum. All four patients receiving azoles and concurrent phenytoin and/or carbamazepine failed to respond to treatment or suffered a relapse of their fungal infection. Four of five patients with cryptococcosis who received itraconazole and rifampin responded despite decreases in their serum itraconazole concentrations; synergy between itraconazole and rifampin was documented by in vitro analysis of inhibition and of killing of Cryptococcus neoformans isolates from all patients receiving this combination. In contrast, two patients with coccidioidomycosis failed to respond to itraconazole/rifampin. Moreover, two patients with cryptococcosis suffered a relapse or persistence of seborrheic dermatitis while receiving itraconazole/rifampin. The latter combination showed synergy in vitro in the inhibition of the mycelial phase of Coccidioides immitis and, to a lesser extent, of the pathogenic spherule phase of this fungus; synergy in the killing of C. immitis was not noted, nor was synergy seen against Malassezia furfur, the purported etiologic agent of seborrheic dermatitis. These findings illustrate several drug interactions that may affect clinical outcome and that must be considered in the management of antifungal therapy.

Adult↗