Detection of Paracoccidioides brasiliensis gp70 Circulating Antigen and Follow-Up of Patients Undergoing Antimycotic Therapy

Serological diagnosis and follow-up of paracoccidioidomycosis (PCM) patients have relied mainly on the detection of antibody responses by using techniques such as complement fixation (CF) and immunodiffusion. We recently described a novel inhibition enzyme-linked immunosorbent assay (inh-ELISA) which proved to be useful in the diagnosis of PCM via the detection of an 87-kDa determinant in patient sera (B. L. Gomez, J. I. Figueroa, A. J. Hamilton, B. Ortiz, M. A. Robledo, R. J. Hay, and A. Restrepo, J. Clin. Microbiol. 35:3278–3283, 1997). This test has now been assessed as a means of following up PCM patients. A total of 24 PCM patients, classified according to their clinical presentation (6 with the acute form of the disease, of whom two had AIDS, 12 with the multifocal form of the disease, and 6 with the unifocal form of the disease), were studied. The four human immunodeficiency virus-negative patients with acute PCM showed a statistically significant decrease in circulating antigen levels after the start of antifungal therapy. Antigen levels in this group became negative by our criteria (≤2.3 μg/ml) before week 20 and remained so in three of four of these patients. In contrast, the two AIDS patients who also presented with the acute form of PCM showed no statistically significant decrease in circulating antigen levels even after 68 weeks of therapy. Taken together as a group, the patients with the multifocal form showed a statistically significant decrease in antigenemia after 28 weeks of therapy. In addition, five of six patients with the unifocal form became antigen negative by week 40. Antigen level decrease mirrored clinical cure in the majority of patients in all clinical groups; in contrast, measurement of anti-PCM antibodies via the CF test showed wide fluctuations in titers during the follow-up period. The inh-ELISA for the detection of the 87-kDaParacoccidioides brasiliensis determinant would appear to be a valuable additional tool in the follow-up of PCM patients.

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Detection of Circulating Paracoccidioides brasiliensis Antigen in Urine of Paracoccidioidomycosis Patients before and during Treatment

Journal of Clinical Microbiology ◽

10.1128/jcm.36.6.1723-1728.1998 ◽

1998 ◽

Vol 36 (6) ◽

pp. 1723-1728 ◽

Cited By ~ 38

Author(s):

Margarete Aparecida Salina ◽

Maria Aparecida Shikanai-Yasuda ◽

Rinaldo Poncio Mendes ◽

Benedito Barraviera ◽

Maria José Soares Mendes Giannini

Keyword(s):

Enzyme Immunoassay ◽

Treatment Period ◽

Paracoccidioides Brasiliensis ◽

Urine Samples ◽

Control Group ◽

Clinical Recovery ◽

Circulating Antigen ◽

Urine Specimens ◽

Efficacy Of Treatment

For the diagnosis and follow-up of paracoccidioidomycosis patients undergoing therapy, we evaluated two methods (immunoblotting and competition enzyme immunoassay) for the detection of circulating antigen in urine samples. A complex pattern of reactivity was observed in the immunoblot test. Bands of 70 and 43 kDa were detected more often in urine samples from patients before treatment. The immunoblot method detected gp43 and gp70 separately or concurrently in 11 (91.7%) of 12 patients, whereas the competition enzyme immunoassay detected antigenuria in 9 (75%) of 12 patients. Both tests appeared to be highly specific (100%), considering that neither fraction detectable by immunoblotting was present in urine samples from the control group. gp43 remained present in the urine samples collected during the treatment period, with a significant decrease in reactivity in samples collected during clinical recovery and increased reactivity in samples collected during relapses. Reactivity of some bands was also detected in urine specimens from patients with “apparent cure.” The detection of Paracoccidioides brasiliensis antigens in urine appears to be a promising method for diagnosing infection, for evaluating the efficacy of treatment, and for detecting relapse.

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Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652009000100008 ◽

2009 ◽

Vol 51 (1) ◽

pp. 45-48 ◽

Cited By ~ 10

Author(s):

Carlos Andrés Agudelo ◽

Carolina Muñoz ◽

Alex Ramírez ◽

Jonhairo Gutierrez ◽

Santiago Velez ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Adrenal Glands ◽

Paracoccidioides Brasiliensis ◽

Direct Visualization

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

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Negative Immunodiffusion Test Results Obtained with Sera of Paracoccidioidomycosis Patients May Be Related to Low-Avidity Immunoglobulin G2 Antibodies Directed against Carbohydrate Epitopes

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.5.802-807.2003 ◽

2003 ◽

Vol 10 (5) ◽

pp. 802-807 ◽

Cited By ~ 23

Author(s):

Andréia R. Neves ◽

Ronei L. Mamoni ◽

Cláudio L. Rossi ◽

Zoilo P. de Camargo ◽

Maria Heloísa S. L. Blotta

Keyword(s):

Paracoccidioides Brasiliensis ◽

False Negative ◽

Enzyme Linked Immunosorbent Assay ◽

Test Results ◽

Sodium Metaperiodate ◽

Negative Results ◽

Carbohydrate Epitopes ◽

False Negative Results ◽

Specific Igg

ABSTRACT Immunodiffusion (ID) is the serologic test most frequently used for the diagnosis and posttherapy follow-up of patients with paracoccidioidomycosis (PCM). The ID test is highly specific (100%), but its sensitivity is relatively low (90%), leading to false-negative results. The aim of this study was to determine the profiles of antibodies in sera from patients with proven PCM and with negative results in the ID test (IDneg) versus positive results in the ID test (IDpos). We analyzed 46 sera from patients with active PCM for total immunoglobulin G (IgG) and IgG subclass responses to Paracoccidioides brasiliensis gp43 antigen (treated or not treated with sodium metaperiodate) by enzyme-linked immunosorbent assay and immunoblotting. Immunoblotting showed that both IDneg and IDpos sera recognized predominantly the gp43 fraction of the P. brasiliensis antigen used in the ID test. IDneg sera contain low-avidity antibodies, low levels of specific IgG (total) and IgG1, and high levels of IgG2 compared with IDpos sera. The antibodies present in IDneg sera were predominantly directed against carbohydrate epitopes, since treatment with sodium metaperiodate resulted in a significant decrease in antibody reactivity. These data suggest that the lack of reactivity of sera from PCM patients in the ID test may be related to the production of low-avidity IgG2 antibodies directed against carbohydrate epitopes.

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Long-term outcome of neuroparacoccidioidomycosis treatment

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822011000100006 ◽

2011 ◽

Vol 44 (1) ◽

pp. 22-25 ◽

Cited By ~ 15

Author(s):

Fabio Francesconi ◽

Marcus Tulius Teixeira da Silva ◽

Regina Lana Braga Costa ◽

Valeska Albuquerque Francesconi ◽

Eleonora Carregal ◽

...

Keyword(s):

Paracoccidioides Brasiliensis ◽

Pathogenic Fungus ◽

Case Series ◽

Neurological Deficits ◽

Common Finding ◽

Neurological Sequela ◽

Long Term Outcome ◽

Oral Fluconazole

INTRODUCTION: Neuroparacoccidioidomycosis (NPCM) is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8%) cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM). A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP) was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

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Case report: Multifocal chronic paracoccidioidomycosis in an adult

Colombia Medica ◽

10.25100/cm.v42i2.776 ◽

2011 ◽

pp. 228-232

Author(s):

Karen Zapata ◽

Janeth Villanueva ◽

Adriana Arrunátegui ◽

Juana Gabriela López

Keyword(s):

Paracoccidioides Brasiliensis ◽

Giant Cells ◽

Systemic Mycosis ◽

Adequate Treatment ◽

Lung Lesions ◽

History Of ◽

One Year ◽

Lost To Follow Up

Paracoccidioides brasiliensis is the ethiological agent of one of the most prevalent systemic mycosis in Latin America, where around ten-million individuals are affected. Brazil has the highest incidence but in Venezuela, Colombia, Ecuador, and Argentina cases have also been reported. We describe a 56-year-old male with a one year history of lip, oral mucosa, and lung lesions. Granulomas and multinucleated giant cells were observed in histopathological evaluation with haematoxilyn-eosin stain. Mycologic studies (KOH and Gomori Grocott stain) showed blastoconidias with multiple budding. Serologic tests for paracoccidioidine were reactive. A diagnosis of chronic multifocal paracoccidioidomycosis was made. Initially, amphotericin B 0.7 mg/kg per day was started for fifteen days and consecutively itraconazole (400 mg/day) was administered orally with improvement of skin and lung lesions; however, an important residual fibrosis was observed. The patient was lost to follow up. We highlight the importance of an early diagnosis and adequate treatment to decrease sequelae in patient quality of life.

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Wuchereria bancrofti recombinant antigen-derived poly- and monoclonal antibodies for the detection of circulating antigen(s) in the sera of lymphatic filarial patients

Journal of Helminthology ◽

10.1017/s0022149x00015157 ◽

1996 ◽

Vol 70 (1) ◽

pp. 69-74 ◽

Cited By ~ 4

Author(s):

J.G. Theodore ◽

P. Kaliraj

Keyword(s):

Monoclonal Antibodies ◽

Membrane Filtration ◽

Wuchereria Bancrofti ◽

Recombinant Antigen ◽

Parasite Antigen ◽

Filarial Antigen ◽

Finger Prick ◽

Circulating Antigen ◽

Antibody Elisa

AbstractA sandwich antibody ELISA was employed for the detection of circulating filarial antigen in patients with bancroftian filariasis. Wuchereria bancrofti recombinant antigen-derived polyclonal and monoclonal antibodies were successfully used as the revealing antibodies and their efficiency was compared. All the microfilariae (mf) positive (by finger prick and examination of 20 μl of blood under the microscope) individuals tested showed the presence of circulating antigen(s). Among the antigen positive endemic normals (mf negative by the finger prick method), 43% showed microfilariae by a sensitive parasitological method viz. membrane filtration of the night blood samples. A significant correlation was observed between the parasite antigen levels and the blood microfilaria counts among the mf carriers. This information on the parasite antigen levels could be an ideal monitor to indicate the degree of active infection and in the follow up of chemotherapy.

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CEA Determination in the Follow-Up of Extracolorectal Neoplasms

The International Journal of Biological Markers ◽

10.1177/172460089200700309 ◽

1992 ◽

Vol 7 (3) ◽

pp. 171-178 ◽

Cited By ~ 6

Author(s):

R. Lamerz

Keyword(s):

Clinical Indication ◽

Course Of Disease ◽

Serial Determination ◽

Tumor Stages ◽

Circulating Antigen ◽

Organ Specific ◽

Serum Cea ◽

Fetal Organs ◽

Radio Chemotherapy

CEA was initially described as a tumor and organ specific colorectal antigen, but later found by more sensitive methods in other tumors (stomach, pancreas, lung, breast) and in minor amounts in inflammatory, normal adult and fetal organs of the gastrointestinal tract. The main clinical application of CEA concerns its pretherapeutic and serial determination as circulating antigen in serum and other body fluids by means of CEA-specific, commercially available test kits. By clinical studies a significant correlation has been proven between the pretherapeutic serum CEA level and tumor stages and prognosis. Moreover, serial CEA level changes have been shown a valuable monitor following operation or during radio/chemotherapy anticipating and reflecting the clinical course of disease. In combination with newly established tumor markers, the main clinical indication for CEA determination in addition to colorectal cancer concerns monitoring of patients with stomach (+ CA 72-4), lung (+ NSE/SCC) and breast cancer (+ CA 15-3/MCA).

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Relevance of circulating antigen detection to follow-up experimental and human cystic hydatid infections

Parasite Immunology ◽

10.1046/j.1365-3024.1998.00177.x ◽

1998 ◽

Vol 20 (11) ◽

pp. 541-549 ◽

Cited By ~ 15

Author(s):

G Ferragut ◽

I Ljungstrom ◽

A Nieto

Keyword(s):

Antigen Detection ◽

Circulating Antigen ◽

Cystic Hydatid

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Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

Behavioral and Brain Sciences ◽

10.1017/s0140525x1800105x ◽

2019 ◽

Vol 42 ◽

Cited By ~ 2

Author(s):

John P. A. Ioannidis

Keyword(s):

Mental Health ◽

Mental Disease ◽

Brain Disorders ◽

Social Stressors ◽

Labor Education ◽

Mental Diseases ◽

Long Term Follow Up ◽

Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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