Detection of Cryptococcus neoformans capsular polysaccharide antigen in asymptomatic HIV-infected patients

Negroni, R.; Cendoya, C.; Arechavala, A.I.; Robles, A.M.; Bianchi, M.; Bava, A.J.; Helou, S.

doi:10.1590/S0036-46651995000500002

Abstracts

Serum samples from 242 HIV-positive persons were studied for the detection of capsular polysaccha-ride antigen of Cryptococcus neoformans; 193 of these patients presented less than 300 CD4+ cells/µl of blood and 49 patients had more than 300 CD4+ cells/µl. None of them had symptoms or signs characteristic of cryptococcosis. The capsular antigen of C. neofarmans was detected by latex agglutination technique with pronase pre-treatment (IMMY, Crypto-Latex Antigen Detection System, Immunomycologics Inc., OK, USA); in 61% of the samples, ELISA technique was also used (Premier, Cryptococcal Antigen, Meridian Diagnostic Inc., Cincinatti, Oh, USA). The comparative study of both methods showed that the results obtained were similar in 96.9% of the cases. The capsular antigen was detected in 13 out of 193 (6.7%) patients with less than 300 CD4+ cells/µl. Cryptococcosis was confirmed mycologically in 3 of these 13 cases (23%) by the isolation of C. neoformans in CSF or blood cultures. Three patients, who had presented negative results of both tests for capsular antigen, suffered disseminated cryptococcosis 4 to 8 months later. The predictive diagnostic value of capsular antigen detection of C. neoformans seems tobe low and we believe that it should not be done routinely in asymptomatic HIV-positive persons.

Cryptococcosis; Antigenemia; Latex agglutination; ELISA tests

Fueron examinadas las muestras de suero de 242 personas, HIV positivas, para determinar la presencia de antígeno capsular del C. neoformans, 193 de estos pacientes tenían recuentos de células CD4 + inferiores a los 300/µl y 49 pacientes presentaron recuentos superiores a este límite. Ninguno de los enfermos tenía sintomatología que hiciese sospechar criptococosis. El antígeno capsular del C. neoformans fue determinado por una técnica de aglutinación de partículas de látex previo tratamiento con pronasa (IMM, latex-Crypto antigen detection system, Immunomycologics, Oh, USA) y 61% de las muestras fueron también examinadas mediante la técnica de ELISA (Premier, Cryptococcal Antigen, Medirian Diagnostic Inc, Cincinatti, OH, USA). Los resultados de ambas técnicas fueron coincidentes en 96.9% de los casos. Pudo comprobarse la presencia de antígeno capsular del C. neoformans en 13 casos entre los 193 pacientes HIV positivos, con recuentos de células CD4+ menores de 300/µl (6.7%), ningún paciente con recuentos superiores a este límite presentó antigenemia positiva. En 3/13 enfermos (23%) pudo confirmarse el diagnóstico de criptococcosis mediante el aislamiento del C. neoformans en LCR o hemocultivos. Tres pacientes que habían presentado antigenemias negativas sufrieron 4 a 8 meses después, criptococosis diseminada. Se considera que el valor diagnóstico predictivo de la detección de antígeno capsular del C. neoformans es bajo y que la realización sistemática de esta reacción no se justifica.

MICOLOGY

Detection of Cryptococcus neoformans capsular polysaccharide antigen in asymptomatic HIV-infected patients

Detección del antígeno capsular del Cryptococcus neoformans en pacientes asintomáticos infectados por HIV

R. Negroni; C. Cendoya; A.I. Arechavala; A.M. Robles; M. Bianchi; A.J. Bava; S. Helou

^{Correspondence to} Correspondence to: Mycology Unit, Infectious Diseases Hospital "F.J. Muñiz" Uspallata 2272 (1282) Buenos Aires, Argentina

SUMMARY

Serum samples from 242 HIV-positive persons were studied for the detection of capsular polysaccha-ride antigen of Cryptococcus neoformans; 193 of these patients presented less than 300 CD4+ cells/µl of blood and 49 patients had more than 300 CD4+ cells/µl.

None of them had symptoms or signs characteristic of cryptococcosis.

The capsular antigen of C. neofarmans was detected by latex agglutination technique with pronase pre-treatment (IMMY, Crypto-Latex Antigen Detection System, Immunomycologics Inc., OK, USA); in 61% of the samples, ELISA technique was also used (Premier, Cryptococcal Antigen, Meridian Diagnostic Inc., Cincinatti, Oh, USA). The comparative study of both methods showed that the results obtained were similar in 96.9% of the cases.

The capsular antigen was detected in 13 out of 193 (6.7%) patients with less than 300 CD4+ cells/µl. Cryptococcosis was confirmed mycologically in 3 of these 13 cases (23%) by the isolation of C. neoformans in CSF or blood cultures. Three patients, who had presented negative results of both tests for capsular antigen, suffered disseminated cryptococcosis 4 to 8 months later.

The predictive diagnostic value of capsular antigen detection of C. neoformans seems tobe low and we believe that it should not be done routinely in asymptomatic HIV-positive persons.

Keywords: Cryptococcosis; Antigenemia; Latex agglutination; ELISA tests.

RESUMEN

Fueron examinadas las muestras de suero de 242 personas, HIV positivas, para determinar la presencia de antígeno capsular del C. neoformans, 193 de estos pacientes tenían recuentos de células CD4 + inferiores a los 300/µl y 49 pacientes presentaron recuentos superiores a este límite. Ninguno de los enfermos tenía sintomatología que hiciese sospechar criptococosis. El antígeno capsular del C. neoformans fue determinado por una técnica de aglutinación de partículas de látex previo tratamiento con pronasa (IMM, latex-Crypto antigen detection system, Immunomycologics, Oh, USA) y 61% de las muestras fueron también examinadas mediante la técnica de ELISA (Premier, Cryptococcal Antigen, Medirian Diagnostic Inc, Cincinatti, OH, USA). Los resultados de ambas técnicas fueron coincidentes en 96.9% de los casos.

Pudo comprobarse la presencia de antígeno capsular del C. neoformans en 13 casos entre los 193 pacientes HIV positivos, con recuentos de células CD4+ menores de 300/µl (6.7%), ningún paciente con recuentos superiores a este límite presentó antigenemia positiva. En 3/13 enfermos (23%) pudo confirmarse el diagnóstico de criptococcosis mediante el aislamiento del C. neoformans en LCR o hemocultivos. Tres pacientes que habían presentado antigenemias negativas sufrieron 4 a 8 meses después, criptococosis diseminada.

Se considera que el valor diagnóstico predictivo de la detección de antígeno capsular del C. neoformans es bajo y que la realización sistemática de esta reacción no se justifica.

Full text available only in PDF format.

Texto completo disponible sólo en PDF.

Recebido para publicação em 27/03/1995

Aceito para publicação em 07/11/1995

This paper was supported by the AMSA award granted by the National Academy of Medicine in memory of Prof. Dr. Pablo Negroni, and subsidy by Janssen Research Foundation.

1. BAVA, A.J., ARECHAVALA, A.; ROBLES, AM. et al. - Estudio de la criptococosis en nuestro medio (1981' 1992). Academia Nacional de Medicina, Premio A. Bachmann, 1994.
2. DESMET, P.; KAYEMKE, K.D. & DE VROEY, C. - The value of cryptococcal serum antigen screening among HIV positive/AIDS patients in Kinshasa, Zaire. AIDS, 3: 77-78, 1989.
3. GADE, W.; HINNFELD, S.W.; BAKCOCK, L.S. et al. - Comparison of the Premier Cryptococcal antigen enzyme immunoassay and the latex agglutination assay for detection of cryptococcal antigens. J. clin. Microbiol., 29: 1616-1619, 1991.
4. HOFFMAN, S.; STENDERUP, J. & MATHIENSEN, L.R. - Low yield of screening for cryptococcal antigen by latex agglutination assay on serum and cerebrospinal fluid from Danish patients, with AIDS or ARC. Scand. J. infect. Dis., 23: 697-702, 1991.
5. KAUFMAN, L. - Laboratory methods for the diagnosis and confirmation of systemic mycosis. Clin. infect. Dis., 14 (suppl. 1): S23-S29, 1992.
6. KOHNO, S.; YASOUKA, A.; KOGA, H. et al. - High detection rates of cryptococcal antigen in pulmonary cryptococcosis by Eiken latex agglutination test with pronase pretreatment. Mycopathologia (Den Haag), 123: 75-79, 1993.
7. KOZEL, T.R. - Assay and analysis of cryptococcal polysaccharide by latex agglutination and monoclonal based ELISA. In: INTERNATIONAL CONFERENCE ON CRYPTOCOCCUS AND CRYPTOCOCCOSIS, 2, Milano, 1993. Abstracts. p. 72.
8. NEGRONI, R.; ARECHAVALA, A.; ROBLES, A.M.. et al. - Revisión clínica y evolución terapéutica de pacientes con criptococosis asociada al SIDA. Rev. Iberoamer. Micol., 11: 77-80, 1994.
9. POWDERLY, W.G. - Antigen testing in cryptococcosis. In: INTERNATIONAL CONFERENCE ON CRYPTOCOCCUS AND CRYPTOCOCCOSIS, 2, Milano, 1993. Abstracts. p. 80.
10. ROLAND, H.; LOYOLA, S. & DIAZ, M. - Complicaciones en SIDA: estudio retrospectivo de 137 casos. Actualiz. SIDA 2(6): 198-206, 1994.
11. SCOTT, E.N.; MUCHMORE, H.G. & FELTON, F.G. - Comparison of enzyme immunoassay and latex agglutination methods for detection of Cryptococcus neoformans antigen. Amer. J. clin. Path., 73: 790-794, 1980.
12. SUGAR, A. - Overview: cryptococcosis in patients with AIDS. Mycopathologia (Den Haag), 114: 153-157, 1991.
13. TABORDA, A.; NEGRONI, R.; ARECHAVALA, A. & ROBLES, A.M. - Criptococosis asociada al SIDA. Estudio retrospectivo de las terapéuticas antifúngicas en 43 casos. Rev. Iberoamer. Micol., 10: 10-13, 1993.
14. TANAKA, K.; KHONO, S.; MIYAZAKI, T. et al. - The Eiken latex test for detection of cryptococcal antigen in cryptococcosis: comparison with a monoclonal antibody-based latex agglutination test. Pastorex R. Cryptococcus. Mycopathologia (Den Haag), 127: 131-134, 1994.
15. VANDEPITTE, J. - Clinical aspects of cryptococcosis in patients with AIDS. In: VANDEN BOSSCHE, H. et al. Mycoses in AIDS patients, New York, Plenum Press, 1990. p. 115-122
16. WESTERINK, M.A.J.; AMSTERDAN, D.; PETELL, R.J.; STRAM, M.N. & APICELLA, M.A. - Septicemia due to DF-2: cause of a false-positive cryptococcal latex agglutination result. Amer. J. Med., 83: 155-158, 1987.

Correspondence to:

Mycology Unit, Infectious Diseases Hospital "F.J. Muñiz"

Uspallata 2272

(1282) Buenos Aires, Argentina

Publication Dates

Publication in this collection
21 Sept 2006
Date of issue
Oct 1995

History

Accepted
07 Nov 1995
Received
27 Mar 1995

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BAVA, A.J., ARECHAVALA, A.; ROBLES, AM. et al. - Estudio de la criptococosis en nuestro medio (1981' 1992). Academia Nacional de Medicina, Premio A. Bachmann, 1994.

[2] 2. DESMET, P.; KAYEMKE, K.D. & DE VROEY, C. - The value of cryptococcal serum antigen screening among HIV positive/AIDS patients in Kinshasa, Zaire. AIDS, 3: 77-78, 1989.

[3] 3. GADE, W.; HINNFELD, S.W.; BAKCOCK, L.S. et al. - Comparison of the Premier Cryptococcal antigen enzyme immunoassay and the latex agglutination assay for detection of cryptococcal antigens. J. clin. Microbiol., 29: 1616-1619, 1991.

[4] 4. HOFFMAN, S.; STENDERUP, J. & MATHIENSEN, L.R. - Low yield of screening for cryptococcal antigen by latex agglutination assay on serum and cerebrospinal fluid from Danish patients, with AIDS or ARC. Scand. J. infect. Dis., 23: 697-702, 1991.

[5] 5. KAUFMAN, L. - Laboratory methods for the diagnosis and confirmation of systemic mycosis. Clin. infect. Dis., 14 (suppl. 1): S23-S29, 1992.

[6] 6. KOHNO, S.; YASOUKA, A.; KOGA, H. et al. - High detection rates of cryptococcal antigen in pulmonary cryptococcosis by Eiken latex agglutination test with pronase pretreatment. Mycopathologia (Den Haag), 123: 75-79, 1993.

[7] 7. KOZEL, T.R. - Assay and analysis of cryptococcal polysaccharide by latex agglutination and monoclonal based ELISA. In: INTERNATIONAL CONFERENCE ON CRYPTOCOCCUS AND CRYPTOCOCCOSIS, 2, Milano, 1993. Abstracts. p. 72.

[8] 8. NEGRONI, R.; ARECHAVALA, A.; ROBLES, A.M.. et al. - Revisión clínica y evolución terapéutica de pacientes con criptococosis asociada al SIDA. Rev. Iberoamer. Micol., 11: 77-80, 1994.

[9] 9. POWDERLY, W.G. - Antigen testing in cryptococcosis. In: INTERNATIONAL CONFERENCE ON CRYPTOCOCCUS AND CRYPTOCOCCOSIS, 2, Milano, 1993. Abstracts. p. 80.

[10] 10. ROLAND, H.; LOYOLA, S. & DIAZ, M. - Complicaciones en SIDA: estudio retrospectivo de 137 casos. Actualiz. SIDA 2(6): 198-206, 1994.

[11] 11. SCOTT, E.N.; MUCHMORE, H.G. & FELTON, F.G. - Comparison of enzyme immunoassay and latex agglutination methods for detection of Cryptococcus neoformans antigen. Amer. J. clin. Path., 73: 790-794, 1980.

[12] 12. SUGAR, A. - Overview: cryptococcosis in patients with AIDS. Mycopathologia (Den Haag), 114: 153-157, 1991.

[13] 13. TABORDA, A.; NEGRONI, R.; ARECHAVALA, A. & ROBLES, A.M. - Criptococosis asociada al SIDA. Estudio retrospectivo de las terapéuticas antifúngicas en 43 casos. Rev. Iberoamer. Micol., 10: 10-13, 1993.

[14] 14. TANAKA, K.; KHONO, S.; MIYAZAKI, T. et al. - The Eiken latex test for detection of cryptococcal antigen in cryptococcosis: comparison with a monoclonal antibody-based latex agglutination test. Pastorex R. Cryptococcus. Mycopathologia (Den Haag), 127: 131-134, 1994.

[15] 15. VANDEPITTE, J. - Clinical aspects of cryptococcosis in patients with AIDS. In: VANDEN BOSSCHE, H. et al. Mycoses in AIDS patients, New York, Plenum Press, 1990. p. 115-122

[16] 16. WESTERINK, M.A.J.; AMSTERDAN, D.; PETELL, R.J.; STRAM, M.N. & APICELLA, M.A. - Septicemia due to DF-2: cause of a false-positive cryptococcal latex agglutination result. Amer. J. Med., 83: 155-158, 1987.

Brasil