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Cryptococcal Meningitis: False-Negative Antigen Test Results and Cultures in Nonimmunosuppressed Patients

Cryptococcal Meningitis: False-Negative Antigen Test Results and Cultures in Nonimmunosuppressed... Abstract • All cases of cryptococcal meningitis at Yale-New Haven (Conn) Hospital seen during a 41/2-year period were reviewed to calculate the rate of false-negative antigen test results and cultures preceding diagnosis. Of 13 patients, 9 were immunosuppressed and were diagnosed following the initial lumbar puncture, with both antigen test results and cultures positive in all cases. Among 4 nonimmunosuppressed patients, the rate of false-negative antigen test results was 77%, and of cultures, 89%. The diagnosis was consequently delayed in 3, 2 of whom died despite treatment. Cryptococcal meningitis may be underdiagnosed and undertreated to a significant degree in nonimmunosuppressed patients. References 1. Anderson WAS, Scotti TM. Synopsis of Pathology . 10th ed. St Louis, Mo: CV Mosby Co; 1980:200. 2. Zuger A, Louie E, Holzman RS. Cryptococcal disease in patients with the acquired immune-deficiency syndrome . Ann Intern Med . 1986;104:234-240.Crossref 3. Fraser DW, Ward JI, Ajello L, et al. Aspergillosis and other systemic mycoses: the growing problem . JAMA . 1979;242:1631-1635.Crossref 4. Eng RHK, Bishburg E, Smith S. Cryptococcal infections in patients with acquired immune deficiency syndrome . Am J Med . 1986;81:19-23.Crossref 5. Drutz DJ. Antigen detection in fungal infections . N Engl J Med . 1986;314:115-117.Crossref 6. Bennett JE, Wilson JD, Martin JB, Fauci AS. Fungal infection . In: Braunwald E, Isselbacher KJ, Petersdorf RG, eds. Harrison's Principles of Internal Medicine . 11th ed. New York, NY: Mc-Graw-Hill International Book Co; 1987:736-745. 7. Butler WT, Alling DW, Spickard A, Utz JP. Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis . N Engl J Med . 1964;270:59-67.Crossref 8. Hoeprich PD. Cryptococcus . In: Hoeprich PD, ed. Infectious Diseases . 2nd ed. New York, NY: Harper & Row Publishers Inc; 1977:902-912. 9. Sarosi GA, Parker JD, Doto IL, et al. Amphotericin B in cryptococcal meningitis: longterm results of treatment . Ann Intern Med . 1969;71:1079-1087.Crossref 10. Sabetta JR, Andriole VT. Cryptococcal infection of the central nervous system . Med Clin North Am . 1985;69:333-344. 11. Prevost E, Newell R. Commercial cryptococcal latex kit: clinical evaluation in a medical center hospital . J Clin Microbiol . 1978;8:529-533. 12. Kaufman L, Blumer S. Value and interpretation of serological tests for the diagnosis of cryptococcosis . Appl Environ Microbiol . 1968;16:1907-1912. 13. Gordon MA, Vedder DK. Serologic tests in diagnosis and prognosis of cryptococcosis . JAMA . 1966;197:961-967.Crossref 14. Stockstill MT, Kauffman CA. Comparison of cryptococcal and tuberculous meningitis . Arch Neurol 1983;40:81-85.Crossref 15. Bloomfield N, Gordon MA, Elmendorf DF Jr. Detection of Cryptococcus neoformans antigen in body fluids by latex particle agglutination . Proc Soc Exp Biol Med . 1963;114:64-67.Crossref 16. Wu TC, Koo SY. Comparison of three commercial cryptococcal latex kits for detection of cryptococcal antigen . J Clin Microbiol . 1983;18:1127-1130. 17. Spickard A, Butler WT, Andriole V, Utz JP. The improved prognosis of cryptococcal meningitis with amphotericin B therapy . Ann Intern Med . 1963;58:66-83.Crossref 18. Kaplan MH, Rosen PP, Armstrong D. Cryptococcosis in a cancer hospital . Cancer . 1977;39:2265-2274.Crossref 19. Diamond RD. Cryptococcus neoformans . In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and Practice of Infectious Disease . 2nd ed. New York, NY: John Wiley & Sons Inc; 1985;1460-1467. 20. Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis . Ann Intern Med . 1974;80:175-181.Crossref 21. Gonyea EF. Cisternal puncture and cryptococcal latex kit: clinical evaluation in a medical center hospital . J Clin Microbiol . 1978;8:529-533. 22. Myerowitz RL. The Pathology of Opportunistic Infections: With Pathogenic, Diagnostic and Clinical Correlations . New York, NY: Raven Press; 1983:145-160. 23. Ley A, Jacas R, Oliveras C. Torula granuloma of the cervical cord . J Neurosurg . 1951;8:327-335.Crossref 24. Ramamurthi B, Anguli VC. Intramedullary cryptococcal granuloma of the spinal cord . J Neurosurg . 1954;11:622-624.Crossref 25. Carton CA, Mount LA. Neurosurgical aspects of cryptococcosis . J Neurosurg . 1951;8:143-156.Crossref 26. Litvinoff J, Nelson M. Extradural lumbar cryptococcosis: case report . J Neurosurg . 1978;49:921-923.Crossref 27. Rao SB, Rao KS, Dinaker I. Spinal epidural cryptococcal granuloma: a case report . Neurol India . 1970;18:192-193. 28. Rubin RA. Infection in the immunocompromised host . In: Rubenstein E, Federman DP, eds. Medicine . New York, NY: Scientific American; 1985:11-14. 29. Boom WH, Piper DJ, Ruoff KL, Ferraro MJ. New cause for false-positive results with the cryptococcal antigen test by latex agglutination . J Clin Microbiol . 1985;22:856-857. 30. Salom IL. Cryptococcal meningitis: significance of positive antigen test on undiluted spinal fluid . NY State J Med . 1981;81:1369-1370. 31. Goodman JS, Kaufman L, Koenig MG. Diagnosis of cryptococcal meningitis: value of immunologic detection of cryptococcal antigen . N Engl J Med . 1971;285:434-436.Crossref 32. Snow RM, Dismukes WE. Cryptococcal meningitis: diagnostic value of cryptococcal antigen in cerebrospinal fluid . Arch Intern Med . 1975;135:1155-1157.Crossref 33. Berger MP, Jaz J. Diagnosis of cryptococcal meningitis . JAMA . 1976;236:2517-2518.Crossref 34. Haldane DJM, Bauman DS, Chow AW, et al. False negative latex agglutination test in cryptococcal meningitis . Ann Neurol . 1986;19:412-413.Crossref 35. Utz UP. Histoplasma and Cryptococcus meningitis . Res Publ Assoc Res Nerv Ment Dis . 1968;44:378-392. 36. Edwards VE, Sutherland JM, Tyrer JH. Cryptococcosis of the central nervous system: epidemiological, clinical and therapeutic features . J Neurol Neurosurg Psychiatry . 1970;33:415-425.Crossref 37. Kaufman L, Blumer S. Latex-cryptococcal antigen test . Am J Clin Pathol . 1973;60:285-286. 38. Ransohoff DF, Feinstein AR. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests . N Engl J Med . 1978;299:926-930.Crossref 39. Stamm AM, Polt SS. False-negative cryptococcal antigen test . JAMA . 1980;244:1359.Crossref 40. Campbell GD, Currier RD, Busey JF. Survival in untreated cryptococcal meningitis . Neurology . 1981;31:1154-1157.Crossref 41. Sande MA, Mandell GL. Antimicrobial agents: fungal agents . In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. The Pharmacological Basis of Therapeutics . 7th ed. New York, NY: Macmillan Publishing Co Inc; 1985:1220-1223. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Cryptococcal Meningitis: False-Negative Antigen Test Results and Cultures in Nonimmunosuppressed Patients

Archives of Neurology , Volume 46 (12) – Dec 1, 1989

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Publisher
American Medical Association
Copyright
Copyright © 1989 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1989.00520480054020
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Abstract

Abstract • All cases of cryptococcal meningitis at Yale-New Haven (Conn) Hospital seen during a 41/2-year period were reviewed to calculate the rate of false-negative antigen test results and cultures preceding diagnosis. Of 13 patients, 9 were immunosuppressed and were diagnosed following the initial lumbar puncture, with both antigen test results and cultures positive in all cases. Among 4 nonimmunosuppressed patients, the rate of false-negative antigen test results was 77%, and of cultures, 89%. The diagnosis was consequently delayed in 3, 2 of whom died despite treatment. Cryptococcal meningitis may be underdiagnosed and undertreated to a significant degree in nonimmunosuppressed patients. References 1. Anderson WAS, Scotti TM. Synopsis of Pathology . 10th ed. St Louis, Mo: CV Mosby Co; 1980:200. 2. Zuger A, Louie E, Holzman RS. Cryptococcal disease in patients with the acquired immune-deficiency syndrome . Ann Intern Med . 1986;104:234-240.Crossref 3. Fraser DW, Ward JI, Ajello L, et al. Aspergillosis and other systemic mycoses: the growing problem . JAMA . 1979;242:1631-1635.Crossref 4. Eng RHK, Bishburg E, Smith S. Cryptococcal infections in patients with acquired immune deficiency syndrome . Am J Med . 1986;81:19-23.Crossref 5. Drutz DJ. Antigen detection in fungal infections . N Engl J Med . 1986;314:115-117.Crossref 6. Bennett JE, Wilson JD, Martin JB, Fauci AS. Fungal infection . In: Braunwald E, Isselbacher KJ, Petersdorf RG, eds. Harrison's Principles of Internal Medicine . 11th ed. New York, NY: Mc-Graw-Hill International Book Co; 1987:736-745. 7. Butler WT, Alling DW, Spickard A, Utz JP. Diagnostic and prognostic value of clinical and laboratory findings in cryptococcal meningitis . N Engl J Med . 1964;270:59-67.Crossref 8. Hoeprich PD. Cryptococcus . In: Hoeprich PD, ed. Infectious Diseases . 2nd ed. New York, NY: Harper & Row Publishers Inc; 1977:902-912. 9. Sarosi GA, Parker JD, Doto IL, et al. Amphotericin B in cryptococcal meningitis: longterm results of treatment . Ann Intern Med . 1969;71:1079-1087.Crossref 10. Sabetta JR, Andriole VT. Cryptococcal infection of the central nervous system . Med Clin North Am . 1985;69:333-344. 11. Prevost E, Newell R. Commercial cryptococcal latex kit: clinical evaluation in a medical center hospital . J Clin Microbiol . 1978;8:529-533. 12. Kaufman L, Blumer S. Value and interpretation of serological tests for the diagnosis of cryptococcosis . Appl Environ Microbiol . 1968;16:1907-1912. 13. Gordon MA, Vedder DK. Serologic tests in diagnosis and prognosis of cryptococcosis . JAMA . 1966;197:961-967.Crossref 14. Stockstill MT, Kauffman CA. Comparison of cryptococcal and tuberculous meningitis . Arch Neurol 1983;40:81-85.Crossref 15. Bloomfield N, Gordon MA, Elmendorf DF Jr. Detection of Cryptococcus neoformans antigen in body fluids by latex particle agglutination . Proc Soc Exp Biol Med . 1963;114:64-67.Crossref 16. Wu TC, Koo SY. Comparison of three commercial cryptococcal latex kits for detection of cryptococcal antigen . J Clin Microbiol . 1983;18:1127-1130. 17. Spickard A, Butler WT, Andriole V, Utz JP. The improved prognosis of cryptococcal meningitis with amphotericin B therapy . Ann Intern Med . 1963;58:66-83.Crossref 18. Kaplan MH, Rosen PP, Armstrong D. Cryptococcosis in a cancer hospital . Cancer . 1977;39:2265-2274.Crossref 19. Diamond RD. Cryptococcus neoformans . In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and Practice of Infectious Disease . 2nd ed. New York, NY: John Wiley & Sons Inc; 1985;1460-1467. 20. Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis . Ann Intern Med . 1974;80:175-181.Crossref 21. Gonyea EF. Cisternal puncture and cryptococcal latex kit: clinical evaluation in a medical center hospital . J Clin Microbiol . 1978;8:529-533. 22. Myerowitz RL. The Pathology of Opportunistic Infections: With Pathogenic, Diagnostic and Clinical Correlations . New York, NY: Raven Press; 1983:145-160. 23. Ley A, Jacas R, Oliveras C. Torula granuloma of the cervical cord . J Neurosurg . 1951;8:327-335.Crossref 24. Ramamurthi B, Anguli VC. Intramedullary cryptococcal granuloma of the spinal cord . J Neurosurg . 1954;11:622-624.Crossref 25. Carton CA, Mount LA. Neurosurgical aspects of cryptococcosis . J Neurosurg . 1951;8:143-156.Crossref 26. Litvinoff J, Nelson M. Extradural lumbar cryptococcosis: case report . J Neurosurg . 1978;49:921-923.Crossref 27. Rao SB, Rao KS, Dinaker I. Spinal epidural cryptococcal granuloma: a case report . Neurol India . 1970;18:192-193. 28. Rubin RA. Infection in the immunocompromised host . In: Rubenstein E, Federman DP, eds. Medicine . New York, NY: Scientific American; 1985:11-14. 29. Boom WH, Piper DJ, Ruoff KL, Ferraro MJ. New cause for false-positive results with the cryptococcal antigen test by latex agglutination . J Clin Microbiol . 1985;22:856-857. 30. Salom IL. Cryptococcal meningitis: significance of positive antigen test on undiluted spinal fluid . NY State J Med . 1981;81:1369-1370. 31. Goodman JS, Kaufman L, Koenig MG. Diagnosis of cryptococcal meningitis: value of immunologic detection of cryptococcal antigen . N Engl J Med . 1971;285:434-436.Crossref 32. Snow RM, Dismukes WE. Cryptococcal meningitis: diagnostic value of cryptococcal antigen in cerebrospinal fluid . Arch Intern Med . 1975;135:1155-1157.Crossref 33. Berger MP, Jaz J. Diagnosis of cryptococcal meningitis . JAMA . 1976;236:2517-2518.Crossref 34. Haldane DJM, Bauman DS, Chow AW, et al. False negative latex agglutination test in cryptococcal meningitis . Ann Neurol . 1986;19:412-413.Crossref 35. Utz UP. Histoplasma and Cryptococcus meningitis . Res Publ Assoc Res Nerv Ment Dis . 1968;44:378-392. 36. Edwards VE, Sutherland JM, Tyrer JH. Cryptococcosis of the central nervous system: epidemiological, clinical and therapeutic features . J Neurol Neurosurg Psychiatry . 1970;33:415-425.Crossref 37. Kaufman L, Blumer S. Latex-cryptococcal antigen test . Am J Clin Pathol . 1973;60:285-286. 38. Ransohoff DF, Feinstein AR. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests . N Engl J Med . 1978;299:926-930.Crossref 39. Stamm AM, Polt SS. False-negative cryptococcal antigen test . JAMA . 1980;244:1359.Crossref 40. Campbell GD, Currier RD, Busey JF. Survival in untreated cryptococcal meningitis . Neurology . 1981;31:1154-1157.Crossref 41. Sande MA, Mandell GL. Antimicrobial agents: fungal agents . In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. The Pharmacological Basis of Therapeutics . 7th ed. New York, NY: Macmillan Publishing Co Inc; 1985:1220-1223.

Journal

Archives of NeurologyAmerican Medical Association

Published: Dec 1, 1989

References