Abstract
Immunoassays for the detection of viral antigens in clinical specimens and virus-specific IgM responses in serum have shortened the time required to make a laboratory diagnosis of several infections. A range of antigen detection systems are available, varying in sensitivity, complexity, and expense, and each may have a role to play depending upon the laboratory setting. Technical advancements to eliminate false-positive results in solid-phase IgM assays have provided an awareness of very early IgM responses in diseases such as rubella, hepatitis A, and mumps. When clinical specimens contain large numbers of virus particles, a rapid diagnosis is easily made using electron microscopy. Detection of antigens, virus particles, and IgM responses is creating increased demands for viral diagnostic services in primary care settings. Other approaches using sensitive probes for viral nucleic acids or enzymes will also serve as viable laboratory techniques in the future.
Full text
PDF



















Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Almeida J. D. Practical aspects of diagnostic electron microscopy. Yale J Biol Med. 1980 Jan-Feb;53(1):5–18. [PMC free article] [PubMed] [Google Scholar]
- Anderson N., Doane F. W. Agar diffusion method for negative staining of microbial suspensions in salt solutions. Appl Microbiol. 1972 Sep;24(3):495–496. doi: 10.1128/am.24.3.495-496.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berg R. A., Yolken R. H., Rennard S. I., Dolin R., Murphy B. R., Straus S. E. New enzyme immunoassays for measurement of influenza A/Victoria/3/75 virus in nasal washes. Lancet. 1980 Apr 19;1(8173):851–853. doi: 10.1016/s0140-6736(80)91356-2. [DOI] [PubMed] [Google Scholar]
- Bidwell D. E., Bartlett A., Voller A. Enzyme immunoassays for viral diseases. J Infect Dis. 1977 Oct;136 (Suppl):S274–S278. doi: 10.1093/infdis/136.supplement_2.s274. [DOI] [PubMed] [Google Scholar]
- Bradburne A. F., Almeida J. D., Gardner P. S., Moosai R. B., Nash A. A., Coombs R. R. A solid-phase system (SPACE) for the detection and quantification of rotavirus in faeces. J Gen Virol. 1979 Sep;44(3):615–623. doi: 10.1099/0022-1317-44-3-615. [DOI] [PubMed] [Google Scholar]
- Braun R., Doerr H. W., Horing C. Rapid detection of rubella-specific IgM antibodies by the use of microimmunobeads (MIB-IgM). J Virol Methods. 1981 Jul;3(1):45–49. doi: 10.1016/0166-0934(81)90021-5. [DOI] [PubMed] [Google Scholar]
- Burke D. S., Nisalak A., Ussery M. A. Antibody capture immunoassay detection of japanese encephalitis virus immunoglobulin m and g antibodies in cerebrospinal fluid. J Clin Microbiol. 1982 Dec;16(6):1034–1042. doi: 10.1128/jcm.16.6.1034-1042.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cappel R., de Cuyper F., de Braekeleer J. Rapid detection of IgG and IgM antibodies for cytomegalovirus by the enzyme linked immunosorbent assay (ELISA). Arch Virol. 1978;58(3):253–258. doi: 10.1007/BF01317608. [DOI] [PubMed] [Google Scholar]
- Chao R. K., Fishaut M., Schwartzman J. D., McIntosh K. Detection of respiratory syncytial virus in nasal secretions from infants by enzyme-linked immunosorbent assay. J Infect Dis. 1979 Apr;139(4):483–486. doi: 10.1093/infdis/139.4.483. [DOI] [PubMed] [Google Scholar]
- Cohen S. M., Ducharme C. P., Carpenter C. A., Deibel R. Rubella antibody in IgG and IgM immunoglobulins detected by immunofluorescence. J Lab Clin Med. 1968 Nov;72(5):760–766. [PubMed] [Google Scholar]
- D'Alessio D., Williams S., Dick E. C. Rapid detection and identification of respiratory viruses by direct immunofluorescence. Appl Microbiol. 1970 Aug;20(2):233–239. doi: 10.1128/am.20.2.233-239.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denoyel G. A., Gaspar A., Peyramond D. Diagnosis of recent rubella virus infection by demonstration of specific immunoglobulin M antibodies: comparison of solid-phase reverse immunosorbent test with sucrose density gradient centrifugation. J Clin Microbiol. 1981 Apr;13(4):698–704. doi: 10.1128/jcm.13.4.698-704.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diment J. A., Chantler S. M. Enzyme immunoassay for detection of rubella specific IgM antibody. Lancet. 1981 Feb 14;1(8216):394–395. doi: 10.1016/s0140-6736(81)91723-2. [DOI] [PubMed] [Google Scholar]
- Dittmar D., Cleary T. J., Castro A. Immunoglobulin G- and M-specific enzyme-linked immunosorbent assay for detection of dengue antibodies. J Clin Microbiol. 1979 Apr;9(4):498–502. doi: 10.1128/jcm.9.4.498-502.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duermeyer W., Stute R., Hellings J. A. An enzyme-linked immunosorbent assay for an antigen related to non-A, non-B hepatitis and its antibody: partial characterization of the antigen and chimpanzee transmission. J Med Virol. 1983;11(1):11–21. doi: 10.1002/jmv.1890110103. [DOI] [PubMed] [Google Scholar]
- Duermeyer W., Wielaard F., van der Veen J. A new principle for the detection of specific IgM antibodies applied in an ELISA for hepatitis A. J Med Virol. 1979;4(1):25–32. doi: 10.1002/jmv.1890040104. [DOI] [PubMed] [Google Scholar]
- EVANS A. S., MELNICK J. L. Electron microscope studies of the vesicle and spinal fluids from a case of herpes zoster. Proc Soc Exp Biol Med. 1949 Jun;71(2):283–286. doi: 10.3181/00379727-71-17165. [DOI] [PubMed] [Google Scholar]
- Ellens D. J., de Leeuw P. W. Enzyme-linked immunosorbent assay for diagnosis of rotavirus infections in calves. J Clin Microbiol. 1977 Nov;6(5):530–532. doi: 10.1128/jcm.6.5.530-532.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elwing H., Nilsson L. A., Ouchterlony O. A simple spot technique for thin layer immunoassays (TIA) on plastic surfaces. J Immunol Methods. 1977;17(1-2):131–145. doi: 10.1016/0022-1759(77)90084-9. [DOI] [PubMed] [Google Scholar]
- Ertl H. C., Gerlich W., Koszinowski U. H. Detection of antibodies to Sendai virus by enzyme-linked immunosorbent assay (ELISA). J Immunol Methods. 1979;28(1-2):163–176. doi: 10.1016/0022-1759(79)90338-7. [DOI] [PubMed] [Google Scholar]
- Frisch-Niggemeyer W. A solid-phase radioimmunoassay for quantitative measurement of class-specific antibodies against tick-borne encephalitis virus. J Virol Methods. 1982 Jan;3(6):319–328. doi: 10.1016/0166-0934(82)90036-2. [DOI] [PubMed] [Google Scholar]
- Frohman M. A., Frohman L. A., Goldman M. B., Goldman J. N. Use of protein A--containing Staphylococcus aureus as an immunoadsorbent in radioimmunoassays to separate antibody-bound from free antigen. J Lab Clin Med. 1979 Apr;93(4):614–621. [PubMed] [Google Scholar]
- Gerlich W. H., Lüer W. Selective detection of IgM-antibody against core antigen of the hepatitis B virus by a modified enzyme immune assay. J Med Virol. 1979;4(3):227–238. doi: 10.1002/jmv.1890040308. [DOI] [PubMed] [Google Scholar]
- Giraldo G., Beth E., Lee J., de Harven E., Chernesky M. Solid-phase immune electron microscopy-double-antibody technique for rapid detection of papovaviruses. J Clin Microbiol. 1982 Mar;15(3):517–521. doi: 10.1128/jcm.15.3.517-521.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hacham M., Leventon-Kriss S., Sarov I. Enzyme-linked immunosorbent assay for detection of virus-specific IgM antibodies to varicella-zoster virus. Intervirology. 1980;13(4):214–222. doi: 10.1159/000149128. [DOI] [PubMed] [Google Scholar]
- Harmon M. W., Drake S., Kasel J. A. Detection of adenovirus by enzyme-linked immunosorbent assay. J Clin Microbiol. 1979 Mar;9(3):342–346. doi: 10.1128/jcm.9.3.342-346.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heinz F. X., Roggendorf M., Hofmann H., Kunz C., Deinhardt F. Comparison of two different enzyme immunoassays for detection of immunoglobulin M antibodies against tick-borne encephalitis virus in serum and cerebrospinal fluid. J Clin Microbiol. 1981 Aug;14(2):141–146. doi: 10.1128/jcm.14.2.141-146.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hofmann H., Frisch-Niggemeyer W., Heinz F. Rapid diagnosis of tick-borne encephalitis by means of enzyme linked immunosorbent assay. J Gen Virol. 1979 Mar;42(3):505–511. doi: 10.1099/0022-1317-42-3-505. [DOI] [PubMed] [Google Scholar]
- Hsiung G. D., Fong C. K., August M. J. The use of electron microscopy for diagnosis of virus infections: an overview. Prog Med Virol. 1979;25:133–159. [PubMed] [Google Scholar]
- Isaac M., Payne R. A. Antibody class capture assay (ACCA) for rubella-specific IgM antibody. J Med Virol. 1982;10(1):55–64. doi: 10.1002/jmv.1890100108. [DOI] [PubMed] [Google Scholar]
- Jamnback T. L., Beaty B. J., Hildreth S. W., Brown K. L., Gundersen C. B. Capture immunoglobulin M system for rapid diagnosis of La Crosse (California encephalitis) virus infections. J Clin Microbiol. 1982 Sep;16(3):577–580. doi: 10.1128/jcm.16.3.577-580.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeansson S., Elwing H., Nilsson L. A. Thin-layer immunoassay for determination of antibodies to herpes simplex virus. J Clin Microbiol. 1979 Mar;9(3):317–322. doi: 10.1128/jcm.9.3.317-322.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johansson M. E., Uhnoo I., Kidd A. H., Madeley C. R., Wadell G. Direct identification of enteric adenovirus, a candidate new serotype, associated with infantile gastroenteritis. J Clin Microbiol. 1980 Jul;12(1):95–100. doi: 10.1128/jcm.12.1.95-100.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jordan J., Rytel M. W. Detection of herpes simplex virus (HSV) type-1 IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA). Am J Clin Pathol. 1981 Oct;76(4):467–471. doi: 10.1093/ajcp/76.4.467. [DOI] [PubMed] [Google Scholar]
- Kangro H. O. Evaluation of a radioimmunoassay for IgM-class antibodies against cytomegalovirus. Br J Exp Pathol. 1980 Oct;61(5):512–520. [PMC free article] [PubMed] [Google Scholar]
- Kangro H. O., Pattison J. R., Heath R. B. The detection of rubella-specific IgM antibodies by radioimmunoassay. Br J Exp Pathol. 1978 Dec;59(6):577–583. [PMC free article] [PubMed] [Google Scholar]
- Kimmel N., Friedman M. G., Sarov I. Enzyme-linked immunosorbent assay (ELISA) for detection of herpes simplex virus-specific IgM antibodies. J Virol Methods. 1982 May;4(4-5):219–227. doi: 10.1016/0166-0934(82)90068-4. [DOI] [PubMed] [Google Scholar]
- Knez V., Stewart J. A., Ziegler D. W. Cytomegalovirus specific IgM and IgG response in humans studied by radioimmunoassay. J Immunol. 1976 Nov;117(5 PT2):2006–2013. [PubMed] [Google Scholar]
- Krech U., Wilhelm J. A. A solid-phase immunosorbent technique for the rapid detection of rubella IgM by haemagglutination inhibition. J Gen Virol. 1979 Aug;44(2):281–286. doi: 10.1099/0022-1317-44-2-281. [DOI] [PubMed] [Google Scholar]
- Lee F. K., Nahmias A. J., Stagno S. Rapid diagnosis of cytomegalovirus infection in infants by electron microscopy. N Engl J Med. 1978 Dec 7;299(23):1266–1270. doi: 10.1056/NEJM197812072992302. [DOI] [PubMed] [Google Scholar]
- Locarnini S. A., Garland S. M., Lehmann N. I., Pringle R. C., Gust I. D. Solid-phase enzyme-linked immunosorbent assay for detection of hepatitis A virus. J Clin Microbiol. 1978 Sep;8(3):277–282. doi: 10.1128/jcm.8.3.277-282.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McQuillin J., Gardner P. S. Rapid diagnosis of respiratory syncytial virus infection by immunofluorescent antibody techniques. Br Med J. 1968 Mar 9;1(5592):602–605. doi: 10.1136/bmj.1.5592.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meurman O. H. Antibody responses in patients with rubella infection determined by passive hemagglutination, hemagglutination inhibition, complement fixation, and solid-phase radioimmunoassay tests. Infect Immun. 1978 Feb;19(2):369–372. doi: 10.1128/iai.19.2.369-372.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meurman O. H., Ziola B. R. IgM-class rheumatoid factor interference in the solid-phase radioimmunoassay of rubella-specific IgM antibodies. J Clin Pathol. 1978 May;31(5):483–487. doi: 10.1136/jcp.31.5.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meurman O., Hänninen P., Krishna R. V., Ziegler T. Determination of IgG- and IgM-class antibodies to mumps virus by solid-phase enzyme immunoassay. J Virol Methods. 1982 May;4(4-5):249–256. doi: 10.1016/0166-0934(82)90071-4. [DOI] [PubMed] [Google Scholar]
- Middleton P. J., Szymanski M. T., Petric M. Viruses associated with acute gastroenteritis in young children. Am J Dis Child. 1977 Jul;131(7):733–737. doi: 10.1001/archpedi.1977.02120200015004. [DOI] [PubMed] [Google Scholar]
- Minnich L., Ray C. G. Comparison of direct immunofluorescent staining of clinical specimens for respiratory virus antigens with conventional isolation techniques. J Clin Microbiol. 1980 Sep;12(3):391–394. doi: 10.1128/jcm.12.3.391-394.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miranda Q. R., Bailey G. D., Fraser A. S., Tenoso H. J. Solid-phase enzyme immunoassay for herpes simplex virus. J Infect Dis. 1977 Oct;136 (Suppl):S304–S310. doi: 10.1093/infdis/136.supplement_2.s304. [DOI] [PubMed] [Google Scholar]
- Monroe J. H., Brandt P. M. Rapid semiquantitative method for screening large numbers of virus samples by negative staining electron microscopy. Appl Microbiol. 1970 Aug;20(2):259–262. doi: 10.1128/am.20.2.259-262.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Naot Y., Barnett E. V., Remington J. S. Method for avoiding false-positive results occurring in immunoglobulin M enzyme-linked immunosorbent assays due to presence of both rheumatoid factor and antinuclear antibodies. J Clin Microbiol. 1981 Jul;14(1):73–78. doi: 10.1128/jcm.14.1.73-78.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pronovost A. D., Baumgarten A., Hsiung G. D. Sensitive chemiluminescent enzyme-linked immunosorbent assay for quantification of human immunoglobulin G and detection of herpes simplex virus. J Clin Microbiol. 1981 Jan;13(1):97–101. doi: 10.1128/jcm.13.1.97-101.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson P. W., Kertesz V., Cloonan M. J. Elimination of false-positive cytomegalovirus immunoglobulin M-fluorescent-antibody reactions with immunoglobulin M serum fractions. J Clin Microbiol. 1977 Aug;6(2):174–175. doi: 10.1128/jcm.6.2.174-175.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roggendorf M., Heinz F., Deinhardt F., Kunz C. Serological diagnosis of acute tick-borne encephalitis by demonstration of antibodies of the IgM class. J Med Virol. 1981;7(1):41–50. doi: 10.1002/jmv.1890070105. [DOI] [PubMed] [Google Scholar]
- Salonen E. M., Vaheri A., Suni J., Wager O. Rheumatoid factor in acute viral infections: interference with determination of IgM, IgG, and IgA antibodies in an enzyme immunoassay. J Infect Dis. 1980 Aug;142(2):250–255. doi: 10.1093/infdis/142.2.250. [DOI] [PubMed] [Google Scholar]
- Schmitz H. Detection of immunoglobulin M antibody to Epstein-Barr virus by use of an enzyme-labeled antigen. J Clin Microbiol. 1982 Aug;16(2):361–366. doi: 10.1128/jcm.16.2.361-366.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmitz H. Improved detection of virus-specific IgM antibodies. Elimination of non-specific IgM binding. J Gen Virol. 1978 Aug;40(2):459–463. doi: 10.1099/0022-1317-40-2-459. [DOI] [PubMed] [Google Scholar]
- Schmitz H., von Deimling U., Flehmig B. Detection of IgM antibodies to cytomegalovirus (CMV) using an enzyme-labelled antigen (ELA). J Gen Virol. 1980 Sep;50(1):59–68. doi: 10.1099/0022-1317-50-1-59. [DOI] [PubMed] [Google Scholar]
- Schwanzerová I., Schwanzer V. Determination of rubella IgM antibodies by solid-phase immunosorbent technique. Acta Virol. 1982 Jan;26(1-2):110–110. [PubMed] [Google Scholar]
- Smedile A., Lavarini C., Crivelli O., Raimondo G., Fassone M., Rizzetto M. Radioimmunoassay detection of IgM antibodies to the HBV-associated delta (delta) antigen:" clinical significance in delta infection. J Med Virol. 1982;9(2):131–138. doi: 10.1002/jmv.1890090208. [DOI] [PubMed] [Google Scholar]
- Sumaya C. V., Ench Y., Pope R. M. Improved test for IgM antibody to Epstein-Barr virus using an absorption step with Staphylococcus aureus. J Infect Dis. 1982 Oct;146(4):518–523. doi: 10.1093/infdis/146.4.518. [DOI] [PubMed] [Google Scholar]
- Sundqvist V. A. Frequency and specificity of varicella zoster virus IgM response. J Virol Methods. 1982 Nov;5(3-4):219–227. doi: 10.1016/0166-0934(82)90012-x. [DOI] [PubMed] [Google Scholar]
- Ukkonen P., Granström M. L., Penttinen K. Mumps-specific immunoglobulin M and G antibodies in natural mumps infection as measured by enzyme-linked immunosorbent assay. J Med Virol. 1981;8(2):131–142. doi: 10.1002/jmv.1890080207. [DOI] [PubMed] [Google Scholar]
- Voller A., Bartlett A., Bidwell D. E. Enzyme immunoassays with special reference to ELISA techniques. J Clin Pathol. 1978 Jun;31(6):507–520. doi: 10.1136/jcp.31.6.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolters G., Kuijpers L. P., Kacaki J., Schuurs A. H. Enzyme-linked immunosorbent assay for hepatitis B surface antigen. J Infect Dis. 1977 Oct;136 (Suppl):S311–S317. doi: 10.1093/infdis/136.supplement_2.s311. [DOI] [PubMed] [Google Scholar]
- Yolken R. H. Enzyme-linked immunosorbent assay (ELISA): a practical tool for rapid diagnosis of viruses and other infectious agents. Yale J Biol Med. 1980 Jan-Feb;53(1):85–92. [PMC free article] [PubMed] [Google Scholar]
- Yolken R. H., Leister F. J. Enzyme immunoassays for measurement of cytomegalovirus immunoglobulin M antibody. J Clin Microbiol. 1981 Oct;14(4):427–432. doi: 10.1128/jcm.14.4.427-432.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yolken R. H., Stopa P. J. Analysis of nonspecific reactions in enzyme-linked immunosorbent assay testing for human rotavirus. J Clin Microbiol. 1979 Nov;10(5):703–707. doi: 10.1128/jcm.10.5.703-707.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yolken R. H., Stopa P. J. Comparison of seven enzyme immunoassay systems for measurement of cytomegalovirus. J Clin Microbiol. 1980 Jun;11(6):546–551. doi: 10.1128/jcm.11.6.546-551.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yolken R. H., Torsch V. M., Berg R., Murphy B. R., Lee Y. C. Fluorometric assay for measurement of viral neuraminidase--application to the rapid detection of influenza virus in nasal wash specimens. J Infect Dis. 1980 Oct;142(4):516–523. doi: 10.1093/infdis/142.4.516. [DOI] [PubMed] [Google Scholar]
- Yolken R. H., Torsch V. M. Enzyme-linked immunosorbent assay for detection and identification of coxsackieviruses A. Infect Immun. 1981 Feb;31(2):742–750. doi: 10.1128/iai.31.2.742-750.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yolken R. H., Torsch V. Enzyme-linked immunosorbent assay for the detection and identification of coxsackie B antigen in tissue cultures and clinical specimens. J Med Virol. 1980;6(1):45–52. doi: 10.1002/jmv.1890060107. [DOI] [PubMed] [Google Scholar]
- Ziegelmaier R., Behrens F., Enders G. Class-specific determination of antibodies against cytomegalo (CMV) and rubella virus by ELISA. J Biol Stand. 1981 Jan;9(1):23–33. doi: 10.1016/s0092-1157(81)80062-5. [DOI] [PubMed] [Google Scholar]
- van Loon A. M., Heessen F. W., van der Logt J. T., van der Veen J. Direct enzyme-linked immunosorbent assay that uses peroxidase-labeled antigen for determination of immunoglobulin M antibody to cytomegalovirus. J Clin Microbiol. 1981 Mar;13(3):416–422. doi: 10.1128/jcm.13.3.416-422.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Loon A. M., van Der Logt J. T., van der Veen J. Diagnosis of herpes encephalitis by elisa. Lancet. 1981 Nov 28;2(8257):1228–1229. doi: 10.1016/s0140-6736(81)91461-6. [DOI] [PubMed] [Google Scholar]
- van der Logt J. T., van Loon A. M., van der Veen J. Detection of parainfluenza IgM antibody by hemadsorption immunosorbent technique. J Med Virol. 1982;10(3):213–221. doi: 10.1002/jmv.1890100307. [DOI] [PubMed] [Google Scholar]
- van der Logt J. T., van Loon A. M., van der Veen J. Detection of parainfluenza IgM antibody by hemadsorption immunosorbent technique. J Med Virol. 1982;10(3):213–221. doi: 10.1002/jmv.1890100307. [DOI] [PubMed] [Google Scholar]
- van der Logt J. T., van Loon A. M., van der Veen J. Hemadsorption immunosorbent technique for determination of rubella immunoglobulin M antibody. J Clin Microbiol. 1981 Mar;13(3):410–415. doi: 10.1128/jcm.13.3.410-415.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]