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DIAGNOSIS OF HERPES SIMPLEX INFECTIONS BY THE COMPLEMENT FIXATION TEST FREE

D. Carleton Gajdusek, M.D.; Mary Louise Robbins, Ph.D.; Frederick C. Robbins, M.D.
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This study was supported by a grant from the National Foundation for Infantile Paralysis.


JAMA. 1952;149(3):235-240. doi:10.1001/jama.1952.02930200021006
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Herpes simplex is among the most ubiquitous of viruses capable of infecting man, and the clinical manifestations of the infection it induces are various. Until recently no simple and rapid serologic test has been available by which the antibody response to infection with this virus could be determined. When serologic studies have been carried out, the virus neutralization test usually has been employed, although antigens for use in complement fixation and skin tests have been described.

The present study was undertaken to explore the value as antigens in the complement fixation test of amniotic and allantoic fluid from infected chick embryos. When such materials were shown to be effective in this respect, the reliability of the test as a diagnostic procedure and as a tool for the epidemiological study of herpes infections was investigated. Earlier workers who applied complement fixation tests to the assay of herpes antibody used antigens prepared

REFERENCES

Todorovitch, K.:  La réaction de fixation au cours des inoculations herpétiques chez l'homme et chez le singe , Compt. rend. Soc. biol. 92: 1017-1018, 1925;.
Stroian, N.:  Réaction de fixation du complément chez les lapins immunisés contre le virus herpétique , Compt. rend. Soc. biol. 100:610-612, 1929;.
Bedson, S. P., and Bland, J. O. W.:  Complement-Fixation with Filterable Viruses and Their Antisera , Brit. J. Exper. Path. 10:393-404, 1929;.
Brain, R. T.:  Demonstration of Herpetic Antibody in Human Sera by Complement-Fixation, and Correlation Between its Presence and Infection with Herpes Virus , Brit. J. Exper. Path. 13:166-171, 1932;.
Hayward, M. E.:  Serological Studies with Herpes Simplex Virus , Brit. J. Exper. Path. 30:520-529, 1949;
 Serological Diagnosis of Herpes Simplex Infections , Lancet 1: 856-858, 1950;.
Dudgeon, J. A.:  A Complement Fixation Test for Herpes Simplex Infections , J. Clin. Path. 3: 239-247, 1950;.
Fowler, M.:  The Demonstration of Complement-Fixing Antibodies to Herpes Febrilis Virus , Australian J. Exper. Biol. & M. Sc. 28:339-342, 1950;.
Coriell, L. L.; Schipper, M., and Scott, T. F. M.: To be published.
Afzelius-Alm, L.:  Aseptic (Nonbacterial) Encephalomeningitides in Gothenburg 1932-1950; Clinical and Experimental Investigation with Special Reference to the Viruses of Herpes, Influenza, Mumps and Lymphocytic Choriomeningitis , Acta med. scandinav. , (supp. 263) , p. 1, 1951;.
Shaffer, M. F., and Enders, J. F.:  Quantitative Studies on the Infectivity of the Virus of Herpes Simplex for Chorio-Allantoic Membrane of the Chick Embryo, Together with Observations on the Inactivation of the Virus by its Specific Antiserum , J. Immunol. 37: 383-411, 1939;.
Florman, A. L., and Trader, F. W.:  A Comparative Study of Pathogenicity and Antigenicity of 4 Strains of Herpes Simplex , J. Immunol. 55:263-275, 1947;.
Enders, J. F., and Levens, J. H.:  Mumps  in, Diagnostic Procedures for Virus and Rickettsial Diseases , New York, American Public Health Association, 1948;, pp. 139-164.
Reed, L. J., and Muench, H.:  A Simple Method of Estimating 50 Per Cent Endpoints , Am. J. Hyg. 27:493-497, 1938;.
Paul, J. R.:  The Filterable Viruses , in Laboratory Methods of the United States Army , edited by J. S. Simmons and C. J. Gentzkow, ed. 5, Philadelphia, Lea & Febiger, 1944;.
Dr. Isaac Ruchman, Children's Hospital Research Foundation, Cincinnati, provided the serum from patients 4, 13, and 14 and the neutralization indexes on these serums, which he determined with the use of the RE strain of virus.
The viruses were isolated by Drs. Robert J. Huebner and Edward A. Beeman, Laboratory of Infectious Diseases, Microbiological Institute, National Institutes of Health, Bethesda, Md., who supplied us with the serums from these cases.
Morgan, H. R., and Finland, M.:  Isolation of Herpes Virus from a Case of Atypical Pneumonia and Erythema Multiforme Exudativum: with Studies of 4 Additional Cases , Am. J. M. Sc. 217:92-95, 1949;.
Scott, T. F. M.:  Diseases Caused by the Virus of Herpes Simplex , in Viral and Rickettsial Infections of Man , edited by T. M. Rivers, Philadelphia, J. B. Lippincott Company, 1948;.
Anderson, S. G., and Hamilton, J.:  The Epidemiology of Primary Herpes Simplex Infection , M. J. Australia 1:308-311, 1949;.
Dodd, K., and Ruchman, I.:  Herpes Simplex Virus Not the Etiologic Agent of Recurrent Stomatitis , Pediatrics 5: 883-887, 1950;.
Blank, H.; Burgoon, C. F.; Coriell, L. L., and Scott, T. F. M.:  Recurrent Aphthous Ulcers, Correspondence , J. A. M. A. 142:125-126 ( (Jan. 14) ) 1950;.
Steigman, A. J., and Scott, T. F. M.:  Evidence That Virus of Herpes Simplex Does Not Cause Vincent's Angina of the Tonsil , Proc. Soc. Exper. Biol. & Med. 64: 244-245, 1947;.
Huebner, R. J., and others:  Herpangina: Etiological Studies of a Specific Infectious Disease , J. A. M. A. 145:628-633 ( (March 3) ) 1951;.
Brain, R. T.:  Treatment of Virus Diseases of the Skin , Brit. M. J. 2: 1064-1066, 1937;.
Hudson, N. P.; Cook, E. A., and Adair, F. L.:  Relation of Herpes Antiviral Property of Human Blood to Sex, Pregnancy and Menstruation , J. Infect. Dis. 59:60-64, 1936;.

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Todorovitch, K.:  La réaction de fixation au cours des inoculations herpétiques chez l'homme et chez le singe , Compt. rend. Soc. biol. 92: 1017-1018, 1925;.
Stroian, N.:  Réaction de fixation du complément chez les lapins immunisés contre le virus herpétique , Compt. rend. Soc. biol. 100:610-612, 1929;.
Bedson, S. P., and Bland, J. O. W.:  Complement-Fixation with Filterable Viruses and Their Antisera , Brit. J. Exper. Path. 10:393-404, 1929;.
Brain, R. T.:  Demonstration of Herpetic Antibody in Human Sera by Complement-Fixation, and Correlation Between its Presence and Infection with Herpes Virus , Brit. J. Exper. Path. 13:166-171, 1932;.
Hayward, M. E.:  Serological Studies with Herpes Simplex Virus , Brit. J. Exper. Path. 30:520-529, 1949;
 Serological Diagnosis of Herpes Simplex Infections , Lancet 1: 856-858, 1950;.
Dudgeon, J. A.:  A Complement Fixation Test for Herpes Simplex Infections , J. Clin. Path. 3: 239-247, 1950;.
Fowler, M.:  The Demonstration of Complement-Fixing Antibodies to Herpes Febrilis Virus , Australian J. Exper. Biol. & M. Sc. 28:339-342, 1950;.
Coriell, L. L.; Schipper, M., and Scott, T. F. M.: To be published.
Afzelius-Alm, L.:  Aseptic (Nonbacterial) Encephalomeningitides in Gothenburg 1932-1950; Clinical and Experimental Investigation with Special Reference to the Viruses of Herpes, Influenza, Mumps and Lymphocytic Choriomeningitis , Acta med. scandinav. , (supp. 263) , p. 1, 1951;.
Shaffer, M. F., and Enders, J. F.:  Quantitative Studies on the Infectivity of the Virus of Herpes Simplex for Chorio-Allantoic Membrane of the Chick Embryo, Together with Observations on the Inactivation of the Virus by its Specific Antiserum , J. Immunol. 37: 383-411, 1939;.
Florman, A. L., and Trader, F. W.:  A Comparative Study of Pathogenicity and Antigenicity of 4 Strains of Herpes Simplex , J. Immunol. 55:263-275, 1947;.
Enders, J. F., and Levens, J. H.:  Mumps  in, Diagnostic Procedures for Virus and Rickettsial Diseases , New York, American Public Health Association, 1948;, pp. 139-164.
Reed, L. J., and Muench, H.:  A Simple Method of Estimating 50 Per Cent Endpoints , Am. J. Hyg. 27:493-497, 1938;.
Paul, J. R.:  The Filterable Viruses , in Laboratory Methods of the United States Army , edited by J. S. Simmons and C. J. Gentzkow, ed. 5, Philadelphia, Lea & Febiger, 1944;.
Dr. Isaac Ruchman, Children's Hospital Research Foundation, Cincinnati, provided the serum from patients 4, 13, and 14 and the neutralization indexes on these serums, which he determined with the use of the RE strain of virus.
The viruses were isolated by Drs. Robert J. Huebner and Edward A. Beeman, Laboratory of Infectious Diseases, Microbiological Institute, National Institutes of Health, Bethesda, Md., who supplied us with the serums from these cases.
Morgan, H. R., and Finland, M.:  Isolation of Herpes Virus from a Case of Atypical Pneumonia and Erythema Multiforme Exudativum: with Studies of 4 Additional Cases , Am. J. M. Sc. 217:92-95, 1949;.
Scott, T. F. M.:  Diseases Caused by the Virus of Herpes Simplex , in Viral and Rickettsial Infections of Man , edited by T. M. Rivers, Philadelphia, J. B. Lippincott Company, 1948;.
Anderson, S. G., and Hamilton, J.:  The Epidemiology of Primary Herpes Simplex Infection , M. J. Australia 1:308-311, 1949;.
Dodd, K., and Ruchman, I.:  Herpes Simplex Virus Not the Etiologic Agent of Recurrent Stomatitis , Pediatrics 5: 883-887, 1950;.
Blank, H.; Burgoon, C. F.; Coriell, L. L., and Scott, T. F. M.:  Recurrent Aphthous Ulcers, Correspondence , J. A. M. A. 142:125-126 ( (Jan. 14) ) 1950;.
Steigman, A. J., and Scott, T. F. M.:  Evidence That Virus of Herpes Simplex Does Not Cause Vincent's Angina of the Tonsil , Proc. Soc. Exper. Biol. & Med. 64: 244-245, 1947;.
Huebner, R. J., and others:  Herpangina: Etiological Studies of a Specific Infectious Disease , J. A. M. A. 145:628-633 ( (March 3) ) 1951;.
Brain, R. T.:  Treatment of Virus Diseases of the Skin , Brit. M. J. 2: 1064-1066, 1937;.
Hudson, N. P.; Cook, E. A., and Adair, F. L.:  Relation of Herpes Antiviral Property of Human Blood to Sex, Pregnancy and Menstruation , J. Infect. Dis. 59:60-64, 1936;.
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