Occurrence of Acute Upper Respiratory Diseases among Children as a Result of Infection by Herpes Simplex Virus

Abstract

One hundred and twenty-one children showing symptoms of acute upper respiratory disease were bled during a period of nine months, from winter to summer, for detection of complement-requiring neutralizing (CRN) antibody against herpes simplex virus. Six of the cases, all from children under the age of 13 years, were unequivocally related to herpetic infection as evidenced by the presence of anti-herpes CRN antibody. During the same period, 144 other children who were normal healthy or suffering from unrelated non-febrile diseases were tested as controls; anti-herpes CRN antibody was not detected in any of them. Further, the age distribution of individuals with antibodies was compared between patients in the acute upper respiratory disease group and the control group. This analysis showed that approximately 5 to 7% of the acute upper respiratory diseases in the young children in this study would be attributed to herpetic infection.It has been hitherto believed that, although a variety of disease manifestations may result from primary and repeated infections of herpes simplex virus in man, the lesions are limited mainly to the skin and the outer mucous membrane, with the exception of some unusual instances such as encephalitis or generalized infection in newborn infants [1,2]. A recent report of Scott and Tokumaru [3], however, revealed the occurrence of upper respiratory diseases due to herpes virus. Thus, herpes virus has been registered anew as a member of the family of respiratory viruses. As a result of this last report, the author attempted to estimate the importance of herpetic infections as a cause of acute upper respiratory disease (ARD) in children.In the present study, determination of herpes infection as a cause of ARD was done by detection of CRN antibody against herpes virus [5], since this method did not require paired serum samples for diagnosis and consequently enabled the handling of a large number of sera with ease. The results indicated that some of the ARD cases were related to herpetic infection as evidenced by this serological test. Further analysis was then made upon the age distribution of ARD patients and control children with antibodies, to test the possibility that some cases of herpetic infection were missed by this serological method of diag-

Distribution of Complement‐Requiring Neutralizing Antibody against Herpes Simplex Virus in Human Population

“…ment by complement was mostly 2-or 4fold, rarely 8-fold and very rarely 16-fold. This is in agreement with the results of tests on healthy young adults and patients with miscellaneous diseases reported, without specifying their age, by Yoshino and Taniguchi [6,8] and on children with acute respiratory and other diseases by Yazaki [4].…”

“…They also made a similar observation in human herpetic infections and proposed an application of the phenomenon to the early diagnosis of the disease [8]. Attempts at the application of the diagnostic method to human herpetic infections with various clinical manifestations have been reported [1][2][3][4][5].…”

“…Another aspect of importance in establishing the diagnostic criterion is to assess how frequently herpetic illnesses are missed by criterion. For this assessment, informa-tion regarding the development of C(-) NT and C(+)NT titers in patients with herpetic illnesses is far from adequate [1][2][3][4][5], and further information is needed to evaluate how frequently herpetic illnesses are missed by these criteria.…”

Complement Requirement of Neutralizing Antibodies Appearing after Primary and Booster Immunizations with Herpes Simplex Virus

“…Physiological saline containing 0.01% MgCl2 was first adjusted to neutral pH with NaOH, then Tris-HCl buffer at pH 7.8 was added to make a final concentration of 0.0025 M, and the mixture was autoclaved. This solution could be kept for a long period in an ice box if tightly sealed [20]. It was used as a diluent for serum and C'.…”

Further Simplification of the Serum Neutralization Test with Herpes Simplex Virus

“…When complement-requiring neutralizing antibody was titrated, one part of virus was added to mixtures of 2 parts of serum and one part of complement. The strength of complement was 10 hemolytic units per 0.1 ml as measured by a standardized method [24], and the diluent for serum and complement was Tris-buffered magnesium saline [23]. A control series of virus-serum mixtures replacing complement with the diluent served for titration of non-complement-requiring neutralizing antibody.…”