Takehiko Yazaki

LIVE VACCINE USED TO PREVENT THE SPREAD OF VARICELLA IN CHILDREN IN HOSPITAL

Abstract A strain (Oka strain) of varicella virus was attenuated by cultivating it serially in human embryonic lung cells and then in guineapig embryo (G.P.E.) cells. Subcutaneous injection of the virus stimulated the production of complement-fixing (C.F.) antibody without clinical reactions in normal susceptible children. The virus propagated in human diploid (WI-38) cells after passage in G.P.E. cells was also effective in inducing an immunological response without clinical reactions in normal susceptible children. The attenuated virus derived from G.P.E. cells was used in 23 children in hospital with no history of varicella and no detectable C.F. antibody immediately after symptoms of varicella were found in a patient in the childrens ward. There was an antibody response in all the vaccinated children including those who were receiving steroid therapy. No troublesome clinical reactions were noticed and the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. 16 children with nephritis and nephrotic syndrome were also vaccinated. An immunological response was observed in all the vaccinated children, with no clinical reactions and no abnormal laboratory findings when blood and urine samples were examined. These results suggest that it is possible to prepare a live varicella vaccine which may be safely and effectively used for high-risk children as well as normal children.

Viremia and neutralizing antibody response in infants with exanthem subitum

Mononuclear cell-associated viremia caused by human herpesvirus type 6 was detected in 39 (66%) of 59 blood samples from 38 children with exanthem subitum between day 0 and day 7 of the disease. The rate of virus isolation from mononuclear cells was 100% (26/26) on days 0 to 2 (just before appearance of skin rash), 82% (9/11) on day 3, 20% (2/10) on day 4, 7% (2/12) on days 5 to 7, and 0% (0/37) on day 8 and thereafter. The cell-free virus was detected in blood in 10 (21%) of 47 blood samples during the same period. The antibody activity to the virus, evaluated by a newly developed neutralization assay, was first detected on day 3 of the disease with a positive rate of 18% (2/11). It became 60% (6/10) on day 4, 75% (9/12) on days 5 to 7, and 100% on day 8 and thereafter. Thus the disappearance of the virus from blood was associated with the induction of specific immunity to the virus.

A prospective study of human herpesvirus-6 infection in renal transplantation

Sixty-five kidney transplant recipients and their (22 living related and 43 cadaveric) donors were studied prospectively to determine the relationship between kidney transplantation and human herpesvirus-6 (HHV-6) infection. The virus isolation from peripheral blood and other tissues and sequential determination of neutralizing antibodies to HHV-6 were performed during 3 months following the transplantation. All of the donors and their recipients examined had neutralizing antibodies to HHV-6 at the time of renal transplantation and the virus was not isolated from them. HHV-6 was isolated from 3 renal tissues (2 living related and 1 cadaveric) obtained during transplant surgery, but not from their blood at that time. HHV-6 viremia occurred in 9 (14%) of the 65 recipients around 2 to 4 weeks after the transplantation. An additional 27 recipients showed a significant rise in the antibody titer. Thus, the infection with HHV-6 was confirmed in 36 (55%) of the 65. These results indicate that the virus is activated in many cases in the early posttransplant period and that HHV-6 establishes in vivo latency in the kidney tissue. There was no correlation between HHV-6 infection and acute rejection or the antirejection prophylaxis.

Severity of human herpesvirus-6 viremia and clinical findings in infants with exanthem subitum.

The degree of viremia with human herpesvirus-6 was evaluated in 176 blood samples from 89 infants with exanthem subitum and viremia, and compared with the severity of clinical features and complications of the disease. Fever persisted for 3 to 4 days in 73% of infants and for more than 5 days in 22%, followed by a rubella- or measles-like rash. The viremia was observed between the first day of fever (day 0) and day 4 of the disease. The number of infected cells per 10 million mononuclear cells was 3.45 +/- 1.00 (log10, mean +/- SD) on days 0 to 2, 3.30 +/- 1.14 on day 3, and 3.09 +/- 2.05 on day 4 of the disease. The number of infected cells on days 3 to 4 in infants with a febrile period longer than 4 days and free virus in plasma was significantly greater than that in infants with a febrile period of less than 3 days and without free virus in plasma. The amount of virus in blood on days 0 to 2 did not relate to the duration of fever, and that on days 0 to 4 did not relate to the presence or absence of diarrhea, bulging fontanelle, or bronchopneumonia. These findings suggest that the magnitude of the virus replication in infants with exanthem subitum is reflected in the severity of the disease.

Viremia is present in incubation period in nonimmunocompromised children with varicella

Articles in this section should require no more than three Journal pages, the text 1000 words or less. A combined total of two illustrations or tables and up to 10 references will be accepted. An abstract is not necessary.

IgM Neutralizing Antibody Responses to Human Herpesvirus-6 in Patients with Exanthem Subitum or Organ Transplantation

The assay for detecting IgM neutralizing (NT) antibody activity to human herpesvirus‐6 (HHV‐6) was developed by using pretreatment of blood sample with staphylococcal protein A. The activity was mostly present in IgM fractions of serum but not in IgA fractions separated by ultracentrifugation. The assay was used for seroepidemiological studies for HHV‐6 infection. In primary HHV‐6 infection, IgM NT antibodies appeared 5 to 7 days after onset of exanthem subitum, reached maximum titers at 2 to 3 weeks, and tended to decline to undetectable levels after 2 months. In contrast, reactivation of HHV‐6 observed in organ transplants showed somewhat greater degree of IgM NT antibody responses that persisted for 2 to 3 months and became undetectable 5 to 6 months after transplantation. The level and persistence of NT antibody titers measured by the conventional method was generally greater than those of the IgM titers. The prevalence of the IgM NT antibodies was examined in healthy individuals. The antibody was first detected at 4 to 7 months of age (5%), reached maximum level at 8 to 11 months (40%), and was detectable by 4 to 6 years (17%). A few (4 to 5%) of adolescents and adults were positive for the antibody.

Varicella‐zoster virus replication site in internal organs of an otherwise healthy child with varicella and sudden death

Pathological findings of an otherwise healthy 17 month old boy who was exposed to Varicella‐zoster virus (VZV) in his family and unexpectedly died 3 days after onset of varicella are reported. They showed a disseminated VZV infection with involvement of skin, lung, liver, spleen, gastrointestinal tract and other organs where VZV antigen was detected by the enzyme‐immunoassay with monoclonal antibodies to VZV. Since the subject was the full‐term product of an uncomplicated pregnancy, who grew and developed normally, and had no symptoms or laboratory findings suggestive of immunodeficiency until his death, these findings suggest that many organs are involved as major internal sites of viral replication before or during infection of skin with VZV in the immunocompetent host.

Developmental Changes in the NGF Content in the Brain of Young, Growing, Low-Birth-Weight Rats

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla ob-longata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Pharmacokinetic Study of Oral Prednisolone in Children with Nephrotic Syndrome Serum Concentration of Prednisolone in both Nephrotic and Remission Stage

We studied the absorption and excretion of orally given prednisolone in children with nephrotic syndrome, measuring the serum concentration of prednisolone. The peak concentration of prednisolone was low at the nephrotic stage when more than 1 gram of the urine protein was excreted a day, and that was high at the remission stage when the urine protein was negative. The average ascending rate between the two stages was 43.4%. It is thought that chiefly the fall of absorption of prednisolone from the intestines and the enlargement of the distribution space cause a decline of the peak concentration of prednisolone at the nephrotic stage. It is also thought that hypoproteinemia and the liver metabolism little influence the decline. Now we will suppose that in the therapy of children with nephrotic syndrome, when the urine protein turns to negative, immidiately the amount of orally given prednisolone may be reduced by about 30%. (Acta Paediatr Sep. 24(3):393 1982)