Hiromi Miyagawa

Enhancement of immunity against VZV by giving live varicella vaccine to the elderly assessed by VZV skin test and IAHA, gpELISA antibody assay

The enhancement of immunity against varicella-zoster vaccine (VZV) by subcutaneous injection of a live varicella vaccine was assessed by the VZV skin test for cell-mediated immunity (CMI), and immunoadherence hemagglutination assay (IAHA) and gpELISA antibody assays in the elderly people of 50-79 years of age. A total of 127 subjects were examined: 79 aged 50-59, 25 aged 60-69, and 25 aged 70-79. All were seropositive by the gpELISA assay (one was seronegative in the IAHA antibody assay). In contrast, a notable decline was observed in the VZV skin test with increasing age. Negative reaction was observed in 16/79 (20.2%) of the subjects in their 50s, 12/25 (48.0%) in their 60s and 14/25 (56.0%) in the 70s. After the vaccination, the results of the VZV skin test changed from negative to positive in 15/16 (91.8%) of subjects in their 50s, 11/12 (91.7%) in their 60s and 12/14 (85.7%) in their 70s. The mean antibody titer in the IAHA and the gpELISA increased approximately two-fold after the vaccination in each group. Immunity to VZV in 35 elderly subjects who were vaccinated previously was followed up for 4 years. All were positive by the VZV skin test after the previous vaccination. After 4 years, 31 (88.6%) were positive by the skin test, 4 were negative and became positive after revaccination. Although this study was uncontrolled open study, the results suggest that administering live varicella vaccine to the elderly is effective for enhancing immunity, particularly CMI to VZV.

Human Herpesvirus 6B Infection of the Large Intestine of Patients with Diarrhea

Four patients had severe diarrhea after undergoing stem cell transplantation. Human herpesvirus 6B (HHV-6B) DNA was detected in large intestine tissue specimens and in peripheral blood mononuclear cells. In situ hybridization was positive for HHV-6B DNA in the nuclei of goblet cells and, sometimes, in the histiocytes in the submucous region of the large intestine, which suggests that HHV-6B may infect and reactivate in these cells.

Recognition of a Novel Stage of Betaherpesvirus Latency in Human Herpesvirus 6

ABSTRACT Latency-associated transcripts of human herpesvirus 6 (H6LTs) (K. Kondo et al. J. Virol. 76:4145-4151, 2002) were maximally expressed at a fairly stable intermediate stage between latency and reactivation both in vivo and in vitro. H6LTs functioned as sources of immediate-early protein 1 at this stage, which up-regulated the viral reactivation.

Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a patient with HIV infection.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from lytic infection of oligodendrocytes by the papovavirus JC (JCV). PML has also been recognized as an AIDS-defining illness. The incidence of PML has increased since 1987 and it occurs in up to 4% of patients with AIDS. To date, there is no treatment available for PML and it usually results in death within 3-6 months of diagnosis. However, there are some reports of remission of PML after antiretroviral therapy. We report a 12-year-old child with hemophilia B and developing AIDS with the onset of PML. With highly active antiretroviral therapy, PML subsided with an increase of CD4 count from 10 to 300/microl in spite of about 1.0 X 10(4) human immunodeficiency virus (HIV)-1-RNA copies. He has survived more than 1 year without specific therapy against JCV. Highly active antiretroviral therapy appears to have improved his prognosis in HIV-associated PML.

The epidemiology and pathogenesis of infections caused by the high numbered human herpesviruses in children: HHV-6, HHV-7 and HHV-8.

Human herpesvirus 6 may be transmitted from saliva to infants, but other routes of transmission, such as organ and bone marrow transplantation, have also been reported. Intrauterine infection has also been suggested. Although the clinical symptoms during the primary infection in children are mild, human herpesvirus 6 may have neurotropic properties and be involved in the pathogenesis of febrile seizures in infants. The clinical symptoms caused by human herpesvirus 7 are not yet clear, but reports have described neurological symptoms. Human herpesvirus 8 has been identified from Kaposis sarcoma tissue using molecular procedures. Serological study shows that human herpesvirus 8 is not so common in society and the mode of transmission is still unclear. Several routes of infection have, however, been considered, including sexual transmission.

Sequential measurement of human herpesvirus 6 DNA with polymerase chain reaction method in pediatric living‐related liver transplantation

Background: Human herpesvirus 6 (HHV‐6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV‐6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living‐related liver transplantation (LTx). 
 Methods: Subjects consisted of 5 post‐operative biliary atresia patients undergoing living‐related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8–18 within 1 month and 5–10 ng/mL thereafter) and low‐dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV‐6 DNA was semiquantified as follows: 1+, 1–10; 2+, 10–100; 3+, 100–1000; 4+, over 1000 copies/105 PBMCs. 
 Results: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV‐6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2–3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post‐LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV‐6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively. 
 Conclusion: HHV‐6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living‐related LTx. Although HHV‐6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.