Masaro Kaji

The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: With special reference to the prevaccination antibody and its interaction with age

The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0-50% at > or = 1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer > or = 1:128) among those with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054): as age increased, those with no preexisting antibody (< 1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer > or = 1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to 74%), respectively.

Differentiation of herpes simplex virus 1 and 2 in cerebrospinal fluid of patients with HSV encephalitis and meningitis by stringent hybridization of PCR-amplified DNAs

Differentiation of herpes simplex virus (HSV) types 1 and 2 in cerebrospinal fluid of 17 patients with serological1y diagnosed HSV encephalitis and meningitis or acute limbic encephalitis was determined by stringent hybridization of polymerase chain reaction — amplified DNAs. Ten of 17 patients were positive; six with HSV 1 isolates and four with HSV 2 isolates. We detected HSV type 1 in two cases of meningitis, although meningitis is generally thought to be caused by type 2. Additionally, HSV type 2 was found in one case of acute adult encephalitis, which is generally due to HSV type 1. HSV DNAs could be detected for over I month after onset, although our patients included several prolonged and recurrent cases. HSV DNA genomes were not detected in three cases of acute limbic encephalitis. Our study indicates that this method can be used for type differentiation in HSV CNS infections.

Japanese encephalitis in the Kurume region of Japan: CT and MRI findings.

SummaryNeurological, computed tomography (CT) and magnetic resonance imaging (MRI) findings were recorded from 13 patients with Japanese encephalitis (JE) in the Kurume region diagnosed by serological criteria. The patients averaged 63 years of age, and 5 were older than 70 years. The serological data mostly indicated a primary response. Hemiplegia and tetraplegia were common, together with extrapyramidal signs. A few cases had a stroke-like onset and cerebral haemorrhage during the course of JE. CT and MRI in 7 cases revealed abnormalities in the thalamus and basal ganglia including the putamen. The CT and MRI findings from the acute stage to the convalescent stage were considered to be characteristic of JE.

History of influenza vaccination programs in Japan

In 1976, influenza mass vaccination among schoolchildren was started under the Preventive Vaccination Law, which was intended to control epidemics in the community. However, in the late 1980s, questions about this policy and vaccine efficacy arose, and a campaign against vaccination began. In 1994, influenza was excluded from the target diseases list in the Preventive Vaccination Law, without considering the immunization policy with respect to the common indications in high-risk groups. In 2001, the Law was again amended, specifying target groups, such as the elderly aged 65 or over, for influenza vaccination. In the 2005--2006 season, vaccine coverage among the elderly reached 52%. This shows that the need for vaccination has gradually become understood. However, the anti-vaccination campaign, which claims that the influenza vaccine has no efficacy, is still active. Vaccine efficacy studies that were not properly conducted are also being reported. In 2002, the Ministry of Health, Labor, and Welfare organized a research group on vaccine efficacy consisting of epidemiologists. The present symposium, as part of the 9th Annual Meeting of the Japanese Society for Vaccinology in 2005, was planned to further introduce epidemiological concepts useful in studying influenza vaccine efficacy.

Phase 1 clinical tests of influenza MDP-virosome vaccine (KD-5382)

MDP-virosome vaccine, which contains haemagglutinin (HA) and neuraminidase (NA) antigens isolated from influenza virus combined with 6-O-(2-tetradecylhexadecanoyl)-N-acetylmuramoyl-L-alanyl-D-isoglutamine) (B30-MDP) and cholesterol was tested, in comparison with a currently used HA vaccine, for immunogenicity and adverse reactions on 77 adult male volunteers. The volunteers were divided into eight groups, and each individual was injected subcutaneously once, or twice at a 4 week interval, in their upper arm with one of seven different MDP-virosome vaccine preparations or with HA vaccine as control. Of the three virus strains used as vaccine antigens, MDP-virosome vaccines induced higher haemagglutination inhibiting (HI) antibody to A/Yamagata/120/86 (H1N1) and A/Fukuoka/C29/86 (H3N2) than did HA vaccine, whereas it induced lower HI antibody to B/Nagasaki/1/87, comparable with that induced by HA vaccine. Regarding local adverse reactions, MDP-virosome vaccinees frequently developed mild local pain, reddening and swelling, which disappeared within 5 days; as regards systemic no adverse reactions, leucocytosis developed among the MDP-virosome vaccines, but no other reactions were observed. The leucocytosis may have been caused by the pharmacoimmunological activity of B30-MDP derivatives.

Age-Specific Prevalence of Hepatitis B e Antigen (HBeAg) and Antibody to HBeAg (Anti-HBe) among Asymptomatic Hepatitis B Surface Antigen (HBsAg) Carriers in Okinawa and Kyushu, Japan

A total of 1,741 asymptomatic hepatitis B surface antigen (HBsAg) carriers in two areas (Okinawa and Kyushu) in Japan were surveyed for the presence of hepatitis B e antigen (HBeAg) and the corresponding antibody (anti‐HBe) to determine the age‐specific prevalence of these markers and the mean age of carriers with HBeAg. Prevalence of HBeAg was significantly higher in Kyushu (36.4% of 755 carriers) than in Okinawa (20.0% of 986 carriers) (P<0.001). The mean age of carriers with HBeAg was 25.5 years in Kyushu and 16.1 years in Okinawa, suggesting that HBeAg converted to anti‐HBe earlier in Okinawa than in Kyushu. In contrast, the prevalence of anti‐HBe was significantly higher in Okinawa (74.6% of 986) than in Kyushu (56.3% of 755) (P<0.001). The prevalence of HBeAg decreased with age up to 40–49 years of age and then increased in both areas. Prevalence of anti‐HBe was inversely related to the prevalence of HBeAg in both areas. These data suggest that HBeAg and anti‐HBe are chronological markers of chronic hepatitis B virus infection and that the duration of HBeAg persistence can be different in different area, even in the same country.

Influenza vaccine effectiveness and confounding factors among young children

This study, done during the 2002--2003 season among children <6 years of age to investigate influenza vaccine effectiveness and confounding factors, involved 2913 children (1512 vaccinees, 1401 non-vaccinees) recruited from 54 paediatric clinics. Between December 2002 and April 2003, parents reported their childrens maximum body temperatures weekly. Influenza-like illness (ILI) was defined as an acute febrile illness (> or =38.0 degrees C) during the peak epidemic period. Adjusted odds ratios (ORs) for ILI were obtained using a logistic regression model. In analysis for total subjects, the ORs were significantly decreased for vaccinees (OR: 0.76, 95% CI: 0.66-0.88) and significantly increased for younger age groups, including children aged 2.0-3.9 years (1.42, 1.18-1.72) and those < 2.0 years (2.02,1.61-2.54), compared to those between 4.0 and 5.9 years. ORs were significantly increased for children who visited a physician within the last 6 months for a cold (1.27, 1.08-1.50), attended preschool (1.72, 1.45-2.04), and had > or =3 siblings (1.42, 1.15-1.74). These confounding factors are suggested to be considered in estimating vaccine effectiveness among young children. In subgroup analysis by age groups, significantly decreased ORs were seen in 2.0-3.9-year-old (0.59, 0.47-0.74) and 4.0-5.9-year-old (0.75, 0.58-0.98) vaccinees; no significant vaccine effectiveness was detected for those < 2.0 years (1.07, 0.80-1.44). Thus, among very young children vaccine effectiveness could not be demonstrated.

HTLV-I-Associated Myelopathy and Adult T-Cell Leukemia Cases in a Family

Familial cases of HTLV-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL), developing in a daughter and father, respectively, are reported. The coexistence of both diseases in a family has not been reported before. This supports the recent findings that ATL and HAM may be brought about by an identical virus on an apparently different immunogenetic background.

GM1 ganglioside reduces edema and monoaminergic neuronal changes following experimental focal ischemia in rat brain

Seventy-two hours following a middle cerebral artery occlusion, the associated increase in water content on the ischemic side was significantly reduced by the exogenous administration of monosialoganglioside GM1 (30 mg/kg, i.p.). The levels of dopamine and serotonin on the ischemic side were approximately 50% and 80% of those on the contralateral non-ischemic side, respectively. Treatment with GM1 (5 times during the first 48 h after occlusion) produced a significant reduction in the levels of dopamine and serotonin loss. The present findings are compatible with the observed protective action of the exogenously administered GM1 following ischemic brain injury.

Reactogenicity of trivalent inactivated influenza vaccine in young children: Pronounced reactions by previous successive vaccinations.

In order to assess factors associated with reactogenicity of trivalent inactivated influenza vaccine (IIV3) among young children, data on 1538 vaccinees aged 0-5 years in a previous vaccine effectiveness study were analyzed. The most frequent reaction was redness (19%), followed by induration, swelling, itching, and pain (6-12%); there were no serious adverse events. For some local reactions, multivariate analyses indicated associations of younger age, preschool attendance, presence of siblings, and allergy with lower risk, and use of thinner needles with higher risk. Most notably, administration of one or more IIV3 vaccines during the previous 3 seasons was positively associated with each local reaction (adjusted odds ratios: 3.6-5.4). For subjects aged ≥3 years, prior successive annual vaccinations were associated with substantially increased local reactions, with clear dose-response relationships (P for trend: <0.001 for each); for example, an 9.8-fold greater risk of swelling following three successive annual vaccinations before the study season.