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Aim: As a result of the 2012–2013 rubella epidemics in Japan, many cases of congenital rubella syndrome have been reported. Given the frequent changes to rubella vaccination policy in Japan, we investigated antibody prevalence among pregnant women according to birth year. Subjects and methods: Participants comprised 55,400 pregnant Japanese women for whom rubella-specific hemagglutination inhibition antibody had been measured during early pregnancy in our institute from 1987 to 2016. Birth year was considered for the 47,978 cases for which age was known. Results: The ratio of rubella antibody-negative cases among pregnant women born after 1962 decreased significantly with mandatory vaccination. In the transition phase, during which the administration target was changed from schoolgirls to children of both sexes (born 1979–1987) as temporary vaccination, the ratio of rubella antibody-negative pregnant women started increasing in the latter period of this phase. For generations born in or after 1988, the ratio of rubella antibody-negative pregnant women clearly increased when the vaccination target changed to non-mandatory vaccination of children of both sexes. Conclusions: Prevalence of antibody titers depends on vaccine coverage rates. Suitable information needs to be provided prior to conception to all women, their husbands, and family members. [ABSTRACT FROM AUTHOR]

Background: Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disorder caused by the measles virus (MV) and is identified by positive MV‐specific antibody titers, detected mainly by hemagglutination inhibition (HI) tests in the cerebrospinal fluid (CSF). However, an alternative method, the enzyme immunoassay (EIA), has increasingly become a preferred method for detecting MV antibodies. To establish the index for SSPE diagnosis using EIA, we investigated the correlation between HI and EIA titers of MV antibodies in SSPE patients. Methods: Data on MV antibody titers and measurement methods at the time of diagnosis in 89 Japanese SSPE cases diagnosed between 1979 and 2006 were obtained by a survey. We also assessed the serum and CSF MV antibody titers in three patients with SSPE and serum MV antibody titers in 38 healthy adults using immunoglobulin G (IgG)‐EIA and HI. Results: In all cases diagnosed as SSPE, IgG‐EIA titers in the CSF were ≥0.49 IU/mL. There was a positive correlation between serum antibody values in the controls measured by IgG‐EIA and HI. In patients with SSPE, both serum and CSF antibody values, measured by IgG‐EIA, and HI, were positively correlated, and a positive correlation was found between the serum and CSF MV antibody titers as measured by IgG‐EIA. The serum/CSF MV antibody titer ratios determined by IgG‐EIA were <20 in most SSPE patients. Conclusions: Immunoglobulin G‐EIA may be a suitable alternative method for SSPE diagnosis; however, its potential utility and the cut‐off point of ≥0.49 IU/mL should be tested with additional patient cohorts. [ABSTRACT FROM AUTHOR]

Background: Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs.Methods: To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice.Results: The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation.Conclusions: Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity. [ABSTRACT FROM AUTHOR]

Background Patients with underlying disease represent a high-risk group for influenza-associated complications and hospitalization. However, few studies investigated the immunogenicity of influenza vaccine in patients with liver disease. Objective To examine immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with liver disease and to explore the associated factors on lowered immune response. Patients/Methods A single subcutaneous dose of monovalent inactivated unadjuvanted split-virus influenza A(H1N1)pdm09 vaccination was performed in 80 patients with chronic hepatitis C virus infection at Osaka City University Hospital in Japan. To measure the hemagglutination inhibition antibody titer, serum samples were collected before and 3 weeks after vaccination. Results No serious adverse events were observed. After vaccination, antibody titers ≥1:40 were observed in 56 patients (71%). The corresponding seroconversion proportion was 72%, and the mean fold rise was 10·3. Immune responses were robust regardless of severity of liver disease or existence of probable cirrhosis. However, patients with older age, lower body mass index, or receiving Stronger Neo-Minophagen C tended to show lower antibody responses to A(H1N1)pdm09 vaccine. In addition, reduced immune responses were observed in patients who had received the 2009/10 seasonal vaccination prior to A(H1N1)pdm09 vaccination. Conclusions Single dose of A(H1N1)pdm09 vaccine achieved a sufficient level of immunity among patients with chronic hepatitis C. Antibody response may be affected by age, body mass index, Stronger Neo-Minophagen C administration, and recent seasonal influenza vaccination. [ABSTRACT FROM AUTHOR]

In April 2007, seven students belonging to the same class at Teikyo University developed measles. To prevent the spread of infection, 27 of 106 students in the same class who had low anti-measles antibody titers as measured by hemagglutination inhibition (HI) assay were vaccinated. After the outbreak had subsided, the HI values were investigated in 103 students, and they answered questionnaires about their health condition during the period of the outbreak and their previous clinical histories of measles, including vaccination records. There was no new case of measles after introduction of the vaccination program. However, the HI titers of 42% of the students who were not vaccinated in this program were significantly elevated. Fever and catarrhal signs occurred in 7 of these students with pre-exposure titers of 8 or less. The post-exposure HI titers of 71% of students who were unaffected by measles and had high HI titers (>8) before the epidemic did not increase. These results suggested that people with low HI titers may become potential carriers of measles and that measurement of pre-exposure HI anti-measles antibody titer is a useful method for selection of candidates to undergo vaccination. [ABSTRACT FROM AUTHOR]

Summary: Objective: To assess the prevalence including asymptomatic infection, infection risk of exposure to patients, and effectiveness of personal protective equipment (PPE) among health care workers (HCWs) during the first pandemic (H1N1) 2009 (pH1N1) outbreak in Kobe, Japan in May 2009. Methods: A cross-sectional seroepidemiological study was conducted on 268 HCWs in the two hospitals in Kobe to which all pH1N1 inpatients were directed. Participating HCWs completed a self-administrated questionnaire and provided a single serum sample which was analyzed using a hemagglutination-inhibition (HI) antibody test. Results: Of 268 subjects, 14 (5.2%) were found to have positive antibodies to the pH1N1 by HI assay; only 1 reported a febrile episode. Among the 14 seropositive cases, 8 received chemoprophylaxis. 162 HCWs (60.4%) had been exposed to patients. The seropositive rate (SPR) for pH1N1 of the exposed group was higher than that of the unexposed group, however not statistically significant (6.8% vs. 3.1%, p = 0.197). There were no statistically significant differences in SPR for any PPE. Conclusion: The SPR for pH1N1 in the exposed group was higher than that of the unexposed group in HCWs; however, most of these individuals were asymptomatic. There was no statistically significant association between PPE implementation and pH1N1 seropositivity. [Copyright &y& Elsevier]

The article presents a study on the prevalence of H3 subtype infection in cats and dogs in Japan. The researchers used the neuraminidase inhibition (NI) and hemagglutination inhibition (HI) tests to carry out a sero-epidemiological survey. They gathered serum samples from 237 cats and 582 dogs from no less than 25 and 44 prefectures of Japan respectively from the Veterinary Medical Centre of Tottori University. They concluded that the importance of cats and dogs in the epidemiology of influenza A virus in the country is possible due to the presence of the antibodies against the influenza A virus human H3 and N2 subtypes.

The article presents a study on the successive deaths of a serval or Leptailurus serval and a captive snow leopard or Uncia uncia due to infection with feline panleukopenia virus (FPLV) at Sapporo Maruyama Zoo in Hokkaido, Japan. The researchers carried out a hemagglutination inhibition (HI) test to determine the antigenic type of the isolates, which showed that both isolates possessed an antigenic epitope for mink enteritis virus (MEV) and FPLV. They found that the safety in exotic animals is not confirmed by the attenuated nature of viruses in the vaccines.

Please cite this paper as: Shoda A, Hayashi M, Takayama N, Oshima K, Nishikawa M, Okazaki T, Negishi M, Hayashida S, Watanabe H, Inaba N. Maternal screening and postpartum vaccination for measles infection in Japan: a cohort study. BJOG 2011;118:88-92. We investigated the prevalence of measles-sensitive pregnant women and the clinical usefulness of measles vaccination in postpartum women. Measles antibody levels were measured in 751 pregnant women. Forty-four women were vaccinated postpartum, and screened for antibody levels and adverse effects 1 month after vaccination. The prevalence of measles-sensitive pregnant women was 10-20%, with the highest prevalence in those under 24 years of age. Almost all (97.7%) vaccinated women acquired immunity, and did not show any adverse effects. Serum measles antibody levels should be determined in all pregnant women as a screening tool, and sensitive women should be vaccinated immediately after delivery. [ABSTRACT FROM AUTHOR]

ABSTRACT A phase III observational study evaluating a single-dose of an inactivated, split-virus, unadjuvanted AH1pdm vaccine in HCW was conducted. A safe and effective vaccine was needed after the emergence of AH1pdm in April 2009. We analyzed the immunogenicity and safety of the vaccine. A total of 409 subjects were enrolled and given 15 μg hemagglutinin antigen by s.c. injection. Antibody titers were measured using hemagglutination-inhibition antibody assays before vaccination and 28 days after. The co-primary immunogenicity end-points were the proportion of subjects with antibody titers of 1:40 or more, the proportion of subjects with either seroconversion or a significant increase in antibody titer, and the factor increase in geometric mean titer. We collected 389 pair samples. Antibody titers of 1:40 or more were observed in 148 of 389 subjects (38.0%, 95% CI: 33.2-42.9). The immunogenicity was also confirmed in other end-points, but was not sufficient and was lower than in previous reports. A total of 96 of adverse events was reported: 51 local events and 57 systemic events. There were 12 subjects with both local and systemic events. Nearly all events were mild to moderate except in four subjects. A single 15-μg dose of AH1pdm vaccine did not induce sufficient immunogenicity in HCW, with mild-to-moderate vaccine-associated adverse events. We need to consider further improvement of the AH1pdm vaccine program in HCW for the prevention of nosocomial infection, as well as for the benefit of HCW. [ABSTRACT FROM AUTHOR]

To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. The total frequency of ORVs was 2.6% (45/1,734) during the 2007-08 season and 99.7% (1,477/1,482) during the 2008-09 season, indicating a marked increase in ORVs in Japan during 1 influenza season. The NA gene of ORVs in the 2007-08 season fell into 2 distinct lineages by D354G substitution, whereas that of ORVs in the 2008-09 season fell into 1 lineage. NA inhibition assay and M2 sequencing showed that almost all the ORVs were sensitive to zanamivir and amantadine. The hemagglutination inhibition test showed that ORVs were antigenetically similar to the 2008- 09 vaccine strain A/Brisbane/59/2007. Our data indicate that the current vaccine or zanamivir and amantadine are effective against recent ORVs, but continuous surveillance remains necessary. [ABSTRACT FROM AUTHOR]

Antigenicity of all the A(H3) viruses which we isolated from specimens collected in Sendai and Fukuoka, Japan in 2002–2003 influenza season was examined by hemagglutination inhibition test (HI) using the ferret antiserum against A/Panama/2007/99 (H3N2), the vaccine strain for the past three influenza seasons, provided by WHO Influenza Collaborating Center, Japan. All the viruses were isolated in MDCK cell system. From the beginning of the epidemic, we found that many isolated virus strains reacted with the standard antiserum more than 4- to 16-fold less than its homologous titer, in both cities. The number of isolation of such antigenic drifted viruses increased and dominated the isolates in this season. We show here the chronological appearance of such variants in this season. Furthermore, we performed genetic analyses on the HA genes of the isolates along with those of previous two consecutive seasons. Thus it was revealed that the isolates of this season make a clear cluster different from the cluster in the previous seasons, and the variants of 2002–2003 season make a different cluster from those of previous two seasons. Moreover, no difference was found in clusters which could explain the difference between these variants and nonvariants, and among variants isolated in four cities. [Copyright &y& Elsevier]

The article presents a serological survey of arthropod-borne viruses among wild boars in the Kyushu region of Japan. It states that 90 blood samples from wild boars in Japan are gathered and a survey for seven arthropod-borne viruses is done through the use of hemagglutination inhibition tests. It is found that the rate for Japanese encephalitis virus (JEV) is 52.2%, 47.8% for Getah virus (GETV), 13.3% for Akabane virus, 10% for Aino virus, and less than 5% for Bluetongue, Chuzan, and Ibaraki viruses. Moreover, the results indicates that JEV and GETV infections are dominant over the other viruses and in wild boars which determines that boars are involved in the transmission cycle of those viruses in Japan.

Leptospirosis is a zoonotic and disaster-related infectious disease. It is mainly endemic in subtropical or tropical countries and has not been reported since 2009 in the Tohoku region (northern Japan), including the Yamagata and Miyagi Prefectures. However, we experienced four patients with leptospirosis in the Tohoku region from 2012 to 2014; three patients (#1-3) live in the agricultural areas of the Yamagata Prefecture and one patient (#4) was a visitor to the Miyagi Prefecture. Patient 1 (81-year-old female) is a villager, with a rat bite, while Patient 2 (77-year-old male) and Patient 3 (84-year-old female) are farmers and were infected probably during agriculture work. Patient 4 (40-year-old male US citizen) was infected while traveling in Thailand. They had chief complaint of fever, headache, and myalgia and showed manifestations of hyperbilirubinemia (mean, 4.35 mg/dL), thrombocytopenia and acute kidney injury (AKI). All patients were diagnosed by polymerase chain reaction using blood and/or urine samples and a microscopic agglutination test for the anti-Leptospira antibody. All the patients were treated with infused antibiotics, including minocycline. The patients underwent hemodialysis due to severe AKI (mean serum creatinine, 4.44 mg/dL), except for Patient 2 with the normal serum creatinine level (1.12 mg/dL). All the patients recovered and were discharged. The presence of the three patients in the Yamagata Prefecture implies that leptospirosis does re-emerge in the Tohoku region. Therefore, careful survey of the pathogen is necessary for febrile patients with AKI who engage in agriculture or have a recent history of travelling in subtropical or tropical countries.

Pleurocybella porrigens is a mushroom-forming fungus, which had been consumed as a traditional food in Japan. However, in 2004, 55 people got poisoned by eating the mushroom and 17 people among them died of acute encephalopathy. We have already reported the purification, characterization, and cDNA cloning of a lectin from the mushroom (PPL) which might have caused the poisoning. Here, we report the heterologous expression of recombinant PPL by basidiomycete Phanerochaete sordida YK-624. The glyceraldehyde 3-phosphate dehydrogenase gene promoter was used to drive the expression of the PPL gene (ppl) in P. sordida YK-624. Furthermore, the signal peptide of lignin peroxidase which is an extracellular protein was used to secrete rPPL into extracellular region. Fifteen regenerated clones were cultured on Kirk HNHC broth, and the presence of lectin activity in the culture broth was checked by agglutination assays. The results indicated that the culture broth of rPPL-6 clone showed the strongest hemagglutination activity, and it was therefore used for subsequent analysis. The heterologous expression of rPPL by P. sordida YK-624 was confirmed by SDS-PAGE, lectin activity by the hemagglutination assay, and mass of rPPL by MALDI-TOF respectively, indicating that the extracellular secretion of rPPL as active form was successful., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: In the USA, live attenuated varicella-zoster virus (VZV) vaccine is licensed for use in people 50 or older, to reduce the incidence and/or severity of herpes zoster. However, this vaccine is not yet available in Japan, and the immunity profile for VZV in older people has not been investigated in detail in Japan., Objectives: The aim of this study was to conduct a detailed survey about the immunity profile for VZV in older people in Japan., Study Design: A panel of immunologic tests (skin test, ELISPOT, gpELISA, IAHA and NT) were used to analyze the immunity to VZV in the subjects. And an interview about zoster history was carried out with each of the subjects., Results: Cellular immunity test (skin test and ELISPOT) results declined with increasing age; on the contrary, humoral immunity test (gpELISA, IAHA and NT) results increased with advancing age. In addition, strongly boosted humoral immunity was found in the subjects with zoster history, however relatively small increase was found in cellular immunity test results., Conclusions: Cell-mediated immunity (CMI) to VZV decreased and humoral immunity increased with increasing age in this population., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid., Methods/results: To elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009., Conclusions: These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008.

Background/purpose: Alveolar echinococcosis of the liver (AEL) is a zoonosis that is distributed in cold regions of the northern hemisphere. The disease is mostly found in adults and rarely in pediatric patients because it tends to be slow growing., Patients and Methods: Ten Japanese pediatric patients (under 15 years old) with AEL have been operated on in Hokkaido University Hospital from January 1936 to June 2008. We examined these children and revealed the characteristics of AEL., Results: The patients included three males and seven females whose mean age was 10.9 years old, ranging from 7 to 15. The length of follow-up was from 3 months to 33 years (median 19 years). Six cases were picked up by mass screening; nine cases who underwent hepatectomy are still alive and one case whose tumors were unresectable died of liver failure., Conclusion: Our cases indicate that some AEL pediatric patients advanced rapidly, so early detection is imperative. Thus, screening examinations are essential for children in contaminated areas and, if a liver tumor is found on a screening examination and diagnosed as AEL, complete radical resection should be performed.

In hepatitis B virus (HBV) infection-preventing programs, serum or plasma levels of antibody to hepatitis B surface antigen (anti-HBs) are important to determine whether individuals are protective or not. We compared anti-HBs responses using passive hemagglutination assay (Mycell) and chemiluminescent immunoassay (Architect) among four recipient groups of HB vaccines, Meinyu, HBY, Bimmugen and Heptavax II, that have been approved in Japan. Overall, in a total of 1875 vaccinees Mycell results showed recipient groups of Meinyu and HBY acquired higher anti-HBs levels than those of Bimmugen and Heptavax II. Comparison of anti-HBs responses by both Mycell and Architect in recipient groups of Meinyu (n=150), HBY (n=218), Bimmugen (n=260), and Heptavax II (n=47) demonstrated the order of vaccinees' responses, such as geometric mean titers, ratios of acquiring high antibody levels (Mycell titers over 1024, Architect measurements over 1000 mIU/mL), and ratios of having unsuccessful antibody responses (Mycell titers under 8, Architect measurements under 10 mIU/mL), were somewhat different between the two assays. Comparison of Architect measurements at given Mycell titers revealed Bimmugen-recipients showed significantly lower values than HBY- or Heptavax II-recipients. Around critical protective levels, 5 of 22 Bimmugen-recipients with Mycell titers 16 or 32 showed Architect measurements under 10 mIU/mL, while 8 of 11 Heptavax II-recipients with Mycell titers below 8 demonstrated Architect measurements over 10 mIU/mL. Thus, discrepancies in anti-HBs evaluation between Mycell and Architect seemed to partly depend on administered vaccines. These results indicate anti-HBs concentration should be evaluated carefully so that we could completely prevent HBV infection.

A total of 39 Bacillus thuringiensis isolates were recovered from 38 leaves collected from 5- to 10-m-high canopies of 8 micro-/meso-phanerophyte species in a lucidophyllous forest of Japan. B. thuringiensis-positive leaves accounted for 1.4% of a total of 2805 leaves from 15 tree species. The frequency of the organism was 0.8% among the Bacillus cereus/B. thuringiensis group. Of 39 isolates obtained, 27 (69.2%) were allocated to 11 H serovars, and 12 isolates remained unidentified: 11 were motile but lacked reactivity to the 55 reference antisera, and 1 isolate was not flagellated. Two H serovars, kurstaki (H3abc) and tohokuensis (H17), occurred predominantly on canopy phylloplanes. Larvicidal activities against Bombyx mori and/or Aedes aegypti were associated with 49% of the canopy isolates. Strong hemolysis was induced by parasporal inclusion proteins of the two isolates of serovar israelensis (H14). Hemagglutinating (lectin) activity was associated with parasporal proteins of nine isolates. There was little correlation between insecticidal activity and lectin activity.

Given the absence of recent reports on the isolation rate of Serratia marcescens by pili type, clinical isolates from respiratory and urinary tract specimens--prime loci of infection by this organism--were subjected to examination. The 123 S. marcescens strains (serotype O2, 67 strains, serotype O14, 56 strains) used in this study were isolated from inpatients at Showa University Fujigaoka Hospital during the 5 years from April 1997 to March 2002. Higher rates of S. marcescens O2 with mannose-resistant (MR)/K Klebsiella-like pili were detected among the respiratory tract-derived strains. On the other hand, more non-hemagglutinating O14 strains were found among the urinary tract-derived strains. Analysis by study phase revealed a rise in the isolation rate of non-hemagglutinating strains, from 0-17.4% for O2 strains and 34.5%-66.7% for O14 strains, between phase I (April 1997 to March 1999) and phase II (April 1999 to March 2002) of the study. In order to examine the increasing non-hemagglutinating strains in detail, the 28 serotype O14 non-hemagglutinating strains, and 8 strains with only mannose-sensitive (MS) pili were subjected to genotyping by pulsed-field gel electrophoresis (PFGE), revealing the presence of 10 clones with disparate genotypes. The A1 strain isolated at the highest frequency was non-hemagglutinating in all cases and possessed the same genotype, indicating proliferation within the hospital over the 5 years of the study. These results indicate that non-hemagglutinating strains were transmitted among patients within the hospital.

A total of 236 fecal specimens collected from infants and children with gastroenteritis in Maizuru city, Japan from July 2002 to June 2003, were tested for the presence of rotaviruses, noroviruses, sapoviruses, astroviruses, and adenoviruses by RT-PCR, PAGE, RPHA, and latex agglutination methods. Among diarrheal viruses detected, group A rotavirus was the most prevalent (32.2%; 76 of 236) followed by norovirus GII (21.2%; 50 of 236), group C rotavirus (10.2%; 24 of 236), adenovirus (3.8%; 9 of 236), sapovirus (2.5%; 6 of 236), astrovirus (1.3%; 3 of 236), and norovirus GI (0.8%; 2 of 236), respectively. It is noteworthy that group C rotavirus infection was apparently confined only within the period of 5 months (December 2002 through April 2003). This pattern of infection implied that the outbreak of group C rotavirus in these patients, which was the first outbreak of gastroenteritis attributed to group C rotavirus in Maizuru city. Moreover, about half (12 of 24) of group C rotavirus infected cases were confined to infants and young children less than 3 years old. Another interesting feature of the study was the demonstration of the mixed infections with group C rotavirus and group A rotavirus, as well as group C rotavirus and norovirus GII in 20.8% (5 of 24) and 8.3% (2 of 24), respectively. This is the first report of gastroenteritis associated with the mixed infections with group C rotavirus and other viral enteropathogens such as norovirus. The results indicate that group C rotavirus could infect not only older children and adults but also infants and young children under 3 years old.

Medical records, for 2000 and 2001, of symptomatic amoebic patients who were treated at our hospitals in Tokyo, Yokohama and Osaka were studied retrospectively for the purpose of gathering epidemiological data on symptomatic Entamoeba histolytica infection. A total of 58 patients were treated. Fifty-five of them were male, and 96% of the male patients were Japanese. The mean age of patients was 44.9 years old, and 91% of patients contracted the disease in Japan. Fifty-six per cent of the male patients indicated that they were practising homosexuals, and 44% of the male patients denied these practices or left the question unanswered. The serum Treponema pallidum haemagglutination test was positive in 45% of the patients, and antibody to human immunodeficiency virus (HIV) was positive in 45%. Our study revealed that recent symptomatic E. histolytica infection almost exclusively afflicted middle-aged males in the big cities of Japan, that a majority of the patients were probably exposed to the causative organism during homosexual activity, and that an increasing number of patients will be co-infected with HIV.

Objective: To compare the characterization of hemagglutination and the sequence of HA1 region of the influenza A (H3N2) virus in Zhejiang province and Japan in recent years., Methods: Hemagglutinin antigenic analysis of influenza A (H3N2) viruses which were isolated in Zhejiang province was carried out and to compare their characterization of hemagglutination and the sequence of amino acids in HA1 region with the virus strains from Japan during the same period., Results: The antigenicity and the amino acid sequence in HA1 region of the virus strains prevalent in Zhejiang in recent years have changed to some extent. Most of the virus strains were lack of hemagglutination reaction to chicken red blood cell and became "O" phase virus strains. The amino acid sequence of HA1 region of the virus strains exhibited only 94.82% of its homology with that of A/Wuhan/359/95 strain. The virus strains of Japan in the same period showed similar characteristics., Conclusion: HA1 gene variation of influenza A (H3N2) viruses was the main cause leading to the spread of influenza in the last years.

Purpose: Screening for colorectal cancer using a guaiac-based fecal occult blood, or Hemoccult, test has been demonstrated to reduce colorectal cancer mortality. However, the magnitude of effectiveness is relatively low because of poor sensitivity of the Hemoccult test. The immunochemical fecal occult blood test has been shown to be much more sensitive than the Hemoccult test in detecting preclinical colorectal cancer in an asymptomatic population. The purpose of this article is to discuss the validity of the immunochemical fecal occult blood test and the efficacy of a population-based screening program using the test., Methods: Relevant articles were primarily identified through MEDLINE search. Review was focused on the studies of population screening programs with the immunochemical fecal occult blood test., Results: Sensitivities for colorectal cancer calculated in the same population were reported to be 67 to 89 percent and only 33 to 37 percent for the immunochemical test and Hemoccult test, respectively. Case-control studies and other observational studies showed that screening programs using the immunochemical fecal occult blood test by hemagglutination reaction would reduce the risk of dying of colorectal cancer by 60 percent or more for those screened annually compared with those unscreened. It was also shown that a screening strategy using the immunochemical fecal occult blood test had the best cost-effectiveness ratio among the methods available. Nearly 5 million persons are currently screened per year in Japan, yielding 0.15 to 0.2 percent colorectal cancer cases among persons with positive fecal occult blood test results., Conclusions: These results strongly suggest that a screening program with immunochemical fecal occult blood test has promising advantages in terms of effectiveness over programs with the Hemoccult test. More stress is warranted on introduction of immunochemical fecal occult blood testing as a screening test in place of the guaiac fecal occult blood test.

Repeated binary responses provide efficient information for two purposes: (1) estimating two misclassification (false-positive and false-negative error) probabilities and (2) testing the hypothesis that either is zero in a reliability study. We focus on the assessment of reliability of a diagnostic test when there is no gold standard. This paper uses a latent class model and illustrates some of its properties. In addition, application to data containing variation among individuals is considered. We apply this model to the serological data on the MNSs blood group of atomic bomb survivors and their children. The results provide valuable information for examining measurement reliability.

A case control study to evaluate the occult blood screening for colorectal cancer was conducted in a town where colorectal cancer screening had been performed by Hemoccult test during the early years and subsequently by an immunochemical hemagglutination test. All residents aged >/=40 years had been offered the annual screening. Case series consisted of 51 subjects with fatal colorectal cancer. Three controls per case were selected from the list of residents who were alive at the time of diagnosis of the corresponding case and had been living in the town, matched by gender and by age. The odds ratio (OR) of dying of colorectal cancer for those having their most recent screening histories with Hemoccult test or the immunochemical test during the preceding 1 year and 1-2 year segment before case diagnosis were 0.20 [95% confidence interval (CI): 0.08-0.49] and 0. 17 (95% CI: 0.04-0.75), respectively. The OR increased towards 1.0 as the number of years since the most recent screening increased. The OR of dying of colorectal cancer was calculated to be 0.19 (95% CI: 0.05-0.70) for those screened with the immunochemical test alone during the preceding 1 year after adjustment for previous screening histories with the Hemoccult test. Corresponding OR was 0.36 (95% CI: 0.11-1.17) for those screened with Hemoccult test during the preceding 1 year. These results suggest that screening for colorectal cancer by fecal occult blood testings or immunochemical test alone would reduce mortality and that efficacy of the screening would be higher for the immunochemical test than for Hemoccult test.

Newcastle disease virus (NDV), named MET95, was isolated from a non-vaccinated broiler flock in Japan in 1995. The MET95 strain was determined to be a lentogenic NDV. The strain has the properties of eluting rapidly at 4 C and has low thermostability in hemagglutinating activity with chicken erythrocytes. In these studies, no difference could be found between the MET95 strain and the Hitcher B1 vaccine strain. However, the chickens inoculated with the MET95 strain, as well as chickens that they were in contact with, had a much higher hemagglutination-inhibition antibody response than those inoculated with the B1 strain. Accordingly, the MET95 strain is thought to be a promising candidate as a live ND vaccine strain. In Japan, this is the first report on the isolation of lentogenic NDV from chickens since the paper on the Ishii strain isolated in 1966.

Bovine coronavirus (BCV) was detected by reverse transcriptase-PCR, immune electron microscopy or virus isolation from adult cows at 6 out of 6 outbreaks of epizootic diarrhea in Japan. Six BCVs isolated in feces, intestinal content or tracheal exudate of the cows were analyzed for their antigenic properties by cross virus neutralization (VN) tests. The isolates were divided into two groups, one of which had closely related antigenicity with the reference Mebus and Kakegawa strains of BCV, and another which showed significant differences in VN antibody titers from the reference strains. Two isolates in the latter group, which were from the enteric and respiratory tracts of the same cows, respectively, were distinguished from each other by ELISA using monoclonal antibodies against the Kakegawa strain. The isolates showed various hemagglutination and receptor destroying enzyme titers against chicken or mouse erythrocytes.

In 1988, a mass outbreak of epidemic diarrhea, i.e., consisting of 296 cases, occurred in Fukuoka Prefecture. Fecal samples from patients of the outbreak were cultured for bacteria, but all samples were negative. Although direct electron microscopy (DEM) revealed the existence of rotavirus-like particles (diam. 60-70 nm) in the fecal samples, serological studies could not detect any antigenic relation to the ordinary rotaviruses by the reverse passive hemagglutination (RPHA) and enzyme-linked immunosorbent assay (ELISA) tests or immune electron microscopy (IEM) examination. The outbreak appeared to be caused by group C rotaviruses, based on the pattern of electrophoretic migration of RNA genome segments in polyacrylamide gel electrophoresis (PAGE). Furthermore, IEM examination showed large aggregates of virus particles and antibodies when the virus particles were incubated with a reference serum specific for group C rotaviruses.

Antibody against Mycoplasma bovis in sera of 48 calves introduced to a farm, in which calf pneumonia associated with M. bovis had been occurring in the last 3 years, was detected by an indirect hemagglutination test. Significant rises of antibody titers in sera of calves belonging to the groups A (16 calves) and B (14 calves) were recorded by day 60 post-introduction. On the other hand, a significant increase of antibody titers of 18 calves in group C, which had been administered antibiotics as a preventive therapy, was demonstrated at day 248 after arrival. These results indicated that the spread of M. bovis infection occurred easily on the contaminated farm, and a preventive therapy could delay the outbreak of calf pneumonia associated with M. bovis.

Among 39,656 voluntary blood donors in Okinawa Prefecture, Japan, 115 (0.29%) were repeatedly reactive for antibody to hepatitis C virus (anti-HCV) by second generation (2nd-gen) passive hemagglutination assay (PHA). Positive serum samples were tested for anti-HCV using three different enzyme immunosorbent assays (ELISAs; Abbott 2nd EIA, UBI-HCV-EIA, JCC-2) and for HCV-RNA by the polymerase chain reaction (PCR). The 115 2nd-gen PHA-positive sera were divided into three groups according to the agglutination titers; > 2(10) (high titer group), 2(7)-2(9) (median), 2(5)-2(6) (low). All but one serum (44/45) in the high PHA titer group reacted in each of the three second screening ELISAs. Furthermore, 43 (97.7%) of the 44 sera contained HCV-RNA by PCR. In the median titer group, 11 of the 13 samples tested were positive by each of the three ELISAs, and 4 (36.4%) of the 11 showed reaction by PCR. On the other hand, all of the 38 sera tested in the low titer group were negative for HCV-RNA by PCR, and 24 of the 38 were also negative by each of the three ELISAs. Most of the low titer positive reactions in the 2nd-gen agglutination assay seemed to be false positive. In Okinawa Prefecture, the prevalence of anti-HCV among blood donors is much lower than in the rest of Japan (0.29% vs. 1.11%). Moreover, a significant proportion of these sera were low titer by the PHA assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case-control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17-0.92], 0.41 (95% CI 0.20-0.82), and 0.48 (95% CI 0.25-0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.

A human-mouse heterohybridoma (HMR0921) secreting human monoclonal IgG3, lambda antibody was produced from peripheral blood lymphocytes of a healthy blood donor with serum antibody to Jra, by EBV transformation and hybridization with mouse myeloma cell line P3X63Ag8.653. The reactivity of HMR0921 antibody was assessed by antiglobulin test with a panel of red cells including 14 different rare blood types. Only Jr(a-) red cells were negative. The strict specificity of this antibody to Jra antigen was further confirmed by absorption test with fluorescence flow cytometry. On screening of 28,744 blood donor samples by HMR0921 antibody, we detected 19 agglutination-negative samples, which were confirmed as Jr(a-) by conventional anti-Jra antisera. Therefore, our HMR0921 antibody is extremely useful for detecting rare Jr(a-) blood.

We assessed hepatitis C virus (HCV) infection in 99 asymptomatic blood donors positive using a first-generation HCV antibody assay. When tested with second-generation assays, 86 (87%) donors were reactive (group 1), 2 (2%) were indeterminate (group 2), and 11 (11%) were non-reactive (group 3). Viraemia was revealed by polymerase chain reaction in all group 1 cases. The 2 group 2 cases and 6 (55%) group 3 cases were also viraemic. Viraemia was confirmed by a branched DNA assay in the 2 group 2 cases and 4 (36%) group 3 cases. Serum HCV RNA levels were further studied using a competitive reverse transcription-polymerase chain reaction assay. All cases in groups 2 and 3 were low viraemic (range 10(4)-10(5.5) copies/ml) compared with the 9 group 1 cases examined (range 10(7)-10(9) copies/ml). No correlation was evident between viraemic levels and antibody cut-off index in the first-generation assay. These findings indicate the possibility that low levels of viraemia can occur in individuals non-reactive in second-generation HCV antibody assays.

In November 1989, Japanese Red Cross Blood Centres started screening for hepatitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61-80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2) and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with > or = 2(12) agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive.(ABSTRACT TRUNCATED AT 250 WORDS)

To develop a more dependable method of diagnosing hepatitis C, serum anti-hepatitis C virus (HCV) was examined by using a new assay (anti-HCV second generation). The results were compared with those of either the conventional assay (anti-HCV first generation) or HCV-RNA analysis. With the first generation assay, anti-HCV was detected in 69% of post-transfusion acute hepatitis (AH), 44% of sporadic AH, 50% of needlestick exposed AH, 72% of chronic hepatitis (CH), 77% of liver cirrhosis (LC) and 86% of hepatocellular carcinoma (HCC). These results were remarkably increased by using the second generation assay (92% in post-transfusion AH, 72% in sporadic AH, 100% in needlestick exposed AH, 96% in CH, 96% in LC and 97% in HCC). Furthermore, in the early stages of AH (from 1-5 weeks after onset), anti-HCV was not detected in all 18 patients by the first generation assay, but was found in 10 of them by using the second generation assay. The failure to detect anti-HCV with the first generation assay was mainly due to a lack of the core region coding peptide (C22-3) in this assay. In the AH-resolving group, anti-HCV second generation did not disappear, but the titre tended to be lower than that in the CH-developing group. Thus, the second generation assay for anti-HCV was considered to be a more useful tool for not only the diagnosis of hepatitis C but also for determining prognosis.

We surveyed the extent of rat virus (RV) infections in Japan and isolated new RV strains. The new strains were similar to the prototype RV strain in stability, morphology in electron microscopy and structural polypeptides. There were slight differences, however, in hemagglutination activity and the antigenicity.

A seroepidemiologic time-comparison study was conducted to evaluate changes in IgG antibody to varicella-zoster virus (VZV) and to determine VZV prevalence in Japan with randomly collected serum samples from two healthy Japanese populations: 1973 (n = 670) vs. 1984 (n = 677). Enzyme-linked immunosorbent assay (ELISA) was found to be superior to the immune adherence hemagglutination test (IAHA) especially for detecting seropositivity in adults. Serologic results showed essentially no significant difference between the 1973 and the 1984 age-specific prevalences; with the exception of a slightly lower prevalence in the 5-year-old age group in 1973 than that in 1984. In general, the age-specific prevalence was lowest in the 1-year-old group (mean 11%) and increased in a linear fashion until age 9 (mean 82.9%); prevalence continued to increase slowly after age 9 and plateaued at 100% for ages greater than or equal to 25-29.

A total of 142 seronegative volunteers were given one of the following rubella vaccines: Cendehill, HPV77. DE-5, RA27/3, or a new Japanese vaccine, To-336. To-336 vaccine produced a slightly higher geometric mean antibody titre (G.M.T.) (65.7) than did the HPV77. DE-5 (63.1) or RA27/3 vaccine (61.9) but the G.M.T. induced by Cendehill vaccine was much lower (39.3).Reactions, particularly joint symptoms, occurred least commonly after vaccination with To-336 vaccine. Joint symptoms occurred within seven days of menstruation in 30 out of 37 (81%) vaccines (P <0.01); their incidence was not related to oral contraception.Though there is evidence to suggest that Japanese virus strains may be non-teratogenic further data on the incidence of congenitally acquired infection in Japan must be collected before this conclusion can be supported on epidemiological grounds.

A frequency of positive hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) was determined among 2566 atomic bomb survivors in Hiroshima and Nagasaki, Japan during the two-year period 1975 to 1977. The frequency of positive HBsAg (79% of subjects remained persistently antigen positive) was significantly higher in those exposed to 100 rad or more than in the controls. This difference between exposure groups was more marked among the younger age groups. However, contrary to expectation, there was no difference between the dose groups in the distribution by high vs. low titers among the antigen-positive individuals. There was no difference between the two comparison groups in the occurrence of positive anti-HBs reactions (prevalence of hepatitis B virus). The above findings suggest that immune competence, using the prevalence of positive HBsAg as an index, is depressed in the high dose group, but further study, including follow-up of those with persistent positive HBsAg reactions, is called for. With respect to HBsAg subtypes, adr occurs with higher and adw with lower frequency in Nagasaki than in Hiroshima, corresponding to earlier reports for the Japan archipelago of reverse and complementary distributions of these two subtypes.

Clinical studies were conducted to evaluate the role of the house dust mite. Dermatophagoides pteronyssinus, as an allergen in children's asthma in Japan. Skin testing and Prausnitz-Küstner type skin testing showed good correlations between the allergenicity of house dust and the mite. A positive Prausnitz-Küstner type skin reaction to house dust was neutralized by a mite extract. Radioallergosorbent test showed good correlation between house dust and the mite (r=0.687). The mite exhibited in vitro inhibition of radioallergosorbent test to house dust. The inhalation provocation test resulted in an acute respiratory attack in one of the patients. These results suggest that the house dust mite is an important allergen in asthmatic children in Japan.

'Naturally occurring' anti-Kell (K1) was found in a Japanese male who has never received a transfusion. The antibody agglutinated K:1 cells suspended in saline at 4 and 22 degrees C as well as cells suspended in albumin and treated with proteolytic enzymes.

Hepatitis-Associated (Australia) Antigen (HAA) was detected in 13 (5.8%) of 223 patients with Down's syndrome and in 14 (3.7%) of 378 patients with other forms of mental retardation. The frequency of HAA was 2.4 per cent in 127 noninstitutionalized patients with Down's syndrome, and 10.4 per cent in 96 institutionalized patients. The frequency of HAA with Down's syndrome was lower on the average in Japan than in the United States or Germany. HAA was detected in one (1.3%) of 78 mothers of infants with Down's syndrome. Our study suggests that maternal exposure to HAA, as reflected by the presence of either HAA or anti-HAA, was not associated with the subsequent birth of an infant with Down's syndrome.

Sera collected from healthy adults and children were examined by the passive hemagglutination test for the presence of antibodies to exfoliatin A and B.

We report a new platelet antigen (Yuka) defined by the sera of 2 mothers whose babies developed alloimmune thrombocytopenia. These antiplatelet antibodies were IgG detected by Mixed Passive Hemagglutination (MPHA). In the study of two families, the Yuka antigen was found to be inherited as an autosomal dominant trait. The frequency of the Yuka phenotype in the Japanese population was estimated to be 1.7% (5/300).

A nationwide investigation on the incidence of anisakiasis over a period of 5 years from 1973 through to 1977 was conducted by questionaire sent to 851 main medical centers throughout Japan. The number of cases for all Japanese for a period of 5 years were 334 cases of gastric anisakiasis and 45 intestinal anisakiasis. We investigated both a random group of 3,108 inhabitants of Hokkaido and 42 anisakiasis patients using skin test, indirect hemagglutination test and measurement of serum IgE. We have demonstrated that the etiologic mechanism of acute anisakiasis involved anaphylactic reaction as well as Arthus reaction in the digestive tract.