The United States Department of Health and Human Services (DHHS) plays a key role in biodefense, which accounts for almost 80％of the U.S. civilian biodefense budget, which itself has amount to over ¥500 billion a year since the 2001 anthrax mailings and has involved programs based on the HSPD-10 “Biodefense for the 21st Century”. To promote R&D on medical countermeasures, the DHHS has invested in basic research and ensuring market, and closely communicated with stakeholders to overcome R&D bottlenecks, fulfill pipelines and increase the number of players in the market. Japan must consider infectious disease research as part of national security and implement ways to make basic research pay off in the form of products. Japan must also design ways to develop and deploy medical countermeasures against terrorism by bringing government agencies and private developers closer together and collaborating internationally in the fields of biological agents and others involving nuclear, radiological, and chemical disasters.

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The wide spread use of Diphteria-Pertussis-Tetanus (DPT) vaccination has made pertussis rare among infants, but reports have noted the rise in adult pertussis in the United States and in Japan. Adult pertussis vaccination in the US has been approved and is becoming widely disseminated, but not in Japan, where only way to prevent adult pertussis is vaccination using infantile DPT vaccine. Reducing the Japanese DPT vaccine dose to 0.2mL in the hope of minimizing adverse events, we studied its efficacy and safety. We nearly equalized diphteria and tetanus antigenic titers to a 0.1mL dose of diphteria-tetanus bivalent vaccine, -the booster dose regularly used in Japan- containing anti-FHA antibody titers similar to effective pertussis vaccines approved in the US. Subjects were 30 healthy volunteers who gave oral and written consent, testing anti-PT and anti-FHA antibody titers 4 weeks after vaccination. Of the 30, 29 showed a titer increase. Anti-tetanus toxoid titers tested showed increased titers in 28 subjects, the remaining 2 assumed to not have undergone previous tetanus vaccination. The incidence of local adverse effects was higher in adults than in children, but none were serious. A Japanese DPT vaccine dose of 0.2mL thus proved effective against pertussis in adults.

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Objective : To identify specific infectious diseases about which the Japanese public should be informed. Materials and Methods : A Delphi survey was conducted, recruiting 26 physicians who are engaged in clinical practice of infectious diseases and working at designated medical institutions of infectious diseases in Japan. Results : Following HIV/AIDS (first ranked), tuberculosis (second) and influenza (third), 24 diseases in total were identified based on “knowledge, awareness and behavior of inhabitants ”or “social and clinico epidemiological circumstances”. Scores for the top three ranked diseases were more than two-folds of those for following diseases. Among the top 10 ranked diseases, 9 were in common with the previous survey result among public health physicians and veterinarians working for governmental agencies. Discussion : Our findings of scores for specific diseases most likely reflect an importance of performing preventions and early diagnoses of severe diseases and promoting prophylaxis for travelersʼdiseases which tend to be factors for prioritizing infectious diseases among clinicians. The top-scored diseases among clinicians were consistent with those among public health officers, indicating the critical need to inform the public about these diseases. Nevertheless, both clinicians and public health experts have already attempted to promote preventions and/or treatment for these diseases in the previous time, and thus, the previous experience must be critically reviewed and reconsidered for improvements. In future, the similar surveys to ours should target specific subjects of experts and investigate more specific types of infectious diseases. Following such an expert survey, concrete action plans to inform the public about prioritized diseases are also called for.

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Throat swab specimens collected from 439 patients with influenza-like symptoms visiting a clinic in the 2004-2005 influenza season were subjected to cell culture virus isolation and viral antigen detection using a rapid diagnostic kit, QuickVue Rapid SP influ (Quidel Corporation, San Diego, CA, U.S.A.). The sensitivity and specificity of diagnostic kit results were analyzed based on cell culture results, considered the diagnostic standard. Kit sensitivity was 87.8％(72/82) and specificity 90.2％(322/357) for type A influenza, and 80.4％(176/219) and 95.0％(209/220) for type B influenza, roughly comparable to results reported so far for nasopharyngeal swabs and/or nasal aspirates. Sensitivity and specificity calculated separately dividing patient age but no significant difference was seen. The antigen-detection kit thus appears clinically useful in diagnosing influenza, provided that is collected and processed properly.

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In 2004, a Japanese-government-supported research group recommended that women without rubella antibody or with low titers /1 : 16 of HI antibody should be vaccinated to decrease the risk of congenital rubella syndrome. We compared HI antibody titer with EIA-IgG levels in 520 college students with /1 : 64,HI antibody measuring rubella antibodies in the same specimen using HI and EIA assay kits from Denka Seiken Co. (Japan) and Dade Behring Co. (Germany). The positive predictive value of the EIA assay using the kit from Denka Seiken Co. was 99.8％and the negative predictive value 91.3％, respectively, compared to 97.9％(positive /15IU/mL), 98.1％(positive /10IU/mL), and 93.4％, using the kit from Dade Behring Co.. Between HI titers and EIA-IgG measured with the Denka kit, the coefficient index was 0.715 (p＜0.0001). Between those measured with the Dade kit, the coefficient index was 0.610 (p＜0.0001). Between EIA-IgG levels measured using the two kits, the coefficient index was 0.753 (p＜0.0001). The HI value of 1 : 16 corresponds approximately to 9.0 with the kit (positive /4.0) from Denka, and to 30IU/mL with the kit from Dade. EIA-IgG levels /10IU/mL are considered globally as protective antibody titers, meaning that the Japanese recommendation of /1 : 16 for vaccination is too loose. Japanese EIA kit values for the rubella antibody should also be expressed in IU/mL using the global standard.

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As part of medical risk management in a long-term stay facility for the elderly, we introduced probiotic fermented milk containing Lactobacillus casei strain Shirota (LcS-fermented milk) in an open case-control study of its effect of (1 bottle a day) on winter-time norovirus gastroenteritis. During the 1 month from December 1 to 31, 2006, norovirus gastroenteritis occurred in 21 (55％) of 38 cases in the nonmilk group, and in 27 (64％) of 39 cases in the milk group, showing no statistically significant difference. The mean duration of ＞37℃fever after disease onset, however, was 2.9±2.3 days in the nonmilk group and 1.5±1.7 days in the milk group, showing significant shortening (p＜0.05). The duration of ＞38℃fever after disease onset also tended to be shorter. No significant differences were seen in age, gender, days of antipyretic use, or stool-free days. These results suggested that continuous intake of LcS-fermented milk could shorten fever duration in elderly long-term rest home residents although it probably did not prevent noroviral gastroenteritis onset.

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We examined water from 182 non-circulating hot spring bathing facilities in Japan for possible Legionella occurrence from June 2005 to December 2006, finding Legionella-positive cultures in 119 (29.5％) of 403 samples. Legionellae occurrence was most prevalent in bathtub water (39.4％), followed by storage tank water (23.8％), water from faucets at the bathtub edge (22.3％), and source-spring water (8.3％), indicating no statistically significant difference, in the number of legionellae, having an overall mean of 66 CFU/100mL. The maximum number of legionellae in water increased as water was sampled downstream : 180 CFU/100mL from source spring, 670 from storage tanks, 4,000 from inlet faucets, and 6,800 from bathtubs. The majority 85.7％- of isolated species were identified as L. pneumophila : L. pneumophila serogroup (SG) 1 in 22％, SG 5 in 21％, and SG 6 in 22％of positive samples. Multivariate logistic regression models used to determine the characteristics of facilities and sanitary management associated with Legionella contamination indicated that legionellae was prevalent in bathtub water under conditions where it was isolated from inlet faucet/pouring gate water (odds ratio [OR]＝6.98, 95％confidence interval [CI]＝2.14 to 22.8). Risk of occurrence was also high when the bathtub volume exceeded 5m³ (OR＝2.74, 95％CI＝1.28 to 5.89). Legionellae occurrence was significantly reduced when the bathing water pH was lower than 6.0 (OR＝0.12, 95％CI＝0.02 to 0.63). Similarly, occurrence was rare in inlet faucet water or the upper part of the plumbing system for which pH was lower than 6.0 (OR＝0.06, 95％CI＝0.01 to 0.48), and when the water temperature was maintained at 55℃or more (OR＝0.10, 95％CI＝0.01 to 0.77). We also examined the occurrence of amoeba, Mycobacterium spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus in water samples.

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Human parvovirus B19 infection in adults features clinical symptoms and laboratory abnormal findings unlike those in children commonly associated with cheek rash. We diagnosed 15 adult cases based on the positive increase in anti-parvovirus B19 IgM antibody (8.89±7.86 mean±SD, enzyme immunoassay (EIA)). Antibody titer was measured in 78 patients clinically showing fever, edema, exanthema, arthralgia, and myalgia among 11,040 outpatients first visiting the hospital from January 2005 to December 2007. Based on clinical and laboratory findings for these 15 cases, we recommended that physicians taking anti-parvovirus B19 antibody blood samples note whether (1) the level of C reactive protein is negative or low and without leucocytosis ; (2) a miliary rash is observed in short duration (rarely facial) ; (3) arthralgia and/or myalgia is present in the extremities (sometimes asymmetrical) ; (4) edema is present in the extremities, especially finger, ankle, or sole of the foot ; (5) contact has been made with ill children ; (6) flu-like symptoms occur such as fatigue, headache, or fever ; and (7) normo- or hypocomplementemia and/or antinuclear antibody is positive. Patients who fullfill requirement (1) plus at least three of requirements (2) through (7) should have a blood sample taken. We retrospectively studied 78 cases using these requirements, finding their sensitivity to be 100％(15/15), specificity to be 88.9％(56/63), positive predictive value to be 68.1％(15/22) and negative predictive value to be 100％(56/56). These requirements are thus useful in selecting patients for measuring antibody titer and definitively diagnosing severe or persistent parvovirus B19 infection occationally observed in adults.

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As the most common cause of neonatal sepsis, Lancefield Group B Streptococcus (GBS) must be diagnosed as early as possible in pregnant women is prevent neonatal infection. A selective enrichment broth medium has been widely recommended to optimally recover GBS from genital and anorectal samples. To establish a culture suitable for screening vaginal swab specimens, we compared subcultures of three selective enrichment media to direct culture on agar medium. Vaginal swab samples were inoculated di rectly onto 5％sheep blood agar and into New Granada medium (Eiken), Lim broth (Becton, Dickinson, and Company), and Todd Hewitt broth with gentamicin and nalidixic acid (Becton, Dickinson, and Company,Todd). Of the 288 specimens tested, GBS was recovered from 43 samples (14.9％) on direct agar media, with 82 (28.5％), positive on New Granada medium subculture, 67 (23.3％) on Lim broth subculture, and 61 (21.2％) on Todd, subculture. These results demonstrates that selective enrichment broth media provides more superior sensitivity than direct agar media for detection of GBS colonization in vaginal specimens, underscoring the usefulness of selective enrichment broth media in GBS screening for vaginal swabs in pregnant woman.

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A 55-year-old man admitted on April 1, 2008, for sudden abdominal pain onset whose laboratory data demonstrated apparent inflammation and whose computed tomography (CT) results showed free air and ascites underwent emergency surgery. An ascetic fluid sample submitted for bacteriological examination yielded Streptococcus gallolyticus subsp. pasteurianus, Escherichia coli, Citrobacter freundii, andBacteroides thetaiotaomicron. He was treated for 6 days with flomoxef (FMOX ; 3g/day) and recovered, being discharged on hospital day 17. This is, to our knowledge, the first case reported in Japan of bacterial peritonitis due to S. gallolyticus subsp. pasteurianus.

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A 32-year-old Japanese woman admitted November 1 for a 4-day fever and who had traveled in India October 14-22 was found to have no abnormal findings except for fever and luekocytopenia and thrombocytopenia. Negative rapid-test anti-dengue virus IgM antibody findings, however, became positive on hospital 2, with hemophagocytic cells found in the bone marrow, yielding a definitive diagnosis of dengue fever with viral-associated hemophagocytic syndrome. Some such cases with hemophagocytic syndrome have been reported in patients with sever dengue fever, but the rarity of the need for bone marrow examination means that it is unknown whether hemophagocytic syndrome occurs in mild dengue fever or whether our case was unusual.

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