The importance of accounting for testing and positivity in surveillance by time and place: an illustration from HIV surveillance in Japan.

The number of tests performed is an important surveillance indicator. We illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa, two prefectures with high HIV notification rates in Japan. Restricting to data reported from local public health centres and affiliate centres where testing data are accessible, we assessed HIV surveillance data during 2007-2014, based on the annual HIV notification rate (per 100 000 population), HIV testing rate (per 100 000 population) and proportion testing HIV-positive (positivity). Nationally, testing activity and positivity showed an inverse relationship; in 2008, the testing rate peaked, but positivity was lowest. While notification rates were higher for Tokyo (median = 0.98, range = 0.89-1.33) than Okinawa (median = 0.61, range = 0.42-1.09), Okinawa had slightly higher testing rates (median = 187, range = 158-274) relative to Tokyo (median = 172, range = 163-210). Positivity was substantially lower in Okinawa (median = 0.34%, range = 0.24-0.45%) compared with Tokyo (median = 0.57%, range = 0.46-0.67%). Relative to the national testing rate (median = 85, range = 80-115) and positivity (median = 0.34%, range = 0.28-0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa, all three indicators increased, providing a strong reason to be concerned as positivity increased despite more testing. Together with other information, accounting for testing and positivity improve interpretation of surveillance data to guide public health assessments.

Web survey-based selection of controls for epidemiological analyses of a multi-prefectural outbreak of enterohaemorrhagic Escherichia coli O157 in Japan associated with consumption of self-grilled beef hanging tender.

An outbreak of enterohaemorrhagic Escherichia coli O157 occurred in multiple prefectures of Japan in November 2009. We conducted two case-control studies with trace-back and trace-forward investigations to determine the source. The case definition was met by 21 individuals; 14 (66.7%) were hospitalised, but no haemolytic uraemic syndrome, acute encephalopathy or deaths occurred. Median age was 23 (range 12-48) years and 14 cases were male (66.7%). No significant associations with food were found in a case-control study by local public health centres, but our matched case-control study using Internet surveys found that beef hanging tender (or hanger steak), derived from the diaphragm of the cattle, was significantly associated with illness (odds ratio = 15.77; 95% confidence interval, 2.00-124.11). Pulsed-field gel electrophoresis analysis of isolates from patients and the suspected food showed five different patterns: two in faecal and food samples, and another three in patient faecal samples only, although there were epidemiological links to the meat consumed at the restaurants. Trace-back investigation implicated a common food processing company from outside Japan. Examination of the logistics of the meat processing company suggested that contamination did not occur in Japan. We concluded that the source of the outbreak was imported hanging tender. This investigation revealed that Internet surveys could be useful for outbreak investigations.

Prevention of secondary household transmission during Shiga toxin-producing Escherichia coli outbreaks.

Prevention of secondary household transmission of Shiga toxin-producing Escherichia coli (STEC) is important in outbreak settings. We examined factors contributing to secondary household transmission during STEC outbreaks in daycare centres in Japan. Suspected STEC outbreaks in daycare centres were identified by the National Epidemiological Surveillance of Infectious Diseases. Questionnaires were sent to local health centres that responded to outbreaks. Secondary household transmission rates were calculated, and factors affecting secondary household transmission rate were analysed by multilevel analysis. The secondary household transmission rates in 16 outbreaks ranged from 0% to 34·4% (median 4·4%). The highest rate (23·0%) was observed in siblings aged 6-9 years, and the infection rate was significantly higher for mothers than for fathers and grandparents (P < 0·05). Using multilevel analysis, the following variables were selected in the best model: information provided face-to-face (vs. letter or telephone) to families of children in daycare centres (at initial response), STEC type and lag time (days) between onset and providing information. Early response and hygiene education by visiting local health centre staff may be effective measures to prevent secondary household transmission in STEC outbreaks. Hygiene education should be emphasized for children aged 6-9 years, as well as for younger children.

Comparative study on the effectiveness of corticosteroid injections between trigger fingers with and without proximal interphalangeal joint flexion contracture.

UNLABELLED: Trigger fingers with proximal interphalangeal joint flexion contracture are suggested to have a poorer response to corticosteroid injection than those without contracture, though this has not been proven scientifically. We compared the clinical response to corticosteroid injection between trigger fingers with and without proximal interphalangeal joint contracture, and investigated the influence of the injection on the A1 pulley and flexor digitorum tendons using ultrasonography. One month after injection, pain was significantly reduced in the no contracture group, and 56% of trigger fingers with proximal interphalangeal joint contracture resolved. Before injection, relative thickening of the A1 pulley and flexor digitorum tendons, and a partial hypoechoic lesion of the flexor digitorum superficialis tendon were observed in the contracture group. One month after injection, the thickening of the tendons and the A1 pulley was reduced, but the partial hypoechoic lesion was still observed in significant numbers. We have demonstrated that the presence of a proximal interphalangeal joint contracture was associated with a reduced clinical response to corticosteroid injection, and we suggest that the pathologic change in the flexor digitorum superficialis tendon, represented by the partial hypoechoic lesion, contributed to corticosteroid injection resistance. LEVEL OF EVIDENCE: IV.

Increase in paratyphoid fever cases in Japanese travellers returning from Cambodia in 2013.

In 2013, an unusual increase of paratyphoid fever cases in travellers returning from Cambodia was reported in Japan. From December 2012 to September 2013, 18 cases of Salmonella Paratyphi A infection were identified. Microbiological analyses revealed that most isolates had the same clonal identity, although the epidemiological link between these cases remains unclear. It was inferred that the outbreak was caused by a common and persistent source in Cambodia that was likely to have continued during 2014. The information of surveillance and laboratory data from cases arising in travellers from countries with limited surveillance systems should be timely shared with the country of origin.

Use of quantitative intra-operative electrodiagnosis during partial ulnar nerve transfer to restore elbow flexion: the treatment of eight patients following a brachial plexus injury.

The transfer of part of the ulnar nerve to the musculocutaneous nerve, first described by Oberlin, can restore flexion of the elbow following brachial plexus injury. In this study we evaluated the additional benefits and effectiveness of quantitative electrodiagnosis to select a donor fascicle. Eight patients who had undergone transfer of a simple fascicle of the ulnar nerve to the motor branch of the musculocutaneous nerve were evaluated. In two early patients electrodiagnosis had not been used. In the remaining six patients, however, all fascicles of the ulnar nerve were separated and electrodiagnosis was performed after stimulation with a commercially available electromyographic system. In these procedures, recording electrodes were placed in flexor carpi ulnaris and the first dorsal interosseous. A single fascicle in the flexor carpi ulnaris in which a high amplitude had been recorded was selected as a donor and transferred to the musculocutaneous nerve. In the two patients who had not undergone electrodiagnosis, the recovery of biceps proved insufficient for normal use. Conversely, in the six patients in whom quantitative electrodiagnosis was used, elbow flexion recovered to an M4 level. Quantitative intra-operative electrodiagnosis is an effective method of selecting a favourable donor fascicle during the Oberlin procedure. Moreover, fascicles showing a high-amplitude in reading flexor carpi ulnaris are donor nerves that can restore normal elbow flexion without intrinsic loss.

Assessment of secondary attack rate and effectiveness of antiviral prophylaxis among household contacts in an influenza A(H1N1)v outbreak in Kobe, Japan, May-June 2009.

This report describes the assessment of the secondary attack rate (SAR) and the effectiveness of post-exposure antiviral prophylaxis among household contacts in the first domestic outbreak of a novel influenza A(H1N1)v between mid-May and early June 2009 in Kobe city, Japan. Of the 293 subjects, 14 (4.8%) household contacts met the case definition and most secondary cases were probably infected around the time of symptom onset date of the respective index case. The SAR among household contacts who did not receive prophylaxis was 7.6%, similar to the rate of seasonal influenza, and the attack rate in siblings was significantly higher than that in parents. We conclude that it is important to establish routine infection control measures for households in order to prevent the spread of the virus among household contacts and, possibly, to the community. We could not conclude whether antiviral prophylaxis was effective or not. However, among close contacts with underlying disease who received prophylaxis, nobody developed a severe form of the disease.

Epidemiology of influenza A(H1N1)v virus infection in Japan, May-June 2009.

Between 9 May and 4 June 2009, a total of 401 laboratory-confirmed cases of influenza A(H1N1)v virus were reported in Japan, from 16 of the 47 Japanese prefectures. The two areas most affected were Osaka prefecture and Kobe city where outbreaks in high schools occurred leading to school closures. To date all cases have had symptoms consistent with seasonal influenza and no severe or fatal cases have been reported.

The dependence of low-energy electron attachment to CF3Br on electron and vibrational energy.

In a joint experimental and theoretical effort, we have studied dissociative electron attachment (DEA) to the CF3Br molecule at electron energies below 2 eV. Using two variants of the laser photoelectron attachment method with a thermal gas target (T(G) = 300 K), we measured the energy dependent yield for Br- formation over the range E = 3-1200 meV with resolutions of about 3 meV (E < 200 meV) and 35 meV. At the onsets for excitation of one and two quanta for the C-Br stretching mode nu3, downward cusps are detected. With reference to the recommended thermal (300 K) attachment rate coefficient k(A)(CF3Br) = 1.4 x 10(-8) cm3 s(-1), absolute cross sections have been determined for Br- formation. In addition, we studied Br- and (CF3Br)Br- formations with a seeded supersonic target beam (10% CF3Br in helium carrier gas, with a stagnation pressure of 1-4 bars and nozzle temperatures of 300 and 600 K) and found prominent structure in the anion yields due to cluster formation. Using the microwave pulse radiolysis swarm technique, allowing for controlled variation of the electron temperature by microwave heating, we studied the dependence of the absolute DEA rate coefficient on the mean electron energy E over the range of 0.04-2 eV at gas temperatures T(G) ranging from 173 to 600 K. For comparison with the experimental results, semiempirical resonance R-matrix calculations have been carried out. The input for the theory includes the known energetic and structural parameters of the neutral molecule and its anion; the parameters of the resonant anion curves are chosen with reference to the known thermal rate coefficient for the DEA process. For the gas temperature T(G) = 300 K, good overall agreement of the theoretical DEA cross section with the experimental results is observed; moreover, rate coefficients for Br- formation due to Rydberg electron transfer, calculated with both the experimental and the theoretical DEA cross sections, are found to agree with the previously reported absolute experimental values. At T(G) = 300 K, satisfactory agreement is also found between the calculated and experimental attachment rate coefficients for mean electron energies E = 0.04-2 eV. The strong increase of the measured rate coefficients with rising gas temperature, however, could be only partially recovered by the R-matrix results. The differences may result from the influence of thermal excitations of other vibrational modes not included in the theory.

Evaluation of a mass influenza vaccination campaign.

Kawaura, a rural town in Kumamoto Prefecture, Japan, population approximately 6,800, started a mass influenza vaccination campaign in the 1999-2000 season for all residents > or = 3 years of age. The town provided free vaccinations to children < or = 13 years and the elderly > or = 65 years. Only 900 yen (US$8.80) was charged to the other residents for two vaccinations. In the 1999-2000 season, a total of 5,563 doses of vaccine were administered to 2,952 residents. Over 90% of the vaccinees received two doses. The program resulted in a vaccination rate of 43% of all residents. The vaccination rates for females and males were 40.7% and 36.8%, and for those of 3-14 years, 15-64 years, and > or = 65 years population were 75%, 31%, and 55%, respectively. The town spent a total of 5.78 million yen (US$56,700) for the campaign. The per-shot cost was estimated as 1,683 yen (US$16.50). From December 1999 through March 2000, a total of 233 town residents (15-101 years old, median 72) were admitted to the town hospital. Of the 233 inpatients, 22 (66-98 years old, median 78) developed respiratory illness, with 4 fatal outcomes. Of these 22 cases, 3 had been vaccinated twice, while 19 had not been vaccinated at all. The relative risk of vaccinees' hospitalization due to respiratory illness decreased to 0.13 compared with that of non-vaccinees (3/1,203 versus 19/1,003, vaccine efficacy = 0.87). Likewise, the relative risk of vaccinees death due to respiratory illness decreased to 0.28 compared with that of non-vaccinees (1/1,203 versus 3/1,003). The results of the Kawaura town's initiative should be helpful for better modeling of mass influenza vaccination campaigns.

Climbazole is a new potent inducer of rat hepatic cytochrome P450.

We examined the effect of climbazole on the induction of rat hepatic microsomal cytochrome P450 (P450), and compared the induction potency with other N-substituted azole drugs such as clorimazole. We found that climbazole is found to be a potent inducer of rat hepatic microsomal P450 as clorimazole. Induced level of P450 by climbazole was almost similar in extent to clorimazole when compared with other imidazole drugs in a dose- and time-dependent manner. Parallel to the increase in P450, climbazole increased aminopyrine and erythromycin N-demethylase, ethoxycoumarin O-deethylase, and androstenedione 16 beta- and 15 alpha/6 beta hydroxylase activities; however, clorimazole did not induce aminopyrine N-demethylase activity irrespective of its marked increase in P450 content. Immunoblot analyses revealed that climbazole induced CYP2B1, 3A2 and 4A1. The present findings indicate that climbazole is a new potent inducer of hepatic microsomal P450 and drug-metabolizing enzymes like clorimazole, but it may have some differential mechanism(s) for these enzymes' induction in rat liver.

[Relationship between changes in skin lipids by ultraviolet exposure and the cell toxicity].

The oxidative decomposition of skin lipids by UV exposure and its cell toxicity were studied in vivo and in vitro, using guinea pigs, to investigate the role of oxidative damage in cell membranes and mitochondria in nuclear genome DNA damage resulting in skin cell death by ultraviolet (UV) exposure. Two new methods were developed for this research: selective methylation by trimethylsilyldiazomethane (TMSCHN2) of free fatty acids in crude skin lipids for gas chromatography-mass spectrometry (GC-MS) analysis, and the improvement of the thiobarbituric acid (TBA) reaction for lipid peroxide analysis, which was obtained by adding 0.01% BHT and 1 mM EDTA, an antioxidant additive, into the reaction system described by Ohkawa. The following findings were noted: 1. Using an optical microscope, the infiltration of inflammatory cells such as neutrophils, lymphocytes and monocytes was noted after skin tissue was exposed to UV. 2. The increase of lipid peroxide in exposed areas was small. In the epidermis the increase was about 2 times higher than the non-exposed areas. 3. The fragments of lipid were generated in accordance with the increase of free fatty acids (C16:0, C18:1,:2, C18:0) in the surface of the exposed skin by GC-MS precise assay, and the level of 7-dehydrocholesterol was decreased. 4. The skin homogenate received peroxidation by ultraviolet more easily than living skin, and its peroxidation was inhibited with fat-soluble antioxidative agents such as flavonoids, BHT, BHA, and vitamin E and the metal chelating agent such as Fenton reaction inhibitor as expected; however, it was promoted by water soluble antioxidative agents such as glutathione and vitamin C, which are useful to the human body. 5. Steroids and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and aspirin, had no inhibitory effect on lipid peroxidation by ultraviolet as properties of chemicals.

Cell proliferation and death of growth plate chondrocyte caused by ischemia and reperfusion.

The aim of this study was to assess the short-term response of cell kinetics of growth plate chondrocytes under conditions of warm ischemia and reperfusion. To understand the time-course changes that occur after reperfusion, 0 and 6 h of warm ischemia was produced in the right hindlimb of 35-day-old Wistar rats by isolating the vascular pedicle occlusion. The animals were killed at 12, 24, 48, or 96 h postoperatively after reperfusion, and proximal tibia growth plates were investigated. To investigate the effect of the ischemia period on the kinetics of growth plate chondrocytes, 0, 2, 4, 6, and 8 h of ischemia was induced, and the animals were killed for evaluation 24 h after reperfusion. For evaluation of cell kinetics, BrdU was used to observe the changes in cell proliferation of growth plate chondrocytes, and TUNEL was used to estimate the changes in rate of cell death. In the time-course study, both 0 and 6 h of ischemia increased cell proliferation at 12 and 24 h after reperfusion; however, at 48 and 96 h, the proliferation rate was not further increased. At 12 and 24 h postoperatively, 6 h of ischemia increased chondrocyte proliferation more than 0 h of ischemia with significant differences; 6 h of ischemia led to an increased cell death rate at 12, 24, and 48 h postoperatively, whereas 0 h of ischemia did not affect the cell death rate. In the ischemia time-dependent study, the cell proliferation rate induced by 4 h of ischemia was highest in all controlled periods of ischemia. Cell death rate increased gradually with increases in ischemia time 24 h after reperfusion. This experiment showed that ischemic damage causes short-term postoperative changes in the kinetics of growth plate chondrocytes.