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.

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.

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.

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.

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.

Three Japanese encephalitis cases in Okinawa, Japan, 1991.

Since 1974, no Japanese encephalitis (JE) case had been reported on Okinawa island in either Okinawan people or US servicemen. In 1991, three US marines stationed on Okinawa island developed encephalitis symptoms. Neutralization (N) test and IgM-capture ELISA were carried out on the serial samples of serum and cerebrospinal fluid (CSF) taken from the patients. In each patient N test on both serum and CSF samples gave a significant rise in JE antibody titer in the comparison between the acute and convalescent phases, indicating that all the cases were infected with JE virus. The IgM-capture ELISA also showed a significant rise of antibody titer of the serum and CSF samples in the convalescent phase in patients 2 and 3, while in patient 1 a significant rise in IgM antibody was observed in the serum sample, but not in the CSF sample. None of the patients had been administered JE vaccine. This report underscores the importance of JE vaccination.

[Viral infection related to the appearance of acute bacterial respiratory tract infections].

To investigate what viruses are related to acute bacterial respiratory tract infections, we prospectively evaluated 113 cases with respiratory tract infections (always accompanying by purulent sputum) experienced between July 1998 and March 2000. Acute viral infections were detected in 25 cases (22%); 10 cases of influenza A virus and 6 cases of respiratory syncytial (RS) virus. The epidemiology of the influenza A virus and RS virus was mainly identified as from December to February in both winter seasons. A bacteriological examination of sputum cultures isolated 12 cases of Streptococcus pneumoniae and 10 cases of Haemophilus influenzae during the same periods and mixed infections of both viruses and bacteria were recognised in 16 cases (14%). These results suggest a significantly high percentage of mixed infections of both viruses and bacteria. However, it was unknown whether the patients with acute bacterial respiratory infections had been infected with viruses prior to the bacterial infections. The frequency of appearance of respiratory tract infections tended to increase with the seasonale epidemiology of viral infections.

[A case with infectious mononucleosis-like syndrome caused by human herpes virus-6 infection].

A 26-year-old female was admitted because of multiple fractures in lower extremities. While in the hospital, she developed a high fever and generalized skin eruption. Physical examination revealed bilateral cervical lymphadenopathy and mild hepatosplenomegaly. The white cell count was 11,200 with 11% atypical lymphocytes. Serum GOT, GPT, LDH were markedly elevated. Infectious mononucleosis was suspected, but the serological test for EB virus did not show evidence of acute EB virus infection. Anti-HSV, CMV, hepatitis A virus antibody titers also did not show significant change during the coarse. The serological test for HHV-6 only showed increased titer of IgM and IgG antibodies. Rapidly elevated IgG antibody titer was indicative of reactivation of HHV-6. So, she was diagnosed as mononucleosis-like syndrome caused by HHV-6, probably reactivated infection. Her symptoms gradually disappeared during a month.

[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.

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.