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.

Association between meteorological factors and reported cases of hand, foot, and mouth disease from 2000 to 2015 in Japan.

The purpose of this study was to clarify the association between hand, foot, and mouth disease (HFMD) epidemics and meteorological conditions. We used HFMD surveillance data of all 47 prefectures in Japan from January 2000 to December 2015. Spectral analysis was performed using the maximum entropy method (MEM) for temperature-, relative humidity-, and total rainfall-dependent incidence data. Using MEM-estimated periods, long-term oscillatory trends were calculated using the least squares fitting (LSF) method. The temperature and relative humidity thresholds of HFMD data were estimated from the LSF curves. The average temperature data indicated a lower threshold at 12 °C and a higher threshold at 30 °C for risk of HFMD infection. Maximum and minimum temperature data indicated a lower threshold at 6 °C and a higher threshold at 35 °C, suggesting a need for HFMD control measures at temperatures between 6 and 35 °C. Based on our findings, we recommend the use of maximum and minimum temperatures rather than the average temperature, to estimate the temperature threshold of HFMD infections. The results obtained might aid in the prediction of epidemics and preparation for the effect of climatic changes on HFMD epidemiology.

Morphological characters and occurrence patterns of juveniles of two estuarine gobies, Acentrogobius kranjiensis and Acentrogobius malayanus, verified by molecular identification.

Juveniles of two Acentrogobius species collected in a mangrove estuary in Sikao Creek, southern Thailand, were identified by morphological and molecular methods. A total of 1315 Acentrogobius specimens were collected and grouped into types A (n = 1107, 4.4-12.0 mm standard length, L(S)) (melanophore absent or indistinct on posterodorsal contour of caudal peduncle; two rows of melanophore blotches on lateral midline) and B (n = 208, 4.8-12.6 mm L(S)) (distinct melanophore on posterodorsal contour of caudal peduncle; a single row of melanophore blotches on lateral midline). Based on the reverse series method, the melanophore patterns of larger juveniles were linked with the smallest specimens possessing adult characters. The homogeneities of mitochondrial cytochrome b region sequences between the two juvenile types and adult Acentrogobius species collected in the study area indicated type A to be A. kranjiensis (homogeneity between type A and A. kranjiensis: 99.3-100%), and type B to be A. malayanus (homogeneity between latter 98.1 and 99.7%). No Acentrogobius juveniles were collected from the surf zone outside the creek mouth, both species apparently spending most of their life histories within the estuarine habitat. During their pelagic phase, A. kranjiensis and A. malayanus dispersed in the upper, middle and lower reaches of the creek. On the other hand, occurrence patterns during the benthic phase of A. kranjiensis and A. malayanus differed, the former showing upstream movement and the latter downstream movement with growth. These results emphasize the necessity of analysing early fish life histories at the species level, and the collaboration between morphological and molecular methods should prove valuable in accurately identifying of larvae and juveniles.

[Research and development of beraprost sodium, a new stable PGI2 analogue].

A novel prostaglandin I2 (PGI2) analogue, beraprost sodium, is the first launched drug as an orally active PGI2. PGI2 was discovered in 1976, and has attracted much attention as a medicine for cardiovascular diseases such as strokes and heart attacks because of its potent antiplatelet and vasodilating effect. However, PGI2 is extremely unstable for the use as practical medicines. Thus, stable PGI2 analogues have been explored by a large number of researchers in the world. Just after the discovery of PGI2, we started a research on chemically and metabolically stable PGI2 derivatives with longer duration of action and less adverse reaction. We invented a novel class of stable PGI2, 5,6,7-trinor-4,8-inter-m-phenylenePGI2 analogues that have the phenol moiety instead of the enolether moiety of PGI2. Further efforts were devoted to enhance the efficacy of the PGI2 analogues and to eliminate their side effects, and an orally active analogue, beraprost sodium, was obtained. In order to establish the synthetic route of beraprost sodium, various novel processes were invented, including ortho-selective metalation of bromoanisoles by means of Grignard reagents, copper-catalyzed SN2' cyclization to prepare cyclopenta[b]benzofuran, and stereo-selective elongation of the omega-side chain by Prins reaction. Beraprost sodium inhibit platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen and arachidonic acid. It was shown that the drug has a potent antiplatelet effect both in vitro and ex vivo in human and several animal species. In clinical studies, beraprost sodium exerted a marked effect to improve arteriosclerosis obliterans. No serious adverse effects related with the drug have been reported. It was highly evaluated as an orally active PGI2 by pharmaceutical companies overseas as well, and now clinical trials are under way in U.S.A. and Europe.