Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.

ABSTRACT' In a longitudinal study, of hayperendemic, malaria in a vilge in eastern Thailand (from October IMS to No, ember 19S7). mian-biting anophehine mosqitres m ere col. lected for 16 moin-mghts, per month in 22 of 26 mo. Mosquitoes %iere separated according -to collection sites (inner, central, more popualated, Outer, peripheral, more forested). biting p eriod. and parity, and then they u erc tested for sporozoite antigen using an enayme-hrikedC\ immunosorbent assay (ELIS -1). Abundance of Anopheles dimu Pe) ton & I larrison masgreater__ in outer than inner sdilage sitc. . fill bimodal peaks in the pustmonsoon COctnlsr-Xosesn=her) Tw and early rainy (April orMay) seasons. Parity rates at both sites siere high in postnsonsonJ. seasons (f about TM%). lose in cool dry (December-January. <56%) and monsoon (uneSeptember, <60%) seasons, and variable in other seasons. Of 1.861 An dials collected. 16 0-(09%) miere positive for Plaooocllm falkiparum (PF) and aine (04%) for P. rnve (Mg. uieas of &86 An. rnnlas.ir one (0M3) and three (0.8%) %iere PF. and PV-pocitis, respectively. Entomological inoculiatinn rates (EIR) siere higher in outer (9 PP -091. P'V S 0 31) than inner % dlage sites (f =0 01 for PP and PV). The EiPI of PP appeared bimodala high it, postmonsooin (October-.Nor ember) and early rainy (April or May) seasons, lorw inmomsoon seasons. and variable in other seasons. The rectorial rapa~city of An. dimus -sca higher than that of An. minimus. indicating that the tooa species %ere primary and secondary rectors. respectively. Huoman malaria prevalence data indicated that transmission depended greatly on the higher year-round sector abundance in outer than in inner sillag., sites. 1990), although other s ector species also occur tltereWe studied) the same vtllage from October 1983 (Prasittisuk, 1985). Originally considered a species to Nosmnbec 19S7. Our objectis vscre to deterof hieavily forested mountainous regions. An. dlius minte possible chianges ii moalaria tratsmiission dyhas adapted to peripheral areas wehere natural for-natnics, ss ith emphases ok mnalarta vector incrirmcats mrer replaced with orchards, tea, coffee, and ination. locality of transmission, malaria rubber plantations (Rosenberg et al, 1999). In prevalcnice-incidcnce, vector infection indices. Cliantaburt Province, eastern Thailand, Rosenberg seasonal and diurnal abundance, and ilia diras ct al. (1990) conducted a study from IM8 to 1985 larval breeding habitats in Ban Plihuang, a village where nmalaria was lty. perendemric, dreribing in detail the epidemiology of malaria transtmission, Only Art. diris wias in.Materials and Methodsi erimitiated; 765, of infected mosquitoes contained Plasmiodirumt .facipauim Welch (Pr) spsorooites, Study Sites.lDetailsof tlielocation dctnographiy, the remainder being infected with P. rlusx Grasst dsscllings. terrain, vegetative compositiotn, and & rcletti (P'V). Transmsissiotn \%as focal ceet in the economny Of thle village. Ban Plluatig, %%ere

An unexpected outbreak of Japanese encephalitis (JE) in Bangkok in 1985 led us to investigate the vector ecology of urban JE from January 1986 to June 1987 at three suburban sites that displayed a wide range of factors imputed to influence JE transmission. Culex tritaeniorhynchus Giles and Cx. gelidus Theobald, suspected vectors, comprised 71-96% of all mosquitoes collected by CO2-baited CDC traps at the three sites. Mean of mosquito abundance per two trap-nights per month ranged from 28 to 5,728 mosquitoes at the sites of lowest and highest abundance, respectively. Cx. tritaeniorhynchus yielded more JE isolates (n = 16) than Cx. gelidus (n = 7), but the minimum infection rates of the two species (number of JE isolates per 1,000 mosquitoes tested; MIR, 0.17 and 0.47, respectively) were comparable and covaried with vector abundance. Moreover, the proportion of sentinel pigs that had JE antibodies generally increased proportionately with vector abundance at the sites. Vector abundance was high in monsoon (May-October), moderate in transition (March-April and November-December), and low in dry (January-February) seasons. Mosquitoes collected in monsoon seasons yielded 96% of the JE isolates, whereas 4 and 0% of the isolates were obtained from transition and dry season collections, respectively. More pigs seroconverted in monsoon and transition seasons than in dry seasons. Indices of JE transmission activity (vector abundance, pig seroconversions, and MIRs) increased proportionately with rainfall. Despite higher indices at the site of greatest vector abundance than elsewhere, the risk of human infection appeared greatest at the site with moderate vector abundance because of its greatest human population density.