Trends in Flavivirus Infections in Japan.Although Japanese encephalitis Japanese Encephalitis Definition Japanese encephalitis is an infection of the brain caused by a virus. The virus is transmitted to humans by mosquitoes. has declined as an important cause of illness and death in Japan, infection with other flaviviruses has become a public health concern. Recently, reports of imported dengue dengue or breakbone fever or dandy fever Infectious, disabling mosquito-borne fever. Other symptoms include extreme joint pain and stiffness, intense pain behind the eyes, a return of fever after brief pause, and a characteristic rash. cases, as well as isolations of tick-borne encephalitis virus tick-borne encephalitis virus n. An arbovirus of the genus Flavivirus that occurs in two subtypes, Central European and Eastern, causing two forms of encephalitis; it is transmitted by ticks. , have increased. The family Flaviviridae consists of approximately 70 viruses, nearly 40 of which cause human disease (1). Japanese encephalitis virus (JEV JEV Jesuit European Volunteers JEV Joinville Eau Vive (France) ) was an important cause of illness and death in Japan for many years, with [is greater than] 1,000 Japanese encephalitis (JE) cases reported annually in the late 1960s. The number of JE cases has decreased dramatically, and fewer than 10 cases have been reported annually since 1992 (2). Infection by other flaviviruses, including an increase in imported dengue cases and isolations of tick-borne encephalitis encephalitis (ĕnsĕf'əlī`təs), general term used to describe a diffuse inflammation of the brain and spinal cord, usually of viral origin, often transmitted by mosquitoes, in contrast to a bacterial infection of the meninges (TBE) virus, is becoming a public health threat. Imported Dengue Cases Dengue viruses dengue virus n. A virus of the genus Flavivirus that is the cause of dengue. are transmitted by infected mosquitoes, mainly Aedes aegypti and A. albopictus (3,4). The clinical manifestations of dengue virus infections range from asymptomatic infection to dengue fever dengue fever (dĕng`gē, –gā), acute infectious disease caused by four closely related viruses and transmitted by the bite of the Aedes mosquito; it is also known as breakbone fever and bone-crusher disease. and dengue hemorrhagic fever hemorrhagic fever (hĕm'ərăj`ĭk), any of a group of viral diseases characterized by sudden onset, muscle and joint pain, fever, bleeding, and shock from loss of blood. (5). Dengue epidemics caused by dengue virus type 1 occurred in Nagasaki, Osaka, Kobe, and Hiroshima from 1942 to 1945 (6,7). No outbreaks of dengue virus infection have been reported since then in Japan, and no domestic dengue virus infections have been identified. However, during this period there have been imported dengue cases (8,9) in persons who visited dengue epidemic areas, were infected with dengue viruses, and became ill after returning to Japan. In addition, some foreign visitors who were infected in their own countries became ill with dengue while in Japan. Dengue virus infections were diagnosed in serum specimens of suspected dengue cases submitted from hospitals and clinics by IgM-capture enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay n. ELISA. Enzyme-linked immunosorbent assay (ELISA) A diagnostic blood test used to screen patients for AIDS or other viruses. , hemagglutination inhibition tests hemagglutination inhibition test n. A test to determine the amount of a specific antigen in a blood serum sample. Also called HI test. , and reverse transcriptase-polymerase chain reaction. Neutralization tests and virus isolation were also performed for some specimens. Dengue cases were confirmed by these laboratory tests at the National Institute of Infectious Diseases infectious diseases: see communicable diseases. , Japan, from 1985 to 1999 (Table). The number of imported dengue cases has recently increased. Only two dengue hemorrhagic fever cases were identified, one each in 1990 and 1991; all the other cases were dengue fever. Most of these Japanese dengue patients became infected in Southeast Asia Southeast Asia, region of Asia (1990 est. pop. 442,500,000), c.1,740,000 sq mi (4,506,600 sq km), bounded roughly by the Indian subcontinent on the west, China on the north, and the Pacific Ocean on the east. (Thailand, India, Philippines, and Indonesia), although some patients became infected in Central America Central America, narrow, southernmost region (c.202,200 sq mi/523,698 sq km) of North America, linked to South America at Colombia. It separates the Caribbean from the Pacific. and Africa in recent years. We believe that these dengue cases account for only a fraction of the total imported cases, although the exact number of imported cases is not known. Under a new infectious disease Infectious disease A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. control law, which took effect on April 1, 1999, dengue fever/dengue hemorrhagic fever is a reportable disease re·port·a·ble disease n. See notifiable disease. . Thus, an accurate annual number of imported dengue cases will be known in the near future. Table. Cases of imported dengue and countries that persons visited before onset of symptoms, by year, Japan Countries '85 '86 '87 '88 '89 '90 No. of cases(a) 4 1 4 4 1 11(b) Asia Thailand 3 0 3 1 0 7 India 0 0 2 0 0 2 Philippines 2 1 1 1 0 1 Indonesia 0 0 0 1 0 0 Malaysia 0 0 1 0 0 2 Myanmar 0 0 0 0 0 0 Cambodia 1 0 0 0 0 0 Singapore 0 0 0 0 1 0 Nepal 0 0 1 0 0 0 Laos 0 0 0 0 0 0 Vietnam 0 0 0 0 0 0 Bangladesh 0 0 1 0 0 0 Maldives 0 0 0 0 0 1 Taiwan 0 0 0 2 0 0 China 0 0 0 0 0 0 Sri Lanka 0 0 0 0 0 0 Oceania/South Pacific Australia 0 0 0 0 0 0 Fiji 0 0 0 0 0 0 New Caledonia 0 0 0 0 0 0 Tahiti 0 0 0 0 0 0 Central America Dominica 0 0 0 0 0 0 Guatemala 0 0 0 0 0 0 Africa Nigeria 0 0 0 0 0 0 Liberia 0 0 0 0 0 0 Cote d'Ivoire 0 0 0 0 0 0 Countries '91 '92 '93 '94 '95 No. of cases(a) 6(b) 14 7 11 16 Asia Thailand 3 7 1 6 8 India 1 2 1 1 4 Philippines 3 1 3 1 1 Indonesia 0 3 1 2 2 Malaysia 0 0 0 0 1 Myanmar 0 0 0 0 1 Cambodia 0 0 1 0 1 Singapore 0 1 0 0 1 Nepal 0 1 0 1 0 Laos 1 0 0 1 0 Vietnam 0 0 0 1 0 Bangladesh 0 0 0 0 0 Maldives 0 0 0 0 0 Taiwan 0 0 0 0 0 China 0 0 0 0 0 Sri Lanka 0 0 0 0 0 Oceania/South Pacific Australia 1 0 0 0 0 Fiji 0 0 1 0 0 New Caledonia 0 0 0 0 1 Tahiti 0 0 0 0 0 Central America Dominica 0 1 0 0 0 Guatemala 0 0 0 0 0 Africa Nigeria 0 0 0 0 0 Liberia 0 0 0 0 0 Cote d'Ivoire 0 0 0 0 0 Countries '96 '97 '98 '99 Total No. of cases(a) 15 6 42 11 153 Asia Thailand 4 1 19 2 65 India 5 0 6 3 27 Philippines 1 1 8 1 26 Indonesia 3 1 5 0 18 Malaysia 2 0 1 1 8 Myanmar 0 0 3 4 8 Cambodia 0 0 3 1 7 Singapore 1 1 2 0 7 Nepal 0 1 1 0 5 Laos 0 1 2 0 5 Vietnam 0 1 2 0 4 Bangladesh 1 0 1 0 3 Maldives 0 0 1 1 3 Taiwan 0 0 0 0 2 China 0 0 2 0 2 Sri Lanka 0 0 1 0 1 Oceania/South Pacific Australia 0 0 0 0 1 Fiji 0 0 0 0 1 New Caledonia 0 0 0 0 1 Tahiti 0 1 0 0 1 Central America Dominica 0 0 0 0 1 Guatemala 0 0 1 0 1 Africa Nigeria 1 0 0 0 1 Liberia 0 0 1 0 1 Cote d'Ivoire 0 0 1 0 1 (a) Some patients visited more than one country. (b) in 1990 and 1991, one patient each year had dengue hemorrhagic fever. Tick-Borne Encephalitis Central European encephalitis and Russian spring-summer encephalitis Russian spring-summer encephalitis see Russian spring-summer encephalitis. (RSSE RSSE Reduced-State Sequence Estimation ) viruses are TBE viruses prevalent in Eurasia (1). The presence of TBE virus in Japan was first confirmed when Negishi virus was isolated from an encephalitis patient in 1948. This virus was later determined by antigenic analysis to be TBE virus (10). No further cases of tick-borne encephalitis were identified in Japan until 1993, when Takashima et al. reported a tick-borne encephalitis case in Hokkaido, the northern island of Japan (11). The patient, a dairy farmer, had high fever, double vision, convulsions Convulsions Also termed seizures; a sudden violent contraction of a group of muscles. Mentioned in: Heat Disorders , and motor paralysis motor paralysis n. Loss of voluntary control of muscular contraction. . The 6- and 43-day serum samples showed highest neutralizing antibody neu·tral·iz·ing antibody n. An antibody that reacts with an infectious agent, usually a virus, and destroys or inhibits its infectiveness and virulence. titer titer /ti·ter/ (ti´ter) the quantity of a substance required to react with or to correspond to a given amount of another substance. to RSSE virus, but the level of neutralizing antibody to Japanese encephalitis virus was low. Serologic tests indicated that the encephalitis was caused by TBE virus. Takashima et al. demonstrated that sentinel dogs were seropositive seropositive /se·ro·pos·i·tive/ (-poz´i-tiv) showing positive results on serological examination; showing a high level of antibody. se·ro·pos·i·tive adj. for RSSE virus (11). They then isolated viruses from the dogs' sera and demonstrated that the isolated virus was related most closely to RSSE virus by nucleotide sequencing. Takeda et al. isolated TBE virus from Ixodes ovatus ticks collected in the region and demonstrated that the isolated viruses were antigenically close to RSSE virus (12). They also showed that captured rodents had antibodies to TBE virus and that the viruses isolated from the rodents were also antigenically close to RSSE virus (13). These reports indicate that the TBE virus endemic in Hokkaido is closely related to RSSE viruses. Further studies are necessary for understanding the ecologic features of TBE virus in other islands of Japan. Dr. Kurane is director of the Department of Virology virology, study of viruses and their role in disease. Many viruses, such as animal RNA viruses and viruses that infect bacteria, or bacteriophages, have become useful laboratory tools in genetic studies and in work on the cellular metabolic control of gene expression I, National Institute of Infectious Diseases, Tokyo, Japan. His research interests include human T-cell responses to dengue viruses and pathogenesis of dengue hemorrhagic fever. References (1.) Monath TP, Heinz FX. Flavivirus. In: Fields BN, editor. Fields virology. Philadelphia: Lippincott-Raven Publishers; 1996. p. 961-1034. (2.) Matsunaga Y, Yabe S, Taniguchi K, Nakayama M, Kurane I. Current status of Japanese encephalitis in Japan. J Jap Assoc Infect Dis 1999;73:97-103. (Japanese) (3.) Monath TP. Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A 1994;91:2395-400. (4.) Henchal EA, Putnak R. The dengue viruses. Clin Microbiol Rev 1990;3:376-96. (5.) World Health Organization. Dengue haemorrhagic fever Noun 1. haemorrhagic fever - a group of illnesses caused by a viral infection (usually restricted to a specific geographic area); fever and gastrointestinal symptoms are followed by capillary hemorrhage : diagnosis, treatment and control. Geneva Geneva, canton and city, Switzerland Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. : World Health Organization; 1997. p. 12-23. (6.) Hotta S. Dengue epidemic in Japan, 1942-1945. J Trop Med Hyg 1953;56:83. (7.) Fujita N, Yoshida K. Follow-up studies on dengue endemic in Nagasaki, Japan: detection of specific antibodies in the sera taken more than 30 years after a single attack of dengue. Kobe J Med Sci 1979;25:217-24. (8.) Yabe S, Nakayama M, Yamada K, Kitano T, Arai Y, Horimoto T, et al. Laboratory virological virological pertaining to viruses. diagnosis of imported dengue cases. J Jap Assoc Infect Dis 1996;70:1160-9. (Japanese) (9.) Yamada K, Takasaki T, Nawa M, Nakayama M, Arai Y, Yabe S, et al. The features of imported dengue fever cases from 1996 to 1999. Jap J Infect Dis 1999;52:257-9. (10.) Ando K, Kuratsuka S, Arima S, Hironaka N, Honda Y, Ishii K. Studies on the viruses isolated during epidemic of Japanese B encephalitis Jap·a·nese B encephalitis n. An epidemic encephalitis or encephalomyelitis of Japan, Siberia, and other parts of Asia, caused by a virus of the genus Flavivirus. in 1848 in Tokyo area. Kitasato Exp Med 1952; 24:49-61. (11.) Takashima I, Morita K, Chiba M, Hayasaka D, Sato T, Takezawa C, et al. A case of tick-borne encephalitis in Japan and isolation of the virus. J Clin Microbiol 1997;35:1943-7. (12.) Takeda T, Ito T, Chiba M, Takahashi K, Niioka T, Takashima I. Isolation of tick-borne encephalitis virus from Ixodes ovatus (Acari: Ixodidae) in Japan. J Med Entomol 1998;35: 227-31. (13.) Takeda T, Ito T, Osada M, Takahashi K, Takashima I. Isolation of tick-borne encephalitis virus from wild rodents and a seroepidemiologic survey in Hokkaido, Japan. Am J Trop Med Hyg 1999;60:287-91. Ichiro Kurane, Tomohiko Takasaki, and Ken-ichiro Yamada National Institute of Infectious Diseases, Tokyo, Japan Address for correspondence: Ichiro Kurane, Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640 Japan. Tel & Fax: +813-5285-1169. |
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