| Project/Area Number |
63044136
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Nihon University |
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Principal Investigator |
TAKASU Toshiaki Nihon University School of Medicine, Dept. of Neurology, 医学部, 教授 (90010024)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Ikuo Hokkaido University School of Veterinary Medicine, Dept. of Veterinary Public He, 獣医学部, 助教授 (30002083)
KAMIMURA Kiyoshi Toyama Medical and Pharmaceutical University, Dept. of Pathology, 助教授 (00115164)
HASHIMOTO Nobuo Hokkaido University School of Veterinary Medicine, Dept. of Veterinary Public He, 獣医学部, 教授 (60082103)
TAKAHASHI Mitsuo National Institute of Health, Division of Medical Entomology, 部長 (00072893)
DOI Rikuo Yokohama Municipal University School of Medicine, Dept. of Hygiene, 医学部, 教授 (70091585)
IGARASHI Akira Nagasaki University Institute of Tropical Medicine, Division of Virology, 熱帯医学研究所, 教授 (40029773)
ANWAR Wagar アガハン大学, 健康科学部, 教授
ISHII Keizo Special Reference Laboratory, 特別顧問 (40001789)
ISOMURA Shin Aichi Prefectural Institute of Health, 所長 (00064832)
YOSHIKAWA Yasuhiro Tokyo University Institute of Medical Science, Division of Animal Pathology ; si, 国立予防衛生研究所筑波医学実験用霊長類センター・助教授, 所長 (80109975)
YAMANOUCHI Kazuya Tokyo University Institute of Medical Science, Laboratory Animal Research Center, 研究所, 教授 (30072888)
KONDO Kiyotaro Hokkaido University School of Medicine, Dept. of Public Health, 医学部, 教授 (80018366)
YASMEEN Akba アバンシャヒード病院, 医長
MUBINA Agbor ダウ医科大学, 助手
AKRAM D. S. Dow Medical College, Dept. of Pediatrics, 教授
SHAISTA Rauf ダウ医科大学, 助手
AKHTAR Ahmed ダウ医科大学, 教授
AKBANI Yasmeen Abassi Shaheed Hospital, Dept. of Pediatrics
AGBOATWALLA Mubina Dow Medical College, Dept. of Pediatrics
AHMED Akhtar Dow Medical College, Dept. of Neurology
RAUF Shaista Dow Medical College, Dept. of Neurology
WAQAR Anwar Aga Khan University School of Health Sciences, Dept. of Biochemistry
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥19,000,000 (Direct Cost: ¥19,000,000)
Fiscal Year 1990: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1989: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1988: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Subacute sclerosing panencephalitis / age at occurrence of measles / case control study / vaccination / HLA analysis / hemaglutinin (HA) protein / Japanese encephalitis / 日本脳炎 |
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| Research Abstract |
We reported formerly that in Karachi the incidence of subacute sclerosing panencephalitis (SSPE) could be more than fifty times higher than in Japan and in many Western countries and that there had been the occurrence of acute encephalitis in Karachi serologically suspected to be due to Japanese encephalitis (JE) virus infection. This time we focused on the factor analysis of the higher incidence of SSPA and the aetiology of the JE-like disease.
To sum up ; there was remarkable progress on the SSPE study, especially its epidemiological and sero-virological aspects, while no remarkable progress was achieved on the JE-like disease study.
1. Factor analysis of the higher SSPE incidence in Pakistan
SSPE is a disease of brain due to its invasion by a variant or variants of measles virus which can occur in some measles sufferers belatedly during the course of persistent infection by measles virus.
(1) Epidemiological results : The ages at occurrence of measles in SSPE patients in Pakistan were f
… More
ound to be higher than in Japan and in many Western countries ; the rate of early measles (EM ; measles which occurred below 2 years of age) being 0.353, that of below 5 years late measles (LM5> ; measles which occurred at 2, 3, or 4 years of age) 0.340, and that of at or above 5 years late measles (LM5D5 ; measles which occurred at or above 5 years) 0.307. Thus the majority of the ages at occurrence of measles was found to be represented by late measles (LM ; LM5> and LM5 combined) in the SSPE patients in Pakistan. This is in a striking contrast to the EM predominance in Japan and in many Western countries. On this basis the attack rate of SSPE among measles sufferers in Pakistan were estimated to be 308.1 x 10^<-6> from EM. 197.4 x 10^<-6> from LM5>, 585.2 x 10^<-6> from LM5D5, 265.4 x 10^<-6> from LM, and 280.2 X 10^<-6> from whole measles, all found higher than the corresponding figures in Japan, notably 46 times higher from LM5> and 296 times higher from LM5D5. The Pakistan to Japan ratio of the measles incidence among general population was at most two even if stratified according to the age at occurrence of measles. Therefore, the major reason for the higher SSPE incidence in Pakistan would lie in the higher attackrate of SSPE among measles sufferers, especially late measles sufferers. [Takasu et al.]
Secondly our SSPE case control study revealed the lower birth weight and the higher incidence of head injury and of convulsion in SSPE than in control, suggesting that some environmental factors might be working for the development of SSPE before and after measles virus infection. [Kondo et al.]
Thirdly we confirmed the reasonably high level of knowledge about measles in the Pakistani mothers, the vaccination rate in Karachi to be 66%, and the effective rate of vaccination to be around 78% in Karachi for the time of survey (1988-1990). [Isomura, Akram et al.]
(3) Virological and serological results : We suggested the possible higher positive rate of anti-M protein in serum andin CSF of SSPE patients in Karachi than in Japan and the structural homology between measles virus hemaglutinin (HA) protein and the active site of long neurotoxin, i. e. bungarotoxin. [Yoshikawa et al.]
(4) Host antigen analysis : The HLA frequency pattern in Karachi was found to be different from any of Cocacians, Japanese and Negros and the frequency of some antigens in SSPE was different from control but not with definite statistical significance.
(5) Clinical results : We found the shorter incubation period for the development of SSPE after measles virus infection in SSPE in Karachi and noticeable clinical improvements in many early cases of SSPE treated with inosiplex, which lasted at least for a while. [Akhtar Ahmedet al.]
The number of new cases of SSPE obtained during the three years' course of this study from December 1987 to November 1990 was 29, among which 23 were probable cases with characteristic electroencephalographic findings and definite serological evidence. The rest (6 cases) were either serologically possible of electroencephalographically possible. The total number of our series for the past eight years reached 96, of which 64 were probable cases. [Akhtar Ahmed, Takasu, Yoshikawa et al.]
2. Aetiology of JE-like disease in Pakistan
(1) Virological results : One strain of flavivirus other than both from JE virus and from West Nile (WN) virus was isolated from one pool of Culex mosquitoes other than Culex tritaeniorhyncus and Culex pipiens quinquefaciatus collected in Karachi in August 1988. Otherwise, the result of virus isolation from acute CSF in acute encephalitis and from mosquitoes were all negative. The results of lgM capture ELISA in the acute CSF and serum in acute encephalitis were also all negative. [Igarachi, Kamimura et al.]
(2) Animal epidemiology : The positive rate of anti-JE or -WN virus HI antibodies was relatively low in buffaloes and cows compared with horses, donkeys, sheep and goats, and we found many sera specifically positive for WN virus. The domestic animals in Karachi were found to be infected with WN virus, but only slightly and sporadically with JE virus if any. [Takashima, Hashimoto et al.] Less
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