Studies on epidemiology in Korea and vaccine of Japanese encephalitis
During August and September 1949 in Korea a severe epidinic of Japanese encephalitis (JE) resulted in 5,616 cases with 2,729 deaths reported, and was identified as being due to Japanese encephalitis virus (JEV). Serologic surveys against indigneous persons and animals indicated wide dissemination of JEV and the
most high incidence showed in the province of Choola Pukto.
The author attempted to investigate the factors involved epidemiology of the diseases, the methods of application of the vaccine against JEV and the evaluation of the vaccine through it's massive field application were experimented.
Historically, the epidemics of JE in Korea was not recognized with the epidemiological significance until the 1949 epidemic. Furthermore, not established with any obvious acknowledgements. However, the large epidemic in Korea in 1949 had guided that the disease was confirmed as JEV infection, and that has become an
important public health problem in Korea.
The epidemic curve through past twelve years (1949-1960) has shown a small epidemic peak in every three years and a large epidemic peak in every nine years. This is revealing a small group-accumulation of the secseptability to the people in every three years and a large group accumulation of that in every nine years.
The incidences in a large epidemic through whole country has shown 6,000 cases, and that in a small epidemic 2,000 cases. The case-fatality had been over 40% until 1957, but decreased as lower as 31.4% in 1958. The results of the decreasing case-fatality rates were observed due to the improvement if the early diagnosis and better medical card.
In regard to the geographical distribution through past twelve years (1949-1960), the highest morbidity rate was indicated in the province of Cholla-Pukto (23.2 per 100,000), and the province of Cho-Ha-Nam (12.1 per 100,000), and Kyongsang-Pukto
(8.2 per 100,000) were in next, and in comparison therefore the ratio of these four provinces were "4:2:1:1".
The province of Chungchong-Pukto, Chungchong-Namdo, Kamgwon-Do, and Special City of Seoul were 4 to 8 per 100,000 in the morbidity rate, and the province of Cheju-Do was the lowest (0.7 per 100,000). Hereby, the province of Cholla-Pukto which showed a significant epidemic focus of the disease in Korea. It is
interesting to note that the morbidity rates of the province of Cholla-pukto, Cholla-Namdo, Kyongsang-Namdo, and Kyongsang-Pukto (4:2:1:1:) were correlated with the biological suitability of those provinces for the possible animal reservoirs and vectors.
The incidence rate in the major cities and rural areas through past three years (1958-1960), the major cities showed higher attack rates than in rural areas, and the major cities showed lower fatality rates than in rural areas. It is presumed that the early diagnosis and medial care with better medical facilities to the major cities than in rural areas.
In regard to the age distribution through six years(1955-1960), 90.8% of total cases occurred from the age group of under 14, and 50.2% of total cases from the age group of 4 to 8. The highest morbidity rate was in the age group of 5 to 9 (32.2 per 100,000), and 0 to 4 was followed. However, the highest case-fatality rate was in the older age group (52.8% over the age of 30 ), and the lowest was in the age group of 0 to 4 (31.4%). The fact of the highest morbidity rate in the age group of 4 to 8 is presumed that due to the concentration of the accumulated susceptibility in the age group, and it reveals as to be an important epidemiological features of the diseases in Korea.
The incidence ratio between male and female was 1.62:1, and male showed slightly increased attack rate than in regard through six years (1955-1960). However, the fatality rate between both sexes showed no significant differences. It is assumed that male sex has more tendency to expose their naked bodies than in female, particularly in the susceptable age gorup of under 14 in Korean custom, although there must be many unknown factors are involved in this regard.
The main epidemic period was observed between August and September (99.5% to total) regardless of the epidemic size through past five years 91956-1960). The first cases were usually reported from late of June or early August, and reached to the peak in late of August or early of September, and cased almost in late of October. This period of epidemic are related to the dry and hot climate which is crucial factor with the proliferation of JEV in the vectors and the mosquito populations. Therefore, with the consideration of the incubation period of two weeks, the active control measure against disease should be started before middle of July although the epidemiologically the period between middle of July and middle of September is crucially important.
Vaccine was prepared according to the method initiated by the U.S. Army Medical Department Research and Graduate School. The Nakayama strain infected mice brain were made 10% suspension in buffered salibem centrifuged at 3,000 RPM for 15 minutes and the supernatant was used further procession.
Added formalin to give final concentration of 0.2% and let it stand at the 4 C for 2 weeks for inactvation.
Safety and potency tests were carried out according to the "Minumum Requirement of the National Institute of Health, U.S.A."
The vaccine batches which used in this study were varied from I.D. 50 of 0.01 to 0.013 ml. The procedure of the preparation of the normal control vaccine was exactly same as that of test vaccine except the JEV inoculation.
Vaccine Field Trial :
The author decided that the vaccine inoculation to the children less than the age of 15 and 0.1ml. of the administration, twice a 7 days apart because (here are several main) following reasons : (1) in view of the limited amount of vaccine was available in this study. (2) the vaccine inoculation should be limited to children less than the age of 10 because the case-fatality rate was so high, and (3) 0.1ml. of the vaccine inoculation by route of intradermal vould be convenient its application.
In 1957, 30,000 children, age ranging 8-10 years in both Kimchae-and Ocku-Gun in Cholla-Pukdo province veceived 2 doses of 0.1 ml, of the vaccine intradermally with the interval of 7 days.
In 1958, 100,000 children, age ranging 5-10 years in Kimchae, Jungup, and Buan-Gun in Cholla-Pukdo province, were administered with the vaccine.
In 1959, 200,000 children, age ranging 4-10 years in six Guns, Iri city, and Kusan city in Cholla-Pukdo province, were inoculated.
In 1960, 100,000 children, age ranging 5-10 years in the area as in 1959,were inoculated with same method as mentioned above.
1. Serological response following intradermal administration.
1957 : Fifteen children were selected from the vaccinated by the ramdom sampling method and bled before (as a base-line) and after 2 dises of vaccination for the tests of antibody responses.
The hemagglutination inhibition and neutralization antibodies against JEV are descrived in table 1.
Among the fifteen specimens only four children who originally did not possess antibodies (base-line) subsequently developed HI antibodies average 1:40 after receiving 2 doses of 0.1 ml. of the vaccine. Other eleven children previously posess HI antibodies average 1:10 showed the increased HI antibody titer reached
about 1:80 approximately 4 weeks after the inoculation.
1960. Among the vaccinated group, twenty children were selected for serological study. Six children out of twenty children did not possess antibodies when the vaccine administered. Other fourteen children were possessed HI antibodies in average titer of 1:10. Four weeks after 2 doses of the vaccine inoculation, HI
antibodies against JE developed average titer of 1:40 in children previously did not possess antibody and fourteen children who previously had antbiodies showed average HI titer of 1:80 (3 cases of HI titer of 1:160 showed neutralizing index 320). Among the control group received normal mouse brain vaccine (100 children), twenty children were selected for comperative study of the antibody reponse. As indicated in table 2, six children showed increased HI antibody titer from 1:10 to 1:20 and from 1:20 to 1:40 respectively.
2. The results of JE vaccine field trial :
1958 : Among the vaccinated 95,648 children, 110(11.5 per 100,000)suspected cases from Cholla-pukto province (were reported), whereas among the 287,176 non-vaccinated children of same age group, 985(33.4 per 100,000) suspected cases of JE were reported. Fiteen (13.6%) deaths among the vaccinated and 214 deaths (22.3%) among the non-vaccinated were reported.
1959 : Among the vaccinated 188,837 children, there were 16 cases of suspected cases and 8 deaths, whereas among the 295,839 non-vaccinated children, 184 cases and 47 deaths were observed respectively in Cholla-pukto province.
1960 : Among the vaccinated 94,473 children, clinically 12 cases of JE and 1 deaths were observed, whereas among non-vaccinated 225,318 children, 110 cases and 40 deaths were observed in Choll-Pukto province.
Over a four year period(1957-1960), JEV vaccine was administered intradermally, with dosage of 0.1 ml twice a 7 days apart to 430,000 children, age ranging 5 to 10 years in Cholla-Pukto province, the most endemic area of the disease.
The serologic response by the vaccine was studied in the years of 1957 and 1960. and similar serological results were obtained as follows ; four weeks after 2 doses of the vaccine inoculation, HI antibody avererage titer of 1:40 in children who previously did not possess the antibody, whereas in children who previously had the antibodies average HI titer of 1:10 showed HI titer of average 1:80 (Neutralizing index 160-320). Through the four years of field trails, case ratio between the vaccinated group and non-vaccinated group were 1:3.3 in the average and death ratio 1:2.7 in the average.