Bull. Org. mond. Sante 11969, 41, 353-359 Bull. Wld Hlth Org.

Summary Report on Hong Kong Influenza in

HIDEO FUKUMI 1

In the 2 months following the onset of the influenza epidemic in Hong Kong in July 1968, there must have been many importations ofthe virus into Japan both from Hong Kong andfrom other countries subsequently involved in the epidemic. Over a dozen such incidents were reported in Japan and confirmed serologically or by direct virus isolation. Although they must have seeded the virus at least in and near the ports ofimportation, a true epidemic of Hong Kong influenza did not start until October. It spread gradually, first to the larger and more crowded cities and then to smaller urban areas, but in a sporadic manner and without massive involvement of the rural areas. This was in marked contrast to an influenza B epidemic that affected the whole country during the same period-September-October 1968 to March 1969-and also in contrast to the 1957-58 Asian influenza epidemic.

On 25 July 1968 information reached the Japanese A2/Hong Kong, while the Japanese Influenza Centre Influenza Centre that an influenza epidemic with an inclined rather to the view that it should be called A3. unusually high attack rate was taking place in Hong The present paper describes further developments Kong. On 31 July the present author went to of the Hong Kong influenza epidemic in Japan. Hong Kong at the request of the Japanese Govern- ment to obtain detailed information on the epidemic IMPORTATION OF HONG KONG INFLUENZA VIRUS and to bring back strains of the virus causing the INTO JAPAN epidemic. He returned on 3 August with several isolates given to him by Dr W. K. Chang of the It was not until early October 1968 that a true Hong Kong Influenza Centre, which were promptly epidemic of Hong Kong influenza began in Japan, submitted to antigenic analysis. although more than a dozen importations of Hong Also on 25 July, an Israeli cargo vessel, the Kong virus were reported in August and September Tevirya, arrived from Hong Kong at the Japanese and confirmed (mostly by virus isolation and in some port of with a number of the crew ill with instances serologically). These came not only from influenza. Two strains of influenza virus were Hong Kong but also from other countries subse- isolated on 1 August and forwarded to the Japanese quently involved in the epidemic but did not imme- Influenza Centre laboratories for analysis. diately lead to further spread of the infection. On 12 August, the Japanese Influenza Centre There were very few infections among contacts of announced that the isolates from the Hong Kong influenza patients. For instance, although many of epidemic seemed to belong to a new antigenic the crew of a fishing boat from Goto Islands, variant, with an antigenic shift so considerable that it , in western Japan, returned in September was highly improbable that the available vaccine, from Taiwan with what was later virologically prepared from previously isolated A2 strains, would confirmed as Hong Kong influenza, the infection be effective against an epidemic caused by the new showed no tendency to spread to other people in variant. the town or to the neighbouring villages. Shortly afterwards, the Centre received essentially Also of interest are a few laboratory infections similar information from the World Influenza which occurred in vaccine-manufacturing labora- Centre, except for a very minor point of nomen- tories. On 13 August 1968 the Japanese Influenza clature in that the World Influenza Centre considered Centre delivered a 3rd egg-passage virus, A2/Aichi/2/ the new strain to be a variant of A2, calling it 68 (Hong Kong isolate from the vessel Tevirya), to those laboratories as the strain for vaccine manu- 1 Chief, Department of Bacteriology, National Institute facture. A number of laboratory infections, con- of Health, , Japan. firmed by virus isolation, were reported from almost

2374 -33 - 354 H. FUKUMI all the manufacturers. It was said that the infections Tokyo, and was gradually followed by others, took place only when virus of early passage was first in the Tokyo- area and then in being used. A very few contact cases in families , Nagoya and other prefectures, almost all were reported, but the infections soon subsided and these outbreaks being in schools. neither showed any tendency to spread further nor Although there were no confirmed cases or out- seem to have become sources for subsequent breaks between August and October, it seems fairly outbreaks. certain that a smouldering seeding of virus had been occurring from imported cases because, as shown THE START OF THE HONG KONG EPIDEMIC IN JAPAN in Table 1, Hong Kong influenza outbreaks were reported in the earlier part of the epidemic chiefly All reported cases and outbreaks of influenza-like in or near the ports of virus importation. This is in disease were investigated (by virus isolation, sero- marked contrast to the B-type influenza epidemic logical diagnosis or both) by central, prefectural or which took place during the same period. other laboratories but none was confirmed by Fig. 1 shows the general trend of influenza-like laboratory methods as being due to Hong Kong disease by week from May 1968 through April virus until the beginning of October 1968, except for 1969. Since it is not based on laboratory examina- imported cases, laboratory infections and their tions, it cannot indicate the virus type responsible, immediate contacts. The first Hong Kong influenza (although both B and Hong Kong types must be outbreak occurred in Ryogoku Middle School in involved) or exclude non-influenzal respiratory

FIG. 1 CASES OF INFLUENZA-LIKE DISEASE REPORTED IN JAPAN, MAY 1968 TO APRIL 1969,a AND NUMBERS OF SCHOOL CLASSES CLOSED b 100000.~ 0o000 60 000 * Nuumber of classes closed owing 0o influenza 40 000 o Number of cases reported as influenza 20 000

10000.- 8000.- 6 000 . 4000.-

In 2 000

1000 - Ir 600Soo .- 0 400 -

200

100 - 0 80 - 60 - In 40 -

D z 20 -

10 - a -

4 -

M691632 WEEKS IN 1968 WEEKS IN 1969 a The arrow indicates the time of the first outbreak of Hong Kong influenza (in Tokyo). b Schools were closed for the summer holidays during weeks 30-36. HONG KONG INFLUENZA IN JAPAN 355

TABLE 1 CONFIRMED INFLUENZA OUTBREAKS IN JAPAN, SEPTEMBER 1968 TO MARCH 1969

Hong Kong influenza Type B influenza Prefec- ture a Oct. Nov. Dec. Jan. Feb. March Sept. Oct. Nov. Dec. Jan. Feb. 1968 1968 1968 1969 1969 1969 1968 1968 1968 1968 1969 1969

______.______

Hokkaido 3 I 5 1 3 2 Iwate 4 2 Miyagi 3 1 5 Gunma 3 I baragi 4 1 Tochigi 6 3 4 2 2 4 3 2 8 4 1 2 Tokyo 5 2 3 2 1 5

Kanagawa 2 12 1 2 1 7 Yaman- ashi 6 2 1 5 2 Aichi 3 2 5 2 3 3 1 3 3 Miye 9 2 3 5 Shiga 2 5 6 1 8 7 7 b 2 2 4 2 4 3 2 Osaka 4 4 5 Waka- yama 2 10 1 Ehime 8 2 Toku- shima 2 Kago- shima 2 2 6 2 8 1 Kuma- moto 3 2 4 Nagasaki 1 2 3

a Prefectures in italics are ports of virus importation. b There was also an outbreak of type B influenza in Kyoto in May 1968. 356 H. FUKUMI diseases. Nevertheless, it does serve to outline the Hong Kong antibody and then at titres as low as picture and shows clearly that there was a main 1: 16 to 1: 32 or at most 1: 64 (see, for instance, epidemic period in January to February 1969, Table 2). preceded by a wave of moderate size, whose start Table 2 is presented as an example, taken from almost corresponds with the first Hong Kong findings in Japanese Self-Defence Forces camps in influenza outbreak in Ryogoku Middle School. many parts of the country, to show to what extent Fig. 1 also gives the curve for the number of classes the Hong Kong influenza epidemic affected com- closed owing to influenza-like illnesses; the curve munities. The results (not tabulated here) of a (not shown) for the number of schools closed for number of serological investigations in other popula- the same reason closely follows that for the classes. tion groups conducted immediately before the epidemic suggest that the antibody patterns in these PREVALENCE OF HONG KONG INFLUENZA IN JAPAN camps are representative of the country as a whole. Sera were drawn twice in the camps-in October Even after the Hong Kong influenza epidemic had 1968, just before the epidemic, and in April 1969, started, its spread was not as rapid as might be after the epidemic had subsided. Taking a 4-fold expected when a new antigenic variant appears and antibody rise as the criterion, 495 out of 1325 it can hardly be said to have developed typically soldiers are considered to have been infected with epidemic features until January 1969. And then the Hong Kong influenza, an infection rate of 37 %. epidemic still seemed reluctant to increase its speed The infection rates for the various camps have been of spread or to infiltrate further from urban into plotted on a map of Japan in Fig. 2, the percentages rural areas, a feature that was not expected from of those with a 4-fold antibody rise being shown experience with the Asian influenza epidemic in 1957. within double parentheses-e.g., Fukuoka ((25 %)). Prior to the Hong Kong influenza epidemic, only Where paired October/April sera were not available a small fraction of the population of Japan had any and serum samples were drawn only in the period

TABLE 2 SHIFT OF HONG KONG ANTIBODY TITRES IN RANDOMLY SAMPLED INDIVIDUALS IN SELF-DEFENCE FORCES CAMPS IN JAPAN, OCTOBER 1968 TO APRIL 1969

Hi antibody titre in April 1969 Total <1: 16 1:16 1:32 1:64 1:128 1:256 1:512 1:1024 1:2 048

1:2 048 | 1:1024 1:512 -oD 1 u 1:256 0 1:128 1 C o. 1:64 3 ~0 2 1 15 D2 1: 32 6 4 14 1 1 3 1 39 X1 :16 13 a 15/ 4 2 2 6 50 <1::16 70 71 97 133 71 25 10 1219

Total 729 57 89 85 107 139 80 28 11 1 325

4-fold or greater anti- body rise No. 60 75 104 138 79 28 11 495 67 85 97 99 99 100 100 HONG KONG INFLUENZA IN JAPAN 357

FIG. 2 HONG KONG INFLUENZA INFECTION RATES (CRUDE AND CORRECTED) a IN JAPANESE SELF-DEFENCE FORCES CAMPS

Mihoro (I15%)123%l Nayoro (22%) [38%) ((21%)) Higashichitose ((47%)) / ((38%)) /

Hirosaki(1 0%)[2 1%l bihiro ((43%)) Akita (9%) (17%) Z inmachi ((2 6%))) Aomori ((33%)) Takada (17%) (38%) (41%)[34%) Sohmagahara (4%) (19%) Matsumoto (31%)[43%1 (23%)[40%1 (26%)[37%) \ukushima(17%)[23%) \ (J\ d tX1 Koriyama(1O0%)(13%l

Yon,ago(l 1%)(20%l \ \g\ f ,7_ (28%)[46%3 \ \ % 14/ > ~~~~~~~Shinmachi ((45%)) Kaidaichi((38%)) Ih\J. l,Cc-'5A (17%)(28%) \? , Nerimaa((76%)) Fukuoka (( 2 5% ))\\ j\ ohm((4%)

Ai,,oiwa)17%)(27%] ~~~~~~~~~~~Toshim,a(48%)) Ainoura (1 7%)[27%|ui(6)tSg' Fuji )46%)(57%]

Toyokawa (29%)[42%I Nagoya((35%)) WHO91631 Ohtsu (( 56%)) Senzo (21%)(34%l )(12%)(28%1 Z entsuji (30%)t38%] ( 18%)[33%) al \ \ Beppu t29%)l9¶% ((1 3%)) Kokubu ()2%) 4%l

a Paired sera were drawn in October 1963 and April 1969; single sera from early May to early July 1969. Figures within single parentheses-e.g. (17%)-are percentages of persons with antibody titres >1 :128; figures within square brackets-e.g. [28%]-are the corrected values (see text). Figures within double parentheses-e.g., ((23%))-are percentages of persons showing a 4-fold or greater antibody rise in the paired sera.

May to July 1969, the infection rate was calculated (Fukumi, 1959), particularly in the west and south on the assumption that an antibody titre > 1: 128 (Kokubu, Kumamoto, Ainoura, Fukuoka, Yama- represented infection since there was no one with guchi, Yonago), the north (Akita, Hirosaki, Mihoro) so high a titre in October 1968 (see Table 2); this and some other areas (Koriyama, , Sohma- rate is shown in Fig. 2 within single parentheses-e.g., gahara). It seems to run parallel with the prevalence Yamaguchi (17 %). However, among those with in the civil population. antibody titres of 1: 32 or 1: 64 after the epidemic, some were found to have been infected on the basis AN EXAMPLE OF HONG KONG INFLUENZA IN THE EARLY of a 4-fold antibody rise. A correction factor was EPIDEMIC PERIOD IN SCHOOLCHILDREN therefore calculated to take this into account and applied to the values within double parentheses in The epidemic situation is typified by the records Fig. 2; these corrected values are shown within of the Ohmukou Primary School, located in a fairly square brackets-e.g., Yamaguchi [28 %]. It will crowded part of Tokyo and involved in the Hong be seen from the figure that the infection rate in the Kong influenza epidemic at the end of October 1968. camps was variable, ranging from [57%] to [4.0%] The numbers of children with influenza-like illness during the epidemic, and it was considerably lower in each class of the 4th, 5th and 6th grades are given than in the Asian influenza epidemic of 1957-58 in Table 3 by 5-day or 6-day period. It will be seen 358 H. FUKUMI

TABLE 3 NUMBERS OF CHILDREN WITH INFLUENZA-LIKE DISEASE IN OHMUKOU PRIMARY SCHOOL, BY SCHOOL GRADE AND CLASS, OCTOBER-NOVEMBER 1968

I______i______- Date in October Date in November Total Grade Class affected/Total 1-5 6-10 11-15 16-20 21-25 26-31 1-5 6-10 in class

1 0 1 2 1 1 4 1 0 10/37 2 2 1 1 0 2 1 2 0 9137 4th 3 3 1 0 1 2 6 5 0 18137 4 0 3 0 1 0 3 2 0 9/38

1 0 3 0 3 2 1 8 5 22/48 5th 2 2 1 1 0 2 3 5 3 17/48 3 0 2 2 0 0 4 13 2 23/47

1 1 1 2 1 2 6 4 1 18/49 6th 2 2 2 1 0 0 4 8 3 20/48 3 1 0 2 3 14 17 1 0 38/48 that there was a remarkable accumulation of there should have been such a difference between patients in class 3 of the 6th grade at the end of two classes in the same school or why the epidemic October but not in the other classes except for a did not promptly spread from class 3 of the 6th slight clumping of cases in class 2 of the 6th grade grade to the other classes cannot be answered from and class 3 of the 5th grade in early November. the serological or epidemiological data. However, On 12 November sera were collected from the events of this sort were a general feature of the children in classes 2 and 3 of the 6th grade and epidemic, especially at the start. examined for their Hong Kong antibody titres (Table 4). STUDY IN TWO TOKYO SANATORIA Of the 48 children in class 3, 33 had antibody titres > 1 : 128. If these are taken as indicating In another study, two lots of sera were collected infection, there is a 69 % infection rate. However, in two sanatoria in the outskirts of Tokyo and tested if a titre of 1: 64 is considered to represent possible for Hong Kong and B-type influenza antibody. infection, then the rate rises to 75 %. In class 2, on In Fuchu sanatorium they were drawn from 114 the other hand, only 3 had antibody titres 2 1: 128; patients in mid-February and mid-April; and in and even if those with a titre of 1: 64 are taken into Nakano sanatorium from 484 patients and 109 consideration, the infection rate is only 13 %. Why sanatorium personnel in mid-February and at the

TABLE 4 FREQUENCY DISTRIBUTION OF HONG KONG ANTIBODY TITRES IN A NON-EPIDEMIC AND AN EPIDEMIC CLASS IN OHMUKOU PRIMARY SCHOOL

Hong Kong antibody titre Class [ <1:16 1:16 ] 1:32 [ 1:64 J 1:128 1:256 1:512 1:1024 >1:2048

Grade 6, class 2 (non-epidemic) 40 0 1 3 0 1 1 1 0

Grade 6, class 3 (epidemic) 13 0 0 2 2 7 10 9 5 HONG KONG INFLUENZA IN JAPAN 359 end of May. The results showed that, while the 1: 64 titre as the criterion). The corresponding Hong Kong and B viruses were both already present figures in Nakano sanatorium were 34% or 40%. in February, there were further infections with both These figures indicate that some 30 %-40 % of people types between the first and second serum collections. became infected by the end of the epidemic in the By the time the epidemic subsided, the Hong Kong Tokyo area, or at any rate in such groups as the virus infection rates amounted to 19% in Fuchu inmates of sanatoria, which are relatively closed sanatorium (on the basis of a 4-fold antibody titre communities but with some contact with the general rise or of a > 1:128 titre)_or to 29% (taking a population.

REFERENCES

Fukumi, H. (1959) Bull. Wld Hlth Org., 20, 187-198