General discussion—Session I

General Discussion-Session I DR J. F. P. HERS. The attack rate of Hong Kong influenza in the Netherlands was estimated, from data received from the Chief Medical Officer of Epidemiology and Public Health, to have been about 30%, but influenza B was prevalent at the same time. The disease was, generally speaking, mild, but several general practitioners and clinicians were impressed by the fact that some patients showed severe constitutional illness in which the respiratory symptoms were present but relatively less prominent. The excess mortality due to Hong Kong influenza in the winter of 1968-69 was nearly the same as that found in 1967-68, when A2 influenza virus was pre- sent in the Netherlands, but there was a difference in age distribution. Younger age-groups were more frequently attacked by Hong Kong influenza and the deaths showed more or less the same age distribution as in 1957. Our department examined 50 fatalities suspected to be associated with Hong Kong influenza from all over the country; of these, 28 (56 %) were confirmed by virological methods. In 13 cases (26%) a rapid diagnosis could be made by immunofluorescence. In 48 cases (96%) the histological characteristics of influenza tracheobronchitis were present. Influenza virus pneumonia was established on histological grounds in 1 case. Staphylococcal pneu- monia occurred in about 36% of all cases tested. Most of the deaths were caused by pneumococcal infections. Haemophilus influenzae as a secondary invader was rare. Streptococci were not found. Most of those who died in the Netherlands had pre- existing disease; very few were previously healthy. DR A. PUMAROLA. The National Influenza Centre, Barcelona, carried out 2 serological surveys to determine the incidence and age distribution of HI antibodies to the Hong Kong variant in healthy people before and after the epidemic of Hong Kong influenza. In September 1968, before the epidemic, 24.7% of the people showed titres of 10 or greater, 13.9% showed titres of 20 or greater, and 7.5% showed titres of 40 or greater. All positive sera showed titres between 10 and 80. With one excep- tion, no antibodies were found in persons aged less than 60 years, and the greatest incidence and highest titres were found in those aged more than 80 years, 55% of whom showed titres of 40 or greater. In March and April 1969 an outbreak of influenza associated with the Hong Kong variant occurred in Barcelona. From July to September another sero- logical survey was carried out to determine the changes produced by the spread of the virus in the population. Of the group tested, 63.6% showed titres of 10 or greater, 53.4% showed titres of 20 or greater, and 37.3 % showed titres of 40 or greater. All positive sera showed titres between 10 and 360. Antibodies were found in all age-groups. They appeared to seme extent in those aged 4 years or less, but the incidence was much greater in those aged 5-14 years. In persons aged 15-60 years, the incidence remained at a lower level with little variation. From the age of 60 years onwards, the incidence increased progressively, reaching its highest level in those aged 80 years and over. Antibody titres were also highest in the latter age-grcup. The high incidence of antibodies in those aged 5-14 years can undoubtedly be ascribed to recent infections, but the rise at age 80 and over is more difficult to interpret. It may be due to the persistence of residual low-titre antibcdies, as shown in the first survey, or-in persons having residual anti- bodies-to recent infections that gave rise to an accelerated response. The high incidence of antibcdies in people aged less than (0 years and the estimated 10%-I5 % mor- bidity in the epidemic indicate that the number of subclinical infections was very high. Hong Kong influenza appeared in Barcelona dur- ing the last week of February 1969. The epidemic reached its peak 1 month later, then declined pro- gressively and ended at the beginning of May. The entire Barcelona province was affected, with the epidemic beginning in the city and subsequently spreading to towns, villages, and rural areas. There were sporadic cases, family outbreaks, and limited outbreaks among groups such as university students and military recruits. The real incidence is difficult to evaluate. Only 25228 cases were reported in March and April, but the data cbtained from several medical services suggest that the epidemic affected 10%-15% of the population. The disease was clinically mild, but tracheobronchitis with persistent cough was frequent. The mortality rate was very low and deaths occurred only among people aged more than 60 years. Mortality was lower than in the previous epidemic - 407 GENERAL DISCUSSION-SESSION I in 1968, which was associated with a virus similar to the Tokyo variant. For example, in March 1969 the disease-specific mortality rate from influenza was 10.9 per thousand deaths, whereas in the same month of 1968 it was 16.4 per thousand deaths. Eight strains of virus A2 were isolated from 48 clinical influenza cases and were found to be similar to the Hong Kong variant. These results were confirmed by the World Influenza Centre. In a military camp the simultaneous spread of adeno- virus and of Hong Kong influenza virus infections was verified. MISS M. VICENTE. During the past 3 years, Chile has experienced various influenza outbreaks of dif- ferent sizes and origins. This report is based mainly on laboratory findings and partial information obtained from the Epidemiology Department of the National Health Service. During the winter of 1966 a fairly large outbreak of influenza B occurred during July and August. This outbreak was confirmed by many virus isola- tions and by serological evidence. During the same period, a few sporadic cases of influenza A2 were observed. Owing to a severe drought, the central and north- ern areas of the country received no rain for more than 2 years, and very mild temperatures were experienced during the winters of 1967 and 1968. A few confirmed cases of influenza A2 occurred during April and May 1967. In January 1968 an influenza A2 outbreak occurred in an isolated little town in the northern desert zone of the country. After this solitary episode, a larger outbreak occurred during the period from April to June. The epidemic was mild and no significant increase in mortality was observed. This outbreak was also caused by an influenza A2 virus that was more closely related to the previously existing A2 variants than to the A2/Hong Kong/68 variant. The climatic pattern became normal in 1969, and we suffered a severe epidemic during the winter. The first cases were observed at the end of May, when the first virus isolations were made. In Santiago and the central provinces the epidemic reached its peak during the week of 20-27 July. Clinical evi- dence of influenza was observed in the southern provinces in August and September. The number of deaths increased during July to almost twice the June figure. The outbreak declined during August and the last cases were observed at the end of the month. Absenteeism was quite exten- sive during the outbreak but it did not reach the levels of the 1957 pandemic. The mortality was also much lower than that of 1957. Viruses were isolated from mild cases and also from the lung tissue of persons who died. The isolations were made in embryonated eggs. Strains were typed with standard antisera and were found to be identical with the A2/Hong Kong/68 variant. Serological conversions for the latter were observed in HI tests. DR M. F. WARBURTON. After the introduction of the A2/Hong Kong virus into the Northern Territory of Australia in August 1968, virus was isolated from a patient in Melbourne as early as September. Further isolations were made in Melbourne in December and in Victoria and New South Wales during the first 4 months of 1969. The results of HI antibody tests on the sera of over 1000 young servicemen entering camp from the 4 southern states in early May, excluding those already vaccinated, was compared with the results of tests on similar sera taken early in 1968. The results indicate that 30% of the men had experienced the virus by May and that this was true for each of the states. By the middle of July the figure had risen to 45% and by the end of September it was over 50%. In view of the very low incidence of clinical influenza in these states there must have been a high level of subclinical infection in Australia. A second wave of A2/Hong Kong influenza has just occurred in the Northern Territory and it has been more widespread and severe than in 1968. DR J. C. MCDONALD. Contrary to the general impression, Canada was also affected by the Hong Kong influenza epidemic of 1968-69, though much less severely than its neighbours to the south. Analysis of death statistics and other data from the Canadian labour force survey showed that both excess morbidity in the working population and excess mortality were similar to that of the winter of 1967-68, when an A2 epidemic of moderate size also occurred. In a serological survey of a random sample of families in 4 major Quebec cities, persons were bled in the autumn of 1968 and again after the epidemic in the spring of 1969. Results suggest that the infec- tion rate was about 15% and was similar at all ages, and that about 18% of those studied had HI antibody (at titres greater than 1: 15) against the Hong Kong virus before the epidemic. 408 GENERAL DISCUSSION-SESSION I We are inclined to conclude that one of the reasons for the relatively favourable experience of Canada compared with that of the USA may have been the epidemic of the previous winter; fortuitous factors, such as timing-which apparently led to an interruption in the build-up of cases by the Christmas holiday period-may also have been involved. DR T. D. Y. CMIN. It is of interest to compare cer- tain epidemiological characteristics of Hong Kong influenza with those of influenza observed in 1957. During the winter of 1968 a questionnaire survey was conducted in a high school in Kansas City when influenza was prevalent in the general popula- tion. A similar study had been conducted in the same school in 1957. The occurrence of influenza-like illness was first observed in the first part of November and reached a peak in the middle of December. The total attack rate for influenza-like illness was 39 %. The age distribution of cases during the 1968 epidemic differed from that in 1957 in that in the former the attack rates among persons in the older age-groups were similar to those of school-age chil- dren. In 1957 the rates among school-age children were significantly higher than those in the older age-groups. Our observations on the age distribu- tion in 1968 were similar to those made by Dr James Maynard in Arizona. It is also of interest to compare the ages of those who first contracted influenza in families during the 1957 and 1968 epidemics. Chil- dren of school age constituted 85% of the index cases in 1957 and 50% in 1968. These data suggest that the 1968 epidemic was not school-centred and that school-age children were no more likely to introduce the virus into families than were adults. DR J. W. MILLAR. In 156 families in a residential community in Montgomery County, Maryland, influenza was probably introduced by adults and not by schoolchildren. From December 1968 to the end of February 1969 only 18% of the index cases were in schoolchildren, who either showed the symptoms of influenza before the rest of the family or were the only members of the family to contract the disease. In 40% of the families influenza first occurred in an adult, usually in a college-age sibling or the father. In 42% of the families no respiratory disease was reported. Very little intra-family spread of the illness was noted. DR V. F. GUINEE. Epidemics of A2 influenza oc- curred in New York City during the winters of 1967-68 and 1968-69. In 1967 the disease first appeared in schools and gradually affected adults. In 1968 there was an explosive appearance in adult working groups. Typically there would be a high attack rate in one office, with the office next door unaffected. Both epidemics had approximately the same duration of 8-10 weeks. It was estimated that about 20% of the population were affected in 1967-68 and 25% in 1968-69. During both epidemics there was an increase in the number of deaths from all causes- 3% in 1967-68 and 14% in 1968-69. However, the epidemic ofHong Kong influenza was more severe in those under 65 years of age. In this age-group there were 596 excess deaths in the first epidemic and 1327 in the second. In those aged 65 years and over, there were 2458 excess deaths in 1967-68, but only 1946 in 1968-69. DR J. H. S. GEAR. Studies carried out by Miss Harwin and Dr Joosting of our Institute's Respira- tory Virus Unit showed that no influenza A infec- tions occurred in South Africa during 1966. Epi- demics caused by a strain closely related to A2/ Tokyo/67 occurred in July-August 1967 and April- June 1968. The first outbreak caused by the Hong Kong strain affected US Air Force personnel who came to South Africa to help to monitor the flight around the moon in December 1968. The virus was isolated from 4 of 5 airmen who were investigated, but the infection did not spread to their immediate contacts and was presumably acquired before they left the USA. Hong Kong influenza in epidemic form broke out at the end of March 1969 among mine workers recruited in the subtropical territory bordering South Africa. It spread rapidly among the mine workers and then to the general population, later affecting particularly the infants and children. It is of some interest to recall that the epidemics of 1918 and 1957 first affected mine workers in the centre of the country. In the 1969 epidemic the number of cases among mine workers was less than in the 1957 Asian epidemic, and there was little interference with the work of the mines. Millions of doses of vaccine were available for administration before the epidemic began and it was possible to carry out limited studies of its value. It is also of some interest that a wave of influenza B virus infection occurred at the same time as the Hong Kong influenza outbreak. 6 409 GENERAL DISCUSSION-SESSION I DR E. FARKAS. In 1968 Hungary experienced a widespread influenza A2 epidemic caused by a strain closely related to A2/Tokyo/67. The intensity of the epidemic varied considerably in different areas of the country: south-western areas were affected most heavily, whereas the eastern areas were affected hardly at all. In 1969 the A2/HongKong/68 virus was the causative agent and the situation was reversed: both morbidity and the severity of the infection were greater in some eastern areas. SIR CHRISTOPHER ANDREWES. I have been increas- ingly puzzled by the accounts of different incidence of Hong Kong influenza in different countries. I venture to put forward an hypothesis invented on the spur of the moment-might there not be 2 vari- ants of the virus circulating around the world, differing in virulence and power to spread? The outcome in a particular country might depend on quantitative factors and/or timing. For instance, the epidemic in the USA might have been caused by a virulent variant that spread rapidly from eastern Asia, and the United Kingdom might have been seeded by a milder variant before being seriously affected by a virulent one. Hypotheses are valuable only if they can be tested. It might be worth while to look for markers differentiating Hong Kong viruses from milder ones. Since all the viruses are antigenically alike, people may not have troubled to look for other differences. DR S. FAZEKAS DE ST GROTH. I think the observa- tions can be just as well accounted for by a difference in the populations at risk as by a difference in the virus. I shall present the evidence for this at a later session, but the gist of the findings is that the A2 era had a main stream of viruses that were typically A2 and also a second lineage starting about 1960 that was restricted fo the Australia-New Zealand area. This group has the characteristics of the main A2 viruses, but has also anticipated the mutation that sets off the Hong Kong type. I call them " bridging antigens ". Now, since Australia had years of experience with these antigens, I predicted that we should not have a Hong Kong-type epi- demic comparable in incidence with that in the Northern hemisphere. This is one of the few of my predictions that have come true. DR D. A. J. TYRRELL. Following up Sir Chris- topher's comments, I suggest that ability to spread should be considered more carefully. We know there have been antigenically new strains of influenza B virus that have produced only local epidemics and then disappeared. Two influenza strains might be the same antigenically, but one might produce a higher secondary attack rate than the other among non-immune family contacts; a laboratory model might be difficult to find, but I could suggest the transmission from donor to recipient ferrets as in the experiments of Dr Schulman and Dr Kilbourne with mice. DR C. H. STUART-HARRIS. In attempting to predict the future of Hong Kong influenza in Britain, the results of 2 serological surveys using the HI test carried out in Sheffield are of interest. The first was made on 129 sera collected in Hong Kong in 1964 through the courtesy of Professor McFadyean. Dr Schild tested these against swine, PR/8, FM/i, A2/57 and Equi-2 viruses and compared the results with those of a study of sera collected in Sheffield during 1961-62. When different age-groups were compared, the antibody patterns of the 2 sets of sera were remarkably similar. The Hong Kong sera still available were recently tested against Hong Kong virus, but antibody was detected in only I specimen from a person over 70 years of age. The second study involved the comparison of 270 pre-epidemic sera collected between September and December 1968 with 453 post-epidemic sera collected after May 1969. The usual short period of virus-serum contact was employed in order to esti- mate the shift in antibodies as a result of the epi- demic, though it was known that low titres of HI antibodies were demonstrable in sera collected from children before the epidemic when virus and serum were incubated for 1 hour. All sera were treated with cholera filtrate. The proportion of pre-epidemic sera containing antibodies at a 1: 6 or greater dilu- tion varied from 4% to 18 % in the various decades. All of 59 sera from children less than 12 years of age were negative; the sera of those aged 70-79 years gave the highest proportion of positive results, and 3 sera from those aged over 80 years contained anti- bodies. The titres of antibodies in the older adults were greater than those in younger persons. Of the post-epidemic sera, 20%-85% contained antibodies. The figure was about 30% in those under 12 years of age to 40% in those aged 20-29 years, and 12 of 14 sera from persons over 80 years of age contained antibodies. High titres of antibodies were present in those aged 15-30 years. The results indicated that in the post-epidemic period, apart from those 410 GENERAL DISCUSSION-SESSION I aged 80 years or over, more than 50% of persons in the different age-groups had no antibodies at a 1: 6 serum dilution. Thus, a return of Hong Kong influenza appears probable, particularly because more than 60% of the children under 12 years of age still have no antibodies. However, the time of the second wave cannot be foreseen. DR W. HOEPKEN. In the Federal Republic of Ger- many the first outbreaks were reported et the end of December 1968 and in January 1969. The infec- tion was introduced from the USA, the Netherlands, and other unknown sources. Only A2/Hong Kong strains were isolated. The spread in the population was slow. During the first week of February the number of sickness-benefit claims was only 30% higher than in normal years. In most areas of the Federal Republic of Germany the epidemic reached its peak between 10 and 20 March, when sickness- benefit claims were about 100% higher than in 1967. In 1968 a severe A2 epidemic began on 10 January and reached a peak between 7 and 12 February. A comparison of the 1968 and 1969 epidemics gave results similar to those in the United Kingdom. About 20% of the population developed antibody, and the morbidity increased by about 10%. The death rates during the epidemics were quite different. In February 1968 the excess death rate was 43% higher than the average figure for February of the 3 previous years, and was similar to that of October 1957. The excess mortality during the Hong Kong influenza epidemic was low-about one-third of that of the 1968 epidemic. Comparisons of the age distribution of influenza deaths also showed differ- ences. In 1957 many deaths occurred in younger people, whereas in 1968 there was excess mortality in those aged over 60 years. During the Hong Kong influenza epidemic excess mortality was observed only in persons older than 70 years. Many cases of influenza B infection occurred in the northern part of the Federal Republic of Ger- many. About 12% of the school-age children and young adults were immunized. The disease was very mild. 411