381
Public Health INFLUENZA VACCINATION AND MORTALITY FROM BRONCHOPNEUMONIA IN THE ELDERLY C. H. L. HOWELLS C. K. VESSELINOVA-JENKINS A. D. EVANS JOCELYN JAMES Public Health Laboratory, University Hospital Heath Park, Cardiff CF4 4XW
RESULTS
of Wales,
In a three-year influenza vaccination programme carried out among elderly these were found to have a lower hæmagpatients glutination-inhibiting antibody level and a poorer serological response to vaccination than younger persons in the same city. Although there was little difference in overall respiratory illness between the vaccinated and unvaccinated groups until the third year of observation, those who received vaccine showed a substantially smaller incidence of bronchopneumonia and a significantly lower mortality than those not so protected. The observations are believed to justify the giving of influenza vaccine in this agegroup.
Sum ary
INTRODUCTION
MORTALITY from epidemic influenza is usually substantial in the elderly. The Department of Health and Social Security therefore advises vaccination whenever an outbreak is expected. Despite the amount of vaccine used, however, there have been few direct studies in the U.K. justifying this advice, describing the serological responses that occur and illustrating the effect of vaccine on mortality. In the investigation described here the antibody response to influenza vaccine, the incidence of bronchopneumonia, and the mortality therefrom have been examined in vaccinated and unvaccinated residents of old people’s homes. Some of the serological findings have been compared with those obtained from younger persons in the
same
city.
METHODS
AND MATERIALS
The observations began in November, 1971, when all residents requesting immunisation had 10 ml. of blood taken before being given 1 ml. of saline-based influenza vaccine (’Admune’, B.D.H.) (see below) subcutaneously. Venesection was repeated six weeks later. Those not immunised were surveyed for illness, but the authorities responsible for the homes considered that a controlled trial would be inappropriate in elderly patients. The unvaccinated group, therefore, were not, strictly speaking, controls ". Thus, they were not randomly selected from the total population although their age and general health were roughly comparable. All residents, whether vaccinated or not, were under constant surveillance. Respiratory illness was therefore recorded easily, although notification was not always as prompt as we had hoped. Nose and throat swabs were transported to the laboratory without delay in chilled transport medium. Whenever possible, blood samples were repeated at this time and also fourteen days later. Serological specimens were also obtained from the staff "
of the homes and from volunteers from the staff of Glamorgan County Council. All specimens were examined by standard laboratory methods. The vaccination programme for the residents of the homes was repeated in the autumn of 1972 and 1973. During the first two years the vaccine contained 400 i.u. A2/HK/ x 31/68 and 200 i.u. B/Vic.98926/70 in 1 ml. In the third year the composition was 400 i.u. A/Eng/ 42/72 (HN2) (xPR8), 100 i.u. B/Vic/98926/70, and 100 i.u. B/Hong Kong/8/73.
Table I shows the numbers and ages of those vaccinated and surveyed. Most were over 71; the majority were female Before immunisation, only 44% had hæmagglutination-inhibiting (H.I.) antibody >10 (reciprocal of to influenza and A/HK/68 dilution) 18% to the B strain. In 1972, 68% of those immunised in the previous year had antibody to A/HK/68 and 23% to B. Following vaccination these proportions rose to 77% and 33%, respectively. Pre-vaccination results for those receiving vaccine for the first time in 1972 were similar to those for 1971, but fewer showed an antibody response to A. Although influenza A/Eng/42/72 had not been isolated in Cardiff at that
already present, particularly during the previous year. By 1973 most residents, whether immunised previously or not, had achieved good antibody levels both to the Hong Kong and to the 42/72 variants. Indeed, all those who had received vaccine previously had antibody to the latter following repeat immunisation. A good proportion also acquired antibody to influenza
time, antibody
was
amongst those immunised
B.
Similar results were obtained with influenza A It was forecast that infections with this strain would occur during 1973. Again, many participants already had antibody before immunisation
(929/73).
(table II). Table ill shows the percentage of persons with A2 antibody in various communities. The per-
H.I.
TABLE I-AGE DISTRIBUTION OF PATIENTS IMMUNISED AND SURVEYED
382
centage of those with antibody amongst the elderly is lower than in other age-groups. Particularly noteworthy is the difference between the elderly and the county-hall employees, since the latter lived in the same city and were examined in the same laboratory in the same year. Table iv shows the geometric mean titre (G.M.T.) of the H.I. level obtained over the years from the TABLE III-PERCENTAGE WITH H.I. ANTIBODY > INFLUENZA A IN VARIOUS COMMUNITIES
10 TO
Fig. I-Antibody
For comparison, the figures obtained with volunteers from the staff of Glamorgan County Council are included. The G.M.T. rose progressively, but even at the end did not approach the figure obtained initially from the Glamorgan County Council employees (a younger age-group). Fig. 1 shows the effect of vaccination on the G.M.T. of the elderly compared with that obtained from the Glamorgan County Council employees. Initially, the G.M.T. is higher in the younger age-group and the effect of vaccination is more striking among them. Fig. 2 shows the G.M.T. plotted against age for 900 inhabitants of Cardiff in 1971. The latter comprised staff of the homes and Glamorgan County Council employees. Both the G.M.T. and the effect on vaccination appear to diminish up to the age of 80 -t- ; there are, of course, comparatively few in this group. Table v shows the incidence of respiratory illness, bronchopneumonia, and its mortality in the three years. Until 1973-74 there is little difference between the two groups with regard to overall respiratory illness. In the last year of observation, however, there were no respiratory illnesses whatever in immunised patients, compared with 5% among the others. It was, of course, during this year that the highest anti-
elderly.
TABLE V-OVERALL RESPIRATORY
body
response to A2 components before and after vaccination against influenza.
attained. It should be noted that laboratory proof of influenza infection was only obtained in 1 case in 1971-72, in 10 cases in 1972-73, and in 2 cases in 1973-74 (see below). The number and percentage of those developing bronchopneumonia are also shown. In each year substantially more unvaccinated persons developed this complication and the difference in mortality between the two groups is statistically significant (r>001). levels
were
DISCUSSION
In this
study the small percentage of the elderly possessing antibody before vaccination in 1971, compared with younger subjects, is somewhat surprising in view of the presumed lifetime exposure to influenza virus. After vaccination, however, the majority of the elderly readily acquired antibody. Indeed, by 1974, 100% possessed H.I. antibody to the 42/72 strain. Significantly perhaps at this time there were no respiratory illnesses among them. It also appears that the amount of antibody present (shown by the G.M.T. of the H.I. titre) increased from 1971 to 1974 (table iv). Even at the end of the period of observation, however, the amount of antibody before and after vaccination was less in elderly persons than in younger
ILLNESS, BRONCHOPNEUMONIA,
AND MORTALITY
383
The response to vaccination too decrease with age (figs. 1 and 2). The reason for these findings remains
people.
appeared
to
lower incidence of lower case mortality.
a
bronchopneumonia
and thus
a
conjectural. 1
We thank Prof. R. E. O. Williams for editorial advice; the Epidemiological Research Laboratory, Colindale, for general support and supply of vaccine; the technical staff of the Cardiff
hormonal deterioration and alteration of lymphocytes with age are thought to operate. The usefulness of influenza vaccine in this age-group
Public Health Laboratory for their assistance; Dr Donald Anderson (late medical officer of health for Cardiff) and Dr Philip Revington (late medical officer of health for Glamorgan) and their staffs for cooperation; and Mr R. G. Newcombe for statistical advice.
Possibly immunological
senescence occurs
and tissue
response decreases with age. Certainly, Makinodan has found this effect in animals where such factors as
to assess because of some of the of the present study. Not only did the idea of a controlled trial prove unacceptable to the authorities at that time, but there were also difficulties in demonstrating that the respiratory illnesses were always influenzal in origin. Thus, despite all efforts, there was often a delay in notification so that the viraemic phase may have been over by the time swabs were taken. Again, in some cases there was a determined reluctance for further venesection by some patients so that specimens could not be taken. In addition, several patients developed bronchopneumonia (occasionally fatal) with few preliminary upperrespiratory symptoms before investigations could be started. Notwithstanding these limitations the vaccinated group did indeed have a better experience than the unvaccinated, particularly with regard to bronchopneumonia and mortality. In the absence of any other detectable factor which could have accounted for this difference, therefore, it seems reasonable to attribute it to the vaccination. Thus, it appears that there is some justification for the official advice to give vaccine in this age-group. Before vaccination there may be a low antibody level, so presumably resistance to infection is small. After vaccination a serological response can be expected in the majority, although the magnitude of this response may be smaller than in younger subjects. Finally, and most importantly, the giving of vaccine may result in
is
more
difficult
special problems
REFERENCES 1.
Makinodan, T. in Tolerance, Autoimmunity and Aging (compiled and edited by M. M. Sigel and R. A. Good). Springfield, Illinois, 1972.
Howells, C. H. L., Evans, A. D., Vesselinova-Jenkins, C. Lancet, 1973, i, 1436. 3. Hoskins, T. W., Davies, Joan R., Allchin, A., Miller, Christine L., Pollock, T. M. ibid. 1973, ii, 116.
2.
Occasional
Survey
TETANUS IN HAITI FLORENCE N. MARSHALL* MULLER J. GARNIER KENNETH J. DAVISON † FRANK J. LEPREAU, JR. &Dag er; Departments of Anesthesia, Pediatrics, and Surgery,
Hôpital Albert Schweitzer, Deschapelles, Haiti
1958-72, 985 cases of tetanus (excluding tetanus of the newborn) were admitted to a hospital in Haiti. Mortality was 22 %, and in later years (1966-72) mortality fell. During this period the dosage of tetanus antitoxin was lowered to 10,000 units and, for sedation, diazepam has satisfactorily replaced multiple-drug regimens used in earlier years. However, good nursing, including close attention to breathing, is probably the most important item in treatment. As a result of a programme of maternal immunisation, admissions for neonatal tetanus have fallen, and mortality for this condition has been reduced to 26%. Sum ary
In
INTRODUCTION
Hopital Albert Schweitzer is a general charity hospital of 162 beds which has often had 2 or 3 children in a bed. In 1972 we had 74,570 outpatient visits, excluding those coming for immunisation. The hospital serves primarily a district of 90,000-100,000 people in 110 square miles of the Artibonite Valley which extends inland from St. Marc, but tetanus patients come from beyond this area. PATIENTS
We have analysed all 985 cases of tetanus seen since the hospital opened in 1957, paying special attention to the 663 cases treated in the seven years 1966-72. Of the entire group, 64% were children with 19% mortality and 36% were adults with 29% mortality. Few adults were over fifty years of age; the oldest was eightyone. Most patients were slender, muscular, and in good general health before their tetanus. Of the 663 cases
Fig. 2-Geometric mean titre of H.I. level to influenza A (N) and B (8) among 900 inhabitants of Cardiff before and after vaccination.
* Present address: 312 Greenwich Street, Hempstead, N.Y. 11550. &dag er; Present address: Department of Anesthesia, Massachusetts General Hospital, Boston, Massachusetts 02109. ‡ Present address: Frontier Nursing Service, Hyden, Leslie County, Kentucky 41749.
Public Health INFLUENZA VACCINATION AND MORTALITY FROM BRONCHOPNEUMONIA IN THE ELDERLY C. H. L. HOWELLS C. K. VESSELINOVA-JENKINS A. D. EVANS JOCELYN JAMES Public Health Laboratory, University Hospital Heath Park, Cardiff CF4 4XW
RESULTS
of Wales,
In a three-year influenza vaccination programme carried out among elderly these were found to have a lower hæmagpatients glutination-inhibiting antibody level and a poorer serological response to vaccination than younger persons in the same city. Although there was little difference in overall respiratory illness between the vaccinated and unvaccinated groups until the third year of observation, those who received vaccine showed a substantially smaller incidence of bronchopneumonia and a significantly lower mortality than those not so protected. The observations are believed to justify the giving of influenza vaccine in this agegroup.
Sum ary
INTRODUCTION
MORTALITY from epidemic influenza is usually substantial in the elderly. The Department of Health and Social Security therefore advises vaccination whenever an outbreak is expected. Despite the amount of vaccine used, however, there have been few direct studies in the U.K. justifying this advice, describing the serological responses that occur and illustrating the effect of vaccine on mortality. In the investigation described here the antibody response to influenza vaccine, the incidence of bronchopneumonia, and the mortality therefrom have been examined in vaccinated and unvaccinated residents of old people’s homes. Some of the serological findings have been compared with those obtained from younger persons in the
same
city.
METHODS
AND MATERIALS
The observations began in November, 1971, when all residents requesting immunisation had 10 ml. of blood taken before being given 1 ml. of saline-based influenza vaccine (’Admune’, B.D.H.) (see below) subcutaneously. Venesection was repeated six weeks later. Those not immunised were surveyed for illness, but the authorities responsible for the homes considered that a controlled trial would be inappropriate in elderly patients. The unvaccinated group, therefore, were not, strictly speaking, controls ". Thus, they were not randomly selected from the total population although their age and general health were roughly comparable. All residents, whether vaccinated or not, were under constant surveillance. Respiratory illness was therefore recorded easily, although notification was not always as prompt as we had hoped. Nose and throat swabs were transported to the laboratory without delay in chilled transport medium. Whenever possible, blood samples were repeated at this time and also fourteen days later. Serological specimens were also obtained from the staff "
of the homes and from volunteers from the staff of Glamorgan County Council. All specimens were examined by standard laboratory methods. The vaccination programme for the residents of the homes was repeated in the autumn of 1972 and 1973. During the first two years the vaccine contained 400 i.u. A2/HK/ x 31/68 and 200 i.u. B/Vic.98926/70 in 1 ml. In the third year the composition was 400 i.u. A/Eng/ 42/72 (HN2) (xPR8), 100 i.u. B/Vic/98926/70, and 100 i.u. B/Hong Kong/8/73.
Table I shows the numbers and ages of those vaccinated and surveyed. Most were over 71; the majority were female Before immunisation, only 44% had hæmagglutination-inhibiting (H.I.) antibody >10 (reciprocal of to influenza and A/HK/68 dilution) 18% to the B strain. In 1972, 68% of those immunised in the previous year had antibody to A/HK/68 and 23% to B. Following vaccination these proportions rose to 77% and 33%, respectively. Pre-vaccination results for those receiving vaccine for the first time in 1972 were similar to those for 1971, but fewer showed an antibody response to A. Although influenza A/Eng/42/72 had not been isolated in Cardiff at that
already present, particularly during the previous year. By 1973 most residents, whether immunised previously or not, had achieved good antibody levels both to the Hong Kong and to the 42/72 variants. Indeed, all those who had received vaccine previously had antibody to the latter following repeat immunisation. A good proportion also acquired antibody to influenza
time, antibody
was
amongst those immunised
B.
Similar results were obtained with influenza A It was forecast that infections with this strain would occur during 1973. Again, many participants already had antibody before immunisation
(929/73).
(table II). Table ill shows the percentage of persons with A2 antibody in various communities. The per-
H.I.
TABLE I-AGE DISTRIBUTION OF PATIENTS IMMUNISED AND SURVEYED
382
centage of those with antibody amongst the elderly is lower than in other age-groups. Particularly noteworthy is the difference between the elderly and the county-hall employees, since the latter lived in the same city and were examined in the same laboratory in the same year. Table iv shows the geometric mean titre (G.M.T.) of the H.I. level obtained over the years from the TABLE III-PERCENTAGE WITH H.I. ANTIBODY > INFLUENZA A IN VARIOUS COMMUNITIES
10 TO
Fig. I-Antibody
For comparison, the figures obtained with volunteers from the staff of Glamorgan County Council are included. The G.M.T. rose progressively, but even at the end did not approach the figure obtained initially from the Glamorgan County Council employees (a younger age-group). Fig. 1 shows the effect of vaccination on the G.M.T. of the elderly compared with that obtained from the Glamorgan County Council employees. Initially, the G.M.T. is higher in the younger age-group and the effect of vaccination is more striking among them. Fig. 2 shows the G.M.T. plotted against age for 900 inhabitants of Cardiff in 1971. The latter comprised staff of the homes and Glamorgan County Council employees. Both the G.M.T. and the effect on vaccination appear to diminish up to the age of 80 -t- ; there are, of course, comparatively few in this group. Table v shows the incidence of respiratory illness, bronchopneumonia, and its mortality in the three years. Until 1973-74 there is little difference between the two groups with regard to overall respiratory illness. In the last year of observation, however, there were no respiratory illnesses whatever in immunised patients, compared with 5% among the others. It was, of course, during this year that the highest anti-
elderly.
TABLE V-OVERALL RESPIRATORY
body
response to A2 components before and after vaccination against influenza.
attained. It should be noted that laboratory proof of influenza infection was only obtained in 1 case in 1971-72, in 10 cases in 1972-73, and in 2 cases in 1973-74 (see below). The number and percentage of those developing bronchopneumonia are also shown. In each year substantially more unvaccinated persons developed this complication and the difference in mortality between the two groups is statistically significant (r>001). levels
were
DISCUSSION
In this
study the small percentage of the elderly possessing antibody before vaccination in 1971, compared with younger subjects, is somewhat surprising in view of the presumed lifetime exposure to influenza virus. After vaccination, however, the majority of the elderly readily acquired antibody. Indeed, by 1974, 100% possessed H.I. antibody to the 42/72 strain. Significantly perhaps at this time there were no respiratory illnesses among them. It also appears that the amount of antibody present (shown by the G.M.T. of the H.I. titre) increased from 1971 to 1974 (table iv). Even at the end of the period of observation, however, the amount of antibody before and after vaccination was less in elderly persons than in younger
ILLNESS, BRONCHOPNEUMONIA,
AND MORTALITY
383
The response to vaccination too decrease with age (figs. 1 and 2). The reason for these findings remains
people.
appeared
to
lower incidence of lower case mortality.
a
bronchopneumonia
and thus
a
conjectural. 1
We thank Prof. R. E. O. Williams for editorial advice; the Epidemiological Research Laboratory, Colindale, for general support and supply of vaccine; the technical staff of the Cardiff
hormonal deterioration and alteration of lymphocytes with age are thought to operate. The usefulness of influenza vaccine in this age-group
Public Health Laboratory for their assistance; Dr Donald Anderson (late medical officer of health for Cardiff) and Dr Philip Revington (late medical officer of health for Glamorgan) and their staffs for cooperation; and Mr R. G. Newcombe for statistical advice.
Possibly immunological
senescence occurs
and tissue
response decreases with age. Certainly, Makinodan has found this effect in animals where such factors as
to assess because of some of the of the present study. Not only did the idea of a controlled trial prove unacceptable to the authorities at that time, but there were also difficulties in demonstrating that the respiratory illnesses were always influenzal in origin. Thus, despite all efforts, there was often a delay in notification so that the viraemic phase may have been over by the time swabs were taken. Again, in some cases there was a determined reluctance for further venesection by some patients so that specimens could not be taken. In addition, several patients developed bronchopneumonia (occasionally fatal) with few preliminary upperrespiratory symptoms before investigations could be started. Notwithstanding these limitations the vaccinated group did indeed have a better experience than the unvaccinated, particularly with regard to bronchopneumonia and mortality. In the absence of any other detectable factor which could have accounted for this difference, therefore, it seems reasonable to attribute it to the vaccination. Thus, it appears that there is some justification for the official advice to give vaccine in this age-group. Before vaccination there may be a low antibody level, so presumably resistance to infection is small. After vaccination a serological response can be expected in the majority, although the magnitude of this response may be smaller than in younger subjects. Finally, and most importantly, the giving of vaccine may result in
is
more
difficult
special problems
REFERENCES 1.
Makinodan, T. in Tolerance, Autoimmunity and Aging (compiled and edited by M. M. Sigel and R. A. Good). Springfield, Illinois, 1972.
Howells, C. H. L., Evans, A. D., Vesselinova-Jenkins, C. Lancet, 1973, i, 1436. 3. Hoskins, T. W., Davies, Joan R., Allchin, A., Miller, Christine L., Pollock, T. M. ibid. 1973, ii, 116.
2.
Occasional
Survey
TETANUS IN HAITI FLORENCE N. MARSHALL* MULLER J. GARNIER KENNETH J. DAVISON † FRANK J. LEPREAU, JR. &Dag er; Departments of Anesthesia, Pediatrics, and Surgery,
Hôpital Albert Schweitzer, Deschapelles, Haiti
1958-72, 985 cases of tetanus (excluding tetanus of the newborn) were admitted to a hospital in Haiti. Mortality was 22 %, and in later years (1966-72) mortality fell. During this period the dosage of tetanus antitoxin was lowered to 10,000 units and, for sedation, diazepam has satisfactorily replaced multiple-drug regimens used in earlier years. However, good nursing, including close attention to breathing, is probably the most important item in treatment. As a result of a programme of maternal immunisation, admissions for neonatal tetanus have fallen, and mortality for this condition has been reduced to 26%. Sum ary
In
INTRODUCTION
Hopital Albert Schweitzer is a general charity hospital of 162 beds which has often had 2 or 3 children in a bed. In 1972 we had 74,570 outpatient visits, excluding those coming for immunisation. The hospital serves primarily a district of 90,000-100,000 people in 110 square miles of the Artibonite Valley which extends inland from St. Marc, but tetanus patients come from beyond this area. PATIENTS
We have analysed all 985 cases of tetanus seen since the hospital opened in 1957, paying special attention to the 663 cases treated in the seven years 1966-72. Of the entire group, 64% were children with 19% mortality and 36% were adults with 29% mortality. Few adults were over fifty years of age; the oldest was eightyone. Most patients were slender, muscular, and in good general health before their tetanus. Of the 663 cases
Fig. 2-Geometric mean titre of H.I. level to influenza A (N) and B (8) among 900 inhabitants of Cardiff before and after vaccination.
* Present address: 312 Greenwich Street, Hempstead, N.Y. 11550. &dag er; Present address: Department of Anesthesia, Massachusetts General Hospital, Boston, Massachusetts 02109. ‡ Present address: Frontier Nursing Service, Hyden, Leslie County, Kentucky 41749.
