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The immunological response to polyvalent meningococcal vaccine in Bauchi State, Nigeria
351 TIZANSACTIONS OF THE ROYAL SOCIETYOF TROPICALMEDK~NE AND HYGIENE, VOL. 76, No. 3, 1982
The immunological
response to polyvalent meningococcal Bauchi State, Nigeria IDRIS
MOHAMMED* AND M. M. DAMISAHt
Dept. of Medicine,
Specialist Hospital,
The uost-vaccination antibody response to both Group A and Group C meningoc&cal-polysaccharide antigen was studied in 397 male and 359 female vaccinated persons aged between 4 and 40 years from Bauchi Town and neighbouring villages in Nigeria. No difference in response was observed between the sexes. Highest antibody levels occurred in those aged between 13 and 28 years. Haemoglobin genotype did not affect response. Malnourished children had significantly lower mean IgG, IgA and IgM levels and the response to meningovaccine was also lower than in normal children. Introduction
As early as 1963 LAPEYSSONNIE had shown that it was possible to prevent an attack of meningococcal meningitis by vaccination. Since then, several studies have been carried out to determine the efficacy of meningococcal vaccines (ERWA et al., 1973; ETTORI et al., 1977). Limited campaigns have been in progress in French-soeakinP: West Africa, but it was only recently tha’t mass immunization campaigns we& started in Nigeria. The results of vaccination have been variable and in some casesdisappointing. The capsular meningococcal polysaccharide evokes antibody response which appears to be affected by age, malnutrition and haemoglobin genotype (GREENWOOD et al., 1.9@)..When certain levels of antibody are reached, the vaccine offers protection from clinical meningitis in most individuals (GOLDSCHNEIDER et al., 1973; GREENWOOD et al., 1980). A mass immunization programme was mounted to cover the susceptible population of Bauchi State of Nigeria (approximate population 4,000,000) over a period of four years and it was decided to carry out a limited immunological evaluation of the effects of this exercise. The polyvalent group A and Group C polysaccharide vaccine (Institut Merieux) was used. Antibody responses measured one month after vaccination were maximal between the agesof 9 and 32. They were not affected by haemoglobin genotype but relative imnumodeficiency causeda diminution of the response. This study provides confirmation of some earlier observations made by several other workers. There is need to carry out further immunological evaluations of the response to vaccination with currently available polyvalent vaccines. Patients
vaccine in
and Methods
A total of 756 vaccinated persons (397 males and 359 females) aged between 4 and 40 years were studied. 350 of the 756 were living in and around Bauchi Town itself and the remainder in surrounding villaaes 10 to 50 km awav. Venous blood was taken for %nmunoglobulin and meningococcal antibody studies from all subjects before vaccination. The
Bauchi,
Nigeria
vaa&&tin. _wascared ,ut by pe&o-jet injectors which delivered O-5 ml of the polyvalent (Groups A and C) vaccine which was purchased from Institut Merieux. France. bv the Ministrv of Health of Bauchi State. Bl&d was’taken again f&m the same subjects one month after vaccination. Antibodies to Groups A and C meningococcal polysaccharide vaccine were determined by passive haemagglutination using human blood group 0 Rhesus negative cells coated with pure Group A or C polysaccharide antigen. Serum immunoglobulins were measured by standard radial immunodiffusion. The haemoglobin genotype was measured by cellulose acetate electrophoresis. A group of 14 clinically undernourished children was included in the study, and compared with another group of age- and sex-matched normal children. tiesuIts
Antibodies to Group A or C vaccine were undetectable in all but 11 subjects pre-vaccination, in whom values of 0.1 to 0.4 titres (mean + s.d. 0.2 + 0.15) were obtained. Pre-vaccination data are therefore not shown in the Fig. 1 which shows the post-vaccination antibody response to both Group A and Group C meningococcal polysaccharide vaccine. The response to Group A is higher and more sustained than that to Group C. An analysis of the responseto Group A and Group C polysaccharide showed no difference between the sexes. Response to both Groups in the vaccine was fairly good at one month, and the highest antibody levels were found in subjects aged between 13 and 28 years. Table I shows the mean antibody levels amongst the various age groups studied. Tho& aged 9 to 12 and 29 to 32 years also showed good reswnses. The antibody response to both Groups A and C did not differ Gong% subjects with hairnoglobin genotype AA or AS. The mean Group A antibody levels for those with genotype AA was 8.35 It 2.29, compared to 8.23 ? 2.45 for those with genotype AS, whereas the antibody levels to group C were 5.16 t- 2.28 and 5.12 + 2.29 respectively. ‘l‘able II is a comparison of pre-immunization immunoglobulin levels. as well as post-vaccination meningococcal antibody titres amongst malnourished and normal children. Malnourished children had significantly lower mean IgG, IgA and IgM levels as compared with normal children (P
Mass vaccination against cerebrospinal meningitis usin the polysaccharide A and C vaccine produced *Present address and correspondence to: Dr. Idris Mohammed, Dept. of Medicine (Immunology Unit), Alunadu Be110 University Hospital, Zaria, Nigeria. tMr. Damisah died in a tragic motor accidenton 3.1.82.
352
IMMUNOLOGICAL
RESPONSE TO POLYVALENT
MENINGOVACCINE
IN NIGERIA
F-
[7
Male
8-
5-28 29-32 3336 3-l-40 Age in years Fig. 1. The response to GroupsA andC polyvalenrmeningococcal vaccine.The figuresfor GroupC werebrokendowninto malesandfemalesbur
becausethere was no differencebeoveensexesin responsethe Group A responseis shownas a single line.
Table I-Mean meningococcal antibody amongst various age groups studied
Age
Group Ez 13-16 17-20 21-24 25-28 29-32 33-36 37-40
levels
Mean + s.d. Group C Group A 3*45+0*39 7.18?0-41 9.85f0.42 11~25~0~41 10*10~0~38 96OkO.38 9.40+0-34 8.10f0.37 7.55kO.35
2.45kO.39 5.10t0.41 6.95rtO.42 8*00+044 7.7OkO.42 5.15+0*40 3.4OCO.38 14OkO.23
good antibody responses in normal persons aged 9 to 32. Fairly high levels of antibody were attained which could confer clinical protection against meningococcal meningitis. However, how long this protection lasts is still unresolved (BRANDT & ARTENSTEIN, 1975; LEPOW er al., 1977; MAKELA, 1979). It has been suggested(G~~~h'~00~8zW~~1, 1980),thatbecause there was a rapid decline in haemagglutinating antibody titres after vaccination in West Africa (SALlOU et al., 1976; GREENWOOD et al., 1980) immunity conferred by vaccination may be shortlived. It is, therefore, too early to assess the long term
effects of vaccination with the currently available vaccines because of the epidemiological nature of the disease; epidemics in West Africa tend to occur every five to ten years and although there has been no epidemic since 1978 this must not be attributed solely to the success of vaccination. However, a recent study in Nigeria (MOHAM.%~ED& ZARUBA, 1981) suggests that mass vaccination provides the best hope of containing the disease. In spite of this it would be necessary to monitor antibody titres for a long time to determine the length of protection which vaccination with the polyvalent vaccine could confer on individuals as well as on the community. In addition, strict surveillance has to be maintained for the next two to seven years before any definite conclusions can be drawn about long term benefits of vaccination. In contrast with the findings of GREENWOODet al. (1980), we have observed that haemoglobin genotype had no effect on the response to the vaccine. It is therefore difficult to sustain the argument that malaria-induced immunosuppression in those with genotype AA was responsible for the lower antibody titres. The reasons for this remain unclear. However, the results of the comparative study of malnourished and normal children provide further support for the concept of immunosuppression accounting for failure to respond adequately to the vaccine and may explain also why such immuno-compromised sublects are more susceptible to the lethal effects of meningococcal meningitis. There is currently a vogue amongst State
I. MOHAMMED
AND
Table II-A comparison of serum immunoglobulin normal and malnourished children
M.
M.
levels as well as meningococcal
Mean Serum ImmunoglobulinLevels Normal Children Malnourished children Student’s (t) test
I& 246*0+15.5 110.5+29.6 P<0*0001
Iid 83.5+9.8 58.5+7-5 P
Governments in the meningitis belt in Nigeria to mount yearly mass vaccination campaigns against meningococcal meningitis. As these go on, it becomes more and more necessary to monitor not only the epidemiological and clinical outcome, but also the immunological resposes to large scale immunization with these vaccines. Acknowledgements We are grateful to officials of the Bauchi State Ministry of-Health particularly Dr. N. H. Sajid and Professor K. Zaruba for assistance and encouragement. References Brandt,, B. L. & Artenstein, M. S. (1975). Duration of armbody responseafter vaccination with group C Neisseria meningiti&s polysaccharide. Journal of Infkious Diseases, 131, 569-572.
Erwa, H. H., Hasseb, M. A., Lapeysonnie, L., Sanborn, W. R. & Sippel? J. E. (1973). A serogroup meningococcal polysacchande vaccine. Studies in the Sudan to combat cerebrospinal meningitis caused by N&s&a meningitides Group A. Bulletin of the World Health Organization, 49, 301-305. Ettori, D., Saliou, I’., Renaudet, I. & Stoeckel. Ph. (19771. Le vaccin anti-tiingoccoque du type A: premiers essais ~;~;;!y~l&sen Afrique de 1’Ouest. Mtdecine tropicale, 37, Goldschneiier, I., Lepow, M. L., Gotshlich, E. C., Mauck, F. T., Bach], F. & Randolph, M. (1973). Immunogenicity of Group A and C meningococcal polysaccharides in human infants. Journal of Infectious Diseases, 128, 769-776.
353
DAMISAH
(IUiml)
kM 216k42.8 102k36.7 P
antibody levels among Antibody
Titre
Group A 4.37+0.39 2.9 +0.59 P
Log,
Group C 3*6+0.38 2.2+0.43 P
Greenwood, B. M., Bradley, A. K., Blakebrough, I. S., Whittle, H. C.., Marshall, T. F. de C. & Gilles, H. M. (1980). The nnmune response to a meningococcal polysaccharide vaccine in an African village. Transactions of the Rqal Society of Tropical Medicine and Hygiene, 74,
340-346. Greenwood, B. M. & Wali, S. S. (1980). Control of meningococcalinfection in the African meningitis belt by selective vaccination. Lancer, i, 729-732. Lapeysotie, L. (1963). La meningite cerebrospinale en Afrique. Bulletin of the World Health Organization, 28, suppi., 3-114. Lepow, M. L., Goldschneider, I., Gold, R., Randolph, M. & Gotschlich. E. C. (19771. Persistence of antibodv following immunisation of ihildren with group A and group C meningococcal polysaccharide vaccines. Paediatrics, 60, 673-680.
Makela, P. H. (1979). Meningococcal vaccination in Finland. WHO Third International Conference on Immunity and Immunisation in Cerebrospinal Meningitis Marburg,
October, 19.79. Mohammed, I. & Zaruba, K. (1981). Control of epidemic meningococcal meningitis b) ma& vaccination.-Lancer, ii. 80-83. Saliou, P., Lafaye, A. 81,Ettori, D. (1976). Vaccination antin&ingococcique par le vaccin polysaccharidede type A: Surveillance serologique par la technique haemagglutination passive an tours de l’annk suivant la vaccinade coordination tion. Documents Technique~rganisation et de cooperation pour la Lutte contre les Grandes Endemies,
no. 6185.
Accepted for publication
20th September,
1981 e
The immunological
response to polyvalent meningococcal Bauchi State, Nigeria IDRIS
MOHAMMED* AND M. M. DAMISAHt
Dept. of Medicine,
Specialist Hospital,
The uost-vaccination antibody response to both Group A and Group C meningoc&cal-polysaccharide antigen was studied in 397 male and 359 female vaccinated persons aged between 4 and 40 years from Bauchi Town and neighbouring villages in Nigeria. No difference in response was observed between the sexes. Highest antibody levels occurred in those aged between 13 and 28 years. Haemoglobin genotype did not affect response. Malnourished children had significantly lower mean IgG, IgA and IgM levels and the response to meningovaccine was also lower than in normal children. Introduction
As early as 1963 LAPEYSSONNIE had shown that it was possible to prevent an attack of meningococcal meningitis by vaccination. Since then, several studies have been carried out to determine the efficacy of meningococcal vaccines (ERWA et al., 1973; ETTORI et al., 1977). Limited campaigns have been in progress in French-soeakinP: West Africa, but it was only recently tha’t mass immunization campaigns we& started in Nigeria. The results of vaccination have been variable and in some casesdisappointing. The capsular meningococcal polysaccharide evokes antibody response which appears to be affected by age, malnutrition and haemoglobin genotype (GREENWOOD et al., 1.9@)..When certain levels of antibody are reached, the vaccine offers protection from clinical meningitis in most individuals (GOLDSCHNEIDER et al., 1973; GREENWOOD et al., 1980). A mass immunization programme was mounted to cover the susceptible population of Bauchi State of Nigeria (approximate population 4,000,000) over a period of four years and it was decided to carry out a limited immunological evaluation of the effects of this exercise. The polyvalent group A and Group C polysaccharide vaccine (Institut Merieux) was used. Antibody responses measured one month after vaccination were maximal between the agesof 9 and 32. They were not affected by haemoglobin genotype but relative imnumodeficiency causeda diminution of the response. This study provides confirmation of some earlier observations made by several other workers. There is need to carry out further immunological evaluations of the response to vaccination with currently available polyvalent vaccines. Patients
vaccine in
and Methods
A total of 756 vaccinated persons (397 males and 359 females) aged between 4 and 40 years were studied. 350 of the 756 were living in and around Bauchi Town itself and the remainder in surrounding villaaes 10 to 50 km awav. Venous blood was taken for %nmunoglobulin and meningococcal antibody studies from all subjects before vaccination. The
Bauchi,
Nigeria
vaa&&tin. _wascared ,ut by pe&o-jet injectors which delivered O-5 ml of the polyvalent (Groups A and C) vaccine which was purchased from Institut Merieux. France. bv the Ministrv of Health of Bauchi State. Bl&d was’taken again f&m the same subjects one month after vaccination. Antibodies to Groups A and C meningococcal polysaccharide vaccine were determined by passive haemagglutination using human blood group 0 Rhesus negative cells coated with pure Group A or C polysaccharide antigen. Serum immunoglobulins were measured by standard radial immunodiffusion. The haemoglobin genotype was measured by cellulose acetate electrophoresis. A group of 14 clinically undernourished children was included in the study, and compared with another group of age- and sex-matched normal children. tiesuIts
Antibodies to Group A or C vaccine were undetectable in all but 11 subjects pre-vaccination, in whom values of 0.1 to 0.4 titres (mean + s.d. 0.2 + 0.15) were obtained. Pre-vaccination data are therefore not shown in the Fig. 1 which shows the post-vaccination antibody response to both Group A and Group C meningococcal polysaccharide vaccine. The response to Group A is higher and more sustained than that to Group C. An analysis of the responseto Group A and Group C polysaccharide showed no difference between the sexes. Response to both Groups in the vaccine was fairly good at one month, and the highest antibody levels were found in subjects aged between 13 and 28 years. Table I shows the mean antibody levels amongst the various age groups studied. Tho& aged 9 to 12 and 29 to 32 years also showed good reswnses. The antibody response to both Groups A and C did not differ Gong% subjects with hairnoglobin genotype AA or AS. The mean Group A antibody levels for those with genotype AA was 8.35 It 2.29, compared to 8.23 ? 2.45 for those with genotype AS, whereas the antibody levels to group C were 5.16 t- 2.28 and 5.12 + 2.29 respectively. ‘l‘able II is a comparison of pre-immunization immunoglobulin levels. as well as post-vaccination meningococcal antibody titres amongst malnourished and normal children. Malnourished children had significantly lower mean IgG, IgA and IgM levels as compared with normal children (P
Mass vaccination against cerebrospinal meningitis usin the polysaccharide A and C vaccine produced *Present address and correspondence to: Dr. Idris Mohammed, Dept. of Medicine (Immunology Unit), Alunadu Be110 University Hospital, Zaria, Nigeria. tMr. Damisah died in a tragic motor accidenton 3.1.82.
352
IMMUNOLOGICAL
RESPONSE TO POLYVALENT
MENINGOVACCINE
IN NIGERIA
F-
[7
Male
8-
5-28 29-32 3336 3-l-40 Age in years Fig. 1. The response to GroupsA andC polyvalenrmeningococcal vaccine.The figuresfor GroupC werebrokendowninto malesandfemalesbur
becausethere was no differencebeoveensexesin responsethe Group A responseis shownas a single line.
Table I-Mean meningococcal antibody amongst various age groups studied
Age
Group Ez 13-16 17-20 21-24 25-28 29-32 33-36 37-40
levels
Mean + s.d. Group C Group A 3*45+0*39 7.18?0-41 9.85f0.42 11~25~0~41 10*10~0~38 96OkO.38 9.40+0-34 8.10f0.37 7.55kO.35
2.45kO.39 5.10t0.41 6.95rtO.42 8*00+044 7.7OkO.42 5.15+0*40 3.4OCO.38 14OkO.23
good antibody responses in normal persons aged 9 to 32. Fairly high levels of antibody were attained which could confer clinical protection against meningococcal meningitis. However, how long this protection lasts is still unresolved (BRANDT & ARTENSTEIN, 1975; LEPOW er al., 1977; MAKELA, 1979). It has been suggested(G~~~h'~00~8zW~~1, 1980),thatbecause there was a rapid decline in haemagglutinating antibody titres after vaccination in West Africa (SALlOU et al., 1976; GREENWOOD et al., 1980) immunity conferred by vaccination may be shortlived. It is, therefore, too early to assess the long term
effects of vaccination with the currently available vaccines because of the epidemiological nature of the disease; epidemics in West Africa tend to occur every five to ten years and although there has been no epidemic since 1978 this must not be attributed solely to the success of vaccination. However, a recent study in Nigeria (MOHAM.%~ED& ZARUBA, 1981) suggests that mass vaccination provides the best hope of containing the disease. In spite of this it would be necessary to monitor antibody titres for a long time to determine the length of protection which vaccination with the polyvalent vaccine could confer on individuals as well as on the community. In addition, strict surveillance has to be maintained for the next two to seven years before any definite conclusions can be drawn about long term benefits of vaccination. In contrast with the findings of GREENWOODet al. (1980), we have observed that haemoglobin genotype had no effect on the response to the vaccine. It is therefore difficult to sustain the argument that malaria-induced immunosuppression in those with genotype AA was responsible for the lower antibody titres. The reasons for this remain unclear. However, the results of the comparative study of malnourished and normal children provide further support for the concept of immunosuppression accounting for failure to respond adequately to the vaccine and may explain also why such immuno-compromised sublects are more susceptible to the lethal effects of meningococcal meningitis. There is currently a vogue amongst State
I. MOHAMMED
AND
Table II-A comparison of serum immunoglobulin normal and malnourished children
M.
M.
levels as well as meningococcal
Mean Serum ImmunoglobulinLevels Normal Children Malnourished children Student’s (t) test
I& 246*0+15.5 110.5+29.6 P<0*0001
Iid 83.5+9.8 58.5+7-5 P
Governments in the meningitis belt in Nigeria to mount yearly mass vaccination campaigns against meningococcal meningitis. As these go on, it becomes more and more necessary to monitor not only the epidemiological and clinical outcome, but also the immunological resposes to large scale immunization with these vaccines. Acknowledgements We are grateful to officials of the Bauchi State Ministry of-Health particularly Dr. N. H. Sajid and Professor K. Zaruba for assistance and encouragement. References Brandt,, B. L. & Artenstein, M. S. (1975). Duration of armbody responseafter vaccination with group C Neisseria meningiti&s polysaccharide. Journal of Infkious Diseases, 131, 569-572.
Erwa, H. H., Hasseb, M. A., Lapeysonnie, L., Sanborn, W. R. & Sippel? J. E. (1973). A serogroup meningococcal polysacchande vaccine. Studies in the Sudan to combat cerebrospinal meningitis caused by N&s&a meningitides Group A. Bulletin of the World Health Organization, 49, 301-305. Ettori, D., Saliou, I’., Renaudet, I. & Stoeckel. Ph. (19771. Le vaccin anti-tiingoccoque du type A: premiers essais ~;~;;!y~l&sen Afrique de 1’Ouest. Mtdecine tropicale, 37, Goldschneiier, I., Lepow, M. L., Gotshlich, E. C., Mauck, F. T., Bach], F. & Randolph, M. (1973). Immunogenicity of Group A and C meningococcal polysaccharides in human infants. Journal of Infectious Diseases, 128, 769-776.
353
DAMISAH
(IUiml)
kM 216k42.8 102k36.7 P
antibody levels among Antibody
Titre
Group A 4.37+0.39 2.9 +0.59 P
Log,
Group C 3*6+0.38 2.2+0.43 P
Greenwood, B. M., Bradley, A. K., Blakebrough, I. S., Whittle, H. C.., Marshall, T. F. de C. & Gilles, H. M. (1980). The nnmune response to a meningococcal polysaccharide vaccine in an African village. Transactions of the Rqal Society of Tropical Medicine and Hygiene, 74,
340-346. Greenwood, B. M. & Wali, S. S. (1980). Control of meningococcalinfection in the African meningitis belt by selective vaccination. Lancer, i, 729-732. Lapeysotie, L. (1963). La meningite cerebrospinale en Afrique. Bulletin of the World Health Organization, 28, suppi., 3-114. Lepow, M. L., Goldschneider, I., Gold, R., Randolph, M. & Gotschlich. E. C. (19771. Persistence of antibodv following immunisation of ihildren with group A and group C meningococcal polysaccharide vaccines. Paediatrics, 60, 673-680.
Makela, P. H. (1979). Meningococcal vaccination in Finland. WHO Third International Conference on Immunity and Immunisation in Cerebrospinal Meningitis Marburg,
October, 19.79. Mohammed, I. & Zaruba, K. (1981). Control of epidemic meningococcal meningitis b) ma& vaccination.-Lancer, ii. 80-83. Saliou, P., Lafaye, A. 81,Ettori, D. (1976). Vaccination antin&ingococcique par le vaccin polysaccharidede type A: Surveillance serologique par la technique haemagglutination passive an tours de l’annk suivant la vaccinade coordination tion. Documents Technique~rganisation et de cooperation pour la Lutte contre les Grandes Endemies,
no. 6185.
Accepted for publication
20th September,
1981 e