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Influenza morbidity and some peculiarities of antiinfluenza immunity and prevention during influenza pandemics
International Congress Series 1263 (2004) 787 – 790
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Influenza morbidity and some peculiarities of antiinfluenza immunity and prevention during influenza pandemics Anatoly N. Slepushkin *, Elena I. Bourtseva, Alexey L. Belyaev, Liliya N. Vlassova, Elena L. Feodoritova Laboratory of Etiology and Epidemiology of Influenza, The D.I. Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences, 16 Gamaleya Street, 123098 Moscow, Russia
Abstract. The etiological factors of pandemics are usually fast spreading among the world population. These include the New Influenza Virus Reassortants of epidemic Influenza virus A and some bird or mammalian Influenza virus A from the biosphere. About 30 – 50% of the world population are usually affected by that virus during the first wave of a pandemic. According to the data from various regions of the world, during the Influenza A(H2N2) pandemic, when the pandemic virus differed from previous A(H1N1) by HA and NA, the highest morbidity was among children and youth of 3 – 29 years old. The morbidity among people 65 and older and children of 1 – 2 years was minimal. Thus, immunity from previous, repeated contacts with Influenza A viruses are playing a definite role in protection from a new virus. To diminish the influence of pandemic influenza on people’s health and the economy, it is important to organize mass vaccinations of children and youth. Good-quality vaccination using live influenza vaccines from previous Influenza A strains decreased the influenza and ARD morbidity by 26.5% during the first pandemic wave of A(H2N2). During the influenza pandemic A(H3N2) in 1969, morbidity decreased by 27.5 – 40.2% for bivalent vaccine A(H2N2)+B and by 37.8 – 53.9% for vaccine A(H2N2). According to the results of our controlled observations of varied vaccines, the live recombinant influenza vaccine gives more wide and long-lived immunity and higher efficacy than the inactivated one in schoolchildren and youth. D 2004 Published by Elsevier B.V. Keywords: Influenza pandemics; Morbidity; Prevention; Live vaccine
1. Introduction The etiological factors of influenza pandemics are usually fast spreading among the world population. These include the New Influenza Virus Reassortants of epidemic virus A, circulating in human and some bird or mammalian influenza virus A from the biosphere. About 30 –60% of the world population are affected by influenza during the first wave of the pandemic. The highest morbidity during the first wave of A(H2N2) pandemic was among * Corresponding author. Tel.: +7-95-190-3046; fax: +7-95-190-2867. E-mail address: [email protected] (A.N. Slepushkin). 0531-5131/ D 2004 Published by Elsevier B.V. doi:10.1016/j.ics.2004.01.019
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A.N. Slepushkin et al. / International Congress Series 1263 (2004) 787–790
Fig. 1. Agewise distribution of influenza morbidity during the first wave of the 1957 – 1959 pandemic.
children and youth from 3 to 29 years of age. The morbidity among people 65 years and older and children of 1 – 2 years old was minimal [1 – 4] (Fig. 1). Thus, immunity from previous, repeated contacts with Influenza A viruses is playing a definite role in protection from a new virus. To diminish harm of pandemic on people’s health and the economy, it is important to vaccinate not only people 60 and older but to organize mass vaccinations of children and youth [1,5]. 2. Materials and methods Most of this article’s main statements came from epidemiological trials, detailed descriptions of which were published in papers cited at the end of this publication. With the exception of a trial made during the first wave of the 1957– 1959 pandemic, all others were placebo-controlled observations. In all controlled trials, as a diagnostical test, the WHO-recommended HI was performed with paired sera taken at the beginning and after recovery from disease. 3. Results The new A(H1N1) drift-variant A/Netherland caused a small epidemic in Moscow in March – April 1957. After that, there were two waves of Influenza A(H2N2); a minor one in the summer and a major one at the beginning of autumn. The etiology of epidemics was confirmed by virological and serological diagnostic methods [6]. Some of the workers of the big enterprise, 1st Ball bearing Factory (BF), were vaccinated by live trivalent A, A1 and B influenza vaccines in February 1957 (Table 1). The study of influenza and ARD morbidity among vaccinated and unvaccinated showed that the coefficient of efficacy was 46.8% during the A(H1N1) epidemic in March – April. The efficacy of the vaccine decreased during the A(H2N2) summer wave, but was still equal to 26.5%. The controlled trials of live influenza divaccine A(H2N2)B and A(H2N2) monovaccine were conducted under our supervision during the first wave of the A(H3N2)
A.N. Slepushkin et al. / International Congress Series 1263 (2004) 787–790
789
Table 1 Results of live influenza vaccine trials during A(H2N2) and A/Hong-Kong/1/68(H3N2) pandemics Time of study, etiology, type vaccines
Group
AA1 and B influenza vaccine 25 March – 3 April 1957, A(H1N1) AA1 and B influenza vaccine 10 June – 24 July 1957, A(H2N2) Vaccines for adults, pandemic, 1969, A(H3N2)
Cold-adapted vaccine for children, pandemic, 1969, A(H3N2)
Number of persons in group
Incidence of influenza and ARD (%)
Efficacy Index
Coefficient (%)
t between incidence among vaccinated and placebo or B
vaccinated unvaccinated
2572 2448
5.9 11.1
1.9
46.8
6.75
vaccinated unvaccinated
2571 2528
10.0 13.6
1.4
26.5
4.0
A(H2N2)B vaccine A(H2N2) vaccine B vaccine A(H2N2)B vaccine placebo
1216
13.4
1.4
27.5
3.4
1084
11.5
1.6
37.8
4.7
1284 1548
18.5 13.1
1.7
40.2
6.7
1519
21.9
pandemic in 1969 (Table 1). The statistically proved coefficient of efficacy for adults was equal to 27.5% for divaccine and 37.8% for monovaccine A(H2N2). It was a little higher for A(H2N2)B cold adapted live vaccine for children—40.2% [6,7]. At the same time, we had the possibility of estimating the influence of a 5-year-long vaccination of Live Influenza A(H2N2)B divaccine on the influenza and ARD morbidity for
Fig. 2. Incidence of influenza and other ARD in Smolensk, Kaluga and Vitebsk (per 100 population).
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A.N. Slepushkin et al. / International Congress Series 1263 (2004) 787–790
the population of the city of Smolensk, 45– 50% of which had been vaccinated yearly. In Fig. 2, there are curves of influenza and ARD morbidity in the population of Smolensk, in comparison to the same in the populations of Vitebsk and Kaluga, where such mass vaccination had not taken place. It is obvious from Fig. 2 that mass vaccination with the Live Influenza A(H2N2)B vaccine had an essential influence on the epidemic process in the city of Smolensk [6,7]. All three epidemics, which took place after the first mass vaccination of 1964, including the first wave of A(H3N2) pandemic in 1969, were about two times less intensive on the pike but about one-half point longer lasting than during the Influenza A(H2N2) epidemic in 1962 before mass vaccination. In 3 years of observation of schoolchildren mass vaccinated in the city of Novgorod, organized by us together with scientists of the Research Institute of Experimental Medicine, St. Petersburg, and American colleagues from CDC&P and Michigan University, we compared the efficacy of Russian live and inactivated whole virus influenza vaccines [5,8]. During epidemic A(H3N2) in 1989 –1990, the efficacy of the live influenza vaccine was higher, especially among children 11 – 14 years old (coefficient of efficacy 51.9%). The Live Influenza Vaccine’s efficacy was also higher during the Influenza B outbreak in 1990– 1991 with a coefficient of efficacy of 39.5% among children 7– 10 years old. 4. Discussion The immunity from previous repeated contacts with Influenza A viruses played a definite role in protection from the new pandemic virus. Yearly mass vaccination by Live Influenza Vaccine (LIV) had an essential influence on the epidemic process. Children and young adults need to be mass vaccinated. Good-quality LIV from previous Influenza A epidemic viruses may be in use for protection and lowering the clinical severity of disease during the first wave of the influenza pandemic. References [1] L.N. Rybinskaya, About influenza morbidity in varied age groups of population, In: Influenza and Respiratory Virus Infections, Kiev, 1966, pp. 18 – 22, in Russian. [2] H. Fukumi, Summary report on the Asian influenza epidemic in Japan, Bull. World Health Organ. 20 (1959) 187 – 198. [3] J. Fry, Influenza pattern, Br. Med. J. 1 (52270) (1961) 745. [4] A.S. Monto, F.M. Davenport, J.A. Napier, et al., Modification of an influenza outbreak in Tecumseh, Michigan, by vaccination of schoolchildren, J. Infect. Dis. 122 (1970) 16 – 25. [5] L.G. Rudenko, A.N. Slepushkin, A.S. Monto, et al., Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod Russia, J. Infect. Dis. 168 (1993) 881 – 887. [6] A.N. Slepushkin, T.K. Bobyleva, A.E. Russina, et al., Evaluation of the effectiveness of large-scale vaccination against influenza in the USSR, Bul. Worlld Health Organ. 36 (1967) 385 – 395. [7] A.N. Slepushkin, T.K. Bobyleva, A.E. Russina, et al., Evaluation of the effectiveness of large-scale vaccination against influenza, (results of five-year observation), Proc. Symposium on Acute Respir. Diseases, Zagreb, 1969, pp. 367 – 380. [8] L.G. Rudenko, A.N. Slepushkin, A.S. Monto, et al., Comparative studies of efficacy of live attenuated and inactivated vaccines in children of Novgorod, in: C. Hannoun, et al. (Eds.), Options for the Control of Influenza II, Elsevier, 1993, pp. 85 – 90.
www.ics-elsevier.com
Influenza morbidity and some peculiarities of antiinfluenza immunity and prevention during influenza pandemics Anatoly N. Slepushkin *, Elena I. Bourtseva, Alexey L. Belyaev, Liliya N. Vlassova, Elena L. Feodoritova Laboratory of Etiology and Epidemiology of Influenza, The D.I. Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences, 16 Gamaleya Street, 123098 Moscow, Russia
Abstract. The etiological factors of pandemics are usually fast spreading among the world population. These include the New Influenza Virus Reassortants of epidemic Influenza virus A and some bird or mammalian Influenza virus A from the biosphere. About 30 – 50% of the world population are usually affected by that virus during the first wave of a pandemic. According to the data from various regions of the world, during the Influenza A(H2N2) pandemic, when the pandemic virus differed from previous A(H1N1) by HA and NA, the highest morbidity was among children and youth of 3 – 29 years old. The morbidity among people 65 and older and children of 1 – 2 years was minimal. Thus, immunity from previous, repeated contacts with Influenza A viruses are playing a definite role in protection from a new virus. To diminish the influence of pandemic influenza on people’s health and the economy, it is important to organize mass vaccinations of children and youth. Good-quality vaccination using live influenza vaccines from previous Influenza A strains decreased the influenza and ARD morbidity by 26.5% during the first pandemic wave of A(H2N2). During the influenza pandemic A(H3N2) in 1969, morbidity decreased by 27.5 – 40.2% for bivalent vaccine A(H2N2)+B and by 37.8 – 53.9% for vaccine A(H2N2). According to the results of our controlled observations of varied vaccines, the live recombinant influenza vaccine gives more wide and long-lived immunity and higher efficacy than the inactivated one in schoolchildren and youth. D 2004 Published by Elsevier B.V. Keywords: Influenza pandemics; Morbidity; Prevention; Live vaccine
1. Introduction The etiological factors of influenza pandemics are usually fast spreading among the world population. These include the New Influenza Virus Reassortants of epidemic virus A, circulating in human and some bird or mammalian influenza virus A from the biosphere. About 30 –60% of the world population are affected by influenza during the first wave of the pandemic. The highest morbidity during the first wave of A(H2N2) pandemic was among * Corresponding author. Tel.: +7-95-190-3046; fax: +7-95-190-2867. E-mail address: [email protected] (A.N. Slepushkin). 0531-5131/ D 2004 Published by Elsevier B.V. doi:10.1016/j.ics.2004.01.019
788
A.N. Slepushkin et al. / International Congress Series 1263 (2004) 787–790
Fig. 1. Agewise distribution of influenza morbidity during the first wave of the 1957 – 1959 pandemic.
children and youth from 3 to 29 years of age. The morbidity among people 65 years and older and children of 1 – 2 years old was minimal [1 – 4] (Fig. 1). Thus, immunity from previous, repeated contacts with Influenza A viruses is playing a definite role in protection from a new virus. To diminish harm of pandemic on people’s health and the economy, it is important to vaccinate not only people 60 and older but to organize mass vaccinations of children and youth [1,5]. 2. Materials and methods Most of this article’s main statements came from epidemiological trials, detailed descriptions of which were published in papers cited at the end of this publication. With the exception of a trial made during the first wave of the 1957– 1959 pandemic, all others were placebo-controlled observations. In all controlled trials, as a diagnostical test, the WHO-recommended HI was performed with paired sera taken at the beginning and after recovery from disease. 3. Results The new A(H1N1) drift-variant A/Netherland caused a small epidemic in Moscow in March – April 1957. After that, there were two waves of Influenza A(H2N2); a minor one in the summer and a major one at the beginning of autumn. The etiology of epidemics was confirmed by virological and serological diagnostic methods [6]. Some of the workers of the big enterprise, 1st Ball bearing Factory (BF), were vaccinated by live trivalent A, A1 and B influenza vaccines in February 1957 (Table 1). The study of influenza and ARD morbidity among vaccinated and unvaccinated showed that the coefficient of efficacy was 46.8% during the A(H1N1) epidemic in March – April. The efficacy of the vaccine decreased during the A(H2N2) summer wave, but was still equal to 26.5%. The controlled trials of live influenza divaccine A(H2N2)B and A(H2N2) monovaccine were conducted under our supervision during the first wave of the A(H3N2)
A.N. Slepushkin et al. / International Congress Series 1263 (2004) 787–790
789
Table 1 Results of live influenza vaccine trials during A(H2N2) and A/Hong-Kong/1/68(H3N2) pandemics Time of study, etiology, type vaccines
Group
AA1 and B influenza vaccine 25 March – 3 April 1957, A(H1N1) AA1 and B influenza vaccine 10 June – 24 July 1957, A(H2N2) Vaccines for adults, pandemic, 1969, A(H3N2)
Cold-adapted vaccine for children, pandemic, 1969, A(H3N2)
Number of persons in group
Incidence of influenza and ARD (%)
Efficacy Index
Coefficient (%)
t between incidence among vaccinated and placebo or B
vaccinated unvaccinated
2572 2448
5.9 11.1
1.9
46.8
6.75
vaccinated unvaccinated
2571 2528
10.0 13.6
1.4
26.5
4.0
A(H2N2)B vaccine A(H2N2) vaccine B vaccine A(H2N2)B vaccine placebo
1216
13.4
1.4
27.5
3.4
1084
11.5
1.6
37.8
4.7
1284 1548
18.5 13.1
1.7
40.2
6.7
1519
21.9
pandemic in 1969 (Table 1). The statistically proved coefficient of efficacy for adults was equal to 27.5% for divaccine and 37.8% for monovaccine A(H2N2). It was a little higher for A(H2N2)B cold adapted live vaccine for children—40.2% [6,7]. At the same time, we had the possibility of estimating the influence of a 5-year-long vaccination of Live Influenza A(H2N2)B divaccine on the influenza and ARD morbidity for
Fig. 2. Incidence of influenza and other ARD in Smolensk, Kaluga and Vitebsk (per 100 population).
790
A.N. Slepushkin et al. / International Congress Series 1263 (2004) 787–790
the population of the city of Smolensk, 45– 50% of which had been vaccinated yearly. In Fig. 2, there are curves of influenza and ARD morbidity in the population of Smolensk, in comparison to the same in the populations of Vitebsk and Kaluga, where such mass vaccination had not taken place. It is obvious from Fig. 2 that mass vaccination with the Live Influenza A(H2N2)B vaccine had an essential influence on the epidemic process in the city of Smolensk [6,7]. All three epidemics, which took place after the first mass vaccination of 1964, including the first wave of A(H3N2) pandemic in 1969, were about two times less intensive on the pike but about one-half point longer lasting than during the Influenza A(H2N2) epidemic in 1962 before mass vaccination. In 3 years of observation of schoolchildren mass vaccinated in the city of Novgorod, organized by us together with scientists of the Research Institute of Experimental Medicine, St. Petersburg, and American colleagues from CDC&P and Michigan University, we compared the efficacy of Russian live and inactivated whole virus influenza vaccines [5,8]. During epidemic A(H3N2) in 1989 –1990, the efficacy of the live influenza vaccine was higher, especially among children 11 – 14 years old (coefficient of efficacy 51.9%). The Live Influenza Vaccine’s efficacy was also higher during the Influenza B outbreak in 1990– 1991 with a coefficient of efficacy of 39.5% among children 7– 10 years old. 4. Discussion The immunity from previous repeated contacts with Influenza A viruses played a definite role in protection from the new pandemic virus. Yearly mass vaccination by Live Influenza Vaccine (LIV) had an essential influence on the epidemic process. Children and young adults need to be mass vaccinated. Good-quality LIV from previous Influenza A epidemic viruses may be in use for protection and lowering the clinical severity of disease during the first wave of the influenza pandemic. References [1] L.N. Rybinskaya, About influenza morbidity in varied age groups of population, In: Influenza and Respiratory Virus Infections, Kiev, 1966, pp. 18 – 22, in Russian. [2] H. Fukumi, Summary report on the Asian influenza epidemic in Japan, Bull. World Health Organ. 20 (1959) 187 – 198. [3] J. Fry, Influenza pattern, Br. Med. J. 1 (52270) (1961) 745. [4] A.S. Monto, F.M. Davenport, J.A. Napier, et al., Modification of an influenza outbreak in Tecumseh, Michigan, by vaccination of schoolchildren, J. Infect. Dis. 122 (1970) 16 – 25. [5] L.G. Rudenko, A.N. Slepushkin, A.S. Monto, et al., Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod Russia, J. Infect. Dis. 168 (1993) 881 – 887. [6] A.N. Slepushkin, T.K. Bobyleva, A.E. Russina, et al., Evaluation of the effectiveness of large-scale vaccination against influenza in the USSR, Bul. Worlld Health Organ. 36 (1967) 385 – 395. [7] A.N. Slepushkin, T.K. Bobyleva, A.E. Russina, et al., Evaluation of the effectiveness of large-scale vaccination against influenza, (results of five-year observation), Proc. Symposium on Acute Respir. Diseases, Zagreb, 1969, pp. 367 – 380. [8] L.G. Rudenko, A.N. Slepushkin, A.S. Monto, et al., Comparative studies of efficacy of live attenuated and inactivated vaccines in children of Novgorod, in: C. Hannoun, et al. (Eds.), Options for the Control of Influenza II, Elsevier, 1993, pp. 85 – 90.