The status of measles after five years of mass vaccination in the USSR

Bull. Org. mond. Santo 1973. 49, 571-576 Bull. Wid Hith Org.J The status of measles after five years of mass vaccination in the USSR P. N. BURGASOV,1 0. G. ANDZAPARIDZE,2 & V. F. POPOV 3 Mass vaccination ofchildren from 10 months to 8 years old with the original live vaccine preparedfrom the Leningrad-16 strain has led to a sharp decline in measles morbidity and mortality, and changed its epidemic pattern. In 1972, after S years ofmass vaccination, the morbidity rate was 117.5per 100 000 persons, whereas before vaccination the average annual morbidity rate was about 827.0. The periodicity of increases in morbidity every 3 years was also broken, the last peak of measles morbidity occurring in 1965. Another result of vaccination is that theformerly much higher morbidity rate in urban areas is now lower than that in rural areas. The mortality rate decreased more than 3-fold compared with the period before vaccination, and recently no deaths were registered in a number of regions. The serologic examination of 7585 vaccinated children from 10 different regions revealed antibodies with a mean geometric titre of 78.6+1.16 in 90 % of individuals. The high antibody level was maintainedfor 7 years after vaccination. The effect ofvaccination is both epidemiological and economical. The saving in the use ofgamma-globulin alone covered the cost of the vaccine and the expenses involved during vaccination. Until recently, measles was one of the most frequent of children's droplet infections in the USSR affecting 1.5 to 2 million children annually. This was before the introduction of measles vac- cination, and the number of measles cases came second only to that of influenza and other acute respiratory diseases. While the control measures, including the administration of gamma-globulin, had a substantial effect on the lethality of the disease, there was no significant influence on morbidity. Because of its high incidence and the fairly frequent complications recorded among patients, it was necessary to introduce vaccination against this infection. After extensive field tests with the original live measles vaccine from the Leningrad-16 strain that established its safety and high efficacy, the vaccine was recommended for use in public health practice. This paper describes, with the results of epi- 1 Deputy Minister of Health of the USSR, Ministry of Health, Moscow, USSR. 2 Director of the Moscow Institute for Research on Virus Preparations. a Head of the Respiratory Virus Diseases Laboratory, L. A. Tarassevich State Research Institute for Standardiza- tion and Control of Medical and Biological Preparations, Moscow. demiological and serologic investigations, the effec- tiveness of live measles vaccine under the condi- tions of mass administration throughout the country. Mass vaccination against measles in most of the USSR was begun in the second half of 1967, but in some republics it was started in 1963-64. Prior to this, a great amount of work was carried out to establish the age groups to be vaccinated, to determine the methods for administering the vac- cine in the light of serologic examinations, and to decide the role of other control measures. MATERIALS AND METHODS Children from the age of 10 months to 8 years were inoculated with live measles vaccine of the Leningrad-16 strain, which was produced by a group of Leningrad scientists under A. A. Smoro- dincev. A detailed computer analysis of measles morbid- ity throughout the country and in the Union Rep- ublics, covering the 18 years prior to vaccination and the 5 years after its introduction, was carried out to determine the effect of inoculation on the epidemio- logy of measles. The incidence by age groups and the number of cases among those attending and those not attending pre-school institutions were 3154 -571 P. N. BURGASOV ET AL. established, as was also the proportion of urban to rural morbidity. With a view to observing the establishment and persistence of immunity, 7 585 samples of blood serum from children inoculated with live measles vaccine in different years were subjected to the haemagglutination-inhibition test. RESULTS The epidemiological effectiveness of vaccination Prior to vaccination in the USSR, where since 1924 cases of measles have been subject to com- pulsory notification, a high morbidity was always recorded. For many years the average incidence was 827.1 per 100 000 population, fluctuating in different years between 580.0 in 1950 and 1 067.4 in 1957. Before mass vaccination, no large-scale epidemics were observed, the changes in incidence being marked by small rises only. These periods of higher incidence alternated with periods of decline every 2-3 years but, on average, morbidity re- mained at a high level. After measles vaccination the periodicity of increased morbidity stopped. The last rise was observed in 1965 and the next one should have occurred in 1968-69, but in this and in the succeeding years there was a drop in the number of measles cases. As the scale of vaccina- tion increased a steady decline in morbidity fol- lowed (Fig. 1). As early as 1969, measles incidence per 100 000 population was down to 212.7. Five years after the beginning of mass vaccination, morbidity was one-seventh of what it had been, WYHO 40264 Fig. 1. Measles morbidity and the number of persons vaccinated in the USSR, 1964-72 (shaded columns: measles cases; stippled columns: numbers vacci- nated). the rate in 1972 being 117.5 per 100000 popula- tion. Thus, computer processing of data has revealed a statistically significant drop in measles morbidity throughout the country (Fig. 2), while compara- tive analysis has made it possible to identify the basic trends in the epidemic process of measles. 1 200 110_C Vaccination 600 e \ -- A 2z 900 _ 73001 7 900 III 1950 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 1972 WHO 40265 Fig. 2. The epidemic trend of measles in the USSR before and after mass vaccination, 1950-72. (A and C are the upper and lower limits respectively of the range and B is the mean of the morbidity before 1967.) 572 MEASLES AFTER MASS VACCINATION The morbidity rates before vaccination were al- ways higher in urban than in rural areas. As a result of vaccination, however, these indices by 1969 had undergone a major change and by the end of 1970 were about equal, standing at 194.0 and 194.5 for urban and rural areas respectively per 100000 population. In the last few years the morbidity rates have been much lower in urban than in rural areas. The analysis of the age structure of measles cases before and after the beginning of vaccina- tion shows convincingly that the strategy of vac- cination selected was fully justified. A real reduc- tion in morbidity has been observed in persons between 10 months and 8 years old, while in the most vulnerable age group, children under 5 years old, there were 2.9-4.3 times fewer cases after the introduction of vaccination than before. Before vaccination, measles morbidity for children at- tending creches and nursery schools was 2-3 times that for children of the same age not attending. After vaccination, the morbidity rate per 100 000 children in both groups had by 1970 become nearly equal (3000 and 3800, respectively). A reliable method of evaluating the efficacy of mass vaccination is to study the morbidity among those who were vaccinated. From an analysis of the results it was established that of 13.5 million individuals vaccinated throughout the country 23 400 (0.17%) contracted the disease. The num- ber of cases among those vaccinated differed in the various regions, which may be due to inevi- table errors during the initial period of mass vaccination. In addition, major differences in the sizes of foci were observed. Whereas prior to vaccination foci of 5 and more cases were the general rule, after the introduction of vaccination the foci consisted mainly of single cases. It should also be stressed that mortality from measles in the period since vaccination has de- clined by a factor of 3 in comparison with the prevaccination period. In a number of regions no deaths at all from measles were registered in the past 2-3 years. At the same time, it should be noted that vaccination so far has not had any appreciable effect on the seasonal distribution of morbidity. As previously, the majority of cases now are recorded in the winter months. The rise in morbidity begins in November/December and reaches a peak in January. The lowest morbidity is recorded in August/September. Post-vaccinal immunity after inoculation with live measles vaccine One means of assessing the effectiveness of a vaccine is to study the immune response to vac- cination. All research workers studying this prob- lem are unanimous in confirming that immunity after inoculation with live measles vaccine is maintained over a long period (2-4, 6-8). For the study of immunity, the blood sera of children from 10 different regions who had been inoculated with live measles vaccine were examined by the haemagglutination-inhibition test. Of 7 585 sera, 6809 (89.8%) were found to have a mean geometric antibody titre of 78.6+1.16 to the measles virus (Table 1). The serologic examination of 4793 children of different ages who had been vaccinated in differ- ent years provided an opportunity to obtain objective data on the persistence of immunity (Table 2). At the end of the first year after vaccination 88.2% of children demonstrated anti- bodies in the blood, but in subsequent years a small proportion of the children (2.5% to 6.4%) appeared to have lost their antibodies. For all the years studied the antibody titre was maintained at a sufficiently high level with only slight fluctua- tions (from 56.57+5.9 to 82.3+3.5), and no appreciable decline in the level of antibodies was observed in children belonging to different age groups. In the course of the serologic examinations, no antibodies could be found in the blood of some of the vaccinated children. At the same time, a number of these children had been in contact with measles cases and did not contract the disease. In order to check the reliability of this finding, these negative sera were examined with a reduced num- ber of units of antigen. The blood sera of 776 children negative with 4 haemagglutinin units were tested with 1 unit of antigen. In 283 cases (35%), an antibody titre capable of protecting the children from measles was discovered. These data showed that in assessing the presence or absence of antibodies after vaccination it is essential to take into account the number of units of antigen used in the titration of sera. The quantity of virus required in a single dose of vaccine to establish immunity is also a matter of great interest. In studying this problem many investigators did not discover any essential differ- ences in administering vaccine containing different quantities of virus (1, 5, 9). According to their 573 P. N. BURGASOV ET AL. 0 CV) 0) CV ad -H 0) N 4: I'. I. -H NCV) ad C'. co C'. -H U) 0 co D U) -H U) 0CD U) oo4: -D No CD -H 0 0 CV -HOD 0o - oqco)00 CV) T- -H C4. rUU) D CD C) 4 U) r N v- C N a I I I N O N CO _ N U CD 4 4. C .* 0U) _- v- v- t U CV)CV)- N 0 c) _ N NC) r- I'. 4. 00 cf) U) 0) U) 4. N tDco0C' 0) CD q 0 CV - 00 CD 0)U) 4. V) U) co le 0mCV) m le N N 0 N U) Lo4. C' N 0 0) to 00 0 CD 0) N co U)l to CV) Lor'. 00 N 00 T-) MV coNq CD C 0) N CVl) N - 0 v- v- v- C N 004. C NCV) 4. CD N N CV 00 400 o 0 0)0 O N o0 0) 0 000OD n o b ooo o N 0) N U_) 0o ou CV N CD CD CV CD CV) N N N 0 CV) N C N _ 0) N _- c CD CV) CV) N N U)_ N _ N CVco c c'.o ro 04C4 mLO _4 co -H CD4 CY) 0) 00 co coco r- LO co Lo 0) co 0) CV) N Lo co coo CD U) 0 co r'a C) U) U) 0 C C) n C. E 0 -c ._ C. C 0 C- -_ C. 0 C._ s C 0 CB 0) amE ,-O~~~~~~~~~~~~~~~~~~~~1oa~~~~~~20* 0 4) *0 0- '. c 0 co A 0T- o 0 o - 0 - 0 U) T- o 1- 0 0* 08.o4D o.-> to * .r _ 0Z ,~ zo" 2 eM U, (D C6 D Ca* 0 %O oOC co 4 -H 0 0 U) CrV -H r.Zr'. U) cvi -H CV)CV)coNo CN CV) -H co co CV U)c'i 4H U) 4.tC'. 0O CD -H 0) 4. CDi 0l)aH r' U) U) 4. U) C CO _- U N _ CV CV) .t 0 0 0 0 0O 0 00- CD 0 4C' CD C' 00 U) 00 00 0). 0) 00- 4 it 00 00 0 00 oo w_ wo CD 0 00 rb U) N 0 r-. 0 r'. N CV 00 N 4.t 1- U)m N N 04.r 00 00 CD 4.C 0) CV U) U N _ N _N O CD U) C N 004.0o CV) 14 cn N CD CV CV U) U) 4. CO WCO c9o ND 00 N CD7 I' CD 0 00 000 000 00 0 000oc)4 0o4. CD CDt 1 0 CV) 0CD - 0) COD cD CD0) 00 00 N N N 4. O 00 0 0 0 0 0 0 0 0 0 0 0 0 _ N CV 4. U) CD r 574 ZD lb. 02 E*- 0 0)Om 0 - 0 .0 "P 0co V v 0 0 - 0 v- 0 o v- 0 UO 1- oN 1- v- D 0 C 0 E 0 0 0 0 -C co 0 C. 0 C 0 C. E 0 U) 0 0 ._ ._ 0 ._ 0) 0) . 0 0> Wor 0-00 C CL 0.> X Z 0 z X c 0 ._m 0 I I,- MEASLES AFTER MASS VACCINATION 575 data, the immunity conferred by a vaccine was sufficient provided that 60 or more virus units were introduced in one dose. At the same time it was established that the introduction of only 15-20 virus units considerably reduced the immu- nity conferred by the vaccine. The level of immune response in relation to the dose of vaccine was studied by serologic examina- tions of 3 164 blood sera from children vaccinated with different batches of vaccines. It was found that, regardless of the TCID50, the proportion of seropositive children was roughly the same, i.e., 89.4% and 82.4%, when 50 and 1 050 virus units respectively were administered. After vaccination with different batches of vaccine, the mean geometric antibody titres were held at a fairly high level, fluctuating between 40.0±7.12 and 161.41+6.3 (Table 3). From these data, the conclusion may be drawn that children vaccinated with different doses of measles virus developed a sufficiently strong immunity to protect them from the disease. DISCUSSION This study of measles mass vaccination has shown that epidemics can be eliminated with the help of live measles vaccine of the Leningrad-16 strain. The morbidity rates bear excellent witness to the successful control of the disease on a nation-wide scale. The vaccination of children from 10 months to 8 years of age has brought about a sharp decline in measles morbidity throughout the country and changed the epidemic pattern of this disease. Vaccination against measles has also had an economic effect. During the 5 years of measles vaccination the country has saved more than S244 million.' The saving in the use of gamma-globulin alone during the period of vaccination has repaid all expenses connected with the cost of the vaccine and its administration. A study of the immunity response in those who were inoculated with live measles vaccine has confirmed the presence of a high level of immunity conferred by this preparation. Antibodies were found in 90% of those vaccinated and were maintained at a sufficiently high level for 7 years after vaccination. Confirmation of the persistence 1 Reckoned as of the end of 1972. C - I- N -- (V o N N co .o X _ D N v-- v- -- W > wo_ooa CD CD c r c6 c _ C -HH -H -H -H+ -H + E ~@v'- CO 0) c) 0) 0) D No 0)Cu C; 'ro (D C ) C 0 N )O 0 CO OD w co r- c o cC_ _ '° N 0' - CO Nc W N U C a)CD C a Co O b X ~O NCD _DCO _v -D 0 CDD W W 0 COLoN W N C') ._~~~ ~CW.as co It0P0. WO. tU ) C.) D- W) w NCO '- O 00CD C O O 1L m NO 00 0 00 0 N a) > ) CD NO 0 O -0 D N _0E ei CD Z Q N C' N 00 W CD W ra) COno 0 CD- 0 0 0co) C C D0 C E 0) 0 W CO 0) N0'COC4C-_ N O O Su -=¢ - N 1_ CD C' N C') s a)~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~CI .0 O IL) 0) CL)Ce~N~C ) C 0 ) v-') C') (V)-- N C cCD~~~~~~~~C C~~~Q N CD 0) N~~~0CO C-N OCv O t O E- C'~ 576 P. N. BURGASOV ET AL. of immunity is also to be found in epidemiological observations showing low measles morbidity among those vaccinated (0.17%), compared with 5.0-6.8% among the unvaccinated. In analysing the data, the possibility of a booster effect under conditions where "wild " measlesvirus still has fairly wide circulation was not excluded and there is at present no indication for the need to revaccinate. This matter can be examined only under conditions of greatly reduced circulation of the measlesvirus. The results of this study of the experience of 5 years of vaccination against measles in the USSR suggest that mass vaccination in the coming 2 or 3 years will succeed in reducing measles morbidity to sporadic cases. RJISUMt LA SITUATION EN MATIERE DE ROUGEOLE APRkS CINQ ANNEES DE VACCINATION DE MASSE EN URSS L'experience acquise en URSS apres 5 ann6es d'emploi du vaccin antirougeoleux vivant, pr6par6 a partir de la souche Leningrad-16, montre que la lutte contre les 6pid6mies de rougeole peut etre menee avec succes. La vaccination de masse des enfants de 10 mois A 8 ans a entrain6 un declin accentu6 de la morbidit6 rougeoleuse et modifie les caract6ristiques 6pid6miologiques de l'affec- tion. En 1972, cinq ans apres le debut de la vaccination de masse (1967), la morbidite avait decru de 7 fois: elle n'etait plus que de 117,5 cas pour 100 000 personnes alors qu'auparavant le taux moyen annuel atteignait 827,0 pour 100000. GrAce A la vaccination, l'augmentation cyclique de la morbidit6 ne s'est pas manifestee. Le dernier clocher de morbiditd a dt6 observ6 en 1965 et le suivant devait se produire en 1968-69, mais ace moment et ulterieurement la morbiditW a constamment diminu6. Avant la campagne, la morbidite etait 2 A 3 fois plus elevee dans les villes que dans les campagnes. En 1970, les taux 6taient pratiquement egaux, et depuis ils sont moins 6lev6s chez les citadins que dans les populations rurales. Les vaccinations ont eu pour effet de r6duire fortement la morbidit6 dans le groupe d'age de 10 mois A 8 ans. Chez les enfants de moins de 5 ans, les plus vuln6rables, la morbidit6 a r6gress6 de 2,9 A 4,3 fois. Parmi les enfants fr6quentant les cr&ehes et les jardins d'enfants, le taux de morbidit6 6tait autrefois 2 A 3 fois plus elev6 que parmi les autres enfants du m8me age. En 1970, les taux pour ces deux categories 6taient respectivement de 30,0 et 38,0 pour 1000. Le taux de mortalite a diminue de plus de 3 fois pendant la campagne de vaccination, par rapport A la periode pr6c6dente. Au cours des 2 A 3 demieres ann6es, on n'a enregistr6 aucun cas mortel de rougeole dans de nom- breuses regions. Le vaccin antirougeoleux vivant a fait preuve d'une remarquable efficacit6. Les examens serologiques prati- ques chez 7585 enfants vaccines, dans dix r6gions du pays, ont r6vel6 une moyenne geom6trique de titres d'anticorps de 78,6 ± 1,16 pour 90% d'entre eux. Les titres se sont maintenus A un niveau eleve pendant les 7 ann6es suivant la vaccination. Les economies r6alis6es par suite d'un emploi plus limit de gammaglobuline ont permis de couvrir les frais de la campagne et le cofit du vaccin. REFERENCES 1. ANDiAPARIDZE, 0. G. ET AL. In: Specifiteskaja pro- filaktika Kori (The specific prophylaxis of measles). Leningrad, 1970, p. 121. 2. ANDEAPARIDZE, 0. G. ET AL. Idem, p. 125. 3. BOJ&UK, L. M. ET AL. Idem, p. 9. 4. SIKINA, E. S. ET AL. Idem, p. 142. 5. SIKINA, E. S. ET AL. In: Problenia likvidacii Kori (The problem of eradicating measles). Leningrad, 1968, p. 109. 6. BORGON-O, J. M. & GREIBER, R. In: Proc. internat. conf. on the application of vaccines against viral, rickettsial, and bacterial diseases of man, Washington, D.C., December 1970. Washington, D.C., PAHO, 1971, p. 203. 7. KRUGMAN, S. & GILEs, J. P. Idem, p. 195. 8. LEPOW, M. L. & NAHKERVIS, G. A. J. Pediat., 75:407 (1969). 9. ROSENBLOOM, A. L. ET AL. J. trop. Med. Hyg., 73: 183 (1970).