Poliomyelitis control in Israel, the West Bank and Gaza Strip: changing strategies with the goal of eradication in an endemic area.

Reviews IAnalyses Poliomyelitis control in Israel, the West Bank and Gaza Strip: changing strategies with the goal of eradication in an endemic area N. Goldblum,1 C.B. Gerichter,2 T.H. Tulchinsky,3 & J.L. Melnick4 Israel has faced the challenge presented by epidemic poliomyelitis by using different immunization strat- egies. In the 1950s, inactivated poliovirus vaccine (IPV) helped to reduce the total burden of the dis- ease, but cases continued to occur. Introduction of oral poliovirus vaccine (OPV) in mid-1961 had a dramatic effect in controlling an extensive epidemic of poliomyelitis; however, poliovirus activity and cases continued during the 1970s, and at a low level in the 1980s. A localized outbreak of 15 cases of poliomyelitis in 1988 occurred in an area using enhanced potency IPV (eIPV) only. This led to a revi- sion of poliomyelitis immunization policy. The successful poliomyelitis control in the West Bank and the Gaza Strip using both OPV and IPV since 1978 shows the advantages of a combined approach. This programme was therefore adopted in modified form in the whole of Israel, the West Bank and Gaza. Since late 1988, no cases of poliomyelitis have occurred in any of these three areas, indicating the suc- cess of the combined poliomyelitis immunization programme. These experiences may be helpful to other countries, especially those where there is a danger of importation of wild poliovirus, and to pre- vent vaccine-associated disease. The combined approach provides an additional immunization model in the international effort to eradicate poliomyelitis. Introduction Since 1949 Israel has faced the difficult challenge of controlling poliomyelitis. We report this experience here, since it could be helpful for identifying appro- priate strategies suited to specific countries, especial- ly those in endemic areas, in the current international effort to eradicate poliomyelitis. In the 1940s and 1950s, the pattems of endemic and epidemic poliomyelitis in Israel were similar to those in the USA and Europe. In 1957, the Salk inac- I Professor, Department of Virology, Hebrew University-Hadas- sah Medical School, P.O. Box 1172, Jerusalem 91010. Requests for reprints should be sent to this author. 2 Associate Professor, School of Public Health, Hebrew University- Hadassah Medical School, Jerusalem. Formerly: Director, Divi- sion of Laboratories, Ministry of Health, Jerusalem. 3 Director, Preventive Health Services, Ministry of Health, Jeru- salem, and Associate Professor, School of Public Health, Hebrew University-Hadassah Medical School, Jerusalem. 4 Distinguished Service Professor, Division of Molecular Virolo- gy, College of Medicine, Baylor University, Houston, TX, USA. Reprint No. 5530 tivated poliovirus vaccine (IPV) was first used in Israel, resulting in a substantial reduction in the inci- dence of the disease, although cases continued to be reported. In 1961, during a large epidemic, Sabin attenuated oral poliovirus vaccine (OPV) was intro- duced in Israel and employed on a large scale, stop- ping the epidemic in its tracks. OPV was then adopt- ed for general use in the country and has continued to be used in place of IPV since 1961 for basic immunization. In 1967, following the "Six-Day War", Israel became administratively responsible for the Palestin- ian population of the West Bank and the Gaza Strip. Establishment of large-scale poliomyelitis immuni- zation in these areas using up to four doses of OPV nevertheless failed to prevent substantial poliomyeli- tis epidemics during the mid-1970s. In 1978, adop- tion of an OPV/IPV programme led, however, to a remarkable reduction in poliomyelitis cases in Gaza and the West Bank. In 1979, Israel experienced a resurgence of cases, especially among the non-Jewish, primarily Arab population. This led to the institution of an annual immunization campaign using OPV type 1 in Bulletin of the World Health Organization, 1994, 72 (5): 783-796 © World Health Organization 1994 783 N. Goldblum et al. addition to the routine infant immunization pro- gramme using trivalent OPV. These campaigns help- ed to reduce the incidence of poliomyelitis to sporadic cases during the 1980s, with no cases being reported after 1985 except for an outbreak in 1988. This out- break in 1988 occurred in a district of Israel where a trial of the new enhanced IPV (eIPV) as the prime vaccine for infant immunization had been carried out over a period of 6 years. As a result of this outbreak, and the success of the combined OPV/IPV pro- gramme used since 1978 in Gaza and the West Bank, Israel also adopted the combined OPV/IPV pro- gramme in 1989. Since the 1988 outbreak, there have been no cases of poliomyelitis in Israel, in the West Bank, or Gaza. However, continued vigilance is essential, since wild poliovirus has been found in sewage in Gaza, and there have been substantial outbreaks of poliomyelitis in Oman and neighbouring Jordan as well as chronic endemicity in Egypt. The changing poliomyelitis control strategy in Israel over the past four-to-five decades has been the result of lessons learned from the complex experience of attempting to eradicate the disease in a part of the world highly endemic to wild poliovirus. Historical survey Transition from endemic to epidemic poliomyelitis in Israel, 1948-56 Like other countries in the period 1940-48, this area suffered from outbreaks of poliomyelitis and was considered to be endemic, there being approximately 30 cases of paralytic poliomyelitis per annum with an annual incidence of 5 per 100 000 population. Beginning in 1949, there was a sharp transition from endemic to epidemic poliomyelitis; in 1949 there were 128 cases; in 1950, 1621 (145 per 100000); and in 1951, 918 paralytic cases (69 per 100 000) (see Table 1). This serious epidemic could have arisen because of a combination of factors. The massive immigra- tion of Jews from post-war Europe and from Middle- Eastem and North African countries caused a doubling of the population within 3 years. This was associated with crowded, unsanitary conditions in immigrant camps, and there was a general deterioration of liv- ing standards in the country. The immigrant popula- tion may also have imported poliovirus strains from their original homelands and shed the virus among the indigenous local population. Many of the immi- grants originated from North African countries that also suffered from endemic poliomyelitis (1). Following the large epidemics of 1949-51, the incidence of poliomyelitis levelled off to a hyperen- demic steady state. In the period 1952-56, Israel experienced an average of 650 cases per annum (Table 1). The predominant poliovirus was type 1 over the period 1949-56. Use of the Salk IPV in Israel, 1957-61 Salk IPV was first prepared in Israel in 1957 by Goldblum et al. at the Ministry of Health Central Virus Laboratory, then located in Jaffa (2-4). Chil- dren aged 4 months to 4 years were immunized with IPV as part of the routine infant immunization pro- gramme (together with diphtheria-pertussis-tetanus (DPT) and BCG). Infant vaccination at a coverage of approximately 90% of 1-year-olds was carried out through the extensive network of matemal and child health stations established in rural settlements, Arab villages, and urban neighbourhoods throughout the country. There was an immediate impact, with a reduc- tion in the number of cases from an annual average of 650 in the period 1952-56 to 57 in 1957 (3 per 100 000). This was followed by an increase to 573 cases in 1958 (30 per 100 000) and a subsequent reduction in 1959-60 to 36 and 39 cases, respective- ly (1.7-2.0 per 100 000). In 1961, however, another epidemic of poliomyelitis occurred, with 207 cases (9.5 per 100 000) (see in Table 1) (5-8). This epi- demic led to the replacement of IPV by OPV, as dis- cussed below. Introduction of OPV, 1961 Despite routine immunization with IPV since 1957, a large number of cases of paralytic poliomyelitis occurred in Israel in the spring and early summer of Table 1: Number of poliomyelitis cases and attack rates, 1940-61, in Israel Attack rate Vaccinea No. of cases (per 100 OOO)b 1940-48 1949 1950 1951 1952-56 1957 1958 1959 1960 1961 IPV IPV IPV IPV 'PVc 30 128 1 621 918 650 57 573 36 39 207 5.0 15.0 145.0 69.0 40.5 3.0 30.0 1.7 2.0 9.5 a IPV = inactivated poliovirus vaccine. b The rates for 1940-48 and 1952-56 are annual average rates. c During the 1961 epidemic, a widespread campaign with OPV was carried out, after which the epidemic ceased. WHO Bulletin OMS. Vol 72 1994784 Poliomyelitis control in Israel, the West Bank and Gaza Strip 1961. In this renewed outbreak, many cases involved the non-Jewish population, which experienced attack rates as much as 10 times higher than those among the Jewish population, mostly among unimmunized children. In view of this, a mass immunization cam- paign with OPV type 1 was carried out rapidly dur- ing June 1961. As a result, the number of new cases of poliomyelitis declined sharply and transmission of poliovirus was interrupted. Following these encour- aging results, use of IPV was stopped (9, 10). Fig. 1 shows the rapid decline in the number of cases and the differences between the monthly incidences of poliomyelitis during the epidemic years (1952-56) compared with that in 1961. In 1961, hundreds of thousands of children aged between 6 months and 4 years were vaccinated with OPV type 1 and type 2. Type 1 continued to be administered in 1962 when type 3 was added. All of the OPV vaccines were stabilized with magnesium chloride. In 1963, trivalent OPV was adopted as part of routine infant immunization, with three doses 6 weeks apart and a booster dose 6 months later (11). This routine OPV immunization programme resulted in a significant reduction in the incidence of paralyt- ic poliomyelitis, but not in its complete disappear- ance (see Table 2). In 1962 and 1963 the annual inci- dence fell to 18 and 6 cases, respectively (0.8 and 0.3 per 100 000, resp.). In the months following the Six-Day War of June 1967, the number of cases of poliomyelitis in Israel began to increase (Fig. 2), probably as a result of contact between the Israeli population and that of Gaza and the West Bank, where poliomyelitis was still highly endemic. The peak in the number of Fig. 1. Monthly incidence of paralytic poliomyelitis in Israel in the epidemic period, 1952-56, and during the outbreak in 1961. (Data for 1952-56 are the average monthly incidences). F M A M J Months Fig. 2. Monthly incidence of paralytic poliomyelitis in Israel in 1967. 10 _8o IA0(D0 0404 z 0 - ..- . ..- - .. -J F M A M J J A S Months N cases in 1967 was followed by a high level of ende- micity during the 1970s. In 1974, there was a peak of 26 cases, followed by 14 cases in 1978, rising to 29 cases in 1979. These cases, primarily caused by poliovirus type 1, occurred mainly among under-5-year-olds (12), chiefly in the non-Jewish population. This may have been due to several factors: poorer sanitary condi- tions; insufficient vaccination coverage; and the greater risk of exposure to imported fresh wild polio- virus from the West Bank and Gaza (13). Following the 1967-68 peak of 27 cases, the Jewish population experienced 0-6 cases of poliomyelitis annually, except during the localized outbreak of 1988. Table 2 shows the incidence of poliomyelitis in Israel from 1961 to 1993; Fig. 3 illustrates the trend among the Jewish population and Fig. 4 that among the non- Jewish population. Additional campaigns with OPV Because of the continuing high incidence of polio- myelitis, particularly among the non-Jewish popula- tion over the period 1974-79, a special OPV immu- nization programme to supplement routine infant immunization was introduced in 1979. Each year during May-June, a 2-week campaign was carried out in which OPV type 1 was administered to all children aged 0-3 years, irrespective of their pre- vious vaccination history; this was carried out in areas of the country where there had been cases of poliomyelitis over the previous 3 years. Over the next several years poliomyelitis control improved greatly in these areas, with a reduction in the total incidence as follows: to 10 cases in 1980, 8 in 1981, 5 in 1982, and 4 in 1983. Between 1983 and 1987 there were a total of five cases in the Jewish population and four cases in the non-Jewish popula- tion. WHO Bulletin OMS. Vol 72 1994 785 N. Goldblum et al. Table 2: Number of paralytic poliomyelitis cases, inci- dence by population group, and vaccine-associated cases, Israel, 1961-938 Jews r Incidence n (per 100 000) n 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 101 7 4 2 2 3 18 9 3 0 4 4 6 2 2 2 0 5 5 1 4 2 4 1 0 0 0 15 0 0 0 0 0 5.20 0.34 0.19 0.09 0.09 0.13 0.76 0.37 0.12 0.00 0.15 0.18 0.21 0.07 0.07 0.07 0.00 0.16 0.16 0.03 0.10 0.06 0.12 0.03 0.00 0.00 0.00 0.41 0.00 0.00 0.00 0.00 0.00 106 11 2 19 1 6 12 3 7 10 9 2 3 26 11 8 7 14 29 9 4 3 0 0 2 0 2 2 0 0 0 0 0 N4on-Jews Incidence (per 100 000) 42.76 4.27 0.75 6.78 0.34 1.96 3.40 0.75 1.69 2.32 1.96 0.43 0.73 5.16 2.10 1.50 1.21 2.85 4.69 1.41 0.60 0.44 0.00 0.00 0.27 0.00 0.00 0.25 0.00 0.00 0.00 0.00 0.00 a Department of Epidemiology, Ministry of Health, Jerusalem. An additional 9 vaccine-associated cases were reported over this period, involving 2-, 3-, 6-, 12-, and 13-month-olds, and 22- and 34-year-olds; 5 of these cases were reported in 1982-84 alone. Fig. 3. Incidence of paralytic poliomyelitis among the Jewish population in Israel, 1960-93. (Vaccine-associated cases are not included). 120 100 _ 180 0 z 40 20 0 1960 1965 1970 1975 1980 19851988 -1993 Year accounted for 72-90% of virus isolates from paralytic cases, especially during the epidemic years (Table 4). Serological surveys as an index of immunity to poliovirus during 1962-87 In order to maintain surveillance on protective anti- body levels, serological surveys (using serum dilu- tions of .1:4) have been carried out in Israel since 1962. Several examples of these serological surveys are given below and others are described elsewhere (14, 30). Following the 1961 poliomyelitis epidemic, and the mass immunization with OPV, a survey was car- ried out in 1962. Among 261 children aged between Fig. 4. Incidence of paralytic poliomyelitis among the non-Jewish population in Israel, 1960-93. 120 100 During this period, vaccine-associated cases began to be of concern, with a total of five such cases being reported between 1982 and 1984 (Table 2). Also over this period, there were seven cases of paralytic poliomyelitis caused by wild poliovirus among the Jewish population and three cases among the non-Jewish population (see Fig. 1). Over the period 1949-81, 85-90% of the cases of poliomyelitis occurred among children aged under 5 years (Table 3). During the outbreak in 1988, how- ever, there was a sharp upward shift in the age of cases. The predominant poliovirus was type 1, which 80 Uc a) Cuco0) 60 z40 20 1960 1965 1970 1975 1980 19851988 1993 Year WHO Bulletin OMS. Vol 72 1994786 Poliomyelitis control In Israel, the West Bank and Gaza Strip Table 3: Poliomyelitis in Israel, by age group, 1971-93 Age group (years) 0 1-4 5-9 10-14 15-24 25-34 .35 Total 1971 10 2 1 - - - - 13 1972 4 2 - - - - - 6 1973 6 2 - - 1 - - 9 1974 13 13 1 - 1 - - 28 1975 8 5 - - - - - 13 1976 7 1 - - - - - 10 1977 6 1 - - - - - 7 1978 7 12 - - - - - 19 1979 12 18 - 1 2 1 - 34 1980 2 6 2 - - - 1 11 1981 5 - - 1 1 - - 8 1982 1 3 - - 1 - - 5 1983 1 2 - - 1 - - 4 1984 1 - - - 1 - - 1 1985 - 2 - - - - - 2 1986 - - - - - - - 1987 1 - - - - - - 1 1988 2 1 1 2 4 3 2 15 1989 - - - - - - - - 1990 - - - - - - - - 1991 - - - - - - - - 1992 - - - - - - 1993 - - - - 6 months and 4 years, high levels of antibodies were found against type 1 and type 2 (>95%) but lower levels against type 3 (78%). The high levels of circu- lating antibodies to poliovirus type 1 and type 2 were probably the result of the OPV mass campaign and the poliomyelitis epidemic of 1961. In 1972 a survey of 129 children aged 1-3 years from different parts of the country detected that neu- tralizing antibody levels were >95% to all three Table 4: Distribution of poliomyelitis cases in Israel, by pollovirus type, 1953-63a No. of strains No. of type: Type 1 typed 1 2 3 (%) 1953-54 56 54 1 1 96 1955 94 68 13 13 72 1956 70 67 3 0 96 1657 36 4 19 13 11 1958 429 406 9 14 94 1659 17 5 0 12 30 1960 31 6 18 7 19 1961 152 149 0 3 98 1962 14 0 0 14 - 1963 4 1 1 2 25 a See ref (13). types of poliovirus. This indicates that the national immunization programme with four doses of OPV in infancy was highly effective. In 1974, a survey of non-Jewish children aged 12-16 months was carried out in the Akko subdis- trict. In one village (Sakhnin), more than 90% of such children had protective antibodies to poliovirus type 1 and type 2, but only 72.5% to type 3. Howev- er, children from another village (Nahaf) had unsatis- factory levels of antibodies to all three types: 66%, 81%, and 67% for type 1, type 2, and type 3, respec- tively. This arose because in 1974 there was an out- break of poliomyelitis, with 26 cases among the non- Jewish population of the whole country. Of these cases, 14 occurred in nine Arab villages in the Akko subdistrict, including four cases in Sakhnin, but no cases in Nahaf. The differences in levels of neutraliz- ing antibodies may therefore have arisen because children in some villages in this area received a booster effect against poliovirus type 1, while those in other villages did not. In 1975, a survey of 107 children aged 6 years in Netanya and Tel Aviv found various levels of antibodies to all three types of poliovirus: 78-84% for type 1; 89-100% for type 2; and 73-84% for type 3. In 1974-75, there were only two cases of polio- myelitis among the Jewish population in the whole WHO Bulletin OMS. Vol 72 1994 787 N. Goldblum et al. of Israel. The low level of virus activity in the Jewish population in the early 1970s therefore failed to boost the immune status of 6-year-olds. A study of 68 physiotherapy students in contact with post-poliomyelitis patients in the early 1970s found that >90% had protective levels of circulating antibodies to all three poliovirus serotypes. These high levels may have been the result of exposure to the wild virus excreted by their patients. In the period 1982-87, a series of serosurveys among children and adolescents aged 6-17 years found good levels of poliovirus neutralizing antibod- ies among 6-year-olds. Low levels of circulating antibodies were found for poliovirus type 1 among 12- and 17-year-olds (80-87%), although protective levels were found against type 2 (94-96%) and type 3 (89-90%). In the late 1980s, a serosurvey of 18- year-old recruits to the Israeli Defence Forces (IDF) found satisfactory antibody levels to poliovirus type 2 and type 3 (96%-93%) but not to type 1 (85%) (14). These low levels of type-I neutralizing anti- bodies may have been caused by a combination of factors, including a lack of booster effect by circulat- ing wild poliovirus and a fall-off in circulating anti- bodies with age. Poliomyelitis control in the West Bank and Gaza Since 1967, the West Bank and Gaza have been under Israeli control. In 1970 the population of Gaza was 350 000, and the levels of hygiene, sanitation, and living standards were poor. About 55% of the population lived in refugee settlements-crowded slums adjacent to the main urban centres. The West Bank had a population of 575 000, a third of whom lived in 15 urban settlements and two-thirds in 450 villages, where the sanitary and socioeconomic conditions were better than those prevalent in Gaza. Some immunization with OPV was carried out prior to 1967 in Gaza and the West Bank, but the coverage levels were low. A serosurvey in 1967 in Nablus found very low levels of circulating antibod- ies to all three poliovirus serotypes among children aged 6-18 months. In a sample of 69 children, the distribution of antibodies was as follows: 51% had type-1; 36% had type-2; and 19% had type-3 anti- bodies at serum levels of 1:4 dilution). This indicates low levels of protection and immunization coverage. Since 1967, based on Israel's experience in developing primary health care and control of vac- cine-preventable disease, a great effort has been placed on achieving high levels of infant immuniza- tion for a broad range of vaccines, including polio- virus vaccine. The immunization programme is delivered through an expanding network of primary care facilities and vaccination teams who visit the vil- lages, and is staffed by local personnel. This pro- gramme was initiated in the West Bank and Gaza and used three doses of OPV, given at 2-3, 5, and 7 months of age. This schedule continued until 1973, when a booster dose given 6 months after the third dose was added, in line with practices in use in Israel. In 1973, the Nasser Children's Hospital was opened in Gaza in place of a fever hospital; this pro- vided an opportunity to investigate all suspected cases of poliomyelitis. Close working relations with the Central Virus Laboratory of the Ministry of Health in Israel were established for examination of clinical specimens. Despite the use of four doses of OPV among infants in Gaza from 1973, serious out- breaks of poliomyelitis occurred in 1974 (75 cases) and 1976 (77 cases). The situation in the West Bank was less critical, but in 1974 there were 29 cases, and in 1976, 35 cases of poliomyelitis. Most cases involved children under 2 years of age, with some involving over-3- year-olds. In the epidemic period between 1973 and 1977 in Gaza, paralytic poliomyelitis had a poliovi- rus type 1 etiology, while in the non-epidemic peri- odic poliovirus type 3 was isolated. Over this period the predominant poliovirus isolated from cases in the West Bank was type 3 (15). The poliomyelitis epidemics in Gaza were partly due to insufficient vaccination coverage in the early 1970s (estimated to be 75% of infants, increasing after 1973 to 85%). The infrastructure for primary health care was very limited prior to 1967, although the United Nations Relief and Works Agency (UNRWA) did provide such care to the Palestinian refugee population. The government health service subsequently developed services for the non-refugee population and provided vaccine to UNRWA. Vacci- nation policy has been fully coordinated between the government health service and UNRWA since the 1970s. In 1974 and 1976, the attack rate of poliomyeli- tis in Gaza for children immunized with three or four documented doses of OPV was 0.72 and 0.67 per 1000 children, respectively. The attack rate among partially (i.e., <3 doses of OPV) or unvaccinated chil- dren was 3.90 and 4.71 per 1000 children, respec- tively. Unimmunized or partially immunized chil- dren were approximately six times more likely to develop paralytic poliomyelitis than fully immunized children (15). Serosurveys at that time showed that children who had been immunized lacked protective antibod- ies to one or two poliovirus serotypes. Surveys with 1:4 serum dilutions carried out in 1973-77 showed that 36% (n = 61) of children previously immunized with three or four doses of OPV lacked antibodies to one poliovirus serotype, while 26% lacked antibod- WHO Bulletin OMS. Vol 72 1994788 Poliomyelitis control In Israel, the West Bank and Gaza Strip ies to two poliovirus serotypes. Random vaccine samples collected from field conditions during this period were tested in the Central Virus Laboratory and found to be fully potent. It was suspected that interference with OPV by other enteroviruses in the area occurred among cases of poliomyelitis involving fully and partially immu- nized children. Circulation of wild poliovirus may have been facilitated by the stream of visitors from surrounding countries where poliomyelitis was still endemic. In 1976-77, a survey of enteroviruses in the stools of a sample of children up to 18 months of age showed that isolates of non-polio enteroviruses from those with gastroenteritis (n=39) and those who were healthy (n=1 14) were nearly identical (41% and 40%, resp.). A 1974-75 serosurvey among 142 children in Gaza revealed low levels of neutralizing antibodies to poliovirus at 12 months of age, but the proportion of children with protective antibody levels increased gradually with age. The proportion of infants aged 10-12 months who had neutralizing antibodies (at 1:10 serum dilutions) was as follows: 20-38% had antibodies against type 1: 60-71%, against type 2; and 52-70%, against type 3. A total of 88% of chil- dren aged 2-3 years had neutralizing antibodies against type 1 and type 2, and 94-96% against type 3. Children over 3 years of age had high levels of antibodies against type 1 and type 2 (93-100% and 100%, resp.), but for type 3 there was a decline in protective antibody levels to 75-80% (Central Virus Laboratory, unpublished data, 1975). In 1975, an epi- demic of poliomyelitis type 1 in Gaza with 75 cases may have contributed to the increased levels of anti- bodies to poliovirus type 1 and type 2 in the popula- tion. The occurrence of paralytic poliomyelitis among under-2-year-olds arose because of low levels of antibodies in this age group. In view of the difficulty in controlling poliomye- litis, despite relatively high coverage with OPV in an area experiencing continued importation of poliovi- rus from neighbouring areas, an expert review of the situation was carried out. As a result, it was suggest- ed that the continuing problem of poliomyelitis was associated with interference in the uptake of OPV caused by other enteroviruses and was not the result of cold chain deficiencies.a A new programme of immunization was adopted for Gaza and the West Bank, starting in 1978, as outlined in Table 5. As the first step, this included a massive campaign carried out within 7-10 days with OPV type 1 for all chil- a Melnick JL. Recommendations for the control of poliomyelitis in Israel, West Bank and Gaza Strip, 13-26 October 1977. Unpublished document WHO EM/VIR/7. EM/EPID.54, December 1977. Table 5: Immunization schedules in Gaza and the West Bank, 1978 Schedule used in: a Gaza Strip West Bank OPV type 1 at 1 month of age TOPV at 2 months of age with BCG TOPV + IPV at 2.5 months TOPV + IPV at 3.5 months of age with DPT of age with DPT TOPV + IPV at 4 months TOPV + IPV at 3.5 months of age with DPT of age with DPT TOPV at 5.5 months of age TOPV at 6.5 months of age with DPT with DPT TOPV at 12 months of age TOPV at 12 months of age with DPT with DPT a TOPV = trivalent oral poliovirus vaccine; IPV = inactivated poliovirus vaccine; and DPT = diphtheria-pertussis-tetanus vaccine. dren aged 0-2 years in Gaza and the West Bank. A second major change in immunization policy was the introduction of two doses of IPV in addition to four- to-five doses of OPV, given as an integral part of the immunization programme during the first year of life. The rationale for this combined vaccine pro- gramme was to establish high levels of immunity, both intestinal and humoral, as early in infancy as possible. The combined immunization programme was reviewed in 1981 and it was recommended that it be continued.b Over the next few years following insti- tution of the combined OPV/IPV immunization pro- gramme, there was a dramatic reduction in the num- ber of cases of poliomyelitis, with a total of 22 sporadic cases over the period 1981-88. This includ- ed two cases in 1988, when 15 cases of paralytic poliomyelitis occurred in Israel (16-21). In 1991, wild poliovirus was found in sewage samples in Gaza, indicating that it had probably recently been imported into the area from neighbour- ing countries and that if vaccination efficiency were not high there would be a risk of an outbreak of poliomyelitis. In 1991-92 an outbreak of the disease in Jordan raised the possibility that wild poliovirus could be imported by the large number of visitors from that country. A precautionary mass immuniza- tion campaign was therefore carried out by adminis- tering OPV to children up to the age of 5 years in both the West Bank and Gaza. A serosurvey of antibodies circulating to six strains of wild poliovirus among children vaccinated b Gregg MB, Lundbeck H, Melnick JL. Report of a consulta- tion on poliomyelitis control to Israel, and the Territories of Gaza and the West Bank. Unpublished document WHO EM/INZ/17. EMNIR/15, September 1981: 1-19. WHO Bulletin OMS. Vol 72 1994 789 N. Goldblum et al. with four doses of OPV only was carried out in 1990. These children were compared with others who had received OPV/IPV (4 doses and 2 doses, resp.). There were no differences in the humoral neu- tralizing antibodies for various strains of poliovirus type 1 and type 2. However, only 70-80% of chil- dren who had been immunized with OPV alone had neutralizing antibodies to all three strains of wild poliovirus type 3, whereas over 95% of those vacci- nated with OPV/IPV had protective antibody levels (22). The control of poliomyelitis in Gaza and the West Bank, despite sanitary conditions conducive to the spread of the disease, and the regular influx of large numbers of visitors from areas where the dis- ease is endemic, indicates that the immunization pro- gramme has been successful. No cases of poliomye- litis have been identified since 1988 in either area (see Fig. 5 and Fig. 6). The combined OPV/IPV pro- gramme in the routine infant immunization schedule, with over 90% coverage, played a ing, and ultimately eliminating, cl tis in Gaza and the West Bank in th achieved despite the presence of i the environment and the real poss introduction into the area from ne tries. Poliomyelitis control, 1981-93 Hadera outbreak At the beginning of the 1980s the using enhanced potency IPV (e with this vaccine in some Europear ted very high levels of antibody pr There was concern about the con of some cases of paralytic polior Fig. 5. Incidence of poliomyelitis 1967-93. 01 l,,, 6 1967 1970 1975 1980 Year Fig. 6. Incidence of pollomyelltis In the West Bank, 1967-93. 1980 Year key role in reduc- despite high coverage with four doses of OPV, and linical poliomyeli- with vaccine-associated cases of paralytic polio- te 1980s. This was myelitis among infants and their contacts (28, 29). wild poliovirus in This interest was also based on the successful control ,ibility of its fresh of poliomyelitis in Gaza and the West Bank follow- .ighbouring coun- ing the addition of IPV to the OPV used since 1978 in the routine infant immunization programme. A limited field programme of immunization and the 1988 with eIPV was carried out over the period 1982-88in two districts of Israel (Hadera and Ramle), both of which have well-organized public health services. re was interest in Hadera, which is located midway between Tel Aviv IPV). Experience and Haifa, had a population of 161 000 in 1982, 54% n countries indica- of whom were Jewish. A total of 20 cases of polio- roduction (23-27). myelitis had occurred among the non-Jewish popula- tinued occurrence tion and two cases among the Jewish population over myelitis in Israel, the period 1971-87. Ramle, which lies south-east of Tel Aviv, had a population of 109 000 in 1982, 87% in the Gaza Strip, of whom were Jewish. Only three cases of poliomy- elitis occurred in the non-Jewish population over the period 1975-87, and none among the Jewish popu-| lation. The Hadera-Ramle programme consisted of administering three doses of eIPV as part of a quad- ruple vaccine, DPT/eIPV, given at 2, 3.5, and 10 months of age. Over the 6-year period 1982-88, chil- dren were routinely immunized with eIPV. During 1979-84, both the Jewish and non-Jewish children in Ramle also received OPV type 1 during the annual spring booster campaigns. However, in Hadera, the additional dose of OPV type 1 was given only to the non-Jewish population. No cases of poliomyelitis occurred among the Jewish children immunized with eIPV, while there was one case among non-Jews-a _a-- ~ * * & , 5-year-old child who had received three doses of 1985 1988 1993 eIPV in infancy (30). WHO Bulletin OMS. Vol 72 1994790 Poliomyelitis control in Israel, the West Bank and Gaza Strip Between 31 July and 3 October 1988 an out- break of poliomyelitis, with 12 paralytic cases, occur- red in Hadera district. Most cases were among per- sons over 12 years of age who had been immunized in childhood with three or four doses of OPV. There were three additional cases in other parts of the country. Details of this outbreak have appeared else- where (30). Laboratory tests were carried out at the Ministry of Health Central Virus Laboratory, Tel Hashomer, on samples isolated during the epidemic, with the following findings: wild poliovirus type 1 was isolat- ed from 12 of the 15 paralytic cases, while neutraliz- ing antibodies were found in three other cases; of 36 stool samples of non-contact children and adults liv- ing in the town where the first cases of paralytic poliomyelitis were identified (Or Akiva), five yield- ed wild poliovirus type 1. Among 28 household con- tacts of the index cases, six yielded wild poliovirus type 1; among 17 non-household contacts of the index cases, there was only one isolate of wild polio- virus. No wild poliovirus was isolated from 75 stool samples from healthy non-contacts in other parts of the country. Of the 15 clinical cases of paralytic poliomyelitis in Israel in 1988, three involved indi- viduals who were not immunized at all; these includ- ed one infant aged 2 months, a girl aged 21 months, and a woman aged 50 years who had immigrated from Argentina (30). The three doses of eIPV given up to 10 months of age in Hadera and Ramle produced high levels of neutralizing antibodies, which except for one case, protected this age group from poliomyelitis in the 1988 outbreak. However, eIPV apparently produced low levels of intestinal immunity, as indicated by the detection of wild poliovirus type 1 in stool samples from children and adults in Hadera during the out- break. Paralytic cases occurred in Hadera in 1988 among the adult Jewish population, but not among the non-Jewish population. This suggests that the non-Jewish children developed high levels of intesti- nal immunity through the annual springtime cam- paign with OPV type 1 over the period 1979-84. This extra dose of OPV may have provided a booster of vaccine to these children and their families, and prevented them from shedding wild poliovirus in the environment during the Hadera outbreak. The occurrence of paralytic poliomyelitis cases in the teenage and adult populations in Hadera could have arisen because of a lack of neutralizing antibod- ies to the wild poliovirus type 1. This is reflected by the low levels of type-I antibodies observed in vari- ous serosurveys of young adults (14, 30). Individuals immunized before 1972 received OPV that had a lower concentration of poliovirus type 1 than that currently being used (30). Also, there may have been a gradual decline in antibody levels over time, since booster doses of OPV were not given as part of the routine immunization programme for schoolchildren. Support for this latter explanation is provided by a recent study that reported immunological memory among different age groups against various strains of type-I vaccine and wild poliovirus; in this study, subjects responded to a booster dose of OPV by pro- ducing antibodies to all strains, even among those with low levels prior to receiving the booster (31). In Ramle, no cases of poliomyelitis have been reported for many years, and all children in the dis- trict have received OPV type 1 in the annual booster campaign in addition to the eIPV routine pro- gramme. The occurrence of wild poliovirus in sew- age in the district points to the substantial presence of the virus, but the absence of clinical cases of poliomyelitis suggests that intestinal immunity has been sufficient to prevent an outbreak (30). The role of sewage in the Hadera outbreak has not been uni- versally accepted. Some workers hold that sewage contamination was one of the factors in the transmis- sion of the poliomyelitis, while others suggest that wild poliovirus was present in sewage because it was shed in the stools of those who had received eIPV; these individuals were exposed to, infected with, and shed the virus, despite being protected from develop- ing the disease. The Israeli Ministry of Health invited WHO to assist in assessing the Hadera outbreak and its con- trol. As a result, a massive OPV campaign was con- ducted, which apparently aborted the outbreak.c The whole population of Israel up to 40 years was cov- ered, except for infants below 2 months of age and pregnant women, who were given eIPV. Just at the end of the Hadera outbreak, a mass campaign was also carried out in the West Bank and Gaza with OPV being given to all those in the age range 2 months to 40 years. Revision of the poliomyelitis immunization strategy In light of the Hadera outbreak, the policy discus- sions on future poliomyelitis immunization policy considered the following requirements: - rapid induction of both humoral and intestinal immunity; - prevention of vaccine-associated cases; and -the cost-effectiveness of different immunization policies. c Melnick JL, Orenstein WA, Rey M. Poliomyelitis control - follow-up to the 1988 outbreak. Report on a visit to Israel, 5-6 October 1988. Unpublished document WHO.lsr/EPI 001, 1988. WHO Bulletin OMS. Vol 72 1994 791 N. Goldblum et al. As a result, Israel adopted a modification of the combined programme used in Gaza and the West Bank since 1978. This modified, combined OPV/IPV programme was also implemented in the latter two areas, with eIPV being given as the first dose of vac- cine, followed by two doses of eIPV in the first year of life. In the West Bank three doses of OPV + three doses of eLPV are given, while in Gaza four doses of OPV + three doses of eIPV are given because of its poorer sanitary conditions and higher prevalence of enteroviruses. There were no cases of poliomyelitis in Gaza and the West Bank over the period 1989 to 1994, despite the presence of wild poliovirus in sew- age, and the Jordanian outbreak of 1992 (32). The previous 10 years' experience of controlling poliomyelitis in Gaza and the West Bank was con- sidered to have been a successful application of the OPV/IPV combination in an area endemic to poliovi- rus and exposed to its fresh importation from neigh- bouring countries. This programme satisfied the need for early and rapid induction of high levels of both humoral and intestinal immunity. The Ministry of Health Advisory Committee on Immunization Policy therefore recommended adop- tion of the combined IPV/OPV programme with the following modifications; the first dose of poliovirus vaccine administered should be eIPV, in order to produce high levels of humoral antibodies and to prevent or diminish the possibility of vaccine-asso- ciated cases; and the number of doses of eIPV should be increased to three. This programme, which has been operating since 1989, includes a mix of three doses of eIPV and three doses of OPV up to the age of 12 months, with booster doses of OPV at 6 and 16 years of age (Table 6). A similar programme was adopted in the West Bank and Gaza. Following the 1988 outbreak, no cases of polio- myelitis have been reported in Israel, the West Bank, or Gaza. Discussion The proclamation of the State of Israel in 1948 was accompanied by large poliomyelitis epidemics, as newcomers moved in from countries around the world. Poliovirus vaccines, both IPV and OPV, were developed in the USA in the 1950s. By 1957, IPV was being produced in Israel and widely used. While the number of cases decreased, poliomyelitis con- tinued to be a problem, particularly in 1958 and 1961 (Table 1). In 1961, thermostabilized OPV became avail- able and was used successfully to abort the polio- myelitis epidemic in Israel. Since then, administra- tion of OPV on its own has greatly reduced poliovi- Table 6: Poliomyelitis immunization schedule used In Israel since 1989 Age Vaccinea 2 months elPV 4 months TOPV + elPV 6 months TOPV 12 months TOPV + elPV 6 years TOPV 16 years TOPV a elPV = enhanced inactivated poliovirus vaccine; TOPV = trivalent oral poliovirus vaccine. rus circulation and successfully interrupted the chain of transmission of wild poliovirus, as in other coun- tries. However, worldwide, approximately 100 000 cases of clinical poliomyelitis still occur each year, particularly in tropical countries (37). During the period 1961-79, Israel's routine immunization programme for infants was based on OPV alone, initially using three and then four doses. Outbreaks, although relatively small, occurred in the 1970s, and additional doses of OPV were given in annual springtime mass campaigns that were initiat- ed in 1979. As a result, poliomyelitis was reduced to only a few cases during the 1980s, but this drew attention to the vaccine-associated cases, which accounted for five of the total of 32 paralytic cases in the period 1980-87. In other countries where OPV is used alone, there were a number of outbreaks of paralytic polio- myelitis during the 1980s and 1990s. Examples of countries where recent outbreaks have occurred include China (Province of Taiwan), Jordan, and Oman. For example, a serious outbreak occurred in China (Province of Taiwan) in 1982 with 1031 cases of paralytic poliomyelitis caused by poliovirus type 1 (incidence, 5.8 per 100 000 population); prior to the outbreak two doses of OPV were administered at 80% vaccination coverage, with an average of nine cases per year over the period 1975-81 (33). In Oman an outbreak of poliomyelitis occurred in 1988-89 with 118 cases caused by poliovirus type 1, and an incidence of 87 per 100 000 children aged <2 years. Here the immunization programme included three doses of OPV up to 12 months of age with 87% coverage (34). In Jordan, an outbreak of para- lytic poliomyelitis occurred in late 1991 with 32 con- firmed cases, despite a reported 92% coverage of those aged <1 year, and 95% coverage with three doses of OPV for those aged <2 years (32). On the other hand, OPV has been used success- fully in eradicating poliomyelitis in North America (35), and more recently in South America (36), as well as in many European countries (37). In the WHO Bulletin OMS. Vol 72 1994792 Poliomyelitis control in Israel, the West Bank and Gaza Strip USA, no cases of paralytic poliomyelitis caused by wild poliovirus have been reported over the past 10 years, despite low vaccination coverage in infancy. However, 5-10 cases of vaccine-associated paralytic cases are reported annually (29, 37). In some devel- oping countries, where OPV has been used alone, the incidence of paralytic poliomyelitis has been reduced, but the disease continues to be endemic (29, 38, 39). In Cameroon, the incidence of poliomyelitis in Yaounde, the capital, was reduced by 85% as a result of immunization with three doses of OPV in infancy, at a coverage of only 35% (40). In Madras, India, the risk of clinical poliomyelitis among immu- nized children was five times greater than that ex- perienced by children immunized with three doses of OPV (efficacy, 86%) (41). Use of IPV alone has also been associated with outbreaks of poliomyelitis. For example, although IPV was used in Finland for over 20 years at a coverage of 95%, this did not prevent an outbreak of nine cases of paralytic poliomyelitis in 1984, most of whom were adults. Wild poliovirus type 3, the cause of the outbreak, was found in eight sewage samples, which indicated the presence of infected persons in the community (42). In the Netherlands, where IPV has been used since 1961, and eIPV since 1984, there have been several outbreaks of poliomyelitis, the latest in 1992 with 54 paralytic cases. Although all the outbreaks occurred among religious groups that opposed immunization on ideological grounds, the outbreaks indicated that despite very high immunity levels among the Dutch children immunized with this vac- cine, there was a lack of herd immunity among those who were unimmunized. Furthermore, many of the children immunized with eIPV excreted wild polio- virus (43, 44). Another example of the failure of eIPV alone to prevent poliomyelitis outbreaks occurred in Senegal in 1986. A field trial programme in Kolda, where tri- valent OPV was used until 1980, had a relatively high success rate-reducing the number of cases to 1-7 per annum. In 1980 the immunization pro- gramme substituted eIPV for OPV and continued using it until 1986. In the latter year, an outbreak of 69 cases of paralytic poliomyelitis occurred, prob- ably indicating that IPV alone is insufficient in tropi- cal areas with endemic poliomyelitis (45, 46). Use of IPV in Israel was not favoured because of the general success of the OPV programme; how- ever, in the early 1980s the availability of eIPV raised interest in its advantages over previous types of IPV. This led to the approval of a trial programme of eIPV in two subdistricts, in the expectation that if successful in a field setting eIPV would be adopted for the whole country. The Hadera outbreak emphasized a number of noteworthy phenomena: 7.6% of the Israeli popula- tion lived in Hadera and Ramle districts; the majority of cases were aged 15-24 years; the attack rate in Hadera was 67.4 per million compared with 3.5 per million for the total population of the country. For the age range 25-29 years, the attack rate for the Hadera population was 240 per million, compared with 9.2 per million for the whole country, a 26-fold difference. Wild poliovirus type 1 occurred through- out Israel, as suggested by the three cases of polio- myelitis caused by it that were identified in 1988 in different parts of the country. Type-I isolates were also made in sewage samples from Hadera and in Ramle districts during the outbreak. Serosurveys showed that young people aged .12 years had low levels of antibodies against poliovirus type 1, which was responsible for the outbreak. The OPV vaccine used up to 1972 had a lower concentration of poliovirus type 1 (3 x 105 TCID50) than the vaccines that were used subsequently (1 x 106 TCID50). The lower concentration of type 1 in the vaccines used up to 1972 may have resulted in lower antibody levels than those produced by subse- quent vaccines. Genetic changes were observed in the wild poliovirus type 1 isolated from cases during the 1988 Hadera poliomyelitis outbreak, but these changes were also found among the three cases in other parts of the country where there was no out- break (30). Over the period 1981-88, sporadic cases of poliomyelitis (including 5 vaccine-associated cases) continued to occur in Israel, despite the OPV vacci- nation programme that had been operating since 1961. On the other hand, the use of eIPV alone in two districts, as described above, did not prevent the largest poliomyelitis outbreak in Israel since 1979. The lack of booster doses of OPV after the first year of life may have contributed to the occurrence of cases of poliomyelitis among adolescents and young adults in the Hadera outbreak. A review by the Min- istry of Health recognized the advantages of the combined OPV/IPV programme as carried out in Gaza and the West Bank since 1978. As a result, the combined OPV/IPV schedule was adopted as part of the routine infant immunization programme along with boosters of OPV for those of school-age (see Table 6). In Denmark, following a large outbreak in 1961 with 141 paralytic cases of poliomyelitis, a combined IPV/OPV schedule was adopted in 1968. Three doses of IPV are administered at 5, 6, and 15 months of age, followed by three doses of OPV at 2, 3, and 4 years of age (47). Because in Israel, poliomyelitis has largely been infantile, and because of concem that delaying administering OPV until 2 years of age WHO Bulletin OMS. Vol 72 1994 793 N. Goldblum et al. would interfere with the development of intestinal immunization, the Danish sequential approach was not adopted. In Israel, the Danish approach could have resulted in the transmission of wild poliovirus by children who were themselves immune to the dis- ease. Administration of OPV is accepted as the best way of achieving intestinal immunity by vaccination, while IPV (either original or enhanced) produces considerably less intestinal immunity (37). A clinical trial, carried out in the USA in 1991, in which one group of children was given OPV and another IPV and were subsequently challenged with poliovaccine virus type 1, found that among the OPV group 25% of the children shed the challenge virus in their stools, while 63% of the IPV group shed the virus. This significant difference showed that those immunized with OPV had a higher degree of intesti- nal immunity to poliovirus, confirming work carried out over 30 years ago in Moscow (48, 49). The suggestion that the "genetic drift" of wild poliovirus could cause outbreaks of poliomyelitis is not well documented, while there is evidence that antibodies produced by OPV are polyclonal, with broad defensive capacities (37). Genetic drift has been proposed as a potential factor in outbreaks in areas using IPV alone. The wild poliovirus type 3 that caused the poliomyelitis outbreak in Finland in 1984 exhibited some genetic changes, but these were not considered epidemiologically significant by the Finnish investigators, who attributed the outbreak to poor immunogenicity induced by the type-3 compo- nent of the IPV preparation (42). Trials in Germany and former Czechoslovakia of the Finnish strain of poliovirus type 3 (P3/Finland/23127/84) in children immunized with standard OPV found high levels of neutralizing antibodies against this strain. These workers found that only three amino acids of the 12 in the VP1 region of the Finnish strain were exchanged, but that this had little immunological sig- nificance (50). A study in the USA found that 96-99% of chil- dren aged up to 7 years had protective antibodies to the Finnish strain and 99-100% to Sabin type-3 strain; 75% of the children aged 10-12 years had neutralizing antibodies to the Finnish strain and 92% to Sabin type 3. It was concluded that in the USA, children in these age groups would have been protect- ed if they had been exposed to the Finnish strain (51). Global eradication of poliomyelitis has been tar- geted by WHO, and this involves consideration of appropriate immunization strategies using currently available vaccines. Several alternative immunization strategies have been used over the past 40 years: use of OPV alone, either in a routine infant programme or in periodic mass campaigns; use of enhanced IPV alone; and use of a combination of OPV and IPV. OPV alone has been used widely and successfully in the majority of countries over the past 30 years; IPV alone has also been used successfully, mainly in western and northern European countries (37). Use of a combination of OPV and IPV has been successful in a small number of locations including Denmark, and as described above Gaza, the West Bank, and Israel. The experience in Israel, Gaza, and the West Bank suggests that the combined approach to poliomyelitis immunization is most suitable in areas where sanitation is compromised and there is continued importation of wild poliovirus (16, 21). The combined OPV/IPV immunization pro- gramme adopted in the Gaza and the West Bank in 1978 produced a dramatic reduction in the incidence of poliomyelitis. Since 1988 there have been no cases despite the presence of wild poliovirus in sew- age and the fresh importation of wild poliovirus from neighbouring areas. The effect of the modified com- bined programme adopted in Israel in 1989 has been the absence of cases of poliomyelitis since its adop- tion. This combined OPV/IPV programme is suitable for developing countries or areas where sanitation and hygienic conditions are compromised. Even in developed countries that use IPV alone there is the potential for the introduction of wild poliovirus, as occurred in the Netherlands in 1986 and 1992, with outbreaks of poliomyelitis among unvaccinated groups because of lack of environmental herd immu- nity. In our view, the combined OPV/IPV approach is very relevant to the needs of developing countries, and even to those of some developed countries, in the international effort to eradicate poliomyelitis. Acknowledgement We would like to thank Ms H. Buchbinder for editorial assistance. Resume Lutte antipoliomy6litique en Israel, en Cisjordanie et dans la Bande de Gaza: application de diverses strat6gies visant A obtenir l'6radication de la maladie dans une r6gion d'end6mie Le degr6 d'endemie de la poliomyelite etait dlev6 en Israel dans les annees 50 et l'on avait r6ussi a I'abaisser en utilisant le vaccin Salk pr6par6 a partir de poliovirus inactive (VPI). Cependant, des epid6mies ont continu6 a se produire jusqu'en 1961, ann6e au cours de laquelle une vaste epi- WHO Bulletin OMS. Vol 72 1994794 Pollomyelitis control In Israel, the West Bank and Gaza Strip d6mie a ete stopp6e grace a la vaccination de masse par le vaccin antipoliomy6litique buvable (VPO) Sabin. Depuis lors, le VPO est rest6 le vaccin classiquement utilis6, mais on a continu6 a observer de faibles flamb6es de poliomy6lite jusqu'a la fin des ann6es 70. Dans la Bande de Gaza et en Cisjordanie, on a observ6 de petites 6pid6mies de poliomy6lite jusqu'a la fin des annees 70, ou l'on a adopt6 I'association VPO plus VPI dans les programmes de vaccination de base. Des cas sporadiques de poliomy6lite ont encore Wt6 notifi6s dans les ann6es 80 en lsrael, notamment 5 cas associ6s a la vaccination au cours de la p6riode 1981-1987. En 1988, une flamb6e de 15 cas, survenus pour la plupart chez de jeunes adultes, a 616 enregistr6e dans une region ou l'on avait utilis6 le VPI seul pour la vac- cination de routine des nourrissons. Le calendrier vaccinal associant VPI et VPO, utilis6 en Cisjorda- nie et dans la Bande de Gaza des 1978, a ete adopt6 sous une forme modifiee en Israel en 1989. Depuis lors, aucun cas de poliomy6lite n'a 6te notifi6 en lsraeI, en Cisjordanie ni dans la Bande de Gaza malgr6 l'introduction continuelle de poliovirus par les visiteurs venus des pays voi- sins. Dans les r6gions tropicales ou l'on trouve encore le poliovirus sauvage a l'etat end6mique, les strat6gies de vaccination visant a 6radiquer cette maladie devront donc peut-etre faire appel a l'association de plusieurs vaccins. L'6radication de la poliomy6lite suppose une certaine souplesse dans les strat6gies de vaccination appliqu6es, notamment I'adoption du calendrier associ6 dont il est question ici. References 1. Yekutiel P et al. 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