Preventive strategies against poliomyelitis T.A. Swartz

Successful poliomyelitis prevention depends upon the epidemiological characteristics of the infection and the immune status of the population in the area. Presently available polio vaccines may prove very useful for progress with polio control, provided the prevention programme has been adequately chosen and the limitations of the vaccine used have been taken into consideration. In the present and near future, polio prevention should aim at the containment and local elimination of the paralytic disease, which can be obtained with either OP V or E-IP V. The vaccine-associated disease remains an unsolved issue in an OP V programme. The association of O P V and E-IPV offers a clear advantage over the immunization with a single vaccine, particularly with O P V alone. Global eradication of polio, possible in principle, will be difficult to achieve by the year 2000, because of the present global dimensions of polio infection and the unequal environmental development of the world. Keywords: P o l i o m y e l i t i s

; vaccine ; OPV ; IPV ; EPI

INTRODUCTION Since the appearance of vaccines against poliomyelitis in the mid 1950s (inactivated polio vaccine (IPV)) and the early 1960s (oral polio vaccine ( O P V ) ) great effort has been made to achieve satisfactory control of the disease. The success of the last ten years, mainly in the developed countries, has been an incentive for the W H O Expanded Programme on Immunization to embark on a programme targeted at the global eradication of poliomyelitis by the year 2000. The three-phase model initially proposed by Evans 1 and that recommended later by W H O 2 have become the basis for the strategic approach aimed at the eradication of the disease (Table 1). While the Evans model is more broadly and exhaustively conceived, the W H O proposal precisely refers to: phase 1, a considerable limitation of the number of cases (less than ten per year) and no more epidemics; phase 2, the complete elimination of the disease associated with wild virus; and phase 3, the absence of wild virus in the physical and biological environment throughout the world. The epidemiological characteristics of polio infection, which differ with the extent of implementation of the vaccination programme, and the environmental development of the area may serve as a guide for understanding the still existing difficulties in progress with polio control and formulating the recommendations for the best strategy for polio prevention, adapted to the conditions in the area. For a satisfactory preventive strategy against poliomyelitis, the following three steps should be taken into consideration: evaluation of what has already been Department of Epidemiology and Preventive Medicine, TeI-Aviv University, Sackler School of Medicine, Tei-Aviv, Israel 0264-410)(/92/130904-05 © 1992 Butterworth-HeinemannLtd 904

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achieved; a critical approach to the available preventive means; and an effort to agree on a prescription of how to proceed. What has been achieved, and where we are today

The epidemiological pattern of poliomyelitis is different in countries with control programmes unequally implemented ( Table 2)3. In developing countries with partial vaccination programmes, the present pattern of poliomyelitis is expressed by periodically occurring epidemics, the disease affecting older age groups than in countries without a preventive programme. In developed countries, two different situations can be observed, of which the most important is the presence and circulation of wild virus of indigenous origin, due to the high rate of infected persons, who excrete the virus in the community. At a vaccine coverage considered satisfactory, the disease occurs either sporadically or in small outbreaks, and the main reasons for it are social failure (pockets of insufficient coverage, inadequate immune response in terms of extent, intensity and possibly also specificity, or a refusal of vaccination); introduction of wild virus; and a direct association with the administration of the oral polio vaccine. In contrast, in the absence of indigenous activity, the disease is usually sporadic, following the introduction of wild virus, or is vaccine associated. There is no doubt that presence of indigenous virus in a focus means also a risk of circulation outside the focus of activity, and that as long as the virus is present in the human reservoir or its environment, there is no country in the world provided with a shelter against introduction and (re)infection of the population 4. Therefore the crucial question is, once the introduction has occurred, what is the risk that it will be followed by spread of virus ?

Poliomyelitis prevention strategies: T.A. Swartz Table 1 Level 1 2 3 4

Levels of control of poliomyelitis Evans model

WHO model Containment (Stage B)

Absence of clinical manifestations Absence of human infection Absence of virus in the environment

Elimination" (Stage A) Eradication a

aOf disease associated with wild virus only

Table 2

Present epidemiological pattern of poliomyelitis

1 Developing countries • periodic epidemics • disease: in childhood due to: • partial vaccination • vaccine failure 2 Developed countries • with indigenous wild virus activity • disease: sporadic, in small outbreaks due to: • social failure • introduction • vaccine associated • without indigenous wild virus activity • disease: sporadic due to: • introduction • vaccine associated

Table 3 Factors which control polio activity following introduction of wild virus Immune status

Environmental conditions

Vaccine coverage Immune response • Proportion • Intensity • Persistence • Strain specificity

Antigenic structure of virus Physical environment Human behaviour Social environment

In its answer resides the basic information necessary to design the strategy to be pursued for effective prevention of the disease. Schematically presented in Table 3, two groups of factors are responsible for the control of polio activity following introduction of the wild virus: the immune status of the population and the environmental conditions. On one side of the system there are the operative index (a coverage which would ensure an immune status >~95% 5 of the population at risk of exposure to polio) and the biological index : the immune response which includes the proportion of seroresponse or seropositivity (degree of failure), its intensity (the value of neutralizing antibody (NA) titres considered protective), persistence (immunological memory) and the recently observed role of the strain specificity in protection against the disease 4. On the other side of the system operate the environmental conditions: the potential for evolution of the wild virus which can attain epidemiological significance in certain situations, as illustrated by the antigenic variation of the epidemic strains in the Finland 6 and Israeli 7 events, during the 1980s ; circumstantial evidence of survival of polio virus

for months or even years in sewage waters (the so-called environmental storage of the virus4); the capability of poliovirus to circulate in partially immune populations and even in highly immune communities7; it is well known that there exists a strong correlation between the community spread of enteric agents, including polio virus, and the level of family hygiene, which favours a faecal-oral mode of transmission and repeated exposure which can considerably increase the infective dose; and finally, the increased mobility of rural populations and/or concentration in big urban conglomerations with substandard sanitation considerably contributes to the community spread of virus. This means that even a highly satisfactory vaccine coverage and an excellent immune status following vaccination may not always guarantee a complete community protection because of the numerous environmental factors which act adversely. Practically, the preventive strategy for polio elimination should be simultaneously anchored on both sides of the system with a double purpose: first, to modify the environment so as to avoid virus introduction, persistence and transmission, and secondly, to strengthen the immunity of the individual so as to prevent clinical disease and infection, and that to an extent which will ensure the community protection in case of virus introduction. Available means for poliomyelitis prevention It is very probable that in the next few years and possibly until the end of the decade, the same two vaccines known for the last 30 years, and labelled as very effective and safe, will continue to be used in polio mass prevention. Observations from epidemic events which mostly occurred in the 1980s 6-11, changes in the technology of vaccine production 12 and progress in molecular virology 13 have added new information about the characteristics of both vaccines to our previous knowledge. The advantages of OPV are well known (Table 4), among14 16 which the most important are a good local secretory antibody response and interruption of gut replication of wild virus following mass administration of vaccine, as recommended in epidemics. Its main limitations are its immunogenicity, safety and thermostability. Table 4

OPV characteristics



1 Good humoral immunity

1 Humoral immunity needs boosting

2 Good secretory IgA response

2 May prevent seroconversion after three doses or more

3 In mass administration, blocks the gut replication of the epidemic virus

3 Lower immune response to epidemic than to the vaccinal strain

4 Satisfactory protective efficacy

4 Gut immunity transient, needs boosting

5 Routine administration easy

5 May fail to prevent replication and transmission of wild virus in vaccinated communities

6 Cheap

6 Vaccine-associated disease 7 Poor thermostability

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Poliomyelitis prevention strategies: T.A. Swartz Concerning immunogenicity, it should be mentioned that humoral immunity needs boosters in absence of re-exposure ; the failure to seroconvert is well known, but less stressed is its important consequence: the risk of paralytic disease among the vaccinated but non-immune following exposure to wild virus; the NA level to the epidemic strain may be definitely lower compared to the usually satisfactory NA values to the vaccinal strains. The gut immunity seen as the most important advantage of OPV is not only transient but possibly not sufficiently protective: recent observations from the Israel 7 and Oman al epidemics indicate that in well vaccinated communities, the replication of wild virus and its circulation were not prevented, even at a high vaccine coverage. Vaccine-associated disease remains a controversial issue only when its true extent is evaluatedl 7,18. With respect to E-IPV (Table 5), among its advantages 15.19,20 besides the high and uniform immune response, is its capability to induce an excellent immunological memory, which may be obtained even by priming at birth, provided a sufficiently potent antigen is used 21 Concerning its limitations, the lower gut immunity induced by the vaccine deserves some comment. It has been repeatedly observed that E-IPV vaccinated children when boosted with OPV develop a local immunity similar to that observed in OPV vaccinated children 22'23. Its limitations in preventing local replication and circulation

Table 5

E-IPV characteristics



1 Very high humoral immune response

1 Lower gut immunity than observed with OPV

2 Similar antibody response to epidemic and vaccinal strains

2 Limitation in preventing replication and spread of wild virus not different from OPV

3 Good immunological memory

3 Community protection requires a very high coverage

4 Protective efficacy fair excellent

4 Cost

5 No risk of vaccine-associated disease 6 Can be combined with other vaccines

Table 6

of wild virus, its main disadvantage, might not be very different from OPV particularly in epidemic situations 7'aa and the very high coverage necessary to afford community protection is not, in the final analysis, a particular characteristic of E-IPV. C a n w e a g r e e on a p r e s c r i p t i o n ?

The interrelationships between the vaccination options and the epidemiological pattern of the infection have a definite impact on the prevention of poliomyelitis

(Table 6). In conditions of indigenous activity, OPV does not prevent wild virus- a n d / o r vaccine-associated disease, and spread of virus into the community will persist. At a good coverage with E-IPV, or an association of OPV and E-I PV, the community spread of virus is still possible but limited, and neither wild virus- nor vaccineassociated disease are expected. In absence of indigenous activity and of introduction, a good control is expected with each of the three options, except vaccine-associated disease in an OPV programme. If introduction occurs in an area free of indigenous polio virus, besides imported polio, spread of virus to contacts may also occur, and a risk of vaccine-associated disease is present in OPV areas, in contrast to absence of paralytic disease of any cause in the E-IPV or OPV and E-IPV associated programmes. According to present observations, the association of the two vaccines appears to be the best option for each of the three epidemiological patterns presented. The benefits and limitations of the vaccination options in the achievement of the different levels of polio control, at least for the years to come, might be looked at as follows (Table 7). At a good coverage, OPV can contain the disease in conditions of limited indigenous activity, provided vaccine-associated disease is accepted as a by-product. The recurrence of paralytic disease after an interval of several polio-free years is another risk to consider 24 (and R. Cook, personal communication). At a coverage of ~>95%, and in the absence of indigenous transmission, OPV can achieve the elimination of the disease, provided that environmental sanitation and other environmental factors do not play an adverse role. Vaccine-associated disease still remains a threat. E-IPV is a very effective tool in the containment and elimination of the clinical disease, including the

Expected impact of vaccination option on the epidemiological pattern of poliomyelitis No indigenous activity


Indigenous activity

Without introduction

With introduction


WVAD Spread of virus VAD

No WVAD No spread of virus VAD

'Imported' polio Spread virus to contacts VAD


No WVAD Spread of virus No VAD

No WVAD No spread of virus No VAD

'Imported' polio Spread virus to contacts No WVAD No VAD


No WVAD Spread of virus limited No VAD

No WVAD No spread of virus No VAD

'Imported' polio No spread of virus No WVAD No VAD

WVAD, Wild virus associated disease; VAD, Vaccine associated disease


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Poliomyelitis prevention strategies: T.A. Swartz Table 7 1990s

Vaccination options for the strategy of polio prevention in the

Vaccination option Containment



Good coverage" Limited indigenous activity

Very high coverag& No indigenous activity Good environmental sanitation


Good coverage

Very high coverage Satisfactory immune status of all age groups at risk of infection

OPV+ E-IPV Good coverage

Very high coverage Satisfactory immune status of all age groups at risk of infection

a90-95% > 95%

vaccine-associated form, if a high rate of vaccine acceptance has been reached and of equal importance - maintained. The very high immune response and the immunological memory observed in virtually all the vaccinees compensates to a certain extent for the effect of the indigenous activity of the wild virus and induces a protective effect. Consequently, a considerable decrease in the quantity of circulating virus may be observed. E-IPV should be considered for use also in developing countries with strategies aimed at the containment of the disease, where the control of poliomyelitis with OPV has been unsatisfactory 2s. In countries where a substantial improvement of the environmental sanitation cannot soon be expected, the basic condition for progress with prevention is a good coverage with a practically identical immune response, implemented in a simplified schedule, anchored in the D P T component of the immunization schedule. On theoretical grounds and on the basis of observations coming from Denmark 26 and Israel v, two countries with contrasting environmental conditions, the association of the two vaccines seems an attractive alternative for the containment and elimination of the disease. Such a programme benefits from the advantages of each vaccine and reduces/eliminates their principal limitations. The association of the two vaccines should be considered in the developed countries with OPV programmes, which move towards the phase of elimination and want to get rid of the vaccine-associated disease burden, as well as in the developing countries, wanting to substantially reinforce a partially satisfactory immunity induced by a routine OPV programme. Eradication is not an easy step, either from the epidemiological or from the operational point of view. Many believe that eradication can be achieved with OPV only 4. Besides the advantages of this vaccine, there is at least one limitation of unquestionable significance: the unequal development of community sanitation and hygiene at the global level will not avoid persistence of indigenous activity of virus in certain areas, and its circulation followed by introduction in new areas, which might delay the eradication phase possibly for a considerable period of time. If the disturbing observation on the limitation of OPV to prevent the spread of virus into vaccinated communities gets further support, a second problem to be resolved might be added to the effort to eradicate poliomyelitis with OPV.

On the other hand, E-IPV, which at a very high coverage and in the presence of a good immunity level of all the groups at risk supports the elimination of the disease in the community, could be a valuable tool for its eradication. The elimination phase could be geographically expanded and, not less important, should be maintained. The effect of the association of OPV and E-IPV on the elimination of the disease is also valid when considering their combined role in eradication. The effect of the vaccine association on local immunity is expected to contribute to the prevention of gut replication of the wild virus, as has been recently shown in studies of the local immune response following the administration of the two vaccines 21'22. In the long run, one could even conceive a moment when eradication following a combined programme enters its consolidation phase and the prevention policy comes back to the exclusive use of E-IPV 25. CONCLUSIONS At the present level of knowledge and experience, the successful prevention of poliomyelitis does not depend only upon vaccines used in programmes with a high rate of acceptance and high immune response, neither can it be conditioned by the exclusive use of a particular vaccine. It depends upon the interrelationship between the immune status of the community as induced by vaccination, and the adverse factors of the environment. Each of the two available vaccines may prove very useful for progress with polio prevention, provided the objectives and the limitations of the programme have been clearly stated. Both vaccines can lead to the containment and elimination of the disease, according to the present definition of WHO. In any case, comparing the range of their effects, E-IPV or the combined OPV and E-IPV option are superior to OPV alone. If a more general definition of the concept of polio control is applied, which means prevention of paralytic disease associated with either the wild or vaccine polio virus strains, the elimination phase would be much harder to achieve without E-IPV, in exclusive or combined use. In principle, the eradication of poliomyelitis is possible, and the goal could be reached with the present vaccines. To achieve polio eradication in its broadest meaning the complete absence in the environment of polio viruses carrying a potential or actual risk of paralytic disease, which is in fact the human message of eradication E-IPV alone or in association with OPV seems an indispensable tool. The global dimensions of polio infection and the unequal social and environmental development of the countries participating in the eradication programme are the present obstacles to its success, and an important reason to suspect strongly that considerable difficulties will prevent its fulfilment by the year 2000. REFERENCES Evans, A.S. Criteria for assessing accomplishment of poliomyelitis control. Rev. Infect. Dis. 1984, 6 (Suppl. 2), $571-$576 WHO/EPI. Global polio eradication by the year 2000. Manual for Immunization Programme Managers on Activities Related to Polio Eradication. Expanded Programme on Immunization, WHO, 1989, pp. 11 13

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108, 1-18 16 Lemon, S.M. and Robertson, S.E. Global eradication of poliomyelitis: recent progress, future prospects and new research priorities. Prog. Med. Virol. 1991, 38, 42-55 17 Editorial. Polio reconsidered. Lancet 1984, ii, 1309-1310 18 Nkowane, A.M., Wassilak, S.G.E., Orenstein, W.A., Bart, K.J., Schonberger, L.B., Hinman, A.R. et al. Vaccine associated paralytic poliomyelitis in the United States, 1983 through 1984. J. Am. Med. Assoc. 1987, 257, 1335-1340 19 Beale, J, Polio vaccines: time for a change in immunization policy? Lancet 1990, 335, 839-842 20 Beale, J. Efficacy and safety of oral poliovirus vaccine and inactivated poliovirus vaccine. Pediatr. Infect. Dis. J. 1991, 10, 970-972 21 Swartz, T.A., Handscher, R., Stoeckel, P., Drucker, J., Caudrelier, P., van Mezel, A.L. et al. Immunologic memory induced at birth by immunization with inactivated polio vaccine in a reduced schedule. Eur. J. Epidemiol. 1989, 5, 143 145 22 Zhaori, G., Sun, M., Faden, S.H. and Ogra, P.L. Nasopharyngeal secretory antibody response to poliovirus type 3 virion proteins exhibit different specificities after immunization with live or inactivated poliovirus vaccines. J. Infect. Dis. 1989,159, 1018-1024 23 Faden, H., Modlin, J.F., Thomas, M.L., McBean, A,M, Ferdon, M.B. and Ogra, P.L. Comparative evaluation of immunization with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines in childhood: systemic and local immune responses. J. Infect. Dis. 1980, 162, 1291-1297 24 Expanded Programme on Immunization. Polio outbreak in Bulgaria, 1991. EPI Alert 1991, 2, 9 25 Plotkin, S.A. Current issues in evaluating the efficacy of oral poliovirus vaccine and inactivated poliovirus vaccine immunization. Pediatr. Infect. Dis. J. 1991, 10, 979-981 26 Pedersen, I. and Ronne, T. Control of poliomyelitis with inactivated and oral vaccines. 4th European Meetings of National Programme Managers on the Expanded Programme on Immunization, St Vincent, Italy, May 1991, WHO, 1991, ICP/EPI 027/38, pp. 1-4

Preventive strategies against poliomyelitis.

Successful poliomyelitis prevention depends upon the epidemiological characteristics of the infection and the immune status of the population in the a...
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