Indian Pediatrics 2003; 40:455-462 

Polio Eradication in India: What is the Future?

Correspondence to: Dr. T. Jacob John, Chairman, IAP Polio Eradication Committee, 439, Civil Supplies Godown Lane, Kamalakshipuram, Vellore, Tamil Nadu 632 002, India.

E-mail: [email protected]

It may seem too premature in February of 2003 to look towards the future beyond eradication of polio in India, as there was a serious setback on the battlefront against polio, by way of a large outbreak in northern India in the second half of 2002. Yet, in looking towards the future we do express our confidence that polio will soon be eradicated in India. While it is true that India will be either the very last country or one among the very few last countries in the world to achieve eradication, as predicted and warned years ago(1,2), there is no need for despair or frustration. All stakeholders must now plan ahead for the final stage of global polio eradication and the years thereafter.

What is Eradication?

The World Health Organization (WHO) defines polio eradication essentially as ‘zero incidence of wild poliovirus transmission anywhere in the world’(3). By its policy WHO had ensured that all developing countries used only the oral polio vaccine (OPV) to achieve this goal. The WHO definition is flawed or incomplete(1,4), since OPV itself causes paralytic polio, albeit infrequently(5,6). Even though directly caused by the vaccine virus, the disease is often called ‘vaccine-associated’ paralytic polio (VAPP). The attenuation of neuro-virulence in Sabin vaccine strains of polio-viruses is mediated by one or more nucleotide substitutions (point mutations) of the virus genome. Neurovirulence may re-establish with the following nucleotide substitutions in vaccine viruses (7-10): (i) For type 1 virus, at position 480 in the 5' noncoding region change from G to A, and at position 525 change from U to C. (ii) For type 2 virus, at position 481 change from A to G. (iii) For type 3 virus, at position 472 change from U to C.

The vaccine genotypes are unstable and vaccine viruses may, and usually do, back-mutate quite often to increasing neuro-virulence during multiplication in the human host(11). In Japan, where wild viruses were eliminated many years ago, river and sewage waters carry vaccine-derived viruses shed by vaccinated children(12). Among the strains of polioviruses in the environment, 69% of type 1, 92% of type 2 and 55% of type 3 viruses were found to be neurovirulent revertants (12). This is clearly a signal for the hidden risk inherent in the continued use of OPV. As long as immunity levels are maintained high with early vaccination of all children, the risk of infection by vaccine-derived neurovirulent mutants will remain low. However, if vaccination slackens, then the risk of infection from environmental source may increase.

The WHO Technical Consultative Group (TCG) on Global Polio Eradication estimates that globally (mostly in the developing countries) some 120 cases of VAPP occur annually, as the direct result of using OPV(6). The same number of VAPP would continue even after achieving the eradication of wild viruses(6). My own estimate is about 400-800 cases of vaccine-virus polio annually(13). In 1999 in India alone there were 181 cases of vaccine-induced polio, clearly showing that the TCG had missed the mark by a large margin(14). Many rich countries have already abandoned OPV in favour of the injectable (inactivated) polio vaccine (IPV) precisely to overcome VAPP. For all the reasons elaborated above, I have proposed a new definition of polio eradication as ‘zero incidence of human poliovirus infection, wild or vaccine-derived’(1,4). Table I presents the estimated annual numbers of cases of polio with the application of the two eradication definitions.
 

TABLE  I

The Annual Numbers of Estimated Cases of Polio Due to Wild or Vaccine Viruses According 
to Two Definitions of Eradication

Control status of polio	Cases of Wild-virus polio	Cases of Vaccine-virus polio
Endemicity	600,000-800,000.	400-800
Eradication (WHO Definition)	0	400-800
Eradication (Proposed definition)	0	0

 

We can justify the use of OPV to get rid of wild polioviruses, but not when they are no longer prevalent. Since the purpose of polio eradication is to ensure that no child should ever get polio, the continued occurrence of vaccine-virus-polio beyond the time when wild viruses cease to circulate is counter-productive, unnecessary, unethical and scientifically ‘defeatist’(4).

Newly Recognized Risks from Vaccine Viruses

In addition to causing VAPP in vaccinated children and their close contacts, two more risk-involving qualities of vaccine viruses have come to light in recent years(15-17). Fortunately attenuation had resulted not only in markedly reduced neurovirulence but also in decreased infectivity resulting in infrequent transmission from vaccinated children to contacts(18). Vaccine virus transmission occurs only occasionally within families and among very close contacts. This is a silent phenomenon except when VAPP occurs in contacts of vaccinated children. The property of inefficient transmissibility is also genetically determined, but since molecular virologists did not believe that attenuation resulted in lowered infectiousness, the genetic basis has not been investigated. Earlier, the ‘dogma’ was that OPV was ideal for the developing countries as it immunized all unimmunized contacts of vaccinated children, spreading just like the wild viruses(19). Inefficient transmissibility is reversible, albeit even more rarely than reversion to neurovirulence.

If both neurovirulence and transmissibility are re-acquired by the vaccine strain, then the resultant virus is virtually wild-like(15). Careful intra-typic differentiation (wild versus vaccine-derived) of polioviruses isolated from polio cases, and molecular characterization of all virus strains of vaccine-lineage, are essential for detecting such vaccine-derived wild-like (VDWL) viruses. Four instances of VDWL viruses causing small or large outbreaks of typical polio have so far been conclusively proved (Ayelward B and Wood D, personal communication, 2002). A strain of VDWL type 2 virus circulated in Egypt from 1988 to 1993 and caused 30 cases of polio. Since one case represents 1000 infections by type 2 virus, its circulation had reached 30,000 children. From July 2000 till January 2001 a number of cases of acute flaccid paralysis occurred in the island of Hispaniola in the Caribbean(15). Only in October was the clinical diagnosis of polio made, as the two nations in Hispaniola (Dominican Republic and Haiti) had eradicated wild polioviruses one decade earlier. Virus investigations were begun in October, resulting in the detection of a vaccine-lineage virus type 1 causing the outbreak(15). This virus had been in circulation for about 2 years, based on the proportion of nucleotide sequence variations from the Sabin original virus(15). A total of 22 cases were virologically confirmed to be caused by this virus, but obviously several cases were missed by not being investigated in a timely manner. Since one case represents 200 infections by type 1 virus, the outbreak involved 4400 children from October 2000 to January 2001; the number infected prior to the detection of this virus cannot be estimated. A cluster of 3 cases of polio due to VDWL type 1 virus was detected in the Philippines in 2001 and another cluster of 4 cases due to VDWL type 2 virus in Madagaskar in 2002. The occurrence and spread of VDWL viruses are rare and unpredictable events. However, declining coverage of OPV immunization resulting in increasing proportions of non-immune children mixing with vaccine-virus infected children seems to set the stage for their emergence and spread.

The second problem is chronic infection and prolonged shedding of vaccine-derived revertant viruses by a small number of individuals with primary immuno-deficiency(16,17). So far 19 cases have been described, each person shedding virus for a few to several years (Wood D Personal communication, 2002). They were detected in England (8 cases), USA (7 cases), and in Japan, Argentina, Taiwan and Iran (one case each). The longest recorded duration of chronic infection and virus shedding in one individual is 15 years(17). Alhough no secondary spread of virus has been documented from them, they may act as a source of virus only after polio eradication. The real risk will be known after the discontinuation of vaccination, when susceptible children may come into contact with them. Since ‘incidence’ refers to new infections, these chronic infection cases do not contradict the definition of eradication as ‘zero incidence’.

The Current Status of Polio Eradication

The world is divided into 6 WHO Regions. When three years elapse without any indigenous case of wild-virus polio in a WHO Region inspite of highly sensitive surveillance, it is certified polio eradicated. As of today, the American, Western Pacific and European Regions are so certified, in 1991, 1997 and 1998, respectively. The remaining South East Asian, Eastern Mediterranean, and African Regions are yet to achieve eradication. In 2002, indigenous circulation of wild polioviruses occurred only in India (SE Asia), Pakistan, Afghanistan and Egypt (E. Med), Nigeria, Niger and Somalia (African).

The number of cases of poliomyelitis caused by wild polioviruses in India had declined from 1126 in 1999 to 268 in 2001. However, there were 1509 cases during 2002, accounting for over 85% of cases detected globally (Francis P, Deshpande JM, Personal communication, 2002). Only three lineages of wild poliovirus type 1 had survived in Uttar Pradesh and Bihar in 2001. These lineages of type 1 accounted for 1404 (93%) cases, indicating that it was an outbreak of polio even in the face of intense eradication efforts. The remaining cases were due to poliovirus type 3. The number of districts with polio had declined to 63 in 11 States in 2001, but in 2002 cases occurred in 146 districts in 16 States. Karala, Tamil Nadu, Andhra Pradesh and Karnataka remained unaffected; in these States, routine and pulse immunizations have remained robust through the years.

Wild polioviruses were introduced from UP and Bihar to other States in 2001 and 2002. The root cause of this problem has now been identified as inadequate routine immunization, compounded by incomplete vaccination coverage during the pulse immunization rounds, in both these States. Remedial actions are being designed and instituted; there is hope for interrupting wild virus transmission in 2003(20). When all stakeholders are working hard together to complete the task, it is not polite to fix blame for this sorry state of affairs in India. At the same time it is essential for our own self-esteem to understand that global experts had misread the science, strategy and tactics of polio control and eradication as applicable to India while advising and guiding the Government of India. The Government was also at fault in not asserting its own autonomy while accepting advice and guidance, without applying its own mind. India will surely succeed in eradicating polio; there need be no doubt about it. Let us look to the future and cut out for us the tasks that lay ahead.

Guideposts to the Future

The goal of polio eradication has humanitarian and economic benefits. The humanitarian goal is to ensure that no child will ever get polio paralysis by eliminating the infectious agents from humans altogether. But the economic goal is to discontinue the use of vaccine against polio, thus saving enormous amounts of funds for ever. The ‘victory point’ is when polio vaccination can be stopped without risk of re-emergence of polio. Until only a few years ago, the WHO had maintained that OPV could be discontinued after making sure that wild viruses are completely eliminated from transmission. It is obvious that vaccine-induced polio will not occur after OPV is discontinued. Until then vaccine-induced polio was to be accepted as a small price for wild-virus eradication, with the estimated global total number of cases of vaccine-polio being 120 annually(6). In the more realistic estimate of 400-800 cases per year, India’s share would be between 100 and 200(13,14). This burden is not acceptable ethically or necessary scientifically since an alternative and totally safe vaccine, namely IPV, is already available. The safety, efficacy and ‘herd protective effect’ of IPV have been proven beyond doubt(21). The continued use of OPV after wild viruses are eliminated is unwise and unethical(4). Yet, its abrupt cessation without establishing IPV coverage will be risky for several reasons as enumerated below.

(i) One cannot be absolutely confident that three years are sufficient time to prove wild poliovirus has not survived somewhere in human communities. The Hispaniola incident showed that virus could spread silently for about 2 years before reaching sufficient numbers of susceptible children and causing polio.

(ii) The current disease surveillance and virological investigations could possibly miss cases in some overcrowded or remote population. If immunization is discontinued prematurely, infection can spread from such foci.

(iii) Wild polioviruses or virus-containing specimens are held in innumerable laboratories in many countries. Accidental transmission can result in spread in an underimmunized popula-tion. It will take time and effort to ensure that all such laboratories are identified and containment measures instituted. WHO will require a few years to achieve this globally. Until then immunization must continue. Similarly, the potential of polioviruses as a weapon for bio-terrorism has to be considered by the WHO and member nations. Even if current stocks of neurovirulent viruses are destroyed or well contained, poliovirus can be synthesized in the laboratory, using the blueprint of its genome sequence, which is public knowledge(22).

(iv) Vaccine viruses may revert to wild-like and establish circulation at unexpected times and places, if OPV is continued or discontinued. Maintaining high levels of immunity through vaccination is essential to preempt such occurrence. Immunization with OPV protects from wild and VDWL viruses; continued high coverage prevents the emergence of VDWL viruses. Discontinuing OPV without an umbrella of protection with IPV is literally ‘asking for trouble’.

My conclusions are simple and straight-forward: OPV must be discontinued as early as possible, but there should be no vacuum of immunity while it is being withdrawn. Therefore, first IPV must replace OPV and only later can we consider the discontinuation of polio immunization altogether.

Milestones on Our Future Path

In all probability we may achieve the elimination of circulation of wild viruses in India within a short time, perhaps in 2003 itself(20). Therefore, it is important that we look at the milestones ahead in order to manage correctly the final phase of polio eradication. The milestones and their proposed timing are enumerated in Table II.

TABLE II

Summary of Proposed Milestones

Milestones for future		Target year
1.	Establish comprehensive policy for future management	2003
2.	Eliminate wild poliovirus transmission	2003
3.	Certification of ‘eradication’ of wild viruses	2006
4.	Introduction of IPV in routine immunization	2006
5.	Complete withdrawal of OPV	2009
6.	Certification of ‘true eradication’ of polioviruses	2012
7.	Discontinue polio immunization	2015

 

(i) The first milestone is the articulation our policy of managing the future of eradication processes. Indian policy-makers and polio experts, in consultation with the WHO and other experts, must evolve our future policies in 2003 itself.

(ii) The second milestone will be the elimination of wild virus transmission throughtout the country. As indicated above, this can be achieved in 2003 itself. There will be no ‘excuse’ for not doing this, except for any reluctance or diffidence on the part of the Government of India to assert its own autonomy and ‘intellectual freedom’.

(iii) The third milestone will be the day of certification of wild virus eradication in the SE Asia region. Most likely, that will be in the year 2006. If this milestone is delayed, every ensuing milestone will be delayed as well.

(iv) The fourth milestone will be the the day we begin to introduce IPV in the national immunization program. This will signal our shift to IPV and the beginning of the end to OPV. I would strongly argue that this milestone should either coincide with the certification of polio eradica-tion itself or as soon as possible thereafter.

(v) The next milestone will be the withdrawal of OPV from the immuniza-tion system. This may be done three years after the introduction of IPV, and after achieving infant coverage of over 85% in every population unit. According to the above time schedule, OPV may be withdrawn in 2009, while continuing IPV. Obviously, VAPP will continue to occur, but with decreasing frequency, during the interval between the introduction of IPV and withdrawal of OPV. At this juncture, a decision regarding the need for maintaining stocks of OPV will have to be made. My personal opinion is that it should be the responsibility of the Polio Eradication Initiative of the WHO to maintain and manage such stocks as well as to ensure that the practice and skills of manufacturing OPV are maintained for a further period of time.

(vi) The sixth milestone will be when we could declare there is zero incidence of polio due to vaccine viruses or vaccine-derived wild-like viruses. That will usher in the state of true polio eradication. This may happen in 2012, after three years of exclusive use of IPV.

(vii) The seventh and final milestone will be the day we can confidently discontinue polio vaccination altogether. The proposed year is 2015. Obviously, AFP surveillance has to continue up till this point and also beyond. By this time the surveillance system would have been expanded to all vaccine-preventable diseases and other selected diseases of Public Health importance. It will be in the nation’s interest to maintain stocks of IPV for use in emergency. The competence and capacity of IPV manu-facture will have to be kept up to be able to face the unlikely possibility of polioviruses being used as a weapon of bioterrorism.

The current polio situation in India calls for urgent, honest and systematic efforts, fully backed by political will and accountability on the part of Government of India and State Governments, to eradicate wild polioviruses, if possible in the first half of 2003(20). The Indian Academy of Pediatrics will not be found wanting in any responsibility assigned to it or voluntarily assumed. While our attention is necessarily drawn to the immediate task of interrupting wild virus transmission, it is imperative, and in the best interests of the nation, to begin a thorough review of policy issues for the future. The milestones enumerated above give the pro-posed sequence of objectives to be achieved.

First of all, the Government of India must develop a clear policy and plan of actions, instead of working from year to year. The Government must issue approval for allowing the entry of IPV and the combination vaccine of DPT-plus-IPV in the country, and encourage their manufacture within the country. Unless the future market is assured, manufacturers may not invest the needed finances to develop IPV in India. With foresight and sound advice from national experts, the Government led by Late Mr. Rajiv Gandhi had initiated the establishment of a public sector industry to manufacture IPV, measles vaccine and the modern cell-culture rabies vaccine, but subsequent Governments decided to close it down mainly because the Health Ministry refused to approve IPV for use in India(23). The decision to establish the unit was taken after transparent deliberations but its closure was surreptitiously managed(23). Currently, at least 22 rich countries are exclusively using IPV and several more are in the process of replacing OPV with IPV. Globally the demand for IPV is greater than supply, and prices remain very high. Supply will remain short of demand in the foreseeable future, thereby maintaining high prices not afforded by poorer countries like India. India must decide on the processes of introduction of IPV and withdrawal of OPV, so that manufacturers can get on with their job with confidence. In my view, it is inevitable that sooner than people believe, the whole world will be using IPV. In addition to achieving self-sufficiency, IPV manufactured in India will also become a foreign exchange earner for the nation.

The introduction of IPV would be best done with the replacement of all DPT with DPT-IPV. Thus, IPV will get into the routine immunization under the national immuni-zation programme. As long as we continue to use OPV it has to be given in pulse fashion, since routine OPV immunization neither fully protected children from polio nor interrupted wild virus transmission. The distraction of pulse immunization has not helped the strengthening of routine immunization in several northern Indian States. With the use of DPT-IPV, we can rebuild an efficient immunization programme against all vaccine-preventable diseases. We should be able to revitalize routine immunization in three years. Until its coverage catches up to 85 % in infants, OPV should also be continued, but exclusively by pulse immunization. This phase of routine IPV and pulse OPV may be needed for three years, after which, OPV could be discontinued.

While the past cannot be re-enacted, the future can certainly be redesigned. The victory point of smallpox eradication was the discontinuation of ‘vaccinia’ vaccination. Of all the vaccines used in modern times, two vaccines put the lives or limbs of children at risk: the vaccinia and the OPV. The victory point of polio eradication will also be the discontinuation of polio immunization, but we have to touch the earlier milestone of stopping OPV without risking the re-emergence of wild polioviruses. This is our destiny and no force can prevent our success.

 References