Indian Pediatrics 2000;37: 210-214
Poliovirus Infection in the Gastrointestinal Tracts of Children
Please enlighten us on following aspects regarding polio virus and its habitation in the guts of children.
1. For how long can polio virus harbour in the intestine of children in whom there is serological resistance but poor gut immunity?
2. Is there a healthy carrier state like other viral diseases in polio infection?
3. If it is so, in future is there be a possibility that Indian children and even adolescents will be restricted from entering the polio free global zones and they may be asked to undergo repeated stool culture tests in quarantine period before being allowed to mix with civil population? Or whether we will be summarily rejected by those polio free countries as it happened in the last plague epidemic?
4. For how long does the gut immunity for polio virus last after Pulse Polio Immuniza-tion program?
5. What other modified strategies can we adopt for polio eradication in our four pronged attack against polio virus, namely, routine Immunization; mass immunization; surveillance and mopping up operation.
The questions raised by Dr. Virudhagiri on the duration of poliovirus infection in the gastrointestinal tracts of children and the nature and duration of mucosal immunity induced by oral poliovaccine (OPV) are extremely important, relevant and timely at this time in history when we are striving to eradicate poliomyelitis. I must point out here that there is a lack of clear understanding of these issues even in the minds of some international leaders of global polio eradication, with whom I have had recent opportunities to discuss these and related matters. Therefore, I shall take this forum to elaborate on some basic concepts and data, in addition to answering the specific questions posed by Dr. Virudhagiri.
1. How long does poliovirus (wild or patho-genic) replicate in the gastrointestinal tracts of children who are non-immune or are antibody positive but have poor gut immunity?
In a non-immune child with poliovirus infection, the virus may be detected in the stools for several days to weeks, as long as 4 to 8 weeks. We usually examine the stools of children for poliovirus only after the detection of paralysis, which itself occurs only after an incubation period of 1 to 4 weeks, during which time the child had been excreting poliovirus. In most children with poliomyelitis, the stool will remain virus positive for at least another 2 weeks, and in some children even for yet another week or two. As virus excretion (detected by routine virus culture) stops, virus particles complexed with antibody continue to be excreted for some more time, but these are non-infectious and missed in routine virus culture(1). Special techniques to dissociate antibody from virus will be necessary to culture the virus in order to demonstrate such virus-antibody complexes(1). It is important to realize that subclinical poliovirus infections were very common among children before the widespread use of immunization(2). We have documented that at any given point of time, 4% of preschool children had such asymptomatic poliovirus infections in Vellore town(2).
In developing countries even immunized and protected children participate in the circulation of poliovirus, as first pointed out by me in a retrospective analysis of an epidemic of polio in Taiwan(3). This thesis was later proven by the prospective study of an outbreak of polio in Oman(4). Thus it has become widely recognized that in some developing/tropical countries, OPV induces insufficient mucosal immunity to prevent infection and interrupt wild poliovirus transmission, even when it has induced sufficient immunity to protect from paralysis. This dichotomy of protective immunity and mucosal immunity had been recognized and reported(5), but most experts from temperate/developed countries did not accept it until after attempts to eradicate polio forced them to adopt the overuse of OPV even in children who had been given more than adequate number of doses for their own protec-tion from polio. It is not possible to conduct an ethically acceptable study in which sero-protected children are given wild poliovirus to measure their duration of virus excretion. Obviously we cannot measure this parameter by infecting immunized children with vaccine poliovirus. We have therefore tested mucosal immunity in poliovirus susceptible monkeys under two experimental protocols(6,7). First, we infected monkeys by mouth with 100 median monkey infectious doses of wild poliovirus and screened monkey stools and throat swabs for virus excretion. Monkeys shed virus by both routes for about 20 days. After ensuring that virus shedding had ceased by repeated testing, monkeys were fed the same dose of virus and surprisingly every monkey got infected and shed the virus, by both routes for about the same duration. Once again, after virus shedding stopped we inoculated the same dose, and once again all monkeys got infected, but this time the duration of virus shedding was less than one week(6). We had not anticipated this un-expected result and the experiment had been concluded as planned earlier. Had we given one more inoculation, probably the monkeys would not have been infected or if infected, they would have shed virus very transiently. This experi-ment had conclusively proven that mucosal immunity develops only after repeated infections(6). Therefore it was not surprising that in Brazil, the average number of OPV consumed by children was about 10 per head, supporting our conclusion that mucosal immunity requires many more doses than needed for individual protection. The second experiment is not very relevant here, but for the sake of completion it is briefly presented. Monkeys previously given inactivated polio-vaccine had markedly superior mucosal immunity(7), thereby confirming that monkeys do develop mucosal immunity by which they become resistant to gut infection with wild poliovirus(7).
2. Is there a healthy carrier state in poliovirus infection?
In immunocompetent children there is no chronic carrier state, but as stated above, children can get infected and shed virus repeatedly. As more doses of vaccine are given, or presumably with a fewer number of wild virus infections, presumably the gut becomes refractory to infection. On the other hand, children with immunodeficiency have been recorded to shed virus for several months or more, a state which meets with the general understanding of a carrier state. You cannot, strictly speaking, designate this as `healthy' carrier state. The epidemiological importance of this phenomenon is not clear. Our current worry is whether in future children with Immunodeficiency virus disease may become chronic carriers and add to our difficulty in eradication. This is an important reason why we want polioviruses to be eradicated as early as possible, before more HIV infected children are born.
3. In future, will there be a possibility that children from recently poliovirus-endemic countries will be restricted from entering poliovirus free countries? Will permission to travel be rejected like in the days of the recent (1994) plague epidemic?
Such restrictions are very unlikely to be instituted, even if countries like India remain poliovirus-endemic for some more time. Already, when children and adolescents travel to some countries such as the United States, they are required to take an additional dose of OPV or IPV, as I have recently been informed. Once India is certified free of poliovirus, even such requirements might not exist.
The travel restrictions and quarantine which were applied during the plague days were because the epidemic was declared to be one of pneumonic plague. There is hardly any predict-able prevention from droplet spread of Yersinia pestis, especially by persons in the incubation period of plague. That is why quarantine was important. Such fear will not occur in the case of polio. In the very unlikely event of a few cases of polio occurring in a country in which poliovirus eradication had been certified, immediate intensive immunization of all con-tacts, real and potential, will arrest any trans-mission. Travellers might be given additional doses of vaccine, but travel restrictions are unlikely to be imposed.
4. How long will mucosal immunity last after pulse immunization?
You will notice that I have used the term mucosal immunity rather than gut immunity. That is because I suspect that poliovirus transmission is both respiratory and faeco-oral. This is contrary to the classical teaching that all poliovirus transmission is faeco-oral in India. On account of the rapidity with which polioviruses get around, and infect very young children, with the median age of polio at 12 months in the pre vaccine era and 18 months to date in the vaccine era, one has to accept that much of poliovirus transmission is respiratory, rather akin to rotavirus transmission. In contrast, the median age of measles, due to a virus undisputedly respiratory transmitted, even in the pre vaccine era was only 2.5 years. Polivirus is a more efficient transmitter, unlike other faeco-orally transmitted viruses. Therefore, naso-pharyngeal mucosal immunity and gut mucosal immunity may be important against poliovirus infection.
I suspect that the mucosal immunity due to OPV is short-lived. I believe that pulse immu-nization with 3 doses of OPV in consecutive months are necessary to obtain significant mucosal immunity for interrupting wild virus transmission(8). Two doses do not provide sufficient mucosal immunity for interrupting transmission. In Brazil, several years of 2-dose pulsing did not result in interruption of trans-mission and even more vaccine had to be distributed for eradication. I am afraid that even after 3 doses, the mucosal immunity might be short lived; hence, break in transmission must be achieved with one 3-dose pulse rather than attempting it by several cycles of 2-dose pulses.
5. What other tactics can we adopt to eradicate polio, other than routine immunization, mass immunization, mopping up immunization and surveillance?
I have changed the word strategy and replaced it with tactic. Globally we have one strategy, namely, to interrupt virus transmission by the tactical use of vaccine (oral or injected), without necessarily immunizing every child to become refractory to infection. Tactics can vary. The vaccine may be OPV or IPV or a combination. We have, rightly or wrongly chosen OPV, for the time being. Routine immunization is meant for the individual protection of children from paralytic polio, although the early leaders of Expanded Program of Immunization got the goal mixed up with interruption of transmission by sufficient immunization coverage (defined as 80%) for the so-called `herd immunity'. That was proved untenable, and that process of revised understanding took several years during which time hundreds of thousands of children became paralysed either because they belonged to the 20% not targetted for immunization, or to the 30 odd per cent who got vaccine-failure polio in spite of taking the stipulated 3 doses of OPV.
Pulse immunization with 3 doses rapidly shrinks the susceptible pool of children within the total pool of children. Such rapid shrinking results in break of transmission, rather like an epidemic which ends with no further cases because the susceptibles are exhausted or are too few and far betwen for transmission to reach them. If 3-dose pulse is done well, we should break transmission, no matter what the routine coverage has been. If transmission survived in some places, one more 3-dose pulse should interrupt it even there.
In short, 3-dose pulse immunization is what we need to interrupt transmission. The purpose of surveillance, clinical and virological, is to monitor progress and to enable certification of achievement of eradication. Mopping up and other supplementary immunization is for fulfilling abundant caution and they are not epidemiologically essential, but in a major national program of eradication we need to err on the side of over response rather than what is just sufficient. Using OPV, these are the necessary and sufficient tactics to eradicate polioviruses. Had we been knowledgeable enough to have chosen the enhanced potency IPV, we might have been able to interrupt transmission of wild virus within a shorter time, without using the pulsing tactic, and without the fear of vaccine caused paralysis. However that is only a theoretical issue now. We must eradicate polio before the end of 2000, although we had wanted to do so by the end of 1997, and be certified by the end of 2000. That too is only a theoretical issue now. It is heartening to note that the Government has taken the matter very seriously and is seeking expert opinion outside the traditional (and disappointing) circles.
T. Jacob John,
1. John TJ, Samuel BU, Christuraj S. Method to increase the sensitivity of poliovirus isolation. Lancet 1992; 340: 975.
2. John TJ, Kamath KR, Feldman RA, Christopher S. Infection and disease in a group of south Indian families. 9. Poliovirus infection among preschool children. Indian J Med Res 1970; 58: 1188-1193.
3. John TJ. Poliomyelitis in Taiwan: Lessons for developing countries. Lancet 1985; i: 872.
4. Sutter RW, Patriarca PA, Brogan S. Outbreak of paralytic poliomyelitis in Oman: Evidence for widespread transmission among fully vaccinated children. Lancet 1991; 338: 715-720.
5. John TJ. Immunization against polioviruses in developing countries. Rev Med Virol 1993; 3: 149-160.
6. Selvakumar R, John TJ. Intestinal immunity to poliovirus develops only after repeated infections in monkeys. J Med Virol 1989; 27: 112-116.
7. Selvakumar R, John TJ. Intestinal immunity induced by inactivated poliovirus vaccine. Vaccine 1987; 5: 141-144.
8. John TJ, Pandian R, Gadomski A. Control of poliomyelitis by pulse immunization in Vellore, India. Brit Med J 1983; 286: 31-32.