12128: Polio issue (fwd)

[Bob Corbett <corbetre@webster.edu>]

From: Michelle Jean-Pierre <mich@haitimed.org>


I am neither an expert nor a medical professional. I am simply concerned because I have read a few months ago an editorial in the NEJM written by a specialist and published in the most respected medical journal in the world. I do understand that this is a very controversial issue.

I am forwarding the full article just for information purpose since it has basic explanations on the matter. I do not really intend to make further comments on that topic since this debate goes beyond the borders of Haiti.

Thank you,

Michelle
http://www.haitimedical.com

 -------------------------

The Final Stages of the Global Eradication of Polio
John T. J.
N Engl J Med 2000; 343:805-807, Sep 14, 2000. Editorials

The Final Stages of the Global Eradication of Polio

It is the year 2000, the target date set by the World Health Organization (WHO) for the global eradication of poliomyelitis. In 1999, there were 7090 cases of polio, and in 1848 of these cases, the virus was isolated. During the first half of this year, only 678 cases of polio and 154 wild (natural) poliovirus isolates were documented. Transmission of this virus is now confined to 30 countries in South Asia and West and Central Africa. These were the last regions to eliminate smallpox. Polio will also be eliminated in these regions, albeit a bit later than we had hoped for. The decline has been rapid, and success is within sight.

The vaccination story begins with Salk's development of the inactivated poliovirus vaccine (IPV). It was licensed in the United States in 1955, after its safety and efficacy had been established in the monumental study known as the Francis trial, which involved 1,829,916 persons and was conducted primarily in the United States but also in Canada and Finland.1 The vaccine was effective in approximately 60 to 80 percent of the study population, and its efficacy was correlated with its potency, as measured by the induction of antibody in children. Meanwhile, other investigators were trying to attenuate polioviruses in order to make a live vaccine. As Robbins explained, "The idea of attenuated vaccine as opposed to killed vaccine appealed to many investigators, because it was presumed that an active infection most nearly reproduced the natural situation and could be expected to give longer lasting immunity and greater resistance of the bowel to reinfection."1

Sabin's attenuated strains were ready in 1955, but by then "it was difficult to conduct large scale trials in the US because the Salk vaccine had been licensed and was being used widely."1 A WHO committee recommended field trials, and in 1958, Sabin donated his three strains to Chumakov in Moscow, who produced the three vaccines and gave them to 15 million persons in just one year.1 The vaccines were highly effective against poliomyelitis, and this experience was used to support an application for licensure in the United States. Dorothy Horstman visited the former Soviet Union and eastern Europe to evaluate the reliability of the data and reported favorably.1 On the basis of this experience, the vaccines were licensed in the United States in 1960.

Eventually, the three strains were mixed to make one vaccine, known as the oral poliovaccine (OPV). By the 1970s, the transmission of wild poliovirus had been interrupted in the northern European countries, which were using IPV; in Cuba, where OPV was used; and in the United States, where IPV and OPV were used sequentially. When the Expanded Programme on Immunization was established by the WHO in 1974, OPV was chosen, to the exclusion of IPV, for good and obvious reasons: it was easy to give, and the cost was low. The obvious choice was again OPV when eradication became the goal. However, there were problems with the use of OPV in tropical and developing countries. There were reports of unsuccessful vaccination and of suboptimal seroconversion with three doses of OPV in India and Africa.2,3 The antibody response to five doses of OPV in India was roughly equal to the response to two doses in the United States or Europe.4 In spite of the simplicity of administering a dose of OPV at each of five clinic visits in infancy for the other vaccines used as part of the Expanded Programme on Immunization, the WHO recommended only three doses of OPV.

In 1990, Oman adopted a five-dose regimen of vaccination for infants, since the three-dose regimen had not prevented a large outbreak of polio.5 In this issue of the Journal, Sutter et al. report the results of a study in which a supplemental dose of OPV, type 3 monotypic vaccine, or IPV was administered in order to increase the prevalence of antibody against type 3 poliovirus in infants who had received five doses of OPV.6

In an earlier study, infants in Côte d'Ivoire who had been vaccinated with three doses of OPV were given a supplemental dose of OPV or IPV.7 The IPV used in both studies, and indeed any IPV currently available, is more refined and has greater potency (antigen content) than the original Salk vaccine.8 In the seronegative infants in Côte d'Ivoire, IPV was 2 to 14 times as likely as OPV to induce seroconversion to poliovirus types 1, 2, and 3, was more likely to increase the antibody titer by a factor of 4 or more, and resulted in higher and longer-lasting antibody levels.7

In the current study, vaccination with IPV increased the seroprevalence of poliovirus type 3 from 87.8 percent at base line to 97.1 percent at 30 days (P< 0.001), whereas vaccination with OPV or type 3 vaccine caused little or no increase in the seroprevalence of type 3.6 The median titer of antibodies against poliovirus type 3 increased from 1:228 at base line to 1:1448 or higher at 30 days in the group of infants who received IPV but did not increase in the groups that received live vaccines.6 As predicted in the Francis trial, the efficacy of IPV is determined by its potency (antigenicity), whereas the efficacy of OPV is not closely correlated with its potency (viral titer).

The Oman study has implications for the global eradication of polio. Why do we need to improve on the immune responses to five doses of OPV? The eradication of polio is being attempted not with the use of a five-dose regimen but with annual national immunization days, in order to give an additional two, three, four, or even six doses to each child.9 In many countries, wild polioviruses were eliminated only after young children received an average of 10 to 15 doses of OPV. Had a five-dose regimen of immunization been used, tens of thousands of cases of paralysis due to ineffective vaccination might have been prevented. The eradication of polio would have been achieved faster with better-immunized infants.

But now the pertinent question is, once the world is free of wild-virus–induced polio, when and how can we terminate the vaccination programs? The authors of the Oman study conclude, "Once poliovirus has been eliminated in a country or region, the use of IPV may provide a benefit similar to that of national immunization days, in terms of individual protection, and thus may help maintain a high level of immunity in the population until programs of poliovirus vaccination can be terminated throughout the world."6

The continued use of OPV after the elimination of wild poliovirus will pose scientific, ethical, and practical problems. It is possible that wild virus can infect hosts and be transmitted silently, especially in a population that has been vaccinated and protected from disease. During large-scale outbreaks of polio in Taiwan and Oman, wild poliovirus was transmitted from vaccinated children, who were protected from paralysis, to unvaccinated persons.5,10 The mucosal immunity provided by routine vaccination may be insufficient to interrupt transmission if wild virus is introduced from elsewhere. I doubt that all countries will decide to continue programs of mass vaccination after poliovirus has been eliminated from their area.

The Sabin viruses themselves can cause polio, which means that there could be cases of vaccine-caused polio in the absence of wild poliovirus. If this occurred it could be ethically untenable to continue vaccination programs. Sabin viruses and their genetic revertants can cause chronic infection in immuno- deficient persons,11 who may shed virus in feces for years. One person has been shedding Sabin type 2 neurovirulent revertant virus for 16 years.11 Common sense dictates that programs of vaccination with OPV not be continued one day longer than necessary to eliminate disease caused by wild virus.

Vaccination with IPV offers advantages and challenges. The main challenge is to increase the production of the vaccine and to combine it with the diphtheria–tetanus–pertussis vaccine, in the form of one quadruple product, for global use, so that the use of a separate poliovirus vaccine and additional injections will not be necessary. With this approach, poliovirus vaccination will be synchronized with the schedule of other vaccinations in the Expanded Programme on Immunization and thus will enhance the program, which has begun to lag in many countries. Although the cost of IPV per dose is higher than that of OPV, its cost per child vaccinated may be lower, since 2 or 3 doses of IPV replace 10 to 15 doses of OPV.

IPV has been shown to provide excellent mucosal protection, with the consequent elimination of wild virus in Scandinavian countries. There has been concern that because the vaccine provides protection only against respiratory transmission, it will be ineffective in countries with poor hygiene and thus fecal–oral transmission.1 In India, however, the median age at the time of infection with poliovirus is 12 to 18 months (which is even lower than the age at the time of infection with measles). At this age, respiratory transmission is much more likely than fecal–oral transmission. Thus, even in countries with poor hygiene, respiratory transmission remains the major route. Finally, trials conducted in areas where polio is highly endemic have shown that immunization provides excellent indirect protection, which is the result of mucosal immunity.12 With the exclusive use of IPV, any isolation of poliovirus becomes a clear danger signal, irrespective of its lineage, thus simplifying the laboratory work required for virologic surveillance.

In 2000 the eradication of polio ought to be defined as the absence of any polioviruses in humans instead of the absence of wild polioviruses in humans. It is unwise and unnecessary to risk failure by continuing to use the orally administered vaccine, which is infectious and potentially transmissible and which may have reversible neurovirulence. We have IPV, a safe alternative and a superior immunogen.


T. Jacob John, M.B., B.S., Ph.D.
439 Civil Supplies Godown Lane
Kamalakshipuram, Vellore, TN, 632 002, India

References


Robbins FC. Polio — historical. In: Plotkin SA, Mortimer EA Jr, eds. Vaccines. 2nd ed. Philadelphia: W.B. Saunders, 1994:137-54.
John TJ. Problems with oral poliovaccine in India. Indian Pediatr 1972;9:252-256.[Medline]
Oduntan SO, Lucas AO, Wennen EM. The immunological response of Nigerian infants to attenuated and inactivated poliovaccines. Ann Trop Med Parasitol 1978;72:111-115.[Medline]
John TJ. Antibody response of infants to five doses of oral polio vaccine. BMJ 1976;1:812-812.
Sutter RW, Patriarca PA, Brogan S, et al. Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmission among fully vaccinated children. Lancet 1991;338:715-720.[Medline]
Sutter RW, Suleiman AJM, Malankar P, et al. Trial of a supplemental dose of four poliovirus vaccines. N Engl J Med 2000;343:767-773.[Abstract/Full Text]
Moriniere BJ, van Loon FPL, Rhodes PH, et al. Immunogenicity of a supplemental dose of oral versus inactivated poliovirus vaccine. Lancet 1993;341:1545-1550.[Medline]
van Wezel AL, van Steenis G, van der Marel P, Osterhaus ADME. Inactivated poliovirus vaccine: current production methods and new developments. Rev Infect Dis 1984;6:Suppl 2:S335-S340.[Medline]
Progress toward poliomyelitis eradication -- South-East Asia Region, 1998-1999. MMWR Morb Mortal Wkly Rep 2000;49:568-572.[Medline]
John TJ. Poliomyelitis in Taiwan: lessons for developing countries. Lancet 1985;1:872-873.
Minor P. Characteristics of poliovirus strains from long-term excretors with primary immunodeficiencies. Dev Biol Stand (in press).
John TJ. Immunisation against polioviruses in developing countries. Rev Med Virol 1993;3:149-160.