Poliomyelitis in the United States: Title and subTitle BreakThe Final Chapter?

Epidemic poliomyelitis is a disease that both appeared and disappeared in the United States during the last century. The first recorded outbreak of paralytic disease in the United States occurred near Rutland, Vt, in 1894.¹ Within a decade, thousands of infants and young children were permanently crippled during summertime epidemics that swept through cities on the East Coast and, later, throughout the country.² The likely explanation for the dramatic emergence of epidemic polio during this era lies in the paradox of improved standards of hygiene, particularly the invention of the flush toilet, which reduced exposure to polioviruses in feces and delayed infection until the protective effect of passively acquired maternal antibodies had waned.³

These annual epidemics increasingly affected older children, adolescents, and young adults, and the total number of paralytic cases continuously increased throughout the first half of the 20th century until the introduction of inactivated poliovirus vaccine (IPV) in 1955 and live, attenuated oral poliovirus vaccine (OPV) in 1961. Oral poliovirus vaccine was used exclusively for routine childhood immunization between 1963 and 1997 because of ease of administration, induction of mucosal immunity, beneficial spread of vaccine virus to nonimmune contacts, and superior potency to the IPV vaccines then available.

Paralytic poliomyelitis has been a reportable disease since the early part of the century. Since the advent of immunization, the Centers for Disease Control and Prevention (CDC) has issued surveillance reports approximately once per decade.^{4 - 7} The report in this issue of JAMA by Alexander and colleagues⁸ represents the latest in this series. By the 1970s, the principal focus of these reports became vaccine-associated paralytic poliomyelitis (VAPP), which affected both OPV recipients, mostly young infants receiving their first OPV dose, and close contacts of OPV recipients, mostly nonimmune adolescents and young adults who were caregivers to recently immunized infants. Recipients of OPV and contacts of OPV recipients with primary B-cell immunodeficiency had more than a 3000-fold increased risk of VAPP compared with those with no known immune disorders.⁹ Over the years, the proportion of contact cases decreased as polio vaccination rates improved, and the proportion of cases observed among immunodeficient persons increased, perhaps because of increased awareness of their risk.

However, the total number of VAPP cases did not change, and once disease caused by naturally occurring (wild-type) polioviruses was controlled in the United States, physicians and public health authorities began to question whether the very small risk of VAPP outweighed the perceived advantages of OPV.¹⁰ An “enhanced-potency” IPV that was equally immunogenic to OPV was licensed in 1987.^{11 - 12} However, the will to change policy did not develop until studies showed that a sequential schedule of 2 doses of IPV followed by 2 doses of OPV would likely retain the benefits associated with OPV while reducing the risk of VAPP among first-time OPV recipients.^{13 - 15}

Even this seemingly logical strategy proved to be highly controversial, as respected and influential scientists and clinicians expressed strong views, both pro and con.^{16 - 19} After a 2-year review, the CDC Advisory Committee on Immunization Practices voted to recommend the sequential IPV-OPV schedule for routine immunization of all infants beginning January 1997.²⁰ The American Academy of Pediatrics (AAP) was not prepared to make such a bold change. The AAP rejected the preference of its expert Committee on Infectious Diseases in favor of permitting pediatricians to offer OPV, IPV, or the sequential schedule to their patients.²¹ Thus, there was little impetus for pediatricians to change a practice they had followed for many years. As documented by the National Immunization Survey,⁸ about half of all infants received OPV as the first dose in 1997 and about one third received OPV as the first dose the following year. After additional cases of VAPP occurred in children who received the OPV schedule, the AAP recommended only IPV for the first 2 doses in January 1999, and anticipated the complete switch to IPV, which was agreed on by the AAP, the American Academy of Family Physicians, and the CDC in January 2000.

The data summarized by Alexander and colleagues⁸ document that the recent polio vaccine policy changes have achieved their objectives. No VAPP cases occurred in association with OPV given in the sequential schedule, and no cases of paralytic poliomyelitis from either wild-type or OPV viruses have occurred since 1999. Because virulent polioviruses have not circulated in the United States since the 1970s, and children in the United States now receive only IPV, it is possible to claim that paralytic poliomyelitis has been eliminated and to expect that this will be the final surveillance report on domestic poliomyelitis issued by the CDC.

However, this level of comfort will exist only as long as the risk of importation of polioviruses from outside US borders continues to diminish. The major threat of importation is from the regions of the world where naturally occurring polioviruses still circulate in human populations. Central Africa is now experiencing a large poliomyelitis outbreak that originated in the northern Nigerian state of Kano, where Islamic leaders have held up immunization activities for months because of distrust of OPV and the motives of Western public health authorities.²² As of September 1, 2004, a total of 491 confirmed polio cases have been reported from Nigeria in 2004, representing 78% of all the world’s cases.²³ As a result, paralytic poliomyelitis has spread to at least 10 African countries that were previously polio free. The outbreak is a setback to the World Health Organization (WHO) Global Polio Eradication Program that had previously confined endemic polio to only 6 Asian and African countries. In response to this outbreak, a strategic, synchronized campaign planned this fall will be a massive collaborative effort aiming to immunize 74 million children younger than 5 years in 22 countries.²² While there is no guarantee of success, WHO remains optimistic that the overall goal of global eradication of polio can be achieved in 2005.

However, even when this monumental goal is accomplished, the threat of epidemic paralytic polio will remain from a second source that was unanticipated until 4 years ago, when 21 cases of paralytic poliomyelitis occurred on the island of Hispaniola.²⁴ Sequencing of RNA of the outbreak strain showed that it had evolved from type 1 OPV strain virus, and other studies confirmed that the virus developed a number of markers associated with virulent polioviruses during sustained transmission over a 2- to 3-year period. Subsequent studies have demonstrated that vaccine-derived polioviruses (VDPV) have evolved, circulated, and caused paralytic disease in other settings with low immunization coverage, including Belarus in the 1960s, Egypt in the 1980s, and, more recently, the Philippines and Madagascar.²⁵

In addition, the poliovirus stocks that lie in research and clinical laboratories and in IPV-producing facilities throughout the world represent yet another possible source for reintroduction of virulent polioviruses after eradication is achieved. The potential associated risks have been clearly demonstrated by well-documented fatal laboratory incidents involving smallpox virus in 1978²⁶ and severe acute respiratory syndrome (SARS) coronavirus this past winter.²⁷ WHO is taking measured steps to inventory existing wild-type poliovirus stocks with an ultimate goal of destruction or secure containment.²⁸ The success of this massive effort will depend largely on the cooperation and good will of government leaders and institutional laboratory directors worldwide.

The potential for VDPV to emerge anywhere OPV is used has required a complete reevaluation of the “exit strategy” for discontinuation of polio immunization after global poliomyelitis eradication is certified by WHO. There is now little argument that OPV vaccination will need to cease simultaneously in a globally coordinated manner to reduce the risk of VDPV spreading as the population of susceptible infants and children expands. The risk of catastrophic reappearance of epidemic poliomyelitis will be reduced by maintaining routine immunization levels as high as possible before discontinuation of OPV. The risk will also decrease proportionately with the number of countries that have the resources to continue routine immunization with IPV. Inactivated poliovirus vaccine costs more to produce, store, ship, and administer than OPV. However, on a dose-by-dose basis, IPV is more immunogenic than OPV in underdeveloped regions where diarrheal diseases reduce the efficacy of OPV.^{29 - 30} Mass production worldwide and combination with diphtheria-tetanus-pertussis vaccine can reduce the costs. Also, IPV may be cost-effective in all areas when the potential for VDPV is taken into consideration. Combination vaccines containing IPV are already widely used in the United States and other developed nations, and several countries that currently use OPV are considering use of similar vaccines once OPV immunization is halted. It will be a challenge to WHO and world donors to assist resource-poor nations in obtaining IPV if they wish to continue immunizing against polio after cessation of OPV use.

Another line of defense against the reemergence of poliomyelitis is the creation of a stockpile of vaccine that can be deployed to anywhere in the world. For this purpose, OPV is less costly and has distinct advantages over IPV because of the ability of vaccine virus to spread naturally from person to person, producing immunity in unimmunized contacts and to induce mucosal immunity that provides an additional barrier to spread of virulent polioviruses. Maintenance of a stockpile composed of the 3 separate monovalent OPV components would be the most rational strategy because the seroconversion rate following 1 dose of a monovalent OPV vaccine substantially exceeds the rate following 1 dose of the currently used trivalent OPV formulation,³¹ an advantage that might be critically important in the midst of an outbreak. Use of a monovalent OPV vaccine also averts the unnecessary reintroduction of 2 other poliovirus serotypes into the population. However, the added expense of packaging, labeling, storing, and obtaining regulatory approval of monovalent OPV vaccines will be a substantial barrier for the world community. The CDC is now grappling with the need for a separate US polio vaccine stockpile and with the thorny regulatory problem that OPV is no longer licensed in this country.³²

It is unlikely that a stockpile would need to be used as long as immunity levels can be maintained at the current high rates with routine IPV immunization of children.³³ Overall polio vaccine coverage in the United States is now well above the approximately 80% level commonly associated with herd immunity, and evidence suggests that vaccination rates in inner cities are improving.³⁴ However, some small risk will persist if virulent polioviruses are introduced into and allowed to spread within pockets of US society where immunization is refused for religious or philosophical reasons or where access to immunization is hindered by low socioeconomic status. It is prudent to acquire a US polio vaccine stockpile, despite the existing formidable barriers. At some currently unpredictable but comfortable period of time after the world is certified to be free of circulating virulent polioviruses, it will be possible to discontinue all poliovirus immunization.