Polio Eradication Goal Extended

Luis Fermin Tenorio, the last polio case in the Western hemisphere The goal to eradicate polio by the end of 2000 remains elusive, and the amount of time left in this month won't change that. On Sept. 27, the World Health Organization (WHO), the Centers for Disease Control and Prevention, Rotary International, UNICEF, and various private donors announced at the Polio Partners Summit held at the United Nations that they are joining forces to intensify the eradication campaign, with a new deadline of 2005. Worldwide eradication efforts may be stymied, however, by Mother Nature. Recent reports indicate that not only is wild poliovirus still around, but that vaccine strains can mutate into potentially infectious forms. "The existence of virulent strains in the environment means that individuals are excreting these strains from their guts. But as long as immunization coverage is well maintained, oral polio vaccine or inactive polio vaccine is effective to protect," says Hiromu Yoshida, a virologist at the National Institute of Infectious Diseases in Tokyo, principal investigator of one of the recent investigations. A Vaccine Success Story Polio holds a special place in the memories of those old enough to remember World War II. For parents of young children in the early 1950s, summertime brought the terror of a fever that might explode into "infantile paralysis," a fear propelled by images of Franklin D. Roosevelt's battle with the disease. Although only 1 percent of infected individuals developed severe symptoms as the virus invaded spinal cord cells, the number of cases grew large enough to inspire a massive effort to develop a vaccine, including the founding of the March of Dimes in 1938 to specifically battle polio. For those old enough to remember the Beatles, polio vaccines were part of childhood. By 1955, youngsters in many nations received injections of Jonas Salk's inactivated polio vaccine. By 1962, children were lining up at school, tongues out to receive pink-stained lumps of sugar impregnated with Albert Sabin's live, attenuated oral polio vaccine. So successful was the polio vaccine effort in halting epidemics that by the 1980s, thoughts turned to polio earning the number two position on the list of vaccine-vanquished infectious diseases, following smallpox.1 Credit: Pan American Health Organization Polio vaccination campaign in the Yucatan Peninsula of Mexico "The target date for the polio eradication initiative was the end of the year 2000. That's the date for stopping transmission around the world. We will be extremely close. But as many as 20 countries will still have some poliovirus transmission," explains Bruce Aylward, Global Polio Co-coordinator for the WHO at the Polio Partners Summit. A case in point: Just six weeks after the summit, Bangladesh prime minister Sheikh Hasina had to scrap plans for a Dec. 16 declaration that the nation was officially free of polio--on Nov. 5, an 18-month-old was hospitalized at Dhaka Shishu hospital for a twisted, numb leg. The child suffered from the acute flaccid paralysis that, combined with identification of the virus within two weeks, are the diagnostic criteria for poliomyelitis. Despite recent setbacks, progress in ridding the world of polio has been steady. When the initiative began in 1988, 1,000 children a day were paralyzed from polio; today that figure is 20 or fewer, said Aylward. And the number of countries reporting polio cases has dropped from 125 in 1988. Besides Bangladesh, they include Iran, Turkey, Iraq, India, Nepal, and several African nations, although all have dramatically stepped up efforts to vaccinate their populations. And some parts of the world indeed appear to be free of wild poliovirus, including the 51 members of WHO's European Region,2 which reported its last case of wild polio on Nov. 26, 1998, in Turkey. The European Region is on track to meet the WHO requirement for official eradication--three consecutive years with no confirmed cases. Widespread vaccination can halt the infectious cycle of wild poliovirus by removing the host. Pan American Health OrganizationJonas Salk, who developed the first polio vaccine in 1955 Evidence Against Eradication Countering public health efforts to halt polio transmission, however, is a fact of life about genetic material, even in something as simple as the single-stranded RNA poliovirus--it mutates. The Sabin vaccine's live, albeit attenuated, poliovirus undergoes replication errors, as does any nucleic acid. The problem is that the virus does so within the human gastrointestinal tract, escaping into the environment in feces, ultimately entering water sources in sewage. "The virus excreted from a human after oral polio vaccine might have mutated during replication. This is a normal phenomenon," says Yoshida. His group and colleagues at the Japan Poliomyelitis Research Institute and Toyama Institute of Health have detected mutations in poliovirus derived from the oral vaccine but found in the environment. The team sampled water from sewage and river water in Japan several months after vaccination programs and cultured polioviruses.3 They then used genetic markers and PCR to identify a telltale single base change in a specific noncoding region known to be associated with reversion from the attenuated strain to a neurovirulent strain. Of the 29 strains isolated, the investigators traced all to the oral vaccine, and 16 of these--55 percent--included more than 2 percent revertant viruses. Three of the 29 strains were virulent. Yoshida hypothesizes that the higher temperature in the human gut compared to the lower temperature used in vaccine preparation might select for revertants. "Poliovirus is a mixed population of attenuated and revertant types. The vaccine strain means that the proportion of revertants is approximately less than one percent," he explains. In vitro, higher temperatures lead to an increased proportion of revertants, which could result from accelerated rounds of mutation and selection. Might the same event take place in the human digestive tract? But the work must be interpreted carefully. It shows that the genetic composition of the viral population that constitutes the oral polio vaccine can change and not that these viruses have caused, or even can cause, disease in humans. The researchers caution that certain circumstances are necessary to set the scene for the reappearance of polio: continued use of oral polio vaccine coupled with unvaccinated individuals contacting infectious viral variants in the environment. Poliovirus exposure could theoretically arise from vaccine-derived strains in water or sewage, or from wild poliovirus brought in from any of the 20 countries where it is still endemic. Credit: Pan American Health Organization/Pasteur MerieuxThe late Albert Sabin administers his oral polio vaccine. The solution for staying one evolutionary step ahead of poliovirus is to vaccinate virtually everyone, which is precisely why WHO conducts "National Immunizations Days" when all children in an area under age 5 are immunized. This is in contrast to the age-based vaccine schedules for other diseases. Another approach, instituted in the United States in 2000, is to switch back to the killed Salk vaccine, which isn't shed live with feces. Said U.S. Secretary of Health and Human Services Donna Shalala at the September Polio Summit, "No nation is truly free from polio unless every nation is free of polio." Ironically, as naturally occurring, "wild" polio has been apparently eradicated in many parts of the world, vaccine-associated polio may be a real possibility if vaccination isn't pervasive--hence, the revamped deadline of 2005 for the global eradication initiative. "Derived Sabin vaccine strains will exist in the environment, in sewage and rivers, as long as oral polio vaccine is administered. Under conditions of organic matter and low temperature, poliovirus persists for several months," says Yoshida. An additional paper in the same issue of The Lancet that includes the environmental screening experiment supports the chilling possibility that polio could resurge, rather than vanish.4 Researchers from a consortium of Japanese agencies and universities found eight unreported cases of children with acute flaccid paralysis in Laos, indirectly indicating that the cause was wild poliovirus. In addition, the investigators discovered that vaccination rates were less than 30 percent in 21 of 142 districts in Laos, and less than 60 percent in 70 districts. The team cautions that a convergence of factors--immigration and visiting back and forth across borders with Burma, Vietnam, Thailand, and China; spotty vaccination coverage; and the virus' inherent changeability--could set the stage for a return of polio, a scourge noted as long ago as Egyptian hieroglyphics from 2000 B.C. Ricki Lewis (rickilewis@nasw.org) is a contributing editor for The Scientist. References 1. World Health Assembly. "Global eradication of poliomyelitis by the year 2000," Geneva, Switzerland: World Health Organization, 1998, resolution no. 41.28. 2. "Progress toward poliomyelitis eradication--European region, 1998-June 2000," Morbidity and Mortality Weekly Report, 49:656-60, 2000. 3. H. Yoshida et al. "Characterization of vaccine-derived polioviruses isolated from sewage and river water in Japan," The Lancet, 356:1461-3, Oct. 28, 2000. 4. C. Kuroiwa et al. "Risk of poliomyelitis importation and re-emergence in Laos," The Lancet, 356:1461-3, Oct. 28, 2000.

Polio Eradication Goal Extended

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