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We are now poised to eradicatewild polioviruses from theworld, a long-sought public

health goal. At the close of 2001, wild po-lioviruses remained endemic in only 10countries, and fewer than 1000 cases wererecorded during that year. These numbersrepresent a marked improvement over theprevious year, when almost 3000 caseswere recorded in 20 countries; in 1988, theyear that the global initiative for po-liomyelitis elimination was launched, therewere >350,000 cases worldwide (see thefigure). The report on page 356 of this is-sue by Kew and colleagues (1) has impor-tant implications for current global effortsto eliminate poliomyelitis and for main-taining a polio-free world. These authorsdocument an outbreak of paralytic polioon the island of Hispaniola (Haiti and theDominican Republic) in 2000, the first re-port of poliomyelitis in this region in al-most a decade.

Rapid progress in poliovirus eradica-tion owes its success largely to thewidespread use of the oral poliovirus vac-cine (OPV) developed by Albert Sabin.Eradication of wild poliovirus is plausiblebecause humans are the only hosts of hu-man polioviruses, and because OPV hasseveral major advantages. It is easily ad-ministered by mouth, which has facilitatedthe largest mass immunization campaignin history. OPV provides a long-lastinghigh level of mucosal immunity, thus re-ducing transmissibility of wild poliovirus-es. The live attenuated poliovirus in OPVspreads to some contacts of vaccinees, in-creasing the impact of the vaccine beyondthose actually vaccinated. Finally, theelimination of wild polioviruses frommuch of the world is a testimony to the ef-fectiveness of national and internationalpublic health programs. The progressiveelimination of wild poliovirus began in1963 in Cuba, the first country to imple-ment a national immunization day (NID).This type of campaign led ultimately tothe eradication of poliovirus from the

Americas in 1991 and thereafter from Eu-ropean and Western Pacific regions (seethe figure).

Unfortunately, there is a problematic sideto reliance on OPV. This vaccine containsthree attenuated strains of poliovirus, onefor each of the major immunotypes (types 1,2, and 3). Each attenuated strain of viruswas derived by classical methods of tissue

culture passage and clonalselection for the attenuatedphenotype. Detailed geneticanalysis has revealed that theattenuation was due to asmall number of criticalpoint mutations (2). After in-gestion, OPV replicates inthe human intestine, withthe generation of many mu-tants, some of which exhibitrevertant phenotypes, whichmay resemble the neuroviru-lence of wild polioviruses. Ahigh proportion of immu-nized subjects, perhaps 30%or more, excrete revertantstrains of OPV, now calledvaccine-derived poliovirus-es (VDPVs) (3, 4). VDPVsare highly enterotropic andspread readily to nonimmunesubjects who come in contactwith primary vaccinees.

At a population level,these characteristics haveimportant implications. Ifclose to 100% of a popula-tion is immunized, the vac-cinees are exposed to the at-tenuated vaccine virus anddevelop immunity before re-vertant strains can causeparalysis. However, if im-munization coverage is in-complete and a large pro-portion of the populationdoes not participate, then aVDPV may spread sequen-tially through several non-immunized persons, accu-mulating mutations and re-versions, which will in-crease the likelihood thatsome individuals will devel-op paralytic poliomyelitis. Inessence, a vaccine programmight inadvertently initiatean outbreak of poliomyelitis,similar to natural outbreaksin the past. The circum-stances favorable to such anoccurrence, in particular lowcoverage and poor hygiene,have been reviewed and dis-cussed extensively (5–7).

S C I E N C E ’ S C O M P A S S P E R S P E C T I V E S

P E R S P E C T I V E S : V I R O L O G Y

Poliomyelitis Eradication—

a Dangerous EndgameNeal Nathanson and Paul Fine

1961

1988

1998

2001

Worldwide elimination of wild poliovirus (1961–2001).

Shown in red are countries with indigenous wild poliovirus in

1961, 1988, 1998, and 2001. Maps produced by the CDC after

data from the World Health Organization.

N. Nathanson is in the Departments of Microbiologyand Neurology, University of Pennsylvania, Philadel-phia, PA 19104, USA. E-mail: nathansn@mail.med.upenn.edu P. Fine is at the London School of Hygieneand Tropical Medicine, London WC1E 7HT, UK. E-mail: paul.fine@lshtm.ac.uk

www.sciencemag.org SCIENCE VOL 296 12 APRIL 2002

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12 APRIL 2002 VOL 296 SCIENCE www.sciencemag.org270

The report by Kew et al. (1) provides adetailed documentation of just such anepisode on the island of Hispaniola. The au-thors provide impressive evidence that a sin-gle type 1 OPV virus underwent reversionand recombination with a wild enterovirus,and then spread to cause more than 20virus-conf irmed cases of paralytic po-liomyelitis. Because there are usually 100 to250 infections per paralytic case, it can beinferred that this virulent virus infected sev-eral thousand individuals. Most of the caseswere documented in unvaccinated or incom-pletely vaccinated children under 15 yearsof age, where only about 30% of the popula-tion had received three doses of OPV. Thus,the outbreak took place under exactly theconditions where it was postulated that OPVmight spread (5). It is noteworthy that atleast two other similar small outbreaks havebeen observed, in Egypt and the Philippines,under similar circumstances (8, 9).

What are the implications of these ob-servations for the “endgame” in polioviruseradication? Currently, in areas where wildpoliovirus has been eradicated, childrenare still being immunized, either with OPVor with inactivated poliovirus vaccine(IPV, the Salk vaccine). Immunization ismaintained to protect children against thepossible reintroduction of wild poliovirusor exposure to VDPV. Once completeglobal eradication of wild poliovirus hasbeen achieved and certified, there are sev-eral options. In regions where IPV is avail-

able, OPV could be discontinued, with theeventual discontinuation of IPV once mon-itoring provided the assurance that OPVand VDPV have disappeared from theworld. IPV is much more costly to produceand more difficult to administer than OPV(10), so this option may not be feasible ev-erywhere, at least in the near future.

In regions where IPV is not currentlyavailable, a massive final round of OPVcould be administered, followed by carefulmonitoring for acute flaccid paralysis (theclassic sign of paralytic poliomyelitis) sup-ported by laboratory testing of fecal sam-ples for evidence of circulating VDPV. Inthe event that VDPV were to be identified,it would be necessary to reintroduce rou-tine vaccination or mass campaigns withIPV or OPV. This approach carries severalliabilities because it depends on the as-sumptions that circulating VDPV will beidentified quickly, that a stockpile of vac-cine would be maintained, and that nationaland international agencies would provideeffective assistance wherever it might beneeded. Unfortunately, this strategy couldbe perceived as offering a double standardof public health prevention, because devel-oping countries would be exposed to a riskthat the industrialized nations—those thatcan afford IPV—could avoid.

The “endgame” poses another dilemmathat is not easily addressed. The ultimategoal of the eradication program is the dis-continuation of all polio immunization. In-

evitably, an increasing number of peoplewould become susceptible to these viruses.To ensure that poliovirus could not be intro-duced into a susceptible population, it wouldbe necessary to destroy or contain all stocksof these viruses. This presents a challenge inthat some fecal samples, collected for manydifferent reasons and held in freezers world-wide, may be inadvertently contaminatedwith wild or vaccine-derived polioviruses.The World Health Organization is currentlysetting up a system to identify and minimizethese risks, but the surveillance and contin-gency planning will have to extend long af-ter successful eradication.

The endgame for poliovirus eradicationoffers challenges that would be dauntingeven for a chess master, let alone a worldwhere global coordination of public healthpractice is an ideal yet to be realized.

References1. O. Kew et al., Science 296, 356 (2002).

2. P. D. Minor, J. Gen. Virol. 73, 3065 (1992).

3. G. Dunn et al., J. Med. Virol. 32, 92 (1990).

4. R. Abraham et al., J. Infect. Dis. 168, 1105 (1993).

5. P. E. M. Fine, I. A. M. Carneiro, Am. J. Epidemiol. 150,

1001 (1999).

6. D. A. Henderson, Clin. Infect. Dis. 34, 79 (2002).

7. Technical Consulting Group to the World Health Or-

ganization on the Global Eradication of Poliomyelitis,

Clin. Infect. Dis. 34, 72 (2002).

8. Centers for Disease Control and Prevention (CDC),

Morb. Mortal. Wkly. Rep. 50, 874 (2001).

9. ———, Morb. Mortal. Wkly. Rep. 50, 41 (2001).

10. WHO Collaborative Study Group on Oral and Inacti-

vated Poliovirus Vaccines, J. Infect. Dis. 175 (suppl. 1),

S215 (1997).

S C I E N C E ’ S C O M P A S S

Substances used in chemical synthesismay either be incorporated into thef inal product or pass through the

process and emerge as waste. Increasingly,the chemical industry seeks products withhigh yield and low waste, allowing themto avoid paying first for material inputsand again for waste disposal. The conceptof “atom economy” has been introducedto monitor the fate of the reactants. Anatom-economic process is one in whichthe proportion of materials that is incorpo-rated into the final product is maximized(1, 2).

For most chemical processes, however,the hypothetical zero-waste level will not

be reached in the near future. Furthermore,products that are not recycled or biode-graded turn into waste at the end of theiruseful lifetime. New efficient catalyticmethods therefore have to be developed toeliminate poorly biodegradable chemicalsin industrial sites and in the environment.

For example, chlorinated phenols per-sist for decades in the environment be-cause of their resistance to microbiologicaldegradation, leading to the accumulationof these toxic molecules (3). Polychlorinat-ed aromatic compounds are constituents ofmany pesticides and insecticides and arealso generated in the chlorine-assisteddegradation of lignin in the paper industry.Pentachlorophenol and 2,4,6-trichlorophe-nol (TCP) have been listed as priority pol-lutants by U.S. and European Environmen-tal Protection Agencies.

These “recalcitrant molecules” are keytargets for the evaluation of new catalyticoxidation systems that use metal complex-es as catalysts. On page 326 of this issue,Sen Gupta et al. report a new oxidativecleaning method for chlorinated phenols,using hydrogen peroxide and iron cata-lysts (4). The metal center of these cata-lysts is chelated by tetraamido ligandscalled TAML, a family of macrocyclesthat has been developed by Collins andco-workers over the last two decades (5).

Nearly full conversions of pen-tachlorophenol or TCP are obtained at25°C at pH 10 within a few minutes witha very low catalyst loading (0.05% withrespect to the substrate to be converted).An excess of hydrogen peroxide (100equivalents/TCP) was added by portionsto limit its catalytic decomposition by theiron catalyst (Fe-TAML). The distributionof the degradation products of TCP (seethe figure) indicates that 85% of the initialcarbon atoms of the substrate are recov-ered in noncyclic products. Only 2% ofthe initial carbon atoms are still present aschlorinated aromatics after the catalyticoxidation of TCP, and no dioxin deriva-

P E R S P E C T I V E S : C H E M I S T RY

Catalytic Degradation

of Chlorinated PhenolsBernard Meunier

The author is in the Laboratoire de Chimie de Coor-dination du CNRS, 31077 Toulouse cedex 04, France.E-mail: bmeunier@lcc-toulouse.fr