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Synopsis: The recent occurrence of an outbreak of poliovirus infection due to a mutant strain of vaccine-derived OPV-1 in the Dominican Republic and Haiti, which has left at least 6 children paralyzed, should provoke reconsideration of current OPV vaccine programs in developing countries.
Health care experts around the world have been stunned by the recent news of an outbreak of an infection with an unusual strain of mutant Sabin-derived oral poliovirus-1 (OPV-1) in the Dominican Republic and Haiti. Although reports first began surfacing in December following the recognition of the unusual mutant OPV-1 strain by the PAHO Poliovirus Laboratory in the Caribbean Epidemiology Center in October, a finding was subsequently confirmed by the Poliovirus Laboratory at the Centers for Disease Control and Prevention, although the first case probably occurred in July 2000.1 In all, 6 cases of vaccine-derived poliovirus type-1 have been identified in the Dominican Republic and 1 case in Haiti (which share the mountainous Island of Hispaniola). All of the cases occurred in individuals who were previously either unvaccinated or incompletely vaccinated. No further cases have been reported, although additional cases of acute flacid paralysis (AFP) in both countries are being investigated.
The virus is unusual because, although it is derived from OPV-1 vaccine virus, it shares only 97% genetic similarity to the parent strain, whereas most oral vaccine-derived viruses share more than 99.5% homology. Based on these results, the virus may have been replicating for up to 2 years either in an immunodeficient host or within the community. Studies demonstrate reversion of the virus with enhanced neurovirulence and transmissibility.
These cases serve as a grim reminder of the potential risks posed by inadequate OPV vaccine programs resulting in low rates of vaccination in some countries. Haiti, which has fairly low vaccine coverage (varying from 20-32% in 1993-1998), has been considered polio-free since 1990. The last known case of wild polio infection in Haiti occurred in 1989. The Dominican Republic, which has better vaccine coverage (73-82%), has been polio-free since 1985, although 43 cases of acute flacid paralysis were reported in 1997 and 1998. Two cases of AFP were reported in 1998 in Haiti.
Health care experts descended on the two countries before Christmas to initiate a mass 3-day vaccination program.
Comment by Carol A. Kemper, MD, FACP
It is well known that the administration of live attenuated virus in OPV vaccine results in the excretion of virus in stool. Although potentially advantageous to individuals in countries with high rates of vaccination, where household or environmental contact with excreted virus can provide an additional source of "booster" vaccination, this becomes a potential liability to countries with poor vaccine rates. This liability is further increased by the possible reversion of attenuated virus to a more neurovirulent form during replication in the gut. A longer period of circulation, either within a single individual or within the community, can increase the risk of further genetic mutation and reversion to wild-type virus. Circulation of vaccine virus in the community is known to occur for about 2-3 months following a mass vaccination program. This may be prolonged by continuous vaccine programs. Furthermore, excretion of virus can be prolonged in certain immunodeficient hosts; for example, 1 immunoincompetent individual has reportedly excreted vaccine-derived virus for 16 years.2
The Western Hemisphere is believed by most experts to have been free of wild-type polio virus since 1991 when the last case was reported in Peru (about 7100 cases were reported worldwide last year, mostly in Africa and Asia). New infections in the Western Hemisphere are, therefore, invariably due to transmission of vaccine-derived virus from a recent vaccinee to an inadequately vaccinated or immunodeficient host. These cases are believed to be separate vaccine-related events. There is growing evidence, however, that some of these poliovirus infections may be due to actual "outbreaks" with person-to-person transmission of a variant strain of vaccine-derived virus, as occurred in the Dominican Republic and Haiti.
Based on nucleic acid sequencing studies, a highly divergent strain of vaccine-derived OPV-2 virus may have been circulating in 1 or more people in Israel and Palestine for approximately 6 years during the late 1990s.3 The unusual mutant virus was first isolated from sewage during routine environmental screening in Israel and Palestine in 1998. One of 25 environmental OPV strains identified in sewage was found to be highly divergent from OPV-2 vaccine virus; 4 additional isolates were recovered in 1999. All 5 isolates had reverted at neurovirulence attentuation sites, and 3 were found to be highly virulent for transgenic (PVR-Tg21) mice expressing poliovirus receptor. Sequence analysis found only 90% homology with OPV-2 vaccine-derived virus.
Circulation of OPV-2 vaccine-derived virus is now known to have occurred between 1982-1993 in Egypt, resulting in 32 cases of polio in that country.4 The cases were originally believed to be separate vaccine-related events, but further analysis conducted in 1999 found that all of the viruses were related based on nucleic acid sequencing. Similar analyses suggest that a second outbreak of OPV-derived type-2 infection probably occurred in China in the 1990s.
Such outbreaks are more likely to occur in countries with low vaccine rates. Mass vaccination campaigns, which limit the period of community exposure, may be more optimal in such countries than continuous vaccine programs, although mass vaccination programs require greater effort and expense. Vaccination with IPV has been proposed as an alternative, but the cost is much greater. In addition, IPV may not provide as effective mucosal protection from oral-fecal transmission of virus. Some experts have, therefore, proposed a combined OPV/IPV program, which could enhance safety, improve overall immunogenicity, and limit costs. A large-scale Omani study of 1025 infants aged 9 months assessed the response to a single supplemental dose of 1 of 4 different poliovirus vaccines.5 All of the children had received 5 doses of OPV and were randomized to receive IPV, trivalent OPV, either manufactured in the United States or Europe, or monovalent type 3 OPV. Overall, there was a significantly greater antibody response to type 3 OPV in patients receiving the single booster dose of IPV.
The current outbreak in Haiti and the Dominican Republic probably poses no significant threat to travelers to these countries. A booster dose is generally recommended for any adult traveler to an endemic country (1 lifetime booster with IPV is probably sufficient). Unvaccinated adults should receive the whole series of 3 doses of IPV, and children (in the United States) currently receive 4 doses (at ages 2 and 4 months, 6-18 months, and 4-6 years).
The recent outbreak in the Dominican Republic and Haiti will no doubt stir debate among world health care experts regarding the optimal vaccine program for developing countries. Certainly the continued administration of OPV in areas where wild-type poliovirus has been eradicated poses significant questions, especially in countries with meager resources and poorer rates of vaccination.2 Furthermore, OPV-vaccine programs do not necessarily prevent the circulation of wild-type or variant vaccine-derived virus within a population, as virus can be transmitted from a healthy vaccinated child, who is protected, to an unvaccinated one.
Looming on the horizon, as well, is the possibility of a polio-free earth. Current vaccine programs should be reevaluated in light of these recent outbreaks. Health care experts are going to have to start addressing the challenging questions of how to provide adequate and safe vaccine programs in a world with fewer and fewer cases of wild-type polio, and when these programs may be safely discontinued altogether.
1. ProMED-mail posts, dated December 1, 2000 through January 29, 2001. www.promedmail.org.
2. John TJ. The final stages of the global eradication of polio. N Engl J Med. 2000;343:806-807.
3. Shulman LM, et al. A highly evolved derivative of the Type 2 Oral Poliovaccine strain isolated from sewage in Israel: Molecular and genetic characterization. J Clin Microbiol. 2000;38:3729-3734.
4. Circulation of a type 2 vaccine-derived poliovirus—Egypt, 1982-1993. MMWR Morb Mortal Wkly Rep. 50(3):41-42, 51.
5. Sutter RW, et al. Trial of a supplemental dose of four poliovirus vaccines. N Engl J Med. 2000;343:767-773.