Circulation of a Type 2 Vaccine-Derived Poliovirus --- Egypt, 1982--1993

In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by 2000 (1). Substantial progress has been achieved toward this goal (2,3), and with the circulation of wild poliovirus eliminated in most of the world, attention has focused on examining the potential for vaccine-derived poliovirus to circulate where wild poliovirus has disappeared. During 1999, sequences of historic poliovirus isolates were examined. This report summaries the results of that study, which indicate that oral poliovirus vaccine (OPV)-derived poliovirus type 2 circulated in Egypt during the 1980s and early 1990s and caused widespread infection and paralytic disease. The findings underscore the need for countries using OPV to target communities with low vaccine coverage for intense vaccination activities to prevent circulation of both wild and vaccine-derived polioviruses.

During 1988--1993, 32 polio cases associated with vaccine-derived poliovirus type 2 were found in eight of 27 governorates in Egypt. Although initial antigenic characterization of the isolates indicated that they had nonvaccine-like properties, nucleotide sequence analysis (i.e., comparing the 903 nucleotides encoding the major capsid protein, VP1) performed during 1999 revealed that all of the isolates were related (93%--96% nucleotide sequence identity) to the Sabin type 2 OPV strain (Sabin 2). The isolates were not related (<81% nucleotide sequence identity) to the wild type 2 poliovirus that had been indigenous to Egypt (last isolated in 1979) or to any other wild type 2 polioviruses (3). The isolates also differed from type 2 vaccine-derived polioviruses normally isolated from patients with acute flaccid paralysis that typically are related closely (>99.5% nucleotide sequence identity) to Sabin 2.

Both epidemiologic and genetic data among the 32 case isolates indicate extensive circulation of type 2 vaccine-derived polioviruses in Egypt during 1988--1993. Several type 2 isolates were associated with clusters of cases within the same governorate, and sustained circulation of Sabin 2-derived poliovirus probably occurred in some communities. The isolates grouped into approximately 10 genetic lineages (corresponding to chains of transmission), and isolates from the same governorate usually were closely related. The extent of VP1 sequence divergence from Sabin 2 was similar for isolates for any given year, and divergence increased at a nearly constant rate from 1988 to 1993. However, the sequence diversity (4%--5%) of the early isolates suggested that circulation had started several years before 1988. Although the precise duration and extent of vaccine-derived poliovirus circulation in Egypt is uncertain because of gaps in surveillance before 1990, regression analysis of the VP1 evolution rate suggested that all lineages derived from one OPV infection that occurred approximately during 1982, and that progeny from that initiating infection circulated in Egypt during 1982--1993. The estimate of the time of the initiating OPV infection is based on the assumption that the rate of VP1 evolution was nearly constant throughout the period of virus circulation.

Circulation of the Sabin 2-derived poliovirus occurred when OPV coverage probably was low in the affected communities. OPV coverage rates increased steadily in the mid-1990s, and no highly divergent vaccine-derived poliovirus isolates have been found in Egypt since 1993.

Reported by: WHO Regional Reference Laboratory, Egyptian Institute for Biological Products and Vaccine Production; Ministry of Health; Expanded Programme on Immunization, Regional Office for the Eastern Mediterranean Region, Cairo, Egypt. Respiratory and Enteric Viruses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; Vaccine Preventable Disease Eradication Div, National Immunization Program, CDC.

Editorial Note:

The finding that vaccine-derived polioviruses may circulate under suitable conditions presents an additional challenge to efforts to eradicate polio worldwide (1,2,4). During 2000, circulation of type 1 vaccine-derived poliovirus in the Dominican Republic and Haiti was associated with 19 suspected polio cases (5). Nucleotide sequence relationships among Sabin 2-derived polioviruses isolated in China during the mid-1990s also were consistent with establishment of genetic lineages by person-to-person transmission (6).

Low OPV coverage following the elimination of at least one indigenous wild poliovirus serotype probably is critical for circulation of vaccine-derived polioviruses. Such conditions permit expansion of the cohort of children who are not immune to one or more poliovirus serotypes. The threshold rates of vaccine coverage needed to suppress circulation of vaccine-derived polioviruses are unknown but probably vary by poliovirus serotype and environmental factors (e.g., population density, levels of sanitation, and climate). However, when OPV coverage rates are sufficient to prevent circulation of wild polioviruses, they probably are sufficient to prevent circulation of vaccine-derived polioviruses (4).

Because the outbreak described in this report involved extensive person-to-person transmission of poliovirus, it differs from vaccine-associated paralytic polio (VAPP). Cases of VAPP are not linked epidemiologically or virologically to each other but are associated with separate recent exposures to OPV (7). However, the early events associated with the circulation of vaccine-derived polioviruses may be similar to events associated with contact cases of VAPP: an unimmunized person is exposed to vaccine-derived poliovirus excreted by a recent OPV recipient (7). Excreted vaccine-derived viruses often are more virulent than the original OPV strains (8). Low levels of population immunity may favor the selection and transmission of vaccine-derived variants with biologic properties indistinguishable from those of wild polioviruses.

The outbreak in the Dominican Republic and Haiti involved circulating poliovirus type 1; the cases in China and Egypt (and possibly infections detected by environmental surveillance in Israel [9]) involved circulating type 2 vaccine-derived viruses. The type 2 OPV strain is the most transmissible of the three poliovirus serotypes (4,7). Because circulation of wild type 2 polioviruses probably has ceased worldwide (2,3), the only type 2 polioviruses infecting humans and conferring type-specific immunity are likely to be those derived from OPV.

The potential of vaccine-derived polioviruses to establish and maintain circulation has important implications for developing an appropriate strategy for the cessation of vaccination with OPV after wild poliovirus eradication has been achieved (4). Potential vaccine-derived poliovirus circulation also underscores the importance of maintaining high rates of poliovirus vaccine coverage worldwide. Countries using OPV should target communities with low vaccine coverage for intensified vaccination activities to prevent circulation of vaccine-derived and wild polioviruses. Countries using inactivated poliovirus vaccine should take steps to ensure high coverage rates in all communities to prevent the transmission of imported polioviruses.

References

1. World Health Assembly. Global eradication of poliomyelitis by the year 2000. Geneva, Switzerland: World Health Organization, 1988 (Resolution no. 41.28).
2. CDC. Progress toward global poliomyelitis eradication, 1999. MMWR 2000;49:349--54.
3. CDC. Progress toward the global interruption of wild poliovirus type 2 transmission, 1999. MMWR 1999;48:736--8.
4. Wood DJ, Sutter RW, Dowdle WR. Stopping poliovirus vaccination after eradication: issues and challenges. Bull WHO 2000;78:347--57.
5. CDC. Outbreak of poliomyelitis---Dominican Republic and Haiti, 2000. MMWR 2000;49:1094,1103.
6. Zhang L, Li J, Hou X, Zheng D. Analysis of the characteristics of polioviruses isolated from AFP cases in China. Chin J Vacc Immun 1998;4:247--54.
7. Strebel PM, Sutter RW, Cochi SL, et al. Epidemiology of poliomyelitis in the United States one decade after the last reported case of indigenous wild virus-associated disease. Clin Infect Dis 1992;14:568--79.
8. Minor PD. The molecular biology of poliovaccines. J Gen Virol 1992;73:3065--77.
9. Shulman L, Manor J, Handsher R, et al. Molecular and antigenic characterization of a highly evolved derivative of the type 2 oral poliovaccine strain isolated from sewage in Israel. J Clin Microbiol 2000;38:3729--34.

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