Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993

Abstract

From 1988 to 1993, 30 cases of poliomyelitis associated with poliovirus type 2 were found in seven governorates of Egypt. Because many of the cases were geographically and temporally clustered and because the case isolates differed antigenically from the vaccine strain, it was initially assumed that the cases signaled the continued circulation of wild type 2 poliovirus. However, comparison of sequences encoding the major capsid protein, VP1 (903 nucleotides), revealed that the isolates were related (93 to 97% nucleotide sequence identity) to the Sabin type 2 oral poliovirus vaccine (OPV) strain and unrelated (<82% nucleotide sequence identity) to the wild type 2 polioviruses previously indigenous to Egypt (last known isolate: 1979) or to any contemporary wild type 2 polioviruses found elsewhere. The rate and pattern of VP1 divergence among the circulating vaccine-derived poliovirus (cVDPV) isolates suggested that all lineages were derived from a single OPV infection that occurred around 1983 and that progeny from the initiating infection circulated for approximately a decade within Egypt along several independent chains of transmission. Complete genomic sequences of an early (1988) and a late (1993) cVDPV isolate revealed that their 5' untranslated region (5' UTR) and noncapsid- 3' UTR sequences were derived from other species C enteroviruses. Circulation of type 2 cVDPVs occurred at a time of low OPV coverage in the affected communities and ceased when OPV coverage rates increased. The potential for cVDPVs to circulate in populations with low immunity to poliovirus has important implications for current and future strategies to eradicate polio worldwide.

FIG. 1.

Geographic distribution of polio cases in Egypt associated with type 2 cVDPV from 1988 to 1993. Individual cVDPV cases, represented by filled circles, are mapped by governorate (2 of the 30 cVDPV isolates were not mapped because their source governorates were not recorded). cVDPV cases occurring in different years are differentiated by increasing thickness of circle rims from 1988 to 1993. OPV-like isolates (>99% VP1 sequence identity to Sabin 2) from AFP cases with onset from 1995 to 2000 are identified by open circles. Governorate abbreviations: AL, Alexandria; AW, Aswan; AY, Asyut; BH, Behaira; BS, Beni Suef; CR, Cairo; DQ, Daqahliya; DM, Damietta; FY, Fayyum; GB, Gharbiya; GZ, Giza; IS, Ismailiya; KS, Kafr El-Sheikh; MF, Menufiya; MT, Matrouh; MY, Minya; NS, North Sinai; NV, New Valley; PS, Port Said; QL, Qalyubiya; QN, Qina; RS, Red Sea; SH, Sohag; SQ, Sharqiya; SS, South Sinai; SZ, Suez.

FIG. 2.

Unrooted neighbor-joining tree summarizing VP1 (nucleotides 2482 to 3384) sequence relationships among the Sabin 2 OPV strain, the Egyptian cVDPV isolates Qalyubiya/88-1 and Beni Suef/93, three Egyptian wild type 2 isolates (MEF-1/EGY42, 0317/EGY55, and 0297/EGY79), and nine wild type 2 poliovirus isolates from cases occurring in Africa, Asia, Europe, and South America from 1977 to 1991.

FIG. 3.

Maximum likelihood tree of VP1 sequence relationships among the Sabin 2 OPV strain (root of tree) and 30 type 2 cVDPV isolates from Egypt (1988 to 1993). Brackets enclose separate genetic groups (I to III) and their component clusters (a to k).

FIG. 4.

Estimate of the date of initiating OPV dose from the rate of accumulation of synonymous substitutions into VP1 among the 28 type 2 cVDPV isolates for which the dates of sample collection are known. Abscissa: date of sample collection for each isolate. Ordinate: K_s, the number of substitutions (Sabin 2 sequence set to zero substitutions) at synonymous sites in VP1. The evolution rate was estimated by weighted linear regression (R² = 0.670) as described in the Materials and Methods. The 95% CI for the estimated date of the initiating OPV dose, July 1979 to March 1986, is bounded by parentheses along the abscissa.

FIG. 5.

(A) Nucleotide (upper bars) and amino acid (lower bars) substitutions into the genomes of cVDPV isolates Qalyubiya/88-1 (above) and Beni Suef/93 (below). The reference sequence is that of Sabin 2. The substitution maps are aligned with a schematic of the poliovirus genome; the single open reading frame is indicated by a rectangle, flanked by the 5′ and 3′ UTRs. Asterisks indicate attenuating mutations replaced by recombination (5′ UTR) or nucleotide substitution (VP1). (B) Neighbor-joining trees summarizing sequence relationships in the 5′ UTR and in each interval encoding a major cleavage product from the poliovirus polyprotein; all trees are drawn to the same scale. Isolate sequence abbreviations: S2, Sabin 2; QL, Qalyubia/88-1; BS, Beni Suef/93.

FIG. 6.

Single-step growth curves at 39.5°C in S3 HeLa cells of MEF-1/EGY42 (wild), Qalyubiya/88-1 (cVDPV), Beni Suef/93 (cVDPV), Beni Suef/98 (OPV-like), and Sabin 2.