Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001

Abstract

In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002.

FIG. 1.

Distribution of acute flaccid paralysis cases associated with type 1 cVDPVs in the Philippines in 2001. Three acute flaccid paralysis cases, in Misamis Oriental (isolate Mindanao-01-1), in Laguna (isolate Luzon-01-1), and in Cavite (isolate Luzon-01-2), are mapped by open circles. Isolate Luzon-01-2c was from a contact of the Cavite case. Shading indicates approximate population densities.

FIG. 2.

Phylogenetic analysis of type 1 cVDPVs and the wild type 1 polioviruses based on VP1 nucleotide sequences. The unrooted radial neighbor-joining tree was drawn with the TreeView software. Type 1 cVDPVs (four from the Philippines and one from Haiti, HAI01-007) and Sabin 1 are shaded. Three type 1 wild polioviruses from the Philippines are underlined.

FIG. 3.

Phylogenetic analysis of type 1 VDPV isolates. (A) Complete genomic sequence relationships among type 1 VDPV isolates. cVDPV isolates are from the Philippines, Haiti (HAI), and Dominican Republic (DOR) (25). RUS99-056 is a type 1 VDPV from a sporadic acute flaccid paralysis case in Russia (10). Bootstrap values of >80% for each cluster are shown at the branch nodes. (B) Sequence relationships among Philippines type 1 cVDPV isolates based on the nucleotide sequences derived from Sabin 1 (5′-NTR, capsid, and 2A regions, nucleotides 1 to 3927).

FIG. 4.

Putative recombination crossover site in the 2B noncapsid region of the Philippines type 1 cVDPVs. (A) Schematic diagram of the poliovirus genome. (B) Nucleotide sequence alignment. Sequences derived from Sabin 1 are unshaded, while those derived from the unidentified species C enterovirus are shaded.

FIG. 5.

Single-step growth curves of type 1 Philippines cVDPV isolates, Mahoney, and Sabin 1 strains at 39.5°C in HeLa S3 cells.