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Letter
Recombinant Vaccine–Derived
Poliovirus in Madagascar
Dominique Rousset,* Mala Rakoto-Andrianarivelo,* Richter Razafindratsimandresy,*
Bakolalao Randriamanalina,† Sophie Guillot,‡ Jean Balanant,‡ Philippe
Mauclère,* and Francis Delpeyroux‡
*Institut Pasteur de Madagascar, Antananarivo, Republic of Madagascar;
†Ministry of Health, Antananarivo, Republic of Madagascar; and ‡Institut
Pasteur, Paris, France
Suggested citation for this article: Rousset
D, Rakoto-Andrianarivelo M, Razafindratsimandresy R, Randriamanalina
B, Guillot S, Balanant J, et al. Recombinant vaccine-derived poliovirus
in Madagascar. Emerg Infect Dis [serial online] 2003 Jul [date cited].
Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no7/02-0692.htm
To the Editor: Between October 2001 and April 2002, five cases
of acute flaccid paralysis associated with vaccine-derived poliovirus
(VDPV) type 2 isolates were reported in the southern province of the Republic
of Madagascar. The first patient, an 11-year-old child from the urban
district of Toliara, first experienced paralysis on October 29, 2001.
Three other children, 6, 9, and 14 months of age from Ebakika village,
in a rural district of Taolagnaro (250 miles east of Toliara), showed
signs of poliomyelitis between March 21 and March 26, 2002. The last case-patient,
a 20-month-old child from Ambanihazo village (6 miles north of Ebakika),
came into contact with one of the three case-patients in Ebakika in March
2002, and symptoms developed on April 12, 2002 (1). None
of the patients had been fully vaccinated against poliomyelitis.
Nine type 2 poliovirus (PV) strains were isolated. A restriction fragment
length polymorphism (RFLP) assay, with three different genomic regions
amplified by reverse transcription–polymerase chain reaction (RT-PCR)
and four different restriction enzymes (HinfI, DpnII, RsaI,
and DdeI) were used to characterize the PV isolates at the molecular
level (2). The RFLP profiles of all of the isolates in
the two capsid protein regions were identical to that of the type 2 strain
of the oral polio vaccine (OPV) in the VP1-2A region (nucleotides 2,872
to 3,647) but slightly different in the VP3-VP1 region (nucleotides 1,915
to 2,883). The observed differences allowed us to distinguish two groups
(isolates from Toliara and isolates from Taolagnaro) and two subgroups
(isolates from March and isolates from April). The RFLP profiles of isolates
in the noncapsid region, at the 3'-terminal end of the genome (polymerase
3D and 3'noncoding regions: nucleotides 6,535 to 7,439) also confirmed
the presence of two separate groups. These last profiles were completely
different from those of the three reference vaccine strains, suggesting
recombination with other enteroviruses.
Partial genomic sequencing confirmed these observations. The entire VP1
region (903 nucleotides) of the type 2 PV strains from Toliara and Taolagnaro
differed from the type 2 OPV strain by 1% and 2.5% nucleotides, respectively.
This difference may indicate that the two strains had been multiplying
or circulating for approximately 1 and 2.5 years, respectively. Taolagnaro
strains are closely related to each other (<1% nucleotide difference)
but appear to be very different from Toliara strains (2.9% nucleotide
difference), indicating the existence of two genetic lineages. The sequencing
of the noncapsid region (440 nucleotides corresponding to nucleotide positions
6,705 to 7,144 of the Sabin 2 genome) confirms the existence of two lineages
derived from different recombination events with two nonidentified enteroviruses
of the phylogenetic cluster C. This cluster, based on sequence similarity,
includes some coxsackieviruses and all PV strains (3).
We tried to identify the donor strains for sequences in the 3' terminal
end of these recombinant strains by aligning the nonidentified sequences
with homologous enterovirus sequences available in a nucleotide sequence
database (FASTA, version 3.3 applied to GenBank) (4).
The highest percentages of nucleotide sequence identity were those with
PVs and with most other cluster C enteroviruses available in the database
(87% to 91% nucleotide identities). No wild PV strains have been isolated
in Madagascar since 1997 despite surveillance and investigation of viral
causes of acute flaccid paralysis cases (5). Thus, that
the detected VDPVs were the product of recombination between OPV strains
and two nonpolio enteroviruses is more likely than that they were the
product of OPV strains and two different undetected wild PV strains. However,
we cannot exclude the possibility that wild PVs were imported or circulating
silently for a while.
In response to the outbreak, the local health authorities conducted house-to-house
vaccination with OPV. Further field investigations were carried out to
determine the extent to which VDPV had spread and to search actively for
other cases. Data analysis is in progress.
As with the other epidemics in Egypt and Hispaniola, VDPV circulated
in a province of Madagascar with low OPV coverage (6,7).
Because a high OPV coverage rate helps prevent the circulation of both
VDPVs and wild PVs, obtaining and maintaining high rates of immunization
coverage are essential (8). Moreover, two recombinant
VDPV lineages in Madagascar indicate that recombination is frequent between
OPV and cluster C enteroviruses. Similar recombinant VDPVs have been implicated
in the epidemics in Hispaniola and in the Philippines (6,9).
Determining whether the neurovirulence and transmissibility of these VDPVs
could be the result of the recombination with nonpolio enteroviruses is
important. These VDPVs have major implications for the cessation of immunization
with OPV after certification that wild PV has been eradicated.
Acknowledgments
We thank R. Crainic for support and encouragement, O.
Kew for providing unpublished results; and E. de Gourville, O. Tomori,
D. Wood, and F. Colbere-Garapin for their interest and advice.
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