Shedding of Sabin Poliovirus Type 3 Containing the Nucleotide 472 Uracil‐to‐Cytosine Point Mutation after Administration of Oral Poliovirus Vaccine

Martinez, Claudia V.; Old, Matt O.; Kwock, Douglas; Khan, Shalla S.; García, Joaquín J.; Chan, Christina S.; Webster, Ramothea; Falkovitz-Halpern, Meira S.; Maldonado, Yvonne

doi:10.1086/421703

Cited by 25 publications

(18 citation statements)

References 40 publications

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“…These data demonstrate increased reversion of OPV type 3 in stool samples over time, consistent with previous studies (20). This finding may indicate a large amount of revertant virus in communities using OPV and, along with the data indicating prolonged shedding of OPV3, may predict an increased risk of developing VAPP, particularly if immunity to polio declines as eradication efforts move forward.…”

Section: Discussionsupporting

confidence: 90%

“…These back-mutations of OPV occur during replication within the human gut (28). A previous study in our laboratory investigating OPV3 shedding and reversion demonstrated a bimodal shedding pattern of attenuated and revertant viruses in accordance with the selective pressure favoring the reversion of OPV3 (20). Among U.S. infants who received OPV followed by IPV, we observed high OPV3 shedding rates, which peaked on day 3 to 4 after vaccination and rose again during the second week after vaccination.…”

supporting

confidence: 60%

“…After reverse transcription-PCR, revertants in samples were quantified using a restriction digest (20). The samples underwent restriction digestion with 8.6 l of the sample, 0.3 l EcoRI (Promega, Madison, WI), 0.1 l bovine serum albumin, and 1 l buffer H (Promega).…”

Section: Methodsmentioning

confidence: 99%

“…Quantity One software was used to image the gels and calculate the RP. Detailed statistical methods of the derivation of the RP are provided elsewhere (20).…”

Section: Methodsmentioning

confidence: 99%

“…A final restriction digest using EcoRI distinguished the nonrevertant strains from the revertant strains. The degree of UV fluorescence observed upon imaging of the gels was used to estimate the revertant proportion (RP), defined as the percentage of revertants in a sample (20).…”

mentioning

confidence: 99%

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Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

et al. 2007

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A uracil-to-cytosine mutation at nucleotide position 472 of oral poliovirus vaccine type 3 (OPV3) contributes to the development of vaccine-associated paralytic poliomyelitis (VAPP). To analyze OPV3 shedding patterns, we previously used the multistep method of mutant analysis by PCR and enzyme cleavage (MAPREC). This involves conventional reverse transcription-PCR to detect OPV3, followed by a restriction digest to quantify position 472 reversion. Real-time PCR detects and quantifies nucleic acid as PCR occurs and avoids postreaction processing. The goal of this study was to compare a real-time PCR method to MAPREC. Seventy-three stool samples from Mexican OPV recipients underwent the reverse transcription-PCR step of MAPREC and real-time PCR. Real-time PCR identified 23% more OPV3-positive samples than conventional reverse transcription-PCR. When reversion was compared, the revertant proportion (RP), defined as the percentage of revertants in a sample, differed by <10% in 21/25 (84%) samples. The four samples differing by >10% were obtained within 5 days of OPV administration. The real-time PCR assay identified samples with an RP of >85% with 94% sensitivity and 86% specificity compared to MAPREC. The mean difference in RP between the two methods was 3.6% (95% confidence interval, ؊0.3 to 7.5%). Real-time PCR methods reliably detect OPV3, and reversion estimates correlate more consistently with MAPREC when OPV3 reversion rates are high. Detecting VAPP-related mutations by real-time PCR is rapid and efficient and can be useful in monitoring ongoing global polio eradication efforts.Vaccination using the trivalent, live attenuated oral poliomyelitis vaccine (OPV) led to the elimination of poliomyelitis in the United States and several regions of the world (15, 26). Specifically, OPV is transmitted by the fecal-oral route and by contact with pharyngeal secretions and thereby confers immunity to unvaccinated individuals (10). However, OPV strains also undergo mutations and recombination during replication in humans (13), with the attenuating OPV sequences often being selected against in the human intestinal tract (21). The transmission of these revertant strains leads to vaccine-associated paralytic poliomyelitis (VAPP) (2).Although many industrialized countries have adopted inactivated polio vaccine (IPV) into their immunization programs due to the risk of VAPP (7), several resource-poor nations cannot afford this policy change. Currently, the global VAPP burden is estimated to be 250 to 500 cases annually (14), with most cases occurring in resource-poor settings, and the risk of paralytic polio due to OPV will continue until as long as the oral vaccine is in use.Most cases of VAPP in the United States and in Latin America were due to serotype 3 (1, 7). A point mutation at position 472 of Sabin OPV3 within the 5Ј noncoding region and its internal ribosomal entry site is known to be an attenuating sequence for this serotype, and reversion of this nucleotide has been associated with VAPP (9). These back-mutations of ...

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Section: Discussionsupporting

confidence: 90%

supporting

confidence: 60%

Section: Methodsmentioning

confidence: 99%

“…Quantity One software was used to image the gels and calculate the RP. Detailed statistical methods of the derivation of the RP are provided elsewhere (20).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

et al. 2007

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Three cases of paralytic poliomyelitis associated with type 3 vaccine poliovirus strains in Bulgaria

Korsun

Kojouharova

Vladimirova

et al. 2009

Journal of Medical Virology

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Oral poliovirus vaccine (OPV) can cause, in extremely rare cases vaccine-associated paralytic poliomyelitis in recipients, or contacts of vaccinees. Three cases of vaccine-associated paralytic poliomyelitis (two contacts and one recipient) occurred in the Bourgas region of Bulgaria in the spring of 2006. The first two cases, notified as acute flaccid paralysis, were 55 days old unvaccinated twin brothers, having been in contact with vaccinees. The third case concerned a 4-month-old infant who had received the first OPV dose 37 days prior to the onset of illness. Complete clinical, epidemiological, virological, serological and molecular investigations of the children with paralysis and their contacts were undertaken. In all the three cases type 3 polioviruses were isolated from fecal samples and characterized as Sabin-like poliovirus strains. Type 3 polioviruses isolated from the twin brothers demonstrated by sequence analysis U-to-C back mutation at nt 472 of the 5' UTR, known to correlate with neurovirulence, and mutation in the VP1 region. Type 3 poliovirus isolated from the third child demonstrated in the 3D sequenced region a recombination with Sabin type 1 poliovirus. In the latter region, three silent mutations and one, resulting in amino acid substitution, were also observed. The clinical, epidemiological and virological data and the neurological sequelae observed 60 days following the onset of paralysis, confirmed the diagnosis of vaccine-associated paralytic poliomyelitis in all the three patients.

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Poliovirus

Racaniello¹

2016

Neurotropic Viral Infections

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Shedding of Sabin Poliovirus Type 3 Containing the Nucleotide 472 Uracil‐to‐Cytosine Point Mutation after Administration of Oral Poliovirus Vaccine

Cited by 25 publications

References 40 publications

Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

Three cases of paralytic poliomyelitis associated with type 3 vaccine poliovirus strains in Bulgaria

Poliovirus

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