Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

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Environmental Surveillance of Polioviruses in Armenia, Colombia before Trivalent Oral Polio Vaccine Cessation

Viruses ◽

10.3390/v11090775 ◽

2019 ◽

Vol 11 (9) ◽

pp. 775

Author(s):

María Mercedes González ◽

Magile C. Fonseca ◽

Carlos Andrés Rodríguez ◽

Alejandra María Giraldo ◽

José Joaquín Vila ◽

...

Keyword(s):

Transition Period ◽

Virus Detection ◽

Oral Polio Vaccine ◽

Supplementary Information ◽

Paralytic Poliomyelitis ◽

Environmental Surveillance ◽

Wild Poliovirus ◽

Polio Vaccine ◽

Afp Surveillance ◽

Wastewater Samples

Although acute flaccid paralysis (AFP) surveillance is the “gold standard” for detecting cases of polio, environmental surveillance can provide supplementary information in the absence of paralytic poliomyelitis cases. This study aimed to detect the introduction and/or circulation of wild poliovirus or vaccine-derived polioviruses (VDPV) in wastewater, covering a significant population of Armenia, Colombia, before trivalent oral polio vaccine (OPV) cessation. Between March and September 2015, 24 wastewater samples were collected from eight study sites in eight communes of Armenia, Colombia. Virus detection and characterization were performed using both cell culture (i.e., RD or L20B cells) and RT-PCR. Polioviruses were isolated in 11 (45.8%) of 24 wastewater samples. All isolates were identified as Sabin strains (type 1 = 9, type 3 = 2) by intratypic differentiation. Type 2 poliovirus was not detected in any of the samples. No wild poliovirus or VDPV was detected among the isolates. Non-polio enterovirus was identified in 8.3% (2/24) of the samples. This study revealed the excretion of Sabin poliovirus from OPV-immunized individuals, as well as the absence of VDPV and wild poliovirus in wastewaters of Armenia, Colombia. This confirms that environmental surveillance is an effective method, as an additional support to AFP surveillance, to monitor poliovirus during the OPV-to-IPV (inactivated polio vaccine) transition period.

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Immunogenicity of Oral Polio Vaccine and Salk Inactive Polio Vaccine Against Xinjiang Imported Type 1 Wild Poliovirus

Clinical Infectious Diseases ◽

10.1093/cid/ciz549 ◽

2019 ◽

Vol 70 (9) ◽

pp. 1980-1984 ◽

Cited By ~ 1

Author(s):

Dongmei Yan ◽

Dongyan Wang ◽

Shuangli Zhu ◽

Yong Zhang ◽

Xiaolei Li ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Oral Polio Vaccine ◽

Neutralizing Antibody ◽

Genomic Sequencing ◽

Outbreak Response ◽

Local Immunity ◽

Wild Poliovirus ◽

Polio Vaccine ◽

Antibody Titers

Abstract Background An outbreak of an imported Type 1 wild poliovirus from Pakistan occurred in the Xinjiang Uygur Autonomous Region of China in 2011, although the local immunity status of the oral polio vaccine (OPV) was relatively satisfied. Methods Neutralizing antibody titers against the Xinjiang strain and Sabin 1 strain were measured in 237 sera from 3 groups of fully OPV-vaccinated persons and 1 group of infants fully vaccinated with the inactive polio vaccine (IPV). Additionally, 17 sera collected from 1 Xinjiang poliomyelitis case and his 16 contacts were also tested. Genomic sequencing was conducted the Xinjiang strain. Results The antibody titers against the Xinjiang strain in each of 237 sera were significantly lower than those against the Sabin 1 strain. Notably, 40.0% of children in Group 1 were seronegative against the Xinjiang strain, which indicated that they might play an important role in wild poliovirus transmission, although their antibody titers against the Sabin 1 strain varied between 1:8 and 1:512. Meanwhile, serological results of the Xinjiang poliomyelitis case and his contacts also provided evidence that a proportion of OPV-vaccinated children had indeed been involved in the transmission chain of the Xinjiang outbreak. Genomic sequencing indicated that the Xinjiang strain was greatly distinguishable from the Sabin 1 strain in neutralizing antigenic sites. Conclusion The lack of neutralizing antibodies against the Xinjiang strain in persons vaccinated by OPV may be associated with the transmission of Type 1 wild poliovirus in Xinjiang. Using Salk IPV along with OPV might be considered in a wild poliovirus outbreak response, especially in the countries which continued to have persistent wild poliovirus circulation.

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Sabin Vaccine Reversion in the Field: a Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria

Journal of Virology ◽

10.1128/jvi.01532-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 317-331 ◽

Cited By ~ 31

Author(s):

Michael Famulare ◽

Stewart Chang ◽

Jane Iber ◽

Kun Zhao ◽

Johnson A. Adeniji ◽

...

Keyword(s):

Virus Type ◽

Oral Polio Vaccine ◽

Wild Type ◽

Recombination Rates ◽

Substitution Rates ◽

Wild Poliovirus ◽

Polio Vaccine ◽

Routine Surveillance ◽

Type 3

ABSTRACTTo assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and the individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 substitution rates are increased for Sabin-like isolates relative to the rate for the wild type due to increased nonsynonymous substitution rates. We also inferred substitution rates for attenuating nucleotides and confirmed that reversion can occur in days to weeks after vaccination. We combine our observations for Sabin-like virus evolution with the molecular clock for VP1 of circulating wild-type strains to infer that the mean time from the initiating vaccine dose to the earliest detection of circulating vaccine-derived poliovirus (cVDPV) is 300 days for Sabin-like virus type 1, 210 days for Sabin-like virus type 2, and 390 days for Sabin-like virus type 3. Phylogenetic relationships indicated transient local transmission of Sabin-like virus type 3 and, possibly, Sabin-like virus type 1 during periods of low wild polio incidence. Comparison of Sabin-like virus recombinants with known Nigerian vaccine-derived poliovirus recombinants shows that while recombination with non-Sabin enteroviruses is associated with cVDPV, the recombination rates are similar for Sabin isolate-Sabin isolate and Sabin isolate–non-Sabin enterovirus recombination after accounting for the time from dosing to the time of detection. Our study provides a comprehensive picture of the evolutionary dynamics of the oral polio vaccine in the field.IMPORTANCEThe global polio eradication effort has completed its 26th year. Despite success in eliminating wild poliovirus from most of the world, polio persists in populations where logistical, social, and political factors have not allowed vaccination programs of sustained high quality. One issue of critical importance is eliminating circulating vaccine-derived polioviruses (cVDPVs) that have properties indistinguishable from those of wild poliovirus and can cause paralytic disease. cVDPV emerges due to the genetic instability of the Sabin viruses used in the oral polio vaccine (OPV) in populations that have low levels of immunity to poliovirus. However, the dynamics responsible are incompletely understood because it has historically been difficult to gather and interpret data about evolution of the Sabin viruses used in OPV in regions where cVDPV has occurred. This study is the first to combine whole-genome sequencing of poliovirus isolates collected during routine surveillance with knowledge about the intrahost dynamics of poliovirus to provide quantitative insight into polio vaccine evolution in the field.

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Poliomyelitis: Do We Need to Immunize the Newborn?

PEDIATRICS ◽

10.1542/peds.50.4.661a ◽

1972 ◽

Vol 50 (4) ◽

pp. 661-661

Author(s):

Michael Katz ◽

Roy E. Brown ◽

Stanley A. Plotkin

Keyword(s):

Health Facility ◽

Newborn Infants ◽

Oral Polio Vaccine ◽

Wild Poliovirus ◽

Polio Vaccine

In their article Miller et al. propose administration of oral polio vaccine to newborn infants. This, they suggest, would obviate the difficulty of reaching these children later, when their voluntary return to a health facility cannot be assured. We agree there is merit in the idea that type 1 vaccine should be given as early as possible in areas where infection with wild poliovirus is frequent. In formulating such a program, however, one must consider factors that might interfere with its success.

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Excretion of Wild-Type and Vaccine-Derived Poliovirus in the Feces of Poliovirus Receptor-Transgenic Mice

Journal of Virology ◽

10.1128/jvi.77.11.6541-6545.2003 ◽

2003 ◽

Vol 77 (11) ◽

pp. 6541-6545 ◽

Cited By ~ 11

Author(s):

Hein J. Boot ◽

Daniella T. J. Kasteel ◽

Anne-Marie Buisman ◽

Tjeerd G. Kimman

Keyword(s):

Transgenic Mice ◽

Oral Polio Vaccine ◽

Fecal Excretion ◽

Wild Type ◽

Genetic Determinants ◽

Poliovirus Type ◽

Oral Transmission ◽

Polio Vaccine ◽

Poliovirus Receptor

ABSTRACT The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains.

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Advax-CpG Adjuvant Provides Antigen Dose-Sparing and Enhanced Immunogenicity for Inactivated Poliomyelitis Virus Vaccines

Pathogens ◽

10.3390/pathogens10050500 ◽

2021 ◽

Vol 10 (5) ◽

pp. 500

Author(s):

Yoshikazu Honda-Okubo ◽

Jeremy Baldwin ◽

Nikolai Petrovsky

Keyword(s):

Neutralizing Antibodies ◽

Serum Antibody ◽

Oral Polio Vaccine ◽

Antigen Dose ◽

Polio Vaccine ◽

Antibody Titers ◽

Dose Sparing ◽

Sparing Effect ◽

Eradicate Polio

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries. Live oral polio vaccine (OPV) played a role in the reduction in polio case numbers; however, the risk of OPV developing into circulating vaccine-derived poliovirus makes it unsuitable for eradication programs. Trivalent inactivated polio virus (TIPV) vaccines which contain formalin-inactivated antigens produced from virulent types 1, 2 and 3 reference polio strains grown in Vero monkey kidney cells have been advocated as a replacement for OPV; however, TIPVs have weak immunogenicity and multiple boosts are required before peak neutralizing titers are reached. This study examined whether the incorporation of the novel polysaccharide adjuvant, Advax-CpG, could boost the immunogenicity of two TIPV vaccines, (i) a commercially available polio vaccine (IPOL®, Sanofi Pasteur) and (ii) a new TIPV formulation developed by Statens Serum Institut (SSI). Mice were immunized intramuscularly based on recommended vaccine dosage schedules and serum antibody titers were followed for 12 months post-immunization. Advax-CpG significantly enhanced the long-term immunogenicity of both TIPV vaccines and had at least a 10-fold antigen dose-sparing effect. An exception was the poor ability of the SSI TIPV to induce serotype type 1 neutralizing antibodies. Immunization with monovalent IPVs suggested that the low type 1 response to TIPV may be due to antigen competition when the type 1 antigen was co-formulated with the type 2 and 3 antigens. This study provides valuable insights into the complexity of the formulation of multivalent polio vaccines and supports the further development of adjuvanted antigen-sparing TIPV vaccines in the fight to eradicate polio.

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Post-polio eradication: vaccination strategies and options for India

Healthcare in Low-resource Settings ◽

10.4081/hls.2014.1978 ◽

2014 ◽

Vol 2 (2) ◽

Author(s):

Jayakrishnan Thayyil ◽

Thejus Jayakrishnan

Keyword(s):

International Health ◽

Main Tool ◽

Oral Polio Vaccine ◽

Polio Eradication ◽

World Health ◽

Wild Poliovirus ◽

Polio Vaccine ◽

Vaccination Strategies ◽

Health Agencies ◽

Health Organization

In 1988, the World Health Organization (WHO) resolved to eradicate poliomyelitis globally. Since then, the initiative has reported dramatic progress in decreasing the incidence of poliomyelitis and limiting the geographical extent of transmission. 2013 is recorded as the second consecutive year not reporting wild poliovirus (WPV) from India. If the country can retain this position for one more year India will be declared as polio eradicated. What should be the future vaccination strategies? We searched and reviewed the full text of the available published literature on polio eradication via PubMed and examined Internet sources and websites of major international health agencies. The oral polio vaccine (OPV) has been the main tool in the polio eradication program. Once WPV transmission is interrupted, the poliomyelitis will be caused only by OPV. India could expect 1 vaccine-associated paralytic polio per 4.2-4.6 million doses of OPV. Considering the threat of vaccine-derived viruses to polio eradication, WHO urged to develop a strategy to safely discontinue OPV after certification. The ultimate aim is to stop OPV safely and effectively, and eventually substitute with inactivated polio vaccine (IPV). The argument against the use of IPV is its cost. From India, field based data were available on the efficacy of IPV, which was better than OPV. IPV given intradermally resulted in seroconversion rates similar to full-dose intramuscular vaccine. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.

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Wild poliovirus circulation among healthy children immunized with oral polio vaccine in Antananarivo, Madagascar

Tropical Medicine & International Health ◽

10.1046/j.1365-3156.1999.00350.x ◽

1999 ◽

Vol 4 (1) ◽

pp. 50-57 ◽

Cited By ~ 5

Author(s):

M. Rakoto Andrianarivelo ◽

L. Rabarijaona ◽

P. Boisier ◽

C. Chezzi ◽

Herve G. Zeller

Keyword(s):

Oral Polio Vaccine ◽

Healthy Children ◽

Wild Poliovirus ◽

Polio Vaccine

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Protecting investments in polio eradication: the past, present and future of surveillance for acute flaccid paralysis

Epidemiology and Infection ◽

10.1017/s0950268804002638 ◽

2004 ◽

Vol 132 (5) ◽

pp. 779-780 ◽

Cited By ~ 3

Author(s):

D. L. HEYMANN ◽

E. M. DE GOURVILLE ◽

R. B. AYLWARD

Keyword(s):

Acute Flaccid Paralysis ◽

Oral Polio Vaccine ◽

Policy Decision ◽

Polio Eradication ◽

Global Policy ◽

Wild Poliovirus ◽

The Road ◽

Polio Vaccine ◽

The Past ◽

Consultation Group

In September 2003 a WHO consultation group on vaccine-derived polioviruses (VDPV) concluded that in order to prevent future generations of paralytic polio after interruption of transmission of wild poliovirus, the use of trivalent oral polio vaccine (OPV) must be stopped [1]. Another important global policy decision along the road to polio eradication thus became possible – cessation of OPV use at some time after eradication. The question now is not whether OPV must be stopped, but rather when.

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Environmental Surveillance for Risk Assessment in the Context of a Phase 2 Clinical Trial of Type 2 Novel Oral Polio Vaccine in Panama

Viruses ◽

10.3390/v13071355 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1355

Author(s):

Magda Rojas-Bonilla ◽

Angela Coulliette-Salmond ◽

Hanen Belgasmi ◽

Kimberly Wong ◽

Leanna Sayyad ◽

...

Keyword(s):

Clinical Trial ◽

Risk Mitigation ◽

Oral Polio Vaccine ◽

Surveillance Study ◽

World Health ◽

Environmental Surveillance ◽

Polio Vaccine ◽

Eradication Strategy ◽

Two Samples

Environmental surveillance was recommended for risk mitigation in a novel oral polio vaccine-2 (nOPV2) clinical trial (M5-ABMG) to monitor excretion, potential circulation, and loss of attenuation of the two nOPV2 candidates. The nOPV2 candidates were developed to address the risk of poliovirus (PV) type 2 circulating vaccine-derived poliovirus (cVDPV) as part of the global eradication strategy. Between November 2018 and January 2020, an environmental surveillance study for the clinical trial was conducted in parallel to the M5-ABMG clinical trial at five locations in Panama. The collection sites were located upstream from local treatment plant inlets, to capture the excreta from trial participants and their community. Laboratory analyses of 49 environmental samples were conducted using the two-phase separation method. Novel OPV2 strains were not detected in sewage samples collected during the study period. However, six samples were positive for Sabin-like type 3 PV, two samples were positive for Sabin-like type 1 PV, and non-polio enteroviruses NPEVs were detected in 27 samples. One of the nOPV2 candidates has been granted Emergency Use Listing by the World Health Organization and initial use started in March 2021. This environmental surveillance study provided valuable risk mitigation information to support the Emergency Use Listing application.

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