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Persistence of vaccine-derived polioviruses among immunodeficient persons with vaccine-associated paralytic poliomyelitis.
To estimate long-term poliovaccine virus persistence among immunodeficient patients with vaccine-associated paralytic poliomyelitis (iVAPP), cases reported in the United States during 1975-1997 were reviewed, with subsequent follow-up and virological testing. Six (16.2%) of 37 subjects excreted poliovaccine viruses for > or =6 months. Partial genomic sequencing of their available poliovirus isolates showed considerable divergence from the prototype Sabin strain in all cases. Poliovirus persistence declined over time since the last oral poliovaccine dose: at 6 months, 19.4%; 1 year, 14.3%; 5 years, 4%; and 10 years, 0% (P<.05) of patients. Despite the high prevalence of poliovaccine virus persistence among patients with iVAPP, this group appears to be an unlikely source of poliovirus reintroduction in developed countries because of the rarity and high fatality rate of iVAPP and the possible spontaneous clearance of polioviruses. These results are important for developing "endgame" strategies for the Global Poliomyelitis Eradication Program.
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Vaccine-derived poliomyelitis in Nigeria
Over the past 10 years there have been nine outbreaks of poliomyelitis derived from the oral vaccine in nine countries. Nigeria has seen the largest outbreak; 69 children have been paralysed this year. VDPVs are rare but occur when the live virus in an oral polio vaccine mutates and reverts to neurovirulence.
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Implications of a Circulating VaccineDerived
Poliovirus in Nigeria
The attack rate and severity of disease associated with the recent cVDPV identified
in Nigeria are similar to those associated with WPV. International planning for the
management of the risk of WPV, both before and after eradication, must include
scenarios in which equally virulent and pathogenic cVDPVs could emerge.
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The World Health Organization (WHO) is contemplating discontinuing the use of an oral polio vaccine that’s been linked to ongoing outbreaks of the virus in the developing world.
Nineteen outbreaks of circulating vaccine-derived poliovirus (cVDPV) have been documented in that same period, resulting in 536 cases in some 17 countries, the majority in Africa, Rosenbauer says.
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Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria
Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5′-untranslated region [5′-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries.
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Lessons from the eradication of smallpox: an interview with D. A. Henderson
It has been more than 35 years since the last naturally occurring case of smallpox. Sufficient time has passed to allow an objective overview of what were the key factors in the success of the eradication effort and what lessons smallpox can offer to other campaigns. Professor D. A. Henderson headed the international effort to eradicate smallpox. Here, we present a summary of D. A. Henderson's perspectives on the eradication of smallpox. This text is based upon the Unither Baruch Blumberg Lecture, delivered by D. A. Henderson at the University of Oxford in November 2012 and upon conversations and correspondence with Professor Henderson.
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"Persistent human-to-human transmission of the live attenuated oral polio vaccine was only observed once the goal of global polio elimination approached"
Measles is one of the most contagious human diseases. Administration of the live attenuated measles
vaccine has substantially reduced childhood mortality and morbidity since its licensure in 1963. The live
but attenuated form of the vaccine describes a virus poorly adapted to replicating in human tissue, but
with a replication yield sufficient to elicit an immune response for long-term protection. Given the high
transmissibility of the wild-type virus and that transmission of other live vaccine viruses has been documented,
we conducted a systematic review to establish if there is any evidence of human-to-human
transmission of the live attenuated measles vaccine virus. We reviewed 773 articles for genotypic confirmation
of a vaccine virus transmitted from a recently vaccinated individual to a susceptible close contact.
No evidence of human-to-human transmission of the measles vaccine virus has been reported amongst
the thousands of clinical samples genotyped during outbreaks or endemic transmission and individual
case studies worldwide.
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Vaccine-related poliovirus shedding in trivalent polio vaccine and human immunodeficiency virus status: analysis from under five children
The mean age of the study population was 28.6 months, while the median age was 24 months. Of the children recruited, majority were in the 25–48 months (n = 12; 46.2%) age category. All the HIV-positive children (n = 10) had mild symptomatic HIV status and did shed vaccine-related polioviruses between weeks 2 and 4 respectively. No participant shed polioviruses for ≥ 6 weeks.
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The risk of type 2 oral polio vaccine use in post-cessation outbreak response
Wild type 2 poliovirus was last observed in 1999. The Sabin-strain oral polio vaccine type 2 (OPV2) was critical to eradication, but it is known to revert to a neurovirulent phenotype, causing vaccine-associated paralytic poliomyelitis. OPV2 is also transmissible and can establish circulating lineages, called circulating vaccine-derived polioviruses (cVDPVs), which can also cause paralytic outbreaks. Thus, in April 2016, OPV2 was removed from immunization activities worldwide. Interrupting transmission of cVDPV2 lineages that survive cessation will require OPV2 in outbreak response, which risks seeding new cVDPVs. This potential cascade of outbreak responses seeding VDPVs, necessitating further outbreak responses, presents a critical risk to the OPV2 cessation effort.
Under a broad range of scenarios, the probability that widespread OPV2 use in outbreak response (~2 million doses) establishes new cVDPV2 lineages in this model may exceed 50% as soon as 18 months or as late as 4 years post-cessation.
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Cessation of all Oral Polio Vaccine use after certification of polio eradication will eliminate the risk of Vaccine Derived Polio Disease.
The Global Polio Eradication Initiative plans to introduce a genetically stabilized, novel OPV type 2 for outbreak response in mid-2020 and expand use in 2021. Cessation of all OPV use after certification of polio eradication will eliminate the risk of VDPV emergence.
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