A Cluster of Paralytic Poliomyelitis Cases Due to Transmission of Slightly Diverged Sabin 2 Vaccine Poliovirus.

UNLABELLED: Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. IMPORTANCE: The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly diverged (Sabin-like) viruses on the one hand and those caused by significantly diverged VDPVs on the other. This classification is based on the number of mutations in the viral genome region encoding a viral structural protein. Until now, only sporadic poliomyelitis cases due to Sabin-like polioviruses had been described, and in distinction from the VDPV-triggered outbreaks, they did not require broad-scale epidemiological responses. Here, an unusual outbreak of poliomyelitis caused by a Sabin-like virus is reported, which had an exceptionally high disease/infection ratio. This outbreak blurred the borderline between Sabin-like polioviruses and VDPVs both in pathogenicity and in the kind of responses required, as well as underscoring important gaps in understanding the pathogenicity, epidemiology, and evolution of vaccine-derived polioviruses.

Progress toward laboratory containment of poliovirus after polio eradication.

BACKGROUND: The first steps (phase 1) toward laboratory containment of poliovirus after eradication are a national survey of biomedical facilities and a global inventory of such facilities retaining wild poliovirus (WPV) infectious and potentially infectious materials. METHODS: We reviewed published reports on national laboratory surveys and inventories of WPV materials from each of the 3 polio-free World Health Organization (WHO) regions (the European Region, completed in 2006; the Western Pacific Region, completed in 2008; and the Region of the Americas, completed in 2010), as well as reports on progress in polio-free countries of the remaining 3 regions (the African Region, the Eastern Mediterranean Region, and the WHO South-East Asia Region). RESULTS: Containment phase 1 activities are complete in 154 of 194 WHO Member States (79%), including all countries and areas of the polio-free regions and most polio-free countries in the remaining 3 regions. A reported 227 209 biomedical facilities were surveyed, with 532 facilities in 45 countries identified as retaining WPV-associated infectious or potentially infectious materials. CONCLUSIONS: Completion of containment phase 1 global activities is achievable within the time frame set by the Polio Eradication and Endgame Strategic Plan 2013-2018.

Molecular genotyping and epidemiology of measles virus transmission in the World Health Organization European Region, 2007-2009.

BACKGROUND: In 2002, the World Health Organization (WHO) adopted a goal to eliminate measles in the European Region by 2010. Measles elimination is defined as the interruption of indigenous measles virus (MV) transmission. The molecular epidemiology of MV transmission in the WHO European Region was studied through the investigation of reported cases and outbreaks to monitor the region's progress toward its measles elimination goal. METHODS: National and regional laboratories performed molecular characterization of MV detected between 2007 and 2009 in the WHO European Region. To document indigenous transmission and importations into the region, we analyzed genotyping results and epidemiological data on measles outbreaks reported by the member states. RESULTS: Since 2007, MV genotype D6 has not been reported in the WHO European Region, suggesting that its chains of transmission have been interrupted, whereas several other MV genotypes are still circulating. Although several European countries have already interrupted indigenous MV transmission, genotyping showed that 3 endemic MV transmission chains have been reestablished in other countries. CONCLUSIONS: The WHO European Region 2010 goal will not be met, as indigenous transmission of MV has not been interrupted. As the region begins to document its process of elimination verification to monitor progress toward the goal, countries will need to ensure that genotyping is performed in all measles outbreaks.

Paralytic poliomyelitis associated with Sabin monovalent and bivalent oral polio vaccines in Hungary.

Historical records of patients with vaccine-associated paralytic poliomyelitis (VAPP) in Hungary during 1961-1981 were reviewed to assess the risk of VAPP after oral polio vaccine (OPV) administration. A confirmed VAPP case was defined as a diagnosis of paralytic poliomyelitis and residual paralysis at 60 days in a patient with an epidemiologic link to the vaccine. Archived poliovirus isolates were retested using polymerase chain reaction and sequencing of the viral protein 1 capsid region. This review confirmed 46 of 47 cases previously reported as VAPP. Three cases originally linked to monovalent OPV (mOPV) 3 and one case linked to mOPV1 presented after administration of bivalent OPV 1 + 3 (bOPV). The adjusted VAPP risk per million doses administered was 0.18 for mOPV1 (2 cases/11.13 million doses), 2.96 for mOPV3 (32 cases/10.81 million doses), and 12.82 for bOPV (5 cases/390,000 doses). Absence of protection from immunization with inactivated poliovirus vaccine or exposure to OPV virus from routine immunization and recent injections could explain the higher relative risk of VAPP in Hungarian children. In polio-endemic areas in which mOPV3 and bOPV are needed to achieve eradication, the higher risk of VAPP would be offset by the high risk of paralysis due to wild poliovirus and higher per-dose efficacy of mOPV3 and bOPV compared with trivalent OPV.

Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications.

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These "weak" segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination.

Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification.

Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

Measles and rubella in the World Health Organization European region: diversity creates challenges.

Since 1984, the World Health Organization (WHO) European Region has had targets for reducing the burden of a number of communicable diseases. While some countries have already met the targets for interrupting indigenous measles transmission and for reducing the incidence of congenital rubella syndrome to <1 case per 100,000 births, most have not. The cultural and economic diversity of the region present a number of challenges that must be overcome before the regional targets are met. These include social factors, political will, economic costs associated with supplementary campaigns, and more effective communication with health professionals and the public on the benefits and risks associated with immunization. Most WHO European Region member states are expected to use combined measles-mumps-rubella vaccine within the next 5 years. Consultation within the region is occurring on a strategic plan to meet the targets by 2010.

Retrospective analysis of a local cessation of vaccination against poliomyelitis: a possible scenario for the future.

The global eradication of poliomyelitis will require substantial changes in immunization practices. One of the proposed scenarios includes cessation of vaccination with live oral poliovirus vaccine (OPV) and the creation of an OPV stockpile for emergency response in case of the reintroduction of poliovirus into circulation. We describe here a retrospective analysis of the cessation of OPV usage in a region of the Byelorussian Republic of the former Soviet Union in 1963 to 1966. During this period, a widespread circulation and evolution of independent lineages of vaccine-derived polioviruses took place in the region. Some of these lineages appeared to originate from OPV given to 40 children in the community during this period of essentially no vaccinations. The data demonstrate very high risks associated with both the local cessation of OPV vaccination and the proposed use of OPV to control a possible reemergence of poliovirus in the postvaccination period. The high transmissibility of OPV-derived viruses in nonimmune population, documented here, and the known existence of long-term OPV excretors should be also considered in assessing risks of the synchronized global cessation of OPV usage.