Vaccine-associated paralytic poliomyelitis in the Russian Federation in 1998–2014

Objectives: Different polio vaccination schemes have been used in Russia: oral polio vaccine (OPV) was used in 1998–2007 and inactivated polio vaccine (IPV) followed by OPV in 2008–2014. This article presents the characteristics of vaccine-associated paralytic poliomyelitis (VAPP) cases in Russia during this period. Methods: VAPP cases were identified through the acute flaccid paralysis surveillance system, classified by the National Expert Classification Committee. Criteria for a ‘recipient VAPP’ (rVAPP) case were poliomyelitis symptoms 6–30 days after OPV administration, isolation of the vaccine virus, and residual paralysis 60 days after disease onset. Unvaccinated cases with a similar picture 6–60 days after contact with an OPV recipient were classified as ‘contact VAPP’ (cVAPP) cases. Results: During 1998–2014, 127 VAPP cases were registered: 82 rVAPP and 45 cVAPP. During the period in which only OPV was used, rVAPP cases prevailed (73.8%); cases of rVAPP were reduced during the sequential scheme period (15%). Poliovirus type 3 (39.5%) and type 2 (23.7%) were isolated more often. Vaccine-derived poliovirus types 1, 2, and 3 were isolated from three cases of cVAPP. The incidence of VAPP cases was higher during the period of OPV use (1 case/1.59 million OPV doses) than during the sequential scheme period (1 case/4.18 million doses). Conclusion: The risk of VAPP exists if OPV remains in the vaccination schedule. Keywords: Poliomyelitis, VAPP, Poliovirus vaccine, IPV, OP

Environmental Surveillance for Poliovirus and Other Enteroviruses: Long-Term Experience in Moscow, Russian Federation, 2004–2017

Polio and enterovirus surveillance may include a number of approaches, including incidence-based observation, a sentinel physician system, environmental monitoring and acute flaccid paralysis (AFP) surveillance. The relative value of these methods is widely debated. Here we summarized the results of 14 years of environmental surveillance at four sewage treatment plants of various capacities in Moscow, Russia. A total of 5450 samples were screened, yielding 1089 (20.0%) positive samples. There were 1168 viruses isolated including types 1−3 polioviruses (43%) and 29 different types of non-polio enteroviruses (51%). Despite using the same methodology, a significant variation in detection rates was observed between the treatment plants and within the same facility over time. The number of poliovirus isolates obtained from sewage was roughly 60 times higher than from AFP surveillance over the same time frame. All except one poliovirus isolate were Sabin-like polioviruses. The one isolate was vaccine-derived poliovirus type 2 with 17.6% difference from the corresponding Sabin strain, suggesting long-term circulation outside the scope of the surveillance. For some non-polio enterovirus types (e.g., Echovirus 6) there was a good correlation between detection in sewage and incidence of clinical cases in a given year, while other types (e.g., Echovirus 30) could cause large outbreaks and be almost absent in sewage samples. Therefore, sewage monitoring can be an important part of enterovirus surveillance, but cannot substitute other approaches

Antigenic Evolution of Vaccine-Derived Polioviruses: Changes in Individual Epitopes and Relative Stability of the Overall Immunological Properties

The Sabin oral poliovirus vaccine (OPV) readily undergoes changes in antigenic sites upon replication in humans. Here, a set of antigenically altered descendants of the three OPV serotypes (76 isolates) was characterized to determine the driving forces behind these changes and their biological implications. The amino acid residues of OPV derivatives that lie within or close to the known antigenic sites exhibited a marked tendency to be replaced by residues characteristic of homotypic wild polioviruses, and these changes may occur very early in OPV evolution. The specific amino acid alterations nicely correlated with serotype-specific changes in the reactivity of certain individual antigenic sites, as revealed by the recently devised monoclonal antibody-based enzyme-linked immunosorbent assay. In comparison to the original vaccine, small changes, if any, in the neutralizing capacity of human or rabbit sera were observed in highly diverged vaccine polioviruses of three serotypes, in spite of strong alterations of certain epitopes. We propose that the common antigenic alterations in evolving OPV strains largely reflect attempts to eliminate fitness-decreasing mutations acquired either during the original selection of the vaccine or already present in the parental strains. Variability of individual epitopes does not appear to be primarily caused by, or lead to, a significant immune evasion, enhancing only slightly, if at all, the capacity of OPV derivatives to overcome immunity in human populations. This study reveals some important patterns of poliovirus evolution and has obvious implications for the rational design of live viral vaccines

Vaccine-associated paralytic poliomyelitis in a child: fast transformation from Sabin-like virus to vaccine-derived poliovirus triggered an epidemiological response in two countries of the European region

Objectives: The detection of a vaccine-derived poliovirus (VDPV) requires an epidemiological assessment and response. Using repeated stool sampling from a child who is immunocompetent and was vaccinated against poliomyelitis with acute flaccid paralysis, a case of an extremely rapid evolution of Sabin-like poliovirus (PV) type 3 was traced in the child's body. Methods: The case was independently identified in two countries—Tajikistan and Russia. Stool samples for the study were also independently collected in two countries on different days from the onset of paralysis. Virological, serological, and molecular methods; full genome Sanger; and high-throughput sequencing were performed to characterize isolates. Results: PV isolates from samples collected on days 2, 3, and 14 contained eight, seven, and seven mutations in the VP1-coding region, respectively, and were classified as Sabin-like PV type 3. The isolates from samples collected on days 15 and 18 had 11 mutations and were classified as vaccine-derived PVs, which required an epidemiological response in the two countries. Conclusion: The results indicate the need to continue acute flaccid paralysis surveillance, maintain high vaccination coverage, and develop and introduce new effective, genetically stable PV vaccines

Cases of Acute Flaccid Paralysis Associated with Coxsackievirus A2: Findings of a 20-Year Surveillance in the Russian Federation

Surveillance for acute flaccid paralysis syndrome (AFP) in children under 15 is the backbone of the Global Polio Eradication Initiative. Laboratory examination of stool samples from AFP cases allows the detection of, along with polioviruses, a variety of non-polio enteroviruses (NPEV). The etiological significance of these viruses in the occurrence of AFP cases has been definitively established only for enteroviruses A71 and D68. Enterovirus Coxsackie A2 (CVA2) is most often associated with vesicular pharyngitis and hand, foot and mouth disease. Among 7280 AFP cases registered in Russia over 20 years (2001–2020), CVA2 was isolated only from five cases. However, these included three children aged 3 to 4 years, without overt immune deficiency, immunized with 4–5 doses of poliovirus vaccine in accordance with the National Vaccination Schedule. The disease resulted in persistent residual paralysis. Clinical and laboratory data corresponded to poliomyelitis developing during poliovirus infection. These findings are compatible with CVA2 being the cause of AFP. Molecular analysis of CVA2 from these patients and a number of AFP cases in other countries did not reveal association with a specific phylogenetic group, suggesting that virus genetics is unlikely to explain the pathogenic profile. The overall results highlight the value of AFP surveillance not just for polio control but for studies of uncommon AFP agents