Non-Polio Enteroviruses Isolated by Acute Flaccid Paralysis Surveillance Laboratories in the Russian Federation in 1998-2021: Distinct Epidemiological Features of Types.

More than 100 types of non-polio enteroviruses (NPEVs) are ubiquitous in the human population and cause a variety of symptoms ranging from very mild to meningitis and acute flaccid paralysis (AFP). Much of the information regarding diverse pathogenic properties of NPEVs comes from the surveillance of poliovirus, which also yields NPEV. The analysis of 265 NPEV isolations from 10,433 AFP cases over 24 years of surveillance and more than 2500 NPEV findings in patients without severe neurological lesions suggests that types EV-A71, E13, and E25 were significantly associated with AFP. EV-A71 was also significantly more common among AFP patients who had fever at the onset and residual paralysis compared to all AFP cases. In addition, a significant disparity was noticed between types that were common in humans (CV-A2, CVA9, EV-A71, E9, and E30) or in sewage (CVA7, E3, E7, E11, E12, and E19). Therefore, there is significant evidence of non-polio viruses being implicated in severe neurological lesions, but further multicenter studies using uniform methodology are needed for a definitive conclusion.

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.

Case of Poliomyelitis Caused by Significantly Diverged Derivative of the Poliovirus Type 3 Vaccine Sabin Strain Circulating in the Orphanage.

Significantly divergent polioviruses (VDPV) derived from the oral poliovirus vaccine (OPV) from Sabin strains, like wild polioviruses, are capable of prolonged transmission and neuropathology. This is mainly shown for VDPV type 2. Here we describe a molecular-epidemiological investigation of a case of VDPV type 3 circulation leading to paralytic poliomyelitis in a child in an orphanage, where OPV has not been used. Samples of feces and blood serum from the patient and 52 contacts from the same orphanage were collected twice and investigated. The complete genome sequencing was performed for five polioviruses isolated from the patient and three contact children. The level of divergence of the genomes of the isolates corresponded to approximately 9-10 months of evolution. The presence of 61 common substitutions in all isolates indicated a common intermediate progenitor. The possibility of VDPV3 transmission from the excretor to susceptible recipients (unvaccinated against polio or vaccinated with inactivated poliovirus vaccine, IPV) with subsequent circulation in a closed children's group was demonstrated. The study of the blood sera of orphanage residents at least twice vaccinated with IPV revealed the absence of neutralizing antibodies against at least two poliovirus serotypes in almost 20% of children. Therefore, a complete rejection of OPV vaccination can lead to a critical decrease in collective immunity level. The development of new poliovirus vaccines that create mucosal immunity for the adequate replacement of OPV from Sabin strains is necessary.

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 6-30days after OPV administration, isolation of the vaccine virus, and residual paralysis 60days after disease onset. Unvaccinated cases with a similar picture 6-60days 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.

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.

Adenovirus isolation rates in acute flaccid paralysis patients.

Adenoviruses usually cause asymptomatic or mild infection, but occasionally they produce various severe syndromes including neurological disorders. Association of adenovirus infection with acute flaccid paralysis has been investigated. Shedding of adenovirus with feces was detected in 1.05% of young children (mostly infants) with acute flaccid paralysis syndrome versus 0.42% in healthy contact children (P < 0.01). However, 85% of adenoviruses in the pediatric AFP patients belonged to HAdV-C species, which does not have a known neuropathogenic potential. Also, 40% of adenoviruses were isolated from patients with consequently established diagnosis of traumatic neuritis at the discharge, which was not compatible with virus ethology of neurological lesions. Higher adenovirus prevalence in young neurological patients could be affected by an underlying immune deficiency or by congestion in children's hospitals. Indeed, among 70 patients (40 infants, 30 adults) with primary immune deficiencies, asymptomatic shedding of adenoviruses was found in 10-17%; in one adult patient a mixture of HAdV-C2 and HAdV-D15 persisted for several months. Adenoviruses also could be detected in feces of 12% and 57% of healthy young children from two orphanages, respectively. A significant fraction of samples in these groups contained adenovirus mixtures. Therefore, immune deficiencies and congested groups in children's facilities (orphanages and hospitals) could affect significantly the prevalence of adenovirus shedding. The role of adenoviruses in AFP requires further study.