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.
Hand-foot-and-mouth disease (HFMD) is the most common enteroviral infection in South-East Asia. When evaluating the role of enterovirus 71 (EVA71) as an etiological agent of infectious disease in South Vietnam, we revealed a high proportion of EVA71 among identified species A enteroviruses found in 3542 samples from HFMD cases; 125 samples from cases of enteroviral meningitis; and 130 samples from acute flaccid paralysis (AFP) cases. These represent 50%, 54.8%, and 51.5%, respectively. According to molecular analysis, 90% of EVA71 were attributed to genotype C4 and 10% were attributed to genotype B5. The predominance of EVA71 circulation among the population proves the need to strengthen surveillance (with monitoring of enterovirus circulation for facilitation of HFMD outbreak prediction) and to increase the effectiveness of preventative measures by the implementation of vaccination against EVA71-associated infections. A phase III trial of a Taiwanese vaccine (EV71vac) in Taiwan and South Vietnam showed its safety, tolerability, and efficacy in children aged 2–71 months. This B4 genotype-based vaccine, which features cross-protection against B5 and C4 genotypes, and other existing EV71 vaccines can serve as a good approach to solving the HFMD problem, which is so important for Vietnam.
Цель: характеристика заболеваемости энтеровирусной инфекцией и изучение особенностей циркуляции неполиомиелитных энтеровирусов на ряде территорий России в 2017 г. Материалы и методы: исследовано более 5000 проб фекалий от больных энтеровирусной инфекцией. Выделение и идентификацию энтеровирусов проводили вирусологическим методом и путём частичного секвенирования области генома VP1. Филогенетические деревья были построены методом Bayesian Monte Carlo Markov Chain. Результаты: течение эпидемического процесса и клинические проявления энтеровирусной инфекции на разных территориях отличались. Особенности циркуляции энтеровирусов разных типов на территориях также были разными. В Саратовской области 65% заболеваний были представлены энтеровирусным менингитом. В Мурманской области и в Республике Коми преобладали экзантемные формы энтеровирусной инфекции, составившие 95% и 60% соответственно. В Саратовской области этиологическим фактором энтеровирусного менингита оказался энтеровирус ЕСНО 18. В Мурманской области и в Республике Коми заболевания были обусловлены в основном Coxsackievirus А6. Штаммы энтеровируса ЕСНО 18 распределились по трем кластерам. Штаммы, обусловившие заболевания энтеровирусным менингитом в Саратовской области, вошли в кластер 3, они сформировались отдельно от штаммов этого типа вируса и отличались от штаммов ЕСНО18, которые циркулировали на северо-западе России. Штаммы вируса Coxsackievirus А6, идентифицированные на северо-западе России, относились к трем субгенотипам пандемического генотипа вируса Coxsackievirus А6 – 5, 6 и 8. Большинство штаммов относились к субгенотипам 6 и 8, которые в 2017 г. доминировали в структуре Coxsackieviruses А6 на северо-западе России и в Российской Федерации в целом. Заключение: эпидемические подъемы заболеваемости энтеровирусной инфекцией, представленной различными клиническими формами, были обусловлены разными типами энтеровирусов. Этиологическим агентом энтеровирусного менингита были энтеровирусы ЕСНО 18. Основным этиологическим фактором экзантемных форм заболевания были Coxsackieviruses A6 разных субгенотипов.
Aim: Analysis of the morbidity of vaccine-associated paralytic poliomyelitis and acute flaccid paralysis and the results of virological investigation of the patients on 14 territories of the Russian Federation in 1998-2017. Materials and methods: We investigated nearly 3000 stool samples from paralytic patients and contact persons. Isolation and identification of polioviruses were performed according to WHO recommendations with the help of cell lines RD and L20B. We conducted the sequencing of the genome fragments VP3-VP1, VP1-2A and full sequencing of genome region VP1 of 45 poliovirus strains. Results: From 1998 till 2017 1257 cases of acute flaccid paralysis were registered on 14 territories of Russia, 15 cases of which (1,2%) were classified as vaccine-associated paralytic poliomyelitis. From these patients 9 children were non vaccinated and 6 children received from one to four doses of oral poliomyelitis vaccine. The percentage of the detection of polioviruses from the patients and contact persons in different years was not equal and constituted from 3, 4±0,89% to 9, 5±0,79%. All in all from the patients with acute flaccid paralysis and contact persons we isolated 191 polioviruses, 60 of them belonged to type 1, 55 polioviruses were identified as types 2 and 76 as type 3. Some cases of vaccine-associated paralytic poliomyelitis are described in the article; polioviruses were isolated from all these patients. The sequencing of the genome fragments of 45 poliovirus strains showed that the majority of them had the nucleotide substitutions including neurovirulent substitutions. Conclusion:In order to prevent the risk of the appearance of vaccine-associated paralytic poliomyelitis it is necessary to maintain the high quality of surveillance of poliomyelitis and acute flaccid paralysis, to ensure the 95% coverage of children with poliomyelitis vaccine, to minimize the cases of groundless delays of vaccination according to medical recommendations and parents’ refusals to vaccinate children against poliomyelitis and to respect strictly the National calendar of vaccination.
30 May 2023 in Russian Journal of Infection and Immunity
The epidemiological and etiological aspects of poliomyelitis and acute flaccid paralysis (AFP) in Russia and Vietnam were analysed and compared. The polio-free status is maintained on 14 territories of Russia and 29 provinces of South Vietnam. The quality of epidemiological and virological surveillance for acute flaccid paralysis is in accordance with the requirements of the national and international polio surveillance systems. All AFP cases were revealed, registered, reported and investigated in both countries. The percentage of poliovirus isolation from 2,492 samples collected from patients with acute flaccid paralysis and contact persons in different years in Russia ranged from 1.3±0.89 to 9.8±0.79. In South Vietnam, 2,143 samples from patients with acute flaccid paralysis were investigated. In Russia and Vietnam, we isolated vaccine polioviruses of all three types with predominance of type 3 polioviruses (63% and 50%, respectively) in both countries. From AFP patients in Russia and Vietnam, polioviruses were isolated in 4.9% and 1.0% studied samples, respectively. Some VDPV strains were revealed on the territories of Russia and South Vietnam. Here, we describe five cases of vaccine-associated paralytic poliomyelitis registered in Russia and two cases of AFP caused by VDPV type 2 reported in Vietnam. To prevent the risk of developing vaccine-associated paralytic poliomyelitis, it is indispensable to ensure high-quality surveillance for acute flaccid paralysis, maintain 95% polio vaccine pediatric coverage and strictly comply with sanitary legislation, including the National Vaccination Schedule when vaccinating children, to improve virological surveillance of polioviruses using classical and new virological and molecular methods and to continue research on poliomyelitis, including development of new safe and effective poliovirus vaccines able to induce both humoral and mucosal immunity. The systematic control of adequate polio vaccination is indispensable in order to prevent transmission of imported wild polioviruses into polio free countries as well as circulation of vaccine-derived polioviruses worldwide.