Nonpolio Enterovirus Infections Research Articles

From the "One-Molecule, One-Target, One-Disease" Concept towards Looking for Multi-Target Therapeutics for Treating Non-Polio Enterovirus (NPEV) Infections.

Non-polio enteroviruses (NPEVs), namely coxsackieviruses (CV), echoviruses (E), enteroviruses (EV), and rhinoviruses (RV), are responsible for a wide variety of illnesses. Some infections can progress to life-threatening conditions in children or immunocompromised patients. To date, no treatments have been approved. Several molecules have been evaluated through clinical trials without success. To overcome these failures, the multi-target directed ligand (MTDL) strategy could be applied to tackle enterovirus infections. This work analyzes registered clinical trials involving antiviral drugs to highlight the best candidates and develops filters to apply to a selection for MTDL synthesis. We explicitly stated the methods used to answer the question: which solution can fight NPEVs effectively? We note the originality and relevance of this proposal in relation to the state of the art in the enterovirus-inhibitors field. Several combinations are possible to broaden the antiviral spectrum and potency. We discuss data related to the virus and data related to each LEAD compound identified so far. Overall, this study proposes a perspective on different strategies to overcome issues identified in clinical trials and evaluate the "MTDL" potential to improve the efficacy of drugs, broaden the antiviral targets, possibly reduce the adverse effects, drug design costs and limit the selection of drug-resistant virus variants.

A multiplex SNaPshot assay for the detection of single nucleotide polymorphism associated with clinical severity of enterovirus infections

Non-polio enterovirus infections are known to cause a variety of diseases and neurological complications. It is also known that the severity of these diseases largely differs among individuals with different genotypes and alleles. The Single Nucleotide Polymorphisms (SNPs) within specific genes have a considerable effect on the immune response to enteroviruses and on the outcome of disease, leading to variations in complications and infection susceptibility. Knowing the distribution of such SNPs can be valuable for individual case management and studying epidemiological parameters of enterovirus infections. In this feasibility study, a multiplex version of the primer extension-based technique called the SNaPshot Assay has been developed to examine SNPs in various relevant genes for predicting the clinical severity of enterovirus infections. It is already established that this technique is precise, consistent, scalable, and likely to exhibit high throughput. The multiplex SNaPshot can investigate multiple genetic susceptibility markers simultaneously, and the assay can be used to identify vulnerable populations, understand the epidemiology of infections, and manage the outbreaks of enteroviruses. Based on the literature, 15 SNPs were identified which are suspected for higher susceptibility to the worst outcomes after enterovirus infection and the assay was developed. Blood samples of 100 healthy volunteers were collected and tested for assay feasibility as well as to know the proportions of 15 selected SNPs. After the analysis, seven SNPs have been identified and suggested to be considered for future assays. Based on the pilot test results, it appears that positivity for any three out of the identified seven SNPs might indicate a higher risk, and future studies correlated with clinical studies among patients with and without severe diseases utilizing this assay will provide robust parameters to determine at-risk individuals more accurately.

Энтеровирусные неполиомиелитные инфекции у госпитализированных взрослых Краснодарского края

Objective. Characteristics of non-polio enteroviruses in outpatients in the Krasnodar. Materials and methods. The analysis of the incidence of non-polio enteroviruses in 2006–2022 was carried out in Krasnodar. The clinical course of verified non-polio enteroviruses is characterized based on the materials of a retrospective analysis of the medical stories of 157 outpatients. Results. Non-polio enteroviruses in the Krasnodar are constantly recorded in the form of sporadic morbidity with fluctuations from 0.12 to 11.26 per 100,000 population, mainly in toddlers, more often in the summer and autumn. Enterovirus meningitis prevailed in the clinical forms in the first ten years of follow-up, and in the last seven years – small forms of non-polio enteroviruses. Among adult outpatients with a moderate course of the disease predominate (98.2%), more often in the form of serous meningitis (50.9%) and exanthema of the oral mucosa and extremities (40.1%), less often acute respiratory disease (8,9%). Pathognomonic symptoms are not typical for non-polio enteroviruses. The main clinical signs of non-polio enteroviruses infection in all clinical forms are short-term febrile fever, malaise and weakness, symptoms of upper respiratory tract damage, absolute monocytosis, eosinopenia, lymphopenia, increased levels of C RP, as well as clinical and laboratory signs of serous meningitis in meningeal form and typical exanthem in "exanthem of the oral mucosa and extremities". Laboratory diagnostics should include tests to verify non-polio enteroviruses, as well as differential diagnostic studies to exclude clinically similar diseases that may involve etiotropic treatment with drugs of direct action on pathogens. The lack of approved antiviral drugs and the complexity of diagnosis lead to the inclusion of antimicrobial, broad-spectrum antiviral drugs, pathogenetic and symptomatic therapy in the treatment complex. Key words: non-polio enteroviruses, clinical characteristics, diagnosis, treatment

Non-polio enteroviruses circulation in acute flaccid paralysis cases and sewage in Senegal from 2013 to 2021

ObjectivesSeveral factors can cause acute flaccid paralysis cases including non-polio enteroviruses. In Senegal, few studies on non-polio enteroviruses (NPEV) have been performed. MethodsOur study assess the molecular epidemiology of non-polio enteroviruses in Senegal from 2013 to 2021 through the previously existing programs for surveillance of polioviruses. ResultsA total of 3815 stool samples and 281 sewage samples were collected. After virus isolation by cell culture, non-polio enteroviruses-positive isolates were confirmed by reverse transcriptase-quantitative polymerase chain reaction. Following this detection, the positive samples were subjected to molecular characterization. Our data showed that 15.22% and 52.66% were positive in cell culture for non-polio enteroviruses in acute flaccid paralysis surveillance and environmental surveillance, respectively. These non-polio enteroviruses-positive isolates were detected all year round but tend to unequal peaks of circulation, and the age group 0-5 years was more vulnerable to infection (84.4%). Genetic characterization revealed the circulation of enteroviruses species infecting humans (Enterovirus A – Enterovirus D): Enterovirus A (29.2%) and Enterovirus B (63.1%) isolates from both the acute flaccid paralysis surveillance and environmental surveillance while Enterovirus C (5.3%) and Enterovirus D (2.4%) were only isolated from the acute flaccid paralysis surveillance. However, the highly prevalent Enterovirus B species from the acute flaccid paralysis surveillance included echovirus 7 and echovirus 13, whereas coxsackievirus A6 was the predominant species from the environmental surveillance. ConclusionThis first 8-year period study of NPEV in Senegal showed that NPEV represent important viral etiologies associated with acute flaccid paralysis cases and circulating in environmental surveillance in Senegal and highlighted the need to promote effective long-term strategies for monitoring of non-polio enteroviruses infections.

Non-Polio Enterovirus Surveillance in the Ural Federal District and Western Siberia, 2022: Is There a Need for a Vaccine?

Human non-polio enteroviruses (NPEVs) are the etiological agents involved in most cases of hand-foot-and-mouth disease (HFMD), herpangina and aseptic meningitis. Information on the epidemiology profiles of NPEV in the Ural Federal District and Western Siberia is very limited, with no published data available. The aim of this study is to describe NPEV incidence in the Ural Federal District and Western Siberia among patients with different forms of non-polio enterovirus infections (NPEVIs) during 2022, stratified by age and clinical manifestations. A total of 265 samples that tested positive for NPEV using a polymerase chain reaction (PCR) were genotyped by semi-nested PCR for the VP1 gene. The results showed that 21 genotypes were identified among patients in this study. CVA6 was the most common genotype for HFMD. CVA6, along with CVA10, accounted for the majority of herpangina cases, while CVA9 was implicated in most meningitis cases. Sequence and phylogenetic analysis showed that nearly all of the CVA6 strains identified in this study displayed a close genetic relationship to strains identified in other cities in Russia and strains from China. NPEV surveillance allows for monitoring the circulation of clinically relevant genotypes, resulting in continuous data about NPEV epidemiology. This is important for improving case prevention, diagnosis and guiding clinical management.

Features of the etiological structure of non-polio enterovirus infection in children in the pre-pandemic and post-pandemic periods

BACKGROUND: Regional features of the etiological structure of nonpolio enterovirus infection (NPEVI) in children in the pre- and post-pandemic periods must be registered.
 AIM: To determine the features of the etiological structure of NPEVI in children in the pre- and post-pandemic periods in the KhantyMansiysk Autonomous Okrug.
 MATERIALS AND METHODS: Statistical observation data for 20132022 and results of molecular genetic studies of the structure of NPEVI in children in the pre- and post-pandemic periods were analyzed.
 RESULTS: The tendency of the incidence of NPEVI in the KhantyMansiysk Autonomous Okrug to increase in the pre-COVID-19 pandemic and a predominance of children aged 6 years has been established. In the study period up to 2019 (pre-pandemic), enteroviruses Coxsackie A6 in combination with E A71 were dominant, for which the calculated trends of the short-term forecast were confirmed in 2022. In the same year, these enteroviruses were the most common causes of focal diseases with exanthemic forms of NPEVI. In 2022, the circulation of eight more enteroviruses genovariants was recorded, among which Coxsackie A10 EV prevailed (20.5% of cases), which caused the majority of enterovirus vesicular pharyngitis cases. Enterovirus meningitis was registered in 5 (11.4%) children with the release of ECHO 6, ECHO 9, and Coxsackie A9, which were not noted in other clinical forms and circulated irregularly and in smaller numbers during the pre-pandemic period than in post-pandemic period (2022).
 CONCLUSIONS: The analysis of the monitoring data of the NPEVI in KhantyMansiysk Autonomous Okrug revealed a trend of a gradual increase in incidence in children, which must be considered when organizing epidemiological surveillance of NPEVI. The completeness of the registration of NPEVI cases with mandatory genotyping of the detected enterovirus strains will allow to more accurately determine the spectrum of strains endemic to this territory, assess the probability of their spread, forecast about the true level of morbidity, and conduct appropriate scientifically based antiepidemic and preventive measures among children with NPEVI in KhantyMansiysk Autonomous Okrug.

Current approaches to modeling of epidemic process of non-polio Enterovirus infections

Aim. To study mathematical models for predicting the incidence of non-polio enterovirus infections (NPEVI) in the Kemerovo Region.Materials and Methods. Here we conducted a retrospective epidemiological study of NPEVI incidence in the Kemerovo region from 2006 to 2021 (n = 2152 cases). Epidemic process was studied using autocorrelation analysis, Fourier analysis, and neural networks using STATISTICA Automated Neural Networks (SANN) tool and StatTech v. 3.0.5.Results. The incidence rates of NPEVI were 9,39 per 100,000 population (2009), 15,78 per 100,000 population (2015) and 8,41 per 100,000 population (2019), exceeding the average median value (2006- 2021) by a factor of 2.4, 4.1, and 2.2, respectively. NPEVI incidence was largely determined by enteroviral meningitis. The majority of cases (89.94%) were registered in children. Notably, standard mathematical models failed to provide an objective analysis of the incidence trend. Autocorrelation analysis found the summer-autumn seasonality (August-October) by evaluating the ratio of actual data to 12-month rolling averages. Modeling of the epidemic process of NPEVI using neural networks highly likely predicted its incidence up to 52 months.Conclusion. The epidemic process of NPEVI in Kemerovo region has been characterized by a low intensity and summer-autumn seasonality. Neural networks are suggested as a promising tool to forecast the incidence of NPEVI.

Species spectrum of nonpolio enteroviruses in KhMAO–Yugra during the prepandemic and pandemic periods

BACKGROUND: The characteristics of the regional features of the etiological structure of nonpolio enterovirus infection before and during the coronavirus disease 2019 (COVID-19) pandemic were evaluated.
 AIM: To assess the monitoring of the etiologies of enterovirus infection in the prepandemic and pandemic periods.
 MATERIALS AND METHODS: Data from the forms of statistical observation for 20132022 and the results of molecular genetic studies of nonpolio EVI were used.
 RESULTS: The dynamics of the incidence of enterovirus infection in the KhantyMansi Autonomous Okrug before the COVID-19 pandemic was characterized by high activity levels of the epidemic process, exceeding the average for the Russian Federation by 56 times. The urban population, with a predominance of children aged 6 years, mainly contributed to the total incidence of enterovirus infection. During the period with the highest incidence rates in 2017 and 2019, Coxsackie A6 viruses in combination with ECHO30, Coxsackie A9 dominated, and during the period of their decline, the proportion of enterovirus A71, Coxsackie A16 increased. During the pandemic, the calculated trends of dynamics for 2022 were confirmed for dominant viruses and enterovirus A71. In the same year, Coxsackie B2 and ECHO6 viruses were increasingly identified, which were previously circulated irregularly and in isolated cases. The prevalence of CV-A6 in the epidemic process was accompanied by clinical manifestations of infection, mainly as enterovirus vesicular stomatitis, with a high frequency of ECHO30, computer cases were recorded in most cases.
 CONCLUSION: Based on the results of monitoring the etiological structure of nonpoliomyelitis enterovirus infection in the prepandemic period, a further increase in morbidity in enterovirus infection is predicted in the KhantyMansi Autonomous Okrug. Genotyping of the detected strains makes it possible to determine the spectrum of enterovirus strains endemic to the territory and predict their prevalence, which is necessary to prevent the spread of enterovirus infection and ensure sanitary and epidemiological well-being in the region.

Characteristic of cardiac and neurological forms of non-polio enterovirus infection

Enterovirus infections (EVI) are ubiquitous and generally present with mild symptoms and have a favorable prognosis with full recovery. But sometimes it can be challenging to diagnose mixed forms of EVI which can result in fatal outcomes. An interesting case report on a patient admitted to the Grodno Regional infectious diseases clinical hospital. The patient was diagnosed with enteroviral infection. Histological slides of the brain, heart, lung and other systemic organs were prepared on autopsy and are presented in this scientific paper. Generalized EVI in mixed form can cause primary lesions of the brain (destructive edema), the heart (necrotizing cardiomyopathy), and sepsis while also affecting other organ systems. This can lead to unfavorable outcomes similar to that in our case report. Mixed form EVI (meningitis, myocarditis, and sepsis) can progress rapidly towards an adverse course, with the development of severe life-threatening complications. We strongly suggest that mandatory PCR screening for EVI should be carried out in young individuals with sepsis-like diseases and with a fever of unexplained origin at the time of presentation.

RESULTS OF MONITORING THE INCIDENCE OF NON-POLIO ENTEROVIRUS INFECTION IN THE PRE-PANDEMIC AND PANDEMIC PERIODS

The results of monitoring the incidence of non-polio enterovirus infection (EVI) in the pre-pandemic and pandemic periods in the Khanty-Mansiysk Autonomous Okrug (2006-2021) are presented. It was found that the predominant share in the total incidence of EVI was urban population with a predominance of children under 6 years of age and school age. In the period 2020-2021. The low incidence of EVI was due to ongoing anti-epidemic measures against COVID-19 and was accompanied by the spread of enterovirus serotype CVA6, which is able to effectively implement the aspiration mechanism of transmission of the infectious agent and cause respiratory and exanthemic diseases. The spread of CVA6 was influenced by the growth of migration activity of the population, due to the partial lifting of restrictions and an increase in the non-immune stratum of the population due to a decrease in the incidence of EVI in 2020. The results of the study will contribute to the adoption of measures leading to a decrease in the incidence of EVI in the Khanty-Mansiysk Autonomous Okrug, rational planning of preventive measures, by improving the information and diagnostic subsystems of epidemiological surveillance. To solve these tasks, it is necessary to further study the spectrum of enteroviruses circulating on the territory of the Khanty-Mansi Autonomous Okrug, the frequency of their occurrence in subclinical forms of EVI and as etiological agents of enterovirus meningitis, the development of molecular genetic typing techniques using mass parallel high-performance sequencing technology, the study of molecular genetic characteristics. All this will reduce the risks of EVI morbidity in the post-pandemic period and ensure the sanitary and epidemiological well-being of the population and prevent the spread of EVI in the Khanty-Mansi Autonomous Okrug.

Enteroviral (Picornaviridae: Enterovirus) (nonpolio) vaccines

Non-polio enteroviruses (NPEVs) are ubiquitous and are one of the main causative agents of viral infections in children. NPEVs most commonly infect newborns and young children, due to their lack of antibodies. In children, clinical manifestations can range from acute febrile illness to severe complications that require hospitalization and lead in some cases to disability or death. NPEV infections can have severe consequences, such as polio-like diseases, serous meningitis, meningoencephalitis, myocarditis, etc. The most promising strategy for preventing such diseases is vaccination. No less than 53 types of NPEVs have been found to circulate in Russia. However, of epidemic importance are the causative agents of exanthemic forms of the disease, aseptic meningitis and myocarditis. At the same time, the frequency of NPEV detection in the constituent entities of the Russian Federation is characterized by uneven distribution and seasonal upsurges. The review discusses the epidemic significance of different types of enteroviruses, including those relevant to the Russian Federation, as well as current technologies used to create enterovirus vaccines for the prevention of serious diseases.

EPIDEMIOLOGICAL PREDICTION OF INTESTINAL INFECTION CAUSED BY SOME NON-POLIOENTEROVIRUSES OF COXSACKIE GROUP A AMONG THE POPULATION OF AZERBAIJAN FOR 2015–2024

Background. Despite significant achievements in research and diagnostic practice, as well as in the field of Molecular and Biological Technology, the problem of non-polioenterovirus infections is still at the stage of serious research.
 Purpose. The purpose of the study epidemiological prevalense for some non-polioenteroviruses of Coxsackie group A among the population of Azerbaijan for 2015-2024.
 Materials and methods. In the study, the period of some non-polioenteroviruses belonging to Coxsackie group A – KA18, KA20 and KA21 serotypes was confirmed by polymerase chain reaction among the population in Baku during 2006-2010.
 The study was affirmed by design-descriptively; by method – clinically; by volume – by generalization; by type – scientifically; by material – retrospectively and prospectively; by term – transversely; by place – clinically.
 Statistical analysis was carried out in MS EXCELL-2019 and IBM Statistics SPSS-26 using determinant and regression methods (ARIMA).
 Results. On the basis of results of study the statistical reliability of prognostic model showing prediction of stabil appearing level of intestinal infection caused by some non-polioenteroviruses of Coxsackie group A (KA18, KA20 and KA21) among the child population of Azerbaijan for 2015-2024 have been determined.
 Practical implications. The results of investigation show the advisability of the using of ARIMA models for epidemiological prediction of intestinal infection caused by Coxsackie group A among the population in Azerbaijan.

Prevalence of non-polio enteroviruses infections among children in Northern Nigeria

Background: Human non-polio enteroviruses (NPEVs) have been associated with certain life-threatening disorders in children. However, there is paucity of NPEV infection data in most developing countries. This study determined the 3-year prevalence of non-polio enteroviruses (NPEVs) among children in some Northern States of Nigeria. Materials and Methods: Duplicate stool samples were collected from 27778 children ≤15 years. These samples were processed and analyzed for characteristic NPEVs cytopathic effects (CPE) on L20B and RD cell lines. Tests were considered positive if the duplicate samples produced distinct CPE on both cell lines. Results: Of the 27778 samples processed, 3991 (14.4%) NPEVs were isolated. Participants of the male gender (14.5%) within the age range of 0-5 years (14.7%) from Yobe state (15.3%) whose samples were received in the month of June (22.2%) and in the year 2015 (18.8%) had the highest prevalence of NPEVs. June had significant risk factors of NPEVs (p˂0.001, OR=1.95 [95%CI: 1.60-2.34]). However, there was no significant association between age, sex and location of sample collection with the prevalence of NPEV (p˃0.05) Conclusions: This study revealed a relatively high prevalence of NPEVs among the study population. This calls for the need for government implementation of consistently improved water, food and environmental hygiene.

Non-polio enterovirus infections in children with central nervous system disorders in Shanghai, 2016-2018: Serotypes and clinical characteristics.

Non-polio enrerovirus causes a wide spectrum of neurologic syndromes. The epidemiological and clinical profiles of non-polio enrerovirus-associated central nervous system infections vary by regions and over year. This study aimed to understand the prevalence, serotypes and clinical characteristics of enterovirus-associated aseptic meningitis, encephalitis and meningo-encephalitis in children in Shanghai during 2016-2018. We collected the clinical data and the cerebrospinal fluid specimens from the pediatric patients with aseptic meningitis, encephalitis and meningo-encephalitis during 2016-2018. The nested RT-PCR and sequencing were performed to identify enterovirus and serotypes. A total of 424 patients were included in this study and their non-duplicated cerebrospinal fluid specimens were collected during the acute stage of illness. Based on PCR assay, enterovirus was detected in 272 (64.15 %) patients, of whom, the ratio of male to female subjects was 1.99, and the mean age was 5.71 ± 3.55 years (range: 0.03-16 years). There were 17 serotypes identified. Echovirus 30 (24.63 %), Coxsackievirus A10 (20.96 %), Coxsackievirus A6 (18.01 %) accounted for 63.6 %, followed by Coxsackievirus B5 (7.72 %), Echovirus 6 (5.88 %), and other serotypes (22.8 %). Of the 10 (3.68 %) critically severe patients, all had refractory seizure, 8 required mechanical ventilation, 7 survivors had recurrent attacks of epilepsy and 3 abandoned treatment; Coxsackievirus A10, Echovirus 9, Coxsackievirus A2, Coxsackievirus A6 and Echovirus 6 were identified. Non-polio enterovirus is the major pathogen causing aseptic meningitis, encephalitis and meningo-encephalitis in Chinese children and can cause life-threatening encephalitis and severe sequelae.

Development of broad-spectrum enterovirus antivirals based on quinoline scaffold

Non-polio enteroviruses such as enterovirus A71 (EV-A71), EV-D68, and coxsackievirus B3 (CVB3) are significant human pathogens with disease manifestations ranging from mild flu-like symptoms to more severe encephalitis, myocarditis, acute flaccid paralysis/myelitis, and even death. There is currently no effective antivirals to prevent or treat non-polio enterovirus infection. In this study, we report our progress in developing potent and broad-spectrum antivirals against these non-polio enteroviruses. Starting from our previously developed lead compounds that had potent antiviral activity against EV-D68, we synthesized 43 analogs and profiled their broad-spectrum antiviral activity against additional EV-D68, EV-A71, and CVB3 viruses. Promising candidates were also selected for mouse microsomal stability test to prioritize lead compounds for future in vivo mouse model studies. Collectively, this multi-parameter optimization process revealed a promising lead compound 6aw that showed single-digit to submicromolar EC50 values against two EV-D68 strains (US/KY and US/MO), two EV-A71 strains (Tainan and US/AK), and one CVB3 strain, with a high selectivity index. Encouragingly, 6aw was stable in mouse microsomes with a half-life of 114.7 min. Overall, 6aw represents one of the most potent broad-spectrum antiviral against non-polio enteroviruses, rendering it a promising lead candidate for non-polio enteroviruses with translational potential.

Organization of the epidemiological surveillance on nonpolioenterovirus infection among children in Azerbaijan in modern stage

The aim of investigation is to analyses of some prerequisites for improving of organization of the epidemiological surveillance on nonpolioenterovirus infection among children in Azerbaijan in modern stage. For this purpose the statistic datas about morbidity with «intestinal infection of uncertain etiology» and «nonpolioenterovirus ifection» among children have been and lysed and presented. The results of conducted retrospective and prospective epidemiological analyses aloow to determine the main key steps for improving of the epidemiological surveillance on nonpolioenterovirus infection among children in Aherbaijan, which are the followig: the dynamic of intrayearly and manyyearly morbidity of nonpolioenterovirus infection; the serotypical spectrum and the virulency of nonpolioenteroviruses; the virological control of surface and waste waters for appearing of nonpolioenteroviruses; the regular monitoring of «healthy» viruscarrier among children contingents (organized and nonorganized).

Acute Flaccid Myelitis: Current Status and Diagnostic Challenges.

Acute flaccid myelitis (AFM) is a sudden-onset polio-like neuromuscular disability found commonly in young children. There is an increasing incidence of confirmed AFM cases in the USA and other countries in recent years, and in association with nonpolio enterovirus infection. This represents a significant challenge to clinicians and causes significant concern to the general public. Acute flaccid paralysis (AFP) is the long-known limb paralytic syndrome caused by a viral pathogen. AFM is a subset of AFP that is also characterized by a limb paralytic condition, but it has certain distinct features such as lesions in magnetic resonance imaging of the spinal cord gray matter. AFM leads to spinal cord, brainstem, or motor neuron dysfunction. The clinical phenotypes, pathology, and patient presentation of AFM closely mimic AFP. This article provides a concise overview of our current understanding of AFM and the clinical features that distinguish AFM from AFP and similar other neurological infectious and autoimmune diseases or disorders. We also discuss the diagnosis, clinical pathology, possible pathogenetic mechanisms, and currently available therapies.

Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

ABSTRACT Due to the advanced stage of polio eradication, the possible role of non-polio enteroviruses (NPEVs) associated to acute flaccid paralysis (AFP) cases has been highlighted. In this study, we described epidemiological aspects of NPEVs infections associated to AFP and explore the viral genetic diversity, information still scarce in Brazil. From 2005 to 2017, 6707 stool samples were collected in the scope of the Brazilian Poliomyelitis Surveillance Program. NPEVs were isolated in 359 samples (5.3%) and 341 (94.9%) were genotyped. About 46 different NPEV types were identified with the following detection pattern EV-B > EV-A > EV-C. The major EV-types were CVA2, CV4, EV-A71, CVB3, CVB5, E6, E7, E11, CVA13 and EV-C99, which corresponds to 51.6% of the total. Uncommon types, such as CVA12, EV-90 and CVA11, were also identified. Different E6 genogroups were observed, prevailing the GenIII, despite periods of co-circulation, and replacement of genogroups along time. CVA2 sequences were classified as genotype C and data suggested its dispersion in South-American countries. CVA13 viruses belonged to cluster B and Venezuelan viruses composed a new putative cluster. This study provides extensive information on enterovirus diversity associated with AFP, reinforcing the need of tailoring current surveillance strategies to timely monitor emergence/re-emergence of NPEVs.

Circulation of non-polio enteroviruses in 24 EU and EEA countries between 2015 and 2017: a retrospective surveillance study

Enteroviruses can cause severe infections, especially in young children. Non-polio enterovirus infections are not notifiable in most countries in the EU and European Economic Area (EEA) region, and surveillance varies substantially between countries. We collected and analysed available enterovirus data across EU and EEA countries to assess the current epidemiological situation and need for standardising surveillance. Aggregated data on any enterovirus detected between Jan 1, 2015, and Dec 31, 2017, through national enterovirus reference laboratories were requested from representatives in all 31 EU and EEA countries. Information collected included enterovirus types detected by month, patient age group, symptom, and specimen type. We also collected sequence data on viral capsid sequences for the three most clinically relevant enterovirus types, as identified from the data. Aggregated data were provided by representatives from 24 (77%) of 31 countries. 9914 (66%) of 14 999 enterovirus infections with information about age were in children younger than 5 years, and 3197 (45%) of 7139 individuals for whom symptoms were reported had neurological symptoms. Other symptoms were non-specific fever (in 1607 [23%] patients), respiratory symptoms (in 1197 [17%] patients), hand, foot, and mouth disease (in 528 [7% patients), and myocarditis (in 39 [1%] patients). 68 deaths were temporally associated with enterovirus infection. Typing for 11 559 (67%) of 17 136 specimens revealed 66 enterovirus types. Coxsackievirus A6 was the most frequently detected enterovirus type (in 1556 [13%] of 11 559 typed enteroviruses), and 292 (65%) of 448 patients with coxsackievirus A6 infection with available clinical data presented with hand, foot, and mouth disease. Echovirus 30 was the second most frequently detected enterovirus type, representing 1412 (12%) of 11 559 typed enteroviruses, and 384 (82%) of 467 individuals with echovirus 30 infection with available clinical data had neurological symptoms. Sequences available from 18 countries showed circulation of newly emerging strains of enterovirus A71 and enterovirus D68. To our knowledge, this study is the largest investigation of enterovirus circulation in EU and EEA countries and confirms the availability of non-polio enterovirus data in the region. Our study highlights the wide circulation of non-polio enteroviruses in Europe, mostly affecting young children and leading to neurological symptoms. Collecting data on morbidity and mortality related to enterovirus infections, as well as harmonising case definition for surveillance, should be encouraged. None.

Identification and characterization of nonpolio enterovirus associated with nonpolio-acute flaccid paralysis in polio endemic state of Uttar Pradesh, Northern India.

Despite polio eradication, nonpolio enterovirus (NPEV) detection amid polio surveillance, which is considered to have implications in paralysis, requires attention. The attributes of NPEV infections in nonpolio-AFP (NPAFP) cases from Uttar Pradesh (UP), India, remain undetermined and are thus investigated. A total of 1839 stool samples collected from patients with acute flaccid paralysis (AFP) from UP, India, between January 2010 and October 2011 were analyzed as per the WHO algorithm. A total of 359 NPAFP cases yielded NPEVs, which were subjected to microneutralization assay, partial VP1 gene-based molecular serotyping and phylogenetic analysis. Demographic and clinical-epidemiological features were also ascertained. Echoviruses (29%) and Coxsackievirus (CV)-B (17%) were the most common viruses identified by the microneutralization assay. The molecular genotyping characterized the NPEVs into 34 different serotypes, corresponding to Enterovirus (EV)-A (1.6%), EV-B (94%) and EV-C (5.3%) species. The rarely described EV serotypes, such as EV-C95, CV-A20, EV-C105, EV-B75, EV-B101, and EV-B107, were also identified. NPEV-associated AFP was more prevalent in younger male children, peaked in the monsoon months and was predominantly found in the central part of the state. The NPEV strains isolated in the study exhibited genetic diversity from those isolated in other countries. These form part of a different cluster or subcluster existing in cocirculation, limited to India only. This study augments the understanding of epidemiological features and demonstrates the extensive diversity exhibited by the NPEV strains in NPAFP cases from the polio-endemic region. It also underscores the need or effective long-term strategies to monitor NPEV circulation and its associated health risks in the post-polio eradication era.