Abstract

Non-polio enteroviruses (NPEVs) have been reported frequently in association with acute flaccid paralysis (AFP) cases during Polio Surveillance Programs (PSPs) worldwide. However, there is limited understanding on the attributes of their infections. This study reports characteristics of NPEVs isolated from AFP cases, investigated during PSPs held in 2009–2010, in Karnataka and Kerala states of south-western India having varied climatic conditions. NPEV cell culture isolates derived from stool specimens that were collected from 422 of 2186 AFP cases (<1–14 years age) and 17 of 41 asymptomatic contacts; and details of all AFP cases/contacts were obtained from National Polio Laboratory, Bangalore. The distribution of NPEV infections among AFP cases and circulation pattern of NPEV strains were determined by statistical analysis of the data. Genotyping of all NPEV isolates was carried out by partial VP1 gene sequencing and phylogenetic analysis. NPEV positive AFP cases were significantly higher in children aged <2 years; with residual paralysis; in summer months; and in regions with relatively hot climate. Genotyping of NPEVs identified predominance of human enteroviruses (HEV)-B species [81.9%—Echoviruses (E): 57.3%; coxsackieviruses (CV) B: 15%; numbered EVs: 8.9%; CVA9: 0.7%] and low levels of HEV-A [14.5%—CVA: 6%; numbered EVs: 8.5%] and HEV-C [3.6%—CVA: 2.6%; numbered EVs: 1%] species, encompassing 63 genotypes. EV76 (6.3%) and each of E3, CVB3 and E9 (4.97%) were found frequently during 2009 while E11 (6.7%), CVB1 (6.1%), E7 (5.1%) and E20 (5.1%) were detected commonly in 2010. A marked proportion of AFP cases from children aged <2 years; presenting with fever; and from north and south interior parts of Karnataka state was detected with E/numbered EVs than that found with CVA/CVB. This study highlights the extensive genetic diversity and diverse circulation patterns of NPEV strains in AFP cases from different populations and climatic conditions.

Highlights

  • Acute flaccid paralysis (AFP) is a clinical syndrome known to be manifested in humans by infectious or noninfectious causes or post-infectious autoimmune condition [1], [2]

  • In a total of 312 AFP cases that were followed after 60 days of onset of paralysis, Non-polio enteroviruses (NPEVs) positivity was significantly high in AFP cases with residual paralysis as compared to recovered cases (21/124; 16.9% vs 17/ 188; 9%, p,0.04)

  • A striking rise in the non-polio AFP cases that has been reported during AFP surveillance carried out since 1997 in India for polio eradication [16], has vitalized the studies on the epidemiological and virological characteristics of NPEV infections associated with AFP cases in varied climatic zones

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Summary

Introduction

Acute flaccid paralysis (AFP) is a clinical syndrome known to be manifested in humans by infectious (bacterial or viral) or noninfectious (metabolic disorders or trauma or metal toxicity) causes or post-infectious autoimmune condition (eg: Guillian Barre syndrome [GBS]) [1], [2]. EVs, the members of the genus Enterovirus, family Picornaviridae are non-enveloped icosahedral particles, 27–30 nm in diameter. The genome consists of a positive sense single stranded RNA molecule, 7400–7500 nucleotides in length that encodes a large poly-protein. The post-translational cleavage products include four structural (VP1, VP2, VP3 and VP4) and seven non-structural (2A, 2B, 2C, 3A, 3B, 3C and 3D) viral proteins [5]. Based on the pathogenicity in humans and experimental animals, EVs were classified into four groups, polioviruses (PVs), coxsackieviruses A (CVA), coxsackieviruses B (CVB), and echoviruses (E) [6]. Human enteroviruses (HEVs) have been subdivided into four species (HEV-A, HEV-B, HEV-C and HEV-D) [7] by phylogenetic analysis of variable region of the genome, among which more than 100 genotypes have been described

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