Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis

Mishra, Nischay; Ng, Terry Fei Fan; Marine, Rachel L.; Jain, Komal; Ng, James; Thakkar, Riddhi; Caciula, Adrian; Price, Adam; Garcia, Joel A.; Burns, Jane C.; Thakur, Kiran T.; Hetzler, Kimbell L.; Routh, Janell; Konopka-Anstadt, Jennifer L.; Nix, W. Allan; Tokarz, Rafal; Briese, Thomas; Oberste, M. Steven; Lipkin, W. Ian

doi:10.1128/mbio.01903-19

Cited by 73 publications

(79 citation statements)

References 22 publications

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“…Our earlier study, however, showed seroconversion in confirmed EV-D68 infected children, all of whom developed mild respiratory symptoms [15]. A recent study demonstrated significantly higher antibodies to EV peptides in cerebrospinal fluid (CSF) of patients with AFM than controls [16]. Among AFM patients, 43% (6/14) of CSF samples and 74% (8/11) of sera were immunoreactive to an EV-D68-specific peptide, which was in contrast to the non-immunoreactivity in either CSF or sera from the controls [16].…”

Section: Discussionmentioning

confidence: 74%

Enterovirus D68 seroepidemiology in Taiwan, a cross sectional study from 2017

et al. 2020

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Background Enterovirus D68 (EV-D68) was discovered in 1962 and has unique characteristics compared to the characteristics of other enteroviruses. There were few documented cases before the epidemic in the United States in 2014. The Taiwan Centers for Diseases Control also confirmed that EV-D68 has been endemic, and some cases of acute flaccid myelitis were reported in Taiwan. To understand the current EV-D68 serostatus, we performed an EV-D68 seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6-to 15-year-old students and 16-to 49-year-old people. The participants underwent a questionnaire investigation and blood sampling to measure the EV-D68 neutralization antibody. Results In total, 920 subjects were enrolled from the northern, central, southern and eastern parts of Taiwan with a male-to-female ratio of 1.03. The EV-D68 seropositive rate was 32% (26/82) in infants, 18% (27/153) in 1-year-old children, 43% (36/83) in 2-year-old children, 60% (94/ 156) in 3-to 5-year-old children, 89% (108/122) in 6-to 11-year-old primary school students, 98% (118/121) in 12-to 15-year-old high school students, 100% (122/122) in 16-to 49-yearold women and 100% (81/81) in 16-to 49-year-old males in 2017. Among preschool children, EV-D68 seropositivity was related to age (p for trend <0.0001), size of household ≧4 members (p = 0.037) and kindergarten attendance (p = 0.027). The seropositive rate varied among different geographic regions. Conclusion EV-D68 infection was prevalent, and its seropositive rates increased with age, larger household size and kindergarten attendance among preschool children.

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Section: Discussionmentioning

confidence: 74%

Enterovirus D68 seroepidemiology in Taiwan, a cross sectional study from 2017

et al. 2020

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“…Of note, paralytic syndrome caused by poliovirus is classically characterized by lower extremity weakness of an asymmetric distribution and a preceding mild gastrointestinal illness, features less common among AFM cases in peak years (16). Although multiple viruses are associated with AFM, growing evidence suggests that nonpolio enteroviruses and specifically EV-D68 are linked to the changes in AFM epidemiology that started in 2014 (21,22). Enteroviruses were the most common viruses in nasopharyngeal, oropharyngeal, or fecal specimens from confirmed AFM patients identified by CDC researchers, and EV-D68 was the most frequent enterovirus typed (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015–2018

McLaren¹,

Lopez²,

Kidd³

et al. 2020

Emerg. Infect. Dis.

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In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at http://www.medscape.org/journal/eid; and (4) view/print certificate. For CME questions, see page 399.

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“…Subunits 1 and 4 are present in dark grey to complete the structure. Subunit 2 shows the surface exposed proteins in purple (VP1), sand (VP2), and green (VP3), subunit 3 displays the different putative epitopes (Mishra et al, 2019) (note that the most variable parts of the BC-and DE-loops are not shown, as their structure is not resolved), and subunit 5 highlights variable positions in red, with the different proteins forming the surface indicated by pale colors. Panel B)…”

Section: Discussionmentioning

confidence: 99%

“…A particularly dense cluster of variable positions is formed by the C-terminus of VP1 and central region of VP2. The C-terminus of VP1 was identified by Mishra et al (2019) as a potential EV-D68 specific epitope.…”

Section: Antigenic Evolution Of Ev-d68mentioning

confidence: 99%

“…In particular, the C-terminus of VP1 and a surface exposed patch in VP2 are accumulating amino acid substitutions at a high rate with substantial parallelism between clades. The C-terminus of VP1 was recently described as an EV-D68 specific immunoreactive epitope (Mishra et al, 2019). In the 3D-structure, the C-terminus of VP1 and VP2 forms a contiguous ridge, which is a plausible target for antibody binding that displays substantial differences between the A2 and B3 subclades.…”

Section: Bc-loopmentioning

confidence: 99%

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Evolution, geographic spreading, and demographic distribution of Enterovirus D68

Hodcroft

Dyrdak

Andrés

et al. 2020

Preprint

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BackgroundWorldwide outbreaks of enterovirus D68 (EV-D68) in 2014 and 2016 have caused serious respiratory and neurological disease.MethodsWe collected samples from several European countries during the 2018 out-break and determined 53 near full-length genome (‘whole genome’) sequences. These sequences were combined with 718 whole genome and 1,987 VP1-gene publicly available sequences.FindingsIn 2018, circulating strains clustered into multiple subgroups in the B3 and A2 subclades, with different phylogenetic origins. Clusters in subclade B3 emerged from strains circulating primarily in the US and Europe in 2016, though some had deeper roots linking to Asian strains, while clusters in A2 traced back to strains detected in East Asia in 2015-2016. In 2018, all sequences from the USA formed a distinct subgroup, containing only three non-US samples. Alongside the varied origins of seasonal strains, we found that diversification of these variants begins up to 18 months prior to the first diagnostic detection during a EV-D68 season. EV-D68 displays strong signs of continuous antigenic evolution and all 2018 A2 strains had novel patterns in the putative neutralizing epitopes in the BC- and DE-loops. The pattern in the BC-loop of the USA B3 subgroup had not been detected on that continent before. Patients with EV-D68 in subclade A2 were significantly older than patients with a B3 subclade virus. In contrast to other subclades, the age distribution of A2 is distinctly bimodal and was found primarily among children and in the elderly.InterpretationWe hypothesize that EV-D68’s rapid evolution of surface proteins, extensive diversity, and high rate of geographic mixing could be explained by substantial reinfection of adults.FundingUniversity of Basel and Swedish Foundation for Research and Development in Medical Microbiology

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Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis

Cited by 73 publications

References 22 publications

Enterovirus D68 seroepidemiology in Taiwan, a cross sectional study from 2017

Enterovirus D68 seroepidemiology in Taiwan, a cross sectional study from 2017

Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015–2018

Evolution, geographic spreading, and demographic distribution of Enterovirus D68

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