A complex mosaic of enteroviruses shapes community-acquired hand, foot and mouth disease transmission and evolution within a single hospital

Cobbin, Joanna C. A.; Britton, Philip N; Burrell, Rebecca A.; Thosar, Deepali; Selvakumar, K.; Eden, John‐Sebastian; Jones, Cheryl; Holmes, Edward C.

doi:10.1093/ve/vey020

Cited by 18 publications

(18 citation statements)

References 55 publications

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“…Numerous outbreaks of CVA4 have occurred during recent years in different regions in China, such as Fujian [4], Shandong [5, 6], Sichuan [7], Yunnan [8], and Jiangsu [9]. Other countries, such as Thailand [2, 10], Australia [11] and Italy [12] have also reported CVA4 infections. Genetic recombination between CVA4 and other EVs has been described generating novel emerging strains which may be associated with more severe disease [13].…”

Section: Introductionmentioning

confidence: 99%

“…Although the majority of CVA4 and EV infections are usually subclinical, these agents are highly contagious and exhibit a broad spectrum of disease presentation in symptomatic cases ranging from mild symptoms such as erythematous maculopapular exanthema [12] to severe outcomes such as aseptic meningitis, myocarditis and acute flaccid paralysis [14, 15]. Given the increased frequency of CVA4 circulation globally [11, 16, 17], evidence for complex spatiotemporal dynamics in Asia-Europe [18] and the emergence of novel CVA recombinants with the potential to spread rapidly in immunologically naïve populations [13], greater focus is required both on surveillance and also the development of prophylactic and therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

Zhang

Carr

et al. 2019

Emerging Microbes & Infections

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Coxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

Zhang

Carr

et al. 2019

Emerging Microbes & Infections

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“…Sequence comparison revealed that the Sydney outbreak strains from this study grouped closely with strains from the C4 sub-genotype isolated in China in previous years (Figure 1 & Supplementary Figure 2). Figure 2 shows the comparison of the EV-A sequences with those from a 2016 molecular epidemiology study conducted in Sydney [15]. The results show an overall grouping of our 2013 Sydney strains with the 2016 strains by genotype with high bootstrap support.…”

Section: Diversity Of Hev Genotypes Circulating During An Outbreak Of Ev-a71mentioning

confidence: 94%

“…Sample types included swabs (throat, rectal or nose), nasopharyngeal aspirates, cerebrospinal fluid, faeces or cell culture from children aged 2 months to 14yrs old. We categorised clinical symptoms presented by patients into one of four stages by clinical severity [15][16][17]: uncomplicated HFMD or fever (Stage 1), myoclonic jerks or meningitis (Stage 2), with encephalitis with or without cardiopulmonary failure (Stage 3A/3B).…”

Section: Samplesmentioning

confidence: 99%

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Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations

Stelzer-Braid

Wynn

Chatoor

et al. 2020

Journal of Clinical Virology

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Background-The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications.Objectives-To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype.Study design-We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses.Results-We amplified and sequenced 23/63 (37%) genomes, and identified the majority (61%) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community.Conclusions-This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.

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Reclaiming independence in spatial‐clustering datasets: A series of data‐driven spatial weights matrices

Wang

Xiao

Qian

et al. 2022

Statistics in Medicine

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Most spatial models include a spatial weights matrix (W) derived from the first law of geography to adjust the spatial dependence to fulfill the independence assumption. In various fields such as epidemiological and environmental studies, the spatial dependence often shows clustering (or geographic discontinuity) due to natural or social factors. In such cases, adjustment using the first‐law‐of‐geography‐based W might be inappropriate and leads to inaccuracy estimations and loss of statistical power. In this work, we propose a series of data‐driven Ws (DDWs) built following the spatial pattern identified by the scan statistic, which can be easily carried out using existing tools such as SaTScan software. The DDWs take both the clustering (or discontinuous) and the intuitive first‐law‐of‐geographic‐based spatial dependence into consideration. Aiming at two common purposes in epidemiology studies (ie, estimating the effect value of explanatory variable X and estimating the risk of each spatial unit in disease mapping), the common spatial autoregressive models and the Leroux‐prior‐based conditional autoregressive (CAR) models were selected to evaluate performance of DDWs, respectively. Both simulation and case studies show that our DDWs achieve considerably better performance than the classic W in datasets with clustering (or discontinuous) spatial dependence. Furthermore, the latest published density‐based spatial clustering models, aiming at dealing with such clustering (or discontinuity) spatial dependence in disease mapping, were also compared as references. The DDWs, incorporated into the CAR models, still show considerable advantage, especially in the datasets for common diseases.

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A complex mosaic of enteroviruses shapes community-acquired hand, foot and mouth disease transmission and evolution within a single hospital

Cited by 18 publications

References 55 publications

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations

Reclaiming independence in spatial‐clustering datasets: A series of data‐driven spatial weights matrices

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