Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing

Chronic enterovirus infections can cause significant morbidity, particularly in immunocompromised patients. This study describes a fatal case associated with a chronic untypeable enterovirus infection in an immunocompromised patient admitted to a Dutch university hospital over nine months. We aimed to identify the enterovirus genotype responsible for the infection and to determine potential evolutionary changes. Long-read sequencing was performed using viral targeted sequence capture on four respiratory and one faecal sample. Phylogenetic analysis was performed using a maximum likelihood method, along with a root-to-tip regression and time-scaled phylogenetic analysis to estimate evolutionary changes between sample dates. Intra-host variant detection, using a Fixed Ploidy algorithm, and selection pressure, using a Fixed Effect Likelihood and a Mixed Effects Model of Evolution, were also used to explore the patient samples. Near-complete genomes of enterovirus C104 (EV-C104) were recovered in all respiratory samples but not in the faecal sample. The recovered genomes clustered with a recently reported EV-C104 from Belgium in August 2018. Phylodynamic analysis including ten available EV-C104 genomes, along with the patient sequences, estimated the most recent common ancestor to occur in the middle of 2005 with an overall estimated evolution rate of 2.97 × 10(−3) substitutions per year. Although positive selection pressure was identified in the EV-C104 reference sequences, the genomes recovered from the patient samples alone showed an overall negative selection pressure in multiple codon sites along the genome. A chronic infection resulting in respiratory failure from a relatively rare enterovirus was observed in a transplant recipient. We observed an increase in single-nucleotide variations between sample dates from a rapidly declining patient, suggesting mutations are weakly deleterious and have not been purged during selection. This is further supported by the persistence of EV-C104 in the patient, despite the clearance of other viral infections. Next-generation sequencing with viral enrichment could be used to detect and characterise challenging samples when conventional workflows are insufficient

Improved diagnostic policy for respiratory tract infections essential for patient management in the emergency department

Establishing an optimal diagnostic policy for patients with respiratory tract infections, at the emergency department (ED) of a university hospital in The Netherlands. Methods: Adult patients were sampled at admission, during the respiratory season (2014-2015). The FilmArray-RP was implemented at the clinical virology laboratory. Diagnostics were provided from 8 am to 10 pm, weekends included. Results: 436/492 (89%) results were available while patients were still at the ED. Median TAT from admission to test result was 165 min (IQR: 138-214). No antibiotics were prescribed in 94/207 (45%) patients who tested positive for a virus. 185/330 (56%) hospitalized patients did not need admission with isolation measures. The value-based measure, expressed in euro-hour (€h), increased to tenfold compared with previous policy. Conclusion: An optimal policy is essential for patient management, by providing timely, reliable diagnostics

Improved Detection Criteria for the Multi-dimensional Optimal Order Detection (MOOD) on unstructured meshes with very high-order polynomials

This paper extends the MOOD method proposed by the authors in ["A high-order finite volume method for hyperbolic systems: Multidimensional Optimal Order Detection (MOOD)", J. Comput. Phys. 230, pp 4028-4050, (2011)], along two complementary axes: extension to very high-order polynomial reconstruction on non-conformal unstructured meshes and new Detection Criteria. The former is a natural extension of the previous cited work which confirms the good behavior of the MOOD method. The latter is a necessary brick to overcome limitations of the Discrete Maximum Principle used in the previous work. Numerical results on advection problems and hydrodynamics Euler equations are presented to show that the MOOD method is effectively high-order (up to sixth-order), intrinsically positivity-preserving on hydrodynamics test cases and computationally efficient