Meningitis and epididymitis caused by Toscana virus infection imported to Switzerland diagnosed by metagenomic sequencing: a case report

Abstract

Background We report a rare case of Toscana virus infection imported into Switzerland in a 23-year old man who travelled to Imperia (Italy) 10 days before onset of symptoms. Symptoms included both meningitis and as well epididymitis. This is only the fourth case of Toscana virus reported in Switzerland. Case presentation The patient presented with lymphocytic meningitis and scrotal pain due to epididymitis. Meningitis was initially treated with ceftriaxone. Herpes simplex, tick-borne encephalitis, enterovirus, measles, mumps, rubella and Treponema pallidum were excluded with specific polymerase chain reaction (PCR) or serology. In support of routine diagnostic PCR and serology assays, unbiased viral metagenomic sequencing was performed of cerebrospinal fluid and serum. Toscana virus infection was identified in cerebrospinal fluid and the full coding sequence could be obtained. Specific PCR in cerebrospinal fluid and blood and serology with Immunoglobulin (Ig) M and IgG against Toscana virus confirmed our diagnosis. Neurological symptoms recovered spontaneously after 5 days. Conclusions This case of Toscana virus infection highlights the benefits of unbiased metagenomic sequencing to support routine diagnostics in rare or unexpected viral infections. With increasing travel histories of patients, physicians should be aware of imported Toscana virus as the agent for viral meningitis and meningoencephalitis. Electronic supplementary material The online version of this article (10.1186/s12879-019-4231-9) contains supplementary material, which is available to authorized users.

Two Years of Viral Metagenomics in a Tertiary Diagnostics Unit: Evaluation of the First 105 Cases

“…In three cases, mNGS provided the final diagnosis for viruses not considered or available by routine diagnostic tests (see Case Vignettes 1–3 in Appendix B). Further diagnostic tests were therefore not necessary and empirical antibiotic treatment could be stopped [29]. In other cases, mNGS essentially contributed to exclude an actively replicating virus infection.…”

“…The case was already reported [29]: A 23-year-old man presented with meningitis and epididymitis. Routine diagnostic workup yielded no diagnosis, but viral metagenomics in CSF revealed a Toscana virus infection.…”

“…In 2017, we introduced virus sequence-independent metagenomic high-throughput sequencing at our tertiary diagnostic unit and established protocols for sample preparation, sequencing and bioinformatics analysis [26]. This analysis workflow has proven highly successful enabling us to detect disease causing viral pathogens in complex clinical cases [27,28,29]. Since 2017, viral mNGS was applied in 105 primarily hard-to-diagnose cases upon request by the treating clinician.…”

Improved diagnosis of viral encephalitis in adult and pediatric hematological patients using viral metagenomics

“…Metagenomic next-generation sequencing has the potential to detect the full spectrum of viral pathogens in a single test. An increasing number of case reports have described the application of metagenomics to clinical cases of encephalitis of unknown origin in both immunocompetent and immunocompromised patients [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Immunocompromised patients are most at risk of infection with unexpected and novel pathogens and may present with insidious clinical symptoms [2,16].…”

Ubiquitin and Not Only Unfolded Domains Drives Toscana Virus Non-Structural NSs Protein Degradation

“…Although pauci-symptomatic infections are described in endemic countries [ 4 ], TOSV infection is mostly associated to meningitis or more severe central nervous system (CNS) injuries, such as encephalitis and cerebral ischemia [ 4 , 5 , 6 ]. Nowadays, TOSV is widely present in the Mediterranean basin [ 7 , 8 , 9 , 10 , 11 ] and represents a significant public health threat.…”