Abstract

Pathogens associated with haemorrhagic fever commonly have zoonotic origins. The first documented imported case of likely viral severe haemorrhagic fever in Sweden occurred in 1990. Despite extensive study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of samples collected between 7 and 36 days from onset of symptoms we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient likely suffered from haemorrhagic symptoms due to an atypical severe and undiagnosed dengue infection.

Highlights

  • More than 20 enveloped RNA viruses are known to cause haemor­ rhagic fever, largely from four groups - arenaviruses, filoviruses, bunyaviruses, and flaviviruses [1], the majority of which originate from arthropod vectors and vertebrate animal sources and are of major importance in a One Health context [2]

  • Following inspection of the read hits to known viruses, we were able to identify sequence reads with high sequence similarity to dengue virus (DENV) in 11 of 15 sequencing libraries

  • Based on the clinical data reported for this patient [3,4] and the meta-transcriptomic identification of dengue virus 3 (DENV-3) that was confirmed by a variety of other assays, we suggest that the symptoms, including protracted febrile illness and prolonged viraemia, likely represent clinical manifestations of an atypical severe dengue haemorrhagic fever [11]

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Summary

Introduction

More than 20 enveloped RNA viruses are known to cause haemor­ rhagic fever, largely from four groups - arenaviruses, filoviruses, bunyaviruses, and flaviviruses [1], the majority of which originate from arthropod vectors and vertebrate animal sources and are of major importance in a One Health context [2] These pathogens can induce symptoms ranging from asymptomatic to severe life-threatening con­ ditions, with some haemorrhagic fevers associated with mortality rates as high as 80% [1]. During the haemorrhagic episode, which began at the start of week two and ceased at the end of the third week after symptom onset, the patient had received 65 units of blood It is note­ worthy that the patient had an extensive febrile period, with tempera­ tures consistently above 40 ◦C, that lasted for approximately three weeks despite symptomatic treatment. He was discharged 2.5 months after onset of symptoms

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