Blood virosphere in febrile Tanzanian children

Samuel Cordey,Valérie D’Acremont,Gaël Vieille ,Anne Gleizes,Mylène Docquier,Jacques Fellay,Gasser H Elbanna,Thomas Junier,Tarsis Mlaganile,Nicolas Guex,Zamzam Said,Christian Iseli,Ioannis Xénarios ,Mary-Anne Hartley,Caroline Tapparel,John Masimba,Florian Laubscher,Kristina Keitel,Frank Kagoro,Josephine Samaka,Philippe Le Mercier,Hosiana Temba,Marie-Céline Zanella ,Laurent Kaiser

doi:10.1080/22221751.2021.1925161

Abstract

ABSTRACT Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens. Trial registration: ClinicalTrials.gov identifier: NCT02225769.

Highlights

Humans are infected by a large number of eukaryotic DNA and RNA viruses that, together with prokaryotic phages and endogenous viral elements, comprise what we define as the human virome
We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses, 12% rotaviruses, 11% human herpesvirus type 6)
These diagnoses were obtained using by the clinical decision algorithms of the e-POCT study [20]: (1) “Fever without focus” representing children who would most benefit from further diagnostics; (2) “Severe illness,” representing children in whom the impact of blood viruses may be investigated. (3) “Malaria,” in whom blood viruses may interact with this important and frequent parasite and/or be less likely as the cause of the febrile episode

Summary

Introduction

Humans are infected by a large number of eukaryotic DNA and RNA viruses that, together with prokaryotic phages and endogenous viral elements, comprise what we define as the human virome. Eukaryotic viruses are a diverse group of DNA and RNA viral agents replicating in a variety of human cells and tissues and engaging in a vast permutation of interactions with the human immune system. The presentation of human viral disease depends on both viral and host factors, where a virus may only be pathological in a certain situation (e.g. following immunosuppression), whilst being considered (perhaps over simplistically) as commensal or merely an incidental finding in a “healthy” situation. The composition of the human virome does vary between these populations but it changes over time within individuals according to their personal history of exposure and immunity and their geographic location, access to vaccination

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