Abstract
The cause of acute encephalitis/meningoencephalitis in pediatric patients remains often unexplained despite extensive investigations for large panel of pathogens. To explore a possible viral implication, we investigated the virome of cerebrospinal fluid specimens of 70 febrile pediatric inpatients with clinical compatible encephalitis/meningoencephalitis. Using viral metagenomics, we detected and genetically characterized three novel human Torque teno mini virus (TTMV) species (TTMV-G1-3). Phylogenetically, TTMV-G1-3 clustered in three novel monophyletic lineages within genus Betatorquevirus of the Anelloviridae family. TTMV-G1-3 were highly prevalent in diseased children, but absent in the healthy cohort which may indicate an association of TTMV species with febrile illness. With 2/3 detected malaria co-infection, it remains unclear if these novel anellovirus species are causative agents or increase disease severity by interaction with malaria parasites. The presence of the viruses 28 days after initiating antimalarial and/or antibiotic treatment suggests a still active viral infection likely as effect of parasitic and/or bacterial co-infection that may have initiated a modulated immune system environment for viral replication or a defective virus clearance. This study increases the current knowledge on the genetic diversity of TTMV and strengthens that human anelloviruses can be considered as biomarkers for strong perturbations of the immune system in certain pathological conditions.
Highlights
In sub-Saharan Africa, fever remains one of the most common symptoms of acute pediatric illness and is the main reason for seeking health-care advice
Using viral metagenomics we detected 4 novel human anellovirus species in the cerebrospinal fluid (CSF) and serum from pediatric inpatients presenting with clinical signs of encephalitis or meningoencephalitis, mostly co-infected with malaria parasites or bacteria
Its discovery was followed by the detection of a large and diverse anellovirus population which has been classified in three genera, Alphatorquevirus including the Torque Teno virus (TTV), Betatorquevirus with Torque Teno mini virus (TTMV) and Gammatorquevirus with torque teno midi virus (TTMDV) in the Anelloviridae family[14]
Summary
In sub-Saharan Africa, fever remains one of the most common symptoms of acute pediatric illness and is the main reason for seeking health-care advice. Up to 70% of pediatric patients in sub-Saharan Africa[5] exhibit asymptomatic malaria parasitaemia, other possible causes of encephalitis/meningoencephalitis (e.g., viral or bacterial CNS infection) must be excluded in order to confirm cerebral malaria[4]. A complex analysis of the viral composition in acute CNS infection cases is crucial to better understand the possible causes or interactions within these pathological conditions to improve the clinical management of the patients and reduce disability-adjusted-life-years (DALYs) due to implementation of prevention and treatment programs. The goal of the present study was to use viral metagenomics in order to explore the possible viral implication in CNS infections by determining the cerebrospinal fluid virome profile of 70 acute febrile pediatric inpatients with compatible encephalitis or meningoencephalitis from rural Ghana consulting medical advice
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