Sequence Analysis of the Human Virome in Febrile and Afebrile Children

Abstract

Unexplained fever (UF) is a common problem in children under 3 years old. Although virus infection is suspected to be the cause of most of these fevers, a comprehensive analysis of viruses in samples from children with fever and healthy controls is important for establishing a relationship between viruses and UF. We used unbiased, deep sequencing to analyze 176 nasopharyngeal swabs (NP) and plasma samples from children with UF and afebrile controls, generating an average of 4.6 million sequences per sample. An analysis pipeline was developed to detect viral sequences, which resulted in the identification of sequences from 25 viral genera. These genera included expected pathogens, such as adenoviruses, enteroviruses, and roseoloviruses, plus viruses with unknown pathogenicity. Viruses that were unexpected in NP and plasma samples, such as the astrovirus MLB-2, were also detected. Sequencing allowed identification of virus subtype for some viruses, including roseoloviruses. Highly sensitive PCR assays detected low levels of viruses that were not detected in approximately 5 million sequences, but greater sequencing depth improved sensitivity. On average NP and plasma samples from febrile children contained 1.5- to 5-fold more viral sequences, respectively, than samples from afebrile children. Samples from febrile children contained a broader range of viral genera and contained multiple viral genera more frequently than samples from children without fever. Differences between febrile and afebrile groups were most striking in the plasma samples, where detection of viral sequence may be associated with a disseminated infection. These data indicate that virus infection is associated with UF. Further studies are important in order to establish the range of viral pathogens associated with fever and to understand of the role of viral infection in fever. Ultimately these studies may improve the medical treatment of children with UF by helping avoid antibiotic therapy for children with viral infections.

Wastewater Analysis Indicates that Genetically Diverse Astroviruses, Including Strains Belonging to Novel Clades MLB and VA, Are Circulating within Japanese Populations

“…These observations suggest that MLB-AstVs may be more prevalent than VA-AstVs among children with diarrheal disease. All MLB-AstV strains found in this study were classified as type 2 strains, which have been found in nasopharyngeal swab and plasma samples obtained from febrile children and have been hypothesized to infect extraenteric tissues (7,50,51). Our results suggest that the prevalence of nonenteric MLB-AstVs as well as enteric viruses can be assumed by investigating wastewater samples.…”

The potential of whole genome NGS for infectious disease diagnosis

“…Other advantages of WG-NGS are its ability to provide more detailed taxonomic information than diagnostic PCRs, as viral subtypes or serotypes (see for example [4]) and its good relationship between the number of NGS reads and CT values. [5][6][7] It may also lead to the discovery of new pathogens.…”

Parechovirus como agente etiológico de meningitis y/o sepsis viral en lactantes

“…Entre estas últimas, las sepsis virales y el compromiso del sistema nervioso central (SNC) representan un mayor desafío diagnóstico y terapéutico. Las infecciones virales sistémicas en este grupo etario pueden presentarse con síntomas inespecíficos, rechazo alimentario, fiebre, irritabilidad, y excepcionalmente, muerte 2 . Es así como, ante un lactante con síndrome febril agudo, la primera disyuntiva es el diagnóstico diferencial entre una infección bacteriana y una infección viral sistémica.…”