Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis

Akshaya Ramesh; Sara Nakielny; Jennifer Hsu; Mary Kyohere; Oswald Byaruhanga; Charles de Bourcy; Rebecca Egger; Boris Dimitrov; Yun-Fang Juan; Jonathan Sheu; James Wang; Katrina Kalantar; Charles Langelier; Theodore Ruel; Arthur Mpimbaza; Michael R. Wilson; Philip J. Rosenthal; Joseph L. DeRisi

The evaluation of children with fever is challenging, particularly in the developing world. Within the species rhinovirus, we assembled de novo a total of 13 HRV-C (mean 198 coverage: 39-fold) and 13 HRV-A (mean coverage: 268-fold) genomes (> 500 bp (Figure 4) ). Of 199 these, 10 HRV-A and 9 HRV-C genomes had complete coverage of the VP1 region, which is 200 used to define enterovirus types [19] . HRV types are defined by divergence of >73% in the VP1 201 gene. As such, we found three HRV-A and eight HRV-C types in this cohort. One individual 202 harbored two distinct HRV-A types (genome pairwise identity=75.3%, VP1 pairwise 203 identity=67.1%). Additionally, we assembled two novel HRV-C isolates from two patients 204 admitted with gastroenteritis (patient ID: EOFI-014), and pneumonia, malaria and diarrhea 205 Using mNGS and IDseq, the most common pathogen identified in the blood of febrile 264