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

Ugandan children was P. falciparum, an expected result considering the high incidence of 265 malaria in Tororo District at the time of this study [33] . Some discrepancies were seen compared 266 to blood smear readings, with false positive smears probably due to errors in slide reading, a 267 common problem in African clinics [34] , and false negative smears due to the expected greater 268 sensitivity of mNGS for identification of P. falciparum. In children with only sub-microscopic 269 parasitemia, it is uncertain whether fevers can be ascribed to malaria, and in fact many children 270 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/385005 doi: bioRxiv preprint WHO Essential Medicines List was identified in this study [52] . Three children had genotypic 318 evidence of ESBL producing organisms predicted to be resistant to ceftriaxone, a frontline 319 antibiotic for severe infections in this region [53] . In addition, one of these three children carried 320 IMP-1, which also confers resistance to carbapenems, a class of antibiotics reserved for the most 321 resistant infections. 322 323 Our exploratory pilot study had important limitations. First, our samples were not 324 collected randomly, but rather were a convenience sample due to the logistical constraints of our 325 small clinical study; as such the results should not be seen as broadly representative of pathogens 326