Whole blood genome-wide transcriptome profiling and metagenomics next-generation sequencing in young infants with suspected sepsis in a low-and middle-income country: A study protocol

Gates Open Res. 2020 Nov 26:4:139. doi: 10.12688/gatesopenres.13172.2. eCollection 2020.

Abstract

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have sepsis of bacterial causes. The protocol includes a detailed clinical assessment with vital sign measurements, strict aseptic blood culture protocol with state-of-the-art microbial analyses and RNA-sequencing and metagenomics evaluations of host responses and pathogens, respectively. We also discuss the directions of a brief analysis plan for RNA sequencing data. This study will provide robust epidemiological data for sepsis in neonates and young infants in a setting where sepsis confers an inordinate burden of disease.

Keywords: Newborns; RNA sequencing; blood culture.; diagnosis; epidemiology; low- and middle-income country; metagenomics; prospective study; sepsis; young infants.

Grants and funding

This study is funded by a Stars in Global Health grant: Improving the Early Diagnosis of Neonatal Sepsis in Malawi from Grand Challenges Canada (grant number R-ST-POC-1701-04630). The mNGS component of this study is funded by a Grand Challenges Exploration grant: Improving Diagnosis of Sepsis in Young Infants in Africa: Are We Using Antibiotics Appropriately? from the Bill & Melinda Gates Foundation to Tisungane Mvalo [INV-008947/OPP1211936].