Longitudinal Analysis of Nasopharyngeal Microbial Risk Markers for Fatal Acute Febrile Illness in a Zambian Birth Cohort.

Abstract

Fatal acute febrile illness (fAFI) is a known predecessor of many infant mortality events in low-resource settings, but early risk markers for this condition remain poorly understood. Nasopharyngeal (NP) microbiome patterns may influence the severity of these infections. We analyzed longitudinal changes in the NP microbiota of Zambian infants with fAFI onset compared to healthy controls, aiming to identify microbial indicators associated with severe illness outcomes. We conducted a pooled analysis of a longitudinal nested case-control study composed of 26 samples from 9 infants who developed fAFI compared with 69 samples from 10 healthy infants. Infants underwent nasopharyngeal sampling from 1 week through 14 weeks of age at 2-2.5-week intervals. We performed 16S rRNA gene amplicon sequencing on all infant NP samples and characterized NP microbiome maturation among infants with febrile acute febrile illness (fAFI+) and healthy controls (fAFI-). Beta diversity measures of fAFI- infants were markedly higher than those of fAFI+ infants. The fAFI+ infant NP microbiome was marked by lower abundances of Dolosigranulum, Haemophilus, Streptococcus, and Corynebacterium, with higher relative presence of Pseudomonas. Our findings suggest that specific microbial community patterns and early NP microbiome dysbiosis may be associated with increased illness risk. These findings can motivate further studies to inform foundational markers for fAFI in infants, contributing to precision pediatric care.