Real-time Metagenomic Analysis of Undiagnosed Fever Cases Unveils a Yellow Fever Outbreak in Edo State, Nigeria

Fehintola V Ajogbasile,Chikwe Ihekweazu,Ephraim Ogbaini-Emovon,Jessica N Uwanibe,Oyewale Tomori,Onikepe A Folarin,George O Akpede ,Sylvanus Okogbenin,Judith Oguzie ,Ikponmwosa Odia,Philomena Eromon ,Nosa Akpede,Kayvon Modjarrad,Katherine J Siddle,S Winnicki ,Stephen F Schaffner,Samar B Mehta,Bronwyn Macinnis ,Pardis C Sabeti,Paul E Oluniyi,Christian Happi

doi:10.1038/s41598-020-59880-w

Abstract

Fifty patients with unexplained fever and poor outcomes presented at Irrua Specialist Teaching Hospital (ISTH) in Edo State, Nigeria, an area endemic for Lassa fever, between September 2018 - January 2019. After ruling out Lassa fever, plasma samples from these epidemiologically-linked cases were sent to the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Ede, Osun State, Nigeria, where we carried out metagenomic sequencing which implicated yellow fever virus (YFV) as the etiology of this outbreak. Twenty-nine of the 50 samples were confirmed positive for YFV by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), 14 of which resulted in genome assembly. Maximum likelihood phylogenetic analysis revealed that these YFV sequences formed a tightly clustered clade more closely related to sequences from Senegal than sequences from earlier Nigerian isolates, suggesting that the YFV clade responsible for this outbreak in Edo State does not descend directly from the Nigerian YFV outbreaks of the last century, but instead reflects a broader diversity and dynamics of YFV in West Africa. Here we demonstrate the power of metagenomic sequencing for identifying ongoing outbreaks and their etiologies and informing real-time public health responses, resulting in accurate and prompt disease management and control.

Highlights

Yellow fever (YF) is an acute mosquito-borne viral haemorrhagic fever that is endemic in forty-seven countries across Africa, Central and South America
We established the presence of yellow fever virus (YFV) in Edo State within three days of receiving initial samples, and we shared this information immediately with the referring hospital (ISTH) and the Nigeria Center for Disease Control (NCDC)
Based in part on these findings, NCDC and the Nigeria Federal Ministry of Health declared an outbreak in Edo state the following day[4], prompting more samples to be sent for diagnosis

Summary

Introduction

Yellow fever (YF) is an acute mosquito-borne viral haemorrhagic fever that is endemic in forty-seven countries across Africa, Central and South America. In the last quarter of 2018, clinicians at Irrua Specialist Teaching Hospital in Edo State, Nigeria, a region endemic for Lassa fever, identified a cluster of patients with severe febrile illness who tested negative for Lassa virus.

Results

Conclusion