Field evaluation of a Pan-Lassa rapid diagnostic test during the 2018 Nigerian Lassa fever outbreak

Matthew L Boisen,Luis M Branco,Stephan Günther,Donald S Grant,Wiebke Böhm,Eghosa Uyigue,Patience Akhilomen,Ikponmwosa Odia,Jacqueline Agbukor,Onikepe A Folarin,Peter O Okokhere ,John Demby Sandi,Ephraim Ogbaini-Emovan,Chris Aire ,George O Akpede,Kayla G Barnes,Katherine J Siddle,Michael Airende,Adeyemi T Kayode,Megan L Heinrich,Sophie Duraffour,John Aiyepada,Samar B Mehta ,Christian Happi ,Omigie Omoregie,Mambu Momoh,Blessing Osiemi,Duane J Bush,Pardis C Sabeti,Diana Nelson ,Megan M Rowland,Solomon Ehikhametalor,Grace Okonofua,Augustine Goba,Sylvanus Okogbenin ,John S Schieffelin,Danny Asogun ,Lisa Oestereich,Ekene B Muoebonam,Meike Pahlmann,Ekaete Tobin ,Donatus I Adomeh ,Philomena Eromon,Robert F Garry

doi:10.1038/s41598-020-65736-0

Abstract

Lassa virus (LASV) is the causative agent of Lassa fever (LF), an often-fatal hemorrhagic disease. LF is endemic in Nigeria, Sierra Leone and other West African countries. Diagnosis of LASV infection is challenged by the genetic diversity of the virus, which is greatest in Nigeria. The ReLASV Pan-Lassa Antigen Rapid Test (Pan-Lassa RDT) is a point-of-care, in vitro diagnostic test that utilizes a mixture of polyclonal antibodies raised against recombinant nucleoproteins of representative strains from the three most prevalent LASV lineages (II, III and IV). We compared the performance of the Pan-LASV RDT to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria. For patients with acute LF (RDT positive, IgG/IgM negative) during initial screening, RDT performance was 83.3% sensitivity and 92.8% specificity when compared to composite results of two qPCR assays. 100% of samples that gave Ct values below 22 on both qPCR assays were positive on the Pan-Lassa RDT. There were significantly elevated case fatality rates and elevated liver transaminase levels in subjects whose samples were RDT positive compared to RDT negative.

Highlights

Infection by Lassa virus (LASV), a member of the Arenaviridae, causes a range of clinical outcomes from a mild or inapparent febrile illness to Lassa fever (LF), an often-fatal hemorrhagic disease
The set of stored samples collected during the 2018 Nigeria LF outbreak was used to evaluate the diagnostic potential of a suite of diagnostic immunoassays based on recombinant LASV proteins (ReLASV)[1,20,25,31]
This study evaluated a suite of LF immunoassays based on LASV recombinant proteins using samples from patients referred to the Lassa surveillance program at Irrua Specialist Teaching Hospital (ISTH) during the 2018 LF outbreak in Nigeria[1,20,25,31]

Summary

Introduction

Infection by Lassa virus (LASV), a member of the Arenaviridae, causes a range of clinical outcomes from a mild or inapparent febrile illness to Lassa fever (LF), an often-fatal hemorrhagic disease. Diagnosis on the basis of clinical presentation alone is challenging because the initial symptoms, including fever, headache, malaise and general weakness, are nondescript[15,16,17,18,19] and common to other febrile illnesses in West Africa, such as malaria, typhoid fever, leptospirosis and arbovirus diseases[20]. Laboratory diagnosis of acute LF in West Africa relies on the detection of LASV antigen (Ag) using immunoassays or genomic RNA using molecular diagnostics, such as polymerase chain reaction (PCR)[21,22,23,24,25]. We compare the performance of the Pan-Lassa RDT designed to detect infection with the most common LASV lineage to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria

Methods

Results

Conclusion