Diagnostic applications for Lassa fever in limited-resource settings

Emperador, Devy; Yimer, Solomon Abebe; Mazzola, Laura T; Norheim, Gunnstein; Kelly-Cirino, Cassandra

doi:10.1136/bmjgh-2018-001119

Cited by 16 publications

(16 citation statements)

References 26 publications

(30 reference statements)

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“…4E,F). These cutoffs are consistent with previously determined limits of detection of Lassa qPCR assays 37,38 . Contingency analysis of the proposed qPCR cut-off at the optimal diagnostic likelihood (sensitivity/1-specificity) compared to NGS reveals sensitivity = 79.5% and specificity = 89.9% for Altona at Ct ≤ 31 ( Fig.…”

Section: Resultssupporting

confidence: 89%

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

Boisen

Uyigue

Aiyepada

et al. 2020

Sci Rep

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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.

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Section: Resultssupporting

confidence: 89%

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

Boisen

Uyigue

Aiyepada

et al. 2020

Sci Rep

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“…To this end, we combined the SHERLOCK assay with the HUDSON technique, which integrates heat inactivation with TCEP : EDTA to denature RNAses and release nucleic acid from viral particles, thus eliminating the need for RNA extraction. Furthermore, as LASV and EBOV are secreted in saliva and urine 26,27 , HUDSON enables disease diagnosis without the need for an invasive blood draw or specialized equipment, resulting in a faster end-to-end processing time. To confirm HUDSON's efficacy for viral inactivation and to determine the most sensitive HUDSON protocol for SHERLOCK use, we carried out tests at the BSL4 laboratory facility at the NIH Integrated Research Facilities.…”

Section: Crispr-cas13a Diagnostic Development and Validation Formentioning

confidence: 99%

Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time

et al. 2020

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Recent outbreaks of viral hemorrhagic fevers (VHFs), including Ebola virus disease (EVD) and Lassa fever (LF), highlight the urgent need for sensitive, deployable tests to diagnose these devastating human diseases. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. We perform safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We develop a user-friendly protocol and mobile application (HandLens) to report results, facilitating SHERLOCK's use in endemic regions. Finally, we successfully deploy our tests in Sierra Leone and Nigeria in response to recent outbreaks.

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“…LASV isolates from the Hylomyscus pamfi rodent trapped in Nigeria 8 and from a nosocomial outbreak in Togo 32 have been proposed to represent new lineage VI and lineage VII, respectively. Development of Lassa fever countermeasures is potentially challenged by the high genetic diversity of LASV 14,33 . The genetic variability of LASV could produce differences in the antigenicity of LASV proteins [34][35][36] .…”

mentioning

confidence: 99%

Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages

Heinrich

Boisen

Nelson

et al. 2020

Sci Rep

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Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI’s (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II–IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.

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Diagnostic applications for Lassa fever in limited-resource settings

Cited by 16 publications

References 26 publications

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

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

Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time

Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages

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