Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings

Abstract

Lassa fever virus (LASV) causes acute viral haemorrhagic fever with symptoms similar to those seen with Ebola virus infections. LASV is endemic to West Africa and is transmitted through contact with excretions of infected Mastomys natalensis rodents and other rodent species. Due to a high fatality rate, lack of treatment options and difficulties with prevention and control, LASV is one of the high-priority pathogens included in the WHO R&D Blueprint. The WHO LASV vaccine strategy relies on availability of effective diagnostic tests. Current diagnostics for LASV include in-house and commercial (primarily research-only) laboratory-based serological and nucleic acid amplification tests. There are two commercially available (for research use only) rapid diagnostic tests (RDTs), and a number of multiplex panels for differential detection of LASV infection from other endemic diseases with similar symptoms have been evaluated. However, a number of diagnostic gaps remain. Lineage detection is a challenge due to the genomic diversity of LASV, as pan-lineage sensitivity for both molecular and immunological detection is necessary for surveillance and outbreak response. While pan-lineage ELISA and RDTs are commercially available (for research use only), validation and external quality assessment (EQA) is needed to confirm detection sensitivity for all known or relevant strains. Variable sensitivity of LASV PCR tests also highlights the need for improved validation and EQA. Given that LASV outbreaks typically occur in low-resource settings, more options for point-of-care testing would be valuable. These requirements should be taken into account in target product profiles for improved LASV diagnostics.

Diagnostic applications for Lassa fever in limited-resource settings

“…The high level of genetic diversity between LASVs also poses a diagnostic challenge as only <75% of the genome sequence is conserved. Phylogenetic analysis based on whole genome sequencing showed that LASV is grouped into four main lineages 1 2. A fifth ‘AV’ lineage from Mali/Cote D’Ivoire has recently been proposed 12.…”

“…Despite measures to prevent and control the spread of Lassa virus (LASV), the fight against Lassa fever is hampered by a lack of vaccines, well-documented therapeutics and appropriate diagnostics 1 2. There are currently no commercially available diagnostics capable of capturing the diversity among viral strains and providing a diagnosis at any time-point during the clinical course of illness.…”

“…This indicates that the available LASV diagnostic methods are difficult to operationalise in low-resource health centres and may be less sensitive to detecting new or emerging LASV strains. Building on the Lassa fever diagnostic landscape presented by Mazzola and Kelly-Cirino,1 here we present diagnostic applications to help define priority development for the prevention and control of Lassa fever in LASV-affected countries.…”

Lassa Fever-associated Stigmatization among Staff and Students of the University of Benin, Nigeria

“…LF is also known to be endemic in Benin, Ghana, and Mali [1]. LF disease is an acute viral hemorrhagic disease caused by Lassa Virus (LASV), a bisegmented single-stranded RNA virus, which belongs to the family Arenaviridae [1,6]. The putative reservoir of LASV is the Mastomys natalensis, which is known to exhibit asymptomatic infection but results in copious shedding of the virus in the urine, feces, saliva, and blood of infected rats [1,7].…”

Importance of diagnostics in epidemic and pandemic preparedness

“…It is vital that the current lack of rapid diagnostic tests for priority pathogens is addressed, to ensure that future outbreaks can be more effectively contained. Detailed descriptions of the diagnostic landscapes for selected WHO R&D Blueprint pathogens are provided in this supplement 15–19. Each of these pathogens presents specific challenges, due to differences in factors such as geographical location (Nipah infection primarily occurs in Asia, Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East and Lassa fever in Africa, while Crimean-Congo haemorrhagic fever (CCHF) is widespread) and mode of transmission (MERS-CoV in particular has a significant animal reservoir in dromedary camels, while CCHF is a tick-borne disease), among others.…”