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.

Keywords: LASV; Lassa fever virus; in-vitro diagnostics; outbreak.

Figure 1

Geographic distribution of Lassa fever in West Africa. Adapted from Emergencies—Lassa fever, WHO, Geographic distribution of Lassa fever in west African affected countries, 1969–2018, Copyright 2018.

Figure 2

Bayesian chronogram of LASV based on the genomic L segment. LASV sequences of human origin indicated by ovals and sequences of Mastomys natalensis indicated by squares (black squares indicate ‘strain AV’ sequences). This tree was built under the assumption of a molecular clock and is therefore rooted. Source: Kouadio et al. LASV, Lassa fever virus.