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Hansen, F. Lassa Virus. Encyclopedia. Available online: https://encyclopedia.pub/entry/9599 (accessed on 05 December 2025).
Hansen F. Lassa Virus. Encyclopedia. Available at: https://encyclopedia.pub/entry/9599. Accessed December 05, 2025.
Hansen, Frederick. "Lassa Virus" Encyclopedia, https://encyclopedia.pub/entry/9599 (accessed December 05, 2025).
Hansen, F. (2021, May 13). Lassa Virus. In Encyclopedia. https://encyclopedia.pub/entry/9599
Hansen, Frederick. "Lassa Virus." Encyclopedia. Web. 13 May, 2021.
Lassa Virus
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This entry is adapted from the peer-reviewed paper 10.3390/microorganisms9040772

Lassa virus (LASV), a member of the Mammarenavirus genus in the Arenaviridae family, is the causative agent of Lassa fever (LF). LASV was originally isolated and described in 1969 after a missionary nurse in Lassa, Nigeria became infected and died from the disease.

Lassa LASV antiviral therapeutic antibody animal model

1. Introduction

Lassa virus (LASV), similar to other arenaviruses, is a negative-strand RNA virus whose enveloped virions are pleiomorphic in nature and range from 40 to 300 nm in diameter [1][2]. Arenavirus genomes consist of two ambisense single-stranded RNA segments referred to as the small (S) and large (L) segments. The 7.2 kb L segment encodes both the viral RNA-dependent RNA polymerase (RdRp) as well as the zinc-binding protein. The 3.4 kb S segment encodes the glycoprotein precursor complex (GPC) along with the nucleoprotein [3]. The GPC is co- and post-translationally cleaved into the signal peptide, GP1, and GP2.

The natural reservoir of LASV is the peridomestic multimammate rodent, Mastomys natalensis (Mastomys). Mastomys are distributed throughout sub-Saharan Africa with multiple identified phylogroups throughout their extensive range [4]. Recent studies have also implicated the rodent species Hylomyscus pamfi and Mastomys erthrocyclus as additional reservoirs of LASV, but their impact on overall disease burden is currently undetermined [5]. LASV spillover from Mastomys into humans is thought to occur via many routes, including direct contact with rodent excreta, inhalation of aerosols containing rodent excreta, through rodent bites, and through rodent handling and consumption [6][7]. Incidence rates of LASV have been correlated to seasonal changes, specifically rainfall, which is believed to correspond to alterations in the interaction between Mastomys and humans [8][9]. Direct human to human transmission, including cases of nosocomial transmission, have also been observed through exposure to the virus stemming from contact with the blood or other bodily fluids from infected individuals [6][9][10][11][12].

An approximate 300,000 to 500,000 LASV infections with an associated 5000 to 10,000 deaths, occur annually across sub-Saharan west Africa, with the vast majority of viral burden occurring in Nigeria, Sierra Leone, Liberia, and Guinea [8][13][14]. Consistent with these numbers, it is estimated that 80% of infections result in sub-clinical infection or mild illness, while 20% of infections result in more severe disease that require hospitalization [6]. The case fatality rate from severe/hospitalized cases reaches 15%, with the overall case fatality rate of LF being about 1% [6][11]. The incubation period for LF ranges from 6–21 days. Symptoms of LASV infection can be non-specific and LF is often only considered as a potential cause of illness after exclusion of other diseases such as typhoid fever and malaria. Early clinical symptoms include weakness, malaise, fever, sore throat, body pains, nausea, vomiting, diarrhea, and cough [6][8]. Late stage clinical manifestations include mucosal and internal bleeding, seizures, coma, disorientation, and deafness. Patients typically succumb to disease within 14 days of initial symptom onset [8].

Currently, off label use of ribavirin, fluid replacement, and dialysis are used for treatment of severe LF [15][16]. Since its initial identification in 1969 about 30 cases of exported LASV have been reported in 9 non-endemic countries. LASV therefore represents a serious exposure risk to healthcare workers and a significant public health concern worldwide [17]. Because of its epidemic potential and the current lack of approved vaccines or treatments, LASV was added to the WHO List of Blueprint Priority Diseases/Pathogens in 2018. Together, the substantial disease burden in endemic countries and continued threat from LASV exportation to non-endemic regions emphasizes the need for a maintained effort to develop countermeasures for LASV and to prepare for potential outbreaks.

2. Lassa Virus Treatment Options

LASV was first described in 1969 and although over 50 years have passed, no treatment has thus far been approved. The burden of LASV on much of West Africa combined with its history of nosocomial human to human transmission events, and potential for transmission to non-endemic countries make it critical that viable treatments be developed to control and prevent LASV outbreaks. This need is underscored by LASV’s designation as a priority pathogen by the WHO in 2018. Supportive treatment including fluid replacement, electrolyte balancing, and oxygen supplementation as well as dialysis, when indicated, are the primary medical interventions for LF cases [6][15][16]. Additionally, ribavirin has been used as an off-label treatment option for LF based on a single clinical trial supporting its efficacy [18]. However, recent re-analysis of results from this study call into question some of the findings [19][20] and the use of ribavirin for LF should be reevaluated. Furthermore, no LASV vaccine has moved beyond the preclinical stage and shown safety or efficacy in humans [21]. Rodent control interventions have shown some success in reducing the abundance of Mastomys (the natural reservoir of LASV) in village settings, but numbers rebound shortly after interventions cease and such interventions can be cost and labor intensive in already impoverished communities [22]. Together, the lack of treatments, vaccines, and rodent control strategies leaves infectious disease and public health responses with extremely limited options for preventing and treating LF.

We have discussed the major LF antiviral options currently in development and compiled the details of their corresponding preclinical and clinical studies. Favipiravir and huMAbs are most promising and likely should replace ribavirin as first choice until efficacy of ribavirin is reevaluated. Favipiravir has shown efficacy in mice, guinea pigs, and NHPs, outperforming ribavirin in all comparative published studies [23][24][25][22]. It has also been proven safe for use against emergency influenza virus with licensure in Japan [26]. Therefore, favipiravir should be urgently moved into clinical trials either as a mono- or combined therapy. Comparison with ribavirin monotherapy would be of scientific interest but seems questionable based on recent efficacy data.

Combination drug therapy is common in other virus infections such as HIV/AIDS and hepatitis C virus and should also be considered for LF. Specifically, treatment combinations that target distinct viral mechanisms should be emphasized and could function to increase overall treatment efficacy and avert the potential development of antiviral resistance by LASV against any one drug. To determine the optimal drug combinations, further mechanistic and preclinical efficacy studies should be performed on promising drug candidates. Combination therapy of favipiravir, which is believed to target the RdRp enzyme [27][28][29], and ribavirin, with multiple proposed mechanisms including inosine monophosphate dehydrogenase inhibition [30][31][32][33], could be considered as they have shown synergistic effects in a LASV rodent model [23]. Stampidine, characterized as a retroviral reverse transcriptase inhibitor [34][35], and ST-193, a viral entry inhibitor of LASV [36], also have mechanisms that would be amendable for combination therapy with one another or with ribavirin and favipiravir. Additionally, glycoprotein targeting huMAbs are strong candidates for both individual and combined therapy.

HuMAb therapy for LF has shown astonishing efficacy in preclinical models. Specifically, the cocktail of huMAbs 8.9F + 12.1F + 37.2D, which provided 100% protection against lethal LASV challenge in cynomolgus macaques even when treatment was delayed until 8 dpi [37], should be considered for clinical trials. A drawback of MAbs are their high specificity with treatment cocktails potentially having to be clade- or even strain-adapted; small drug molecules interfering with the replicase complex likely show a broader efficacy. In addition, huMAb treatments will likely continue to be cost prohibitive for those countries where LASV exerts it greatest burden, highlighting the need for research to reduce the cost of producing huMAb treatments and making them broadly available. Alternatively, combined therapy of favipiravir and immune plasma could be considered due to the protection observed in a previous study in which cynomolgus macaques were treated with a combination of ribavirin and immune plasma [38].

In clinical settings, LF is often only considered after other diagnoses such as typhoid and malaria have been ruled out. The importance of initiating LF treatment early was heavily reinforced in  preclinical studies. These findings emphasize the need for diagnostic infrastructure to rapidly and accurately diagnose LASV infections and allow for the initiation of specific treatments as early as possible.

The current COVID-19 pandemic has emphasized the need for preemptive efforts to establish countermeasures for emerging infectious diseases. LASV, having been notorious for importation through infected individuals, needs to be considered as a pathogen of high priority for future clinical investigation.

References

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