Lassa Fever: Causes, Symptoms, and Prevention

 

Table of Contents

• Introduction to Lassa Virus
• Structure of Lassa Virus
• Genome of Lassa Virus
• Epidemiology of Lassa Virus
• Transmission of Lassa Virus
• Replication of Lassa Virus
• Pathogenesis of Lassa Virus
• Clinical manifestations of Lassa Virus
• Diagnosis of Lassa Virus
• Treatment of Lassa Virus
• Prevention and control of Lassa Virus

Introduction to Lassa Virus

Lassa virus is a single-stranded RNA virus that belongs to the Arenaviridae family. It is the causative agent of Lassa fever in humans. This virus is endemic to parts of West Africa, particularly affecting countries such as Nigeria, Sierra Leone, Liberia, and Guinea. Multimammate rats are the primary carriers of the virus, and humans can become infected through contact with the rodents' contaminated excreta or bodily fluids. The symptoms of Lassa fever vary from mild to severe, with some cases resulting in multi-organ failure and death.

Structure of Lassa Virus

• The virus is a single-stranded RNA virus belonging to the Arenaviridae family.
• The virion consists of spherical particles with an average diameter of 90–110 nm.
• Lassa virus is enveloped in lipid with glycoprotein spikes protruding from the outer surface.
• The glycoproteins on the surface of the virion form T-shaped spikes extending 7–10 nm from the envelope.

Genome of Lassa Virus

• It contains two species of RNA, the small and large units, each with two genes at opposite ends that do not overlap.
• The small unit has some double-stranded areas that form stem-loop structures.
• The large species of RNA encodes for the Z and L proteins at the 5’ and 3’ ends, respectively.
• The small species of RNA encodes for glycoprotein and nucleoprotein at the 5’ and 3’ ends, respectively.
• Lassa virus consists of four lineages, with a strain variation of 27% in relation to their nucleotides and 15% in relation to their amino acids.
• The large segment encodes a small zinc-binding protein (Z) that regulates transcription and replication, and the RNA polymerase (L).
• The small segment encodes the nucleoprotein (NP) and the surface glycoprotein precursor (GP, also known as the viral spike), which is proteolytically cleaved into the envelope glycoproteins GP1 and GP2 that bind to the alpha-dystroglycan receptor and mediate host cell entry.
• The gene that encodes the nucleoprotein is 1,710 nucleotides long, and the protein has 569 amino acids.
• The gene that encodes the glycoprotein is 1,473 nucleotides long.

Epidemiology of Lassa Virus

• The Lassa virus was first isolated in 1969 and identified as the causative agent of Lassa fever in a small town called Lassa in northeastern Nigeria.
• Lassa fever is endemic in parts of West Africa, including Sierra Leone, Liberia, Guinea, and Nigeria. Neighboring countries are also at risk due to the widespread distribution of the multimammate rat (Mastomys natalensis), the animal vector for the Lassa virus.
• Lassa virus consists of four lineages, three of which are located in Nigeria, while the fourth can be found in Guinea, Liberia, and Sierra Leone.
• The annual number of Lassa virus infections in West Africa is estimated to be between 100,000 and 300,000, resulting in approximately 5,000 deaths.
• In some areas of Sierra Leone and Liberia, 10%-16% of people admitted to hospitals each year have Lassa fever, highlighting the significant impact of the disease on the region's population.
• There was a recent Lassa fever outbreak in Nigeria in 2024.

Transmission of Lassa Virus

• Humans primarily contract the virus through contact with the contaminated excreta of Mastomys natalensis rodents (commonly known as the multimammate rat), the natural reservoir of the virus.
• The virus can enter the human body through cuts and scratches or be inhaled via dust particles in the air.
• Secondary transmission between humans occurs through direct contact with infected blood or bodily secretions.

Replication of Lassa Virus

• The Lassa virus enters the host cell via the cell-surface receptor alpha-dystroglycan (alpha-DG), which serves as a versatile receptor for extracellular matrix proteins.
• Upon entry into the cell through alpha-dystroglycan-mediated endocytosis, the low-pH environment triggers pH-dependent membrane fusion, releasing the viral ribonucleoprotein (RNP) complex into the cytoplasm.
• Once inside the cytoplasm, the viral RNA is unpacked, initiating replication and transcription.
• During replication, both S and L RNA genomes synthesize antigenomic S and L RNAs, from which genomic S and L RNAs are subsequently synthesized.
• Both genomic and antigenomic RNAs are required for transcription and translation.
• S RNA encodes the glycoprotein (GP) and nucleoprotein (NP), while L RNA encodes the Z and L proteins.
• Primary transcription first transcribes mRNAs from the genomic S and L RNAs, coding for NP and L proteins, respectively.
• Transcription terminates at the stem-loop (SL) structure within the intergenomic region.
• Arenaviruses employ a cap-snatching strategy to obtain cap structures from cellular mRNAs, mediated by the endonuclease activity of the L polymerase and the cap-binding activity of NP.
• Antigenomic RNA transcribes viral genes GPC and Z, encoded in the genomic orientation, from the S and L segments, respectively.
• After translation, GPC undergoes post-translational modification in the endoplasmic reticulum.
• GPC is cleaved into GP1 and GP2 at a later stage in the secretory pathway.
• The cleaved glycoproteins are incorporated into the virion envelope as the virus buds and is released from the cell membrane.

Pathogenesis of Lassa Virus

• When initiating an infection, the Lassa virus attaches to a receptor on the cell surface using the glycoprotein GP-1.
• The virus initially replicates in dendritic cells and macrophage-monocyte cells and is subsequently disseminated throughout the body.
• Infected dendritic cells fail to secrete proinflammatory cytokines, do not upregulate costimulatory molecules such as CD40, CD80, and CD86, and poorly induce T cell proliferation.
• Lassa virus impedes the host’s innate immune response through the activity of its nucleoprotein (NP).
• Patients infected with Lassa virus produce IgM and IgG antibody isotypes.
• Neutralizing antibodies appear months after the acute infection is resolved, and their titers are often low.
• The titers of neutralizing antibodies continue to rise even several months after convalescence, possibly indicating ongoing stimulation of B cells due to low levels of viral persistence.
• Antibodies in seroconverted individuals are specific to the glycoprotein complex (GPC), nucleoprotein (NP), and likely the Z protein.

Clinical manifestations of Lassa Virus

• The incubation period of Lassa fever ranges from 6 to 21 days.
• The clinical effects of Lassa fever can vary widely, from asymptomatic cases to severe multi-organ system failure and death.
• When symptomatic, the disease typically begins gradually with fever, general weakness, and malaise.
• After a few days, symptoms such as headache, sore throat, muscle pain, chest pain, nausea, vomiting, diarrhea, cough, and abdominal pain may develop.
• In severe cases, symptoms can include facial swelling, fluid in the lung cavity, bleeding from the mouth, nose, vagina, or gastrointestinal tract, and low blood pressure.
• In the later stages, shock, seizures, tremor, disorientation, and coma may occur.
• Death from Lassa fever most commonly occurs 10 to 14 days after the onset of symptoms.

Diagnosis of Lassa Virus

• IgM and IgG antibodies, as well as Lassa antigen, can be detected using enzyme-linked immunosorbent serologic assays (ELISA).
• The virus can be identified through reverse transcription PCR (RT-PCR).
• Virus isolation can be performed using cell culture, but this procedure should only be conducted in a high-containment laboratory with stringent laboratory practices.
• Mice and guinea pigs have been evaluated as models for LASV infection.
• Immunohistochemistry, performed on formalin-fixed tissue specimens, can be used for post-mortem diagnosis.

Treatment of Lassa Virus

• Ribavirin is effective only if administered early in the infection, specifically within the first 6 days after the onset of the disease.
• There are currently several Lassa fever vaccine candidates under development, with some showing promise in clinical trials.

Prevention and control of Lassa Virus

• Currently, there is no vaccine available for Lassa fever in humans.
• Prevention strategies focus on promoting good community hygiene to discourage rodents from entering homes.
• Effective measures include storing grain and other foodstuffs in rodent-proof containers, disposing of garbage away from homes, maintaining clean households, and keeping cats to control rodent populations.
• It is important to avoid contact with blood and body fluids when caring for sick individuals.
• In healthcare settings, staff should always adhere to standard infection prevention and control precautions when caring for patients, regardless of their suspected diagnosis.
• These precautions include practicing basic hand hygiene, respiratory hygiene, using personal protective equipment to prevent contact with infected materials, practicing safe injection practices, and following safe burial practices.

References:

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• Centers for Disease Control and Prevention. (2023, January 11). Lassa fever. Centers for Disease Control and Prevention. https://www.cdc.gov/lassa-fever/site.html
• Nigeria Centre for Disease Control and Prevention. (2024, April 10). Update of Lassa Fever Outbreak.
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• CDC. (2020, January 29). Diagnosis of Lassa fever. Centers for Disease Control and Prevention. https://www.cdc.gov/lassa-fever/about/index.html
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• CIDRAP. (2023, June 05). New roadmap addresses Lassa fever, a growing threat to human health. https://hoodline.com/2024/07/university-of-minnesota-s-cidrap-releases-r-d-roadmap-to-combat-lassa-fever-in-west-africa/
• Lassa fever. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/lassa-fever