Lassa fever: A comprehensive review of virology, clinical management, and global health implications

Table 1 Clinical manifestations of Lassa fever

Stage	Duration	Symptoms	Description
Incubation period	Days 2-21	Typical asymptomatic	Virus is replicating; no external signs
Early stage	Days 1-6	Fever, sore throat, muscle aches, chest pain, vomiting, diarrhea	Resembles malaria or typhoid; diagnostic confusion common
Progression to severe	Days 7-14	Facial swelling, mucosal bleeding, pleural/pericardial effusion, hypotension, respiratory distress	Indicates systemic involvement and vascular leakage
Neurological phase	Advanced (≥ day 10)	Confusion, seizures, encephalopathy	May progress to multiorgan failure
Complications	Variable	Hearing loss (up to 30% of survivors), myocarditis, chronic fatigue, spontaneous abortion (pregnancy)	Hearing loss may be permanent; pregnant females are at very high risk
Case fatality risk	Severe cases	15%-20% in hospitalized patients	Higher in late-presenting cases and pregnant females
Recovery phase	After 2-3 weeks	Weakness, fatigue, dizziness, depression	Long recovery; some may need audiological or psychological follow-up

Table 2 Diagnostic techniques for Lassa fever

Method	Type	Sample	Turnaround time	Advantages	Limitations
Reverse transcription PCR	Molecular	Blood or tissue	Few hours	Highly sensitive and specific; early detection	Requires specialized labs and trained personnel
ELISA (IgM, IgG, antigen)	Serological	Serum or plasma	1-2 days	Useful for acute and retrospective diagnosis	Limited sensitivity in early stages
Virus isolation	Culture (definitive)	Blood or tissue	Several days	Confirmatory; research reference standard	Requires Biosafety Laboratory-4 facility; high biosafety risk
Next-generation sequencing	Genomic surveillance	Blood or tissue	Variable	Tracks evolution and strain diversity	Expensive and technology-intensive
Rapid diagnostic tests	Immunochromatography	Blood sample	15-30 min	Fast, suitable for remote settings	Still under development and validation
Supportive laboratory indicators	Clinical chemistry	Blood, urine	Few hours	Suggestive (e.g., elevated aspartate aminotransferase, thrombocytopenia)	Not confirmatory; supportive only

Table 3 Treatment and management strategies for Lassa fever

Component	Objective	Key interventions
Antiviral therapy	Inhibit viral replication	Intravenous ribavirin (ideally within first 6 days); oral ribavirin for mild or remote settings
Supportive care	Stabilize and support vital functions	Intravenous fluids and electrolyte balance; nutritional support; oxygen therapy; antipyretics; blood transfusions
Severe case management	Manage complications and prevent multiorgan failure	Antibiotics for secondary infections; dialysis for renal failure; ventilation support; seizure control
Pregnancy-specific care	Reduce maternal and fetal mortality	Specialized obstetric care; consider therapeutic abortion in advanced pregnancy with severe infection
Post-recovery care	Promote long-term recovery and quality of life	Audiology screening and support; psychological counseling; physical rehabilitation and follow-up

Table 4 Prevention and control strategies for Lassa fever

Level	Key strategies
Community level	Promote hygiene and rodent-proof food storage; educate communities through culturally appropriate materials; improve waste management practices; discourage handling and consumption of rodents
Healthcare level	Mandate personal protective equipment use; ensure patient isolation; train healthcare workers in infection prevention; sterilize equipment; provide obstetric care for pregnant females
National level	Strengthen disease surveillance; expand laboratory networks; integrate Lassa fever control into national health policies; ensure emergency preparedness
International level	Support cross-border data sharing; invest in vaccine and therapeutic research; collaborate with global health organizations (e.g., World Health Organization, Coalition for Epidemic Preparedness Innovations); improve access to rapid diagnostics and antivirals

Table 5 Overview of Lassa fever vaccine candidates: Platforms, clinical stages, and immune responses

Vaccine platform	Stage	Immune response	Protection (models)
VSV-based (VSVΔG -LASVGPC)	Phase I/II	Strong humoral and T cell	Guinea pigs, NHPs
Reassortant ML29	Preclinical	IgG, IFN-γ T cells	Guinea pigs, NHPs
DNA-based (INO-4500)	Phase I	IgG, neutralizing Abs	Guinea pigs, NHPs
Measles virus vector (MV-LASV)	Phase I	CD4/CD8 T cells, IgG	NHPs
Vaccinia virus vector	Preclinical	Mixed	Guinea pigs, NHPs
ChAdOx1 adenovirus vector	Preclinical	T cell and IgG	Mice, Guinea pigs
mRNA-based	Preclinical	Fc-mediated + T cell	Guinea pigs, mice
Yellow fever 17D vector	Preclinical	IgG	Guinea pigs
VEEV RNA replicon	Preclinical	T cell mediated	Guinea pigs
Rabies virus vector	Preclinical	ADCC, IgG	Guinea pigs, NHPs
Protein nanoparticle	Preclinical	Neutralizing Abs	Guinea pigs
Virus-like particles	Preclinical	Neutralizing Abs	Rabbits

NHPs: Non-human primates; VSV: Vesicular stomatitis virus; ADCC: Antibody-dependent cellular cytotoxicity; IFN: Interferon.

Table 6 Comparative overview of Marburg, Ebola and Lassa viruses

Feature	MARV	EBOV	Lassa virus
Virus family	Filoviridae	Filoviridae	Arenaviridae
First identified outbreak	1967: Marburg and Frankfurt, Germany and Belgrade, Serbia	1976: Yambuku, Democratic Republic of the Congo and Nzara, Sudan	1969: Lassa, Nigeria
Origin of outbreaks	African green monkeys imported from Uganda	Suspected zoonotic transmission with bats as reservoirs and transmission to humans or other primates	Contact with Mastomys natalensis rodents
Reservoir hosts	Egyptian fruit bat (Rousettus aegyptiacus) suspected	Fruit bats (Pteropodidae family), particularly Eidolon helvum	Multimammate rats (Mastomys natalensis)
Case fatality rate	24%-90%, depending on outbreak and case management	25%-90%, depending on outbreak and case management	1% overall; up to 15%-20% in hospitalized patients; higher in pregnant females
Geographic distribution	Primarily sub-Saharan Africa	Primarily sub-Saharan Africa	West Africa: Nigeria, Sierra Leone, Liberia, Guinea, others
Symptoms	Hemorrhagic fever, severe malaise, high fever, vomiting, diarrhea, organ dysfunction	Similar to MARV: Hemorrhagic fever, malaise, vomiting, diarrhea, multiorgan failure	Fever, sore throat, vomiting, bleeding, neurological complications
Transmission	Direct contact with bodily fluids (e.g., blood, saliva, urine) of infected persons or animals	Direct contact with bodily fluids of infected persons or animals, contaminated surfaces	Exposure to rodent excreta; human-to-human via body fluids
Laboratory diagnosis	PCR, ELISA, virus isolation	PCR, ELISA, virus isolation	PCR, ELISA (IgM, IgG), virus isolation
Vaccines	No approved vaccine (research ongoing)	Approved vaccines available (e.g., recombinant vesicular stomatitis virus-ZEBOV for Zaire strain)	No approved vaccine (clinical trials ongoing)
Notable outbreaks	Angola (2004-2005), Democratic Republic of the Congo (1998-2000)	West Africa (2014-2016), Democratic Republic of the Congo (multiple outbreaks)	Nigeria (multiple outbreaks annually), Sierra Leone epidemics

EBOV: Ebola virus; MARV: Marburg virus.