Lassa fever is an acute viral hemorrhagic fever caused by the single-stranded RNA Lassa virus (LASV), family Arenaviridae, endemic to West Africa. It is responsible for an estimated 2.7 million infections, ~23,700 hospitalizations, and ~5,000 deaths annually. [1] Approximately 80% of infections are mild or asymptomatic; severe disease develops in ~20% with a case fatality rate of 1% overall but 15–29% among hospitalized patients. [2-3] Over 32 imported cases have been reported in non-endemic countries, one-third of which were fatal. [1]
1. History
- Onset: Gradual (incubation 2–21 days); ask about exact date of symptom onset — ribavirin efficacy drops sharply after day 6 of illness [3-4]
- Key HPI questions:
- Travel to or residence in West Africa (Nigeria, Liberia, Guinea, Sierra Leone) within the past 21 days [5]
- Contact with rodents (Mastomys natalensis), their excreta, or consumption of rodent-contaminated food [2]
- Contact with a known or suspected Lassa fever case or their body fluids [2]
- Healthcare worker exposure (nosocomial risk) [2]
- Funeral attendance in endemic areas [5]
- Symptom characterization: Anorexia (81%), severe fatigue/weakness (72%), fever, headache, nausea/vomiting (44%), sore throat, myalgia, chest pain, cough, diarrhea [1]
- Important negatives: Notably, unusual bleeding occurs in <10% of prospectively identified cases and is more common in fulminant/late disease. Absence of fever does not exclude Lassa fever [1]
2. Alarm Features
- Mental status changes and seizures — strongly associated with mortality [1]
- Acute kidney failure, hyperkalemia, metabolic acidosis — more frequent in fatal cases [1]
- Hemorrhage (mucosal bleeding, hematemesis, melena) — present in ~10–33% of cases; associated with mortality [1]
- Hypotension and shock
- Respiratory distress and facial/neck edema [2][6]
- High viral load (low Ct values <22 on RT-PCR) — strongly predictive of death [1]
- Absent or muted IgM/IgG antibody response during illness — associated with fatal outcome [1]
- Elevated creatinine that fails to normalize — 62% case fatality vs. 0% in those whose creatinine normalized [7]
3. Medications
- Ribavirin (IV preferred): Standard treatment, though robust evidence of efficacy is lacking. Historically associated with reduced mortality when given within the first 6 days of illness [3][8]
- Dosing: IV 100 mg/kg loading dose on day 1 → 25 mg/kg/day on days 2–5 → 12.5 mg/kg/day on days 6–10 [9]
- Dose adjustment required in renal impairment [7]
- Side effects: Hemolytic anemia (monitor CBC); teratogenic — contraindicated in pregnancy (though may be considered given high maternal mortality from Lassa fever) [10]
- Favipiravir: Has shown efficacy in macaque models; used in combination with ribavirin in case reports [3][11]
- Investigational agents: Arevirumab-3 (monoclonal antibody), losmapimod, and other candidates are in early development [11]
- Dexamethasone: Case reports of adjunctive use for concomitant hyperinflammation [12]
- Contraindicated: Avoid nephrotoxic agents (e.g., gentamicin, aminoglycosides) [7]
- Post-exposure prophylaxis: Oral ribavirin for high-risk contacts per CDC guidelines [13]
4. Diet
- Aggressive oral or IV rehydration — fluid and electrolyte replacement is a cornerstone of supportive care [10]
- Anorexia is the most common symptom (81%); nutritional support and small frequent meals are important [1]
- No specific dietary triggers; however, consumption of rodent-contaminated food is a transmission route and should be addressed in endemic settings [2]
5. Review of Systems
- Constitutional: Fever, malaise, severe fatigue, anorexia, weight loss
- HEENT: Sore throat, pharyngitis, facial swelling, hearing loss/deafness (may occur acutely or during recovery — a hallmark feature) [1][6]
- GI: Nausea, vomiting, diarrhea, abdominal pain
- Respiratory: Cough, dyspnea, respiratory distress
- Cardiovascular: Chest pain, hypotension
- Neurologic: Headache, altered mental status, seizures, encephalopathy
- Musculoskeletal: Myalgia, back pain
- Hematologic: Unusual bleeding or bruising (late finding)
- Renal: Decreased urine output, flank pain
6. Collateral History and Family History
- Household contacts: Identify all persons with direct contact with the patient's body fluids; classify by risk level (high, medium, low) [13]
- Occupational exposure: Farmers (especially female farmers, aOR 2.43) and artisans have higher odds of infection [14]
- Community context: Recent Lassa fever cases in the area, rodent infestation in the home
- No known hereditary susceptibility, but muted humoral immune response may be a factor in severe disease [1]
- Pregnancy status: Lassa fever carries extremely high maternal and fetal mortality (up to 80% fetal loss in third trimester)
7. Risk Factors
- Geographic: Residence in or travel to endemic West Africa (Nigeria, Liberia, Guinea, Sierra Leone, and expanding areas including Benin, Ghana, Togo, Mali) [2][15]
- Seasonal: Peak incidence during the dry season (January–March in Nigeria) [14]
- Occupational: Farmers, artisans, religious leaders [14]
- Age: 40–49 years had highest odds of positivity; 43% of cases in one cohort were pediatric (ages 5–17) [1][14]
- Rodent exposure: Living in areas with Mastomys natalensis infestation, poor sanitation, food storage practices [2]
- Healthcare workers: Nosocomial transmission via body fluid contact [2]
- Immunosuppression: Theoretical increased risk; no published SOT cases, but likely underreported [3]
8. Differential Diagnosis
Early Lassa fever is clinically indistinguishable from many common tropical infections: [1]
- Malaria — most common alternative diagnosis; must be ruled out concurrently with thick/thin smear or RDT [5]
- Typhoid fever — overlapping GI and constitutional symptoms
- Other viral hemorrhagic fevers: Ebola, Marburg, Crimean-Congo hemorrhagic fever, yellow fever, dengue [4]
- Influenza — high fever without rhinorrhea/coryza favors Lassa fever [13]
- Meningococcemia — if petechiae/purpura and meningismus present
- Severe sepsis from bacterial infection
- Rickettsial infections
- Acute HIV seroconversion
- Hepatitis A/E — if transaminitis predominates
Pearl: The combination of fever + GI symptoms (aOR 2.15) and fever + neurological symptoms (aOR 6.37) were the strongest symptom-combination predictors of Lassa fever positivity in a Nigerian surveillance study of >20,000 suspected cases. [14]
9. Past Medical History
- Chronic kidney disease — elevated baseline creatinine worsens prognosis; recovery of renal function is crucial for survival [7]
- Liver disease — elevated AST/ALT at baseline complicates assessment
- Prior Lassa fever — seroprevalence up to 45% in hyperendemic areas; prior infection may confer partial immunity [1]
- Pregnancy — dramatically increases mortality risk
- Immunosuppression — transplant recipients, HIV — theoretical increased risk [3]
10. Physical Exam
- Vitals: Fever (may be absent), tachycardia, hypotension (late/severe), tachypnea
- HEENT: Pharyngitis/exudative pharyngitis, facial and neck edema (characteristic), conjunctival injection
- Chest: Pleural effusion, respiratory distress signs
- Abdomen: Tenderness, hepatomegaly
- Skin: Petechiae, ecchymoses, mucosal bleeding (late finding, <10% early) [1]
- Neuro: Altered mental status, tremor, seizures, encephalopathy — ominous signs [1]
- Hearing: Sensorineural hearing loss (may be unilateral or bilateral) [6]
11. Lab Studies
- Confirmatory: LASV RT-PCR (plasma) — clinical diagnostic standard; turnaround <12 hours where available [1][3]
- Antigen detection: LASV antigen ELISA or Pan-Lassa RDT (83–95% sensitivity, 93–100% specificity) — useful for point-of-care in endemic settings [2][16-17]
- Serology: LASV-specific IgM and IgG — IgG early in illness may help rule out acute infection; absent IgM/IgG response during illness is a poor prognostic sign [1][18]
- Routine labs:
- CBC (leukopenia, thrombocytopenia, anemia — especially with ribavirin)
- BMP/CMP: Creatinine (elevated = poor prognosis), hyperkalemia, metabolic acidosis [1][7]
- AST/ALT — transaminitis common; elevated AST associated with mortality [7]
- Coagulation studies (PT/INR, fibrinogen)
- Blood cultures (to rule out bacterial sepsis)
- Malaria smear/RDT — must be sent concurrently; co-infection is common [5]
- Blood glucose, lactate
- Viral isolation in cell culture remains the gold standard but requires BSL-4 facilities and is not clinically practical [3]
12. Imaging
- Chest X-ray: Pleural effusions, pulmonary edema, ARDS findings in severe cases
- Abdominal ultrasound: Hepatomegaly, ascites, pericardial effusion
- CT head: If altered mental status or seizures — to evaluate for cerebral edema or hemorrhage
- Imaging is not diagnostic for Lassa fever and is used primarily to assess complications and severity
13. Special Tests
- Pan-Lassa Rapid Diagnostic Test (RDT): Point-of-care lateral flow immunoassay detecting LASV antigen; 83–90% sensitivity, 93–100% specificity; 100% sensitivity for samples with Ct <22 [2][17]
- LASV antigen ELISA: 95% sensitivity, 97% specificity using recombinant antigens [16]
- Viral load quantification: Ct values on RT-PCR serve as a prognostic marker — lower Ct = higher viral load = worse prognosis [1]
- Audiometry: For assessment of sensorineural hearing loss during recovery
14. ECG
- No pathognomonic ECG findings
- Monitor for hyperkalemia-related changes (peaked T waves, widened QRS, sine wave) — hyperkalemia was more frequent in fatal cases [1]
- Myocarditis has been described in severe VHFs; monitor for ST changes, arrhythmias
- Continuous telemetry recommended in critically ill patients
15. Assessment
Lassa fever presents on a spectrum from asymptomatic (80%) to fulminant multiorgan failure. Early disease is non-specific and mimics malaria, typhoid, and other febrile illnesses, making clinical diagnosis alone unreliable. [1] Key prognostic stratification:
- Mild disease: Fever, malaise, anorexia, myalgia — majority of cases
- Moderate disease: Persistent vomiting, pharyngitis, facial edema, hearing loss
- Severe disease: Hemorrhage, hypotension, respiratory distress, encephalopathy, renal failure, metabolic acidosis — CFR 15–62% depending on organ involvement [1][7]
- Mortality predictors: High viral load (low Ct), absent antibody response, renal failure that does not resolve, elevated AST, mental status changes [1][7]
16. Treatment Plan
Initial stabilization
- Strict contact and droplet precautions with appropriate PPE (see Disposition) [6]
- Aggressive IV fluid resuscitation and electrolyte correction (especially potassium) [10]
- Treat concurrent malaria if smear/RDT positive [9]
Antiviral therapy
- IV ribavirin — initiate as early as possible, ideally within 6 days of symptom onset [3]
- Loading dose: 100 mg/kg IV on day 1
- Days 2–5: 25 mg/kg/day IV
- Days 6–10: 12.5 mg/kg/day IV [9]
- Monitor for hemolytic anemia; adjust dose in renal impairment
- Note: Robust evidence of efficacy is lacking; a systematic review found all supporting studies at critical or serious risk of bias [8]
Supportive care
- Blood transfusion for significant anemia/hemorrhage
- Oxygen therapy, mechanical ventilation for respiratory failure
- Renal replacement therapy for acute kidney injury — recovery of renal function is crucial for survival [7]
- Antipyretics, analgesics, antiemetics
- Seizure management with benzodiazepines
Pregnancy: Extremely high fetal mortality; delivery of the fetus has been associated with improved maternal survival in some reports. Ribavirin is teratogenic but may be considered given the high maternal CFR. [10]
17. Disposition
All confirmed or suspected cases require admission with strict isolation: [6][13]
- Isolation: Single-patient room with private bathroom, door closed [6]
- PPE for stable patients without bleeding/vomiting/diarrhea: Disposable fluid-resistant gown, full face shield, facemask, double gloves with extended cuffs [6]
- PPE for unstable/hemorrhagic patients: Impermeable gown or coveralls, PAPR or N95 respirator, double gloves, boot covers, apron [6]
- Minimize personnel entering the room; maintain a log of all entrants [6]
- Immediately notify local/state health department and CDC Viral Special Pathogens Branch [3][6]
- ICU admission for hemodynamic instability, respiratory failure, renal failure, altered mental status, or active hemorrhage
- Contact tracing: Identify and risk-stratify all contacts; 21-day monitoring period; high-risk contacts should receive oral ribavirin prophylaxis and be isolated until 2 days of prophylaxis completed [13][19]
18. Follow Up / Return Precautions
- Sensorineural hearing loss occurs in up to 25–30% of survivors and may be permanent — arrange audiometry during convalescence [6]
- LASV RNA may persist in plasma ≥15 days from symptom onset despite ribavirin treatment; viral persistence in semen and other body fluids has been documented [1]
- Contacts: 21-day monitoring from last exposure; any fever >38.3°C without rhinorrhea/coryza should prompt immediate evaluation and isolation [13]
- Return precautions for discharged survivors:
- Avoid unprotected sexual contact until viral clearance confirmed
- Return immediately for recurrent fever, bleeding, confusion, decreased urine output, or new hearing loss
- Expected recovery: Most survivors recover over 1–3 weeks; fatigue and hearing loss may persist for months
- Psychological support: Consider for survivors and healthcare workers involved in care
References
1. Lassa Fever Symptomatology, Viral Dynamics, and Host Immune Response (PREPARE): A Prospective, Observational Cohort Study in Liberia. — Wohl DA, Pewu C, Lee C, et al. The Lancet. Infectious Diseases. 2026.
2. Field Evaluation of Validity and Feasibility of Pan-Lassa Rapid Diagnostic Test for Lassa Fever in Abakaliki, Nigeria: A Prospective Diagnostic Accuracy Study. — Elsinga J, Sunyoto T, di Stefano L, et al. The Lancet. Infectious Diseases. 2024.
3. Arenaviruses and West Nile Virus in Solid Organ Transplant Recipients: Guidelines From the American Society of Transplantation Infectious Diseases Community of Practice. — Anesi JA, Silveira FP. Clinical Transplantation. 2019.
4. Lassa Fever: Epidemiology, Clinical Features, Diagnosis, Management and Prevention. — Asogun DA, Günther S, Akpede GO, Ihekweazu C, Zumla A. Infectious Disease Clinics of North America. 2019.
5. Approach to Fever in the Returning Traveler. — Thwaites GE, Day NP. The New England Journal of Medicine. 2017.
6. Post-Travel Evaluation to Rule Out Viral Special Pathogen Infection. — Catherine Brown, Mary J. Choi, Susan McLellan, and Trevor Shoemaker CDC Yellow Book. 2025.
7. Clinical and Laboratory Predictors of Lassa Fever Outcome in a Dedicated Treatment Facility in Nigeria: A Retrospective, Observational Cohort Study. — Okokhere P, Colubri A, Azubike C, et al. The Lancet. Infectious Diseases. 2018.
8. Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1. — Cheng HY, French CE, Salam AP, et al. Emerging Infectious Diseases. 2022.
9. Factors Associated With Progression to Death in Patients With Lassa Fever in Nigeria: An Observational Study. — Strampe J, Asogun DA, Speranza E, et al. The Lancet. Infectious Diseases. 2021.
10. Standard of Care for Viral Haemorrhagic Fevers (VHFs): A Systematic Review of Clinical Management Guidelines for High-Priority VHFs. — Rigby I, Michelen M, Dagens A, et al. The Lancet. Infectious Diseases. 2023.
11. Contemporary and Emerging Pharmacotherapeutic Agents for the Treatment of Lassa Viral Haemorrhagic Fever Disease. — Joseph AA, Fasipe OJ, Joseph OA, Olatunji OA. The Journal of Antimicrobial Chemotherapy. 2022.
12. Two Cases of Lassa Fever Successfully Treated With Ribavirin and Adjunct Dexamethasone for Concomitant Infections. — Okogbenin S, Erameh C, Okoeguale J, et al. Emerging Infectious Diseases. 2022.
13. Lassa Fever in the United States. — Holmes GP, McCormick JB, Trock SC, et al. The New England Journal of Medicine. 1990.
14. Predictors of Lassa Fever Diagnosis in Suspected Cases Reporting to Health Facilities in Nigeria. — Ochu CL, Ntoimo L, Onoh I, et al. Scientific Reports. 2023.
15. Lassa Virus Circulating in Liberia: A Retrospective Genomic Characterisation. — Wiley MR, Fakoli L, Letizia AG, et al. The Lancet. Infectious Diseases. 2019.
16. Field Validation of Recombinant Antigen Immunoassays for Diagnosis of Lassa Fever. — Boisen ML, Hartnett JN, Shaffer JG, et al. Scientific Reports. 2018.
17. Field Evaluation of a Pan-Lassa Rapid Diagnostic Test During the 2018 Nigerian Lassa Fever Outbreak. — Boisen ML, Uyigue E, Aiyepada J, et al. Scientific Reports. 2020.
18. Diagnosis and Clinical Virology of Lassa Fever as Evaluated by Enzyme-Linked Immunosorbent Assay, Indirect Fluorescent-Antibody Test, and Virus Isolation. — Bausch DG, Rollin PE, Demby AH, et al. Journal of Clinical Microbiology. 2000.
19. Infection Prevention and Control Measures for Emerging Infectious Disease: Lessons Learned From the First Case of Imported Lassa Fever in China. — Peng Y, Wang Y, Li S, et al. Antimicrobial Resistance and Infection Control. 2025.