Old World Arenaviruses (Lassa and Lujo viruses)

Boston University
Research Occupational Health Program (ROHP)
617-358-7647

Agent

Lassa virus and Lujo virus are segmented, negative-sense RNA viruses, belonging to the family Arenaviridae.
Lassa virus can cause Lassa fever, which presents with a range of clinical manifestations, spanning from asymptomatic to severe hemorrhagic disease. Limited clinical information is available on Lujo virus which can cause Lujo hemorrhagic fever (LUHF). Both viruses are of zoonotic origin and transmitted mainly by contact with infected rodents. For both viruses, person-to-person transmission occurs rarely and has often been associated with nosocomial clusters.

Disease/Infection

Lassa Fever
Lujo hemorrhagic fever (LUHF)

Pathogenicity

Lassa fever: up to 80% of the cases are asymptomatic. Case fatality rate is 15 to 20% in hospitalized patients and 1-2% of all infected individuals.
LUHF case fatality rate has been reported to be up to 80%.

Risk Group/BSL
Risk group 4
Biosafety level: BSL4

Modes of Transmission

Host Range/Reservoir
Rodents. Humans are accidental hosts.

Symptoms
Lassa fever can be asymptomatic in up to 80% of those infected. Symptomatic cases can range from mild febrile illness with headache and malaise to severe hemorrhagic fever with multi organ failure. In severe illness, there can be rapid decompensation with respiratory, neurological and circulatory collapse.
LUHF resembles severe Lassa fever presentation.

Pregnancy loss is associated with infection in pregnant women with either virus.

Incubation Period
Lassa fever: 5 to 21 days
LUHF: 7 to 13 days

Viability
Lassa and Lujo viruses are structurally very similar. Reagents that inactivate Lassa virus will also inactivate Lujo virus.

Disinfectants: Lassa virus is susceptible to 0.5% sodium hypochlorite, phenolic compounds, 3% acetic acid (pH 2.5), lipid solvents and detergents such as SDS, formaldehyde and paraformaldehyde fixation, formaldehyde fumigation, and β-propiolactone.
Physical inactivation: Lassa virus is by heating serum for 1 hour at 60oC, gamma irradiation, UV irradiation, autoclaving, incineration, and/or boiling

Survival Outside Host
Lassa virus is stable as an aerosol. When kept in the dark at room temperature, viral particles are infectious for several days. Viral load decreases by 4 log10 in 10 days. Reduction of viral load to 37% of the burden occurs in 25 hours.

Information for Lab Workers

Laboratory PPE

One-piece positive pressure ventilated suit with life support system is utilized. Long sleeve scrubs will be worn under the positive pressure suit with inner gloves providing added protection against outer glove tear.

Containment

All work with infectious Lassa and Lujo viruses must be performed in BSL-4/ABSL-4 containment.

PRIMARY HAZARDS:

Accidental parenteral inoculation, respiratory exposure to infectious droplets, and/or direct contact with broken skin or mucous membranes.

SPECIAL HAZARDS:

Work with, or exposure to, infected non-human primates, rodents, or their carcasses represents a risk of human infection; use of sharps when handling virus-containing material.

In Case of Exposure/Disease

Immediately after exposure, lab workers should follow the HIGH AND MAXIMUM CONTAINMENT MEDICAL INCIDENT RESPONSE PLAN (ERP C.1) as provided on site and during training.

• For all lab exposures which involve BSL-4 pathogens (needle sticks, punctures, cuts, scratches, etc.) and for all medical events which require immediate evaluation and treatment (traumatic injury, heart attack, stroke, seizure, etc.):
  • Medical Campus: call or have a coworker call the Control Center at 617-414–6666. You will be referred to or transported to the appropriate health care location by the emergency response team.
  • The Control Center operator will activate a communication tree which includes the BU Research Occupational Health Program (ROHP) Officer will help guide the response.
• To reach the ROHP directly use the 24/7 hour number (617-358-ROHP (7647)).
• You will be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you the appropriate health care location.
• Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
• Present the Medical Surveillance Card that every BSL-4 researcher has been provided by ROHP, this wallet size card identifies the agents that the researcher works with; provide the ID card to the treating physician.

Vaccination

There are no FDA approved vaccinations for either virus.

Information for First Responders/Medical Personnel

Public Health Issues

After exposure: Immediately after an exposure to Lassa or Lujo virus, the lab worker is not considered infectious. He/she can be cared for with standard PPE. On campus exposures will be escorted directly from NEIDL triage room to the Special Pathogens Unit (SPU) at Boston Medical Center (BMC) where lab workers will be received by a team of physicians and nurses. In case of a lab worker presenting to BMC ED or other outside medical facility, either the exposed or the caring physicians should immediately contact ROHP for further instructions.

In case of (suspected) illness: Lab worker should contact ROHP directly and when possible, transport will be arranged to bring the patient to BMC’s Patient Isolation Unit. Patient should prevent close contact with household members pending evaluation, if possible. If the worker presents to BMC ED or other outside medical facility, caring physicians should contact ROHP for further instructions and ROHP will consult infectious diseases specialists at SPU.

Person-to-person transmission is reported via close personal contact with an infected individual or their body fluids during the late stages of the infection. PPE requirements for care of this patient are listed below.

PPE: SPU staff use advanced PPE including coveralls, fluid proof aprons, PAPR’s, and double gloves. CDC recommendations: Airborne, Droplet Precautions plus Contact Precautions, with face/eye protection, emphasizing safety sharps and barrier precautions when blood exposure likely. Avoid aerosol-generating procedures.

Other guidance for outside providers: No blood work should be drawn until contact is made with ROHP.

Specimen should be handled with extreme care and enclosed in appropriate shatter-proof and leak-proof packing for transport to lab. Diagnostic laboratory staff should be notified of suspicion of infection, and tests should be performed under proper containment. Please contact ROHP immediately for further details.

Public health officials will be notified.

Diagnosis/Surveillance

Lassa and Lujo virus can be detected by PCR in bodily fluids about 2- 13 days after onset.

Acute and convalescent serologies are to be drawn.

Potential alternate diagnoses with similar presentation should be considered, such as influenza or other respiratory viruses.

First Aid/Post Exposure Prophylaxis

Standard management of potential exposure to Lassa and Lujo virus is solely based on observation, potential isolation and with symptomatic and supportive treatments. Ribavirin is used in post exposure prophylaxis of Lassa fever.

Additional medical countermeasures maybe available post exposure through CDC and public health bodies and will be done in coordination with the SPU program.

Treatment

Treatment is aggressive supportive care, and is directed at maintaining renal function and electrolyte balance, addressing coagulopathy and combating hemorrhage and shock. Ribavirin has been used to treat infection with both viruses with benefit. In Lassa, most benefit with ribavirin is in first 7 days of illness.

Transfusion of convalescent serum may be beneficial. No treatments are FDA approved for either agent.

Medical countermeasures maybe available during treatment through CDC and public health bodies and will be done in coordination with the SPU program.

Survivors of both diseases may shed virus for weeks after infection in urine and semen.

References

Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition. US Government Printing Office, Washington, 2007.

Lassa Fever Fact Sheet, CDC. https://www.cdc.gov/vhf/lassa/

Lujo Hemorrhagic Fever Fact Sheet, CDC https://www.cdc.gov/vhf/lujo/index.html

Control of Communicable Diseases Manual. David L. Heymann. Washington DC, USA: American Public Health Association Press, 19th edition 2008

Public Health Agency of Canada. Material Safety Data Sheets. Infectious Substances. Lassa virus. http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/lassa-eng.php

Siegel JD, Rhinehart E, Jackson M, Chiarello L. 2007. Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings. American journal of infection control 2007 Dec;35 (10 Suppl 2):S65-164.

Sagripanti, J-L. Rom, AM, Holland, LE. 2010. Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces. Arch Virol 15 (12): 2035-9.