eMedicine Specialties > Infectious Diseases > Viral Infections

Arenaviruses

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Updated: May 15, 2009

Introduction

Background

Arenaviruses are ambistranded ribonucleic acid (RNA) viruses that cause chronic infections in rodents and zoonotically acquired disease in humans. In 1934, the prototypic Arenavirus, lymphocytic choriomeningitis (LCM) virus was first isolated during serial monkey passage of human material that was obtained from a fatal infection in the first documented epidemic of St. Louis encephalitis, a totally unrelated virus. LCM virus was the first recognized cause of aseptic meningitis in humans. Other arenaviruses from South America and Africa are classic causes of viral hemorrhagic fever syndrome. As was recently reported from California and as is observed in other emerging groups of viruses (eg, hantaviruses), newly recognized viruses and niches are observed periodically.¹

Arenaviruses have been divided into 2 groups based on whether the virus is found in the Old World (ie, Eastern Hemisphere) or the New World (ie, Western Hemisphere). LCM virus is the only Arenavirus to exist in both areas but is classified as an Old World virus. The following are the major viruses and the other recognized Arenaviridae listed in relationship to their rodent reservoirs.

Old World Arenaviruses

Lymphocytic choriomeningitis virus

Rodent -Mus musculus and Mus domesticus (ie, house mouse) and Mesocricetus auratus (ie, Syrian hamster)

Location - Europe, Asia, and the Americas

Habitat - Peridomestic, grasslands

Human contact - Primarily within households

Lassa virus^2,3,4

Rodent -Mastomys natalensis (ie, multimammate mouse)

Location - West Africa

Habitat - Savanna, forest clearing

Human contact - Primarily within houses

Mopeia virus

Rodent -M natalensis

Location - Southern Africa

Habitat - Savanna

Human contact - Unclear

Mobala virus

Rodent -Praomys species (ie, soft-furred rat)

Location - Central African Republic

Habitat - Savanna

Human contact - Unclear

Ippy virus

Rodent -Arvicanthus species (ie, Nile grass rat)

Location - Central African Republic

Habitat - Grassland, savanna

Human contact - Unclear

Classic New World Arenaviruses

Junin virus

Rodent -Calomys masculinus (ie, corn mouse), Akodon azarae (ie, grass field mouse), Bolomys obscurus (ie, dark field mouse)

Location - Argentina

Habitat - Grasslands, cultivated fields, and hedgerows

Human contact - Occupational in fields

Machupo virus

Rodent -Calomys callosus (ie, vesper mouse)

Location - Bolivia

Habitat - Peridomestic, grasslands

Human contact - Primarily within houses

Guanarito virus

Rodent -Sigmodon alstoni (ie, cane mouse)

Location - Venezuela

Habitat - Grasslands, brush

Human contact - Within houses

Sabia virus

Rodent - Unknown

Location - Isolated in Brazil

Human contact - Associated with several human cases, including a laboratory worker in Connecticut

Selected Less Common New World Arenaviruses

Tacaribe virus

Rodent -Artibeus species (ie, fruit-eating bat)

Location - Trinidad

Habitat - Tropical forest

Human contact - Unclear

Amapari virus

Rodent -Oryzomys goeldii (ie, rice rat), Neacomys guianae (ie, bristly mouse)

Location - Brazil

Habitat - Tropical forest

Human contact - Unclear

Tamiami virus

Rodent -Sigmodon hispidus (ie, hispid cotton rat)

Location - Florida

Habitat - Grasslands, marsh

Human contact - Unclear

Whitewater Arroyo

Rodent -Neotoma albigula (ie, white-throated wood rat)

Location - California, New Mexico

Habitat - Grasslands

Human contact - Unclear

Other viruses

Flexal virus (Brazil)

Pichinde virus (Columbia)

Latino virus (Bolivia, Brazil)

Parana virus (Paraguay)

Pathophysiology

Arenaviruses are lipid-enveloped, spherical-to-pleomorphic particles ranging in size from 50-300 nm. The envelope that surrounds the virion contains 2 major glycoprotein components (ie, GP1, GP2) that appear as spikelike or clublike projections with variable spacing along the virus lipid coat.

The Arenaviridae generally have been considered negative-sense RNA viruses that contain 2 subgenomic segments referred to as L (large) and S (small) of 2.4 million bases and 1.3 million bases, respectively. The 5' ends of both the L and S strands contain positive-sense RNA; therefore, the viruses are best considered ambisense. Each of the RNA segments consists of 2 nonoverlapped long open reading frames with opposite polarity. The L segment encodes for a Z protein and for the viral RNA-dependent RNA polymerase, and the S segment encodes for the glycoprotein precursors and for the N protein that binds to the positive-sense RNA segments.

A distinguishing characteristic of arenaviruses is the presence of internal granular structures 20-25 nm in size. On electron microscopy, these structures appear sandlike. The virus name (arena) is derived from the Latin root meaning sand. These components are thought to be host cell–derived ribosomes, which are incorporated into the virus during budding. The ribosomal structures are not believed to be essential in virus replication.

Frequency

United States

The number of cases of LCM virus infection is unclear, but a number of clusters have been reported related to pet hamsters or laboratory animals. Recently, 3 fatal cases of infection with a virus similar to Whitewater Arroyo virus were reported in California.

International

Scattered outbreaks of Lassa fever in western Africa and South American hemorrhagic fever occur, representing local public health problems. Public health officials in nonendemic areas must remain vigilant for these infections because imported cases have been described, presumably due to person-to-person spread.⁵

Mortality/Morbidity

Arenaviruses persist in nature by infecting rodents, primarily through a one-virus, one-rodent species relationship. Arenaviruses are transmitted to humans through aerosolization of dried excreta, especially urine that has been deposited in the environment.

• LCM virus: Infection occurs wherever either of the 2 closely related species of the common house mouse (M musculus, M domesticus) exists. The areas include Europe, the Americas, Australia, and Japan. Human infection is more common in rural areas, where a higher rate of infection exists in mice. Sporadic human LCM virus infections have autumn/winter predominance, when mice are more likely to seek human dwellings for shelter and food. Hamsters also can be infected and are more significant disease vectors in laboratory workers and pet owners.
• Lassa virus (ie, Lassa fever): Lassa fever is endemic to West Africa. Originally found in Nigeria, outbreaks have been reported from Sierra Leone, Liberia, and Guinea. Lassa virus was isolated from rodents of the genus Mastomys, members of which aggressively invade houses. Lassa fever is common in the dry season. This viral agent is noteworthy because of its ability to spread from person to person. This also occurs to some degree with South American viruses.^2,3,4
• South American viral hemorrhagic fevers 
  • These are diseases of South American countries, including Argentina, Bolivia, and Venezuela, caused by the viruses Junin, Machupo, and Guanarito, respectively.
  • For Argentine hemorrhagic fever, the main reservoir rodent is C masculinus. This rodent is found in the cornfields, especially from February through May. Therefore, men harvesting corn are particularly at risk. Infectious aerosols are thought to be the most common mode of transmission, but food contamination and direct contact of abraded fingers with blood or tissue from rodents may occur.
  • Bolivian hemorrhagic fever is found in the tropical savanna of the Beni region in northeastern Bolivia. The reservoir rodent is C callosus, which travels freely around this area. Bolivian hemorrhagic fever is commonly found from April to July. Transmission is believed to occur through aerosols from infected rodents or, possibly, through food contaminated by rodenturine.
  • Venezuelan hemorrhagic fever,causedby the Guanarito virus, has the cane mouse Zygodontomys brevicauda as a reservoir. People who have moved to the cleared forest areas for agricultural work are most at risk.

Age

The risk of human acquisition of Arenavirus infection is related to age, race, or sex only to the degree that these variables impact contact with dried rodent urine.

Clinical

History

A short synopsis of some of the historical and clinical points regarding the major Arenavirus illnesses is as follows:

• Lymphocytic choriomeningitis virus
  • This usually benign infection generally begins with fever, myalgia, and headache. Leukopenia and thrombocytopenia are revealed on laboratory studies.
  • The illness can be biphasic.
  • The second febrile period and some of the late complications (see Complications) may be immunologic in origin.
• Lassa fever
  • Most infections due to the Lassa virus are mild or subclinical.
  • Severe multisystem disease is believed to occur in 5-10% of total infections.
  • Incubation period is 7-18 days.
  • Illness begins insidiously with fever, weakness, malaise, joint and/or lumbar pain, cough, and severe headache.
  • In severe cases, illness progresses to include prostration, dehydration, abdominal pain, and facial or neck edema. Serum aminotransferases may be elevated. Note that Lassa fever stands alone among causes of viral hepatitis to have aspartate aminotransferase (AST) levels substantially higher than alanine aminotransferase (ALT) levels. This pattern has been classic for alcoholic hepatitis.
  • Lymphopenia, thrombocytopenia, and defects of qualitative platelet function are found during this stage.
• South American hemorrhagic fevers
  • Junin and Machupo viruses are similar in severity, and anecdotal reports suggest that Guanarito infections may be somewhat more severe overall.
  • The illnesses begin somewhat insidiously with fever, malaise, myalgia, and lumbar pain.
  • Progression may occur over 3-4 days, with prostration, unremitting fever, and mucosal bleeding. Hemorrhage along the gingival margins is characteristic.
  • After 1-2 weeks, most patients improve, but approximately one third progress to profound cutaneous and mucosal hemorrhages, delirium, and convulsions or a combination of CNS and bleeding findings. Capillary leak syndrome also may occur.

Physical

The major physical points regarding the major Arenavirus illnesses are as follows:

• Lymphocytic choriomeningitis virus
  • Conjunctival injection, facial flushing, generalized lymphadenopathy, and orthostatic hypotension are common.
  • Fever and more severe headaches may recur 2-4 days after recovery from the first phase, with overt lymphocytic pleocytotic meningitis with elevated cerebrospinal (CSF) protein. Papilledema may be noted.
• Lassa fever
  • Pharyngitis, often exudative, occurs early. Conjunctivitis also may be seen.
  • Later, in severe disease, CNS signs can be seen, including tremors, confusion, encephalopathy, and seizures. Focal CNS signs usually are absent, and CSF is normal.
  • Bleeding is seen in only 15-20% of patients, it usually is limited to mucosal surfaces, and it is limited in severity.
• South American hemorrhagic fever
  • Conjunctival injection, facial flushing, generalized lymphadenopathy, and orthostatic hypotension are common signs.
  • Many patients have a petechial and/or vesicular palatal enanthem and skin petechiae.
  • At the point of further progression, CNS signs can include tremor of hands and tongue, hyperesthesias, decreased deep-tendon reflexes, and lethargy.
  • Especially with deteriorating illness, leukopenia and thrombocytopenia are common but aminotransferase elevations are uncommon.

Differential Diagnoses

Meningococcemia
Plague
Yellow Fever

Other Problems to Be Considered

Lymphocytic choriomeningitis virus infection

Influenza
Enterovirus meningitis
Enteric cytopathogenic human orphan virus meningitis
Coxsackievirus meningitis
Leptospirosis

Lassa virus hemorrhagic fever

Meningococcemia
Plague
Pneumococcemia
Filovirus infection (Ebola or Marburg)
Falciparum malaria
Yellow fever
Viral hepatitis
Congo-Crimean hemorrhagic fever
Leptospirosis
Dengue

South American Arenavirus hemorrhagic fevers

Meningococcemia
Plague
Pneumococcemia
Falciparum malaria
Yellow fever
Viral hepatitis
Leptospirosis
Dengue

Workup

Laboratory Studies

The diagnosis of acute illness with human Arenavirus is made using antigen and/or antibody measurements, virus isolation, and/or genomic detection by reverse transcriptase-polymerase chain reaction (RT-PCR). For Lassa and the South American hemorrhagic fever agents, laboratory samples from suspected cases should be handled under biosafety level 4 containment until treated chemically (10% hypochlorite, Lysol, formaldehyde, or peracetic acid) or with gamma irradiation.

• Antigen/antibody detection
  • The serodiagnosis of Arenavirus can be made rapidly and with a high degree of sensitivity.
  • In Lassa fever, many acutely ill patients can be found to be immunoglobulin M (IgM) antibody–positive for the Lassa virus upon presentation. Indirect fluorescent antibody (IFA) assay or enzyme-linked immunoabsorbent assay (ELISA) methodology usually determines the IgM antibody. At least 50-75% of patients are IgM antibody–positive (ie, >1:4) by day 5 and 100% positive by days 12-14.
  • In ill patients, Lassa virus ELISA antigenemia has been detected by experimental technology. Antigen testing of liver biopsy specimens also has been accomplished.
  • In the South American hemorrhagic fevers, antibodies usually develop 1-2 weeks later than in Lassa or LCM virus, appearing during the third week of illness. IFA assay and ELISA may not easily distinguish between the different agents (ie, all members of the Tacaribe complex), but plaque-reduction neutralization antibody testing can distinguish between the different agents.
  • Antigen-capture ELISA of blood or tissue may offer the earliest diagnostic test for the South American hemorrhagic fevers.
  • For LCM virus, IgM ELISA appears to have replaced the IFA assay and other antibody assays for serological diagnosis. Antibodies also can be assessed using CSF.
• Virus isolation
  • Lassa virus can be isolated easily (ie, in a biosafety level 4 laboratory) in tissue culture using the E6 clone of Vero cells or in suckling mice. Infected animals represent the highest risk of exposure to laboratory personnel.
  • Viremia can be high grade and sustained in Lassa fever with as many as 6-8 logs of median tissue culture infectious doses per milliliter. Low titers of virus can be found in throat swabs acutely and during convalescence at low titer in the urine. Viremias greater than 3 logs are associated with higher mortality.
  • In the South American hemorrhagic fevers, virus also can be isolated from blood or tissue samples using tissue culture or suckling mice. Cocultivation of peripheral blood mononuclear cells with Vero cells seems to increase sensitivity.
  • In human infection with LCM virus, the virus can be isolated from the blood early in the disease, and, in those who develop meningitis, the virus also can be isolated later from CSF.
• Reverse transcriptase-polymerase chain reaction detection
  • Limited experience exists with RT-PCR.
  • Care must be taken to avoid false-positive results and to use appropriate primers.
  • RT-PCR assays detecting fragments of the S (glycoprotein) gene have been successful, and, after RNA extraction, minimal laboratory risk exists.
• Serum aminotransferase testing in Lassa fever: Admission levels greater than 150 IU/L are associated with a 50% case fatality rate, and, when combined with high viremia, the mortality rate is approximately 80%.

Treatment

Medical Care

No specific medical care is required for mild infections associated with any of the Arenaviridae. Specific and/or careful symptomatic care is needed in more severe infections associated with those agents linked to hemorrhagic fever.

• LCM virus infection requires no more than symptomatic treatment.
• In overt cases of Lassa fever or any of the South American hemorrhagic fevers, aggressive treatment is needed to attempt to diminish morbidity and mortality.
  • The antiviral drug ribavirin is used in Lassa fever and also has shown efficacy in cases of South American hemorrhagic fever.
  • Supportive care related to blood pressure monitoring/control and careful attention to fluid and electrolytic balance can be lifesaving.
  • Convalescent human plasma has been used with some success in the treatment of Junin virus infection. The lack of parallel success in Lassa fever may be related to low and delayed titers of the specific neutralizing antibody in Lassa fever.

Consultations

With a compatible illness and travel history, any individual in whom either Lassa fever or one of the South American hemorrhagic fevers is suggested should have immediate consultation with an infectious disease physician and the local public health authorities.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.⁶

Antivirals

Clinical experience with ribavirin in the treatment of Arenavirus infections is primarily with Lassa fever, but anecdotal experience in the South American arenaviruses also exists.

Ribavirin (Virazole)

Synthetic guanosine analog (1beta-D-ribofuranosyl- 1H-1,2,4-triazole-3-carboxamide) that inhibits viral replication by inhibiting DNA and RNA synthesis.
Phosphorylated in vivo, and the active form may interfere with viral genomic synthesis. Clinically used in combination with interferon for hepatitis C, as aerosol for respiratory syncytial virus, and as potential prophylaxis and/or treatment of Congo-Crimean hemorrhagic fever, hantavirus infections, and Arenavirus hemorrhagic fevers. In vitro evidence exists for activity against West Nile virus. IV form not readily available and the manufacturer should be contacted if the need arises.

Dosing

Adult

Lassa fever (with hepatitis and/or hemorrhagic manifestations): 2 g (30 mg/kg) IV initially; 1 g (15 mg/kg) IV q6h for 4 d; then 500 mg (7.5 mg/kg) IV q8h for 6 d
Suggested prophylactic dose: 600 mg PO qid for 10 d

Pediatric

Prophylaxis
<10 years: 400 mg/dose IV
>10 years: Administer as in adults

Interactions

Zidovudine effects are decreased when administered concurrently

Contraindications

Documented hypersensitivity; women who may become pregnant

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Closely monitor patients with COPD and asthma for deterioration of respiratory function; systemic ribavirin use causes dose-related anemia and hyperbilirubinemia related to extravascular hemolysis, and at higher doses, a bone marrow suppression of the erythroid elements may occur; caution when administered by aerosol for RSV; teratogenic, mutagenic, and, possibly, gonadotoxic

Follow-up

Deterrence/Prevention

• Rodent control
  • Unlike plague, in which a rodent die-off can cause an increased risk of a human outbreak, the rodents carrying arenaviruses do not become ill or shed the virus in their urine.
  • Aggressive rodent control (eg, trapping, rodent poisons) and avoidance of high-density rodent areas are the most important preventative maneuvers.
  • Procedures to avoid rodent droppings and exposure include properly disposing of trash and clutter, moving woodpiles away from residences, properly airing out cabins and buildings prior to reoccupation, and avoiding creating dust when cleaning buildings with signs of rodent infestation.
• Arenavirus vaccination
  • No commercially available vaccines are available to prevent Arenavirus infection.
  • In one study with Lassa virus, a recombinant vaccinia virus that expressed Lassa virus glycoprotein was found to be efficacious in primates.
  • More recently, clinical trials have begun on an attenuated Junin virus vaccine, and the vaccine has shown immunogenicity. This vaccine also may be protective against Machupo virus because of cross-antigenicity.
  • Anecdotal information suggests that antigenically similar but nonpathogenic arenaviruses may be protective against Lassa fever in monkeys.

Complications

• LCM virus infection
  • CNS complications beyond aseptic meningitis include encephalitis and may involve cranial nerve palsies and/or damage to the autonomic nervous system. Hypoglycorrhachia can be found.
  • Non-CNS complications include orchitis, myocarditis, and small-joint arthritis. These develop, if at all, late in the illness, during the recurrence of fever.
  • Intrauterine infection with LCM virus has been described. Infection may manifest as hydrocephalus and/or chorioretinitis with persistent spastic pareses and death within several years.
• Lassa fever
  • Deafness, which can be unilateral or bilateral, is observed in as many as 30% of patients. Recovery of hearing occurs in approximately 50% of patients, but the deafness can be permanent.
  • Maternal and fetal losses during Lassa fever infection are substantial. Maternal mortality rates can approach 30% and may be reduced with abortion. Fetal loss rates are close to 90% and are not affected by the trimester of infection.
  • Renal or hepatic failure is not observed.
• South American hemorrhagic fevers
  • In addition to severe hemorrhagic or CNS complications, convalescence in survivors can be quite prolonged, with weight loss, hair loss, and autonomic instability.
  • As with Lassa fever, South American hemorrhagic fevers have substantial effects on the developing fetus.

Prognosis

• LCM virus infection: Survival with recovery from LCM virus infection is the rule.
• Lassa fever
  • Hemorrhagic features are mild and rarely of prognostic significance.
  • Risk factors for increased mortality are facial and/or neck edema, elevated aminotransferases, and increased viremia. With these in combination, the mortality rate can be higher than 80%.
• South American hemorrhagic fevers
  • Mortality rates can be higher than 30%.
  • Risk factors for mortality include a pronounced bleeding diathesis, severe neurologic deterioration, and shock.

Miscellaneous

Medicolegal Pitfalls

• Recognition of a case of Lassa fever or any of the South American Arenavirus infections is crucial from both infection control and epidemiologic standpoints. Suspected cases should be reported immediately to local public health authorities.

Special Concerns

• Management of contacts of imported cases of Lassa fever: Initially, imported cases of Lassa fever were treated with supportive care under conditions of total isolation. More recently, simple barrier nursing techniques have been found to be effective in preventing transmission to health care personnel. Guidelines have been developed to establish a level of risk for Lassa fever based on the degree of exposure to an index case. Similar criteria can be used for risk of exposure to South American hemorrhagic fever viruses.
  • High-risk: These activities include unprotected contact with index case body fluids or excreta (eg, mouth-to-mouth kissing; sharing food, liquids, or eating utensils; sexual intercourse⁷ ; needle sticks). High-risk exposures usually precipitate ribavirin prophylaxis; closely monitor the contact for fever and/or illness and measure for seroconversion beginning on day 0 and on day 15.
  • Medium-risk: Activities that are medium-risk include unprotected contact with surfaces that probably were contaminated or possible unprotected contact with index case body fluid or excreta (eg, drawing blood or handling lab slides containing unfixed specimen, handling bed sheets or bed pans, or perceived skin or mucosal contact with the aerosolized respiratory secretions from an index case). Medium-risk exposures trigger public health officials to monitor exposure for 21 days after the last exposure. If a fever of 38.3°C or higher occurs, intravenous ribavirin should be given and diagnostic studies of Lassa virus obtained. If the fever is low grade, other criteria, such as aminotransferase levels, should be used to determine action.
  • Low-risk: These exposures include unprotected contact with the index case with little chance of exposure to body fluids/excreta (eg, examining index case without gloves or being within several feet of the case when a cough or sneeze occurs). Patients with low-risk exposures should be monitored for 21 days after the last exposure. If fever is higher than 38.3°C and aminotransferases are elevated, based on clinical judgment, further action (including hospitalization with or without ribavirin) may be indicated.
  • No risk: Such exposure includes proximity of the index case without direct contact to potentially contaminated objects (eg, brief visit to patient's room without contact or handling blood or secretions with gloves).

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Keywords

arenaviruses, lymphocytic choriomeningitis virus, Lassa fever virus, Machupo virus, Junin virus, Guanarito virus, viral hemorrhagic fever

Contributor Information and Disclosures

Author

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Daniel R Lucey, MD, MPH, Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences
Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Clinical guidelines

Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 2003 Jun 6. 42 pages. NGC:003059

Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings 2007. Standard precautions.
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 1996 Jan (revised 2007 Jun). 17 pages. NGC:005766

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