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Copyright 2004 Tara K. Harper.  All rights reserved.

TKH Virology Notes:
Lassa Fever

•  Description      •  Mechanism      •  Outbreaks
•  Location      •  Incubation Period      •  Vaccine
•  Vector      •  Symptoms      •  Odds 'n' Ends
     •  Diagnosis      •  Links
     •  Mortality Rates
     •  Treatment

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NOTE:  This file is for information only.  It is not intended for diagnosis.

Lassa Fever

Description.   An extremely virulent, often fatal, Old-World, viral hemorrhagic illness.  Lassa fever, an arenavirus, is an enveloped, single-stranded, bisegmented RNA virus. As with other arenaviruses, Lassa virus does not have a conventional negative-strand coding arrangement.  

Lassa fever occurs more often in the dry season, rather than in the rainy season.  It is the most commonly "exported" hemorrhagic fever;  its victims carry the disease from Africa to the United States, to the United Kingdom, tp the Netherlands, Israel, and Japan.

Lassa fever is named after the town (in the Yedseram River valley) in which the first cases were isolated in 1969, during a nosocomial outbreak at a local hospital.  (A clinical description of Lassa fever was published in Sierra Leone over a decade earlier, but received little or no attention.)

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Location.   Parts of West Africa, including Guinea, Sierra Leone, Nigeria, and Liberia.  However, sporadic Lassa infections may have also occurred in Senegal and Mali.  One host genus has been identified as spreading at least one Lassalike virus in central Africa.

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Vector.  The rat species Mastomys, in particular, M. natalensis.  This is a consistent host reservoir for the Lassa virus because of congenital neonatal infection, which results in rats with long-lasting and/or lifelong infection.  Because of the mechanism of infection, there is no break in the natural chain from virus to host species.  The rats themselves might show no symptoms of the disease, but they shed the virus freely in urine and droppings, and secrete the virus in their saliva.  

Because certain varieties of Mastomys often live in human homes, the virus is easily transmitted to humans.  Transmission occurs via direct contact with rat urine, feces, and saliva; via contact with excretion- or secretion-infected materials; or via ingestion of excretion-contaminated food.  Victims can also become infected via skin breaks, and via mucous membranes from aerosol transmission from dust-borne particles.  In some areas, the rodents are used as a food source, thus providing additional exposure to the infected rat blood, as well as allowing ingestion of potentially contaminated meat.  Laboratory workers become infected usually from contact with rodent saliva.

Unlike other arenaviruses, Lassa virus can be fairly easily transmitted from human to human.  Humans can contract the disease from other humans via aerosol transmission (coughing), or from direct contact with infected human blood, urine, or semen.  Lassa virus has been isolated from semen 6 weeks after acute illness;  the virus can be transmitted to sexual partners by convalescent men.

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Mechanism.   The virus enters the human body through the bloodstream, lymph vessels, respiratory tract, and/or digestive tract.  It then multiplies in cells of the reticuloendothelial system.  Virus replication in the reticuloendothelial cells causes capillary lesions.  These capillary lesions lead to erythrocyte and platelet loss, with mild to moderate thrombocytopenia and a tendency toward bleeding.  Capillary lesions also cause increased vascular permeability and hemorrhage in various organs, such as the stomach, small intestine, kidneys, lungs, and brain.

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Incubation Period:  Usually about 10 days.  Can range from 1-24 days.  Most patients display symptoms for 4 to 5 days before seeking hospital treatment.

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Symptoms.  Gradual onset of fever and malaise.  Increased fever (which can last 2-3 weeks) and myalgia, with severe prostration, accompanied by involvement of specific organs and serosa.  Patients frequently present with pain behind the sternum and with coughing.  

Additional common symptoms include:  abdominal pain, nausea and vomiting, diarrhea, or constipation; also:  conjunctivitis, pharyngitis (inflammation of mucous membranes and the underlying parts of the pharynx), increased vascular permeability (such as pleural effusions), and proteinuria (protein in the urine).  About 10-30% of patients present with facial and neck swelling.  Approximately 2/3 of patients present with sore throat, usually accompanied by objective inflammatory or exudative (oozing) pharyngitis.  Some patients experience adult respiratory distress syndrome.   Skin rashes and jaundice are rare.

Some patients experience bleeding from the gums.  In addition, capillary lesions cause hemorrhaging in the stomach, small intestine, kidneys, lungs, and brain.  Less than 1/3 of patients present with bleeding; however, bleeding is a predictor of a significantly higher risk of death.  In severe cases of Lassa fever, shock and vascular collapse occur, followed by death.  Research suggests that the shock results from platelet and endothelial dysfunction, which cause hemorrhage and allow fluid to leak into the intravascular system.

Patients who will survive begin to defervesce 2-3 weeks after onset of the disease.  In contrast, patients who are at the greatest risk of dying usually develop shock, clouded mental status, agitation, rales, pleural effusion, and sometimes grand mal seizures.  The four symptoms associated with a 2.5-fold or higher risk of mortality are:  vomiting, sore throat, tachypnea (rapid breathing), or bleeding.

During convalescence, although the virus may no longer be found in the blood, pericarditis can occur, especially in males.  The following conditions may also occur during convalescence:  aseptic meningitis, encephalitis, global encephalopathy with seizures, cerebellar ataxia (uncommon), and deafness (common).  Temporary or permanent deafness in one or both ears occurs in 29% of Lassa fever patients.

Experiments on guinea pigs have shown that Lassa virus can manifest differently, with significantly varying symptoms.  It is suspected that subtle genetic changes in tissue-specific variants of the disease create the differences in disease manifestation.

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Diagnosis.  Lassa virus can be diagnosed in three ways:  
     1.  Isolating the virus from blood, urine, or throat washings.
     2.  Demonstrating the presence of immunoglobuline M (IgM) antibody to Lassa virus.
     3.  Showing a fourfold rise in titer of IgG antibody between acute- and convalescent-phase serum.

The virus can be isolated from the blood or serum during the febrile phase of the disease, up to 2 weeks postonset.  Antibody can be detected by CF, IFA, or ELISA.  In severe cases, patients can die before the appearance of antibodies.  

Other laboratory results:
     •  Leukocyte count can be low, normal, or moderately elevated.
     •  Platelet counts are usually normal, but might be slightly low.  
     •  AST  (SGOT) and ALT (SGPT) are usually elevated (10x normal).
     •  Chest x-rays are usually normal, but may show pleural effusions or basilar pneumonitis.
     •  Albuminaturia (excessive amounts of albumin proteins in the urine) is common.
     •  ECGs are usually abnormal.

Initial possible diagnoses of the Lassa-infected patient may include malaria, shigellosis, and typhoid.

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Mortality Rates.  Prognosis for Lassa patients has a direct correlation to levels of viremia.  However, prognosis does not correlate with the patient's development of IgM or IgG antibodies.  The antibodies do not seem to neutralize the Lassa virus.

The mortality rates for Lassa virus are typically estimated at 15% to 20%.  Some studies estimate mortality as high as 45%.  One survey of Lassa infection vs. mortality rates indicates that less than 1% of all Lassa-virus infections in West Africa will eventually result in fatal disease.  The mortality rates for Lassa appear to be much higher in people of non-African stock.

Lassa virus also causes high fetal mortality and high mortality in pregnant women.  The mortality rate is 92% for fetuses in early pregnancy, 75% for fetuses in the third trimester, and 100% in the neonatal period for full-term babies.  High concentrations of the virus have been found in both fetal tissue and in the placenta.  It is suspected that maternal T cells cannot attack the concentrations of virus in the placenta because placental cells cannot express class I or class II  MHC antigens.

The mortality rate for gravid women is 7% in the first two trimesters, 30% in the last trimester, and 50% for pregnant women who delivered within 1 month.  In contrast, the general mortality rate for nonpregnant women only is 13%.

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Treatment.  For adults, ribavirin:  2-gm loading dose, followed by 1 gm every 6 hours for 4 days;  followed by 0.5 gm every 8 hours for 6 days.  There is no treatment for the deafness (which resembles idiopathic nerve disease) associated with Lassa fever.  Antibiotics may also be administered to patients to ward off or treat secondary and/or opportunistic bacterial infections.

Severely ill patients may receive treatment before the diganosis is confirmed.

Currently, there is no effective prophylactic treatment for Lassa fever.  However, some sources recommend prophylactic doses of Ribavirin for people coming in high-risk contact with viremic patients.

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Outbreaks and History of Infection.
Lassa fever was first recognized in 1969 in Lassa, Nigeria.  Subsequent outbreaks occurred in Nigeria, Liberia, and Sierra Leone.  In some parts of Sierra Leone and Liberia, 10% to 16% of all patients admitted to hospitals have Lassa fever.  Some Lassa fever cases have been "imported" into the U.S. and U.K. through viremic travelers who acquired the disease elsewhere.  

A few notes on outbreaks:
   - 1969, northern Nigeria - first recognized outbreak of the disease.
   - 1970 to present, Liberia.  Most cases were hospital workers who acquired the disease in the hospital from the index patient.
   - 1970 to present, Sierra Leone.  It is estimated that 6% of all residents in the initial endemic area have antibodies to Lassa Fever, even though only 0.2% were recognized as clinically ill.
   - Estimated 100,000-300,000 infections per year in West Africa.

 About 2/3 of all reported cases are women, but this might be a result of exposure, rather than a tendency toward greater susceptibility in women to the disease.

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Vaccine.  No vaccine is currently available.  However, the most promising approach to developing a vaccine appears to be via vaccinia-vectored Lassa genes.  These have been protective in both guinea pigs and nonhuman primates.

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Odds 'n' Ends.   Studies with rodents have shown that infection with lymphocytic choriomeningitis virus (LCMV) or Tacaribe can confer protection against normally lethal attacks of Lassa virus.

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     •  Fact Sheet:  CDC Special Pathogens Branch  --  coming soon!

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Copyright 2004 Tara K. Harper

All rights reserved.  It is illegal to reproduce or transmit in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, any part of this copyrighted file without permission in writing from Tara K. Harper.  Permission to download this file for personal use only is hereby granted by Tara K. Harper.

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