HISTORY In 1969, in a village in Nigeria, Africa, a missionary nurse became ill with a terrible fever while caring for others during an epidemic. The nurse died in two weeks and was followed in death by another nurse who had attended her. A third nurse became ill and was transported to New York for treatment. A virus, never before seen in medicine was isolated from the nurse's serum. This nurse recovered from the disease after 8 weeks. (5) The virus that caused the nurse's illness was named Lassa, after the village in Nigeria where the first cases were observed (3). The disease it caused was named Lassa Fever.
THE LASSA VIRUS The Lassa virus belongs to the family Arenaviridae (1). Arenaviruses are single stranded RNA viruses (5). Unlike DNA viruses, RNA viruses lack proofreading mechanisms and are prone to mutation (11). The Lassa virus is zoonotic - meaning that it's natural host is an animal (4). The multimammate rat (2), is found in West, Central, and East Africa and two species of the multimammate rat (genus Mastomys) carry the Lassa Virus, (M. huberti, which prefers human homes as it's habitat and M. erythroleucus). The Lassa virus is excreted in rat urine and droppings (3).
TRANSMISSION The Lassa virus is transmitted by inhalation of aerosolized rodent droppings (12), indirect contact with fomites or ingestion of food contaminated with rodent droppings or urine, or by eating the rats themselves (3). Person to person transmission can occur by direct contact with the blood or body fluids of a person infected by Lassa. The virus is shed is the urine of Lassa patients for anywhere from 3 to 9 weeks after the illness begins and in semen for up to 3 months (6). The rodents themselves are "congenitally infected" - the virus is transmitted from a pregnant rodent to her offspring. The virus can also be transmitted from rat to rat by the methods listed above. The most effective method of transmission is by a bite from an infected rodent (7).
PATHOGENESIS AND VIRULENCE FACTORS Lassa fever is "an acute multi-organ infection". The incubation period varies between 5 and 21 days (8). The "exact method of pathogenesis" is not understood. Lassa initially multiplies at the site of infection - the lungs, if inhaled, the blood, if through a cut (10). The target cells for viral replication are epithelial cells (12), like those that line blood capillaries and, as the disease progresses, viral nucleic acids and antigen can be found in epithelial cells (10). Lassa virus, like all viruses, is an obligate intracellular parasite. Multiplying inside cells, the virus itself escapes phagocytosis (13). "New viral particles, called "virions", are created by budding from the surface of the host cell" (4) - not by lysis of the cell. Any cellular damage that occurs is actually from the host's own response to infection - "the development of hypersensitivity" and "cytolytic T lymphocytes". This cell-mediated response is crucial, however, for elimination of the virus from the body. Antibodies are not a factor in immune defense of Lassa because "they are not activated for up to 2 days following infection" (10).
CLINICAL PRESENTATION The clinical presentation of Lassa fever can range from asymptomatic infection to an extremely severe illness, ending in death (6). The symptoms and signs of Lassa fever are generalized and the disease is easily mistaken for malaria (5). A frequently encountered symptom of Lassa fever is edema in the face and neck region, most likely caused by extensive leakage of the capillaries. Lassa symptoms can include, include fever, malaise and "prostration" (12), a syndrome characteristic of viral hemorrhagic fevers. Other signs and symptoms can include myalgia (muscle aches), sore throat, headache, nausea, vomiting, diarrhea, chest pain, cough, abdominal pain and "inflammation of the eyes". The most severe cases experience "pleural effusion (fluid in the lungs)", hemorrhage, hypotension, shock, encephalopathy (brain dysfunction), and seizures (6). Death occurs "from organ failure or shock" (10).
DIAGNOSIS PCR techniques, performed on serum or whole blood, allow for early and rapid diagnosis of Lassa fever (5). The most common diagnostic tests are ELISAs, enzyme linked immunosorbent assays, that can detect IgG and IgM antibodies as well as Lassa antigen (3). Lassa virus can also be cultured in VERO cells and their presence demonstrated by immunofluorescence (5).
TREATMENT Lassa fever can be treated with ribavirin. Ribavirin is a "broad spectrum antiviral agent" that acts as an "IMP (inosinate) dehydrogenase inhibitor"… and "suppresses viral RNA synthesis" (9). The ribavirin therapeutic regimen consists of 3 doses (5) of approximately 8mg/kg, (8 mg of drug per kg of body weight) per day for 10 days (6). Anemia is a common side effect of ribavirin therapy and the dosage may have to be reduced if anemia appears. The treatment is most effective if administration of ribavirin begins within 4 days of the onset of symptoms (5). In addition to ribavirin, supportive treatment should be administered. This includes maintenance of fluid and electrolyte levels, blood pressure and oxygenation as well as treatment for any secondary infections or complications. Ribavirin is the only known drug treatment for Lassa fever (3). Immune plasma has not been shown effective in prophylaxis or treatment (5). Although research is presently underway to develop a vaccine for Lassa fever (3), no vaccine is currently available. Immunity against reinfection does occur after recovery from the illness but it is not known how long this immunity lasts (6)
COMPLICATIONS The most common complication of Lassa fever is loss of hearing, which affects approximately 1/3 of those infected. Deafness develops in mild and severe cases- the severity of the illness does not seem to have an effect on the occurrence of this complication (3). Only about * of those that have lost their hearing will recover some function. Recovery of hearing, if it occurs, takes from 1 to 3 months. Other complications that may occur after recovery from Lassa fever include hair loss and loss of coordination (6).
MORBIDITY AND MORTALITY Lassa fever is endemic in portions of West Africa. (3) Cases have also been seen in Guinea, Liberia, Sierra Leone and, of course, Nigeria. (6) The number of Lassa cases seen annually is approximately 300,000. The overall mortality rate ranges from 15%, for those persons treated in a hospital environment, to 60% for untreated persons (7). The mortality rate is even higher for pregnant and post partum women and 80% of pregnancies in infected women result in fetal or neonatal death (6).
CONTROL AND PREVENTION The major areas of control and prevention of Lassa fever are centered around isolation of Lassa patients, disinfection, surveillance and rodent control (6).
· Isolation There are 4 viral hemorrhagic fevers that have been judged to have a high risk of nosocomial transmission and are considered "quarantinable conditions": "Lassa fever, CCHF, Ebola fever and, Marburg disease" (12). When caring for Lassa patients, person to person and nosocomial transmission of the disease can be avoided by health care providers employing standard precautions, called "barrier nursing" techniques, to guard against contact with patients' blood and body fluids. These precautions include wearing protective articles of clothing such as masks, goggles, gloves and gowns when caring for patients and isolating Lassa patients from contact with unprotected persons until they recover (3). Laboratory tests for Lassa should be performed in a "high containment" facility with all available precautions taken, including use of gloves and biosafety cabinets (6).
· Disinfection The excreta, blood, and sputum of the patient as well as all objects with which the patient has come into contact and all laboratory equipment used to test the patient's blood, should be disinfected with "0.5% sodium hypochlorite solution or 0.5% phenol with detergent" then, if at all possible, sterilized with heat, by autoclave, incineration or boiling. A solution of 0.5% sodium hypochlorite or phenolic solution is acceptable for the terminal cleaning of the patient's room, but formaldehyde fumigation of the room can be considered (6).
· Surveillance Lassa fever is a reportable disease within many countries and internationally. In the first three weeks after the onset of patient illness, close contacts of the patient, (defined as "people living with, caring for, testing laboratory specimens from or, having a non-casual relationship with the patient"), should be identified and monitored by conducting body temperature checks, at least twice daily, for the maximum incubation period of 21 days. If the temperature check shows a fever of greater than 38.3°C, (101°F), the contact should immediately be isolated in a hospital. Also, once the town of residence of the patient has been determined, a search should begin for "unreported and undiagnosed cases" (6). Oral ribavirin has been used as prophylaxis for Lassa fever but no evidence of it's efficiency has been found (5).
· Rodent Control The ideal method of prevention in those countries where Lassa is endemic would be to prevent contact between humans and the multimammate rat. However, Mastomys rodents can be found all over West Africa (6), thus, complete control over the rodent reservoir is impossible (3). To the greatest extent possible, persons living in endemic areas should: Restrict entry of rats into their homes (6): Keep the home clean to discourage rodents from entering, and; Set out traps in and around the home to reduce the rodent population (5). Isolate food supplies from rodents (6): Use rodent proof containers for food, and; Do not use the rodent as a food source (3). Eliminate habitats for rats, and; "Minimize activities that produce aerosols" that might contain rodent excreta (6)
Educating the population in endemic areas about rodent control in and around their homes and villages is one way that the threat of Lassa fever is being addressed. New, rapid diagnostic tests are being developed and work is underway to increase the availability of ribavirin to affected areas (3).
INTERNATIONAL IMPLICATIONS
As Lassa fever has a maximum incubation period of 21 days, it is possible that persons travelling from endemic areas could be infected with the disease. It is important that FUOs, (fevers of unknown origin), in people coming from these areas be "investigated for the possibility of Lassa fever" (6).
(1) Büchen-Osmond, C. Lassa Virus. Available at http://life.anu.edu.au/viruses/ICTVdB/03011003.htm. Accessed May 2, 2000. (Last updated 04/08/98).
(2) Division of Quarantine. The Yellow Book: Health Information for International Travel 1996-97. Available at wysiwyg://90/http://www.catis.org/cdcfile/page167.htm. Accessed May 2, 2000. (Last updated 08/08/99).
(3) Special Pathogens Branch. Disease Information: Fact Sheets: Lassa Fever. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lassaf.htm. Accessed April 25, 2000.
(4) Special Pathogens Branch. Disease Information: Fact Sheets: Arenaviridae. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/arena.htm. Accessed April 25, 2000.
(5) Exotic Diseases Resources Associates. Lassa and other Arenaviruses. Available at http://www.coppettswood.demon.co.uk/lassa.htm. Accessed April 25, 2000.
(6) World Health Organization. Lassa Fever. Available at http://www.who.int/inf-fs/en/fact179.html. Accessed April 25, 2000. (Last updated 04/00).
(7) McMasters University. Epidemiology. Available at http://www.science.mcmaster.ca/Biology/Virology/18/epidem.htm. Accessed April 25, 2000.
(8) McMasters University. Clinical Features. Available at http://www.science.mcmaster.ca/Biology/Virology/18/clinic.htm. Accessed April 25, 2000.
(9) McMasters University. Viral Treatment. Available at http://www.science.mcmaster.ca/Biology/Virology/18/treatm.htm. Accessed April 25, 2000.
(10) McMasters University. Pathology and Pathogenesis. Available at http://www.science.mcmaster.ca/Biology/Virology/18/pathol.htm. Accessed April 25, 2000.
(11) Peters, C. Biosafety and Emerging Infections: Key Issues in the Prevention and Control of Viral Hemorrhagic Fevers. Available at http://www.cdc.gov/od/ohs/sympsium/symp43.htm. Accessed April 25, 2000. (Last modified 01/02/97).
(12) McGovern, T. et al. Biological Warfare and its Cutaneous Manifestations. Available at http://telemedicine.org/BioWar/biologic.htm. Accessed May 02, 2000.
(13) Tortora, G. et al. Microbiology, 6th ed. Menlo Park, CA: Benjamin/Cummings Publishing, 1997.