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Lassa fever is an acute viral hemorrhagic fever first described in 1969 in the Nigerian town of Lassa in the Yedseram River valley. Clinical cases of the disease had been known for over a decade earlier but not connected with this viral pathogen.
The infection is endemic in West African countries, causing many deaths. Outbreaks of the disease have been observed in the following countries:

but it is believed that human infections also exist in:

It is also the most common hemorrhagic fever that is exported beyond its endemic area to countries like the United States, United Kingdom, The Netherlands, Japan and Israel.

The virus and epidemiology

The virus belongs to Arenaviridae family; it is an enveloped, single-stranded, bisegmented RNA virus. It has been determined that the virus is zoonotic (transmitted from animals), and that it spreads to man from rodents, specifically multimammate rats (Mastomys natalensis). This is probably the most common rodent in equatorial Africa, ubiquitous in human households and eaten as a delicacy by up to 90% of people in some areas. In these rats infection is in a persistent asymptomatic state. The virus is shed in their excreta (urine and feces), which can be aerosolized.

In fatal cases Lassa fever is characterized by impaired or delayed cellular immunity leading to fulminant viraemia.

The dissemination of the infection can be assessed by prevalence of antibodies to the virus in populations of:

  • Sierra Leone 8–52%
  • Guinea 4–55%
  • Nigeria approx. 21%

Like other hemorrhagic fevers, Lassa fever can be transmitted directly from one human to another. It can be contracted by an airborne route or with direct contact with infected human blood, urine, or semen. Transmission through breast milk has also been observed.

Lassa fever is less deadly compared to ebola, though they share similar symptoms. Because Lassa is a very fast replicating and debilitating virus, the chances of a worldwide epidemic are small. Patients are far too weak to board a plane and spread it to other parts of the world.

Lassa fever is a virus that has emerged relatively recently. It has managed to appear in a relatively short span of history. Because Lassa fever has a reservoir (rodents), it is difficult to eliminate.

The disease

Infection in humans typically occurs via exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infective material (aerosol) is believed to be the most significant means of exposure. It is possible to acquire the infection through broken skin or mucous membranes that are directly exposed to infective material. Transmission from person to person has also been established, presenting a disease risk for healthcare workers. Frequency of transmission via sexual contact has not been established.

In 80% of cases the disease is inapparent, but in the remaining 20% it takes a complicated course. It is estimated that the virus is responsible for about 5,000 deaths annually. The fever accounts for up to 1/3 of deaths in hospitals within the affected regions and 10 to 16% of total cases.

After an incubation period of six to twenty-one days, an acute illness with multiorgan involvement develops. Nonspecific symptoms include fever, facial swelling, and muscle fatigue, as well as conjunctivitis and mucosal bleeding. The other symptoms arising from the affected organs are:

Clinically, Lassa fever infections are difficult to distinguish from other viral hemorrhagic fevers such as Ebola, and from more commom febrile illnesses such as malaria.

The virus is excreted in urine for three to nine weeks and in semen for three months.

Virus Replication

Replication for Lassa virus is very rapid, while also demonstrating temporal control in replication. There are two genome segments. The first step involved is making mRNA copies of the - sense genome. This ensures that there is adequate proteins, which are required for replication. The N and L proteins are made from the mRNA produced. The - sense genome then makes vcRNA copies of itself which are + sense. The vcRNA is a template for producing - sense progeny but mRNA is also synthesised from it. The mRNA synthesised from vcRNA translate the G (spike) proteins and Z proteins. Thus, with this temporal control, the spike proteins are produced last, making the infection further undetected by the host immune system.

Lassa virus will infect just about every tissue in the human body. It starts with the mucosa, intestine, lungs and urinary systems, and then progresses to the vascular system.

Lab tests

There is a range of laboratory investigations that are performed to diagnose the disease and assess its course and complications. ELISA test for antigen and IgM antibodies gives 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever:

Prevention

Control of the Mastomys rodent population is impractical, so measures are limited to keeping rodents out of homes and food supplies, as well as maintaining effective personal hygiene. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person.

No vaccine against Lassa fever is currently available, though development is underway. The Mozambique virus closely resembles Lassa fever, while lacking its deadly effects. This virus is being considered for possible use as a vaccine.

Researchers at the USAMRIID facility, where military biologists study infectious diseases, have a promising vaccine candidate. They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived leathal challenge, while showing no clinical symptoms.

Treatment

All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of.

Early and aggressive treatment using ribavirin was pioneered by Joe McCormick in 1979. After extensive testing, it was determined that early administration is critical to success. Additionally, ribavirin is almost twice as effective when given intravenously as when taken by mouth. The drug interferes with the virus metabolism, inhibiting its replication. The drug is relatively inexpensive, but the cost of the drug is still very high for many of those in poverty-stricken West African states. Fluid replacement, blood transfusion and fighting hypotension are usually required.

Prognosis

About 15%-20% of hospitalized Lassa fever patients will die from the illness. It is estimated that the overall mortality rate is 1%, however during epidemics mortality can climb as high as 50%. Thanks to treatment with ribavirin, fatality rates are continuing to decline. Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.

Lassa fever virus as a biological weapon

The terrorist attack on 11 September, 2001 and threat of biological warfare attack alerted governmental agencies and scientists. Lassa fever virus is also regarded as a possible biological weapon.

References

  • Theiler, Max and Downs, W. G. 1973. The Arthropod-Borne Viruses of Vertebrates: An Account of The Rockefeller Foundation Virus Program 1951-1970. Yale University Press.

  • Geisbert TW, Jones S, Fritz EA, Jahrling P, et al. 2005 Development of a new vaccine for the prevention of lassa fever. PLOS MEDICINE 2 (6): 537-545 JUN 2005.

  • Dato-on, Airam. 2006 Lassa Fever Research Paper.

External links

Infectious diseases | Eponymous diseases | Viruses | Zoonoses | Tropical disease

Lassafieber | Fièvre de Lassa | Lassakoorts | ラッサ熱

 

This article is licensed under the GNU Free Documentation License. It uses material from the "Lassa fever".

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