Lassa fever pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Pathophysiology
Virus
- Lassa virus is zoonotic (transmitted from animals). The reservoir, or host, of Lassa virus is a rodent known as the "multimammate rat" of the genus Mastomys. It is not certain which species of Mastomys are associated with Lassa; however, at least two species carry the virus in Sierra Leone. Mastomys rodents breed very frequently, produce large numbers of offspring, and are numerous in the savannas and forests of West, Central, and East Africa. In addition, Mastomys generally readily colonize human homes.
- All these factors together contribute to the relatively efficient spread of Lassa virus from infected rodents to humans.The Lassa virus is so named because, in 1969, it was first isolated and correlated as the causative agent of Lassa fever in a small town called Lassa in North-eastern Nigeria. Lassa fever is mostly found in West Africa, specifically in Sierra Lione, Guinea, Liberia, and Nigeria. As stated above, Lassa virus consists of four lineages. Three of these lineages (which are ancestral to the fourth) are located in Nigeria, while the other can be found in Guinea, Liberia, and Sierra Lione.
- Often, phylogenetic distance correlates with temporal distance, but in the four lineages of the Lassa virus, it actually correlates more with geographical distance. When people inhabiting Sierra Lione were tested for antibodies for the virus, it was found that those living in the eastern province had the highest amount of antibodies, while those living in the southern coastal areas had the lowest. It was also discovered that people under the age of 20 and over the age of 50 had fewer antibodies and those under the age of one year had none. While many people have antibodies to the virus, the outcome of the virus is usually more dependent on its viremia rather than how many antibodies the person has to respond. One study found that patients with viremia of 103TCID50/ml or higher and aspartate aminotransferase of 120 IU/liter or higher had a statistically higher chance of mortality than those with less.
Vector
- As stated above, the virus is transferred to humans via a rat vector.
Transmission
- 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. In fatal cases, Lassa fever is characterized by impaired or delayed cellular immunity leading to fulminant viremia.
- There are a number of ways in which the virus may be transmitted, or spread, to humans. The Mastomys rodents shed the virus in urine and droppings. Therefore, the virus can be transmitted through direct contact with these materials, through touching objects or eating food contaminated with these materials, or through cuts or sores. Because Mastomys rodents often live in and around homes and scavenge on human food remains or poorly stored food, transmission of this sort is common. Contact with the virus also may occur when a person inhales tiny particles in the air contaminated with rodent excretions. This is called aerosol or airborne transmission. Finally, because Mastomys rodents are sometimes consumed as a food source, infection may occur via direct contact when they are caught and prepared for food.
- Lassa fever may also spread through person-to-person contact. This type of transmission occurs when a person comes into contact with virus in the blood, tissue, secretions, or excretions of an individual infected with the Lassa virus. The virus cannot be spread through casual contact (including skin-to-skin contact without exchange of body fluids). Person-to-person transmission is common in both village and health care settings, where, along with the above-mentioned modes of transmission, the virus also may be spread in contaminated medical equipment, such as reused needles (this is called nosocomial transmission). Frequency of transmission via sexual contact has not been established. Transmission through breast milk has also been observed.
Incubation Period
- Lassa virus has an incubation period of 1-24 days and death usually occurs within 12 days after the onset.
Pathology
- Some of the characteristic symptoms of the virus include: fever, muscle aches, sore throat, nausea, vomiting, chest and abdominal pain, weakness, cough, headache, exudative pharyngitis, anemia, low blood pressure, and diarrhea. Because its symptoms are similar to other febrile illness found in Africa, Lassa virus is hard to diagnose. It can eventually can cause pulmonary edema, pleural and pericardial effusion, facial edema, bleeding from mucosal surfaces, neurological complications, deafness, lymphocytopenia, thrombocytopenia, and ascites. Often sore throat, vomiting, and bleeding are associated with higher fatality. Microscopically, the virus causes hepatocellular necrosis and capillary lesions that can cause certain organs to hemorrhage. Lassa virus travels through the body via the blood, lymph vessels, respiratory tract, and digestive tract. Because of the multitude of dissemination strategies in the body, it is able to infect almost every organ in the human body. It has even been found in the cerebrospinal fluid which suggests a malfunction or defect of the blood brain barrier. Even though the virus targets the entire body, the liver is usually the organ that is most affected. The virus escapes detection by suppressing the immune system. There are four clinical stages of Lassa fever. The first stages occurs within the first three days and its symptoms include a high fever, weakness, and a general depression in activity. The second stage transpires from day 4 to day 7 where the patient experiences some of the more common/characteristic symptoms as stated above. The third stage begins at the seventh day and includes more severe symptoms such as: facial edema, convulsions, mucosal bleeding, internal bleeding, and disorientation. The fourth stage usually occurs after the 14th day and ends in coma and death.
- Only 20% of people who contract Lassa fever have severe multisystem trauma, meaning that 80% of people have only the milder symptoms. It has also been found that most cases of Lassa fever occur as the seasons change from dry to wet.
- The Lassa virus is diagnosed several ways including the discovery of the viral antigen, antibodies, or virus culture. One way to detect the virus antigen is to use the virus’s antibodies in enzyme-linked immunosorbent assays (ELISAs). The virus can also be revealed though indirect immunoflourescence which detects the virus antibodies IgM and IgG. Lastly, the virus can be uncovered using reverse transcription PCR after first reverse transcribing the RNA of the virus into DNA.
- While, at present, there is no vaccine for Lassa virus, the broad-spectrum nucleoside analogue ribaviran has been demonstrated to have therapeutic effect on patients suffering from Lassa fever. Ribaviran works by mutating the progeny genomes of the virus by incorporating itself into the virus’s RNA. While this method has been proven to reduce mortality, it is most successful if it is given within 6-7 days of the start of symptoms. Ribaviran by itself is not enough, the patient also needs rigorous care in the hospital setting. Someone suffering from Lassa virus needs to have their fluids and electrolytes kept in balance, they require the proper amount of oxygen, their blood pressure needs to be monitored, and they need prompt treatment for any complications that may arise.