Arenavirus diseases
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p574-576
2025-12-20
18
Arenaviruses are typified by pleomorphic particles that contain a segmented RNA genome; are surrounded by an envelope with large, club-shaped peplomers; and measure 50–300 nm in diameter (mean, 110–130 nm) (see Figure 1). The arena virus genome consists of two single-stranded RNA molecules with unusual ambisense genetic organization.
Fig1. Electron micrographs of typical arboviruses and rodent-borne viruses. A: An alphavirus, Semliki Forest virus (Togaviridae). B: A representative member of Bunyaviridae, Uukuniemi virus. C: An arenavirus, Tacaribe virus (Arenaviridae). D: Ebola virus (Filoviridae). (Courtesy of FA Murphy and EL Palmer.)
Based on sequence data, arenaviruses are divided into Old World viruses (eg, Lassa virus) and New World viruses. The latter division is divided into three groups, with group A including Pichinde virus and group B containing the human pathogenic viruses, such as Machupo virus. Some isolates, such as Whitewater Arroyo virus, appear to be recombinants between New World lineages A and B.
Arenaviruses establish chronic infections in rodents. Each virus is generally associated with a single rodent species. The geographic distribution of a given arenavirus is determined in part by the range of its rodent host. Humans are infected when they come in contact with rodent excreta. Some viruses cause severe hemorrhagic fever. Several are naviruses are known to infect the fetus and may cause fetal death in humans.
Multiple arenaviruses cause human disease, including Lassa, Junin, Machupo, Guanarito, Sabia, Whitewater Arroyo, and lymphocytic choriomeningitis (see Table1). Because these arenaviruses are infectious by aerosols, great care must be taken when processing rodent and human specimens. High-level containment conditions are required in the laboratory. Transmission of arenaviruses in the natural rodent hosts may occur by vertical and horizontal routes. Milk, saliva, and urine may be involved in transmission. Arthropod vectors are believed not to be involved.
Table1. Classification and Properties of Some Arthropod-Borne and Rodent-Borne Viruses
A generalized replication cycle is shown in Figure 2. Host ribosomes are encapsidated during the morphogenesis of virus particles. Arenaviruses typically do not cause cytopathic effects when replicating in cultured cells.
Fig2. The arenavirus life cycle. (Courtesy of PJ Southern.)
Lassa Fever and Lujo Hemorrhagic Fever Viruses
The first recognized cases of Lassa fever occurred in 1969 among Americans stationed in the Nigerian village of Lassa.
Lassa virus is highly virulent—the mortality rate is about 15% for patients hospitalized with Lassa fever. Overall, about 1% of Lassa virus infections are fatal. In western Africa, estimates are that the annual toll may reach several hundred thousand infections and 5000 deaths. Lassa virus is active in all west ern African countries situated between Senegal and Republic of Congo. Occasional cases identified outside the endemic area usually are imported, often by persons returning from West Africa.
The incubation period for Lassa fever is 1–3 weeks from time of exposure. The disease can involve many organ systems, although symptoms may vary in the individual patient. Onset is gradual, with fever, vomiting, and back and chest pain. The disease is characterized by very high fever, mouth ulcers, severe muscle aches, skin rash with hemorrhages, pneumonia, and heart and kidney damage. Deafness is a common complication, affecting about 25% of patients during recovery; hearing loss is often permanent.
Lassa virus infections cause fetal death in more than 75% of pregnant women. During the third trimester, maternal mortality is increased (30%), and fetal mortality is very high (>90%). Benign febrile cases do occur.
Diagnosis usually involves detection of IgM and IgG antibodies by ELISA. Immunohistochemistry can be used to detect viral antigens in postmortem tissue specimens. Viral sequences can be detected using RT-PCR assays in research and public health laboratories.
A house rat (Mastomys natalensis) is the principal rodent reservoir of Lassa virus. Rodent control measures are one way to minimize virus spread but are often impractical in endemic areas. The virus can be transmitted by human-to human contact. When the virus spreads within a hospital, human contact is the mode of transmission. Meticulous barrier nursing procedures and standard precautions to avoid contact with virus-contaminated blood and body fluids can prevent transmission to hospital personnel.
The antiviral drug ribavirin is the drug of choice for Lassa fever and is most effective if given early in the disease process. No vaccine exists, although a vaccinia virus recombinant that expresses the glycoprotein gene of Lassa virus is able to induce protective immunity both in guinea pigs and in monkeys.
Lujo virus was identified in 2008 as a cause of hemorrhagic fever in South Africa. The source of infection is unknown; it was transmitted from the index patient to three health care workers. A fourth health care worker who was subsequently infected and treated with ribavirin was the only one who survived (80% case fatality rate). Rodents are thought to be the primary host, similar to other arenaviruses.
South American Hemorrhagic Fevers
Based on both serologic and phylogenetic studies of viral RNA, the South American arenaviruses are all considered to be members of the Tacaribe complex. Most have cricetid rodent reservoirs. The viruses tend to be prevalent in a particular area, limited in their distribution. Numerous viruses have been discovered; serious human pathogens are the closely related Junin, Machupo, Guanarito, and Sabia viruses. Bleeding is more common in Argentine (Junin) and other South American hemorrhagic fevers than in Lassa fever.
Junin hemorrhagic fever (Argentine hemorrhagic fever) is a major public health problem in certain agricultural areas of Argentina; more than 18,000 cases were reported between 1958 and 1980, with a mortality rate of 10–15% in untreated patients. Many cases continue to occur each year. The disease has a marked seasonal variation, and the infection occurs almost exclusively among workers in maize and wheat fields who are exposed to the reservoir rodent, Calomys musculinus.
Junin virus produces both humoral and cell-mediated immunodepression; deaths caused by Junin hemorrhagic fever may be related to an inability to initiate a cell-mediated immune response. Administration of convalescent human plasma to patients during the first week of illness reduced the mortality rate from 15–30% to 1%. Some of these patients develop a self-limited neurologic syndrome 3–6 weeks later. An effective live attenuated Junin virus vaccine is used to vaccinate high-risk individuals in South America.
The first outbreak of Machupo hemorrhagic fever (Bolivian hemorrhagic fever) was identified in Bolivia in 1962. It is estimated that from 2000 to 3000 persons were affected by the disease, with a case-fatality rate of 20%. An effective rodent control program directed against infected Calomys callosus, the host of Machupo virus, was undertaken in Bolivia and has greatly reduced the number of cases of Machupo hemorrhagic fever.
Guanarito virus (the agent of Venezuelan hemorrhagic fever) was identified in 1990; it has a mortality rate of about 33%. Its emergence was tied to clearance of forest land for small farm use. Sabia virus was isolated in 1990 from a fatal case of hemorrhagic fever in Brazil. Both Guanarito virus and Sabia virus induce a clinical disease resembling that of Argentine hemorrhagic fever and probably have similar mortality rates.
Lymphocytic Choriomeningitis Virus
Lymphocytic choriomeningitis (LCM) virus was discovered in 1933 and is widespread in Europe and in the United States. Its natural vector is the wild house mouse, Mus musculus. It is endemic in mice but can also infect other rodents. About 5% of mice throughout the United States carry the virus. It may chronically infect mouse or hamster colonies and may infect pet rodents.
LCM virus is occasionally transmitted to humans, presumably via mouse droppings. There is no evidence of horizontal person-to-person spread. LCM in humans is an acute disease manifested by aseptic meningitis or a mild systemic influenza-like illness. Rarely is there a severe encephalomyelitis or a fatal systemic disease in healthy people (mortality rate <1%). Many infections are subclinical. The incubation period is usually 1–2 weeks, and the illness lasts 1–3 weeks.
LCM virus infections can be serious in people with impaired immune systems. In 2005, four solid-organ trans plant recipients in the United States became infected from a common organ donor. Three of the four organ recipients died 23–27 days after transplantation. The source of the virus was determined to be a pet hamster recently purchased by the organ donor. The LCM virus also can be transmitted vertically from mother to fetus, and infection of the fetus early in pregnancy can lead to serious defects, such as hydrocephalus, blindness, and fetal death.
Infections are usually diagnosed retrospectively by serology using ELISA for IgM and IgG antibodies. Other diagnostic approaches include immunohistochemical staining of tissues for viral antigens, RT-PCR for viral nucleic acid, and viral culture using Vero cells. Serologic studies in urban areas have shown infection rates in humans ranging from 2% to 5%.
Experimental studies have shown that the immune response may be protective or deleterious in LCM virus infected mice. T cells are required to control the infection but may also induce immune-mediated disease. The result depends on the age, immune status, and genetic background of the mouse and the route of inoculation of the virus. Mice infected as adults may develop a rapidly fatal disease caused by a T cell-mediated inflammatory response in the brain. Congenitally or neonatally infected mice do not become acutely ill but carry a lifelong persistent infection. They fail to clear the infection because they were infected before the cellular immune system matured. They make a strong antibody response that may lead to circulating viral antigen–antibody complexes and immune complex disease.
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