Arenaviridae
Arenaviridae is a family of highly infectious and virulent zoonotic viruses primarily transmitted to humans through direct contact with rodents or inhalation of aerosols from rodent excreta. This family is divided into two main branches: Old World and New World, reflecting their geographical origins in relation to their rodent hosts. Old World viruses, such as Lassa virus, are predominantly found in sub-Saharan Africa, while New World viruses are largely situated in South America and parts of the southwestern United States. Arenaviruses are characterized by their spherical shape and beaded nucleocapsid structure, containing two single-stranded RNA segments.
There are nine arenaviruses known to cause human disease, with five, including Lassa and Machupo viruses, resulting in severe hemorrhagic fever syndromes. Lassa fever, first recognized in Nigeria in 1969, has become a significant health concern in West Africa, with hundreds of thousands of cases each year. Symptoms often include fever, malaise, and can progress to more severe manifestations, including vascular permeability issues and sensorineural deafness. While ribavirin shows promise in treating some arenavirus infections, no vaccines exist for most of these viruses, highlighting the ongoing need for research and public health measures in at-risk regions.
Arenaviridae
- TRANSMISSION ROUTE: Direct contact, inhalation
Definition
The arenaviridae family comprises highly infectious, virulent, zoonotic, viral pathogens transmitted to humans by rodents. Each arenavirus is associated with a specific host native to its geographical region.
Two branches classify arenaviruses: Old World and New World. These branches represent the geographical origin and subsequent evolutionary pathway to its current locale. The pathway also represents a complicated coevolution between the host and its ribonucleic acid (RNA), with point mutations during genome replications allowing for a large diversity in the arenavirus family.
Natural Habitat and Features
The arenavirus is a beaded nucleocapsid with two single-stranded RNA segments with negative polarity. The virus particles are spherical with an average diameter of 110 to 130 nanometers (nm) and are enveloped in a lipid membrane. The genome includes RNA only. The virus’s replication strategy involves forming virions that are spheroid and 50 to 300 nm. The virions bead off from the host cells, giving off a grainy or sandlike appearance, hence the name “arena,” meaning “sand” in Latin.
The Old World or Lassa virus derives from the rodent family Muridae, subfamily Muridnae, from which viruses including Lassa and lymphocytic choriomeningitis were derived.
The New World or Tacaribe virus comes from rats, bats, and mice of the family Muridae, subfamily Sigmodontinae. These viruses include Amapari, Guanarito, Junin, Latino, Machupo, Sabia, Tacaribe, and Whitewater Arroyo.
Most Old World viruses are found in sub-Saharan Africa, except lymphocytic choriomeningitis, which was first discovered in the United States (Missouri) and is now found worldwide. Three New World viruses are found in the southwestern regions of the United States; Tacaribe is found in Trinidad. Most of the remaining viruses are found in South America. Specialists indicate that a new arenavirus is discovered every three years.
The habitats of the arenaviruses include any location with rodents and mice. Agricultural areas, barns, homes (especially poorly maintained ones), and dry savannas are especially vulnerable to epidemics. Other areas of possible infection are laboratories that use mice or rodents and homes with pet mice, rats, or hamsters. Secondary and nosocomial infections are especially problematic for Lassa and Machupo viruses.
Pathogenicity and Clinical Significance
Arenaviruses are considered highly infectious, virulent pathogens. There are nine arenaviruses associated with human disease. Five of these, Lassa, Junin, Machupo, Guanarito, and Sabia, are known to cause severe hemorrhagic syndromes and have led to regional epidemics. Lymphocytic choriomeningitis causes an acute central nervous system disease that can lead to congenital malformation. Other viruses are virulent to humans but have caused limited, nonlethal, and nonepidemic cases only or have been grown only in the laboratory.
Lassa fever was first seen in Nigeria in 1969. Since then, it has spread throughout West Africa and, because of widespread international travel, has appeared throughout the world. A reported 100,000 to 300,000 cases occur each year, with 5,000 deaths in West Africa alone. In addition to the expected transmission routes, persons in this area consume rodents, leading to infection caused by ingestion. Nosocomial rates are very high, too. Pregnant women are especially at risk, and they risk miscarriage caused by infection at a rate of 75 percent.
The incubation time for Lassa fever is seven to eighteen days, after which the infected person has a fever, is weak, and has general malaise. Cough, severe headaches, sore throat, and gastrointestinal symptoms follow. The next stage of the illness involves vascular permeability, such as facial edema and pleural effusions; if a patient reaches this stage of the illness, the prognosis becomes poor. Rapid deterioration follows, with pulmonary edema, shock, seizures, and coma. Another significant feature of this illness is sensorineural deafness in up to 15 percent of patients.
The South American hemorrhagic fevers (Argentine hemorrhagic fever, Guanarito, Machupo, Junin, and Sabia) are usually found in agricultural areas or hot, dry landscapes, such as the Argentine pampas. Argentine hemorrhagic fever has a mortality rate of 15 to 30 percent. Incubation is one to two weeks, after which the patient experiences fever, malaise, mild neurological symptoms, and vascular damage.
Lymphocytic choriomeningitis usually affects young adults. One common cause in industrialized nations is a bite from a pet hamster. The illness manifests with fever, headache, leukopenia, and thrombocytopenia. After three to four days, the fever may dissipate, but it can return two to four days later with a severe headache and meningitis. Lymphocytic choriomeningitis can cause severe damage to the central nervous system, including hydrocephalus and chorioretinitis.
Drug Susceptibility
No drug combats all the arenaviruses. However, some success has been found with the use of ribavirin, a nucleoside analog that has been shown to help reduce morbidity and mortality in Lassa, Machupo, and Junin infections. Ribavirin must be given early in the course of the infection to target the viral life cycle. Patients with a lower viral load tend to have lower morbidity and mortality rates.
No vaccines are available for any of the arenaviruses except Junin. Candid #1, a live attenuated vaccine for Junin virus, has been developed. The U.S. Army Medical Research Institute of Infectious Diseases has taken a special interest in the South American hemorrhagic viruses as potential biological warfare agents. The institute is also assisting researchers in developing vaccines.
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