Progress in the Experimental Therapy of Severe ArenaViral Infections

Abstract

Summary A number of viruses in the family Arenaviridae cause severe illness in humans. Lassa virus in West Africa and a number of agents in South America produce hemorrhagic fever (HF) in persons exposed to aerosolized excretions of the pathogens’ rodent hosts. Because arenaviruses are not transmitted by arthropods, and person-to-person spread is rare, human infections occur singly and sporadically, and are usually not diagnosed until the patient is severely ill. Because the arenaviruses are naturally transmitted by the airborne route, they also pose a potential threat as aerosolized bioterror weapons. The broad-spectrum antiviral drug ribavirin was shown to reduce mortality from Lassa fever, and has been tested against Argentine HF, but it is not an approved treatment for either disease. Human immune convalescent plasma was proven to be effective for Argentine HF in a controlled trial. New treatments are needed to block viral replication without causing toxicity and to prevent the increased vascular permeability that is responsible for hypotension and shock. In this paper, we review current developments in the experimental therapy of severe arenaviral infections, focusing on drugs that have been tested in animal models, and provide a perspective on future research.

A Host-Oriented Inhibitor of Junin Argentine Hemorrhagic Fever Virus Egress

“…JUNV is endemic in regions of Argentina and West Africa and is the cause of severe episodes of hemorrhagic fever with high mortality rates. The search for effective therapeutics to treat arenavirus infections, particularly those caused by Junin and Lassa viruses, has been an active area of research for many years (8,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). More recent efforts in the field of antiviral therapeutics for emerging RNA viruses have focused on identifying host factors or virus-host interactions, rather than solely viral proteins, as targets for novel antivirals (6, 8-13, 39, 40, 43, 44).…”

Rodents as Potential Couriers for Bioterrorism Agents

“…41,42 In contrast, Old World viruses (ie, Lassa virus and Lujo virus), which are found in Africa, and several New World viruses in South America (eg, Junin, Machupo, Sabia, Guanarito, and Chapere) can cause severe disease and hemorrhagic fever syndrome. 43 Rodent-to-human infections of arenaviruses are thought to occur through aerosols and fomites. 41 This indicates that these agents could potentially be used as bioweapons if propagated to high titer in cell culture and in aerosols.…”

“…41 This indicates that these agents could potentially be used as bioweapons if propagated to high titer in cell culture and in aerosols. 43 Most cases of arenavirus transmission occur in rural, agricultural areas. The lack of rapid diagnostic methods for specific diagnoses of arenaviral hemorrhagic fevers means that diagnoses are usually made late in the illness and in most cases vaccination is not available.…”

“…The lack of rapid diagnostic methods for specific diagnoses of arenaviral hemorrhagic fevers means that diagnoses are usually made late in the illness and in most cases vaccination is not available. 43 Because arenaviruses are rarely transmitted from person-to-person and are not carried by arthropods, each arenaviral disease is tightly constrained in the geographic range of its rodent reservoir host. 43 This means that a bioterrorism attack could increase the infection prevalence in local rodent fauna RODENTS AS COURIERS FOR BIOTERORISM AGENTS in endemic areas only (although a possible spill-over infection in other species cannot be ruled out).…”

“…43 Because arenaviruses are rarely transmitted from person-to-person and are not carried by arthropods, each arenaviral disease is tightly constrained in the geographic range of its rodent reservoir host. 43 This means that a bioterrorism attack could increase the infection prevalence in local rodent fauna RODENTS AS COURIERS FOR BIOTERORISM AGENTS in endemic areas only (although a possible spill-over infection in other species cannot be ruled out). When an attack also involves the release of infected rodents, the spread of the disease would depend on the ability of the infected host to establish itself in a nonendemic area.…”