NAME: Junin virus.
CHARACTERISTICS: Junin virus is a member of the family Arenaviridae, genus Arenavirus , and belongs to the Tacaribe complex (New World arenaviruses)(1). Like all other arenaviruses, it is an enveloped, round, oval or pleomorphic virion, measuring roughly 110 nm to 300 nm in diameter (average is 120 nm), with a single-stranded bi-segmented RNA genome(1,3,9,13). The virion interior contains granules resembling grains of sand, which are characteristic of the family Arenaviridae, while the surface has hollow golf-club shaped projections(1,3).
PATHOGENICITY/TOXICITY: Most infections with Junin virus (80%) result in clinical disease(4). Three phases are recognised in Argentine haemorrhagic fever (AHF) caused by Junin virus: prodromal, neurological-haemorrhagic, and convalescence(4).
Prodromal phase : Usually lasts for 1 week from the onset of symptoms(4). The onset is insidious, with symptoms such as chills, malaise, anorexia, headache, myalgia centered particularly over the lower back, and moderate hyperthermia (38 to 39°C)(3,4,9). Other common symptoms include retro-orbital pain, nausea or vomiting, epigastric pain, photophobia, dizziness, constipation, or mild diarrhoea(4). Physical examination will often reveal flushing of the face, neck, and upper chest, conjunctival congestion, and periorbital oedema(4,9,10). The gums may look congested and may bleed spontaneously or under slight pressure(4). At the end of this phase the patient may be irritable, lethargic, and present with a fine tremor of the hand and tongue(4,9,10). In females, non-menstrual uterine bleeding is common(1).
Neurological-haemorrhagic phase : Around 20 to 30% of AHF cases develop neurological and/or haemorrhagic symptoms, usually between 8 and 12 days after the onset of symptoms(3,4). Patients will present severe haemorrhagic or neurologic manifestations, shock and superimposed bacterial infections(4). Haemorrhagic signs include vomiting of blood, tar coloured stools, blood in the lungs, nose bleeds, haematomas, non-menstrual uterine bleeding, and bloody urine(4,8). Neurological manifestations begin with mental confusion, marked ataxia, increased irritability and tremors that are followed by delirium, generalised convulsions and coma(4). Superimposed bacterial infections presenting as pneumonia and septicaemia may complicate the disease at this period(4).
Convalescence phase : Surviving cases experience a prolonged, protracted convalescence that lasts from 1 to 3 months. Patients experience weakness, irritability, memory loss, and hair loss, but usually suffer without permanent sequelae(3,4,9,13).
When untreated, the case fatality for AHF is 10 to 30%, which is lowered to 1% when treated with serum from patients who have recovered from AHF (convalescent serum/plasma)(3,5,9,10,11,13); however, 10% of patients who receive convalescent serum develop a transient neurological syndrome, characterised by headaches and tremors(3,13).
EPIDEMIOLOGY: Junin virus is endemic to the fertile farming plain of central Argentina, known as the "humid pampas"(12). The emergence of AHF in the 1950s is hypothesised to have occurred due to human alterations of the habitat in relation to agricultural practices(4). The endemic area is inhabited by a population of more than 5,000,000 and covers approximately 150,000 km2 , reaching north of the province of Buenos Aires, southeast of Cordoba, south of Santa Fe, and northeast of La Pampa(1,6,10). Since the recognition of AHF, annual outbreaks have been recognised without interruption, with between 300 and 1,000 recorded cases per year(4,12).Most of the cases of human infection occur between April and July, coinciding with an increase in agricultural activities that facilitate human contact with the rodent reservoirs of Junin virus that also peak in population at the same time(1,14). Indeed, during this time 75% of humans with AHF are male agricultural workers involved in the harvesting of crops(3,14,16).
HOST RANGE: Rodents are natural hosts, mainly Calomys musculinus (dry lands vesper mouse) and Calomys laucha (small vesper mouse), but Junin virus antigens have also been found in Akodon azarae (grass mouse), Bolomys obscurus (dark bolo mouse), Mus musculus (house mouse), and Oligoryzomys flavescens (yellow pigmy rice rat)(1,4,8,9,10,12,13,14). Humans are accidental hosts, and laboratory bred mice, rats, guinea pigs, and non-human primates are experimental hosts(1,2,3,4,5,6,7,9,10,11,12,13,14).
INFECTIOUS DOSE: Unknown.
MODES OF TRANSMISSION: Human exposure to Junin virus is believed to occur mainly through inhalation of aerosolised body fluids (blood, saliva) or excretions (urine, faeces) of infected rodents, typically during agricultural work(1,3,4,11,13). Transmission can also occur via contact of skin lesions to infected rodent secretions and/or excretions(10).
DRUG SUSCEPTIBILITY: Sensitive to ribavirin, trifluoperazine, and chlorpromazine in vitro(2,5). Junin virus is also susceptible in vitro to an antiretroviral zinc-finger active compound known as NSC20625(6).
SUSCEPTIBILITY TO DISINFECTANTS: Like all lipid enveloped viruses, Junin virus is readily inactivated by common fixatives such as glutaraldehyde, formalin, paraformaldehyde; chlorine-based disinfectants, such as 1% sodium hypochlorite; as well as 70% alcohol, hydrogen peroxide, peracetic acid, quaternary ammonium compounds, and iodophor compounds(10,17).
SURVIVAL OUTSIDE HOST: Unknown.
SURVEILLANCE: Monitor for symptoms. Virus isolation from blood and mucosal secretions (and propagation in cell culture) can be done starting from the prodromal phase of the disease; however, RT-PCR offers greater sensitivity for the low viremia encountered during the early period, which allows a faster response to infection(3,9,10). Other techniques such as IgM and IgG ELISA, antigen detection ELISA and neutralisation tests are also frequently used to detect Junin virus(3,9,11,14,15).
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Supportive therapy is important in the management of patients with AHF(4,9,12). Gentle sedation and pain relief with conservative doses of opiates and careful maintenance of hydration is recommended(9). The administration of convalescent serum is the treatment of choice, and has been shown to be highly effective(4,13). Antiviral treatment with ribavirin may prove effective as a treatment, provided that it is administered early in the course of the illness(4,5).
IMMUNIZATION: A live attenuated Junin virus vaccine known as Candid #1 was found to be safe and highly efficacious when tested in AHF-endemic areas(16).
PROPHYLAXIS: The administration of convalescent serum is recommended after exposure to Junin virus in the laboratory or while handling patients(10). At risk individuals may also be administered oral ribavirin(3).
LABORATORY-ACQUIRED INFECTIONS: Twenty-one cases of laboratory-acquired Junin virus infection (1 death) were reported up until 1980(18).
SPECIAL HAZARDS: Centrifugation of virus infected samples is considered the most dangerous of all laboratory manipulations involving Junin virus(10). Additional precautions should be considered with work involving animals or large scale activities(10).
RISK GROUP CLASSIFICATION: Risk Group 4(19).
CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures
PROTECTIVE CLOTHING: Personnel entering the laboratory must remove street clothing, including undergarments, and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes(20).
OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animal activities(20).
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)(20).
DISPOSAL: Decontaminate all materials for disposal from the containment laboratory by steam sterilization, chemical disinfection, incineration or by gaseous methods. Contaminated materials include both liquid and solid wastes(20).
STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory(20).
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: August 2010.
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.
Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Public Health Agency of Canada, 2010