Argentine hemorrhagic fever

Argentine hemorrhagic fever
Other names: Junin hemorrhagic fever[1]
Top:Human transmission vias of Arenavirus.[2] Bottom: Candid #1 vaccine strain of JUNV [3]
Specialty	Infectious disease
Symptoms	Fever, malaise[4]
Complications	Petechiae, digestive tract ulcerations, and hematuria[5]
Causes	Junin virus[6]
Diagnostic method	RT-PCR[7]
Differential diagnosis	Bolivian hemorrhagic fever, Lassa fever, Dengue fever[8][9]
Prevention	Vaccine Candid #1[10]
Treatment	Immune plasma[11][5]

Argentine hemorrhagic fever (AHF) or O'Higgins disease, is a hemorrhagic fever and zoonotic infectious disease occurring in Argentina. It is caused by the Junín virus^[3](an arenavirus, closely related to the Machupo virus, causative agent of Bolivian hemorrhagic fever). Its reservoir of infection is the drylands vesper mouse, a rodent found in Argentina and Paraguay.^[3][8]

Ribavirin also has shown a degree of promise in the treatment of arenaviral diseases.^[12]The disease was first reported in the town of O'Higgins in Buenos Aires province, Argentina in 1958, giving it one of the names by which it is known.^[13]

Signs and symptoms

AHF is a acute disease whose incubation time is within the first couple of weeks, after which the first symptoms appear: fever, headaches, weakness, loss of appetite and will. These intensify less than a week later, forcing the infected to lie down, and producing stronger symptoms such as vascular, renal, hematological and neurological alterations, this stage lasts several weeks.^[4][14][5]

Cause

In terms of the etiology we find that Argentine hemorrhagic disease is caused by the Junin virus (JUNV)^[6] Junin virus^[15] is an arenavirus in the Mammarenavirus genus. Junín virus is a negative sense ssRNA enveloped virion with a variable diameter between 50 and 300 nm. The surface of the particle encompasses a layer of T-shaped glycoproteins, each extending up to 10 nm outwards from the envelope, which are important in mediating attachment and entry into host cells.^[16]

• 
  Schematic structure of an arena virus
• 
  Junin virus

Transmission

The natural reservoir of infection, a small rodent known locally as ratón maicero ("maize mouse"; Calomys musculinus), has chronic asymptomatic infection, and spreads the virus through its saliva and urine. It is found mostly in people who reside or work in rural areas; 80% of those infected are males between 15 and 60 years of age.^[17][13]

Mechanism

As to the(simple) mechanism we find that Junín virus replicates in the lungs after inhalation of rodent excreta.Thereafter, spreads to various organs, including the vascular endothelium, myocardium, kidneys, and central nervous system.We find infection can suppress both innate and adaptive immune responses, allowing the virus to spread systemically. Finally, systemic spread leads to tissue damage, excessive cytokine responses, vascular leakage, and disseminated intravascular coagulation.^[3][18]

Diagnosis

The evaluation for this hemorrhagic fever in an affected individual can be done via the following:^[7]

• CBC
• ELISA
• PCR

Differential diagnosis

The DDx of Argentine hemorrhagic fever in an affected individual is as follows:^[8][9]

• Bolivian hemorrhagic fever(Machupo virus)
• Venezuelan hemorrhagic fever(Guanarito virus)
• Brazilian hemorrhagic fever(Sabia virus)
• Chikungunya virus
• Leptospirosis
• Malaria

Prevention

The Candid #1 vaccine for AHF was created in 1985 by Argentine virologist Dr. Julio Barrera Oro. The vaccine was manufactured by the Salk Institute in the United States, and became available in Argentina in 1990. Antibodies produced by Candid #1 vaccination have also demonstrated cross-reactivity with Machupo virus in Rhesus macaques, and thus Candid #1 been considered for prophylactic use against Bolivian hemorrhagic fever.^[10]

Candid #1 has been applied to adult high-risk population and is very effective. Between 1991 and 2005 more than 240,000 people were vaccinated, achieving a great decrease in the numbers of reported cases.^[20][21][22]

On 29 August 2006 the Maiztegui Institute obtained certification for the production of the vaccine in Argentina. The vaccine produced in Argentina was found to be of similar effectiveness to the US vaccine.^[23][22] Details of the vaccine were published in 2011,^[20] and a protocol for production of the vaccine was published in 2018.^[24]

Demand for the vaccine is insufficient to be commercially appealing due to the small target population, and it is considered an orphan drug; the Argentine government committed itself to manufacture and sponsor Candid #1 vaccine.^[20]

Treatment

The specific treatment includes plasma of recovered patients, which, if started early, is extremely effective and reduces mortality .Ribavirin also has shown some promise in treating arenaviral diseases.If untreated, the mortality of AHF reaches 15–30 percent. ^[11][5]

Epidemiology

Major epidemics often coincide with the harvesting season in Argentina, with peak incidence in May. This is likely due to increased human contact with rodents during agricultural activities and higher rodent populations at this time.The disease is about four times more common in males than females.^[3]

• 
  Map of South America shows the ranges of mammal species associated with New World mammarenaviruses. The species have been identified as hosts from serosurveillance, or have been confirmed as hosts via virus isolation^[25]
• 
  VHF- color denotes the number of VHF with at least one outbreak reported by country - Argentine hemorrhagic fever is ArHF^[26]
• 
  Geographical location of Argentine hemorrhagic fever

History

The disease was first detected in the 1950s in the county of Junín Partido in Buenos Aires, after which its agent, the Junín virus, was named upon its identification in 1958. In the early years, about 1,000 cases per year were recorded, with a high mortality rate . The initial introduction of treatment serums in the 1970s reduced this lethality.^[5][27]

The Junin virus was specifically identified and isolated in 1958 by Dr. Adolfo S. Parodi.^[28]

Society and culture

Argentine hemorrhagic fever was one of three hemorrhagic fevers and one of more than a dozen agents that the United States researched as potential biological weapons before the nation suspended its biological weapons program.^[29] The Soviet Union also conducted research and developing programs on the potential of the hemorragic fever as a biological weapon.^[30]

References

Further reading

External links