Argentine hemorrhagic fever (AHF) or O'Higgins disease, also known in Argentina as ''mal de los rastrojos'' (stubble disease) is a

hemorrhagic fever Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families '' Filoviridae'', '' ...

and

zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...

infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

occurring in Argentina. It is caused by the ''

Junín virus ''Argentinian mammarenavirus'', better known as the ''Junin virus'' or ''Junín virus'' (JUNV), is an arenavirus in the ''Mammarenavirus'' genus that causes Argentine hemorrhagic fever (AHF). The virus took its original name from the city of Jun ...

'' (an

arenavirus An arenavirus is a bisegmented ambisense RNA virus that is a member of the family ''Arenaviridae''. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have ...

, closely related to the '' Machupo virus'',

causative agent In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ge ...

Bolivian hemorrhagic fever Bolivian hemorrhagic fever (BHF), also known as black typhus or Ordog Fever, is a hemorrhagic fever and zoonotic infectious disease originating in Bolivia after infection by ''Machupo mammarenavirus''.Public Health Agency of Canada: ''Machupo Vir ...

). Its

vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...

is the

drylands vesper mouse The drylands vesper mouse (''Calomys musculinus'') is a species of rodent in the family Cricetidae. It is found in Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the sout ...

, a

rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...

found in Argentina and Paraguay.

Epidemiology

The disease was first reported in the town of in Buenos Aires province, Argentina in 1958, giving it one of the names by which it is known. Various theories about its nature were proposed: it was Weil's disease,

leptospirosis Leptospirosis is a blood infection caused by the bacteria '' Leptospira''. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe ( bleeding in the lungs or meningitis). Weil's disease, the acute, sever ...

, caused by chemical pollution. It was associated with fields containing stubble after the harvest, giving it another of its names. The endemic area of AHF covers approximately 150,000 km², compromising the

provinces A province is almost always an administrative division within a country or state. The term derives from the ancient Roman '' provincia'', which was the major territorial and administrative unit of the Roman Empire's territorial possessions ou ...

Buenos Aires Buenos Aires ( or ; ), officially the Autonomous City of Buenos Aires ( es, link=no, Ciudad Autónoma de Buenos Aires), is the capital and primate city of Argentina. The city is located on the western shore of the Río de la Plata, on South ...

, Córdoba, Santa Fe and

La Pampa La Pampa () is a sparsely populated province of Argentina, located in the Pampas in the center of the country. Neighboring provinces are from the north clockwise San Luis, Córdoba, Buenos Aires, Río Negro, Neuquén and Mendoza. History ...

, with an estimated risk population of 5 million. The vector, a small rodent known locally as ''ratón maicero'' ("maize mouse"; ''Calomys musculinus''), has chronic

asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered a ...

infection, and spreads the virus through its

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can ...

and

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

. Infection is produced through contact of skin or mucous membranes, or through inhalation of infected particles. 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.

Clinical aspects

AHF is a grave acute disease which may progress to recovery or death in 1 to 2 weeks. The incubation time of the disease is between 10 and 12 days, 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 about 3 weeks. If untreated, the mortality of AHF reaches 15–30%. The specific treatment includes plasma of recovered patients, which, if started early, is extremely effective and reduces mortality to 1%.

Ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pe ...

also has shown some promise in treating arenaviral diseases. The disease was first detected in the 1950s in the

Junín Partido Junín Partido is a county ('' partido'') in the . Its population is 88,664 inhabitants () and the population density reaches 39.4 inhabitants/km2. Its administrative seat is the city of Junín. Geography Junín occupies an area of , It is bound ...

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 (more than 30%). The initial introduction of treatment serums in the 1970s reduced this lethality.

Vaccine

The ''Candid #1''

vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.

for AHF was created in 1985 by Argentine virologist Dr. Julio Barrera Oro. The vaccine was manufactured by the

Salk Institute The Salk Institute for Biological Studies is a scientific research institute located in the La Jolla community of San Diego, California, U.S. The independent, non-profit institute was founded in 1960 by Jonas Salk, the developer of the polio vacci ...

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

. ''Candid #1'' has been applied to adult high-risk population and is 95.5% effective. Between 1991 and 2005 more than 240,000 people were vaccinated, achieving a great decrease in the numbers of reported cases (94 suspect and 19 confirmed in 2005). On 29 August 2006 th
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. Details of the vaccine were published in 2011, and a protocol for production of the vaccine was published in 2018. Demand for the vaccine is insufficient to be commercially appealing due to the small target population, and it is considered an

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

; the Argentine government committed itself to manufacture and sponsor ''Candid'' #1 vaccine.

Weaponization

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 weapon A biological agent (also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon) is a bacterium, virus, protozoan, parasite, fungus, or toxin that can be used purposefully as a weapon in bioterroris ...

s before the nation suspended its biological weapons program." The

Soviet Union The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen nationa ...

also conducted research and developing programs on the potential of the hemorragic fever as a biological weapon.

References

External links