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They are teeny tiny infectious agents
Since viruses cannot reproduce on their own they must hijack host cell proteins and machinery to do so
After replication, viruses have 3 options:
Undergo lysis - killing the cell
Enter the lysogenic cycle - viral genome is incorporated into the host's chromosome (provirus) - still can lead to lysis
Via budding - viruses leak out of cell through
viral receptors - slowly uses up cell
membrane and eventually leads
to cell death
Isolated in 1958
ID: New World - Arenavirus - genus of virus that infects rodents and occasionally humans
1st identified Arenavirus to cause hemorrhagic fever
The pathogenic strain of Junin virus causes Argentine hemorrhagic fever (AHF)
This virus is considered to be a potential bioterrorism agent
Negative sense ssRNA enveloped virus
Diameter between 50 and 300 nm
Discovered in Argentina (1958):
Geographical areas - Buenos Aires, La Pampa, the southern part of Santa Fe, and the eastern part of Córdoba
Argentine Hemorrhagic fever (AHF), O'Higgins disease, mal de los rastrojos, stubble disease
The disease was first detected in the 1950s in the Junín Partido in Buenos Aires, after which its agent, the Junín virus, was named upon its identification in 1958 in a town called O'Higgins in Buenos Aires province, Argentina (1958)
It was associated with fields containing stubble after the harvest, giving it another of its names
A group of illnesses that are caused by several distinct families of viruses
The term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome
Characteristically:
The overall vascular system is damaged
The body's ability to regulate itself is impaired
Symptoms are often accompanied by hemorrhage (bleeding)
AHF (the pathogenic strain of Junin virus) is a Biosafety Level 4 pathogen
This level is required for work with dangerous agents that pose a high individual risk of aerosol-transmitted laboratory infections
These agents cause severe to fatal disease in humans and have no vaccines or treatment available*
Use of positive pressure personnel suit & segregated air supply hoses
The mortality rate was up to 15% - 30% of all symptomatic cases - lowered to 1% in most cases now
Morbidity is higher in males than in females, the ratio being approximately 5 to 1
Delayed diagnosis/ unnoticed detection of severe cases accounts for the high mortality reported during the first large occurrence of AHF in the mid 1950's
Thanks to improved diagnostic and therapeutic measures (early recognition and timely treatment)
the mortality rate has decreased significantly
AHF is a zoonotic infectious disease - vector is a species of rodent, the corn mouse (ratón maicero/ maize mouse) - Calomys musculinus
The Calomys musculinus suffers from a chronic asymptomatic infection, and spreads the virus through its saliva and urine/ droppings
Infection is produced through contact of skin or mucous membranes, or through inhalation of infected particles
Covers approximately 150,000 km², compromising the provinces of Buenos Aires, Córdoba, Santa Fe, and La Pampa [the Pampa region]
Populous land area, lots of fields (in the summer, corn and sunflower) - during summers with humidity and abundant rain the grassland vegetation is plentiful - this condition is accompanied by an increase in the wild rodent population
Estimated risk population of 5 million - AHF found mostly in people who reside or work in rural areas; 80%
of those infected are males between 15 and 60 yrs
Peak endemic times: April - June
(summer months)
Specific signs and symptoms vary by the type of VHF, but initial signs and symptoms often include:
marked fever, fatigue, dizziness, muscle aches, loss of strength, & exhaustion
Patients with severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears
Severely ill patient cases may also show shock, nervous system malfunction, coma, delirium,
and seizures
Begins with a drop in temperature (lasting 2-4 wks)
Facial edema disappears, hemorrhages reabsorbed to skin
BP & pulse rate return to normal
Fatigue may continue for several weeks
Usually there is a partial and gradual loss of hair, followed eventually by the growth of new hair (noted in women)
Recovery is usually without sequelae
Uncomplicated cases
seldom fatal
Usual onset is vague with flu-like symptoms, such as malaise, fatigue, chills, & lumbar backache
Fever is almost always present
Facial edema (puffiness) & erythema (redness/ flushed)
Headache is almost always constant with associated extraocular pain and sensitivity
Stiffness is present in the neck and upper back
Constipation is frequently seen
Enanthemas (white rash on tongue) & sometimes petechiae (small hemorrhagic spots, purple-red color) are present on buccal mucosa [nonpainful spots, present from 4-6 days, increase in number during acute phase]
Sometimes present: halitosis (bad breath), anorexia, polydipsia (excessive thirst), nausea, vomiting, diarrhea, abdominal distention, and epigastralgia
Feces: fluid, frequent melena (black tarry stool) & hematochezia (blood in stool) [lasts from 2-3 days]
In women: there may be uterine hemorrhages
Although the patient is extremely thirsty, the
pt refuses to drink, in order to avoid spasms of the laryngeal and pharyngeal muscles
At disease peak, temperature may get as high as 104 degrees Fahrenheit
Increased sensitivity of the skin as well as contraction of muscles under the skin upon touch
Photophobia, strabismus, and nystagmus may also be seen
Increased sx of halitosis with odor of decay,
as well as thick brown coating on the
tongue; dry cough promotes
Patient feels dull, drowsy, confused, & often apathetic - not immediately responsive
Tremor of the tongue during its protrusion is accentuated // tremor of the upper extremities when the arms are extended forward (paresis - generalized muscular weakness)
Patient's gait is unsteady & active movement is slow
Common sx: non-inflammatory, painless
generalized lymphadenopathy
Hemorrhagic injury characterized by bleeding of the gums, epistaxis (nose bleed); in some few severe cases, hematemesis (vomiting of blood), melena, & enterorrhagia (intestinal bleeding)
A rash first appears on the trunk and spreads to the extremities (petechial rash - red-purple spots denoting hemorrhage)
Bradycardia (decreased heart rate) & hypotension in 90% of cases
TTP of kidney - associated oliguria (decrease in urine
output) - could develop to anuria (failure to
produce urine) -- could lead to acute renal
failure, uremic coma, & death
The initial introduction of treatment serums in the 1970s reduced lethality of Junin
A vaccine is available - Candid #1 (created 1985)
Candid #1 was manufactured by the Salk Institute in the US & became available in Argentina in 1990
Licensed for use only in areas where Argentine hemorrhagic fever is endemic
95.5% effective
Background: virus cannot reproduce on their own so they must hijack and utilize the cell
Possible way to fix this problem:
In the budding process, attempt to block and reduce the infection to a level a person’s immune system would be able to control more easily
Human protein Tsg101 - important for the virus to break free of the host cell’s plasma membrane and continue infecting other cells [blocking this means viruses would remain stuck to the cell
membrane & not able to perpetuate the
viral infection
In Argentina, infection of the Junin virus is often (and effectively) treated with plasma transfusions from a Junin survivor [reduces mortality to 1%]
Patients may receive supportive therapy
Ribavirin (an anti-viral drug) has also shown some promise in treating arenaviral diseases
Treatment goal: to develop immunologic &
molecular tools for more rapid disease
diagnosis
"Prevention is the best medicine"
Prevention efforts must concentrate on avoiding contact with host species & further transmission from person to person
Rodent based prevention:
Controlling rodent populations
Discouraging rodents from entering or living in homes or workplaces
Encouraging safe cleanup of rodent
nests and droppings
Looking for drugs that target interactions between a virus and host (such as proteins involved in budding) - this reduces the likelihood that a virus would mutate to develop resistance
There's a possibility that a drug might compromise the normal function of the protein...
These drugs could also be offered in a cocktail with additional compounds that
block other stages of the virus
life cycle
Mechanized harvesting and better living situations for harvesters has decreased the prevalence of AHF
Between 1991 and 2005 more than 240,000 people were vaccinated, achieving a great decrease in the numbers of reported cases [94 suspected cases and 19 confirmed cases in 2005]
Morganna Raven Burroughs
Infectious Diseases - 11am
University of Texas at Arlington