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Argentine Hemorrhagic Fever

WELCOME TO

The Junin Virus!

What are Viruses?

The Junin

Virus!

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

INTRO TO

Argentine HEMORRHAGIC FEVER!

Origins of AHF

More About Junin

Viral Hemorrhagic Fevers (VHF)

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

BSL-4

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

Vector

Mortality & Morbidity

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

The Endemic Area

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)

SYMPTOMS of AHF!

Symptoms of Viral Hemorrhagic Fevers

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

Convalescent Period

Symptoms of AHF

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

Continued Symptoms of AHF

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

PICS!

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

PICS!

Peak of AHF

PICS!

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

Progression of

AHF Symptoms

Fully Developed Disease

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

PICS!

HOPE FOR

JUNIN VICTIMS!

The Vaccine

On a Cellular Level

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

Other Treatment

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

Focus for

A Vaccine

Prevention

"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

Occurrence

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

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