View Full Version : AVI BioPharma works to protect monkeys against Ebola

Ed Jewett
08-23-2010, 02:13 AM
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Drugs Protect Monkeys From Ebola, US Study Finds (http://abcnews.go.com/Technology/wireStory?id=11456963)

ABC News - ?4 hours ago?
WASHINGTON (Reuters) - US government researchers working to find ways to treat the highly deadly Ebola virus said on Sunday a new approach from AVI BioPharma Inc saved monkeys after they were infected.
US scientists 'closer to Ebola drug' (http://www.bbc.co.uk/go/rss/int/news/-/news/health-11054523) BBC News

New Drugs Found to Protect Monkeys from Ebola (http://indyposted.com/82884/new-drugs-found-to-protect-monkeys-from-ebola/) IndyPosted

Los Angeles Times (http://www.latimes.com/news/science/la-sci-ebola-marburg-20100823,0,7448168.story) - Independent (http://www.independent.co.uk/news/science/scientists-hail-breakthrough-in-fight-against-deadly-ebola-virus-2059361.html) - AFP (http://www.google.com/hostednews/afp/article/ALeqM5ialqbwk-MJeN4hUhfQ_CHedtEVJA) - PhysOrg.com (http://www.physorg.com/news201528550.html)
all 49 news articles (http://news.google.com/news/more?pz=1&cf=all&ncl=dYBQ6s5pnFK_U7MXFr7_8ZFpQHEYM&topic=m)

Peter Lemkin
08-23-2010, 06:54 AM
One such biological agent that physicians may not recognize and correctly diagnose, until the laboratory data on the victims begins to accumulate, is Ebola or a related viral hemorrhagic fever (VHF).

Ebola breakouts in Africa have been widely reported. But Ebola's use as a bio weapon has not.

A small amount of Ebola (variety Marburg) released into the subways of New York, Boston or Washington, D.C., could result in hundreds of thousands of deaths within days.

Within the last 25 years, scientists in Russia, Iraq and several other countries have created genetically modified organisms, including plague, anthrax, tularemia and glanders, that are resistant to most antibiotics.

The Russian strains of weaponized anthrax are resistant to penicillin and tetracycline, and probably other antibiotics also.

Bacteria, viruses and toxins have been modified to enhance virulence and infectivity, paving the way for development of pathogens with resistance to vaccines.

Viruses such as Ebola have no known effective treatment at this time, and a vaccine has not been developed.

Wearing a chemical or fireman's mask, or even a surgical mask, may possibly offer some protection against contracting the disease, which is caught by inhalation of the virus or contact with a patient's blood or body fluids.

However, it is highly contagious with a very small number of viruses inhaled, and the chances of contracting the disease from close and prolonged contact with acutely ill patients shedding viruses is high.

Caregivers are in serious jeopardy without the Level 4 biohazard suits.

In 1994, President Clinton declared a state of emergency relating to weapons of mass destruction, which has been renewed every year.

The FBI, DOD, USAMRIID (U.S. Army Medical Research Institute of Infectious Diseases) and CDC (Centers for Disease Control and Prevention in Atlanta), along with state health agencies, have been equipped to investigate and identify biological and chemical agents that could be used in an attack.

Delays of several days may be inevitable, however, and many deaths could occur before the alarm is sounded.

Ebola is a hemorrhagic filovirus shaped like a hockey stick, and belongs to one of four groups of the category, family Filoviridae.

Ebola hemorrhagic fever was first recognized in the western equatorial province of the Sudan and the nearby region of Zaire in 1976.

A second outbreak occurred in Sudan in 1979, and in 1995 a large outbreak (316 cases) developed in Kikwit, Zaire, from a single index case.

Subsequent epidemics have occurred in Gabon and the Ivory Coast. The African strains cause severe disease and death. It is not known why this disease appears infrequently.

A related virus (Ebola Reston) was isolated from monkeys imported into the United States from the Philippines in 1989, and the monkeys subsequently developed hemorrhagic fever. While subclinical infections occurred among exposed animal handlers, Ebola Reston has not been identified as a human pathogen.

Ebola Marburg epidemics have occurred on six occasions: five times in Africa, and once in Europe.

The first recognized outbreak occurred in Marburg, Germany, and Yugoslavia, among people exposed to African green monkeys, and resulted in 31 cases and 7 deaths.

Filoviruses can be spread from human to human by direct contact with infected blood, secretions, organs, or semen.

Dr. Ken Alibek believes that Russia may have developed a strain that is transmissible via the respiratory route. The natural reservoirs of the filoviruses are unknown, although some suspect a species of bat in Africa with exposure to bat droppings.

Clinical Features

The clinical syndrome that these viruses may cause is generally referred to as viral hemorrhagic fever, or VHF.

The viruses target mainly small capillary vessels. Attachment of the virus to the lining cells results in leakage of blood and serum into the surrounding tissue.

Antibody directed against the virus enhances uptake by white corpuscles (WBC), and the cell is dissolved, releasing body defense mechanisms called cytokines. The dissolved WBC results in the release of pro-inflammatory cytokines, pro-coagulants, and anticoagulants, which in turn result in vascular injury to the capillary lining cells and marked permeability (leakage), with complement activation, and a systemic coagulation defect (DIC).

The body actually begins to dissolve before your eyes, rapidly becoming a skin sack of bloody fluid and bone.

Common symptoms beginning 2-3 days after exposure are fever, headache, confusion, muscle pain, and prostration. Physical examination may reveal only conjunctival redness, mild hypotension, flushing, and small skin hemorrhages (petichiae).

Full-blown VHF typically evolves to shock and generalized mucous membrane hemorrhage, and often is accompanied by evidence of lung, bone marrow, kidney, and neurologic involvement. Kidney failure is proportional to general capillary damage.

Most varieties of hemorrhagic fever are notable for pulmonary (lung) involvement and a biphasic illness with subsequent brain damage. With involvement of lung capillaries, there is rapidly progressive and severe pulmonary capillary leak, which presents as ARDS, or Adult Respiratory Distress Syndrome, similar to what is seen with Hantavirus.

Subclinical or clinical pulmonary edema occurs very commonly in Ebola.

Mortality may be substantial, ranging from 50 percent to 90 percent among Ebola victims.


Congo-Crimean Fever is a hemorrhagic fever resembling Ebola seen in Afghanistan, but it is caused by either tick bites or person-to-person exposure.

Large numbers of military personnel presenting with VHF manifestations in the same geographic area over a short time period should lead treating medical care providers to suspect either a natural outbreak in an endemic setting, or possibly a biowarfare attack, particularly if this type of disease does not occur naturally in the local area.

VHF should be suspected in any patient presenting with a severe febrile illness and evidence of vascular involvement (postural hypotension -- low blood pressure, small skin hemorrhages, easy bleeding, flushing of face and chest, non-dependent edema) who has traveled to an area where the virus is known to occur or where intelligence information suggests a biological warfare threat.

Symptoms and signs suggesting additional organ system involvement are common (headache, photophobia [sensitivity to light], pharyngitis [inflammation of the pharynx], cough, nausea or vomiting, diarrhea, constipation, abdominal pain, tingling, dizziness, confusion, tremor), but usually do not dominate the picture, with the exceptions listed above under "Clinical Features."

The clinical laboratory can be very helpful. Definitive diagnosis in an individual case rests on specific virologic diagnosis. Diagnosis by virus cultivation and identification will require 3 to 10 days or longer.

Specialized microbiologic containment is required for safe handling of these viruses. Appropriate precautions should be observed in collecting, handling, shipping and processing diagnostic samples. Both the Centers for Disease Control and Prevention (CDC, Atlanta) and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID, Frederick, Md.) have diagnostic laboratories functioning at the highest (BL-4 or P-4) containment level.

Medical Management

General principles of supportive care apply to pulse, blood pressure , blood counts, and pulmonary and neurologic manifestations of VHF, regardless of the specific causative agent. Only intensive care will save the most severely ill patients.

Health care providers employing vigorous IV fluid resuscitation of hypotensive patients (those with low blood pressure) must be mindful of the propensity of some VHFs for pulmonary capillary leak. Pressor agents are frequently required to raise blood pressure. Antiviral agents such as ribavirin and fresh or frozen plasma may be of some benefit to replace some of the consumed clotting factors.

Isolation and Containment

These viruses pose special challenges for hospital infection control. VHF patients generally have significant quantities of virus in their blood and often in other secretions. Special caution must be exercised in handling sharps, needles and other potential sources of parenteral exposure from contact with the patient's blood.

Strict adherence to standard precautions will prevent nosocomial (in hospital) transmission of most VHFs. Lassa Fever, Congo-Crimean Fever, Ebola and Marburg viruses may be particularly prone to aerosol spread. Secondary infections among contacts and medical personnel who were not parenterally exposed are well documented, and evidently have inhaled viruses suspended in the air.

With Ebola, the incubation period is so short and death is so rapid that by the time health authorities know what hit us, everyone would be dead who was exposed. Inhalation of only 5 viruses (or virions) is usually sufficient to be infectious.

Thus, even the chemical mask gives uncertain protection. Any exposure would require a Level 4 biohazard protection suit and self-contained breathing apparatus for assured protection. The only real way to avoid Ebola is to flee the urban areas as soon as the situation is known. Short of that, the people should avoid football games, concerts, subways, convention halls, hospitals and schools, wherever large crowds make an inviting target.

In a village setting, the disease tends to burn out quickly because of rapid incapacity and death of the victims. The picture may be different in large cities with numerous cases and more people exposed.