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6.0  DETECTION OF VIRAL WEAPONS

“Viruses are the simplest microorganisms and consist of a nucleocapsid protein coat containing genetic material, either RNA or DNA. In some cases, the viral particle is also surrounded by an outer lipid layer. Viruses are much smaller than bacteria and vary in size from 0.02 microns to 0.2 microns. Viruses are intracellular parasites and lack a system for their own metabolism; therefore, they are dependent on the synthetic machinery of their host cells. This means that viruses, unlike the bacteria, cannot be cultivated in synthetic nutritive solutions, but require living cells in order to multiply. The host cells can be from humans, animals, plants, or bacteria. Every virus requires its own special type of host cell for multiplication, because a complicated interaction occurs between the cell and virus. Virus-specific host cells can be cultivated in synthetic nutrient solutions and then infected with the virus in question. Another common way of cultivating viruses is to grow them on chorioallantoic membranes (from fertilized eggs). The cultivation of viruses is expensive, demanding, and time-consuming. A virus typically brings about changes in the host cell that eventually lead to cell death.” (Kortepeter 2001, 50)

“Although viruses have probably been around since life on this planet began, they were discovered only a scant hundred years ago. In 1892 a Russian botanist, Dmitry Ivanovsky, was investigating tobacco mosaic disease, which caused mottling and blistering of tobacco leaves. It was an affliction that threatened the tobacco industry of Russia and Europe. Ivanovsky passed the sap of infected plants through a porcelain filter that was believed to trap all types of microorganisms, including bacteria, the smallest know pathogens. The filter had been invented by Charles Chamberlain, the trusted assistant of Louis Pasteur, and was used in many homes to filter and purify drinking water.

Surprising, however, the filter sap still caused infection. Obviously the infectious agent was making it through the filter. Could the disease be caused by a poison or toxin made by the bacteria? Certain human diseases such as diphtheria were indeed caused by potent bacterial toxins that would easily pass through Chamberlain filters. Many scientists believed this to be the case. Alas, they were mistaken.”

(Zimmerman 2003, 102)

A few years later a Dutch scientist Martinus Beijerinck determined that the pathogen was not a toxin nor poison but was a new type of pathogen which he names a virus, which is Latin for poison.

6.1 VIRAL PATHOGENS/ VIRAL WEAPONS

Dr. Ken Alibek told me that there were about 3000 viruses which potentially could be used as weapons. (Alibek 2005)  Fortunately only the viruses from six families of viruses have been considered for weapons. The virus families are:  Arenaviridae, Bunyaviridae, Filoviridae, Flaviviridae, Alphaviridae, and Orthopoxviridae. Four of the above-mentioned virus families (Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae) are considered to be viral hemorrhagic fevers.

6.1.1 The Arenaviridae Family of Viruses

“These viruses of the Arenavirus family all produce similar viral hemorrhagic fever syndromes. Members of this family include Last fever (Lassa virus), and Argentine (Junin virus), Bolivian (Machupo virus), Venezuelan (Guanarito virus), and Brazilian (Sabia virus) hemorrhagic fevers. Mortality rates are up to 30% of all symptomatic cases, depending on the virus. Asymptomatic and mild infections may be common. Mortality rates are 15-20% for Lassa virus and 15-30% for the others. One or more of these viruses have been weaponized by the Russian biowarfare program, and any outbreak should be highly suspect for a bioterrorism attack.”  (Weinstein 2003, 70)

6.1.2  The Bunyaviridae Family of Viruses

“There are several viruses included within this genus of the Bunyaviridae family. For the purposes of bioterrorism, only Hanta virus pulmonary syndrome (HPS) and Asian hemorrhagic fever with renal syndrome (HFRS) are important. Hantaviruses are members of the Hantavirus genus, but all are native only to the Americas. The most important agent in North America is called the Sin Nombre virus. Asymptomatic and mild infections are rare.”  (Weinstein 2003, 64)

“Crimean-Congo hemorrhagic fever (CCHF) is caused by a virus of the Bunyaviridae family and produces a viral hemorrhagic fever syndrome. Ruminants and ticks are primary reservoirs. Asymptomatic and mild infections often occur. Mortality rates are 20-50%. Mortality rates could be higher in an aerosol bioterrorism attack due to a higher initial viral exposure. Any outbreak of hemorrhagic fever in the United States should be highly suspect for a bioterrorism attack.”   (Weinstein 2003, 54)

6.1.3  The Filoviridae Family of Viruses

The Filoviridae family includes Ebola and Marburg. “Both of these viruses of the Filoviridae family produce similar viral hemorrhagic fever syndromes. They are among the most pathogenic viruses known, with mortality rates up to 90%  (25-90% depending on viral strain) of all symptomatic cases. Ebola is more common, but little is known about the ecology of either of these viruses. Asymptomatic and mild infections are known to occur, but they are not common. The Russian biowarfare program has weaponized both viruses, and Iraq is also believed to have attempted weaponization. Any outbreak on any continent other than Africa should be highly suspect for a bioterrorism attack.” (Weinstein 2003, 59)

6.1.4 The Flaviviridae Family of Viruses

“Dengue fever is caused by a virus of the Flavivirus family and produces a viral hemorrhagic fever syndrome with hepatitis, very similar to yellow fever. The attack rate is about 80% of those exposed, but asymptomatic and mild infections are the rule, especially in children. It occurs naturally in South and Central America and often produces cases in the southwestern United States and in Hawaii. Mortality rates are about 1% with good medical care and 20% without. It rarely progresses beyond the prodromal phase, making it a relatively poor choice for a biological weapon.”

(Weinstein 2003, 56)

“Yellow fever is caused by a virus of the Flavivirus family and may produce a viral hemorrhagic fever syndrome with hepatitis, very similar to dengue fever. Asymptomatic and mild infections are common. Yellow fever occurs naturally in South and Central America. Overall mortality is about 8% but climbs to 50% if the hemorrhagic fever develops, which occurs in only about 15% of all cases. The rest of the cases do not progress beyond the prodromal phase, making yellow fever a relatively poor choice for a biological weapon.” (Weinstein 2003, 110)

6.1.5 Information Common to All Viral Hemorrhagic Fevers

“Signs and Symptoms:  VHFs are febrile illnesses which can feature flushing of the face and chest, petechiae, bleeding, edema, hypotension, and shock. Malaise, myalgias, headache, vomiting, and diarrhea may occur in any of the hemorrhagic fevers.

Diagnosis: Definite diagnosis rests on specific virologic techniques. Significant numbers of military personnel with a hemorrhagic fever syndrome should suggest the diagnosis of a viral hemorrhagic fever.

Treatment: Intensive supportive care may be required. Antiviral therapy with ribavirin may be useful in several of these infections (Available only as IND under protocol). Convalescent plasma may be effective in Argentine hemorrhagic fever (Available only as IND under protocol).

Prophylaxis:  The only licensed VHF vaccine is yellow fever vaccine. Prophylactic ribavirin may be effective for Lassa fever, Rift Valley fever, CCHF, and possibly HFRS (Available only as IND under protocol).

Isolation and Decontamination:  Contact isolation, with the addition of a surgical mask and eye protection for those coming within three feet of the patient, is indicated for suspected or proven Lassa fever, CCHF, or filovirus infections. Respiratory protection should be upgraded to airborne isolation, including the use of a fit-tested HEPA filtered respirator, a battery powered air purifying respirator, or a positive pressure supplied air respirator, if patients with the above conditions have prominent cough, vomiting, diarrhea, or hemorrhage. Decontamination is accomplished with hypochlorite or phenolic disinfectants.”  (Kortepeter 2001, 61)

6.1.6 The Orthopoxviridae Family of Viruses

This family includes Smallpox, Monkeypox, and Chickenpox, but the only member that would probably be weaponized is Smallpox.

“Smallpox is caused by Variola Major, an Orthopox virus officially eradicated in 1980. It is known to have been developed as a biological weapon by the Russian biowarfare program. About 20 tons of weaponized smallpox was known to be in the Russian stockpile as of 1992. It is also believed to be in the hands of Iraq and possibly some terrorist groups.” (Weinstein 2003, 98)

“Signs and Symptoms:  Clinical manifestations begin acutely with malaise, fever, rigors, vomiting, headache, and backache. 2-3 days later lesions appear which quickly progress from macules to papules, and eventually to pustular vesicles. They are more abundant on the extremities and face, and develop synchronously.

Diagnosis: Neither electron nor light microscopy are capable of discriminating variola from vaccinia, monkey pox or cowpox. The new PCR diagnostic techniques may be more accurate in discriminating between variola and other Orthopoxviruses.

Treatment: At present there is no effective chemotherapy, and treatment of a clinical case remains supportive.

Prophylaxis:  Immediate vaccination or revaccination should be undertaken for all personnel exposed.

Isolation and Decontamination:  Droplet and Airborne Precautions for a minimum of 17 days following exposure for all contacts. Patients should be considered infectious until all scabs separate and quarantined during this period. In the civilian setting strict quarantine or asymptomatic contacts may prove to be impractical and impossible to enforce. A reasonable alternative would be to require contacts to check their temperatures daily. Any fever above 38 C (101 F) during the 17-day period following exposure to a confirmed case would suggest the development of smallpox. The contact should then be isolated immediately, preferably at home, until smallpox is either confirmed or ruled out and remain in isolation until all scabs separate.”

(Kortepeter 2001, 51)

6.1.7  The Alphaviridae Family of Viruses

The two species in the Alphavirus family that have been considered as possible weapons are Chikungunya and Venezuelan equine encephalitis.

“Chikungunya is found primarily in Africa and Asia and is caused by an Alphavirus similar to those that cause arthropod-borne viral encephalitis, although Chikungunya is not primarily a neurologic illness. The disease it causes consists of a flulike illness with a consistent triad of high fever, rash, and polyarthritis. The clinical illness it produces is difficult to distinguish from other similar Alphaviruses such as Ross River virus, o’nyong-nyong, Sindbis fever, and Mayaro virus. Chikungunya is rarely if ever fatal, making ita relatively poor choice for a weapon, but if released it could produce widespread suffering and disability, overwhelming the medical infrastructure. Aerosol transmission has not been documented, but at least one other Alphavirus (Venezuelan equine encephalitis) is known to spread by this route.”  (Weinstein 2003,48)

“This category includes the Alphavirus diseases Venezuelan equine encephalitis (VEE), Eastern equine encephalitis (EEE), and Western equine encephalitis (WEE) and the Flaviviruses St. Louis encephalitis (SLE), Japanese encephalitis (JR), and West Nile virus (WNV). All are naturally transmitted by a mosquito vector. Except for VEDE, all produce mild or asymptomatic illness in the majority of cases, making them unsuitable weapons. VEE not only produced nearly 100% symptomatic infections with a relatively high percentage of significant neurologic illness, but studies demonstrate that it can be transmitted via the aerosol route and therefore can be effectively weaponized. When released as an aerosol, the number of severe neurologic cases would likely be much higher than in natural occurring cases. VEE has a mortality rate of <1%. Natural human infection usually occurs in summer and early fall and is always preceded by equine cases in the same region. The lack of equine cases and/or an outbreak in winter or spring should suggest a biological weapon attack.”  (Weinstein 2003, 60)

“Signs and Symptoms:  Incubation period 1-6 days. Acute systemic febrile illness with encephalitis developing in a small percentage (4% children; <1% adults). Generalized malaise, spiking fevers, rigors, sever headache, photophobia, and myalgias for 24-72 hours. Nausea, vomiting, cough, sore throat, and diarrhea may follow. Full recovery from malaise and fatigue takes 1-2 weeks. the incidence of CNS disease and associated morbidity and mortality would be much higher after a BW attack.

Diagnosis: Clinical and epidemiological diagnosis. Physical findings are non-specific. The white blood cell count may show a striking leukopenia and lymphopenia. Virus isolation may be made from serum, and in some cases throat swab specimens. Both neutralizing or lgG antibody in paired sera of VEE specific lgM present in a single serum sample indicate recent infection.

Therapy: Treatment is supportive only. Treat uncomplicated VEE infections with analgesics to relieve headache and myalgia. Patients who develop encephalitis may require anticonvulsants and intensive supportive care to maintain fluid and electrolyte balance, ensure adequate ventilation, and avoid complicating secondary bacterial infections.

Prophylaxis:  A live, attenuated vaccine is available as an investigational new drug. A second, formalin-inactivated, killed vaccine is available for boosting antibody titers in those initially receiving the first vaccine. No post-exposure immunoprophylaxis. In experimental animals, alpha-interferon and the interferon-inducer poly-ICLC have proven highly effective as post-exposure prophylaxis. There are no human clinical data.

Isolation and Decontamination:  Patient isolation and quarantine is not required. Standard Precautions augmented with vector control while the patient is febrile. There is no evidence of direct human-to-human or horse-to-human transmission. The virus can be destroyed by heat (80 C for 30 min) and standard disinfectants.”  (Kortepeter 2001, 56)

6.2 THE VIRAL WEAPON PRODUCTION PROCESS

“Pathogenic viruses and rickettsiae are intracellular parasites that can only reproduce inside living cells. There are two approaches to cultivating these agents; in intact living tissue (e.g., chick embryos or mouse brains) or in isolated cells growing in tissue culture. The latter approach is technically simpler because it requires only flasks and nutrient medium, but certain viruses (e.g., influenza) do not grow well in tissue culture and must be cultivated in fertilized eggs. In 1962, Fort Detrick used more than 800,000 eggs for the cultivation of pathogenic viruses.

Growing viruses and rickettsiae in cultured mammalian cells offers greater control but involves certain technical hurdles. The cells must adhere to a surface to grow and also require a complex culture medium based on blood serum obtained from horses and cows. Until recently, cultured mammalian cells were grown on the inner surface of rotating glass bottles, which limited the volume of production. Over the past decade, however, new methods for cultivating mammalian cells have been developed that permit higher concentration of cells and greater recovery of product. For example, allowing the cells to grow on the surface of beads suspended in culture medium has permitted the scaling-up of production. Yield has been improved further by replacing the beads with microcarriers, which have a porous internal structure into which animal cells can grow.

Hollow-fiber technology offer an even more efficient method of growing anchorage-dependent mammalian cells in high concentrations for the cultivation of viruses or rickettsiae. The cells are grown on the outer surface of thin fibers that are immersed in the growth medium; air is pumped through the fibers and diffuses through the fiber wall to reach the cells. Since a single hollow-fiber bioreactor is equivalent to several thousand one-liter bottles, it occupies less than one-twentieth the volume of the previous technology. Advantages include economy and the high concentration and purity of the end-product, which reaches 98 percent on leaving the reactor. In sum, the new cell-culture techniques greatly simplify the production of viruses and rickettsiae and allow large-scale yields from very small facilities.” (Herdman 1993, 89)

In the area of human pathogens the Militarily Critical Technologies List (MCTL) lists the following types of equipment as equipment required to create human pathogens:

Cell culture apparatus, laminar flow facilities, containment equipment, and biological agent detectors. (MCTL ,II-3-11)

6.3 PAST USE OF VIRAL WEAPONS

Dr. Ken Alibek makes the following definitions: (Alibek 2004, Ch 2 Pg 1):


 * Biological Warfare – A specialized type of warfare     conducted by a government against a specific target.
 * Biological Terrorism – The use (or threat of use) of     biological agents to further political, social, and/or religious      objectives.
 * Biocrime – The use of biological agents for murder,     extortion, or revenge.

“In 1763 during Indian Chief Pontiac’s Rebellion in New England, Colonel Henry Bouquet, A British officer, proposed giving the Indians at Fort Pitt, PA, blankets infected with smallpox. An outbreak of smallpox at Fort Pitt, and Fort Carillon erupted, which spread like wildfire among Native American tribes throughout the Ohio River Valley.”  (Parkman 1969)

“During the U.S. Civil War, the Confederates retreating in Mississippi left dead animals in wells and ponds to deny water sources to the Union troops. Dr. Luke Blackburn of Kentucky attempted a more carefull use of BW when he infected clothing with smallpox and yellow fever and sold it to unsuspecting union troops.”  (Leitner 2005)

During the height of the cold war (1972-1992) the Soviets produced more than 100 tons of Smallpox annually at their Zagorsk facility. At their Koltsovo facility they produced dozens of tons annually of both Marburg and Smallpox  At their Pokrov facility they produced over 200 tons annually of both Smallpox and VEE. (Alibek 2004, Lecture 1, pg 2)

6.4 ANALYSIS OF THE VIRAL THREAT

In general viruses are much more difficult to cultivate and grow than bacteria, but antibiotics are only effective against bacteria. There are very few anti-viral drugs currently available. The best protection against viral disease are vaccines, but there is a great deal of reluctance to inoculate the American population against most of the viral diseases than we have vaccines for. The primary reason is the high percentage of immunocompromized people in the general population, perhaps as much as 10% of the population including those with Aids, the elderly, or those undergoing chemotherapy.

Perhaps in a few years the treatment and prophylaxis situation for viruses will be better. There is some research going on in the areas of immumodulators and immunoglobulin treatments, but nothing on the market currently.

Vaccines in the following categories do exist, but as previously mentioned, none are deemed safe enough to be administered to the population as a whole:


 * Vaccines safe for young, healthy people:  Yellow Fever, Smallpox
 * Investigational Vaccine:  VEE
 * Untested Experimental Vaccine:  Chikungunya
 * Vaccine available in Russia only:  Omsk Hemorrhagic fever

6.5 KEY WORDS ASSOCIATED WITH VIRAL WEAPONS

There are three categories of words:  “Category words” which carry a weight of ten points for each occurrence and whose presence places the web page into the category of “Viral Weapons”; “Strong words” which have some association with viral weapons and carry a weight of five points, and “Associated words” which carry a weight of one point for each occurrence. Associated words have a rather weak association with viral weapons but their presence may amplify the presence of category and strong words.

Lists of viral pathogens in both the category word and strong word classifications come from several sources. Two of the most important are:  Control Lists provided by the Australia Group (www.australiagroup.net) , and lists provided in the Military Critical Technologies List (MCTL) (www.fas.org/irp/threat/mctl98-2/index.html).

6.5.1  Viral Category Words

Chikungunya                                       Crimean-Congo                       Hemorrhagic

CCHF                                                 Dengue                                    Ebola

Marburg                                              VHF                                        Venezuelan

VEE                                                    Hantavirus                               Lassa

Nipah                                                  Omsk                                       Rift

Smallpox                                             Variola                                                Hantaan

Spring-Summer

6.5.2 Viral Strong Words

Alphavirus                                           Alphaviridae                           Ross

O’nyong-nyong                                   Sindbis                                    Mayaro

Bunyaviridae                                       Bunyavirus                              Flavivirus

Flaviviridae                                         Hepatitis                                  Filoviridae

Filovirus                                              Equine                                     Encephalitis

EEE                                                     WEE                                       SLE

JE                                                        WNV                                      neurologic

HPS                                                     HFRS                                      Nombre

Flu                                                       Influenza                                 Avian

Hong                                                   Kong                                       Swine

Spanish                                                supervirulent                           1918

HEPA                                                 Amantadine                            Rimantadine

Oseltamivir                                          Polyvalent                               Zanamivir

Kyasanur                                             Forest                                      KFD

Arenaviridae                                       Arenavirus                               Junin

Argentine                                            Bolivian                                   Machupo

Guanarito                                            Brazilian                                  Sabia

Paramyxoviridae                                 RSV                                        Valley

RVF                                                    Interferon                                Orthopox

Yellow                                                            Pox                                          Herpes

Lyssa                                                   Newcastle                               peste

petits                                                   Rinderpest                               Teschen

Stomatitis

6.5.3 Viral Associated Words

These words will be identical to those shown in section 5.5.3 Bacteriological Associated Words/