Thursday, August 21, 2008

prion diseases

PRION DISEASES-AN OVERVIEW
Prince. C.P
Department of Microbiology
Mother Theresa Institute of Health Sciences
Puducherry

Infectious diseases are caused by microorganisms like bacteria, viruses, fungi, protozoan parasites and helminthic parasites.
Recent research by Stanley.B.Prusiner and others discovered the existence of a new group of infectious agents which are responsible for some rare fatal diseases. These agents do not belong to any of the classical pathogens, as they do not posses a nucleic acid (RNA/DNA) and are just infectious protein molecules. They are called as Prions.
Prions are small Self replicating proteinaceous infectious particles which can resist inactivation procedures like sterilization and can modify nucleic acids.
Prions are resistant to denaturation by proteases, heat, radiation, and formalin treatments, although their infectivity can be reduced by such treatments.
Prion diseases are often called Transmissible Spongiform Encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum.
Prion diseases have Common features like long incubation periods (years), characteristic spongiform changes associated with neuronal loss and failure to induce inflammatory response-no antibodies are produced against prions.
Prion diseases in animals
Scrapie: sheep
TME (transmissible mink encephalopathy): mink
CWD (chronic wasting disease): mule -deer, elk
BSE (bovine spongiform encephalopathy): cows
Prion diseases in man
CJD: Creutzfeld-Jacob Disease
GSS: Gerstmann-Straussler-Scheinker syndrome
FFI: Fatal familial Insomnia
Kuru
Alpers Syndrome

These diseases are characterized by loss of motor control, dementia, paralysis, wasting and eventually death, typically following pneumonia.
The first Prion disease identified was Kuru, which was found among the Fore tribe of Papua New Guinea. .Kuru is transmitted among this tribe due to their practice of cannibalism .They eat their relative’s dead body.
Prion proteins induce abnormal folding of normal cellular Prion proteins (PrP) in the brain, leading to brain damage. When infectious PrP-sc enters into nervous tissues it interacts with normal PrP-c of the brain cells and converts them into Prp-sc. This leads into the accumulation of PrP-sc in brain cells.
Diagnosis is mainly based on symptoms. Other useful methods are 1.Electroencephalography — often has characteristic triphasic spikes
2. Cerebrospinal fluid analysis for 14-3-3 protein
3. MRI of the brain
No treatment is available today. The search for viable treatment is going on. Preventive measures like strict quarantine laws and mass slaughtering of infected animals are useful to control the spread of infection.
Prion research in future may provide the clarification for the doubts about origin of life and pathogenesis of diseases like Alzhmer’s and Parkinsonism.

-------------------------------------------------------------------------------------------------

biological weapons

BIOLOGICAL WARFARE-A THREAT TO HUMANKIND
Prince.C.P
Lecturer in Microbiology
Mother Theresa Institute of Health Sciences
Gorimedu
Pondicherry-605006
cpprincepni@yahoo.co.in

Biological weapons deliver toxins and microorganisms, such as viruses and bacteria, so as to deliberately produce disease among people, animals, and agriculture. Biological attacks can result in destruction of crops, temporarily diseasing of a small community, and killing large numbers of people.
The act of bioterrorism can range from a simple threat to the actual use of these biological weapons, also referred to as agents. A number of nations have or are seeking to acquire biological warfare agents, and there are concerns that terrorist groups may also acquire the technologies and expertise to use these destructive agents.
Biological agents may be used for an isolated assassination, as well as to cause death to thousands. If the environment is contaminated, a long-term threat to the population could be created.
History of Biological Warfare
The use of biological agents is not a new concept, and history is filled with examples of their use. Biological warfare has been practiced repeatedly throughout history. Before the 20th century, the use of biological agents took three major forms:
1. Deliberate poisoning of food and water with infectious material
2. Use of microorganisms, toxins or animals, living or dead, in a weapon system
3. Use of biologically inoculated fabrics.
Olden times:
* Scythian archers infected their arrows by dipping them in decomposing bodies or in blood mixed with manure as far back as 400 BC.
* Persian, Greek, and Roman literature from 300 BC quotes examples of dead animals used to contaminate wells and other sources of water.
*During the battle of Tortona in the 12th century AD, Barbarossa used the bodies of dead and decomposing soldiers to poison wells.
*During the siege of Kaffa in the 14th century AD, the attacking Tatar forces hurled plague-infected corpses into the city in an attempt to cause an epidemic within enemy forces.
*In 1710, when the Russians besieging Swedish forces at Reval in Estonia catapulted bodies of people who had died from plague.
*During the French and Indian War in the 18th century AD, British forces under the direction of Sir Jeffrey Amherst gave blankets that had been used by smallpox victims to the Native Americans in a plan to spread the disease.
Modern times:
#During World War I, the German Army developed anthrax, glanders, cholera, and a wheat fungus specifically for use as biological weapons. They allegedly spread plague in St. Petersburg, Russia, infected mules with glanders in Mesopotamia, and attempted to do the same with the horses of the French Cavalry.
#The Geneva Protocol of 1925 was signed by 108 nations. This was the first multilateral agreement that extended prohibition of chemical agents to biological agents. Unfortunately, no method for verification of compliance was addressed.
#During World War II, Japanese forces operated a secret biological warfare research facility in Manchuria that carried out human experiments on prisoners. They exposed more than 3000 victims to plague, anthrax, syphilis, and other agents in an attempt to develop, observe and study the disease. Some victims were executed or died from their infections.
# in 1942, the United States formed the War Research Service. Anthrax and botulinum toxin initially were investigated for use as weapons. Sufficient quantities of botulinum toxin and anthrax were stockpiled by June 1944 to allow unlimited retaliation if the German forces first used biological agents.
# The British also tested anthrax bombs on Gruinard Island off the northwest coast of Scotland in 1942 and 1943 and then prepared and stockpiled anthrax-laced cattle cakes for the same reason.
#The United States continued research on various offensive biological weapons during the 1950s and 1960s. From 1951-1954, harmless organisms were released off both coasts of the United States to demonstrate the vulnerability of American cities to biological attacks. This weakness was tested again in 1966 when a test substance was released in the New York City subway system.
#During the Vietnam War, Viet Cong guerrillas used needle-sharp punji sticks dipped in feces to cause severe infections after an enemy soldier had been stabbed.
#in 1979, an accidental release of anthrax from a weapons facility in Sverdlovsk, USSR, killed at least 66 people. The Russian government claimed these deaths were due to infected meat, and maintained this position until 1992, when Russian President Boris Yeltsin finally admitted to the accident.
Bioterrorism and biowarfare today:
A number of countries have continued offensive biological weapons research and use. Additionally, since the 1980s, terrorist organizations have become users of biological agents.
@In 1985, Iraq began an offensive biological weapons program producing anthrax, botulinum toxin, and aflatoxin. During Operation Desert Storm, the coalition of allied forces faced the threat of chemical and biological agents. Following the Persian Gulf War, Iraq disclosed that it had bombs, Scud missiles, 122-mm rockets, and artillery shells armed with botulinum toxin, anthrax, and aflatoxin. They also had spray tanks fitted to aircraft that could distribute agents over a specific target.
@In September and October of 1984, 751 people were intentionally infected with Salmonella, an agent that causes food poisoning, when followers of the Bhagwan Shree Rajneesh contaminated restaurant salad bars in Oregon.
@In 1994, a Japanese sect of the Aum Shinrikyo cult attempted an aerosolized (sprayed into the air) release of anthrax from the tops of buildings in Tokyo.
@In 1995, 2 members of a Minnesota militia group were convicted of possession of ricin, which they had produced themselves for use in retaliation against local government officials.
@In 1996, an Ohio man attempted to obtain bubonic plague cultures through the mail.
@In 2001, anthrax was delivered by mail to US media and government offices. There were 4 deaths.
@In December 2002, 6 terrorist suspects were arrested in Manchester, England; their apartment was serving as a "ricin laboratory." Among them was a 27-year-old chemist who was producing the toxin. Later, on January 5, 2003, British police raided 2 residences around London and found traces of ricin, which led to an investigation of a possible Chechen separatist plan to attack the Russian embassy with the toxin; several arrests were made.
@On February 3, 2004, 3 US Senate office buildings were closed after the toxin ricin was found in mailroom that serves Senate Majority Leader Bill Frist's office.
Biological agents involved in bioterrorism
There are more than 1200 biological agents that could be used to cause illness or death; relatively few possess the necessary characteristics to make them ideal candidates for biological warfare or terrorism agents. The ideal biological agents are relatively easy to acquire, process, and use. Only small amounts (on the order of pounds and often less) would be needed to kill thousands of people in a metropolitan area. Biological warfare agents are easy to hide and difficult to detect or protect against. They are invisible, odorless, tasteless, and can be spread silently.
Although the list of potential agents is long, only a handful of pathogens are thought to have the ability to cause a maximum credible event to paralyze a large city or region of the country, causing high numbers of deaths, wide-scale panic, and massive disruption of commerce. Diseases like anthrax, smallpox, and plague, notorious for causing large outbreaks, still head that list. In addition, other agents, such as botulinum toxin, hemorrhagic fever viruses, and tularemia, have potential to do the same.
Many other pathogens can cause illness and death, and the threat list will always be dynamic. We must, therefore, have the appropriate surveillance system and laboratory capability to identify other pathogens.



Biological agents involved in bioterrorism or biocrimes

Traditional biological warfare agents
Agents associated with biocrimes and bioterrorism
Pathogens
Bacillus anthracis
Ascaris suum

Brucella suis
Bacillus anthracis

Coxiella burnetii
Coxiella burnetiib

Francisella tularensis
Giardia lamblia

Smallpox
HIV

Viral encephalitides
Rickettsia prowazekii

Viral hemorrhagic fevers
(typhus)

Yersinia pestis
Salmonella typhimurium


Salmonella typhi


Shigella species


Schistosoma species


Vibrio cholerae


Viral hemorrhagic fevers (Ebola)


Yellow fever virus


Yersinia enterocolitica


Yersinia pestis
Toxins
Botulinum
Botulinum

Ricin
Cholera endotoxin

Staphylococcal enterotoxin B
Diphtheria toxin


Nicotine


Ricin


Snake toxin


Tetrodotoxin
Anti-crop agents
Rice blast


Rye stem rust


Wheat stem rust




Diseases considered for weaponization:
Anthrax, ebola, Marburg virus, plague , cholera , tularemia , brucellosis, Q fever , machupo, Coccidioides mycosis , Glanders , Melioidosis , Shigella , Rocky Mountain spotted fever, typhus , Psittacosis, yellow fever, Japanese B encephalitis , Rift Valley fever , and smallpox .
Naturally-occurring toxins that can be used as weapons include ricin, botulism toxin, saxitoxin, and many mycotoxins.
The organisms causing these diseases are known as select agents. Their possession, use, and transfer should be regulated law.

Delivery of biological agents
Biological warfare agents can be disseminated in various ways:
Through the air by aerosol sprays: To be an effective biological weapon, airborne germs must be dispersed as fine particles. To be infected, a person must breathe a sufficient quantity of particles into the lungs to cause illness.
Used in explosives (artillery, missiles, and detonated bombs): The use of an explosive device to deliver and spread biological agents is not as effective as the delivery by aerosol. This is because agents tend to be destroyed by the blast, typically leaving less than 5% of the agent capable of causing disease.
Put into food or water: Contamination of a city's water supplies requires an unrealistically large amount of an agent as well as introduction into the water after it passes through a regional treatment facility.
Absorbed through or injected into the skin: This method might be ideal for assassination, but is not likely to be used to cause mass casualties.
Detection
Biological agents could either be found in the environment using advanced detection devices including microbiological assays or after specific testing or by a doctor reporting a medical diagnosis of an illness caused by an agent.
Animals may also be early victims and shouldn't be overlooked.
Early detection of a biological agent in the environment allows for early and specific treatment and time enough to treat others who were exposed with protective medications. Doctors must be able to identify early victims and recognize patterns of disease. If unusual symptoms, a large numbers of people with symptoms, dead animals, or other inconsistent medical findings are noted, a biological warfare attack should be suspected. Doctors report these patterns to public health officials.
Protective measures
Protective measures can be taken against biological warfare agents. These should be started early (if enough warning is received) but definitely once it is suspected that a biological agent has been used.
1. Use Personal Protective Equipments:
Masks: Currently, available masks such as the military gas mask or high-efficiency particulate air (HEPA) filter masks used for tuberculosis exposure filter out most biological warfare particles delivered through the air. However, the face seals on ill-fitting masks often leak. For a mask to fit properly, it must be fitted to a person's face.
Clothing: Most biological agents in the air do not penetrate unbroken skin, and few organisms stick to skin or clothing. After an aerosol attack, the simple removal of clothing eliminates a great majority of surface contamination. Thorough showering with soap and water removes 99.99% of the few organisms that may be left on the victim's skin.
2. Medical protection:
Health care providers treating victims of biological warfare may not need special suits but should use latex gloves and take other precautions such as wearing gowns and masks with protective eye shields. Victims would be isolated in private rooms while receiving treatment.
Antibiotics: Victims of biological warfare might be given antibiotics orally (pills) or through an IV, even before the specific agent is identified.
Vaccinations: Currently, protective vaccines are available for anthrax, botulinum toxin, tularemia, plague, Q fever, and smallpox. The widespread immunization of nonmilitary personnel has not been recommended by any governmental agency so far. Immune protection against ricin and staphylococcal toxins may also be possible in the near future.
Anti-agriculture Biological warfare
Biological warfare can also specifically target plants to destroy crops or defoliate vegetation. The United States and Britain discovered plant growth regulators (i.e., herbicides) during the Second World War, and initiated an Herbicidal Warfare program that was eventually used in Malaya and Vietnam in counter insurgency. Though herbicides are chemicals, they are often grouped with biological warfare as bioregulators in a similar manner as biotoxins.Scorched earth tactics or destroying livestock and farmland were carried out in the Vietnam War and Eelam War in Sri Lanka.
The United States developed an anti-crop capability during the Cold War that used plant diseases (bioherbicides, or mycoherbicides) for destroying enemy agriculture. Diseases such as wheat blast and rice blast were weaponized in aerial spray tanks and cluster bombs for delivery to enemy water sheds in agricultural regions to initiate epiphytotics (epidemics among plants).
In 1980s Soviet Ministry of Agriculture had successfully developed variants of foot-and-mouth disease and rinderpest against cows, African swine fever for pigs, and psittacosis to kill chicken. These agents were prepared to spray them down from tanks attached to airplanes over hundreds of miles.
Attacking animals is another area of biological warfare intended to eliminate animal resources for transportation and food.
In summary, we know that biological pathogens have been used for biological warfare and terrorism, and their potential for future use is a major concern. Therefore we must be prepared to respond appropriately if they are used again. The technology and intellectual capacity exist for a well-funded, highly motivated terrorist group to mount such an attack.
Beware! We do not know who are our enemy and friend; it can be George Bush or Saddham Hussein!