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Plague - An Historical Perspective
From BioHazard News.Net
From Kim Weber
1-15-3

The first known plague pandemic began in Egypt 541 AD and spread to other parts of the world during the following four years. About 50 to 60% of the world population is estimated to have died from the plague.
 
In 1345 to 1350, the second plague pandemic swept over the world. The disease, also known as the Black Death, erupted about 25 years earlier in central Asia, probably in what is today Mongolia. Following trade routes and human movements the plague moved through China, Russia, the Middle East, the Mediterranean and Europe. It lasted around 130 years, killing more than 13 million in China alone, and about 20 to 30 million in Europe ÷ a third of Europe's total population at the time.
 
The Great Plague of London killed nearly one out of every six citizens of London during the years 1664-65.
 
The third pandemic erupted in China 1855, and led to more than 12 million deaths in China and India alone. It spread around the globe, and reached San Francisco's Chinatown in the year 1900 During the following four years it infected 121 people, with 118 deaths. A secondary plague epidemic occurred in San Francisco 1907, with 160 cases and 77 deaths. This outbreak was probably linked both to plague rats surviving the anti-rat campaign of 1904, and disruptions that followed the 1906 earthquake.
 
As a result of the outbreaks in San Francisco 1900 to 1907, plague is now established permanently in the western and southwestern United States. Infected plague rats have wandered into the forests and exchanged fleas with wild rats, squirrels and prairie dogs that now carry living cultures of dormant plague germs.
 
The last sizable plague outbreak in the U.S. took place in Los Angeles in 1924-25. Forty people were infected; only two survived.
 
Between 1947 and 1996 there were 390 cases of plague reported in the United States, with most cases in New Mexico, Arizona, Colorado, and California.
 
India experienced an outbreak of pneumonic plague in 1994. It occurred in the industrial city of Surat, about 200 miles north of Bombay. The outbreak followed an earthquake where more than ten thousand people were killed and about a million homes were destroyed. The earthquake destroyed farmers' grain storage buildings, which created an excess of food for rats carrying plague fleas. Both the rats and the flies reproduced quickly, and first infected humans with bubonic plague, which soon developed into pneumonic plague, transmitted from person to person through droplets in the air. After rumours started to circulate about tens of thousands infected with the plague and many deaths, about a half million civilians and most medical professionals fled the city by bus, train, and car. In the end, 56 people died, while almost 6,500 were cured with antibiotics.
 
Bubonic plague has survived as an infection of rats and other rodents, squirrels, and prairie dogs on all continents except Australia. Worldwide, on average, about 1700 cases are reported each year.
 
The Bacillus and its Natural Reservoir
 
Plague is caused by Yersinia pestis, a gram-negative bacillus (bacterium). The plague microbe is named after Alexandre Yersin, a Swiss scientist that started his career in the lab of Louis Pasteur, and in the late 19th century discovered the bacillus.
 
Plague is an infectious disease with its natural reservoir in wild rodents. It is transmitted from rodent to rodent by the Xenopsylla cheopis, a flea whose favorite food is the blood of rodents, with human blood as a second choice.
 
Sudden excessive rat die-off is often seen as a prologue to a human plague epidemic. When the fleas are running short of rats live from, they turn to humans. Most people infected by this route develop bubonic plague, with a small minority acquiring primary septicemic plague. A small percentage of those infected with bubonic or septicemic plague also develop pneumonic plague. (See Transmission, below, for more information on types of plague infection.)
 
The bite by a plague-infected flea is like getting a shot of thousands of plague organisms. Those are then transported by the blood system to regional lymph nodes, where they fast reproduce.
 
The plague flea is quite rugged. It can survive for up to a year without a rodent host to feed on.
 
The plague bacillus is highly susceptible to effects of sunlight and heat. It does not survive long in an outdoor environment.
 
Transmission
 
Plague is a zoonotic disease, which means that people can catch it from animals.
 
It can take three forms, depending on whether the infection enters the lymph nodes (bubonic), the bloodstream (septicemic) or the lungs (pneumonic).
 
Bubonic plague is normally transmitted by fleas from rats and other rodents, squirrels, and prairie dogs. Of human cases in the U.S. from 1947 to 1996, fifteen were transmitted from domestic cats infected with plague.
 
A small number of patients infected by fleas develop primary septicemic plague. Secondary septicemic plague can arise from bubonic plague.
 
Secondary pneumonic plague develops in a minority of patients with bubonic or primary septicemic plague. Primary pneumonic plague is caused by direct inhalation of plague bacillus. Pneumonic plague is highly infectious and can be transmitted by respiratory droplets from animals to humans, or humans to humans.
 
In Madagascar in 1997, a patient with bubonic plague developed secondary pneumonic plague, which was transmitted to 18 people, with 8 deaths.
 
Laboratory work with the plague bacillus requires Biosafety Level 2 conditions, with BL-3 precautions when performing activities involving high risk for aerosol or droplet production.
 
Diagnosis and Detection
 
Few U.S. physicians have ever diagnosed a case of pneumonic plague. Early symptoms could easily be mistaken for acute flu-like illness.
 
Rapid diagnostic tests for plague are not currently available. Only some state laboratories, CDC and the military can confirm a suspected diagnosis. Routinely used antibody tests can not be used for early diagnosis, because it takes several days to weeks before antibodies develop in a plague patient.
 
The Association of Public Health Laboratories and the CDC are together developing new standards and training for lab diagnosis of plague.
 
New environmental warning systems that can detect a plague aerosol are under development.
 
Incubation Period
 
A bubonic plague infection from fleabites generally takes 2 to 8 days before symptoms develop.
 
Septicemic plague has an incubation period of 1 to 7 days.
 
The incubation period for pneumonic plague, from exposure to an aerosol of plague, is most often 2 to 4 days.
 
Clinical Manifestations
 
Bubonic plague is characterized by fever, headache, chills and swollen lymph nodes, or "buboes", which ooze pus and blood. The bubo can reach the size of an orange and is extremely painful. Nausea, vomiting and diarrhea are also common symptoms. The hemorrhaging causes cell necrosis and intoxication of the nervous system, which leads to shock or coma.
 
Septicemic plague patients develop a rash, fever, headache, chills, weakness and gastrointestinal disturbances. The disease progresses rapidly, and death can occur within a day of onset of symptoms.
 
Patients with pneumonic plague get high fever, headache, weakness, muscle pains, and pneumonia with a cough that produces watery sputum, and later bloody sputum. The lungs are rapidly destroyed, and the body can't transport enough oxygen, so hands and feet start to turn black. Pneumonic plague can rapidly progress to respiratory failure.
 
Of U.S. cases of plague from 1947-1996, about 84% were bubonic, 13% septicemic, and 2% pneumonic.
 
Mortality
 
While bubonic plague was responsible for most of the plague deaths in the Middle Ages, both septicemic and pneumonic plague are more deadly.
 
As many as 30 to 50 percent of people with bubonic plague may survive, even without treatment.
 
Untreated septicemic plague is always fatal.
 
The fatality rate of patients with pneumonic plague ÷ without treatment, or if not begun within 24 hours of onset of symptoms ÷ is extremely high, or 95% to 100%. The survival rate depends on the dose of plague inhaled, access to advanced supportive care, and the time when antibiotic treatment started. The time from a respiratory exposure of plague to death is normally 2 to 6 days without treatment.
 
Vaccination
 
Dead or inactivated bacteria have been used in plague vaccines since 1896.
 
A plague vaccine, protecting against bubonic plague, was previously licensed and used in the U.S. The whole cell bacterial vaccine, inactivated with formaldehyde and preserved in phenol, was primarily used by at-risk laboratory personnel and people who travel to plague-infected areas. The vaccine was discontinued by its manufacturers in 1999 and is no longer available.
 
Scientists at Porton Down, the British government biological warfare research center, have used genetic engineering to develop a new plague vaccine. The vaccine, currently being tested on human volunteers, uses two harmless proteins used by the plague bacillus to trigger an immune response against the disease.
 
Researchers at U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have developed a new vaccine that works against pneumonic plague in animal experiments. Further tests are underway.
 
Treatment
 
In a mass casualty emergency, such as a bioterrorism attack with pneumonic plague, it will not be possible to offer the kind of hospital treatment advised for a modest number of patients with pneumonic plague. Mass distribution of antibiotics, temporary emergency treatment facilities (with only basic care) and homecare (under supervision by family members) would replace intravenous administration of antibiotics and supportive care at a modern hospital in most cases, during such a crisis.
 
The Johns Hopkins Working Group on Civilian Biodefense recommends that if a pneumonic plague outbreak occurs, all people in the area who develop a temperature of 101.3 degrees Fahrenheit (38.5 degrees Celcius) or higher, or a new cough, should immediately begin antibiotic treatment. People without symptoms that have been in close contact, less than 6.5 feet from contagious pneumonic plague cases, should undergo antibiotic treatment for 7 days, as a preventive step.
 
Tetracycline, doxycycline, sulfonamides, and chloramphenicol are antibiotics that have been used successfully or endorsed against plague by experts. Fluoroquinolones also worked in lab studies on mice.
 
Intravenous administration of streptomycin is the preferred choice for a contained outbreak of pneumonic plague. Oral therapy with doxycycline is recommended by as the first choice treatment for mass casualty settings.
 
In 1995, the first strain of multidrug-resistant plague was discovered in a 15-year-old boy in Madagascar. The strain was resistant to all known antibiotics that work on plague, except trimethoprim.
 
Containment
 
Today, it's possible to contain an outbreak of bubonic plague with antibiotics, surveillance of infected victims, and an aggressive rat-extermination program.
 
Pneumonic plague, which is airborne, could lead to secondary spread of cases. The following measures are advised: quarantine of those infected, surveillance of close contacts, and prescription of antibiotics in all suspected and confirmed cases. Temporary travel restrictions might occur.
 
Infection Control
 
U.S. infection control guidelines for pneumonic plague recommends the use of disposable surgical masks to prevent person-to-person transmission via respiratory droplets.
 
Hospital rooms should get terminal cleaning, with standard precautions. Bedding and clothing of plague patients, contaminated with body fluids, should be disinfected.
 
Laboratory work with the plague bacillus requires Biosafety Level 2 conditions, with BL-3 precautions when performing activities involving high risk for aerosol or droplet production.
 
Contact with remains of plague victims should be limited to trained personnel, and handled with routine strict precautions.
 
Environmental Decontamination
 
A WHO study from 1970 estimated that a plague aerosol would stay infectious for only as long as one hour after an outdoor release. An indoor release of pneumonic plague could possibly stay infectious for a longer period, if protected from sunlight and heat.
 
The Johns Hopkins Working Group on Civilian Biodefense has concluded that there's no need for environmental decontamination of an area exposed to a plague aerosol.
 
Plague as a Biological Weapon
 
The Mongols practiced one of the earliest examples of biological warfare in 1346. During the siege of Kaffa, a coastal town in the Black Sea, the Mongols, also known as the Tartars, catapulted the remains of plague victims from their own army into the city. The goal was to start an epidemic among the defending Genoese, and the attempt was successful. When the Genoese evacuated Kaffa and returned to Italy, they may have brought the plague with them, possibly starting the Black Death in Europe.
 
The Japanese biological warfare program conducted research in occupied Manchuria between 1932 and 1945. About 3,000 scientists worked with to weaponize plague, anthrax, and other disease agents. The program used prisoners for terminal experiments in which they studies how to effectively infect people with plague from fleas. Pathologists conducted autopsies on some plague victims, while they were still alive, and without anesthetic.
 
The biowarfare program operated a plague flea factory with 4,500 flea-breeding machines, producing about 100 million plague-infected fleas every few days. Unit 731, a secret branch of the Japanese army, dropped plague fleas over populated areas of China. About 15 million fleas were released per attack.
 
In June 1944, an assault team of seventeen officers from Unit 731 sailed for Saipan Island, in the Pacific Ocean, in an attempt to deny U.S. forces access to the airstrip by dropping porcelain bombs containing millions of plague-infected fleas. The ship was torpedoed by a U.S. submarine before it reached its target.
 
During the last frenzied months of World War II, Unit 731 prepared a large biological warfare assault on the U.S. involving special balloon bombs planned to carry disease across North America. An operation to use aircraft carried by submarines to drop plague-infected fleas over southern California was planned for September 1945. But the Japanese Emperor admitted defeat and surrendered one month prior. The leadership of the Japanese biowarfare program was after the war granted immunity from war crimes prosecution on the condition that they disclosed information about their research.
 
Nazi Germany built a biological weapons research facility at Posen, in 1943. Hitler's scientists worked with aircraft spray-tank dissemination of plague and other germs, but without success.
 
In the years after World War II, both the United States and the Soviet Union developed techniques to aerosolize plague, eliminating the fleas and creating a more deadly and contagious plague weapon.
 
President Richard Nixon terminated the U.S. offensive biological weapons program in 1969. The U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) was established to proceed with the development of medical defenses against biological warfare. The United States, Soviet Union, Iraq and many other countries signed the 1972 Biological Weapons Convention. Both the Soviets and Iraq secretly continued to develop biological weapons on a large scale.
 
The Soviet biowarfare program produced large quantities of pneumonic plague for bombs and missiles.
 
In the early 1990s, it was discovered that Iraq had produced plague in fermenters and freeze-dried the bacteria for use in bombs. Before the Gulf War, about 1,000 doses of plague vaccine were bought abroad, probably for the leadership, and researchers and production personnel working with the plague germ. Western intelligence sources believe that Iraq still maintains a plague biowarfare program.
 
Plague as a Bioterrorism Agent
 
An intentional bioterrorism-related outbreak of plague would most likely occur via an aerosol of the plague bacillus. A plague aerosol is odorless, colorless, and tasteless. No explosion or cloud would announce the presence of a lethal disease agent in the air.
 
A sudden outbreak of pneumonic plague could suggest the possibility of a bioterrorism attack. The disease would first present itself as a large number of patients with severe pneumonia and sepsis (blood infection), and the presence of bacteria or other infectious organisms or their toxins in the blood or in other tissue.
 
Few western physicians have ever seen a case of pneumonic plague, and early symptoms are quite similar to influenza and other diseases, so the first cases might easily be overlooked.
 
In May 1995, Larry Wayne Harris, an anti-government "Christian Patriot" and former member of the Aryan Nation, a neo-Nazi organization, ordered samples of Yersinia pestis, from the American Type Culture Collection (ATCC). Mr. Harris, a microbiologist, said he feared an "imminent invasion from Iraq of super-germ-carrying mice", and planned to do research for a "plague antidote" out of his home in Lancaster, Ohio.
 
Harris pled guilty to one count of wire fraud, and was placed on probation. The CDC later tightened up requirements for shipping special disease agents and toxins, such as bubonic plague, tularemia and brucellosis.
 
New York City subway. Photo: Hans G. Andersson
 
According to federal prosecutors, Harris once informed a person that he had plans to attack the New York City subway system with light bulbs filled with bubonic plague, using the same method that the U.S. Army used in a test with harmless simulant bacteria in 1966. He forecasted hundreds of thousands of victims and that the government of Iraq would be blamed for the attack.
 
<http://www.biohazardnews.net/scen_anthrax.htm#subway>
Read about the NYC subway test in 1966
 
Larry Wayne Harris has published detailed instructions on how to obtain bubonic plague and other disease agents and use them as biological weapons. He's considered dangerous by the U.S. government.
 
"Given the availability of Y pestis around the world, capacity for its mass production and aerosol dissemination, difficulty in preventing such activities, high fatality rate of pneumonic plague, and potential for secondary spread of cases during an epidemic, the potential use of plague as a biological weapon is of great concern."
 
Plague as a Biological Weapon: Medical & Public Health Management, A Consensus Statement of the Johns Hopkins Working Group on Civilian Biodefense, The Journal of the American Medical Association (JAMA) Vol. 283 No. 17, May 3, 2000.
 
MORE ABOUT PLAGUE
 
BioHazard News: <http://www.biohazardnews.net/scen_plague.htm>Role-playing Scenarios on Plague
 
Plague as a Biological Weapon: Medical & Public Health Management
The Journal of the American Medical Association (JAMA) Vol. 283 No. 17, May 3, 2000. A Consensus Statement of the Johns Hopkins Working Group on Civilian Biodefense. To be used as a practical guide for professionals dealing with medical and public health issues associated with the use of plague as a biological weapon. <http://jama.ama-assn.org/issues/v283n17/abs/jst90013.html>
Abstract
 
<http://www.hopkins-biodefense.org/pages/agents/agentplague.html>
Fact Sheet with consensus recommendations of the Johns Hopkins Working Group on Civilian Biodefense regarding appropriate medical and public health measures to be taken following such an attack.
 
<http://www.ci.nyc.ny.us/html/doh/html/cd/plaguemd.html>
Medical Treatment and Response to Suspected Plague: Information for Health Care Providers During Biologic Emergencies
Draft from July 2000, by New York City Department of Health Bureau of Communicable Disease. A guide and reference source for medical and public health professionals.
 
<http://www.cdc.gov/ncidod/dvbid/plague/index.htm>
CDC Plague Home Page
A great online source for information about plague.
 
<http://www.biohazardnews.net/lit.htm#nardo>
The Black Death, edited by Don Nardo.
 
<http://www.biohazardnews.net/lit.htm#epidemics>
Epidemics, by Geoffrey Marks and William K. Beatty. A historical perspective on epidemics, including plague.
 
<http://www.biohazardnews.net/lit.htm#betrayal>
Betrayal of Trust: The Collapse of Global Public Health, by Laurie Garrett. Includes a good report from the pneumonic plague outbreak in India, 1994.
 
<http://www.discovery.com/stories/history/blackdeath/blackdeath.html> Discovery: The Black Death
Follow the rat and learn more details about the history of bubonic plague.
 
 
http://www.biohazardnews.net/agent_plague.htm


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