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Disease Agents Smallpox as a Disease Agent Quotes About Smallpox A Historical Perspective Smallpox in the 20th Century The Eradication of Smallpox The Virus Transmission Incubation Period Diagnosis and Detection Clinical Manifestations Extreme Smallpox Mortality Survivors Vaccination Treatment Containment Infection Control Environmental Decontamination Smallpox as a Biological Weapon Smallpox as a Bioterrorism Agent More about Smallpox... Quotes About Smallpox "…approximately 500 million people died of smallpox in the century that just ended. This compares with 320 million deaths during the same period as a result of all military and civilian casualties of war, cases of swine flu during the ruinous 1918 pandemic, and all cases of AIDS worldwide. These staggering numbers make painfully clear how grave a global crisis any return of smallpox would represent; the use of it as a weapon would constitute the ultimate crime against humanity." >From Living Terrors, by Michael T. Osterholm & John Schwartz "If there's a single case of smallpox, then it really doesn't matter what we do right now. We'll get it, we'll fix it, we'll get it cured. We eradicated smallpox once before, we'll do it again. The only issue will be whether there will be one or ten or fifty or one hundred cases. Those are bad but not terrible. And if that's all that's going to happen, we'll be able to get away with being a little late to the party with good organization. But if there are fifty aerosolized discharges of smallpox virus in fifty different cities in large, densely populated auditoria, and it happens in the next four months, it could destroy the United States." Dr. Larry Brilliant, who worked with WHO's Smallpox Eradication Program in the 1970s. BIOTERROR MEDICAL ALERT, Volume 1, Number 3, January 5, 2002. A Historical Perspective When the Egyptian pharaoh Ramses V died of "an acute illness" in 1157 B.C., it may have been smallpox, according to twentieth- century scientists who examined the well-preserved mummy. According to some historians, smallpox might first have developed as a common disease among humans in ancient Egypt, sometime before 1500 B.C. From there it presumably traveled eastward along the important trade routes to Persia and India. Others say that smallpox might have originated in China, India, Africa or the Caspian Sea. Not much is known for certain about the origins of smallpox. The people of ancient India had a smallpox goddess. The name of the goddess, Sitala, meaning "the cool one", suggests a power to relieve the high fever and burning pain that goes with the disease. The Chinese called the disease "Hunpox", probably because it was introduced into China by the Hun invaders that conquered the northern part of the country about 250 A.D. The Chinese also visualized a smallpox goddess who had the power to protect children. Boy with smallpox. Photo: CDC/Cheryl Tryon. A fatal disease resembling smallpox swept across northern Italy and southern France in A.D. 580-581. A dead victim was so covered with pustules that "it appeared black and burnt, as if it had been laid on a coal fire," wrote Gregory of Tours, a French bishop. A smallpox epidemic swept western Europe during the 1300s. Some historians believe that the armies of the Crusades might have brought a new lethal strain of smallpox with them when they returned to Europe. Paris was struck by a smallpox epidemic in 1438, with about 50,000 deaths, mostly children. About 60 million people died of smallpox in Europe during the 18th century. When Christopher Columbus and other European explorers began the journey to the New World, smallpox and other infectious diseases traveled with them. The disease was new in the Americas, and the native population had no immunity. A third of the Taino people who welcomed Columbus to the Caribbean island the Spanish called Hispaniola were dead twenty years later. The majority died in epidemics, with smallpox as the number one killer. From Hispaniola smallpox spread to neighboring Puerto Rico and Cuba, slaughtering an ample part of the native populations. Smallpox came to Mexico with infected Spanish soldiers in 1520. Three to four million natives died of smallpox, among them the Aztec king Cuitahuac and many of the Aztec people. From there the disease spread down through Central America and the Mayan empire. It reached the Incas less than ten years later, killing the Inca emperor Huayna Capacthe and hundreds of thousand of his people. The early British, French and Dutch settlements in North America brought more smallpox and other infectious diseases to the approximately 20 million Native Americans to what is today the United States and Canada. Outbreaks of smallpox killed off a large part of the Native American population from 1630 to 1840. About 6 million succumbed, according to one source. The aborigines of Australia were similarly affected when white settlers arrived in the late 1700s. Smallpox in the 20th Century In 1947 a businessman bound for New York boarded a bus in Mexico. He felt unwell, got worse during the trip and collapsed when the bus reached Manhattan. The man, who had an old vaccination offering no immunity, was first taken to Bellevue Hospital, but was later moved to the Willard Parker Hospital for Contagious Diseases. He died there. Then two other patients at the Willard Parker Hospital developed the disease, followed by the death of a woman who had visited the smallpox ward. Other patients at the hospital also brought the disease home to their families. Having problems tracking down all the people that might have been in contact with the businessman at the bus, the hospital and other possible places, the NYC Health Department decided that the entire population of New York City should be vaccinated. Almost four weeks later, nearly seven million New Yorkers had been vaccinated and the outbreak was contained. In a smallpox outbreak in Yugoslavia 1972 the army was mobilized. Villages were closed, public meetings were prohibited, and about ten thousand people were forced into hotels and apartment buildings converted into emergency quarantine wards guarded by the military. Yugoslavia's entire population was, with support from the World Health Organization, revaccinated in record time. "They gave eighteen million doses in ten days," said D.A. Henderson in an interview. The Eradication of Smallpox In 1958 Viktor M. Zhdanov, the Minister of Health of the Soviet Union, proposed that the World Health Organization (WHO) should undertake the mission to eradicate smallpox from the entire world. A global vaccination campaign involving a staff of 150,000 people and led by the World Health Organization accomplished the extermination of the disease between 1967 and 1977. D.A. Henderson, the director of the WHO's Smallpox Eradication Unit at that time, is today a professor at the Johns Hopkins School of Public Health. He's also the founder and director of Johns Hopkins Center for Civilian Biodefense Studies and an outspoken crusader for bioterrorism preparedness. In 1980 smallpox was declared eradicated. The WHO recommended that all countries stop vaccination, and remaining stocks of the virus were sent to WHO reference laboratories, a Russian government lab and to CDC in Atlanta. In May 1999, the World Health Assembly (WHA) passed a resolution postponing an earlier decision to destroy all remaining smallpox stocks. Proponents of the resolution argued that live virus might be needed for research purposes, such as the development of a new vaccine or drugs to fight the disease. The Virus Smallpox is caused by the variola virus, an Orthopoxvirus. It has two known strains: Variola major, which is smallpox as we know it, and Variola minor, a weak mutant which is not usually fatal. The disease was first known as Variola, which presumably comes from the Latin word varius, meaning "spotted", or from the Latin word varus, which means "pimple". In the 16th century, English- speaking people in Europe started to call syphilis "the great pox", because it produces a similar rash in its early stages. Variola became "the small pox". The smallpox virus has no animal reservoir; it only affects human beings. Transmission The virus is highly stable and can remain contagious for long periods outside the host. To survive it must be passed from person to person, through inhalation of air droplets or aerosols. The infectious dose is presumably very small, and it's possible that one could get the disease from inhaling a single particle of smallpox. Smallpox is very contagious. It's most easily spread during a cool, dry winter season. The disease is most transmissable after the patient has developed a skin rash. Most contagious are patients with a cough, or with the hemorrhagic (bleeding) form of smallpox. Experiences from outbreaks in Europe during the 1960s and the 1970s suggests that as many as 10 to 20 second-generation cases were often infected from a single case. In Germany, a smallpox patient with a cough, although isolated to a single room, infected other people on three floors. A smallpox outbreak can run in successive waves, infecting as many as ten times more people every two to three weeks. Incubation Period The incubation period is generally 12 to 14 days. Diagnosis and Detection The earliest symptoms of smallpox can be mistaken for the flu or chickenpox. Doctors usually need special training to be able to diagnose smallpox early — and few American physicians have ever seen a case of smallpox. Most smallpox cases develop a characteristic rash mostly concentrated on the face and limbs. As the disease pregresses, the rash and the severity of the illness may help make the diagnosis. Diagnosis of smallpox is difficult even for experts. Characteristic smallpox rash, Bangladesh 1973. Photo: CDC/ Phil Hicks. Clinical Manifestations First symptoms are typically high fever, malaise and headache and/or backache. After about 2 to 3 days a rash appears, most often on the face, mouth and throat. Soon thereafter the rash spreads to the arms, legs and torso. Initially, the rash doesn't look too serious, and many health professionals could easily mistake it for chickenpox. The next stage has been compared to having one's skin on fire. This is how the author Richard Preston has described the horror in his article "The Demon In The Freezer": "The spots turn into blisters, called pustules, and the pustules enlarge, filling with pressurized opalescent pus. The eruption of pustules is sometimes called the splitting of the dermis. The skin doesn't break. But splits horizontally, tearing away from its underlayers. The pustules become hard, bloated sacs the size of peas, encasing the body with pus, and the skin resembles a cobbled stone street." Extreme Smallpox Some of the victims develop an extreme form of smallpox, often called "black pox". As portrayed by Preston: "Doctors separate black pox into two forms — flat smallpox and hemorrhagic smallpox. In a case of flat smallpox, the skin remains smooth and doesn't pustulate, but it darkens until it looks charred, and it can slip off the body in sheets. In hemorrhagic smallpox, black, unclotted blood oozes or runs from the mouth and other body orifices. Black pox is close to a hundred percent fatal. If any sign of it appears in the body, the victim will almost certainly die. In the bloody cases, the virus destroys the linings of the throat. The stomach, the intestines, the rectum, and the vagina, and these membranes disintegrate. Fatal smallpox can destroy the body's entire skin — both the exterior skin and the interior skin that lines the passages of the body." Mortality Smallpox has a case-fatality rate of 30% or higher. Children have a higher mortality rate. Survivors Survivors are often marked for life with typical smallpox scars. General George Washington is probably the most famous U.S. survivor of smallpox, and his face bore the typical pockmarks. Permanent joint deformities and blindness may also follow recovery in some cases. A patient who survives smallpox gets a long-term immunity and cannot transmit the disease to others after the recovery. Vaccination For centuries, Chinese physicians practiced their own method of smallpox vaccination, by blowing dust from scabs of smallpox patients into the nostrils of healthy people. The inoculation created a mild infection and resulted in immunity to smallpox. >From the early 18th century western physicians and researchers experimented with inoculations, often with smallpox pus or dried scab from smallpox victims. Early in the American Revolution, British troops were inoculated with smallpox. The Americans had tens of thousand of cases, during the early years, before George Washington ordered his entire army immunized. During the Franco- Prussian War of 1870-1871, the Germans vaccinated an army of over 800,000 soldiers, with only 300 smallpox deaths as a result. The French army didn't, and lost more than 23,000 soldiers to the disease. Dr. Edward Jenner of Gloucestershire, England, developed the first vaccine based on a culture of a mild form of cowpox. Smallpox immunizations started to win general acceptance by the mid 19th century. Sweden was the first country to wipe out smallpox within its own borders, by vaccinating all citizens. Great Britain and the Soviet Union followed in the 1930s, the U.S. by the late 1940s. Today most countries have only a small stock of smallpox vaccine. Globally there are about 75 million doses of variable quality available. WHO has a total of 500,000 doses in storage in the Netherlands. The US used to have 15.4 million doses at the CDC in Atlanta. But recently it was discovered that more than half of the vaccine in storage had been destroyed or are of questionable quality. Following the attacks on September 11 the U.S. has taken steps to ensure 300 million doses of the smallpox vaccine will be available in 2002. Until then, in the case of an emergency, the health authorities are working to stretch today's existing stockpile to vaccinate as many as 77 million people with a diluted version of the vaccine. It's an open question if the 300 million doses will go to the pharmaceutical stockpile, to be used in emergency situation, or if the whole population will be vaccinated as a precaution. The HHS secretary has said he would not recommend mandatory vaccinations at this time, but that a voluntary program could be established for civilians. A massive vaccination campaign against smallpox is not without complications. First, few U.S. healthcare providers know the specialized techniques required for smallpox vaccinations. Experts have also reported a shortage of the special bifurcated needles. Second, smallpox vaccination is associated with some risk for serious medical complications. So-called "Postvaccinial Encephalitis" has been reported in 1 case per 300,000 vaccinations, with 25% fatal outcome and reported cases of permanent neurological damage among some survivors. Persons with a weakened immune system (due to an inherited defect, cancer, AIDS or current radiation therapy) can develop a serious complication called "Progressive Vaccinia". It basically means that the virus used in the vaccine continues to grow, and these patients might die if not treated with vaccinia immune globulin, which is in short supply. Other medical complications can also occur. A recently developed pre-exposure vaccination offers the best protection against smallpox. The immunity starts to grow immediately after a vaccination and takes full effect within a week. Vaccination given within 4 days of exposure, according to experts, offers "some protection" against infection and "significant protection against a fatal outcome." The U.S. smallpox vaccine is reported to have less potential side effects than vaccines produced in other countries, and uses different vaccine strains. The Department of Defense also recently ordered 300,000 doses of vaccine for the military. Treatment Supportive therapy and antibiotics against occasional secondary infections are recommended for smallpox victims, but in a mass casualty emergency, such as a bioterrorism attack with smallpox, it may not be possible to offer typical hospital care. For a situation with a large number of infected patients it's most likely that temporary emergency treatment facilities and quarantine units, offering vaccinations and basic care, would replace most supportive care at a modern hospital. Recent lab studies suggests that the antiviral drug cidofovir might be useful against smallpox, if administered within 1 to 2 days after exposure. Containment Michael Osterholm, former Minnesota State epidemiologist and a member of Johns Hopkins Working Group on Civilian Biodefense, has said that the only way we can respond to a smallpox outbreak today is "to literally circle it, much like you'd try to circle a wildfire." Everyone that has been in contact with or near a smallpox victim must be vaccinated. Diagnosed and suspected cases ought to be quarantined, and temporary travel restrictions might be placed on a disease area. There are no other known means of containing a smallpox outbreak. Infection Control There are documented cases of people becoming infected by handling laundry from smallpox patients, which suggests that the virus can stay infectious in such materials for long periods. Bedding and clothing of smallpox patients should be autoclaved or washed in hot water with bleach. Potentially contaminated surfaces should be cleaned with standard hospital disinfectants, such as hypochlorite and quaternary ammonia. Laboratory work with the smallpox virus requires BL-4 high- containment facilities and trained personnel. Remains of smallpox victims should be handled with the highest level of precaution. Contact should be limited to trained and vaccinated personnel. Cremation is strongly advised. Environmental Decontamination An indoor release of an aerosol of the smallpox virus, not exposed to UV light, could possibly survive for 24 hours or longer. However, by the time the first case of the disease is diagnosed, there would be no smallpox remaining in that environment. Bedding and clothing should be handled as described above. Smallpox as a Biological Weapon The most notorious example of early biological warfare involving smallpox occurred in 1763 when British forces intentionally distributed smallpox-infested blankets to Native Americans, among them to the Pontiac, Shawnee, and Delaware peoples. British troops also made efforts to deliberately spread smallpox among American colonial troops, according to General George Washington. The USSR's Biological Weapons Program produced large quantities of bomb- and missile- ready smallpox,, according to the defector and former Russian top biowarfare scientist Ken Alibek. Today's Russia is most likely hiding stocks of the virus at military sites, according to a secret intelligence report from 1998. North Korea and Iraq are may also be concealing the smallpox virus for military use, according to U.S. government officials quoted by the New York Times. A 1994 report from the U.S. Defense Intelligence Agency cites information that Russian smallpox samples were sent to Iraq and North Korea in the late 1980's or early 1990's. In the mid-1990's, UN arms inspectors in Iraq discovered a freeze- drier labeled "smallpox" at the maintenance shop of the State Establishment for Medical Appliances Marketing, a division of the Ministry of Health, which was involved in Baghdad's germ warfare program. Iraq used to produce smallpox vaccine as late as 1989, according to UN inspectors. Blood samples from Iraqi prisoners during the gulf war showed widespread evidence of smallpox immunization. Hazem Ali, a senior Iraqi virologist involved in Saddam Hussein's germ warfare program also told UN inspectors that they had been working on camel pox. A CIA report from 1996 concluded that camel pox "could possibly serve as a research model for smallpox." North Korea has long been publicly accused of keeping secret stocks of smallpox and western intelligence sources have expressed concern about the possibility that North Korean researchers are working on smallpox weaponization. Russia's Foreign Intelligence Service, KGB's successor, said in a 1990 report on the spread of weapons of mass destruction that North Korea was working on smallpox weapons. Recent blood samples from North Korean Special Forces soldiers have shown evidence of fresh smallpox immunization. "The vaccinations are as close to a smoking gun as you can come," according to a U.S. official from the Department of Defense. Smallpox as a Bioterrorism Agent "Although smallpox has long been feared as the most devastating of all infectious diseases, its potential for devastation today is far greater than at any previous time. Routine vaccination throughout the United States ceased more than 25 years ago. In a now highly susceptible, mobile population, smallpox would be able to spread widely and rapidly throughout this country and the world." Smallpox 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. 281 No. 22, June 9, 1999. A bioterrorism attack with smallpox virus is regarded as a possibility today. Such an attack could quickly develop into a global epidemic with wave after wave of smallpox spreading in populations that are largely unprotected. Western intelligence sources are concerned that Russian researchers of the former Biopreparat, many unemployed since the 1990's, could have fallen for the temptation to smuggle a smallpox sample over the border and sell it to nations that are actively seeking an offensive bioweapons capacity, or to a terrorist group with financial resources and microbiology expertise. "I think the chance is about 80 percent of terrorists obtaining smallpox," said Marvin Cetron, president of Forecasting International Ltd., a political assessment company working with the U.S. Defense of Department and the FBI. Experts have warned that a state hostile to the U.S. could supply terrorists with the smallpox virus. Most of the states with a biological weapons program are also named by the U.S. Department of State as sponsors of terrorism. "There is a circumstantial evidence that Iraq, North Korea and Russia have undeclared stocks of smallpox," said Jonathan Tucker, author of a new book titled Scourge: The Once and Future Threat of Smallpox. An intentional bioterrorism-related outbreak of smallpox would most likely occur via an aerosol of the virus, which would show no indication of an attack when dispersed. A smallpox aerosol is odorless, colorless, and tasteless. There would be no explosion; no catastrophic event would announce the presence of a lethal disease agent in the air. The potentially catastrophic consequences of a bioterrorism attack with smallpox has been described in role-playing scenarios such as "Dark Winter." MORE ABOUT SMALLPOX BioHazard News: Role-playing Scenarios on Smallpox Smallpox as a Biological Weapon: Medical & Public Health Management The Journal of the American Medical Association (JAMA), Vol. 281 No. 22, June 9, 1999. 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 smallpox as a biological weapon. Abstract 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. Smallpox: Clinical and Epidemiologic Features D. A. Henderson, Johns Hopkins Center for Civilian Biodefense Studies. The First National Symposium on Medical and Public Health Response to Bioterrorism, Feb. 16-17, 1999. Published in CDC's Emerging Infectious Diseases, Vol. 5, No 4, July — August, 1999 Medical Treatment and Response to Suspected Smallpox: 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. "The Demon In The Freezer" Article by Richard Preston, first published in The New Yorker, July 12, 1999, pp. 44-61. About smallpox as a bioterrorism threat. Based on an interview with D.A. Henderson, with an interesting portrait of the smallpox outbreak in Jugoslavia 1972. Smallpox Virus Destruction Information from the Center For Civilian Biodefense Studies at the Johns Hopkins University. Papers from the WHO and D. A. Henderson. 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