Smallpox

Vaccine

Edward Jenner developed the smallpox vaccine using cowpox fluid (hence the name vaccination is derived from the Latin vacca, cow); his first vaccination occurred on May 14, 1796. However, the first person recorded as vaccinating against smallpox was Benjamin Jesty, a farmer. Jesty noted the common knowledge that dairymaids who had previously contracted the less severe cowpox never suffered with smallpox, even after nursing ill family members. During the smallpox outbreak in the summer of 1774, Jesty inoculated his wife and her children. Jesty's wife became ill but recovered with treatment.

Jenner established the technique and practice of vaccination.

The practice of vaccination against smallpox spread quickly in Europe and then to America. Prior to Jenner's cowpox vaccine, many New England settlers were inoculated by means of making small incisions in the arms of the healthy patient, scraping a pustule from a smallpox victim, and spreading the pus in the arm incisions. The inoculated patients were often sick for weeks but generally recovered. Prior to 1776, Abigail Adams from Massachusetts wrote to her husband John Adams (then in Congress in Philadelphia) that she was taking their children to Boston to be inoculated, after a severe outbreak near their rural home had killed entire neighboring families. The first smallpox vaccination in North America occurred on June 2, 1800. National laws requiring vaccination began appearing as early as 1805.

The last case of wild smallpox occurred on October 26, 1977. One last victim was claimed by the disease in the UK in September 1978, when Janet Parker, a photographer in the University of Birmingham Medical School, contracted the disease and died. A research project on smallpox was being conducted in the building at the time, though the exact route by which Mrs. Parker became infected was never fully elucidated.

Cultures of the virus are kept by the Centers for Disease Control and Prevention (CDC) in the United States and at the Institute of Virus Preparations in Siberia, Russia. (While scientists certified it eradicated in December 1979, WHO formally ratified this on 8 May 1980 in resolution WHA33.3) Smallpox vaccinations were discontinued in most countries in the 1970s as the morbidity and mortality of vaccination by then exceeded the risk of infection by a disease extinct in the wild. Nonetheless, after the 2001 anthrax attacks took place in the United States, concerns about smallpox have resurfaced as a possible agent for bioterrorism. As a result, there has been increased concern about the availability of vaccine stocks. Moreover, President George W. Bush has ordered all American military personnel to be vaccinated against smallpox and has implemented a voluntary program for vaccinating emergency medical personnel.

Infection

The disease is only moderately infectious, far less so than chickenpox. Unlike chickenpox, smallpox is not notably infectious in the prodromal period—viral shedding being delayed until the appearance of the rash. Smallpox transmission is a risk of prolonged social contact, direct contact with infected body fluids or contaminated objects. Infection in the natural disease will be via the lungs. The incubation period to obvious disease is around 12 days. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers. The initial or prodromal symptoms are essentially similar to other viral diseases such as influenza and the common cold—fevers, muscle pain, stomach aches, etc. The digestive tract is commonly involved, leading to vomiting. Most cases are prostrated. Smallpox virus preferentially attacks skin cells and by days 12–15, smallpox infection becomes obvious. The attack on skin cells causes the characteristic pimples associated with the disease. The pimples tend to erupt first in the mouth, then the arms and the hands, and later the rest of the body. At that point the pimples, called macules, should still be fairly small. This is the stage at which the victim is most contagious.

For the general layman in the field, to distinguish between Chickenpox and Smallpox, check the victims palms of the hand and soles of the feet. Chickenpox does not generally and usually present on the palms and soles as does smallpox.

By days 15–16 the condition worsens—at this point the disease can take two vastly different courses. The first form is of classical ordinary smallpox, in which the pimples grow into vesicles, and then fill up with pus (turning them into pustules). Ordinary smallpox generally takes one of two basic courses. In discrete ordinary smallpox, the pustules stand out on the skin separately—there is a greater chance of surviving this form. In confluent ordinary smallpox, the blisters merge together into sheets which begin to detach the outer layers of skin from the underlying flesh—this form is usually fatal. If the patient survives for the course of the disease, the pustules deflate in time (the duration is variable), and start to dry up, usually beginning on day 28. Eventually the pustules completely dry and start to flake off. Once all of the pustules flake off, the patient is considered cured.

In the other form of Variola major smallpox, known as hemorrhagic smallpox, a mortality of 96 percent has been reported. An entirely different set of symptoms starts to develop. The skin does not blister, but remains smooth. Instead, bleeding occurs under the skin, making the skin look charred and black (this is known as black pox). The eyes also hemorrhage, making the whites of the eyes turn deep red (and, if the victim lives long enough, eventually black). At the same time, bleeding begins in the organs. Death may occur from bleeding (fatal loss of blood or by other causes such as brain hemorrhage), or from loss of fluid. The entry of other infectious organisms, since the skin and intestine are no longer a barrier, can also lead to multi-organ failure. This form of smallpox occurs in anywhere from 3–25% of fatal cases (depending on the virulence of the smallpox strain).

The historical modes of death are similar to those in burns, with catastrophic losses of fluid, protein and electrolytes beyond the capacity of the body to replace or assimilate, and fulminating sepsis, both due to the removal of the barrier between the internal milieu and outside world. Supportive treatments have improved since the last large smallpox epidemics, but it would be grossly optimistic to imagine that even with a small number of patients that the most intensive modern treatment would ensure survival even where the damage is predominantly only in the skin. A reduction in the severity of the disease by raising immunity is likely to make a large difference in numbers reaching the threshold of death, and supportive treatment a small one in elevating that threshold.

Eurasia

Historical epidemics and pandemics are believed by some historians to have been early outbreaks of smallpox. But contemporary records are not detailed enough to make a definite diagnosis at this distance.

The Plague of Athens devastated the city of Athens in 430 BC, killing around a third of the population, according to Thucydides. Historians have long considered this an example of the disease plague, but more recent examination of the reported symptoms led some scholars to believe the cause could have been measles, smallpox, typhus, or a viral hemorrhagic fever (like Ebola).

The Antonine Plague that swept through the Roman Empire and Italy in 165–180 is also thought to be either smallpox or measles. A second major outbreak of disease in the Empire, known as the Plague of Cyprian (251–266), was also either smallpox or measles.

The next major epidemic believed to be smallpox occurred in India. The exact date is unknown. Around 400, an Indian medical book recorded a disease marked by pustules, saying "the pustules are red, yellow, and white and they are accompanied by burning pain … the skin seems studded with grains of rice." The Indian epidemic was thought to be punishment from a god, and the survivors created a goddess, Sitala, as the anthropomorphic personification of the disease.. Smallpox was thus regarded as possession by Sitala. In Hinduism the goddess Sitala both causes and cures high fever, rashes, hot flashes and pustules. All of these are symptoms of smallpox.

Smallpox did not enter Europe until about 581. Most of the details about the epidemic that followed are lost, probably due to the scarcity of surviving written records of early medieval society.

The Americas

After first contacts with Europeans and Africans, the death of a large part of the native population of the New World was caused by Old World diseases. Smallpox was the chief culprit.

In 1519 Hernán Cortés landed on the shores of what is now Mexico and was then the Aztec empire. In 1520 another group of Spanish came from Cuba and landed in Mexico. Among them was an African slave who had smallpox. When Cortés heard about the other group, he went and defeated them. In this contact, one of Cortés’ men contracted the disease. When Cortés returned to Tenochtitlan, he brought the disease with him.

Soon, the Aztecs rose up in rebellion against Cortés. Outnumbered, the Spanish were forced to flee. In the fighting, the Spanish soldier carrying smallpox died. After the battle, the Aztecs contracted the virus from the invaders’ bodies. Cortes would not return to the capital until August 1521. In the meantime smallpox devastated the Aztec population. It killed most of the Aztec army, the emperor, and 25% of the overall population. A Spanish priest left this description: “As the Indians did not know the remedy of the disease…they died in heaps, like bedbugs. In many places it happened that everyone in a house died and, as it was impossible to bury the great number of dead, they pulled down the houses over them so that their homes become their tombs.” On Cortés’ return, he found the Aztec army’s chain of command in ruins. The soldiers who lived were still weak from the disease. Cortés then easily defeated the Aztecs and entered Tenochtitlán, where he found that smallpox had killed more Aztecs than had the cannons. The Spaniards said that they could not walk through the streets without stepping on the bodies of smallpox victims.

The effects of smallpox on Tahuantinsuyu (or the Inca empire) were even more devastating. Beginning in Colombia, smallpox spread rapidly before the Spanish invaders first arrived in the empire. The spread was probably aided by the efficient Inca road system. Within months, the disease had killed the Sapa Inca Huayna Capac, his successor, and most of the other leaders. Two of his surviving sons warred for power and, after a bloody and costly war, Atahualpa become the new Sapa Inca. As Atahualpa was returning to the capital Cuzco, Francisco Pizarro arrived and through a series of deceits captured the young leader and his best general. Within a few years smallpox claimed between 60% and 90% of the Inca population, with other waves of European disease weakening them further. However, some historians think a serious native disease called Bartonellosis may have been responsible for some outbreaks of illness.

Even after the two mighty empires of the Americas were defeated by the virus, smallpox continued its march of death. In 1633 in Plymouth, Massachusetts, the Native Americans were struck by the virus. As it had done elsewhere, the virus wiped out entire population groups of Native Americans. It reached Lake Ontario in 1636, and the lands of the Iroquois by 1679, killing millions. The worst sequence of smallpox attacks took place in Boston, Massachusetts. From 1636 to 1698, Boston endured six epidemics. In 1721, the most severe epidemic occurred. The entire population fled the city, bringing the virus to the rest of the Thirteen Colonies. In the late 1770s, during the American Revolutionary War, smallpox returned once more and killed an estimated 125,000 people.

Inoculation

By that time, a preventive treatment for smallpox had finally arrived. It was a process called inoculation, also known as insufflation or variolation. Inoculation was not a sudden innovation, as it is known to have been practiced in India as early as 1000 B.C. The Indians rubbed pus into the skin lesions. The Chinese blew powdered smallpox scabs up the noses of the healthy after discovery that this inoculated non-immune people by a Buddhist nun. The patients would then develop a mild case of the disease and from then on were immune to it. This technique is known as variolation and although variolation had a 0.5-2% mortality rate, this was considerably less than the 20-30% mortality rate of the disease itself. The process spread to Turkey where Lady Mary Wortley Montagu, wife of the British ambassador, learned of it from Emmanuel Timoni (ca. 1670–1718), a doctor affiliated with the British Embassy in Istanbul. She had the procedure performed on her son and daughter, aged 5 and 4 respectively. They both recovered quickly and the procedure was hailed as a success and reported to the Royal Society in England. Timoni, from the University of Padova, Italy and a member of the Royal Society of London since 1703, published “an account, or history, of the procuring the smallpox by incision” in December 1713 in the Philosophical Transactions. His work was published again in 1714 in Leipzig and was followed by those of Pylarino (1715), Leduc (1722), and Maitland (1722).

In 1721, an epidemic of smallpox hit London and left the British Royal Family in fear. When they read about the success of Lady Wortley Montagu’s efforts, they wanted to use inoculation on themselves. Doctors told them that it was a dangerous procedure, so they decided to try it on other people first. The subjects they used were condemned prisoners. The doctors inoculated the prisoners and all of them recovered in a couple of weeks. So assured, the British royal family inoculated themselves and reassured the English people that it was safe.

But inoculation still had its critics. Prominent among them were religious preachers who claimed that smallpox was God’s way of punishing people and that inoculation was a tool of Satan. This resistance only encouraged Montagu and the others to work even harder. By 1723 inoculations were extremely common in England, but even scientific opposition (such as the Fellow of the Royal College of Physicians Pierce Dod) continued for some time.

In 1721, Onesimus (Oh-NES-ih-mus) was the slave of a Boston preacher when smallpox came to Boston via a ship arriving from Barbados.< His owner, Cotton Mather asked his slave if he ever had smallpox. Onesimus said, “Yes and no,” and explained a technique from his homeland in Africa, thought to be in Sudan. He explained that pus from an infected person was deliberately rubbed into a scratch or cut of a non-infected person, and when successful, the person had immunity. This remedy from an African slave was the precursor to inoculations. Cotton Mather, the son of a former Harvard University dean, was waging a campaign of his own to promote the process, although religious resistance to inoculation was very strong. At one point, Cotton Mather was in danger from a crowd that wanted to hang him. After six patients died from the procedure, he was called a murderer. But, when the population of Boston returned after the end of a smallpox epidemic in 1722, he was an instant hero. Out of the population of Boston, 7% had died from smallpox. Out of the 300 people that chose to inoculate themselves, only 2% died. In 1750, the English magazine, Gentleman's Magazine, reprinted a 1725 pamphlet that argued in support of smallpox inoculations. By 1774, it was considered odd not to choose inoculation. Onesimus was later freed by Mather, not for his knowledge and help in combating smallpox, but because Mather considered him to be disobedient.

Even though inoculation was a powerful method of controlling smallpox, it was far from perfect. Inoculation caused a mild case of smallpox which resulted in death in about 2% of the cases. It was also difficult to administer. Sick patients had to be locked away to prevent them from transmitting the disease to others. Thus George Washington initially hesitated to have his Revolutionary War troops inoculated during a smallpox outbreak in February 1777, writing, “should We inoculate generally, the Enemy, knowing it, will certainly take Advantage of our Situation;” but the virulence of the outbreak soon prompted him to order inocculation for all troops and recruits who had not had the disease.

In 1757, a young boy in England by the name of Edward Jenner was inoculated. He suffered from the disease for an entire month. Even though he recovered, he was determined to find a better method of preventing smallpox.

Vaccination

At the age of thirteen, Jenner was apprenticed to Dr. Ludlow in Sodbury. He observed that people who caught cowpox while working with cows were known not to catch smallpox. He assumed a causal connection. The idea was not taken up by Dr. Ludlow at that time. After Jenner returned from medical school in London, a smallpox epidemic struck his home town of Berkeley, England. He advised the local cow workers to be inoculated. The farmers told him that cowpox prevented smallpox. This confirmed his childhood suspicion, and he studied cowpox further, presenting a paper on it to his local medical society.

Perhaps there was already an informal public understanding of some connection between disease resistance and working with cows. The “beautiful milkmaid” seems to have been a frequent image in the art and literature of this period.

In 1796 Sarah Nelmes, a local milkmaid,, contracted cowpox and went to Jenner for treatment. Jenner took the opportunity to test his theory. He inoculated James Phipps, the eight-year-old son of his gardener, not with smallpox but with cowpox. After an extremely weak bout of cowpox, James recovered. Jenner then tried to infect James with smallpox but nothing happened—the boy was immune to smallpox.

Jenner reported his observations to the Royal Society. Further work was suggested, and Jenner published a series of 23 cases, including his son Edward, none suffered severely from smallpox. Two years later a society to oppose vaccination had been established in Boston, Massachusetts — an indication of rapid spread and deep interest. By 1800 Jenner’s work had been published in all of the major European languages. The process was performed all over Europe and the United States. The death rate was close to zero with the process, which became known as vaccination and was continued to around 1974 in the UK. A typical death rate at that time was roughly one per million, making vaccination against smallpox with vaccinia the most dangerous immunisation widely provided in modern times.

The Balmis Expedition (1803) carried the vaccine to Spanish America, the Philippines and China under commission of the Spanish Crown.

Some years before Dr. Jenner, Benjamin Jesty, a farmer at Yetminster in Dorset (he later moved to and is buried at Worth Matravers) is recorded as observing the two milkmaids living with his family to have been immune to smallpox and then inoculating his family with cowpox to protect them from smallpox. This has never been adequately verified, however, and the question of who first initiated smallpox inoculation/vaccination has not been settled to this day.

Louis T. Wright, an African-American and Harvard medical school graduate (1915), introduced intradermal vaccination for smallpox for the soldiers while serving in the Army during WWI.

Eradication

—Edward Jenner (1749-1823)

Jenner's dream was ultimately realized. Since Jenner demonstrated the effectivness of cowpox to protect humans from smallpox circa 1796, various attempts were made to eliminate smallpox. In 1842, England banned inoculation, later progressing to mandatory vaccination instead. In the United States, from 1843 to 1855 first Massachusetts, and then other states required vaccination. This alteration in the relationship of State to citizen was not universally approved. Protests notwithstanding, coordinated efforts against smallpox went on and the disease continued to diminish in the wealthy countries. In poorer countries, vaccines and the necessary infrastructure were less affordable and available.

In 1958 the Soviet Union called for the eradication of smallpox from the planet. At that point, 2 million people were dying every year. In 1967, an international team was formed under the leadership of an American, Donald Henderson. To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as ring vaccination. The key to this strategy was Surveillance and Containment. Surveillance can be best be defined as the monitoring of cases in a community. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities.

The fact that man is the only reservoir for smallpox infection played a significant role in WHO deciding to eradicate smallpox. There are many other pox viruses in nature, including monkeypox, however, none appear be of public health signficance. In addition for smallpox carriers did not exist.

WHO established a network of consultants who assisted countries in setting up surveillance and containment activities.

Eradicating smallpox required huge effort and concentration of manpower. In India and Bangladesh, religion and civil strife along with natural disasters became obstacles. In fear of offending the goddess associated with the disease, many Hindus refused the vaccine. In some countries civil war threaten to interfere with eradication attempts, such as the Sudan. Clearly health teams placed themselves in great danger by working in war torn areas. Surprisingly, none of the team members were hurt in the process.

Natural events also impeded the vaccination team’s efforts. The monsoon rains burst dams and dikes. The rain and flooding forced people to flee, once again allowing smallpox to spread. This outbreak took the team a whole year to stop.

The last major European outbreak of smallpox was the 1972 outbreak of smallpox in Yugoslavia. After a pilgrim returned from the Middle East, where he had contracted the virus, an epidemic infected 175 people, causing 35 deaths. Authorities declared martial law, enforced quarantine and undertook massive revaccination of the population, enlisting the help of the WHO and Donald Henderson. In two months, the outbreak was over. Prior to this, there had been a smallpox outbreak on May-July of 1963 in Stockholm, Sweden, brought from the far east by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of local population .

The last naturally occurring case of Variola Minor was diagnosed in Somalia on a cook named Ali Maow Maalin on the date of October 26, 1977. The last naturally occurring case of the more deadly Variola Major had been detected in October 1975 in a two-year-old Bangladesh girl, Rahima Banu. In the end, 300 million United States dollars had been applied to the eradication process.

Post-eradication

In 1978, there was evidently an escape of smallpox from containment in a research laboratory in Birmingham, England. A medical photographer, Janet Parker, died from the disease itself, and the Professor responsible for the unit, Professor Henry Bedson, killed himself. In light of this accident, all known stocks of smallpox were destroyed, except the stocks at the United States Center for Disease Control (CDC) and the Russian Vector State Research Center of Virology and Biotechnology in Siberia, where a regiment of troops guards it. Under such tight control, smallpox would, it was thought, never be let out again. Even though the destruction of virus stocks was ordered in 1993, 1994, 1995, and 1996, they have not yet been destroyed, since a number of researchers still wish to retain the stocks for scientific purposes.

It is also feared that additional stocks of the virus may exist in research collections, the product of the accumulatory nature of microbiologists. Additional collections of the virus almost certainly exist as the result of certain military and biological warfare programs, such as those undertaken at the Vector Institute, which maintained stocks separate from those held by the Moscow Institute for Viral Preparation.

In March 2003 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. The envelope was labeled as containing the scabs and listed the names of the patients that were vaccinated with them. Assuming the contents could be dangerous, the librarian who found them did not open the envelope. The scabs ended up with employees from the National Centers for Disease Control, who responded quickly once informed of the discovery. The discovery raised concerns that smallpox DNA could be extracted from these and other scabs and used for a biological attack. Even with Variola sequenced, assembling a virus from scratch remains challenging.

Famous Victims

Famous victims of this disease include Ramesses V, the Shunzhi Emperor and Tongzhi Emperor of China (official history), Mary II of England, Louis XV of France and Peter II of Russia. Henry VIII's fourth wife, Anne of Cleves, survived the disease but was scarred by it, as was Henry VIII's daughter, Elizabeth I of England in 1562, Guru Har Krishan 8th Guru of the Sikhs in 1664, Peter III of Russia in 1744 and Abraham Lincoln in 1863. Joseph Stalin, who was badly scarred by the disease early in life, often had photographs retouched to make his pockmarks less apparent.