   #copyright

Smallpox

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Smallpox
   Classifications and external resources

   A child infected with smallpox
     ICD- 10   B 03.
     ICD- 9    050
   DiseasesDB  12219
   MedlinePlus 001356
    eMedicine  emerg/885
   MeSH        D012899
   iVariola virus (Smallpox)
     Virus classification

   Group:   Group I ( dsDNA)
   Family:  Poxviridae
   Genus:   Orthopoxvirus
   Species: Variola vera

   Smallpox (also known by the Latin names Variola or Variola vera) was a
   highly contagious viral disease unique to humans. It is caused by two
   virus variants called Variola major and Variola minor. V. major is the
   more deadly form, with a typical mortality of 20–40 percent of those
   infected. The other type, V. minor, only kills 1% of its victims. Many
   survivors are left blind in one or both eyes from corneal ulcerations,
   and persistent skin scarring—pockmarks—is nearly universal. Smallpox
   was responsible for an estimated 300–500 million deaths in the 20th
   century. As recently as 1967, the World Health Organization ( WHO)
   estimated that 15 million people contracted the disease and that two
   million died in that year.

   After successful vaccination campaigns, in 1979 the WHO certified the
   eradication of smallpox, though 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.

   Famous victims of this disease include Ramesses V (see Koplow, p. 11,
   plus notes), 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, would often have
   photographs retouched to make his pockmarks less apparent.

   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. On at least one occasion,
   germ warfare was attempted by the British Army under Jeffery Amherst
   when two smallpox-infected blankets were deliberately given to
   representatives of the besieging Delaware Indians during Pontiac's
   Rebellion in 1763. That Amherst intended to spread the disease to the
   natives is not doubted by historians; whether or not the attempt
   succeeded is a matter of debate. ^[details]

Vaccine

   Smallpox is described in the Ayurveda books. Smallpox was ameliorated
   by inoculation with year-old smallpox matter. The inoculators would
   travel all across India pricking the skin of the arm with a small metal
   instrument using "variolous matter" taken from pustules produced by the
   previous year's inoculations. The effectiveness of this system was
   confirmed by the British doctor J.Z. Holwell in an account to the
   College of Physicians in London in 1767.

   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 Philadelpha) 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 Ms. Parker became infected was never fully elucidated.

   Note: A recent study by the Centre of Disease Control in Atlanta (CDC)
   have found that every 1 in a million people are carriers of smallpox
   and could quite possibly infect many others with this horrifying
   disease.

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 will be 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 will be
   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.

   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 will deflate in
   time (the duration is variable), and will start to dry up, usually
   beginning on day 28. Eventually the pustules will 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 will occur under the skin, making
   the skin look charred and black (this is known as black pox). The eyes
   will 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 or typhus.

   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

   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.

          See: Population history of American indigenous peoples for a
          discussion of this disease and other issues at the time of
          European contact.

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

   Jenner said, “The annihilation of smallpox—the dreadful scourge of the
   human race—will be the final result of vaccination.” Jenner’s dream was
   ultimately realized. Around the world, attempts would be made to
   annihilate 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 initial problem the WHO team faced was inadequate reporting
   arrangements, as many smallpox cases were not notified to the
   authorities.

   Before WHO could begin to eradicate smallpox it was necessary to
   establish that smallpox carriers did not exist, and that smallpox did
   not exist in the wild, as diseases such as yellow fever did. The fact
   that there has been no case of smallpox since 1977 has confirmed these
   two facts as amongst the most certain in medical science.

   A network of experts was established around the world. When the disease
   emerged, assistance was offered to local governments to vaccinate
   everyone in the area.

   Eradicating smallpox required huge effort and concentration. In India
   and Bangladesh, religion and round-the-clock civil wars became
   obstacles. In fear of offending the goddess associated with the
   disease, many Hindus refused the vaccine. Civil war was the bigger
   problem. Troop movements and crowded encampments have long been
   associated with spread of disease, including smallpox.

   The team’s answer to civil war was to vaccinate all the troops, with or
   without the permission of generals commanding the armies. The team
   placed themselves in great danger by doing this, and the WHO even told
   them to stop. 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.

   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 Centre for Disease Control (CDC)
   and the Russian State Research Centre of Virology and Biotechnology
   (also known as the Vector Institute) 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.

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