The Essex Hospital was a privately built smallpox inoculation hospital on Cat Island (now Children's Island ) where many people were effectively inoculated against smallpox in 1773–1774. About a year after it opened, it was burned to the ground by paranoid and angry townspeople of Marblehead, Massachusetts .
101-433: In June, 1773, Marblehead was stricken by an epidemic of smallpox . The typical response to an outbreak was undertaken by town officials, including daily surveillance of the inhabitants by a Committee of Inspection, fencing off of infected areas, moving infected people to pesthouses , inspecting cargo arriving into the town, and limiting out of town visitors. Some forward-thinking townspeople argued in favor of inoculation of
202-410: A marker gene . This gene, called GFP , or green fluorescent protein, would cause live samples of the virus to glow green under fluorescent light. The insertion of this gene, which would not influence the virulence of the virus, would be the only allowed modification of the genome. The committee stated the proposed modification would aid in research of treatments by making it easier to assess whether
303-613: A boatload of this third class was discharged from the island but attempted to land at Nick's Cove, an unsanctioned landing area in Marblehead. Many townspeople were upset and a period of disorder and riots ensued. On January 12, the hospital boat Mercury was set on fire in Marblehead Harbor . One week later four townsmen were caught stealing contaminated clothing from the island while attempting to smuggle them into Marblehead. Presumably, they were hoping to earn condemnation for
404-443: A clinical case was observed, smallpox was confirmed using laboratory tests. Microscopically , poxviruses produce characteristic cytoplasmic inclusion bodies , the most important of which are known as Guarnieri bodies , and are the sites of viral replication . Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. They are found in virtually all poxvirus infections but
505-415: A discrete rash, in which the pustules stood out on the skin separately. The distribution of the rash was most dense on the face, denser on the extremities than on the trunk, and denser on the distal parts of the extremities than on the proximal. The palms of the hands and soles of the feet were involved in most cases. Sometimes, the blisters merged into sheets, forming a confluent rash, which began to detach
606-518: A doctor in Berkeley, Gloucestershire , rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine from the root word vacca , which is Latin for cow. The procedure was much safer than variolation and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox
707-455: A fatality rate of around 30%, while variola minor’s mortality rate was about 1%. Throughout the 18th century, variola major was responsible for around 400,000 deaths annually in Europe alone. Survivors of the disease often faced lifelong consequences, such as blindness and severe scarring, which were nearly universal among those who recovered. In the first half of the 20th century, variola major
808-475: A four-pound cannon on the island. Both arms were amputated, one eye was destroyed and the other severely injured, and his upper chest and neck were severely injured. Dr. Jackson performed immediate surgery, and Captain Lowell was able to leave the hospital on January 16, 1774. As of January 26, he was still alive. The third class of patients was inoculated at the hospital on December 15, 1773. In early January 1774,
909-614: A host cell varies across the poxviridae . Recombination of the genome occurs within actively infected cells. Following the onset of viral DNA replication, an intermediate set of genes codes for transcription factors of late gene expression. The products of the later genes include transcription factors necessary for transcribing the early genes for new virions, as well as viral RNA polymerase and other essential enzymes for new viral particles. These proteins are then packaged into new infectious virions capable of infecting other cells. Two live samples of variola major virus remain, one in
1010-408: A more extensive rash and higher fever. Variola minor is a less common presentation, causing less severe disease, typically discrete smallpox, with historical death rates of 1% or less. Subclinical ( asymptomatic ) infections with variola virus were noted but were not common. In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. This form
1111-601: A potential treatment was effective in killing viral samples. The recommendation could only take effect if approved by the WHA . When the WHA discussed the proposal in 2005, it refrained from taking a formal vote on the proposal, stating that it would review individual research proposals one at a time. Addition of the GFP gene to the Vaccinia genome is routinely performed during research on
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#17327718524831212-708: A public inoculation hospital on one of the nearby islands. The proposal was rejected, but the majority did agree to allow a private funding of a hospital as long as the Marblehead Selectmen could regulate it. On August 17 a petition to build a private inoculation hospital on an island was sent to Governor Hutchinson who approved the measure. The owners of the future Essex Hospital were four popular Marblehead political figures: John Glover , Jonathan Glover (John Glover's brother), Azor Orne , and Elbridge Gerry ; they purchased Children's Island (Catt Island) on September 2, 1773. Despite having received permission from
1313-423: A region of roughly 100 base pairs necessary for resolving concatomeric DNA (a stretch of DNA containing multiple copies of the same sequence), a few open reading frames , and short tandemly repeating sequences of varying number and length. The ITRs of poxviridae vary in length across strains and species. The coding sequence for most of the viral proteins in variola major virus have at least 90% similarity with
1414-442: A sailor was not particularly remarkable, his writings are of great value in understanding the life of an average sailor at that time. Bowen was a sailor from the age of 13 to the age of 35. Ashley Bowen was born on January 8, 1728. He grew up in the town of Marblehead, Massachusetts , until going to sea at age eleven. Bowen's mother died when he was twelve, and he suffered personal turmoil when his father remarried soon after. At
1515-421: A source of infection”; noted that “Current recommendations for control of secondary smallpox infections emphasize transmission ‘by expelled droplets to close contacts (those within 6–7 feet)’”; but warned that the “emphasis on spread via large droplets may reduce the vigilance with which more difficult airborne precautions [i.e. against finer droplets capable of traveling longer distances and penetrating deeply into
1616-582: Is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and viscera . This form develops in approximately 2% of infections and occurs mostly in adults. Pustules do not typically form in hemorrhagic smallpox. Instead, bleeding occurs under the skin, making it look charred and black, hence this form of the disease is also referred to as variola nigra or "black pox". Hemorrhagic smallpox has very rarely been caused by variola minor virus. While bleeding may occur in mild cases and not affect outcomes, hemorrhagic smallpox
1717-420: Is also a later form of hemorrhagic smallpox (referred to late hemorrhagic smallpox, or variolosa pustula hemorrhagica ). The prodrome is severe and similar to that observed in early hemorrhagic smallpox, and the fever persists throughout the course of the disease. Bleeding appears in the early eruptive period (but later than that seen in purpura variolosa ), and the rash is often flat and does not progress beyond
1818-490: Is also under research as a viral vector for vaccines for unrelated diseases. The genome of variola major virus was first sequenced in its entirety in the 1990s. The complete coding sequence is publicly available online. The current reference sequence for variola major virus was sequenced from a strain that circulated in India in 1967. In addition, there are sequences for samples of other strains that were collected during
1919-541: Is believed to have had a mortality rate of less than 1%, as compared to variola major's 30%. Like variola major, variola minor was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with variola minor virus conferred immunity against the more dangerous variola major virus. Because variola minor was a less debilitating disease than smallpox, people were more frequently ambulant and thus able to infect others more rapidly. As such, variola minor swept through
2020-411: Is caused by infection with variola virus, which belongs to the family Poxviridae , subfamily Chordopoxvirinae , genus Orthopoxvirus . The date of the appearance of smallpox is not settled. It most probably evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago. The wide range of dates is due to the different records used to calibrate the molecular clock . One clade
2121-488: Is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among human DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus . To replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses , the most important of which is a viral-associated DNA-dependent RNA polymerase . Both enveloped and unenveloped virions are infectious. The viral envelope
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#17327718524832222-447: Is consistent with the other published estimates, it suggests that the archaeological and historical evidence is very incomplete. Better estimates of mutation rates in these viruses are needed. Examination of a strain that dates from c. 1650 found that this strain was basal to the other presently sequenced strains. The mutation rate of this virus is well modeled by a molecular clock. Diversification of strains only occurred in
2323-561: Is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. Earlier deaths included six European monarchs , including Louis XV of France in 1774. As recently as 1967, 15 million cases occurred a year. The final known fatal case occurred in the United Kingdom in 1978 . Inoculation for smallpox appears to have started in China around
2424-415: Is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin . Infection with either variola major virus or variola minor virus confers immunity against the other. The more common, infectious form of the disease was caused by the variola major virus strain, known for its significantly higher mortality rate compared to its counterpart, variola minor. Variola major had
2525-493: Is rapidly followed by the development of petechiae and bleeding in the skin, conjunctiva and mucous membranes. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. Some people survive a few days longer, during which time the skin detaches and fluid accumulates under it, rupturing at the slightest injury. People are usually conscious until death or shortly before. Autopsy reveals petechiae and bleeding in
2626-453: Is typically fatal. Vaccination does not appear to provide any immunity to either form of hemorrhagic smallpox and some cases even occurred among people that were revaccinated shortly before. It has two forms. The early or fulminant form of hemorrhagic smallpox (referred to as purpura variolosa ) begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. The skin becomes dusky and erythematous, and this
2727-698: The East India Company stationed in China and another by Clopton Havers . Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire , writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. According to Voltaire (1742), the Turks derived their use of inoculation from neighbouring Circassia . Voltaire does not speculate on where
2828-685: The Royal Navy and British traders. During this time, Bowen made money transporting cargo , serving in the British navy, and trading goods. Bowen was also held prisoner during the Seven Years' War by the French. In 1758, Bowen married Dorothea Chadwick, who bore him six children during their marriage. At the time, Bowen was 30 years old, and the fact that he had a wife on land made him think of retirement. Eventually, Bowen gave up seafaring at
2929-422: The common cold : fever of at least 38.3 °C (101 °F), muscle pain , malaise , headache and fatigue. As the digestive tract was commonly involved, nausea, vomiting, and backache often occurred. The early prodromal stage usually lasted 2–4 days. By days 12–15, the first visible lesions – small reddish spots called enanthem – appeared on mucous membranes of the mouth, tongue, palate , and throat, and
3030-470: The horsepox virus using publicly available sequence data for horsepox. The researchers argued that their work would be beneficial to creating a safer and more effective vaccine for smallpox, although an effective vaccine is already available. The horsepox virus had previously seemed to have gone extinct, raising concern about potential revival of variola major and causing other scientists to question their motives. Critics found it especially concerning that
3131-468: The replication of viral DNA. The first set of expressed genes are transcribed by pre-existing viral machinery packaged within the infecting virion. These genes encode the factors necessary for viral DNA synthesis and for transcription of the next set of expressed genes. Unlike most DNA viruses, DNA replication in variola virus and other poxviruses takes place within the cytoplasm of the infected cell. The exact timing of DNA replication after infection of
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3232-465: The 1500s. Europe adopted this practice from Asia in the first half of the 18th century. In 1796, Edward Jenner introduced the modern smallpox vaccine. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest (a disease of even-toed ungulates ) in 2011. The term "smallpox" was first used in England in
3333-409: The 16th century to distinguish the disease from syphilis , which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague. The United States and Russia retain samples of variola virus in laboratories, which has sparked debates over safety . There are two forms of the smallpox. Variola major is the severe and most common form, with
3434-624: The 18th and 19th centuries. Variola virus is large and brick-shaped and is approximately 302 to 350 nanometers by 244 to 270 nm, with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end. Four orthopoxviruses cause infection in humans: variola, vaccinia , cowpox , and monkeypox . Variola virus infects only humans in nature, although primates and other animals have been infected in an experimental setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. The life cycle of poxviruses
3535-503: The Castle of Pox, General Jackson, commander-in-chief; General Randall, leftenant general of Castle Pox; Arnaold Martin Esq., chief admiral of the white, in sloop Ashley. Tis supposed this siege will last thirty days. By an expressed from Castle Pox General Jackson had a smart engagement and wounded nearly a 100 of Colonel Orne's body of volunteers the first evening they landed, of both sexes from
3636-779: The Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. After publishing The present method of inoculating for the small-pox in 1767, Dr Thomas Dimsdale was invited to Russia to variolate the Empress Catherine the Great of Russia and her son, Grand Duke Paul , which he successfully did in 1768. In 1796, Edward Jenner ,
3737-833: The United States at the CDC in Atlanta, and one at the Vector Institute in Koltsovo, Russia. Research with the remaining virus samples is tightly controlled, and each research proposal must be approved by the WHO and the World Health Assembly (WHA). Most research on poxviruses is performed using the closely related Vaccinia virus as a model organism. Vaccinia virus, which is used to vaccinate for smallpox,
3838-565: The United States, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates. Along with variola major, the minor form has now been totally eradicated from the globe. The last case of indigenous variola minor was reported in a Somali cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980. Variola minor
3939-531: The WHO eradication campaign. A genome browser for a complete database of annotated sequences of variola virus and other poxviruses is publicly available through the Viral Bioinformatics Resource Center . The WHO currently bans genetic engineering of the variola virus. However, in 2004, a committee advisory to the WHO voted in favor of allowing editing of the genome of the two remaining samples of variola major virus to add
4040-507: The absence of Guarnieri bodies could not be used to rule out smallpox. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. If particles with the characteristic morphology of herpesviruses are seen this will eliminate smallpox and other orthopoxvirus infections. Definitive laboratory identification of variola virus involved growing
4141-488: The age of "13 year and three month" Bowen was apprenticed to Captain Peter Hall of Boston . Bowen went to sea as a living from the age of 13 on, suffering cruelly under the harsh beatings of his master. Although repeated escape attempts failed, Bowen was finally able to escape Hall at the age of 17. Finally away from his master, Bowen spent the next eighteen years in the employment of several organizations, including
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4242-493: The age of 3 years to 60 first day, and that General Randall engaged the Colonel himself. Since those exposed to smallpox (including recently inoculated) are not contagious for 10 days, visitors were allowed during this time. A newspaper article at the time notes, the patients "are indeed confined to a strict regimen; but they may every day be seen walking the island, shooting wild fowl, playing at quoits , etc." On November 5, 1773
4343-449: The age of 35, and set up a rigging business in Marblehead, Massachusetts . The business was a moderate success, providing enough income to get by, but never by much. Dorothea died in 1771; the same year, Bowen married Mary Shaw. Shaw died in 1781, and the next year Bowen married Hannah Graves. Bowen's final child was born in 1797. Although Bowen had amassed some wealth through his business and his adventures at sea, as he grew elderly, he
4444-448: The bloodstream in large numbers, a condition known as viremia . This resulted in the second wave of multiplication in the spleen , bone marrow , and lymph nodes. The clinical definition of ordinary smallpox is an illness with acute onset of fever equal to or greater than 38.3 °C (101 °F) followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development without other apparent cause. When
4545-477: The central region of the genome is highly consistent across orthopoxviruses , and the arrangement of genes is consistent across chordopoxviruses. The center of the variola virus genome contains the majority of the essential viral genes, including the genes for structural proteins , DNA replication , transcription , and mRNA synthesis. The ends of the genome vary more across strains and species of orthopoxviruses . These regions contain proteins that modulate
4646-503: The closely related Vaccinia virus . The public availability of the variola virus complete sequence has raised concerns about the possibility of illicit synthesis of infectious virus. Vaccinia , a cousin of the variola virus, was artificially synthesized in 2002 by NIH scientists. They used a previously established method that involved using a recombinant viral genome to create a self-replicating bacterial plasmid that produced viral particles. In 2016, another group synthesized
4747-621: The course of the illness, but this happened most frequently during the first week of the rash when most of the skin lesions were intact. Infectivity waned in 7 to 10 days when scabs formed over the lesions, but the infected person was contagious until the last smallpox scab fell off. Concern about possible use of smallpox for biological warfare led in 2002 to Donald K. Milton's detailed review of existing research on its transmission and of then-current recommendations for controlling its spread. He agreed, citing Rao, Fenner and others, that “careful epidemiologic investigation rarely implicated fomites as
4848-403: The diagnosis of infection. Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox could be distinguished by several methods. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly
4949-595: The disease dates to around 1500 BC in Egyptian mummies . The disease historically occurred in outbreaks . It was one of several diseases introduced by the Columbian exchange to the New World , resulting in large swathes of Native Americans dying . In 18th-century Europe, it is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox. Smallpox
5050-479: The disease included fever and vomiting. This was followed by formation of ulcers in the mouth and a skin rash . Over a number of days, the skin rash turned into the characteristic fluid-filled blisters with a dent in the center. The bumps then scabbed over and fell off, leaving scars. The disease was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person or rarely via contaminated objects . Prevention
5151-399: The disease; diluted, contaminated material (pus) from a person with mild disease would be injected into a healthy person who would, with hope, develop a very mild case of the disease, fully recover, and then be immune. However, most people at the time were terrified of and vehemently opposed to the practice. On August 9, 1773, a Town Meeting in Marblehead was held to debate the construction of
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#17327718524835252-421: The evening after very jovially, as did their friends and acquaintance under inoculation." Most of the first class of patients were able to leave the hospital from November 9-11th. On November 15, the second class of patients, numbering around 100, were inoculated at Essex Hospital. One of the members of this second group was Captain Lowell of Newburyport , who on December 4, 1773 was severely injured while loading
5353-570: The first class of patients were Captain John Glover and his family, all of whom were inoculated and then remained as volunteers. Ashley Bowen , exemplifying some of the bitter feelings toward the hospital, sarcastically noted in his journal on October 19: This day at noon Colonel Orne with a body of volunteers and a number of invalids landed at Cape Pus on the NW end of the Isle of Catt and laid siege to
5454-535: The former Essex Hospital held the Island throughout the American Revolutionary War . Sometime before 1787 both Glovers sold their quarter ownerships to Deacon William Williams of Marblehead. The Deacon then acquired another 16th part to gain majority ownership. After his death in 1787, his wife sold the property to Edward Fettyplace for $ 43.33 on June 25, 1795. Smallpox Smallpox
5555-408: The genome of vaccinia , a related virus used for vaccination against smallpox. Gene expression of variola virus occurs entirely within the cytoplasm of the host cell , and follows a distinct progression during infection. After entry of an infectious virion into a host cell, synthesis of viral mRNA can be detected within 20 minutes. About half of the viral genome is transcribed prior to
5656-429: The group was able to recreate viable virus in a short time frame with relatively little cost or effort. Although the WHO bans individual laboratories from synthesizing more than 20% of the genome at a time, and purchases of smallpox genome fragments are monitored and regulated, a group with malicious intentions could compile, from multiple sources, the full synthetic genome necessary to produce viable virus. Smallpox
5757-508: The hospital be closed that "a committee to cleanse the furniture, etc. in the so just and most satisfactory manner to the Town" be formed. The town refused to buy the hospital and supplies but did form a committee to oversee disinfection. On the following day, the three committee members and eight members of their family spent the next two days on the island cleaning and disinfecting, when on the second night they were suddenly awakened by fire. During
5858-451: The hospital by starting an outbreak of smallpox. The following morning the four were tarred and feathered and paraded through Marblehead into Salem, a source of much entertainment to those witnessing the spectacle. Due to ongoing opposition, the hospital proprietors called for a town meeting on January 24 to ask the town to purchase the hospital and supplies, and to decide if the hospital should be kept open. Alternatively, they requested that if
5959-415: The hospital was clear of infection, many gentlemen of the town accompanied it to the island, and the hospital was thronged in every quarter. In the afternoon the house was cleared and Dr. Jackson proceeded to inoculate the patients, being one hundred and three in number ... The patients are daily displaying their signal of health [by flying flags] from the middle of the island and all are in high spirits Among
6060-649: The hospital. They were jailed in Salem but were freed the same night by a violent mob from Marblehead. Within a week the High Sheriff of the County called for help in apprehending the accused and their rescuers. At the same time, a large group from Marblehead called for arms to defend the two men. To quell the inevitable violence, the four owners of the Essex Hospital nobly dropped all charges and refused to pursue
6161-498: The hosts' immune systems, and are primarily responsible for the variability in virulence across the orthopoxvirus family. These terminal regions in poxviruses are inverted terminal repetitions (ITR) sequences. These sequences are identical but oppositely oriented on either end of the genome, leading to the genome being a continuous loop of DNA. Components of the ITR sequences include an incompletely base paired A/T rich hairpin loop ,
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#17327718524836262-409: The island the new patients would enter the clean room of the small, one-story shifting house where they left a clean set of clothes to be worn upon departing. Another room in the building, the shifting-room, as where at the end of their island stay they would strip, wash, and be fumigated before entering the clean-room and getting dressed in the previously left, uncontaminated clothes. The hospital itself
6363-400: The island, and once returned to Marblehead were to dock only at approved locations within the harbor. People on the island were not to approach the island landing and a fence and trench would separate areas where supplies were dropped off from areas used by people on the island. By early October, the hospital and a shifting-house were completed. Upon arriving on a beach at the northwest part of
6464-436: The lesions remained almost flush with the skin at the time when raised vesicles would have formed in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10% of cases, and most (72%) were children. Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of viremia . The prodromal symptoms continued even after
6565-406: The lower respiratory tract] are maintained”. Once inhaled, the variola virus invaded the mucous membranes of the mouth, throat, and respiratory tract. From there, it migrated to regional lymph nodes and began to multiply. In the initial growth phase, the virus seemed to move from cell to cell, but by around the 12th day, widespread lysis of infected cells occurred and the virus could be found in
6666-408: The malignant and hemorrhagic forms were usually fatal. The modified form was almost never fatal. In early hemorrhagic cases, hemorrhages occurred before any skin lesions developed. The incubation period between contraction and the first obvious symptoms of the disease was 7–14 days. At least 90% of smallpox cases among unvaccinated persons were of the ordinary type. In this form of the disease, by
6767-453: The matter further. The final act of the "smallpox war" occurred in March when one of the men who had been tarred and feathered for attempting to smuggle clothes from the island was caught trying to recover more clothing from the island. That night he was dragged from bed by an unruly mob and publicly whipped. These events were quickly forgotten as thoughts turned toward revolution. The owners of
6868-539: The night, approximately 20 townspeople had snuck onto the island and set the hospital on fire. Everyone escaped alive but all buildings and property were burned or destroyed. For the rest of January and into February, Marblehead was in a general state of uproar. A military watch was formed and the General Court of Massachusetts was petitioned to help restore order. At the end of February, John Watts and John Guillard of Marblehead were arrested for suspicion of burning
6969-404: The onset of the rash. The rash on the mucous membranes ( enanthem ) was extensive. Skin lesions matured slowly, were typically confluent or semi-confluent, and by the seventh or eighth day, they were flat and appeared to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant smallpox
7070-429: The oral, nasal, or pharyngeal mucosa of an infected person. It was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person. Some infections of laundry workers with smallpox after handling contaminated bedding suggested that smallpox could be spread through direct contact with contaminated objects ( fomites ), but this was found to be rare. Also rarely, smallpox
7171-523: The outer layers of skin from the underlying flesh. Patients with confluent smallpox often remained ill even after scabs had formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62%. Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. It was rare in unvaccinated people, with one case study showing 1–2% of modified cases compared to around 25% in vaccinated people. In this form,
7272-421: The patients and staff on the island celebrated Pope's Day (a colonial variant of Guy Fawkes Day ) by lighting tar barrels "and a large fire displayed from the middle of the Island; the hospital was likewise illuminated, and made a most beautiful appearance here. Rockets were ordered from Boston ... a number of gentlemen, who spent the evening in the assembly room, had them played off from their quarters, and spent
7373-588: The person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of smallpox. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of
7474-516: The poor which are considerably numerous, inoculation gratis one poor inhabitant for every ten others inoculated." Two boats were employed, the Mercury Cruiser to transport people, and the Noah's Ark to transport cattle, sheep, deer, and animal feed. On October 19, ... the first class of patients went down to the Essex Hospital. As a number of respectable persons, of both sexes, were in it and
7575-497: The practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming dynasty . If successful, inoculation produced lasting immunity to smallpox. Because
7676-491: The prodromal illness still occurred but may have been less severe than in the ordinary type. There was usually no fever during the evolution of the rash. The skin lesions tended to be fewer and evolved more quickly, were more superficial, and may not have shown the uniform characteristic of more typical smallpox. Modified smallpox was rarely, if ever, fatal. This form of variola major was more easily confused with chickenpox . In malignant-type smallpox (also called flat smallpox)
7777-428: The proprietors agreed. On October 5 to help alleviate some concerns "The Rules and Regulations of the Essex Hospital on Catt Island" were published in the local newspaper, The Essex Gazette. These rules required guards to be posted on the island to ensure no one would come ashore without a permit and no one would leave the island without a health clearance from a physician. No boat other than the hospitals' were to approach
7878-454: The same size since the viral effect progresses more uniformly. A variety of laboratory methods were available for detecting chickenpox in the evaluation of suspected smallpox cases. The earliest procedure used to prevent smallpox was inoculation with variola minor virus (a method later known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before
7979-479: The second day of the rash the macules had become raised papules . By the third or fourth day, the papules had filled with an opalescent fluid to become vesicles . This fluid became opaque and turbid within 24–48 hours, resulting in pustules . By the sixth or seventh day, all the skin lesions had become pustules. Between seven and ten days the pustules had matured and reached their maximum size. The pustules were sharply raised, typically round, tense, and firm to
8080-491: The separation of variola virus from Taterapox (an Orthopoxvirus of some African rodents including gerbils ) at 3,000 to 4,000 years ago. This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. If the mutation rate is assumed to be similar to that of the herpesviruses , the divergence date of variola virus from Taterapox has been estimated to be 50,000 years ago. While this
8181-520: The spleen, kidney, serous membranes , skeletal muscles, pericardium , liver, gonads and bladder. Historically, this condition was frequently misdiagnosed, with the correct diagnosis made only at autopsy. This form is more likely to occur in pregnant women than in the general population (approximately 16% of cases in unvaccinated pregnant women were early hemorrhagic smallpox, versus roughly 1% in nonpregnant women and adult males). The case fatality rate of early hemorrhagic smallpox approaches 100%. There
8282-425: The temperature fell to near-normal. These lesions rapidly enlarged and ruptured, releasing large amounts of virus into the saliva. Variola virus tended to attack skin cells, causing the characteristic pimples, or macules , associated with the disease. A rash developed on the skin 24 to 48 hours after lesions on the mucous membranes appeared. Typically the macules first appeared on the forehead, then rapidly spread to
8383-411: The touch. The pustules were deeply embedded in the dermis, giving them the feel of a small bead in the skin. Fluid slowly leaked from the pustules, and by the end of the second week, the pustules had deflated and began to dry up, forming crusts or scabs. By day 16–20 scabs had formed over all of the lesions, which had started to flake off, leaving depigmented scars. Ordinary smallpox generally produced
8484-430: The town, their decision to inoculate remained contentious. Many Marbleheaders feared that the inoculation process would cause new outbreaks of the disease and that the hospital itself would scare off merchant ships arriving at Marblehead and Salem Harbors. Some opponents of the hospital also denigrated the plan as a get-rich scheme by the proprietors. In response to the fear the town selectmen prescribed strict rules to which
8585-475: The vesicular stage. Hemorrhages in the mucous membranes appear to occur less often than in the early hemorrhagic form. Sometimes the rash forms pustules which bleed at the base and then undergo the same process as in ordinary smallpox. This form of the disease is characterized by a decrease in all of the elements of the coagulation cascade and an increase in circulating antithrombin . This form of smallpox occurs anywhere from 3% to 25% of fatal cases, depending on
8686-439: The virulence of the smallpox strain. Most people with the late-stage form die within eight to 10 days of illness. Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. The case fatality rate for late hemorrhagic smallpox is around 90–95%. Pregnant women are slightly more likely to experience this form of the disease, though not as much as early hemorrhagic smallpox. Smallpox
8787-442: The virus on chorioallantoic membrane (part of a chicken embryo ) and examining the resulting pock lesions under defined temperature conditions. Strains were characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic tests and enzyme linked immunosorbent assays (ELISA), which measured variola virus-specific immunoglobulin and antigen were also developed to assist in
8888-554: The whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process took no more than 24 to 36 hours, after which no new lesions appeared. At this point, variola major disease could take several very different courses, which resulted in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic smallpox. Historically, ordinary smallpox had an overall fatality rate of about 30%, and
8989-421: Was achieved mainly through the smallpox vaccine . Once the disease had developed, certain antiviral medications could potentially have helped, but such medications did not become available until after the disease was eradicated. The risk of death was about 30%, with higher rates among babies. Often, those who survived had extensive scarring of their skin, and some were left blind. The earliest evidence of
9090-431: Was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola. The genome of variola major virus is about 186,000 base pairs in length. It is made from linear double stranded DNA and contains the coding sequence for about 200 genes . The genes are usually not overlapping and typically occur in blocks that point towards the closer terminal region of the genome. The coding sequence of
9191-477: Was an infectious disease caused by variola virus (often called smallpox virus), which belongs to the genus Orthopoxvirus . The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980, making smallpox the only human disease to have been eradicated to date. The initial symptoms of
9292-488: Was completely dependent upon his children for his upkeep. Bowen died in 1813. Although Bowen did not become a master of his own ship or have notable seafaring adventures for his time, his historical contribution is important. Because Bowen was the first American sailor to write an autobiography, his account gives historians valuable insight into life as an 18th-century sailor. Bowen's autobiography and journal had been an important archival source for scholars and in 1973 it
9393-428: Was highly contagious, but generally spread more slowly and less widely than some other viral diseases, perhaps because transmission required close contact and occurred after the onset of the rash. The overall rate of infection was also affected by the short duration of the infectious stage. In temperate areas, the number of smallpox infections was highest during the winter and spring. In tropical areas, seasonal variation
9494-442: Was less evident and the disease was present throughout the year. Age distribution of smallpox infections depended on acquired immunity . Vaccination immunity declined over time and was probably lost within thirty years. Smallpox was not known to be transmitted by insects or animals and there was no asymptomatic carrier state. Transmission occurred through inhalation of airborne variola virus, usually droplets expressed from
9595-451: Was located on the southwestern section of the island, was three stories high, had ten rooms each with four beds, a kitchen, and accommodations for a steward, the physicians, nurses, and their assistants. The proprietors of the hospital employed Dr. Hall Jackson from Portsmouth as hospital superintendent, and Dr. Ananias Randall from Long Island as assistant physician. The proprietors set a fee "for board, nursing, inoculation, etc., and for
9696-404: Was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by viral culture . In addition, there were two very rare and fulminating types of smallpox, the malignant (flat) and hemorrhagic forms, which were usually fatal. The initial symptoms were similar to other viral diseases that are still extant, such as influenza and
9797-421: Was nearly always fatal and death usually occurred between the 8th and 12th day of illness. Often, a day or two before death, the lesions turned ashen gray, which, along with abdominal distension, was a bad prognostic sign. This form is thought to be caused by deficient cell-mediated immunity to smallpox. If the person recovered, the lesions gradually faded and did not form scars or scabs. Hemorrhagic smallpox
9898-473: Was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by the vaccinia virus. Vaccinia is in the same family as cowpox and variola virus but is genetically distinct from both. The origin of the vaccinia virus and how it came to be in the vaccine are not known. Ashley Bowen Ashley Bowen (1728–1813) was the first American sailor to write an autobiography . Although Bowen's career as
9999-440: Was spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. The virus can cross the placenta , but the incidence of congenital smallpox was relatively low. Smallpox was not notably infectious in the prodromal period and viral shedding was usually delayed until the appearance of the rash, which was often accompanied by lesions in the mouth and pharynx. The virus can be transmitted throughout
10100-404: Was the primary cause of smallpox outbreaks across Asia and most of Africa. Meanwhile, variola minor was more commonly found in regions of Europe, North America, South America, and certain parts of Africa. Variola minor virus, also called alastrim, was a less common form of the virus, and much less deadly. Although variola minor had the same incubation period and pathogenetic stages as smallpox, it
10201-516: Was the variola major strains (the more clinically severe form of smallpox) which spread from Asia between 400 and 1,600 years ago. A second clade included both alastrim (a phenotypically mild smallpox) described from the American continents and isolates from West Africa which diverged from an ancestral strain between 1,400 and 6,300 years before present. This clade further diverged into two subclades at least 800 years ago. A second estimate has placed
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