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104-792: Andrew Doria was a brig purchased by the Continental Congress in November 1775. She is most famous for her participation in the Battle of Nassau —the first amphibious engagement by the Continental Navy and the Continental Marines —and for being the first United States vessel to receive a salute from a foreign power. On 13 October 1775, the Continental Congress authorized the purchase of

208-410: 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

312-536: A British snow and assigned Joshua Barney to return the ship to Philadelphia, but was captured with a fouled rudder off Chincoteage by HMS  Perseus . The captain released Barney on pardon in Charleston to return to Philadelphia on foot over 19 days. Andrew Doria returned to Philadelphia where the Continental Navy acquired Racehorse , which it renamed Surprise . Andrew Doria was stationed in

416-435: A brig is the aft one. To improve maneuverability, the mainmast carries a ( gaff rigged ) fore-and-aft sail. Brig sails are named after the masts to which they are attached: the mainsail ; above that the main topsail ; above that the main topgallant sail ; and occasionally a very small sail, called the royal , is above that. Behind the main sail there is a small fore-and-aft sail called the spanker or boom mainsail (it

520-443: 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

624-422: A complicated arrangement of cordage named the " running rigging ". This is opposed to the standing rigging which is fixed, and keeps mast and other objects rigid. A brig is "generally built on a larger scale than a schooner , and may approach the magnitude of a full-sized, three-masted ship ." Brigs vary in length between 75 and 165 ft (23 and 50 m) with tonnages up to 480. A notable exception being

728-415: 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

832-518: 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

936-455: 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

1040-614: 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

1144-408: 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

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1248-601: 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

1352-423: 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

1456-421: 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

1560-411: A virulent fever. This complicated an already serious health problem caused by an outbreak of smallpox on all of the ships except for Andrew Doria whose crew had been protected by inoculation due to the far-sighted insistence of Nicholas Biddle. As a result of the crew's immunization, Andrew Doria was selected to serve as a hospital ship for the fleet and continued in this role for the remainder of

1664-418: Is a fleet of over 500 colliers trading to London alone. Other ports and coastal communities were also served by colliers trading to Britain's coal ports. In the first half of the 19th century, the vast majority were rigged as brigs, and that rig was retained for longer in the northeast of England. In sailing , a full-rigged brig is a vessel with two square rigged masts (fore and main). The main mast of

1768-582: 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

1872-420: 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

1976-490: 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

2080-541: 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

2184-411: 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

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2288-488: 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

2392-447: 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

2496-561: 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

2600-415: 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

2704-493: 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

2808-401: Is somewhat similar to the main sail of a schooner ). On the foremast is a similar sail, called the trysail . Attached to the respective yards of square-rigged ships are smaller spars, which can be extended, thus lengthening the yard, thus receiving an additional sailing wing on each side. These are called studding sails , and are used with fair and light wind only. The wings are named after

2912-453: 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

3016-575: The Dutch island of Sint Eustatius . When the brig reached the island on 16 November, she fired a 13-gun salute and received a reply from Fort Oranje —the first salute to an American flag on board an American warship in a foreign port. Andrew Doria also carried a copy of the Declaration of Independence to the island. The so-called "first salute" was widely reported in the United States at

3120-698: 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

3224-422: 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

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3328-470: 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

3432-468: 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

3536-465: 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

3640-409: 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

3744-402: The 17th century, one of the most famous periods for the brig was during the 19th century when they were involved in famous naval battles such as the Battle of Lake Erie . In the early 19th century the brig was a standard cargo ship. It was seen as "fast and well sailing", but required a large crew to handle its rigging. Brigs were seen as more manoeuvrable than schooners. James Cook requested

3848-624: 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

3952-515: The American fleet had reformed, it retired to New London, Connecticut , where it arrived on the morning of 8 April. From 9 April to 17 September 1776, Andrew Doria patrolled the Atlantic coast from Connecticut to Bermuda , capturing a number of British and Loyalist ships. On 11 July she captured ship "Nathaniel & Elizabeth". Capt. Biddle anchored his brig at Chester, Pennsylvania , on

4056-488: The British frigate opened a fierce fight in which the American ships were unable to fight as a squadron. In attempting to avoid a salvo from Glasgow , Cabot crossed Andrew Doria' s bow , forcing Biddle's brig onto a port tack which avoided collision but took her away from the action. Meanwhile, Alfred and Columbus , Hopkins' largest warships, took on Glasgow but received worse punishment than they inflicted. As

4160-779: 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 ,

4264-557: The Delaware River through the spring and summer of 1777. After Vice Admiral Lord Howe brought his British fleet into the river in September 1777, Andrew Doria was part of the forces charged with defending Philadelphia. Following the British occupation of Fort Mifflin on 16 November, Andrew Doria , with the remaining ships of the Continental Navy, sought shelter under the guns of Fort Mercer , at Red Bank, New Jersey . With

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4368-770: 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,

4472-565: 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

4576-531: 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

4680-507: 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

4784-448: 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

4888-477: 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

4992-503: 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

5096-655: The command of Captain Nicholas Biddle , Andrew Doria departed Philadelphia on 4 January 1776, as a warship in Esek Hopkins ' small fleet of five newly fitted warships ( Alfred , Andrew Doria , Cabot , Columbus , and Providence ), bound for the Chesapeake Bay . Between 11 and 17 February, the fleet was joined by the small sloop Fly , the sloop Hornet , and the schooner Wasp . On 17 February 1776, Hopkins decided to take advantage of

5200-729: The construction of a shipyard which will be located near the Susquehanna Museum at the Lockhouse on the banks of the Susquehanna River . [REDACTED]   This article incorporates text from the public domain Dictionary of American Naval Fighting Ships . Brig Brigs were prominent in the coastal coal trade of British waters. 4,395 voyages to London with coal were recorded in 1795. With an average of eight or nine trips per year for one vessel, that

5304-521: The conversion of the schooner HMS Grenfell to a brig, with the justification of the better control that he would have with a brig versus a schooner. The ability to stop the ship quickly (by backing sails) was particularly important for a vessel doing survey work. The windward ability of brigs (which depends as much on hull shape as the rig) could be comparable to or better than contemporary schooners. The author and naval officer Frederick Marryat characterised brigs as having superior windward performance to

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5408-621: 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

5512-498: The crew of Andrew Doria worked the ship into position to reenter the engagement and opened fire, Glasgow' s captain realized he was overmatched and decided to stand off to the northward. Andrew Doria , followed at a distance by her consorts, gave chase and kept up a running fight with her bow chasers until recalled by Hopkins, lest Glasgow lead his fleet to a Royal Navy squadron then operating in Rhode Island waters. When

5616-403: 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

5720-622: The discretion offered him and skip his missions in the Chesapeake Bay and along the coasts of the Carolinas . Instead, he took the fleet to the Bahamas for a raid on the island of New Providence to seize a large supply of gunpowder reportedly stored in the two forts that protected Nassau . On 1 March, the fleet reached the coast of Abaco Island where the ship Alfred captured two small sloops and Hopkins obtained intelligence from

5824-595: 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

5928-479: 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

6032-479: The eastern approaches to Nassau. The marines and sailors went ashore on 3 March and marched to Fort Montagu whose garrison surrendered without offering any real resistance. On 4 March, the Americans took Fort Nassau and town of Nassau. The fleet remained for almost two weeks, dismantling the guns of the forts and loading the captured materiel . During this stay, large numbers of the crew of each ship were stricken by

6136-409: The evacuation of Fort Mercer on 20 November, Robinson gave orders the next day for the ships to be burned to prevent capture. This was done shortly thereafter. The not-for-profit organization Andrew Doria – The First Salute, Inc., is raising funds to build a working replica of Andrew Doria . On 18 May 2009, the city council of Havre de Grace, Maryland , agreed to lease land to the organization for

6240-546: The evening of 17 September, ending his last cruise on the warship, as he had been selected to command Randolph , one of the four new frigates being built at Philadelphia for the Continental Navy. Capt. Isaiah Robinson took command of Andrew Doria . Robinson sailed Andrew Doria down the Delaware River on 17 October 1776, for a voyage to the West Indies to obtain a cargo of munitions and military supplies at

6344-403: The evolution of the barquentine . The need for large crews in relation to their relatively small size led to the decline of the production of brigs. They were replaced in commercial traffic by gaffsail schooners (which needed fewer personnel) and steam boats . The famous mystery ship Mary Celeste , while sometimes called a brig, was clearly a brigantine . Smallpox Smallpox

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6448-500: The expedition. On 16 March, Hopkin's fleet departed Nassau and headed north. Shortly after midnight on 6 April 1776, a lookout on Andrew Doria sighted two vessels to the southeast. Biddle passed word of the discovery to Hopkins who ordered the fleet to head for the strangers. The larger of the unidentified ships headed toward the Americans and before long she was within hailing distance and identified herself as "... his majesty's ship of war Glasgow ...." A broadside from Cabot into

6552-477: The famous designer Colin Mudie 's 'Little Brigs' ( TS Bob Allen and TS Caroline Allen) , which are only 30 ft (9 m) long and weigh only 8 tonnes. Historically, most brigs were made of wood, although some later brigs were built with hulls and masts of steel or iron. A brig made of pine in the 19th century was designed to last for about twenty years (many lasted longer). The word brig has been used in

6656-676: The fore-and-aft rigged brigantine was "that the sails, being smaller and more numerous, are more easily managed, and require fewer men or 'hands' to work them." The variant was so popular that the term brig came to exclusively signify a ship with this type of rigging. By the 17th century the British Royal Navy defined "brig" as having two square rigged masts. Brigs were used as small warships carrying about 10 to 18 guns. Due to their speed and maneuverability they were popular among pirates (though they were rare among American and Caribbean pirates). While their use stretches back before

6760-408: 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

6864-429: 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

6968-498: 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 ,

7072-436: 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

7176-406: 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

7280-408: 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

7384-530: The merchant brig Defiance . The ship was acquired in mid-November and moored in Wharton and Humphreys shipyard in Philadelphia where she was converted into a warship by Joshua Humphreys ( hull strengthening), John Barry (re- rigging ), and John Falconer ( ordnance and provisioning) at a cost of £ 296.4 s .6 d . She was named Andrew Doria after the 16th-century Genoese admiral Andrea Doria . Under

7488-404: 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

7592-429: 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

7696-420: The other American warships caught up. As the troop-carrying sloops headed into the harbor, Fort Nassau's guns opened fire. The shot fell short but demonstrated that the American fleet had been detected and that its intentions had been surmised. Hopkins recalled his ships. After conferring with his officers, Hopkins decided to land his troops two miles (3 km) down the coast from Fort Montagu , which protected

7800-523: 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,

7904-428: The past as an abbreviation of brigantine (which is the name for a two-masted vessel with foremast fully square rigged and her mainmast rigged with both a fore-and-aft mainsail, square topsails and possibly topgallant sails). The brig actually developed as a variant of the brigantine. Re-rigging a brigantine with two square-rigged masts instead of one gave it greater sailing power. The square-rigged brig's advantage over

8008-588: 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

8112-497: 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

8216-442: The prisoners that New Providence lay undefended. Hopkins planned to take Nassau by frontal assault , slipping his landing party of 270 sailors and marines into the harbor hidden on board the captured sloops. It was hoped that the American troops would not be detected until the landing and assault on Fort Nassau began. Success in this endeavor would enable the fleet to enter the harbor while the fort's guns, then in American hands, held

8320-491: 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)

8424-401: The sails to which they are fastened, i.e. the main studding sails, main top studding sails, and the main top gallant studding sails, etc. A brig's foremast is smaller than the main mast. The fore mast holds a fore sail, fore top sail, fore top gallant sail, and fore royal. Between the fore mast and the bowsprit are the fore staysail , jib , and flying jib . All the yards are manipulated by

8528-454: 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

8632-413: The schooners of that time. Marryat is considered, by maritime historians, to be an authoritative source on such matters. A brig's square-rig also had the advantage over a fore-and-aft–rigged vessel when travelling offshore, in the trade winds, where vessels sailed down wind for extended distances and where "the danger of a sudden jibe was the large schooner-captain's nightmare". This trait later led to

8736-479: 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

8840-491: 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

8944-520: 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

9048-425: 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

9152-560: The time, and later provided the title for Barbara Tuchman 's 1988 book, The First Salute: A View of the American Revolution . On her way back to the Delaware River, Andrew Doria encountered the sloop HMS Racehorse , of 10 guns, and under the command of Commander James Jones. A two-hour single-ship action ensued before Racehorse struck . Andrew Doria had lost four men killed and eight wounded; casualties on Racehorse apparently were higher. Andrew Doria encountered

9256-411: 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

9360-404: The town at bay. The marines and sailors embarked on the two captured sloops on the evening of 2 March and headed for New Providence, hoping to arrive at daybreak. While following the sloops, the fleet attempted to remain out of sight until the landing party had secured the fort. Andrew Doria —popularly referred to as the "Black Brig"—outdistanced her consorts and found it necessary to lay-to until

9464-475: 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

9568-439: 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

9672-442: 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

9776-554: 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

9880-421: 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

9984-431: 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

10088-477: 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

10192-428: 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

10296-442: 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

10400-404: 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

10504-421: 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

10608-440: 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

10712-404: 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

10816-460: 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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