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153-505: The founder of the Mạc dynasty was a descendant of the famed Trần dynasty scholar Mạc Đĩnh Chi . Mạc Đăng Dung chose to enter the military and ascended the ranks to become the senior general in the Lê dynasty army. Later he seized power and ruled Vietnam from 1527 till his death in 1541. Mạc Đăng Dung, got his start as a bodyguard for Lê Uy Mục , the unpopular Lê Emperor, around 1506. Over time, despite

306-810: A dutongshisi : a category only slightly higher than a chieftaincy. After 1540, the Ming received tribute from both the Lê dynasty and the Mạc, a state of affairs that continued through the end of the Southern Ming at which point the two sides became tributary states of the Qing dynasty. 16°28′N 107°36′E  /  16.467°N 107.600°E  / 16.467; 107.600 Tr%E1%BA%A7n dynasty 21°02′15″N 105°50′19″E  /  21.03750°N 105.83861°E  / 21.03750; 105.83861 The Trần dynasty , ( Vietnamese : Nhà Trần, chữ Nôm : 茹陳), officially Đại Việt ( Chữ Hán : 大越),

459-410: 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

612-403: 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 was achieved mainly through

765-577: A Mongol-appointed darughachi . In 1283, Khubilai Khan sent word to the Trần that he intended to send Yuan armies through Trần territory to attack the kingdom of Champa, with demands for provisions and other support to the Yuan army. In the twelfth lunar month of 1284, the second Yuan invasion of Đại Việt was launched under the command of Kublai Khan's prince Toghon . Đại Việt was attacked from two directions, with Toghan himself conducting an infantry invasion from

918-443: 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

1071-562: A defamation campaign against the Emperor which ultimately made Nghệ Tông decide to replace him by Trần Thuận Tông and downgrade Phế Đế to Prince Linh Đức in December 1388. Trần Nghệ Tông died on the 15th day of the twelfth lunar month, 1394 at the age of 73 leaving the imperial court in the total control of Hồ Quý Ly. He began to reform the administrative and examination systems of the Trần dynasty and eventually obliged Thuận Tông to change

1224-473: A disastrous defeat of the Yuan navy at the Battle of Bạch Đằng on the eighth day of the third lunar month, 1288. Besides Trần Quốc Tuấn, other notable generals of the Trần dynasty during this time were Prince Nhân Huệ Trần Khánh Dư , who destroyed the logistics convoy of the Yuan navy at the Battle of Vân Đồn , and general Phạm Ngũ Lão , who took charge of ambushing prince Toghan's retreating troops. After

1377-518: 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

1530-455: 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

1683-614: 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

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1836-597: A land tax in measures of rice that was calculated by land classification. One historical book reveals that the Trần dynasty taxed everything from fish and fruits to betel . Taxpayers were divided into three categories: minors ( tiểu hoàng nam , from 18 to 20), adults ( đại hoàng nam , from 20 to 60), and seniors ( lão hạng , over 60). Manufactured items such as handicrafts, cotton, silk and brocades saw rapid development in this period. Some of these items were exported to China while silver, gold, tin and lead mining increased jewelry-making. State-minted copper coins were set up by

1989-577: 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 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,

2142-730: A marriage with the Vietnamese princess Huyền Trân . Anh Tông accepted this offer, then took and renamed Ô prefecture and Lý prefecture as Thuận prefecture and Hóa prefecture. These two prefectures soon began to be referred to collectively as the Thuận Hóa region. Only one year into the marriage, Chế Mân died and, in line with the royal tradition of Champa, Huyền Trân was to be cremated with her husband . Facing this urgent condition, Anh Tông sent his mandarin Trần Khắc Chung to Champa to save Huyền Trân from an imminent death. Finally Huyền Trân

2295-427: A month, with "plenty of goods", and a market was situated every five miles on the state highway. Inns were also established by the state during the period. During the reign of Trần Thánh Tông members of the Trần clan and imperial family were required by the Emperor to take full advantage of their land grants by hiring the poor to cultivate them. Đại Việt's cultivated land was annually ruined by river floods, so for

2448-504: A more stable agriculture, in 1244 Trần Thái Tông ordered his subordinates to construct a new system of levees along the Red River . Farmers who had to sacrifice their land for the diking were compensated with the value of the land. The Emperor also appointed a separate official to control the system. Towards the end of the Trần dynasty, Hồ Quý Ly held absolute power in the imperial court, and he began to carry out his ideas for reforming

2601-566: A new dynasty, the Hồ dynasty . Being Hồ Quý Ly's own grandson, Thiếu Đế was downgraded to Prince Bảo Ninh instead of being killed like his father. Hồ Quý Ly claimed descent from Duke Hu of Chen (Trần Hồ công, 陳胡公), whose Hồ clan originated in State of Chen (modern day Zhejiang , China ) around the 940s. After the Ming dynasty conquered the Hồ dynasty in 1407, Prince Trần Ngỗi was declared emperor and led

2754-749: A new revolt against the Mạc Emperors. A new revolt was led by Nguyễn Kim (father of Nguyễn Hoàng, the first of the Nguyễn lords who later ruled southern Vietnam ) and his subordinate and son-in-law Trịnh Kiểm (the first of the Trịnh lords who later ruled Đàng Ngoài ). They installed Lê Trang Tông as Emperor of the Revival Lê dynasty and built their base in Thanh Hóa and Nghệ An provinces to resist against Mạc Đăng Dung. Both sides tried to pull in allies, mainly

2907-601: 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

3060-423: 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

3213-421: 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

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3366-454: A wealthy landowner in the area. Trần Lý's grandson, Trần Cảnh , later established the Trần dynasty. From Trần Lý onwards, the Trần clan became related to the Lý clan by intermarriages with several members of the imperial Lý dynasty . During the troubled time of many regional rebellions under the reign of emperor Lý Cao Tông , the imperial crown prince, Lý Sảm sought refuge in the territory of

3519-401: A year later. Then, in 1592, Trịnh Tùng unleashed a massive invasion of the north and conquered Hanoi along with the rest of the northern provinces. Mạc Mậu Hợp was captured during the retreat and was cut to pieces over three days. The Mạc had lost control over most of Northern Vietnam, only retaining areas in and around Cao Bằng Province under the formal protection of the Ming army. In 1592,

3672-582: 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

3825-420: 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

3978-490: 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

4131-541: 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

4284-411: 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

4437-488: 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

4590-521: Is considered superior to Lý literature in both quality and quantity. Initially, most members of the Trần clan were fishermen without any depth of knowledge. For example, Trần Thủ Độ, the founder of the Trần dynasty, was described in Đại Việt sử ký toàn thư as a man of superficial learning. However, after their usurpation of power from the Lý dynasty, Trần emperors and other princes and marquises always attached special importance to culture, especially literature. Two important schools of literature during

4743-447: 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

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4896-415: 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

5049-493: 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

5202-453: 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

5355-527: The Battle of Đồ Bàn , when the Emperor himself, along with many high-ranking mandarins and generals of the Trần dynasty, were killed by the Cham forces. The successor of Duệ Tông, Trần Phế Đế , and the retired Emperor Nghệ Tông, were unable to drive back any invasion of Chế Bồng Nga in Đại Việt. As a result, Nghệ Tông even decided to hide money in Lạng Sơn , fearing that Chế Bồng Nga's troops might assault and destroy

5508-750: 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

5661-512: The Ming dynasty but also from King Phothisarat I of Lan Xang (modern-day Laos ). Mạc Đăng Dung, through submissive diplomacy and massive bribes, convinced the Ming not to attack in 1528. He then abdicated his position as Emperor in favor of his son, Mạc Đăng Doanh a year later. However, this was done purely to solidify his son's position, Mạc Đăng Dung continued to rule with the title of Senior Emperor (Viet: Thái thượng hoàng). The revolt of

5814-470: 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

5967-468: 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

6120-564: 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 the disease dates to around 1500 BC in Egyptian mummies . The disease historically occurred in outbreaks . It

6273-624: 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

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6426-459: 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 the 16th century to distinguish the disease from syphilis , which

6579-779: 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 ,

6732-402: The Emperor was still served by many efficient mandarins like Trần Nhật Duật, Đoàn Nhữ Hài , Phạm Ngũ Lão, Trương Hán Siêu , Mạc Đĩnh Chi , and Nguyễn Trung Ngạn . Anh Tông was very strict in suppressing gambling and corruption, but he also generously rewarded those who served him well. In 1306, the king of Champa , Chế Mân , offered Vietnam two Cham prefectures, Ô and Lý, in exchange for

6885-505: The Emperor when she had been pregnant with Trần Quốc Khang for three months. After the marriage, Thuận Thiên was entitled the new empress of the Trần dynasty, while Chiêu Thánh was downgraded to princess. Furious at losing his pregnant wife to his brother, Trần Liễu rose in revolt against the imperial family. Meanwhile, Thái Tông felt remorse about the situation and decided to become a monk at Yên Tử Mountain in Quảng Ninh in order to avoid

7038-485: The Empress Regnant seemed to have affection towards him, the leader of the Trần clan immediately decided to take this chance to carry out his plot to overthrow the Lý dynasty and establish a new dynasty ruled by his own clan. First Trần Thủ Độ moved the whole Trần clan to the imperial palace and arranged a secret marriage between Lý Chiêu Hoàng and Trần Cảnh there, without the appearance of any mandarin or member of

7191-626: The Kangxi Emperor demanded in 1667 that Trịnh Tạc return Cao Bằng Province to the Mạc. In 1673, the Qing had lost interest in mediating the conflict on behalf of the Mạc. In 1677, the Revolt of the Three Feudatories in southern China prompted the Qing to enlist the aid of the Lê, who accused the Mạc of joining the rebels. The Kangxi Emperor and his advisors agreed to arrest Mạc Kính Vũ as he fled into Guangxi , China, leading to

7344-566: The Lê title of Thông quốc công , reducing the Mạc realm to a duchy under the Lê dynasty. After the fall of the Southern Ming, the Qing dynasty became the mediator in the Lê-Mạc conflict while receiving tribute from both sides. The Kangxi Emperor attempted to negotiate peace between the two states. After the Lê attacked and gained control of Cao Bằng Province without permission from the Qing,

7497-435: The Lý imperial family. After that, he announced the fait accompli to the imperial court and made Lý Chiêu Hoàng cede the throne to her new husband on the grounds that she was incapable of holding office. Thus Trần Cảnh was chosen as her successor. As a result, the 216-year reign of the Lý dynasty was ended, and the new Trần dynasty was created on the first day of the twelfth lunar month ( Gregorian : December 31) 1225. After

7650-560: The Ming. The Ming official position was that the Mạc should rule over the northern half of Vietnam, while the Lê should rule over the southern half (in other words, below the Red River). The Nguyễn and the Trịnh refused to accept this division of the country and the war continued. In 1541, Mạc Đăng Dung died and was succeeded by his grandson Mạc Phúc Hải . Mạc Phúc Hải ruled only for six years before he died due to illness. During his rule, he

7803-457: The Mongol invasions, king Trần Nhân Tông led an attack into modern-day Laos in the winter of 1289–1290 against the advice of his advisors with the goal of preventing raids from the inhabitants of the highlands. Famines and starvations ravaged the country from 1290 to 1292. There were no records of what caused the crop failures, but possible factors included neglect of the water control system due to

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7956-531: The Mongol troops. The elephant-mounted troops were routed by sharpshooters targeting the elephants. In comparison with the previous Ly dynasty, the Tran had strengthened their armed forces and were able to deter the Mongol attacks. At the beginning of the war, the Đại Việt army suffered several defeats at the hands of an overwhelming force that had already conquered a vast area in Asia. Several high-ranking officials of

8109-452: The Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic smallpox. Historically, ordinary smallpox had an overall fatality rate of about 30%, and 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

8262-579: The Revival Lê in the south gathered strength and over the next three years all the provinces south of the Red River were captured by the Lê armies. In 1533 the figurehead Lê Emperor, Lê Trang Tông, was officially crowned at the recaptured Tây Đô castle . This marked the beginning of the Southern and Northern dynasties era . The Lê and Mạc would continue the lengthy civil war over the next 40 years. In 1540, Mạc Đăng Doanh died and Mạc Đăng Dung reclaimed

8415-470: The Tran authorities, so were weapons workshops, court attire workshops and utilities for bronze smelting. Education and literature were largely aided from improvements in the technology of printing and engraved wooden plates. The shipbuilding industry expanded where large 100-oar junks were produced. Thang Long then became the state's commercial center with numerous markets established. A 13th-century Mongolian ambassador mentioned that markets were held twice

8568-615: The Tran dynasty, the Daoist cleric Xu Zongdao originated from Fujian. He recorded the Mongol invasion and referred to the Mongols as "Northern bandits". Nguyễn Trung Ngạn , head of an envoy mission to the Yuan court in 1314, referred to the Yuan dynasty as Hồ (胡), meaning barbarians, in his poem Bắc sứ túc Khâu Ôn dịch (北使宿丘溫驛): 江山有限分南北， The land is divided into North and South 胡越同風各弟兄。 "Hồ" and Viet are brothers with same customs Later on, Wu Bozong 吳伯宗 (b. 1334-d. 1384)

8721-411: The Trần clan, headed by Trần Lý. During this time, the crown prince decided to marry Trấn Lý's daughter Trần Thị Dung in 1209. Afterward, it was the Trần clan who helped emperor Lý Cao Tông and crown prince Lý Sảm to restore their power and return to capital Thăng Long . As a result, the emperor appointed several members of the Trần clan to key positions in the imperial court, such as Tô Trung Từ , who

8874-462: The Trần dynasty were so fearful that Prince Trần Nhật Hiệu , the younger brother of Thái Tông, even suggested to the Emperor that they might escape from Đại Việt to the Song dynasty . Trần Thái Tông submitted to the Mongols after the loss of a prince and the capital. In 1258, the Trần commenced regular diplomatic relations and a tributary relationship with the Mongol court, treating them as equals to

9027-549: The Trần dynasty, Confucianist education began to spread across the country. The principal curricula during this time were the Four Books and Five Classics , and Northern history , which were at the beginning taught only at Buddhist pagodas and gradually brought to pupils in private classes organized by retired officials or Confucian scholars. Smallpox Smallpox was an infectious disease caused by variola virus (often called smallpox virus), which belongs to

9180-509: The Trần loyalists forces against the Chinese. His base was first centered in Ninh Bình Province . He defeated the Ming forces in 1408 but failed to retake Đông Quan (Hanoi). Due to internal purges, his offensive eventually failed and he had to retreat to Nghệ An . A new emperor, Trùng Quang Đế , was installed by the generals in 1409. The Later Trần held the southern provinces before being defeated by Ming forces in 1413. To restore

9333-488: The Trịnh. The Trịnh requested and received aid from the Nguyễn and the joint army (with Nguyễn Hoàng ) defeated the Mạc. In 1598, yet another official Ming commission declared the Mạc to be rulers over Cao Bằng province and so the Mạc rulers stayed in this protected area, occasionally launching raids into Trịnh controlled Vietnam. In 1627, the Lê army attacked Cao Bằng, the Mạc ruler Mạc Kính Khoan had to surrender and accept

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9486-833: 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,

9639-565: 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

9792-531: 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

9945-507: 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

10098-448: 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

10251-463: The capital from Thăng Long to Thanh Hóa in January 1397. On the full moon of the third lunar month, 1398, under pressure from Hồ Quý Ly, Thuận Tông, had to cede the throne to his three-year-old son Trần An , now Trần Thiếu Đế , and held the title Retired Emperor at the age of only 20. Only one year after his resignation, Thuận Tông was killed on the orders of Hồ Quý Ly. Hồ Quý Ly also authorised

10404-496: The capital of Đại Việt. The Trần army could not withstand this attack and the Trần imperial court had to escape from Thăng Long, creating an opportunity for Chế Bồng Nga to violently loot the capital before withdrawing. In the twelfth lunar month of 1376 the Emperor Trần Duệ Tông decided to personally command a military campaign against Champa. Eventually, the campaign was ended by a disastrous defeat of Đại Việt's army at

10557-424: 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, the prodromal illness still occurred but may have been less severe than in

10710-477: 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

10863-503: 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

11016-466: The collapse of the Lý Dynasty, Trần Thủ Độ was still afraid that the newly established Trần Dynasty might be overthrown by its political opponents. He therefore continued to eliminate members of the Lý imperial family: first the former emperor Lý Huệ Tông was coerced into suicide in the tenth lunar month of 1226, then other members of the Lý imperial family were massacred by the order of Trần Thủ Độ in

11169-484: The collection Quốc ngữ thi tập ( Collection of national language poems ) or Hồ Quý Ly who wrote Quốc ngữ thi nghĩa to explain Shi Jing in the Vietnamese language. The achievement of Vietnamese language literature during the Trần era was the essential basis for the development of this language and the subsequent literature of Vietnam. The Trần dynasty was considered a golden age for music and culture. Although it

11322-580: The country's economy, which had been heavily damaged during the turbulent time at the end of the Lý dynasty, Emperor Trần Thái Tông decided to reform the nation's system of taxation by introducing a new personal tax ( thuế thân ), which was levied on each person according to the area of cultivated land owned. For example, a farmer who owned one or two mẫu , equal to 3,600 to 7,200 square metres (39,000 to 78,000 sq ft), had to pay one quan per year, while another with up to four mẫus had to pay two quan . Besides personal taxes, farmers were obliged to pay

11475-621: 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

11628-415: The court ensued to the level of a civil war. From 1516 to 1520, the warlords of Nguyễn Hoàng Dụ and Trịnh Duy Sản , Nguyễn Kính and Trần Cao were fighting for power. Mạc Đăng Dung initially led the forces loyal to King Lê Chiêu Tông against the warlords, he eventually defeated the warlords and gained enough power to force Lê Chiêu Tông to abdicate in 1522 and install the puppet Emperor Lê Cung Hoàng to

11781-416: The deaths of several emperors, Mạc Đăng Dung increased his power and gained many supporters. However, he also gained the enmity of other rivals for power. After a series of political crises that made both Lê Uy Mục and his successor Lê Tương Dực assassinated, Mạc Đăng Dung continued to gain power and rank in the military. With the enthronement of the young emperor Lê Chiêu Tông in 1516, a power struggle in

11934-450: The demise of the Mạc dynasty. The Lê dynasty held a tributary relationship with the Ming dynasty in exchange for recognition and military protection. As part of their tributary relationship, the Ming provided external military support to the Lê state against the Mạc beginning in 1537. After the 1540 surrender of the Mạc to the Ming, the Ming court ceremonially revoked the Lê dynasty's status as an independent kingdom and reclassified it as

12087-472: The destruction of the Mongol navy, both the Đại Việt and Champa decided to accept the nominal supremacy of the Yuan dynasty and serve as tributary states in order to avoid further conflicts. Professor Liam Kelley noted that people from Song dynasty China, such as Zhao Zhong and Xu Zongdao , fled to the Tran dynasty after the Mongol invasion of the Song and helped the Tran fight against the Mongol invasion. Like

12240-403: 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

12393-400: 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 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,

12546-532: The early history of Vietnam. Trần literature had a special role in the history of Vietnamese literature for its introduction and development of the Vietnamese language (Quốc ngữ) written in chữ nôm . Before the Trần dynasty, Vietnamese was only used in oral history or proverbs. Under the rule of the Emperor Trần Nhân Tông, it was used for the first time as the second language in official scripts of

12699-470: The economy of Đại Việt. The most significant change during this time was the replacement of copper coins with paper money in 1396. It was the first time in the history of Vietnam that paper money was used in trading. The Emperor set up trading posts at the coastal town of Vân Đồn , where Chinese merchants from Guangdong and Fujian would move in to engage in commerce. Ethnic Chinese are recorded in Tran and Ly dynasty records of officials. Trần literature

12852-539: The eighth lunar month of 1232. Trần Thái Tông was enthroned when he was only eight years old. There were several rebellions in Đại Việt at that time, so Trần Thủ Độ had to devote all of his efforts to consolidating the rule of Thái Tông in the imperial court and over the country. Right after the coronation of the Emperor in 1226, Nguyễn Nộn and Đoàn Thượng rose in revolt in the mountainous region of Bắc Giang and Hải Dương . By both military and diplomatic measures, such as sending an army and by awarding two leaders of

13005-426: The embattled Southern Song dynasty without renouncing their ties to the Song. Kublai Khan was dissatisfied with the arrangement at the end of the first invasion and requested greater tributary payments, including taxes to the Mongols in both money and labor, "incense, gold, silver, cinnabar, agarwood, sandalwood, ivory, tortoiseshell, pearls, rhinoceros horn, silk floss, and porcelain cups", and direct oversight from

13158-421: The execution of over 370 persons who opposed his dominance in the imperial court, including several prominent mandarins and the Emperor's relatives together with their families, such as Trần Khát Chân, Trần Hãng , Phạm Khả Vĩnh and Lương Nguyên Bưu . The end of the Trần dynasty came on the 28th day of the second lunar month (Gregorian: March 23) 1400, when Hồ Quý Ly decided to overthrow Thiếu Đế and established

13311-409: The family feud. Finally Trần Thủ Độ forcefully yet successfully persuaded Thái Tông to return to the throne, and Trần Liễu had to surrender after judging that he could not stand with his fragile force. All soldiers who participated in this revolt were killed; Trần Thủ Độ even wanted to behead Trần Liễu, but was stopped by Thái Tông. In 1257, the first Mongol invasion of Đại Việt was launched with

13464-531: The fifth lunar month of 1285, Trần Quang Khải fought the decisive battle in the Chương Dương , where the Yuan navy was almost destroyed and the balance in the battlefield tilted definitively in favor of the Trần dynasty. Ten days later Sogetu was killed and the Trần Emperor Nhân Tông and Emperor Emeritus Thánh Tông returned to the capital, Thăng Long, on the sixth day of the sixth lunar month, 1285. In

13617-435: 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 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

13770-423: The first visible lesions – small reddish spots called enanthem – appeared on mucous membranes of the mouth, tongue, palate , and throat, and 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

13923-408: 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

14076-478: 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 the disease included fever and vomiting. This was followed by formation of ulcers in the mouth and

14229-466: The governor of Nghe An. This critical situation for the Trần dynasty began to change after the Toghan made the decision to retreat with the forward troops their victory in the fourth lunar month of 1285 at the Battle of Hàm Tử , where the troops commanded by Trần Nhật Duật , Prince Chiêu Thành, Trần Quốc Toản , and Nguyễn Khoái were finally able to defeat the fleet of general Sogetu. On the tenth day of

14382-429: 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

14535-498: 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 ,

14688-417: The imperial court, besides Chinese . It was Hàn Thuyên , an official of Nhân Tông, who began to compose his literary works in the Vietnamese language, with the earliest recorded poem written in chữ Nôm in 1282. He was considered the pioneer who introduced chữ nôm in literature. After Hàn Thuyên, chữ Nôm was progressively used by Trần scholars in composing Vietnamese literature, such as Chu Văn An with

14841-484: The imperial court. This prompted the Prime Minister Trần Nguyên Trác and his son Trần Nguyên Tiết to plot the assassination of Nhật Lễ, but their conspiracy was discovered by the Emperor and they were killed afterwards. In the tenth lunar month of 1370, the Emperor's father-in-law, Trần Phủ , after receiving advice from several mandarins and members of the imperial family, decided to raise an army for

14994-400: The imperial family of the Trần dynasty defected to the Yuan side, including Thánh Tông's own brother, Prince Chiêu Quốc ( Trần Ích Tắc ), and Trần Kiện, who was the son of Prince Tĩnh Quốc ( Trần Quốc Khang ). To ensure the safety of Thánh Tông and Nhân Tông during their retreat, Princess An Tư was offered as a present and diversion for Prince Toghan, while Marquis Bảo Nghĩa ( Trần Bình Trọng )

15147-489: The imperial palace in Thăng Long. In 1389 general Trần Khát Chân was appointed by Nghệ Tông to take charge of stopping Champa. In the first lunar month of 1390, Trần Khát Chân had a decisive victory over Champa which resulted in the death of Chế Bồng Nga and stabilised situation in the southern part of Đại Việt. During the reign of Trần Nghệ Tông, Hồ Quý Ly , an official who had two aunts entitled as consorts of Minh Tông,

15300-529: The introduction of vernacular Vietnamese into the court was established, alongside Literary Chinese . This laid the foundation for the further development and solidifying of the Vietnamese language and identity. The ancestor of the Trần clan, Trần Kinh, (陳京) migrated from the modern province of Fujian to Đại Việt during the early 12th century. He settled in Tức Mặc village (now Mỹ Lộc , Nam Định ) and lived by fishing. His grandson Trần Lý (陳李; 1151–1210) became

15453-464: 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 the 1500s. Europe adopted this practice from Asia in the first half of

15606-436: 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

15759-406: 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

15912-452: 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 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,

16065-400: The new Mạc leader was Mạc Kính Chỉ. He managed to assemble a large army which defeated the army of Trịnh Tùng but a year later, he and his army were wiped out by a new Trịnh army under Trịnh Tùng. Later, his brother Mạc Kính Cung withdrawn to Cao Bằng province and ruled for more than thirty years (1593–1625). Based out of Van Ninh ( Quảng Ninh Province ) the Mạc army staged many attacks against

16218-431: The northern border while the Yuan navy under general Sogetu advanced from the southern border through the territory of Champa . Initially, Trần Thánh Tông and Trần Nhân Tông had to order the army to retreat to avoid the pressure from the Yuan force when Prince Chiêu Minh Trần Quang Khải commanded his troops to stop Sogetu's fleet in the province of Nghệ An . Meanwhile, several high-ranking officials and members of

16371-404: 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

16524-429: 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

16677-416: 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)

16830-588: 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

16983-447: 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

17136-440: The proclamation Hịch tướng sĩ ( Call of Soldiers ), written by general Trần Quốc Tuấn, which was the most popular work of the hịch (appeal, call) form in Vietnamese literature. Besides members of the Trần clan, there were several mandarins and scholars who were well known for patriotic works such as Trương Hán Siêu , an eminent author of the phú form, or general Phạm Ngũ Lão with his famous poem Thuật hoài . As Buddhism

17289-526: The purpose of opening a southern front against the Song dynasty, whom they were fighting for more than two decades . The Mongols had already conquered parts of modern-day Sichuan and the Dali kingdom in modern-day Yunnan in order to besiege the Southern Song from the west. Trần Thái Tông opposed the encroachment of a foreign army across his territory and so dispatched soldiers on elephants to deter

17442-512: The purpose of overthrowing Nhật Lễ. After one month, his plan succeeded and Trần Phủ became the new emperor of Đại Việt, ruling as Trần Nghệ Tông, while Nhật Lễ was downgraded to Duke of Hôn Đức (Hôn Đức Công) and was killed afterwards by an order of Nghệ Tông. After the death of Hôn Đức Công, his mother fled to Champa and begged King Chế Bồng Nga to attack Đại Việt. Taking advantage of his neighbour's lack of political stability, Chế Bồng Nga commanded troops and directly assaulted Thăng Long ,

17595-416: 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 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

17748-416: The reign of the Trần dynasty were patriotic and Buddhist literature. To commemorate the victory of Đại Việt against the second Mongol invasion the grand chancellor Trần Quang Khải composed a poem, named Tụng giá hoàn kinh ( Return to the capital ), which was considered one of the finest examples of Vietnamese patriotic literature during the dynastic era. Patriotism in Trần literature was also represented by

17901-457: The relations between Đại Việt and Champa remained strained for a long time afterwards. After the death of the retired Emperor Trần Minh Tông in 1357, the Trần dynasty began to fall into chaos during the reign of Trần Dụ Tông . While being modest and diligent under the regency of Minh Tông, the reign of Emperor Dụ Tông saw extravagant spending on the building of several luxurious palaces and other indulgences. Dụ Tông introduced theatre, which

18054-686: The revolt the title of Prince ( Vương ), Trần Thủ Độ was able to put down these revolts in 1229. According to Đại Việt sử ký toàn thư , Thái Tông and his wife, the Empress Chiêu Thánh , did not have their first son for some time. This situation worried the grand chancellor Trần Thủ Độ because he had profited from similar circumstances with the Emperor Lý Huệ Tông in overthrowing the Lý dynasty. Therefore, in 1237 Trần Thủ Độ decided to force Prince Hoài Trần Liễu , Thái Tông's elder brother, to give up his wife, Princess Thuận Thiên, for

18207-454: 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

18360-491: 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

18513-405: 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 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,

18666-481: 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 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

18819-520: 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

18972-464: The third lunar month of 1287, the Yuan dynasty launched their third invasion of Đại Việt. This time, unlike the second invasion, commander-in-chief Prince Hưng Đạo (Trần Quốc Tuấn) assured the Emperor that Đại Việt's army could easily break the Yuan military campaign. After occupying and looting the capital, Toghan decided to retreat with the forward troops. This invasion was indeed ended one year later by

19125-557: The throne in 1400, at the age of five years old in favor of his maternal grandfather, Hồ Quý Ly . The Trần improved Chinese gunpowder , enabling them to expand southward to defeat and vassalize the Champa . They also started using paper money for the first time in Vietnam. The period was considered a golden age in Vietnamese language, arts, and culture. The first pieces of Chữ Nôm literature were written during this period, while

19278-461: The throne of the Lý dynasty to crown princess Lý Chiêu Hoàng in October of the lunar calendar, 1224. Ascending the throne at the age of only six, Lý Chiêu Hoàng ruled under the dominant influence of the commander of the imperial guard, Trần Thủ Độ. Even the Empress Regnant's servants were chosen by Trần Thủ Độ; one of them was his 7-year-old nephew Trần Cảnh . When Trần Cảnh informed Trần Thủ Độ that

19431-492: The throne. Lê Chiêu Tông fled the court with the support of the warlord Trịnh Tuy to Thanh Hóa where they fought against Mạc Đăng Dung until they were defeated and captured in 1526. In 1527 Mạc Đăng Dung removed Lê Cung Hoàng and proclaimed himself as Emperor of the new Mạc dynasty under the title Minh Đức. The usurpation was not well received by the Confucian officials in the government. Some were killed, others fled to join

19584-409: The throne. The Ming dynasty threatened Mạc Đăng Dung with an invasion of 110,000 men ready to invade Vietnam from Guangxi. Mac acceded to Chinese pressure and complied with bitter Ming demands, including crawling barefoot in front of the Chinese officials, giving up land to China, downgrading his status from the Emperor to Governor ( Đô thống sứ 都統使) and giving up official documents like tax registers to

19737-475: 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

19890-439: 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

20043-442: 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

20196-517: The war, the mobilization of men away from the rice fields, and floods or drought. There was a relatively long period of prosperity and peace during the reigns of Trần Anh Tông , Trần Minh Tông , and Trần Hiến Tông . Anh Tông was the first Trần emperor to reign without facing attacks from the Mongol Empire . Despite the deaths of the two most important generals of the early Trần dynasty, Trần Quang Khải in 1294 and Trần Quốc Tuấn in 1300,

20349-581: Was de facto the national religion of the Trần dynasty, there were many works of Trần literature that expressed the spirit of Buddhism and Zen , notably the works of the Emperor Trần Nhân Tông and other masters of Trúc Lâm School. `Besides the literature created by the upper classes, folk narratives of myths, legends, and ghost stories were also collected in Việt Điện U Linh Tập by Lý Tế Xuyên and Lĩnh Nam chích quái by Trần Thế Pháp . These two collections held great value not only for folk culture but also for

20502-410: Was a Vietnamese dynasty that ruled from 1225 to 1400. The dynasty was founded when emperor Trần Thái Tông ascended to the throne after his uncle Trần Thủ Độ orchestrated the overthrow of the Lý dynasty . The Trần dynasty defeated three Mongol invasions , most notably during the decisive Battle of Bạch Đằng River in 1288. The final emperor of the dynasty was Thiếu Đế , who was forced to abdicate

20655-410: Was able to return to Đại Việt, but Chế Chí , the successor of Chế Mân, no longer wished to abide by the peace treaty with Đại Việt. After that event, Anh Tông himself, along with the generals Trần Quốc Chân and Trần Khánh Dư, commanded three groups of Đại Việt military units to attack Champa in 1312. Chế Chí was defeated and captured in this invasion, and Anh Tông installed a hand-picked successor, but

20808-431: 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

20961-472: Was an uncle of Trần Thị Dung, and Trần Tự Khánh and Trần Thừa , who were all Trần Lý's sons. In 1211 the crown prince Lý Sảm was enthroned as Lý Huệ Tông after the death of Lý Cao Tông . By that time the Trần clan's position began to rise within the imperial court. After a period of political crisis, the Emperor Lý Huệ Tông , who had been mentally ill for a long time, ultimately decided to pass

21114-530: Was appointed to one of the highest positions in the imperial court. Despite his complicity in the death of the Emperor Duệ Tông, Hồ Quý Ly still had Nghệ Tông's confidence and came to hold more and more power at the imperial court. Facing the unstoppable rise of Hồ Quý Ly in the court, the Emperor Trần Phế Đế plotted with minister Trần Ngạc to reduce Hồ Quý Ly's power, but Hồ Quý Ly pre-empted this plot by

21267-462: Was born to a couple of hát tuồng performers. To celebrate the victory over the 1288 Mongol invasion, Trần Quang Khải and Trần Nhật Duật created the Múa bài bông ( dance of flowers ) for a major three-day festival in Thăng Long. This dance has been handed down to the present and is still performed at local festivals in the northern region. Although Buddhism was considered the national religion of

21420-410: Was captured and later killed in the Battle of Đà Mạc defending the two emperors. The mass defections were the result of the significant effect that recent Mongol conquest of the Southern Song had on contemporary observers, with a Mongol conquest of Vietnam appearing inevitable to many. At the southern border, Trần Quang Khải also had to retreat under the pressure of Sogetu's navy and the defection of

21573-510: Was considered at the time to be a shameful pleasure, into the imperial court. The Emperor died on the 25th day of the fifth lunar month, 1369, at the age of 28, after appointing his brother's son Dương Nhật Lễ despite the fact that his appointee was not from the Trần clan. Like his predecessor Dụ Tông, Nhật Lễ neglected his administrative duties and concentrated only on drinking, theatre, and wandering. He even wanted to change his family name back to Dương. Such activities disappointed everyone in

21726-408: Was defeated by the Trịnh army and lost more territories. He was succeeded by Mạc Phúc Nguyên (ruled from 1546 to 1561) who had to fight against his uncle Mạc Chính Trung to enthrone. In 1561, he died because of smallpox . Mạc Mậu Hợp succeeded the throne, and ruled from 1562 to 1592. He was the last significant Mạc ruler. In 1572 the capital was captured by the Trịnh army but then he recaptured it

21879-428: 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

22032-442: 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

22185-421: 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

22338-542: 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 is estimated to have killed up to 300 million people in the 20th century and around 500 million people in

22491-476: Was sent as Ming ambassador to Vietnam. Wu wrote in the Rongjinji (榮進集) that when he asked the Tran monarch about Annam's affairs, the Tran ruler said that the kingdom still adhered to Tang dynasty and Han dynasty customs. 欲問安南事， Asking about Annam situation? 安南風俗淳。 Annam customs are traditional 衣冠唐制度， Clothing are Tang's standard 禮樂漢君臣 Music and Rites are similar to Han's court After

22644-440: 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

22797-428: Was still seen as a shameful pleasure at that time, theatre rapidly developed towards the end of the Trần dynasty with the role of Lý Nguyên Cát (Li Yuan Ki), a captured Chinese soldier who was granted a pardon for his talent in theatre. Lý Nguyên Cát imported many features of Chinese theatre (also see 话剧) in the performing arts of Đại Việt such as stories, costumes, roles, and acrobatics. For that reason, Lý Nguyên Cát

22950-404: 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

23103-516: 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

23256-401: 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 a more extensive rash and higher fever. Variola minor is

23409-402: Was traditionally considered the founder of the art of hát tuồng in Vietnam. However this is nowadays a challenged hypothesis because hát tuồng and Beijing opera differed in the way of using painted faces, costumes, or theatrical conventions. The art of theatre was introduced to the imperial court by Trần Dụ Tông and eventually the emperor even decided to cede the throne to Dương Nhật Lễ, who

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