The Kiheitai ( 奇兵隊 , Irregular Militia ) was a volunteer militia raised by Takasugi Shinsaku of the Chōshū domain during the Bakumatsu period of Japan .
105-508: Formed in 1863 by Takasugi Shinsaku in Shimonoseki , Yamaguchi Prefecture , the Kiheitai militia consisted of 300 men, who came from all social classes, including farmers, merchants, samurai and others. Most were from Chōshū, but a few volunteers were from other domains. The Kiheitai was known for its discipline, and use of western-style weapons and military techniques. It was partly funded by
210-410: 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
315-440: A Western army, and convinced the leaders of the domain of the absolute necessity for a thorough military reform. Chōshū soon had no choice but to call on Takasugi again. Shinsaku was then forgiven and put in charge of peace negotiations. The Chōshū domain's administration called on Takasugi not only to carry out this reform as ‘Director of Military Affairs’, but he - only 25 years of age - was also entrusted with negotiating peace with
420-443: 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
525-415: 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
630-513: 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
735-451: 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
840-417: A hermitage Tōgyō-an (東行庵), named after Takasugi's nickname, built close to his gravesite, there Tani Baisho stayed and looked after his grave until her death in 1909. The grave itself was designated a National Historic Monument in 1934. Takasugi Shinsaku, a central figure of the early Meiji Restoration , is as well known for his military talents as he is for his skills as a politician. However, dying at
945-614: 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
1050-408: 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
1155-587: A potential treatment was effective in killing viral samples. The recommendation could only take effect if approved by the WHA . When the WHA discussed the proposal in 2005, it refrained from taking a formal vote on the proposal, stating that it would review individual research proposals one at a time. Addition of the GFP gene to the Vaccinia genome is routinely performed during research on
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#17328693167491260-423: 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
1365-421: 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
1470-666: A special Shotai unit under his direct command called the Kiheitai , which consisted of 300 soldiers (about half of whom were samurai). Later on, while hiding away from assassins, he encountered a shamisen -playing geisha named O-Uno (1843–1909) at a brothel Sakai-ya in Akamaseki, Shimonoseki and went into a relationship with her. After Chōshū fired upon Western warships in the Straits of Shimonoseki on 25 June 1863, British , French , Dutch and American naval forces bombarded Shimonoseki ,
1575-582: 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
1680-420: 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
1785-486: 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
1890-541: 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
1995-411: 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
2100-488: 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
2205-447: 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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#17328693167492310-550: 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
2415-415: 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
2520-493: 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
2625-453: 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
2730-474: The shōgun at Edo ). When his teacher was arrested during the Ansei Purge in 1859, Takasugi visited him in jail. Shōin was later executed on 21 November 1859. In December 1859 he returned home by the clan's command. In January 1860, Takasugi married Inoue Masa [ jp ] (1845–1922), the second daughter of Yamaguchi retainer and magistrate Inoue Heiemon who was also the friend of his father. Masa
2835-719: The Bakufu in autumn 1864 in retaliation for previous Chōshū attempts to seize control of Kyoto . At first, conservative forces, which favored conciliation with the Bakufu in order to secure the domain, were dominant in Chōshū politics, and Takasugi and some of his compatriots had to leave the domain to avoid renewed imprisonment. Takasugi, with only about a dozen followers, including future political leaders Yamagata Aritomo, Itō Hirobumi and Inoue Kaoru , gathered in Kokura in Kyūshū and prepared an attack on
2940-674: 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
3045-551: The Kyohoji incident on 16 August which involved a conflict between the Chōshū's forces Kiheitai and Senkitai (撰鋒隊) at the Kyohoji temple which left two people dead, Hikosuke Miyagi, who was an inspecting officer of the Kiheitai , was forced to commit seppuku at the temple on 27 August. Although Takasugi narrowly escaped the seppuku, he was held liable for the incident and was dismissed as
3150-636: The Second Chōshū expedition sent by the Tokugawa bakufu on 7 June 1866. Takasugi died of tuberculosis on 17 May 1867. The Kiheitai militia played an important role in the Boshin War , which led to the Meiji Restoration . The Kiheitai was disbanded in 1868, with total enlistment of 622 men since 1863. The success of the socially mixed unit and its Western armaments and tactics was an important influence on
3255-607: The Tōhoku region , and there he was associated with Sakuma Shōzan and Yokoi Shōnan . Takasugi, in spite of his young age, was an influential factor within Chōshū as one of the most extreme advocates of a policy of seclusion and expelling the foreigners from Japan. In spite of Japan's policy of national isolation in the Edo period , in 1862 Takasugi was ordered by the domain to go secretly to Shanghai in Great Qing Empire to investigate
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3360-422: 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
3465-470: 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
3570-468: 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
3675-462: 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
3780-409: 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
3885-624: 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
3990-468: The Chōshū domain, but gained the rest of its financial support through donations by wealthy merchants and farmers. Kiheitai followed a developing trend which had been spearheaded by the shogunate following the Convention of Kanagawa to form military units based on ability rather than hereditary social status. Shinsengumi , a Kyoto-based, pro-Tokugawa police force, was founded in the same year as Kiheitai, and
4095-752: 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 ,
4200-442: The Kiheitai and another Chōshū unit Senkitai (撰鋒隊) forces at the Kyohoji temple, leaving two people dead. The Kiheitai's inspecting officer Hikosuke Miyagi was forced to commit seppuku at the temple while Takasugi himself was held liable and was dismissed as the leader of the Kiheitai on 27 August, only about two months after its formation. The Kiheitai was taken over by Kawakami Yaichi and Taki Yataro as its second leaders. In October
4305-478: The Kiheitai was taken over again by Akane Taketo as the third leader with Yamagata Aritomo as the commander. In February 1865, a Second Kiheitai was formed in the Suō Province with Kosuke Shirai as its first leader with Shūzō Sera as the commander. As the military arm of the pro-reform faction within the Chōshū domain, the Kiheitai helped overthrow the pro- bakufu faction in the Chōshū civil war, repulsed
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4410-625: The Sonnô Jôi-movement to promote a more a conciliatory policy towards the West and thus, the ‘movement to expel the barbarians and revere the Emperor’ evolved into an anti- Bakufu movement with the overthrow of the Tokugawa bakufu as a necessary means to strengthen Japan against the foreigners. Weakened by the punitive attack by the Western powers, Chōshū was unable to withstand the expedition mounted by
4515-700: The Tokugawa Shogunate, which found obvious manifestation in his nickname Tōgyō ( 東行 ) , was fulfilled with the Meiji Restoration . Before leaving for Europe in 1869, Yamagata Aritomo presented his thatched hut named Murin-an (無鄰菴) which is also at Mt. Kiyomizu to Takasugi's former mistress and nun Baisho to dwell in and to look after his grave. Kido Takayoshi (formerly Katsura Kogorō) and his wife Matsuko would later take his young son Tōichi under their wings in 1871. In 1884, Takasugi's friends and comrades whom included Yamagata Aritomo, Yamada Akiyoshi , Itō Hirobumi, and Inoue Kaoru among others, raised funds to have
4620-507: The Tokugawa forces, the military power of the Bakufu was discredited, and traditionally rival domains decided to join forces with Chōshū in the subsequent battles which eventually led to the end of the Tokugawa bakufu and the start of the Meiji Restoration in 1868. Takasugi did not live to see this success as his tuberculosis got worse in October 1866, after which he was moved to a residence of
4725-793: 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,
4830-507: 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
4935-517: 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
5040-507: 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
5145-450: The bar manager Hayashi Sankuro. His mistress O-Uno and the Buddhist nun and poet Nomura Bōtō nursed him there. Around February 1867, his wife Masa and their three year-old son Tōichi [ jp ] (aka Takasugi Umenoshin) (1864–1913) arrived from Hagi to visit him. Due to the presence of his wife and not wishing to sully Takasugi's name, O-Uno left and became a Buddhist nun under
5250-564: The barbarians and revere the Emperor') movement, which attracted certain radical sections of Japan's warrior class and court nobility, and Takasugi's ideas found ready support in Chōshū and other parts of Japan. Takasugi was implicated in the 31 January 1863 attack on the British legation in Edo. Takasugi originated the revolutionary idea of auxiliary irregular militia ( shotai ). Under the feudal system, only
5355-448: 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
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#17328693167495460-477: 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
5565-503: 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
5670-429: The conservative forces in Chōshū. The subsequent Chōshū civil war began on 13 January 1865. Takasugi played a major role in this civil war and his former Kiheitai militia proved its superiority over old-fashioned samurai forces. With a series of quick strikes and the support of Katsura Kogorō, Takasugi achieved victory by March 1865. He became one of the main arbiters of the Chōshū domain's policy and continued to act as
5775-621: 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
5880-628: The development of the Imperial Japanese Army , and on the later system of universal military conscription in Japan. The forces defending Aizu-Wakamatsu during the Boshin War in 1868, and the forces of Saigō Takamori in the Satsuma rebellion in 1877 also used the term Kiheitai to describe themselves. Takasugi Shinsaku Takasugi Shinsaku ( 高杉 晋作 , 27 September 1839 – 17 May 1867)
5985-403: 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
6090-580: 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
6195-479: 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
6300-486: The domain's expert on Western military science, devoting his efforts to importing arms and raising troops. These reforms proved to be successful when Chōshū was victorious on four fronts against the Bakufu's Second Chōshū expedition on 7 June 1866, with the Kiheitai itself securing victory on two fronts. Takasugi's efforts had made a small-scale 'nation in arms' out of Chōshū, giving it a military strength out of proportion to its relatively small size. With its victory over
6405-417: The financial wealth of the middle-class merchants and farmers could increase the military strength of the domain, without weakening its finances. Since the leaders of Chōshū were unable - and unwilling - to change the social structure of the domain, limited use of peasants and commoners enabled them to form a new type of military without disturbing the traditional society. In June 1863, Takasugi himself founded
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#17328693167496510-484: The four Western powers. In view of the humiliation of Chōshū forces against the Western powers, Takasugi had come to the realization that direct confrontation with the foreigners was not an option. Instead, Japan had to learn military tactics, techniques and technologies from the West. Takasugi reorganized his Kiheitai militia into a rifle-unit with the latest modern rifles , and introduced training in Western strategy and tactics. Moreover, Takasugi used his influence with
6615-408: 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
6720-429: 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
6825-495: 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 ,
6930-494: The leader of the Kiheitai , only about two months after its formation. The Kiheitai was taken over by Kawakami Yaichi and Taki Yataro, followed by Akane Taketo and Yamagata Aritomo on October. In February 1864, Takasugi tried to dissuade Kijima Matabei from his plan to fight Satsuma and Aizu in Kyoto, but failed and then left the domain to hide in Kyoto himself. He was persuaded by Katsura Kogorō to return, but upon arrival he
7035-436: 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
7140-406: 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
7245-499: The main port of the Chōshū domain the following summer in what was later called the Bombardment of Shimonoseki . Takasugi was put in charge of the defense of Shimonoseki. An anti- Chōshū coup in Kyoto in the 18 August 1863 threatened to jeopardize Chōshū's leading role in national politics, and Chōshū was ousted by a coalition of the Satsuma and Aizu in the imperial court. Following
7350-408: 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
7455-549: The name of Tani Baisho, but was later summoned back by Masa to look after him. However in March 1867, Takasugi's illness worsened yet again, Masa and Tōichi were summoned back to Hagi, while Baisho and Nomura stayed with him until his death on 17 May 1867. Under his will, Takasugi was buried near the Kiheitai' s camp at the Mt. Kiyomizu in Yoshida. Only a year later, Takasugi's dream of overthrowing
7560-514: The name of Tomo ( 智 ) , Sachi ( 幸 ) and Mei ( 明 ) . He had smallpox at the age of ten, but fortunately he had recovered from it. Takasugi joined the Shōka Sonjuku , the famous private school of Yoshida Shōin . Takasugi devoted himself to the modernization of Chōshū's military, and became a favorite student of Yoshida. In 1858, he entered the Shōheikō (a military school under direct control of
7665-404: 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
7770-429: 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
7875-523: 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,
7980-573: 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
8085-493: 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
8190-491: 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)
8295-454: 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
8400-488: The samurai class was allowed to own weapons. Takasugi promoted the recruitment of commoners into new, socially-mixed paramilitary units. In these units, neither recruitment nor promotion depended (at least in theory), on social status. Farmers, merchants, carpenters and even sumo -wrestlers and Buddhist priests were enlisted, although samurai still formed the majority in most of the Shotai . Takasugi clearly saw that utilization of
8505-479: 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
8610-491: 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
8715-520: 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
8820-594: The state of affairs and the strength of the Western powers. Takasugi's visit coincided with the Taiping Rebellion , and he was shocked by the effects of European imperialism even on the Chinese Empire. Takasugi returned to Japan convinced that Japan must strengthen itself to avoid being colonized by the western powers, or to suffer a similar fate as the Qing Empire. This coincided with the growing Sonnō Jōi ('expel
8925-425: 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
9030-411: 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
9135-475: 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
9240-439: 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
9345-442: 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
9450-551: 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
9555-444: The young age of 28, Takasugi was not to become one of Japan's famous leaders in the subsequent Meiji era. In his hometown, the castle town Hagi, Yamaguchi in south-western Japan - he is still remembered as a mystical and energetic hero, who put all his efforts into opening the way to modernization, westernization and reforms, not only in military matters but in political and social matters as well. Smallpox Smallpox
9660-513: Was a samurai from the Chōshū Domain of Japan who contributed significantly to the Meiji Restoration . He used several aliases to hide his activities from the Tokugawa shogunate . Takasugi Shinsaku was born in the castle town Hagi , the capital of the Chōshū Domain (present-day Yamaguchi Prefecture ) as the first son of Takasugi Kochūta, a middle-ranked samurai of the domain and his mother Michi ( 道 ) . He would have three younger sisters by
9765-421: 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
9870-431: 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
9975-619: Was also composed of people from a broad variety of social classes. The Kiheitai militia saw action in the Bombardment of Shimonoseki in June 1863, during which the fleets of Great Britain , France , the Netherlands , and the United States fired upon the Chōshū port city of Shimonoseki , and subsequently landed troops. On 16 August 1863, the Kyohoji incident , which involved the conflict between
10080-466: 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
10185-428: 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
10290-442: 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
10395-404: 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
10500-421: 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
10605-557: Was put in Noyama-Goku Prison for the charge of leaving the domain. He was later released in July and ordered to confine himself at home. In September 1864, a fleet of warships of British, French, Dutch and American naval forces attacked Shimonoseki again and occupied the gun battery there. This was followed by the landing of French marines. Their fighting against Chōshū units demonstrated the inferiority of traditional Japanese troops against
10710-554: Was said to be the most beautiful lady in Suō and Nagato provinces. Their marriage was arranged by his parents, with hope that he would take his mind off of his teacher's death in 1859 and to settle down with his new bride. However, in April 1861, Takasugi would leave his home and undertake naval training on the clan's warship Heishinmaru, and travelled to Edo . Later in September he went to study at
10815-440: 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
10920-404: 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
11025-511: 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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