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132-629: Odonais was born in the Viceroyalty of Peru to a wealthy Criollo family. She was well educated, and met her husband when he came to South America on a scientific expedition. In 1749, her husband, Jean Godin des Odonais , left their home in Riobamba , Ecuador , Spanish South America to visit French Guiana . Because he was a French citizen, he was refused permission by the Spanish and Portuguese authorities to return for his family. After years of waiting for

264-502: A Spanish colonial city in the Viceroy of Peru . She was well-educated and spoke fluent Spanish, French, and Quechua , and understood the use of quipus , the Incan method of communicating information using colored strings and knots . Jean Godin des Odonais was a French cartographer and naturalist who had joined the world's first geodesy expedition to the equator . The team worked in

396-410: 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

528-466: A Spanish colonial administrator who constituted the first Audiencia in Spanish South America, served as the interim viceroy of Peru. Although established, the viceroyalty was not properly organized until the arrival of Viceroy Francisco Álvarez de Toledo , who made an extensive tour of inspection of the region. Francisco de Toledo, "one of the great administrators of human times," established

660-443: 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

792-415: 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

924-513: 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

1056-451: 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

1188-482: A governor. (See, Adelantado .) Provinces which were under military threat were grouped into captaincies general , such as the Captaincy General of Chile (established in 1541 and established as a Bourbon captaincy general in 1789), and which were joint military and political commands with a certain level of autonomy. (The viceroy was captain-general of the provinces which remained directly under his command). At

1320-614: 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

1452-587: 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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1584-423: 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

1716-672: A sizable military force, retired to Jauja , and later to Cusco . On July 26, 1822, San Martín and Simón Bolívar met in Guayaquil to define a strategy for the liberation of the rest of Peru. The meeting was secret, and exactly what occurred is not known. However, afterwards San Martín returned to Argentina while Bolívar prepared to launch an offensive against the remaining royalist forces in Peru and Upper Peru (modern-day Bolivia ). In September 1823 Bolívar arrived in Lima with Antonio José de Sucre to plan

1848-421: 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

1980-588: 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 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,

2112-582: 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

2244-420: 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

2376-486: 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

2508-541: 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

2640-411: 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

2772-488: Is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among human DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus . To replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses , the most important of which is a viral-associated DNA-dependent RNA polymerase . Both enveloped and unenveloped virions are infectious. The viral envelope

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2904-447: 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

3036-441: 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 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

3168-415: 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

3300-493: 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

3432-453: 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

3564-743: The Amazon to test whether the journey would be safe for them to take, and to make the necessary arrangements with the French authorities. Upon arriving in Cayenne, Godin found the Portuguese and Spanish colonial authorities would not let him — a Frenchman of no importance — return through their territory. Unwilling to return to France without his family, he became a reluctant resident of French Guiana, constantly writing pleas to Europe to allow for his return to Riobamba. Eventually, La Condamine wrote on Godin's behalf to

3696-501: The Andean mountains and Amazon Basin was arduous, made worse by the recent devastation by smallpox of the mission station at Canelos (in present-day Pastaza Province ), depriving the party of valuable support nine days into their journey. They found two Indian survivors who agreed to repair a forty-foot canoe, in which they continued down the Amazon. The river journey proved difficult, with

3828-527: The Captaincy General of Chile . Francisco Gil de Taboada reincorporated the region of Puno into the Viceroyalty of Peru. José de Armendáriz stimulated the production of silver and took steps against fraud, corruption and smuggling. Amat y Juniet established the first Regulation of Commerce and Organization of Customs rules, which led to the building of the customshouse in Callao. Teodoro de Croix collaborated in

3960-674: 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

4092-655: The Inquisition in the viceroyalty and promulgated laws that applied to Indians and Spanish alike, breaking the power of the encomenderos and reducing the old system of mita (the Incan system of mandatory labor tribute). He improved the defensibility of the viceroyalty with fortifications, bridges, and la Armada del Mar del Sur (the Southern Fleet) against pirates. He ended the indigenous Neo-Inca State in Vilcabamba , executing

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4224-573: The Jesuits were expelled from the colony. Viceroy José Fernando de Abascal y Sousa promoted educational reforms, reorganized the army, and stamped out local rebellions. During his administration, the Inquisition of Lima was temporarily abolished as a result of the reforms taken by the Cortes in Spain. When the wars of independence broke out in 1810, Peru was the center of Royalist reaction. Abascal reincorporated

4356-654: The Kingdom of Peru (Spanish: Reino del Perú ), was a Spanish imperial provincial administrative district, created in 1542, that originally contained modern-day Peru and most of the Spanish Empire in South America, governed from the capital of Lima . Along with the Viceroyalty of New Spain , Peru was one of two Spanish viceroyalties in the Americas from the sixteenth to the eighteenth centuries. The Spanish did not resist

4488-584: The Portuguese empire after the Treaty of Madrid in 1750. It became a state of the Brazilian Republic in 1889. Several viceroys had scientific, political and economic impact on the Viceroyalty. Manuel de Amat y Juniet organized an expedition to Tahiti . Viceroy Teodoro de Croix also decentralized the government through the creation of eight intendencias in the area of the Audiencia of Lima , and two in

4620-480: The Portuguese expansion of Brazil across the meridian established by the Treaty of Tordesillas . The treaty was rendered meaningless between 1580 and 1640 while Spain controlled Portugal . The creation during the 18th century of the Viceroyalties of New Granada and Río de la Plata (at the expense of Peru's territory) reduced the importance of Lima and shifted the lucrative Andean trade to Buenos Aires , while

4752-487: The Portuguese king , who due to changing political circumstances was eager to befriend the French. In 1765 he ordered a galiot , crewed by thirty oarsmen, to take Godin back to his wife. However, as Godin had written some incendiary letters against the Portuguese, he was suspicious of the offer of passage up the Amazon, and abandoned the ship at its first port. The captain of the galiot continued upriver without him, to fetch

4884-609: The Quito region from 1735 to 1744, during which time Jean and Isabel met. They married on 27 December 1741, when Isabel was fourteen years old. At first Jean decided to remain in Riobamba with his new wife, but in 1743 he offered to accompany La Condamine on his next expedition. He stayed behind to see Isabel through her pregnancy. But, when he heard of his father's death in March 1749, Godin decided to return to France with his family. He planned to travel alone to Cayenne , French Guiana via

5016-454: The Siege of Callao (1826), but after death of King Ferdinand VII of Spain in 1836, the government of Spain renounced its territorial and sovereignty claims over all of continental America. In 1867, Spain signed a peace treaty with Peru and in 1879 it signed a treaty recognizing Peru's independence . The town of Lima , founded by Pizarro on January 18, 1535, as the "Ciudad de los Reyes" (City of

5148-578: The Tribunal del Consulado , a court and administrative body for commercial affairs in the viceroyalty. Diego Fernández de Córdoba, Marquis of Guadalcázar , reformed the fiscal system and stopped the interfamily rivalry that was bloodying the domain. Other viceroys, such as Fernando Torres , Fernández de Cabrera, and Fernández Córdoba expanded the royal navy and fortified the ports to resist foreign incursions, such as those led by privateer Thomas Cavendish . Fernández de Cabrera also suppressed an insurrection of

5280-509: The Uru and Mapuche Indians. Viceroys had to protect the Pacific coast from French contraband and English and Dutch pirates and privateers. They expanded the naval forces, fortified the ports of Valdivia , Valparaíso , Arica and Callao and constructed city walls in Lima (1686) and Trujillo (1685–1687). Nevertheless, the famous Welsh privateer Henry Morgan took Chagres and captured and sacked

5412-629: The Viceroyalty of New Granada was created from the northern territories, the Audiencias of Bogotá , Quito and Panamá . This viceroyalty initially lasted only until 1724, but was reestablished permanently in 1740. With the creation of the Viceroyalty of the Río de la Plata from southern areas that are now Argentina , Bolivia , Paraguay and Uruguay in 1776, the Charcas and Buenos Aires audiencias were similarly lost. The 256-year-old Treaty of Tordesillas

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5544-422: 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

5676-460: 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 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

5808-470: 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

5940-468: 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

6072-624: 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

6204-752: 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 ,

6336-473: The Frenchman's wife as ordered. For most of their 20-year separation, Isabel received no news of her husband, while enduring the death of her children from smallpox . She moved to the smaller community of Guzman . When she heard rumors that a ship was waiting to take her down the Amazon, she sent her servant Joachim and a handful of Indians to investigate. The party returned two years after having discovered

6468-620: The Inca Túpac Amaru , and promoted economic development from the commercial monopoly and mineral extraction, mainly from silver mines in Potosí . The Amazon Basin and some large adjoining regions had been considered Spanish territory since the Treaty of Tordesillas and explorations such as that by Francisco de Orellana , but Portugal fell under Spanish control between 1580 and 1640. During this time, Portuguese territories in Brazil were controlled by

6600-504: The Indian population's tribute labor, even the most remote settlements, and therefore, many encomenderos developed reciprocal, if still hierarchical, relationships with the curacas . By the end of the 16th century the quasi-private encomienda had been replaced by the repartimiento system (known in Peru by the Quechua term, mita ), which was controlled by local crown officials. Politically

6732-543: The Kings/ Magi ), became the seat of the new viceroyalty. As the seat of a viceroy, who had oversight over all of Spanish South America except for Portuguese-dominated Brazil, Lima grew into a powerful city. During the 16th, 17th and most of the 18th centuries, all of the colonial wealth of South America created by the silver mines passed through Lima on its way to the Isthmus of Panama and from there to Seville , Spain. The rest of

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6864-544: The Spanish crown, which did object to the spread of Portuguese settlement into parts of the Amazon Basin that the treaty had awarded to Spain. Still, Luis Jerónimo de Cabrera, 4th Count of Chinchón sent out a third expedition to explore the Amazon River , under Cristóbal de Acuña ; this was part of the return leg of the expedition of Pedro Teixeira . Some Pacific islands and archipelagoes were visited by Spanish ships in

6996-403: The Spanish organized the existing governorates into the Viceroyalty of New Castile, which shortly afterward would be called the Viceroyalty of Peru , in order to properly control and govern Spanish South America. In 1544, Holy Roman Emperor Charles V (King Charles I of Spain) named Blasco Núñez Vela Peru's first viceroy. From September 2, 1564, to November 26, 1569, Lope García de Castro ,

7128-538: The Spanish under Field Marshal José de Canterac . The two armies met on the plains of Junín on August 6, 1824, and the Peruvians were victorious in a battle fought entirely without firearms. The Spanish troops subsequently evacuated Lima for a second time. As a result of a decree of the Congress of Gran Colombia , Bolívar turned over command of the rebel troops to Sucre on October 7, 1824. At this point, royalist control

7260-793: 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,

7392-557: 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

7524-458: The Viceroyalty of Peru was established, gold and silver from the Andes enriched the conquerors, and the viceroyalty became the principal source of Spanish wealth and power in South America. The first coins minted for Peru (and indeed for South America) appeared between 1568 and 1570. Viceroy Manuel de Oms y de Santa Pau sent back an enormous sum of money (1,600,000 pesos) to the king to cover some of

7656-517: 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

7788-507: 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

7920-504: The authorities to relent, Isabel Odonais insisted that she must go to him. Odonais became famous for being the only survivor of a 42-person, 3000-mile expedition through the Amazon Basin to rejoin her husband. They were reunited in 1770 and later returned to France together. Isabel Godin des Odonais née Gramesón was the daughter of Don Pedro Gramesón y Bruno, an administrator in Riobamba,

8052-425: The basin and adjoining Mato Grosso in the 17th and 18th centuries. These groups had the advantage of remote geography and river access from the mouth of the Amazon, which was in Portuguese territory. Meanwhile, the Spanish were barred by their laws from enslaving indigenous people, leaving them without a commercial interest deep in the interior of the basin. A famous attack upon a Spanish mission in 1628 resulted in

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8184-448: 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

8316-514: The canoe unmanageable. The Indians from Canelos deserted them, and one of the party drowned trying recover the hat of one of the Frenchmen. With the canoe weighed down by supplies, the party set up camp and sent Joachim and one of the Frenchmen ahead in the canoe, so they could return with extra transport. Waiting for Joachim to return, the others began to suffer from infected insect bites. Infection killed Isabel's nephew Joaquin, then Rosa and Elvia,

8448-466: The census figures amounted to only 1,100,000 Indians. While the attrition was not an organized attempt at genocide , the results were similar, largely resulting from smallpox and other Eurasian diseases to which the natives had no immunity. Inca cities were given Spanish Christian names and rebuilt as Spanish towns, each centered around a plaza with a church or cathedral facing an official residence. A few Inca cities like Cuzco retained native masonry for

8580-477: 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

8712-514: The city of Panama in the early part of 1670. Also Peruvian forces repelled the attacks by Edward David (1684 and 1686), Charles Wager and Thomas Colb (1708). The Peace of Utrecht allowed the British to send ships and merchandise to the fair at Portobello . In this period, revolts were common. Around 1656, Pedro Bohórquez crowned himself Inca (emperor) of the Calchaquí Indians, inciting

8844-541: The city of Pisco , with the land army under the command of José de San Martín and the navy under the command of Thomas Cochrane . After Cochrane's navy defeated the Spanish navy on the Peruvian coasts, the expedition secured the surrender of Callao. After fruitless negotiations with the viceroy, the expedition occupied the Peruvian capital of Lima on July 21, 1821. The independence of Peru was proclaimed on July 28, 1821. Viceroy José de la Serna e Hinojosa , still in command of

8976-503: 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

9108-564: The costs of the War of the Spanish Succession . This was possible in part because of the discovery of the mines in Caraboya . Silver from mines at Potosí, Bolivia, circulated around the world. Peruvian and other New World silver was so plentiful that it caused inflation in Spain and a collapse in its price. Even today, Peru and Bolivia produce much of the world's silver. While most of the silver from

9240-621: 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

9372-518: The creation of the Junta Superior de Comercio and the Tribunal de Minería (1786). An earthquake demolished Lima and Callao , in 1746. Viceroy Amat y Juniet constructed various public works in Lima, including the first bull ring. Manuel de Guirior also improved the medical care at ten hospitals in Lima and established a foundling home. War between Spain and Britain again broke out (the War of Jenkins' Ear , 1739–1748). Amat y Juniet constructed

9504-403: 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

9636-402: The enslavement of 60,000 indigenous people. In fact, as time passed, they were used as a self-funding occupation force by the Portuguese authorities in what was effectively a low-level war of territorial conquest. In 1617, viceroy Francisco de Borja y Aragón divided the government of Río de la Plata in two, Buenos Aires and Paraguay, both dependencies of the Viceroyalty of Peru. He established

9768-611: The events leading up to their arrival in France, died on 28 November 1780. Jean Godin died in their home on the Rue Hotel-Dieu in Saint-Amand-Montrond , Cher , on 1 March 1792. Isabel died there on 27 September the same year. A species of New World monkey , Isabel's saki ( Pithecia isabela ) is named in honor of her. Viceroyalty of Peru The Viceroyalty of Peru (Spanish: Virreinato del Perú ), officially known as

9900-517: The fall of the mining and textile production accelerated the progressive decay of the Viceroyalty of Peru. Eventually, the viceroyalty would dissolve, as with much of the Spanish Empire, when challenged by national independence movements at the beginning of the nineteenth century. These movements led to the formation of the modern-day country of Peru , as well as Chile , Colombia , Panama , Ecuador , Bolivia , Paraguay , Uruguay , and Argentina ,

10032-621: The finances of the viceroyalty was the maintenance of the Valdivian Fort System built in response to the Dutch expedition to Valdivia in 1643. Luis Jerónimo Fernández de Cabrera prohibited direct trade between Peru and New Spain (Mexico) and the persecution of Portuguese Jews, the principal traders in Lima . A census taken by the last Quipucamayoc indicated that there were 12 million inhabitants of Inca Peru; 45 years later, under viceroy Toledo,

10164-530: The fortress of Real Felipe in Callao in 1774. Nevertheless, throughout this period, rebellions by Native Peruvians were not entirely suppressed. In the eighteenth century alone, there were fourteen large uprisings, the most important of which were that of Juan Santos Atahualpa in 1742, and the Sierra Uprising of Túpac Amaru II in 1780. The Comunero Revolt broke out in Paraguay from 1721 to 1732). In 1767,

10296-504: The foundations of their walls. Other Inca sites, like Huanuco Viejo , were abandoned for cities at lower altitudes more hospitable to the Spanish. Smallpox Smallpox 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

10428-408: 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

10560-429: 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

10692-495: 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 ,

10824-529: The independence of Peru and South America. During this battle, the losing Spanish army sustained 2,000 dead and wounded and lost 3,000 prisoners, with the remainder of the army entirely dispersed. During the battle, Viceroy Serna was wounded and taken prisoner, where he signed the final capitulation whereby the Spaniards agreed to leave Peru. Serna was released soon afterwards and sailed for Europe. Spain made futile attempts to retain its former territories, such as at

10956-462: The indigenous population to revolt. From 1665 until 1668, the rich mineowners José and Gaspar Salcedo revolted against the colonial government. The clergy were opposed to the nomination of prelates from Spain. Viceroy Diego Ladrón de Guevara had to take measures against an uprising of slaves at the hacienda of Huachipa de Lima. There were terrible earthquakes (1655, 1687 ) and epidemics, too. During Baltasar de la Cueva Enríquez 's administration,

11088-514: The laws of the Indies were compiled. Diego de Benavides y de la Cueva issued the Ordenanza de Obrajes (Ordenance of Manufactures) in 1664 and Pedro Álvarez de Toledo y Leiva introduced the papel sellado (literally, sealed paper). In 1683 Melchor de Navarra y Rocafull reestablished the Lima mint, which had been closed since 1572. Viceroy Diego Ladrón de Guevara increased the production of silver in

11220-436: 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

11352-463: The local level there were hundreds of districts, in both Indian and Spanish areas, which were headed by either a corregidor (also known as an alcalde mayor ) or a cabildo (town council), both of which had judicial and administrative powers. In the late 18th century the Bourbon dynasty began phasing out the corregidores and introduced intendants , whose broad fiscal powers cut into the authority of

11484-406: 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

11616-408: 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

11748-453: The mines of Potosí , and stimulated production in other mines at San Nicolás , Cajatambo and Huancavelica . He limited the manufacture of aguardiente from sugar cane to authorized factories, which he taxed heavily. The Churches of Los Desamparados (1672), La Buena Muerte and the convent of Mínimos de San Francisco de Paula were finished and opened. The Hospital of Espiritu Santo in Lima and San Bartolomé hospital were built. In 1717,

11880-607: The offensive. In February 1824 the royalists briefly regained control of Lima. Olañeta's Rebellion started by surprise and the entire royalist army of Upper Peru (today's Bolivia) revolted, led by the royalist commander Pedro Antonio Olañeta against José de la Serna , the liberal viceroy of Peru . This broke the royal army and started a civil war in Upper Peru. Having regrouped in Trujillo , Bolívar in June led his rebel forces South to confront

12012-404: 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

12144-429: 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

12276-464: 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 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

12408-523: 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,

12540-573: 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

12672-493: 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

12804-491: 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)

12936-471: The provinces of Córdoba , Potosí , La Paz , Charcas , Rancagua and Quito into the Viceroyalty of Peru. The Royal Army of Peru during 14 years defeated the patriots armies of Argentinians and Chileans, turning Peru into the last royal bastion in South America. A large fire in Guayaquil destroyed approximately half of the city in 1812. Lord Cochrane unsuccessfully attacked Guayaquil and Callao , but on 4 February he captured Valdivia , called at

13068-558: The remaining Frenchmen and Isabel's brothers. Heloise wandered off in the middle of the night, never to be seen again. With the others dead, Isabel was left wandering alone in the jungle. When the servant Joachim arrived back at the camp, he found only the bodies of the deceased travelers. Unable to identify Isabel's body, he sent word of her death to Don Pedro — news which later reached Jean Godin. Isabel wandered alone and starving for nine days. Half-crazed, she met four Indians who offered her help in reaching Cayenne. With their help, she

13200-454: 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

13332-479: 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

13464-491: 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

13596-565: The sixteenth century, but they made no effort to trade with or colonize them. These included New Guinea (by Ýñigo Ortiz de Retez in 1545), the Solomon Islands (in 1568), and the Marquesas Islands (in 1595) by Álvaro de Mendaña de Neira . The first Jesuit reduction to Christianize the indigenous population was founded in 1609, but some areas occupied by Brazilians as bandeirantes gradually extended their activities through much of

13728-427: The smallpox. Variola major is the severe and most common form, with 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)

13860-520: 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

13992-425: 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

14124-656: The territories that at one point or another had constituted the Viceroyalty of Peru. After the Spanish conquest of Peru , Charles V granted the conquistadors with adelantados , gave them the right to become governors and justices of the region they conquered. Prior to the establishment of the Viceroyalty of Peru, several major governorates formed from these grants, including the Governorate of New Castile (1529), Governorate of New Toledo (1534), Governorate of New Andalusia (1534), and Province of Tierra Firme (1539). In 1542,

14256-648: The time The Key of the South Seas and the Gibraltar of the Pacific , due to its huge fortifications . However, the viceroyalty managed to defend Chiloé Island until 1826. On September 8, 1820, the Expedición Libertadora of Peru, organized mainly by the Chilean government with the objective of executing previous plans laid out by Argentine libertador José de San Martín , landed on the beach at Paracas Bay near

14388-411: 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

14520-475: 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

14652-462: The viceroyalty dependent upon Lima in administrative matters, in a pattern that persists until today in Peru. By the start of the 18th century, Lima had become a distinguished and aristocratic colonial capital, seat of the 250-year-old Royal and Pontifical University of San Marcos and the chief Spanish stronghold in the Americas. At ground level during the first century, Spanish encomenderos depended on local chieftains ( curacas ) to gain access to

14784-512: The viceroyalty ended up in Europe some circulated within South America. Indeed, the Real Situado was an annual payment of silver from the viceroyalty to finance the permanent Spanish army in Chile that which fought a prolonged conflict known as Arauco War . The Spanish in turn traded part of this silver with Mapuches giving origin to a tradition of Mapuche silverwork . Another issue that burdened

14916-448: The viceroyalty of Peru largely depended on the export of silver . The huge amounts of silver exported from the viceroyalty of Peru and Mexico deeply affected Europe, where some scholars believe it caused the so-called price revolution . Silver mining was carried out using contract and free wage labourers, as well as the mita system of unfree labour, a system inherited from pre-Hispanic times. Silver production peaked in 1610. Once

15048-453: The viceroyalty was further divided into audiencias , which were primarily superior tribunals, but which also had administrative and legislative functions. Each of these was responsible to the Viceroy of Peru in administrative matters (though not in judicial ones). Audiencias further incorporated the older, smaller divisions known as "governorships" ( gobernaciones , roughly provinces ) headed by

15180-482: The viceroys, governors and cabildos . ( See Bourbon Reforms . ) With dates of creation: Later Audiencias *Later part of the Viceroyalty of New Granada †Later part of the Viceroyalty of the Río de la Plata 1. Chile (1789) Listed under year of creation: 1783 1. Lima , 2. Puno 1784 3. Trujillo , 4. Tarma , 5. Huancavelica , 6. Cuzco , 7. Arequipa , (10. Chiloé , abolished in 1789) 1786 8. Santiago , 9. Concepción The economy of

15312-439: 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

15444-442: 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

15576-434: The waiting ship, four years after its initial departure. Isabel's father, Don Pedro, went ahead to the ship to make arrangements and to wait for Isabel. On 1 October 1769 a 42-person party set out for the ship: Isabel, her servant Joachim, Isabel's two brothers Antoine and Eugenio Gramesón, Isabel's ten-year-old nephew Joaquin, three servants: Rosa, Elvia, and Heloise, thirty-one Indians, and three Frenchman. The route across

15708-551: 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

15840-486: Was able to reach the waiting ship. The story of her incredible journey soon spread, and she was treated to an increasingly grand reception as she made her way downriver. On 22 July 1770 Isabel and Jean were reunited in the town of Oyapock after more than 20 years of separation. They remained in Cayenne for a few years. On 21 April 1773, Isabel, her husband and her father decided to leave Guiana and finally make their way to France. Don Pedro, having been severely disturbed by

15972-606: 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 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

16104-431: 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

16236-428: 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

16368-442: 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

16500-421: 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

16632-485: Was reduced to Cuzco in the south-central highlands. The viceroy launched a counter-offensive over Ayacucho , and on 9 December 1824. The Battle of Ayacucho (also known as the Battle of La Quinua), took place between royalist Spanish and nationalist ( republican ) troops at Pampa de La Quinua, a few kilometers away from Ayacucho, near the town of Quinua . This battle, led by Bolívar's lieutenant Antonio José de Sucre , sealed

16764-456: 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, 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

16896-440: 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

17028-547: Was superseded by the 1750 Treaty of Madrid which granted Portugal control of the lands it had occupied in South America in the intervening centuries. This Portuguese occupation led to the Guaraní War of 1756. Amazonas is named after the Amazon River , and was formerly part of the Spanish Viceroyalty of Peru, a region called Spanish Guyana . It was settled by the Portuguese in the early 18th century and incorporated into

17160-404: 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

17292-511: 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

17424-420: 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 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

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