document_title: Yellow fever

question_text: who got rid of yellow fever in cuba

question_tokens: who got rid of yellow fever in cuba

text: Yellow fever

text: Signs and symptoms[edit]

text: Yellow fever begins after an incubation period of three to six days.[12] Most cases only cause a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting.[13] In these cases, the infection lasts only three to four days.

text: In 15% of cases, however, people enter a second, toxic phase of the disease with recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain.[14] Bleeding in the mouth, the eyes, and the gastrointestinal tract cause vomit containing blood, hence the Spanish name for yellow fever, vómito negro ("black vomit").[15] There may also be kidney failure, hiccups, and delirium.[16][17]

text: The toxic phase is fatal in about 20 to 50% of cases, making the overall fatality rate for the disease about 3.0 to 7.5%.[18][19] However, the fatality rate of those with the toxic phase of the disease may exceed 50%.[20]

text: Surviving the infection provides lifelong immunity,[21] and normally no permanent organ damage results.[22]

text: Cause[edit]

text:
Yellow fever virus

Virus classification

Group:
Group IV ((+)ssRNA)

Order:
Unassigned

Family:
Flaviviridae

Genus:
Flavivirus

Species:
Yellow fever virus

text: Yellow fever is caused by the yellow fever virus, a 40– to 50-nm-wide enveloped RNA virus, the type species and namesake of the family Flaviviridae.[7] It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes, by Walter Reed around 1900.[23] The positive-sense, single-stranded RNA is around 11,000 nucleotides long and has a single open reading frame encoding a polyprotein. Host proteases cut this polyprotein into three structural (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding genes in the genome.[24] Minimal yellow fever virus (YFV) 3’UTR region is required for stalling of the host 5'-3' exonuclease XRN1. The UTR contains PKS3 pseudoknot structure which serves as a molecular signal to stall the exonuclease and is the only viral requirement for subgenomic flavivirus RNA (sfRNA) production. The sfRNAs are a result of incomplete degradation of the viral genome by the exonuclease and are important for viral pathogenicity.[25] Yellow fever belongs to the group of hemorrhagic fevers.

text: The viruses infect, amongst others, monocytes, macrophages, and dendritic cells. They attach to the cell surface via specific receptors and are taken up by an endosomal vesicle. Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope. The capsid enters the cytosol, decays, and releases the genome. Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing a rearrangement of the 90 homodimers to 60 homotrimers.[24]

text: After entering the host cell, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form and is therefore denoted as prM (precursor M) and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, which cleaves prM to M. This releases E from the complex which can now take its place in the mature, infectious virion.[24]

text: Transmission[edit]

text: Yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti, but other mostly Aedes mosquitoes such as the tiger mosquito (Aedes albopictus) can also serve as a vector for this virus. Like other arboviruses which are transmitted by mosquitoes, the yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or other primate. Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there, they reach the haemocoel (the blood system of mosquitoes) and from there the salivary glands. When the mosquito next sucks blood, it injects its saliva into the wound, and the virus reaches the bloodstream of the bitten person. Transovarial and transstadial transmission of the yellow fever virus within A. aegypti, that is, the transmission from a female mosquito to her eggs and then larvae, are indicated. This infection of vectors without a previous blood meal seems to play a role in single, sudden breakouts of the disease.[26]

text: Three epidemiologically different infectious cycles occur,[10] in which the virus is transmitted from mosquitoes to humans or other primates.[27] In the "urban cycle", only the yellow fever mosquito A. aegypti is involved. It is well adapted to urban areas and can also transmit other diseases, including Zika fever, dengue fever, and chikungunya. The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa. Except in an outbreak in 1999 in Bolivia, this urban cycle no longer exists in South America.

text: Besides the urban cycle, both in Africa and South America, a sylvatic cycle (forest or jungle cycle) is present, where Aedes africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as vectors. In the jungle, the mosquitoes infect mainly non-human primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently the only way humans can become infected, which explains the low incidence of yellow fever cases on the continent. People who become infected in the jungle can carry the virus to urban areas, where A. aegypti acts as a vector. Because of this sylvatic cycle, the yellow fever cannot be eradicated.[10]

text: In Africa, a third infectious cycle known as "savannah cycle" or intermediate cycle, occurs between the jungle and urban cycles. Different mosquitoes of the genus Aedes are involved. In recent years, this has been the most common form of transmission of yellow fever in Africa.[28]

text: Concern exists about yellow fever spreading to southeast Asia, where its vector A. aegypti already occurs.[29]

text: Pathogenesis[edit]

text: After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in particular. From there, they reach the liver and infect hepatocytes (probably indirectly via Kupffer cells), which leads to eosinophilic degradation of these cells and to the release of cytokines. Apoptotic masses known as Councilman bodies appear in the cytoplasm of hepatocytes.[30][31]

text: Fatality may occur when cytokine storm, shock, and multiple organ failure follow.[18]

text: Diagnosis[edit]

text: Yellow fever is most frequently a clinical diagnosis, made on the basis of symptoms and the diseased person's whereabouts prior to becoming ill. Mild courses of the disease can only be confirmed virologically. Since mild courses of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea and vomiting six to 10 days after leaving the affected area) is treated seriously.

text: If yellow fever is suspected, the virus cannot be confirmed until six to 10 days after the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction where the genome of the virus is amplified.[4] Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take one to four weeks.

text: Serologically, an enzyme linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG-titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a fourfold increase in IgG-titer is considered sufficient indication for yellow fever. Since these tests can cross-react with other flaviviruses, like dengue virus, these indirect methods cannot conclusively prove yellow fever infection.

text: Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death.

text: In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses like malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as cause.

text: Prevention[edit]

text: Personal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever is endemic. Institutional measures for prevention of yellow fever include vaccination programmes and measures of controlling mosquitoes. Programmes for distribution of mosquito nets for use in homes are providing reductions in cases of both malaria and yellow fever. Use of EPA-registered insect repellent is recommended when outdoors. Exposure for even a short time is enough for a potential mosquito bite. Long-sleeved clothing, long pants, and socks are useful for prevention. The awareness of peak mosquito exposure is from dusk to dawn. The application of larvicides to water-storage containers can help eliminate potential mosquito breeding sites. Adult mosquitos can be killed through insecticide spray usage, which decreases the transmission of yellow fever.[32]

text:
Use insect repellent when outdoors such as those containing DEET, picaridin, IR3535, or oil of lemon eucalyptus on exposed skin.
Wear proper clothing to reduce mosquito bites. When weather permits, wear long sleeves, long pants and socks when outdoors. Mosquitoes may bite through thin clothing, so spraying clothes with repellent containing permethrin or another EPA-registered repellent will give extra protection. Clothing treated with permethrin is commercially available. Mosquito repellents containing permethrin are not approved for application directly to skin.
The peak biting times for many mosquito species are dusk to dawn. However, A. aegypti, one of the mosquitoes that transmits yellow fever virus, feeds during the daytime. Staying in accommodations with screened or air-conditioned rooms, particularly during peak biting times, also reduces risk of mosquito bites.

text: Vaccination[edit]

text: Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people,[33] and had been reported to last for at least 10 years. WHO now states that a single dose of vaccination is sufficient to confer lifelong immunity against yellow fever disease."[34] The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler.[33] The World Health Organization (WHO) recommends routine vaccinations for people living in affected areas between the 9th and 12th month after birth.[4]

text: Up to one in four people experience fever, aches, and local soreness and redness at the site of injection.[35] In rare cases (less than one in 200,000 to 300,000),[33] the vaccination can cause yellow fever vaccine–associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5%[33] of cases.[4][18]

text: The Yellow Fever Initiative, launched by WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa.[36] No outbreaks were reported during 2015. The campaign was supported by the GAVI Alliance, and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.[37]

text: In March 2017, WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile.[38] In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil.[39]

text: Compulsory vaccination[edit]

text: Some countries in Asia are theoretically in danger of yellow fever epidemics (mosquitoes with the capability to transmit yellow fever and susceptible monkeys are present), although the disease does not yet occur there. To prevent introduction of the virus, some countries demand previous vaccination of foreign visitors if they have passed through yellow fever areas. Vaccination has to be proved by production of a vaccination certificate which is valid 10 days after the vaccination and lasts for 10 years. Although the WHO on 17 May 2013 advised that subsequent booster vaccinations are unnecessary, an older (than 10 years) certificate may not be acceptable at all border posts in all affected countries. A list of the countries that require yellow fever vaccination is published by the WHO.[40] If the vaccination cannot be conducted for some reasons, dispensation may be possible. In this case, an exemption certificate issued by a WHO-approved vaccination center is required. Although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, in many of these countries, less than 50% of their population is vaccinated.[4]

text: Vector control[edit]

text: Control of the yellow fever mosquito A. aegypti is of major importance, especially because the same mosquito can also transmit dengue fever and chikungunya disease. A. aegypti breeds preferentially in water, for example in installations by inhabitants of areas with precarious drinking water supply, or in domestic waste, especially tires, cans, and plastic bottles. These conditions are common in urban areas in developing countries.

text: Two main strategies are employed to reduce mosquito populations. One approach is to kill the developing larvae. Measures are taken to reduce the water accumulations in which the larva develops. Larvicides are used, as well as larvae-eating fish and copepods, which reduce the number of larvae. For many years, copepods of the genus Mesocyclops have been used in Vietnam for preventing dengue fever. It eradicated the mosquito vector in several areas. Similar efforts may be effective against yellow fever. Pyriproxyfen is recommended as a chemical larvicide, mainly because it is safe for humans and effective even in small doses.[4]

text: The second strategy is to reduce populations of the adult yellow fever mosquito. Lethal ovitraps can reduce Aedes populations, but with a decreased amount of pesticide because it targets the mosquitoes directly. Curtains and lids of water tanks can be sprayed with insecticides, but application inside houses is not recommended by the WHO. Insecticide-treated mosquito nets are effective, just as they are against the Anopheles mosquito that carries malaria.[4]

text: Treatment[edit]

text: As for other flavivirus infections, no cure is known for yellow fever. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Different methods for acute treatment of the disease have been shown not to be very successful; passive immunisation after emergence of symptoms is probably without effect. Ribavirin and other antiviral drugs, as well as treatment with interferons, do not have a positive effect in patients.[18] A symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen in the United States). Acetylsalicylic acid (aspirin) should not be given because of its anticoagulant effect, which can be devastating in the case of internal bleeding that can occur with yellow fever.

text: Epidemiology[edit]

text: Yellow fever is common in tropical and subtropical areas of South America and Africa. Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of disease and 30,000 deaths a year occur; the number of officially reported cases is far lower.

text: Africa[edit]

text: An estimated 90% of the infections occur on the African continent.[4] In 2008, the largest number of recorded cases was in Togo. In 2016, a large outbreak originated in Angola and spread to neighboring countries before being contained by a massive vaccination campaign. In March and April, 11 cases were reported in China, the first appearance of the disease in Asia in recorded history.[41][42]

text: Phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to the vector A. aegypti. Five genotypes (Angola, Central/East Africa, East Africa, West Africa I, and West Africa II) occur only in Africa. West Africa genotype I is found in Nigeria and the surrounding areas.[43] This appears to be especially virulent or infectious, as this type is often associated with major outbreaks. The three genotypes in East and Central Africa occur in areas where outbreaks are rare. Two recent outbreaks in Kenya (1992–1993) and Sudan (2003 and 2005) involved the East African genotype, which had remained unknown until these outbreaks occurred.[44]

text: South America[edit]

text: In South America, two genotypes have been identified (South American genotypes I and II).[10] Based on phylogenetic analysis these two genotypes appear to have originated in West Africa[45] and were first introduced into Brazil.[46] The date of introduction into South America appears to be 1822 (95% confidence interval 1701 to 1911).[46] The historical record shows an outbreak of yellow fever occurred in Recife, Brazil, between 1685 and 1690. The disease seems to have disappeared, with the next outbreak occurring in 1849. It was likely introduced with the importation of slaves through the slave trade from Africa. Genotype I has been divided into five subclades, A through E.[47]

text: In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvan or jungle epizootic.[48] It began as an outbreak in brown howler monkeys,[49] which serve as a sentinel species for yellow fever, that then spread to men working in the jungle. No cases had been transmitted between humans by the Aedes aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. In April 2017, the sylvan outbreak continued moving toward the Brazilian coast where most people were unvaccinated.[50] By the end of May the outbreak appeared to be declining after more than 3,000 suspected cases, 758 confirmed and 264 deaths confirmed to be yellow fever.[51] The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March.[52] The CDC issued a Level 2 alert (practice enhanced precautions.)[53]

text: A Bayesian analysis of genotypes I and II has shown that genotype I accounts for virtually all the current infections in Brazil, Colombia, Venezuela and Trinidad and Tobago while genotype II accounted for all cases in Peru.[54] Genotype I originated in the Northern Brazilian region around 1908 (95% HPD: 1870–1936). Genotype II originated in Peru in 1920 (95% HPD: 1867–1958). The estimated rate of mutation for both genotypes was ~5 × 10−4 substitutions/site/year, similar to that of other RNA viruses.

text: Asia[edit]

text: Though the main vector (A. aegypti) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, yellow fever has never occurred in these parts of the globe until the introduction of 11 cases by jet travel from an outbreak in Africa in 2016. Proposed explanations include the idea that the strains of the mosquito in the east are less able to transmit the yellow fever virus, that immunity is present in the populations because of other diseases caused by related viruses (for example, dengue), and that the disease was never introduced because the shipping trade was insufficient, but none is considered satisfactory.[55][56] Another proposal is the absence of a slave trade to Asia on the scale of that to the Americas.[57] The trans-Atlantic slave trade was probably the means of introduction into the Western Hemisphere from Africa.[58]

text: History[edit]

text: The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from nonhuman primates to humans.[59][60] The virus is thought to have originated in East or Central Africa and spread from there to West Africa. As it was endemic in Africa, the natives had developed some immunity to it. When an outbreak of yellow fever would occur in an African village where colonists resided, most Europeans died, while the native population usually suffered nonlethal symptoms resembling influenza.[61] This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity.[62] The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the importation of slaves from Africa, part of the Columbian Exchange following European exploration and colonization.

text: The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados.[63] An outbreak was recorded by Spanish colonists in 1648 in the Yucatán Peninsula, where the indigenous Mayan people called the illness xekik ("blood vomit"). In 1685, Brazil suffered its first epidemic, in Recife. The first mention of the disease by the name "yellow fever" occurred in 1744.[64] McNeill argues that the environmental and ecological disruption caused by the introduction of sugar plantations created the conditions for mosquito and viral reproduction, and subsequent outbreaks of yellow fever.[65] Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs.

text: Although yellow fever is most prevalent in tropical-like climates, the northern United States were not exempted from the fever. The first outbreak in English-speaking North America occurred in New York City in 1668, and a serious one afflicted Philadelphia in 1793.[66] English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669, as well as those occurring later in the 18th and 19th centuries.

text: The southern city of New Orleans was plagued with major epidemics during the 19th century, most notably in 1833 and 1853. At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries, including particularly serious ones in Cartagena in 1741, Cuba in 1762 and 1900, Santo Domingo in 1803, and Memphis in 1878.[67] Considerable debate existed over whether the number of deaths caused by disease in the Haitian Revolution of the 1780s was exaggerated.[68]

text: Major outbreaks have also occurred in southern Europe. Gibraltar lost many to outbreaks in 1804, 1814, and 1828.[69] Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans.[70]

text: In Colonial times and during the Napoleonic Wars, the West Indies were known as a particularly dangerous posting for soldiers due to the presence of yellow fever. The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada, mostly because of yellow fever and other tropical disease such as malaria.[71] Both English and French forces posted there were seriously affected by the "yellow jack". Wanting to regain control of the lucrative sugar trade in Saint-Domingue (Hispaniola), and with an eye on regaining France's New World empire, Napoleon sent an army under the command of his brother-in-law to Saint-Domingue to seize control after a slave revolt. The historian J. R. McNeill asserts that yellow fever accounted for about 35,000 to 45,000 casualties of these forces during the fighting.[72] Only one-third of the French troops survived for withdrawal and return to France. Napoleon gave up on the island, and in 1804, Haiti proclaimed its independence as the second republic in the Western Hemisphere.

text: The yellow fever epidemic of 1793 in Philadelphia, which was then the capital of the United States, resulted in the deaths of several thousand people, more than 9% of the population. The national government fled the city, including President George Washington.[73] Additional yellow fever epidemics struck Philadelphia, Baltimore, and New York City in the 18th and 19th centuries, and traveled along steamboat routes from New Orleans. They caused some 100,000–150,000 deaths in total.[74]

text: In 1853, Cloutierville, Louisiana, had a late-summer outbreak of yellow fever that quickly killed 68 of the 91 inhabitants. A local doctor concluded that some unspecified infectious agent had arrived in a package from New Orleans.[75][76] In 1858, St. Matthew's German Evangelical Lutheran Church in Charleston, South Carolina, suffered 308 yellow fever deaths, reducing the congregation by half.[77] A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855.[78] The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of Norfolk and Portsmouth. In 1873, Shreveport, Louisiana, lost almost a quarter of its population to yellow fever. In 1878, about 20,000 people died in a widespread epidemic in the Mississippi River Valley.[79] That year, Memphis had an unusually large amount of rain, which led to an increase in the mosquito population. The result was a huge epidemic of yellow fever.[80] The steamship John D. Porter took people fleeing Memphis northward in hopes of escaping the disease, but passengers were not allowed to disembark due to concerns of spreading yellow fever. The ship roamed the Mississippi River for the next two months before unloading her passengers.[81] The last major U.S. outbreak was in 1905 in New Orleans.[10][82]

text: Ezekiel Stone Wiggins, known as the Ottawa Prophet, proposed that the cause of a yellow fever epidemic in Jacksonville, Florida, in 1888, was astronomical.

text: The planets were in the same line as the sun and earth and this produced, besides Cyclones, Earthquakes, etc., a denser atmosphere holding more carbon and creating microbes. Mars had an uncommonly dense atmosphere, but its inhabitants were probably protected from the fever by their newly discovered canals, which were perhaps made to absorb carbon and prevent the disease.[83]

text: In 1848, Josiah C. Nott suggested that yellow fever was spread by insects such as moths or mosquitoes, basing his ideas on the pattern of transmission of the disease.[84] Carlos Finlay, a Cuban doctor and scientist, proposed in 1881 that yellow fever might be transmitted by mosquitoes rather than direct human contact.[85][86] Since the losses from yellow fever in the Spanish–American War in the 1890s were extremely high, Army doctors began research experiments with a team led by Walter Reed, composed of doctors James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlay's ″mosquito hypothesis″. Yellow fever was the first virus shown to be transmitted by mosquitoes. The physician William Gorgas applied these insights and eradicated yellow fever from Havana. He also campaigned against yellow fever during the construction of the Panama Canal, after a previous effort on the part of the French failed (in part due to mortality from the high incidence of yellow fever and malaria, which killed many workers).[10]

text: Although Dr. Reed has received much of the credit in United States history books for "beating" yellow fever, he had fully credited Dr. Finlay with the discovery of the yellow fever vector, and how it might be controlled. Reed often cited Finlay's papers in his own articles, and also gave him credit for the discovery in his personal correspondence.[87] The acceptance of Finlay's work was one of the most important and far-reaching effects of the Walter Reed Commission of 1900.[88] Applying methods first suggested by Finlay, the United States government and Army eradicated yellow fever in Cuba and later in Panama, allowing completion of the Panama Canal. While Reed built on the research of Carlos Finlay, historian François Delaporte notes that yellow fever research was a contentious issue. Scientists, including Finlay and Reed, became successful by building on the work of less prominent scientists, without always giving them the credit they were due.[89] Reed's research was essential in the fight against yellow fever. He should also receive full credit for his use of the first type of medical consent form during his experiments in Cuba, an attempt to ensure that participants knew they were taking a risk by being part of testing.[90]

text: Like Cuba and Panama, Brazil also led a highly successful sanitation campaign against yellow fever. Beginning in 1903, the campaign led by Oswaldo Goncalves Cruz, then director general of public health, would come not only to eradicate the disease, but to reshape the physical landscape of Brazilian cities, like Rio de Janeiro, as well. During rainy seasons Rio de Janeiro regularly experienced floods, as water from the bay surrounding the city overflowed into Rio's narrow streets. This coupled with the poor drainage systems found throughout Rio, created swampy conditions in the city's neighborhoods. Pools of stagnant water stood year long in city streets and proved to be a fertile ground for disease carrying mosquitoes. Thus, under Cruz's direction public health units known as "mosquito inspectors" fiercely worked to combat yellow fever throughout Rio by spraying, exterminating rats, and destroying unsanitary housing. Ultimately, the city's sanitation and renovation campaigns reshaped Rio de Janeiro's neighborhoods as its poor residents were pushed from city centers to Rio's suburbs or to towns found in the outskirts of the city. In later years, Rio's most impoverished inhabitants would come to reside in favelas.[91]

text: During 1920–23, the Rockefeller Foundation’s International Health Board undertook an expensive and successful yellow fever eradication campaign in Mexico.[92] The IHB gained the respect of Mexico’s federal government because of the success. The eradication of yellow fever strengthened the relationship between the US and Mexico, which had not been very good in the past. The eradication of yellow fever was also a major step toward better global health.[93]

text: In 1927, scientists isolated the yellow fever virus in West Africa.[94] Following this, two vaccines were developed in the 1930s. The vaccine 17D was developed by the South African microbiologist Max Theiler at the Rockefeller Institute in New York City. This vaccine was widely used by the U.S. Army during World War II.[63] Following the work of Ernest Goodpasture, Theiler used chicken eggs to culture the virus and won a Nobel Prize in 1951 for this achievement. A French team developed the French neurotropic vaccine (FNV), which was extracted from mouse brain tissue. Since this vaccine was associated with a higher incidence of encephalitis, FNV was not recommended after 1961. Vaccine 17D is still in use, and more than 400 million doses have been distributed. Little research has been done to develop new vaccines. Some researchers worry that the 60-year-old technology for vaccine production may be too slow to stop a major new yellow-fever epidemic. Newer vaccines, based on vero cells, are in development and should replace 17D at some point.[4]

text: Using vector control and strict vaccination programs, the urban cycle of yellow fever was nearly eradicated from South America. Since 1943, only a single urban outbreak in Santa Cruz de la Sierra, Bolivia, has occurred. Since the 1980s, though, the number of yellow fever cases has been increasing again, and A. aegypti has returned to the urban centers of South America. This is partly due to limitations on available insecticides, as well as habitat dislocations caused by climate change. It is also because the vector control program was abandoned. Although no new urban cycle has yet been established, scientists believe this could happen again at any point. An outbreak in Paraguay in 2008 was thought to be urban in nature, but this ultimately proved not to be the case.[4]

text: In Africa, virus eradication programs have mostly relied upon vaccination. These programs have largely been unsuccessful because they were unable to break the sylvatic cycle involving wild primates. With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the future spread of the virus more likely.[4]

text: Research[edit]

text: In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective early treatment of many pathological features of the disease.[95] Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in the liver and spleen, prevented hepatocellular steatosis, and normalised levels of alanine aminotransferase, a liver damage marker. The mechanism of action of ribavirin in reducing liver pathology in yellow fever virus infection may be similar to its activity in treatment of hepatitis C, a related virus.[95] Because ribavirin had failed to improve survival in a virulent rhesus model of yellow fever infection, it had been previously discounted as a possible therapy.[96] Infection was reduced in mosquitoes with the wMel strain of Wolbachia.[97]

text: Yellow fever has been researched by several countries as a potential biological weapon.[98]


document_title: The Big Short (film)

question_text: who played jamie shipley in the big short

root

text: The Big Short (film)

text: Plot[edit]

text: The film consists of three separate but concurrent stories, loosely connected by their actions in the years leading up to the 2007 housing market crash.

tag: p

text: Scion Capital storyline

text: In 2005, eccentric hedge fund manager Michael Burry (Christian Bale) discovers that the United States housing market is extremely unstable, being based on high-risk subprime loans. Anticipating that the market will collapse during Q2 2007, as interest rates would rise from adjustable-rate mortgages, he envisions an opportunity to profit. His plan is to create a credit default swap market, allowing him to bet against market-based mortgage-backed securities. He proposes his idea to several major investment and commercial banks who readily accept. Burry's huge long-term bet, exceeding $1 billion, entails paying substantial monthly premiums to the banks. This requirement sparks his clients' vocal unhappiness, believing he is "wasting" capital, and many demand that he reverse and sell, but Burry refuses. He later discovers that the banks collude with a major bond-rating company to maintain ratings on worthless bonds, allowing them to sell off their losing positions before the true values became known. Under pressure, Burry restricts withdrawals from his fund, angering his investors. Eventually the housing market collapses and his fund's value increases by 489% with an overall profit of over $2.69 billion.

text: Front Point Partners storyline

text: Deutsche Bank salesman Jared Vennett (Ryan Gosling) is one of the first to understand Burry's analysis, learning about his actions from one of the bankers who sold Burry an early credit default swap. Vennett uses his quant to verify that Burry's predictions are likely true and decides to put his own stake in the market, earning a fee on selling the swaps to firms who'll be profitable when the underlying mortgage bonds fail. A misplaced phone call alerts Front Point hedge fund manager Mark Baum (Steve Carell) to his plans, and he is convinced to buy credit default swaps from Vennett due to his own personal distaste with the banks. Vennett explains that the market collapse is being further perpetuated by the packaging of subprime loans into collateralized debt obligations (CDOs) large enough to be considered AAA ratings. Baum sends staff to investigate the Miami housing market and they discover that mortgage brokers are making money by selling risky mortgages to the Wall Street banks, which created the bubble. In early 2007, these loans begin to default, but the prices of the CDOs somehow rise. Meanwhile, ratings agencies refuse to downgrade the ratings of these failing bonds. When Baum questions an acquaintance at Standard & Poor's, he discovers conflicts of interest and dishonesty amongst the credit rating agencies. When Baum's employees question Vennett's motives, he maintains his position and invites Baum and his team to the American Securitization Forum in Las Vegas. Baum interviews CDO manager Wing Chau, who creates CDOs on behalf of an investment bank, claiming to represent the interests of investors. Chau describes how synthetic CDOs make a chain of increasingly large bets on the faulty loans, involving up to 20 times as much money as the loans themselves. Baum horrifyingly realizes that the fraud will completely collapse the global economy and decides to purchase as many swaps as possible, profiting from the situation at the banks' expense. Waiting until the last minute to sell their position, Baum's fund makes a profit of $1 billion, but he laments that the banks won't accept blame for the crisis.

text: Brownfield Fund storyline

text: Young investors Charlie Geller (John Magaro) and Jamie Shipley (Finn Wittrock) accidentally discover a prospectus by Vennett, convincing them to become involved in the swaps, as it fits their strategy of buying cheap insurance with big potential payouts. Since they are below the capital threshold for an ISDA Master Agreement required to enter into trades like Burry's and Baum's, they enlist the aid of retired securities trader Ben Rickert (Brad Pitt). When the bond values and CDOs rise despite defaults, Geller suspects the banks of committing fraud. The three also visit the American Securitization Forum, where they learn that the U.S. Securities and Exchange Commission has no regulations to monitor mortgage-backed security activity. They manage to successfully make an even more profitable payout deal than other hedge funds by shorting the higher-rated mortgage securities. These securities were considered highly stable and the banks were willing to sell swaps on them extremely cheaply. Geller and Shipley are initially ecstatic, but Rickert is disgusted, pointing out an impending economic collapse and the human effect that's going to come from it, in particular, the fact that when unemployment goes up 1%, 40,000 more people will die. Furthermore, they realize that the banks have colluded with the ratings agency to maintain the value of their CDO's in order to sell their worthless positions and then short them before the inevitable crash. Horrified, they try to tip off the press and their families about the upcoming disaster and the rampant fraud but nobody believes them. As the housing market begins to collapse, Ben, while on vacation in England, is able to sell their swaps, and points out that Europe is starting to feel the effects of the collapse. Ultimately, they make a profit of $80 million, but their faith in the system is broken.

text: Epilogue

text: Jared Vennett makes $47 million off the selling of swaps. Mark Baum becomes more gracious from the financial fallout, and his staff continue to operate their fund. Charlie Geller and Jamie Shipley go their separate ways after failing to sue the ratings agencies, with Charlie moving to Charlotte to start a family, and Jamie still running the fund. Ben Rickert returns to his peaceful retirement. Michael Burry closes his fund after public backlash and multiple IRS audits, now only investing in water commodities. It is noted that as of 2015, banks are selling CDOs again under a new label: a "bespoke tranche opportunity".

text: Cast[edit]

text:
Christian Bale as Michael Burry, M.D.,[8] the operator of Scion Capital and the first person to discover the massive bubble in the American housing market. He invests over $1.3 billion in credit default swaps based on this assumption. Burry is quirky and socially inept, and much prefers working with numbers than people.

Aiden Flowers as young Michael Burry

Ryan Gosling as Jared Vennett (based on Greg Lippmann),[8] a low-level salesman at Deutsche Bank who stumbles upon Burry's interpretation of the housing market, and persuades Baum to buy credit default swaps from his bank, collecting commissions and fees by doing so. Vennett is egotistical, highly vain and serves as the narrator of the film.
Steve Carell as Mark Baum (based on Steve Eisman),[8] the hot-headed head of Front Point Partners, a hedge fund which also invests millions of dollars into credit default swaps based on the advice of Jared Vennett. Baum is disgusted by the actions of his Wall Street compatriots, and is struggling to cope with his brother's suicide.
Brad Pitt as Ben Rickert (based on Ben Hockett),[8] a paranoid and germaphobic retired former trader who, like Baum, despises the financial world but goes back in as a favor to Jamie and Charlie.
Hamish Linklater as Porter Collins, an employee of Baum's and the most objectively normal.
Rafe Spall as Danny Moses, an employee of Baum's and a rampant optimist.
Jeremy Strong as Vincent "Vinny" Daniel, an employee of Baum's and the most rash and impulsive.
John Magaro as Charlie Geller (based on Charlie Ledley),[9] co-owner of the Brownfield Fund who asks Ben to help them get a seat at the 'big-boy' table.
Finn Wittrock as Jamie Shipley (based on Jamie Mai),[9] co-owner of the Brownfield Fund who asks Ben to help them get a seat at the 'big-boy' table.
Marisa Tomei as Cynthia Baum (based on Valerie Feigen),[9] Mark's loving and understanding wife.
Tracy Letts as Lawrence Fields, an investor of Scion Capital and Burry's mentor.
Adepero Oduye as Kathy Tao, a Morgan Stanley employee who supervises Front Point and Baum.
Byron Mann as Wing Chau, a CDO manager that Vennett introduces to Mark Baum.
Karen Gillan as Evie,[10] the ex-girlfriend of Jamie's brother who leaves the SEC to find a job at an investment bank.
Melissa Leo as Georgia Hale, an employee of credit ratings agency Standard & Poor's, who admits the industry is corrupted.
Max Greenfield as Mortgage Broker #1,[11] a morally bankrupt mortgage broker who specialises in conning strippers into bad loans.
Billy Magnussen as Mortgage Broker #2,[12] a morally bankrupt mortgage broker who specialises in conning immigrants into bad loans.
Rudy Eisenzopf as Lewis Ranieri, a no-name banker who created the first mortgage-backed security.
Margot Robbie as herself, explaining Mortgage-backed securities and Subprime loans[5]
Anthony Bourdain as himself, explaining Collateralized Debt Obligations (CDOs)[5]
Richard Thaler as himself, explaining Synthetic CDOs[5][13]
Selena Gomez as herself, also explaining Synthetic CDOs alongside Thaler[5]

tag: ul

text: Production[edit]

text: Development[edit]

text: In 2013, Paramount acquired the rights to the 2010 non-fiction book The Big Short: Inside the Doomsday Machine by Michael Lewis, to develop it into a film, which Brad Pitt's Plan B Entertainment would produce.[14] On March 24, 2014, Adam McKay was hired to write and direct a film about the housing and economic bubble.[4] Screenwriter Charles Randolph, who co-wrote the film with McKay, said one of the first challenges was finding the right tone for the film. He told Creative Screenwriting, "In general it was trying to find the right tone that was slightly funnier than your average Miloš Forman comedy, which is all grounded character-based but not so satirical where you got Wag the Dog. Somewhere between there was what I was shooting for. Once I got the tone down, then I went through the plot. The market's movements provided you with an underlying plot. You make your short deal, then the bank is trying to squeeze you out, and then it all breaks loose. So that was pretty easy, and it provided character arcs against that."[15] Two years after Randolph wrote his draft, McKay, as director, rewrote Randolph's screenplay. It was McKay's idea to include the celebrity cameos in the film to explain the financial concepts.[15]

text: Casting[edit]

text: On January 13, 2015, Variety reported that Brad Pitt, Christian Bale, and Ryan Gosling were set to star in the film, with Pitt producing the film along with Dede Gardner and Jeremy Kleiner. Plan B Entertainment would finance, with Paramount handling the distribution rights.[16] Before this, Pitt had already starred in the adaptation of the author's Moneyball, for which he was nominated for an Oscar.[4][16] On January 14, it was announced that Steve Carell would also star.[8] On April 21, 2015, more cast was revealed by Deadline, including Melissa Leo, Marisa Tomei, Tracy Letts, Hamish Linklater, John Magaro, Byron Mann, Rafe Spall, Jeremy Strong, and Finn Wittrock.[17] Charles Randolph wrote the initial draft.[17] Max Greenfield joined the ensemble cast of the film on April 23, 2015.[11] Karen Gillan tweeted about her involvement in the film on May 8, 2015.[10]

text: Filming[edit]

text: Principal photography on the film began on March 18, 2015 in New Orleans, Louisiana.[18][19] On March 25, filming was taking place on General De Gaulle Boulevard in the Algiers section of New Orleans.[20] On May 8, Gillan confirmed she was shooting her scenes.[10] On May 20, 2015, filming took place on Mercer, between Prince Street and Spring Street in Manhattan, New York City.[21] On May 22, the production crew recreated the offices of failed investment firm Lehman Brothers in the lobby of the New York State Department of Financial Services in Manhattan.[22] An assistant counsel for the Department of Financial Services played one of the extras in the scene.[22]

text: Release[edit]

text: On September 22, 2015, Paramount set the film for a limited release on December 11, 2015 and a wide release on December 23, 2015.[23][24]

text: The film was released on DVD and Blu-ray on March 15, 2016.

text: Reception[edit]

text: Box office[edit]

text: The Big Short grossed $70.3 million in the United States and Canada and $63.2 million in other countries for a worldwide total of $133.4 million, against a production budget of $50 million.[3]

text: The film was released in eight theaters in Los Angeles, New York, San Francisco and Chicago on December 11, 2015 and earned $705,527 (an average of $88,191 per theater). It set the record for the best ever per-screen gross for a film opening in eight locations, breaking the previous record held by Memoirs of a Geisha ($85,313 per theater),[25] and was the third biggest theater average of 2015 behind the four screen debuts of Steve Jobs ($130,000) and The Revenant ($118,640).[26]

text: The film had its wide release on Wednesday December 23, 2015 and grossed $2.3 million on its first day. In its opening weekend it grossed $10.5 million, finishing 6th at the box office.[27]

text: Critical response[edit]

text: On Rotten Tomatoes, the film has an approval rating of 88% based on 281 reviews, with an average rating of 7.8/10. The site's critical consensus reads, "The Big Short approaches a serious, complicated subject with an impressive attention to detail – and manages to deliver a well-acted, scathingly funny indictment of its real-life villains in the bargain."[28] On Metacritic, the film has a score of 81 out of 100, based on 45 critics, indicating "universal acclaim".[29] Audiences polled by CinemaScore gave the film an average grade of "A–" on an A+ to F scale.[27]

text: IGN gave the film a score of 8.6/10, praising its "energetic direction" and making "a complicated tale palpable for the layperson even as it triggers outrage at the fatcats who helped cause it".[30] The New York Times's "UpShot" series stated The Big Short offered the "strongest film explanation of the global financial crisis".[31]

text: Accolades[edit]


document_title: List of Indian engineering colleges before Independence

question_text: where is the first engineering college in india

text: This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (June 2017) (Learn how and when to remove this template message)

tag: table

text: The impulse for creation of centres of technical training came from the British rulers of India, and it arose out of the necessity for the training of overseers for construction and maintenance of public buildings, roads, canals, and ports, and for the training of artisans and craftsmen for the use of instruments, and apparatus needed for the army, the navy, and the survey department. While superintending engineers were mostly recruited from Britain, lower grade craftsmen, artisans and sub-overseers were recruited locally. The necessity to make them more efficient, led to the establishment of industrial schools attached to the Ordnance Factories Board and other engineering establishments.

text: The first engineering college was established in present day Uttarakhand at Roorkee in the year 1847 for the training of Civil Engineers. Thomason College of Civil Engineering as it was called, made use of the large workshops and public buildings there that were erected for the Upper Ganges Canal. The college was converted to the University of Roorkee in 1948 and upgraded to the Indian Institute of Technology, Roorkee in 2001.

text: In July 1854, College of Engineering, Pune's precursor, The Poona Engineering Class and Mechanical School was opened, with an aim to provide suitable learning to the subordinate officers in the Public Works Department. In June 1865 Mr. Theodore Cooke, M.A , who held that appointment for 28 years was appointed Principal. The foundation stone of the new college was laid by the Governor, Sir Bartle Frere, on the 5th August 1865. College was affiliated to University of Bombay in 1866. In 1868 the College moved to the New Buildings. The college was divided into three departments for matriculated and unmatriculated students. In 1879 two new classes, an Agricultural class and a Forest class , were added to the college , and the name of the college was changed from " The Poona Civil Engineering College " to " The College of Science". The credit for most of the civil infrastructure in India goes to the alumni of COEP, including Bharat Ratna Sir M. Visvesvarayya, in whose honor "Engineers Day" is celebrated.[1]

text: In pursuance of the Government policy, three Engineering Colleges were opened by about 1856 in the three Presidencies.

text: In Bengal, a College called the Calcutta Civil Engineering College was opened at the Writers' Buildings in November 1856. With the establishment of University of Calcutta on 24 January 1857, the college was affiliated to this university in May 1857.  In 1865, the college merged with Presidency College, Kolkata and from 1865 to 1869 the college functioned as the Civil Engineering Department of Presidency College. In 1880, the college was shifted to its present campus at Shibpur, Howrah, and was christened the Government College, Howrah, in the premises of Bishop's College. On 12 February 1920 the name was changed to Bengal Engineering College, Shibpur. The word Shibpur was deleted on 24 March 1921 and it became Bengal Engineering College. The college was subsequently rechristened Bengal Engineering and Science University and upgraded to the Indian Institute of Engineering Science and Technology, Shibpur in 2014.

text: In the Madras Presidency, the industrial school attached to the Gun Carriage Factory became ultimately the College of Engineering, Guindy and was affiliated to the University of Madras in 1858.

text: The Banaras Engineering College was established at Varanasi in the year 1919. The college was rechristened as the Institute of Technology, Banaras Hindu University in 1968. The college was upgraded to the Indian Institute of Technology (Banaras Hindu University), Varanasi in 2012.

text: The British also opened Harcourt Butler Technological Institute, Kanpur for chemical sciences in 1921 in the United Provinces, now Uttar Pradesh. it is now called the Harcourt Butler Technical University.

text: Indian School of Mines, Dhanbad was established by British Indian Government on the lines of the Royal School of Mines, London, and was formally opened on 9 December 1926 by Lord Irwin, the then Viceroy of India. The college was subsequently called the Indian School of Mines University for a while before the word University was dropped from its name. The college was upgraded to the Indian Institute of Technology (Indian School of Mines), Dhanbad in 2016.[2]

text: In 1947 when India became independent, there were 36 institutions for first-degree engineering education, with an annual intake of about 2500 students.[3]

text:
Engineering college
Location
Established
Remarks

Thomason College of Civil EngineeringB
Roorkee, Uttarakhand
1847[4]

Later known as University of Roorkee and now known as the Indian Institute of Technology, Roorkee

College of Engineering, Pune
Pune
1854[5]

Bharat Ratna Sir Mokshagundam Visvesvaraya (1861–1962) is Alumni of COEP. Engineers Day in India is Celebrated on his Birthday

Bengal Engineering College
Shibpur, West Bengal
1856[4]

Now known as the Indian Institute of Engineering Science and Technology, Shibpur

College of Engineering, Guindy
Madras
1794[A]

Started as survey school in May 1749.[4] Upgraded to an engineering college in 1858.

Indian Institute of Science(Tata Institute)

Bangalore

1911[citation needed]

College of Engineering and Technology, Jadavpur
Jadavpur, Calcutta
1912[6]

College of Engineering, Bangalore
Bangalore
1917[7]

Now called the University Visvesvaraya College Of Engineering

Banaras Engineering CollegeB
Varanasi
1919[citation needed]

Now called the  Indian Institute of Technology (Banaras Hindu University), Varanasi

Harcourt Butler Technological Institute(HBTI)
Kanpur
1920[citation needed]

“Government Research Institute, Cawnpore” was established in 1920, which was renamed as “Government Technological Institute” in 1921.

Indian School Of Mines, JharkhandB
Dhanbad
1926[citation needed]

Now known as Indian Institute of Technology (Indian School of Mines), Dhanbad

College of Engineering, Bihar
Patna
1886[A]

Established as a survey training school in 1886. In 2004 the government of India upgraded the college to National Institute of Technology, Patna

College of Engineering, Trivandrum
Trivandrum
1939[8]

Victoria Jubilee Technical Institute
Bombay
1887[A]

Established as a diploma school in 1887. V. J. T. Institute started with only two departments, namely the Sir J. J. School of Mechanical Engineering and the Ripon Textile School for the two branches of industry

Annamalai University
Tamil Nadu
1929[4]

Institute of Chemical Technology, Mumbai
Mumbai
1933

B M S College of Engineering
Bangalore
1946

India's first private engineering college[citation needed]

Arthur Hope College of Technology, Coimbatore
Coimbatore
1945[citation needed]

Government Engineering College, Jabalpur
Jabalpur
1947[citation needed]

PEC University of Technology

Chandigarh

1921[citation needed]

Punjab Engineering College is one of India's pre-eminent institutions in the field of applied sciences, particularly engineering and technology.

Delhi Polytechnic

Delhi

1941[citation needed]

Renamed as Delhi College of Engineering in 1962 under the University of Delhi. Later, it was granted university status in the year 2009 and renamed as Delhi Technological University.

National Institute of Engineering(NIE), mysore

Mysore

1946[citation needed]

Now Autonomous under VTU Karnataka

Faculty of Technology and Engineering, Maharaja Sayajirao University, Vadodara

Vadodara

1890

The Faculty of Technology and Engineering is one of the 14 faculties at the Maharaja Sayajirao University of Baroda.

Government College of Engineering and Leather Technology (GCELT), Kolkata

Kolkata

1919

The Government College of Engineering and Leather Technology, often referred to as GCELT, is an institute affiliated to MAKAUT(Maulana Abul Kalam Azad University of Technology )

University College of Engineering, Osmania University, Hyderabad

Hyderabad

1929

The University College of Engineering, Osmania University (UCE) is an autonomous engineering college located in Hyderabad, India

text:
|-
| JNTU College of Engineering, Ananatpur was started in1946 as extension of College of Engineering Guindy, later became part of SV University and finally part of JNT University.
|Anantapur
|1946 |}

text: Notes[edit]