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104-528: The department was initially set up as the Health Committee (later Commission), a quasi-governmental public health group in response to a yellow fever outbreak in Philadelphia in 1793. Governor John Jay made a proclamation on 13 September 1793 to establish this to regulate the ports of the city and ensure proper quarantines. Three days later, the city, under the leadership of Mayor Richard Varick , created

208-549: A DNA ladder , a molecular weight marker which contains DNA fragments of known sizes, which runs on the gel alongside the PCR products. As with other chemical reactions, the reaction rate and efficiency of PCR are affected by limiting factors. Thus, the entire PCR process can further be divided into three stages based on reaction progress: In practice, PCR can fail for various reasons, such as sensitivity or contamination. Contamination with extraneous DNA can lead to spurious products and

312-671: A Level 2 alert (practice enhanced precautions.) 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 . Genotype I originated in the northern Brazilian region around 1908 (95% highest posterior density interval [HPD]: 1870–1936). Genotype II originated in Peru in 1920 (95% HPD: 1867–1958). The estimated rate of mutation for both genotypes

416-495: A complementary sequence to the target DNA region) and a thermostable DNA polymerase . In the first step of PCR, the two strands of the DNA double helix are physically separated at a high temperature in a process called nucleic acid denaturation . In the second step, the temperature is lowered and the primers bind to the complementary sequences of DNA. The two DNA strands then become templates for DNA polymerase to enzymatically assemble

520-413: 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 . Minimal YFV 3 ′ UTR region is required for stalling of the host 5 ′ -3 ′ exonuclease XRN1. The UTR contains PKS3 pseudoknot structure, which serves as

624-758: 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. 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 supplies, or in domestic refuse, especially tires, cans, and plastic bottles. These conditions are common in urban areas in developing countries. Two main strategies are employed to reduce A. aegypti populations. One approach

728-570: A billion people live in an area of the world where the disease is common. It is common in tropical areas of the continents of South America and Africa, but not in Asia. Since the 1980s, the number of cases of yellow fever has been increasing. This is believed to be due to fewer people being immune, more people living in cities, people moving frequently, and changing climate increasing the habitat for mosquitoes. The disease originated in Africa and spread to

832-464: A biopsy is only advisable post mortem to confirm the cause of death. In a differential diagnosis , infections with yellow fever must be distinguished from other feverish illnesses such as malaria . Other viral hemorrhagic fevers , such as Ebola virus , Lassa virus , Marburg virus , and Junin virus , must be excluded as the cause. Personal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever

936-462: A broad variety of applications including biomedical research and forensic science . The majority of PCR methods rely on thermal cycling . Thermal cycling exposes reagents to repeated cycles of heating and cooling to permit different temperature-dependent reactions—specifically, DNA melting and enzyme -driven DNA replication . PCR employs two main reagents— primers (which are short single strand DNA fragments known as oligonucleotides that are

1040-473: A forty-thousand-year-old mammoth , and also on human DNA, in applications ranging from the analysis of Egyptian mummies to the identification of a Russian tsar and the body of English king Richard III . Quantitative PCR or Real Time PCR (qPCR, not to be confused with RT-PCR ) methods allow the estimation of the amount of a given sequence present in a sample—a technique often applied to quantitatively determine levels of gene expression . Quantitative PCR

1144-431: A method of amplifying any DNA region through repeated cycles of duplication driven by DNA polymerase. In Scientific American , Mullis summarized the procedure: "Beginning with a single molecule of the genetic material DNA, the PCR can generate 100 billion similar molecules in an afternoon. The reaction is easy to execute. It requires no more than a test tube, a few simple reagents, and a source of heat." DNA fingerprinting

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1248-442: 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. Yellow fever belongs to the group of hemorrhagic fevers . The viruses infect, amongst others, monocytes , macrophages , Schwann cells , and dendritic cells . They attach to

1352-441: A new DNA strand from free nucleotides , the building blocks of DNA. As PCR progresses, the DNA generated is itself used as a template for replication, setting in motion a chain reaction in which the original DNA template is exponentially amplified. Almost all PCR applications employ a heat-stable DNA polymerase , such as Taq polymerase , an enzyme originally isolated from the thermophilic bacterium Thermus aquaticus . If

1456-501: A number of advantages. It is fairly simple to understand and to use, and produces results rapidly. The technique is highly sensitive with the potential to produce millions to billions of copies of a specific product for sequencing, cloning, and analysis. qRT-PCR shares the same advantages as the PCR, with an added advantage of quantification of the synthesized product. Therefore, it has its uses to analyze alterations of gene expression levels in tumors, microbes, or other disease states. PCR

1560-493: A rearrangement of the 90 homo dimers to 60 homo trimers . 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, so is denoted as precursor M (prM) and forms a complex with protein E. The immature particles are processed in

1664-549: A reduced volume of vaccine dose, which has been reconstituted as per manufacturer recommendations. The first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the Democratic Republic of the Congo in mid-2016. Available evidence shows that fractional dose yellow fever vaccination induces a level of immune response similar to that of the standard full dose. In March 2017,

1768-405: A small quantity of RNA. Through this combined technique, mRNA is converted to cDNA, which is further quantified using qPCR. This technique lowers the possibility of error at the end point of PCR, increasing chances for detection of genes associated with genetic diseases such as cancer. Laboratories use RT-qPCR for the purpose of sensitively measuring gene regulation. The mathematical foundations for

1872-471: A specific DNA region. PCR supplies these techniques with high amounts of pure DNA, enabling analysis of DNA samples even from very small amounts of starting material. Other applications of PCR include DNA sequencing to determine unknown PCR-amplified sequences in which one of the amplification primers may be used in Sanger sequencing , isolation of a DNA sequence to expedite recombinant DNA technologies involving

1976-514: A tandem committee that ensured both private and commercial needs would be addressed. New York would see additional epidemics in 1795, 1796, 1798, 1799, and 1800, which lead to the creation of the 'New York City Board of Health', which held its first meeting in 1805. In 1866, the New York State legislature enacted a bill establishing the 'Metropolitan Board of Health', consisting of the four Police Commissioners, four Health Commissioners appointed by

2080-421: 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 yellow fever worldwide each year. About 15% of people infected with yellow fever progress to a severe form of the illness, and up to half of those will die, as there is no cure for yellow fever. An estimated 90% of yellow fever infections occur on

2184-421: Is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed study. PCR was invented in 1983 by American biochemist Kary Mullis at Cetus Corporation . Mullis and biochemist Michael Smith , who had developed other essential ways of manipulating DNA, were jointly awarded

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2288-413: Is a very powerful and practical research tool. The sequencing of unknown etiologies of many diseases are being figured out by the PCR. The technique can help identify the sequence of previously unknown viruses related to those already known and thus give us a better understanding of the disease itself. If the procedure can be further simplified and sensitive non-radiometric detection systems can be developed,

2392-699: Is addressed with lab protocols and procedures that separate pre-PCR mixtures from potential DNA contaminants. For instance, if DNA from a crime scene is analyzed, a single DNA molecule from lab personnel could be amplified and misguide the investigation. Hence the PCR-setup areas is separated from the analysis or purification of other PCR products, disposable plasticware used, and the work surface between reaction setups needs to be thoroughly cleaned. Specificity can be adjusted by experimental conditions so that no spurious products are generated. Primer-design techniques are important in improving PCR product yield and in avoiding

2496-462: Is an established tool for DNA quantification that measures the accumulation of DNA product after each round of PCR amplification. qPCR allows the quantification and detection of a specific DNA sequence in real time since it measures concentration while the synthesis process is taking place. There are two methods for simultaneous detection and quantification. The first method consists of using fluorescent dyes that are retained nonspecifically in between

2600-431: Is caused by yellow fever virus (YFV), an enveloped RNA virus 40–50 nm in width, the type species and namesake of the family Flaviviridae . It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes, by American doctor Walter Reed around 1900. The positive- sense , single-stranded RNA is around 10,862 nucleotides long and has a single open reading frame encoding

2704-415: Is commonly carried out in a volume of 10–200  μL in small reaction tubes (0.2–0.5 mL volumes) in a thermal cycler . The thermal cycler heats and cools the reaction tubes to achieve the temperatures required at each step of the reaction (see below). Many modern thermal cyclers make use of a Peltier device , which permits both heating and cooling of the block holding the PCR tubes simply by reversing

2808-625: Is endemic. Institutional measures for prevention of yellow fever include vaccination programmes and measures to control mosquitoes. Programmes for distribution of mosquito nets for use in homes produce 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 application of larvicides to water-storage containers can help eliminate potential mosquito breeding sites. EPA-registered insecticide spray decreases

2912-643: 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% of cases. The Yellow Fever Initiative, launched by the WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign

3016-504: Is known as acquired immunity . The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the trafficking of slaves from Africa, part of the Columbian exchange following European exploration and colonization. However, some researchers have argued that yellow fever might have existed in the Americas during the pre-Columbian period as mosquitoes of

3120-470: Is not recommended by the WHO. Insecticide-treated mosquito nets are effective, just as they are against the Anopheles mosquito that carries malaria. As with 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. Certain acute treatment methods lack efficacy: passive immunization after

3224-409: Is often preceded by a single temperature step at a very high temperature (>90 °C (194 °F)), and followed by one hold at the end for final product extension or brief storage. The temperatures used and the length of time they are applied in each cycle depend on a variety of parameters, including the enzyme used for DNA synthesis, the concentration of bivalent ions and dNTPs in the reaction, and

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3328-483: Is part of the Department of Health and Mental Hygiene and consists of the commissioner of the department, the chairperson of the department's Mental Hygiene Advisory Board, and nine other members appointed by the mayor . Yellow fever Yellow fever is a viral disease of typically short duration . In most cases, symptoms include fever , chills , loss of appetite , nausea , muscle pains—particularly in

3432-410: Is recommended as a chemical larvicide, mainly because it is safe for humans and effective in small doses. The second strategy is to reduce populations of the adult yellow fever mosquito. Lethal ovitraps can reduce Aedes populations, using lesser amounts of pesticide because it targets the pest directly. Curtains and lids of water tanks can be sprayed with insecticides, but application inside houses

3536-536: Is spread primarily by Aedes aegypti , a type of mosquito found throughout the tropics and subtropics . The virus is an RNA virus of the genus Flavivirus . The disease may be difficult to tell apart from other illnesses, especially in the early stages. To confirm a suspected case, blood-sample testing with a polymerase chain reaction is required. A safe and effective vaccine against yellow fever exists, and some countries require vaccinations for travelers. Other efforts to prevent infection include reducing

3640-427: Is taken up by a female mosquito when it ingests the blood of an infected human or another 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

3744-543: Is the absence of a slave trade to Asia on the scale of that to the Americas. The trans-Atlantic slave trade probably introduced yellow fever into the Western Hemisphere from Africa. The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from nonhuman primates to humans. The virus is thought to have originated in East or Central Africa and spread from there to West Africa. As it

3848-460: Is the detection of infectious agents and the discrimination of non-pathogenic from pathogenic strains by virtue of specific genes. Characterization and detection of infectious disease organisms have been revolutionized by PCR in the following ways: The development of PCR-based genetic (or DNA ) fingerprinting protocols has seen widespread application in forensics : PCR has been applied to many areas of research in molecular genetics: PCR has

3952-507: Is to kill the developing larvae. Measures are taken to reduce the water accumulations in which the larvae develop. Larvicides are used, along with 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. This eradicated the mosquito vector in several areas. Similar efforts may prove effective against yellow fever. Pyriproxyfen

4056-500: The Journal of Molecular Biology by Kjell Kleppe and co-workers in the laboratory of H. Gobind Khorana first described a method of using an enzymatic assay to replicate a short DNA template with primers in vitro . However, this early manifestation of the basic PCR principle did not receive much attention at the time and the invention of the polymerase chain reaction in 1983 is generally credited to Kary Mullis . When Mullis developed

4160-447: The 16S rRNA and recA genes of microorganisms). Because PCR amplifies the regions of DNA that it targets, PCR can be used to analyze extremely small amounts of sample. This is often critical for forensic analysis , when only a trace amount of DNA is available as evidence. PCR may also be used in the analysis of ancient DNA that is tens of thousands of years old. These PCR-based techniques have been successfully used on animals, such as

4264-545: 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 . 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, yellow fever virus

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4368-684: The Napoleonic Wars , the West Indies were known as a particularly dangerous posting for soldiers due to yellow fever being endemic in the area. The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada, mostly because of yellow fever and other tropical diseases. Both English and French forces posted there were seriously affected by the "yellow jack." Wanting to regain control of

4472-580: The Nobel Prize in Chemistry in 1993, seven years after Mullis and his colleagues at Cetus first put his proposal to practice. Mullis's 1985 paper with R. K. Saiki and H. A. Erlich, "Enzymatic Amplification of β-globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia"—the polymerase chain reaction invention (PCR)—was honored by a Citation for Chemical Breakthrough Award from

4576-444: The Nobel Prize in Chemistry in 1993. PCR is fundamental to many of the procedures used in genetic testing and research, including analysis of ancient samples of DNA and identification of infectious agents. Using PCR, copies of very small amounts of DNA sequences are exponentially amplified in a series of cycles of temperature changes. PCR is now a common and often indispensable technique used in medical laboratory research for

4680-410: The melting temperature ( T m ) of the primers. The individual steps common to most PCR methods are as follows: To check whether the PCR successfully generated the anticipated DNA target region (also sometimes referred to as the amplimer or amplicon ), agarose gel electrophoresis may be employed for size separation of the PCR products. The size of the PCR products is determined by comparison with

4784-653: The African continent. 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 2016, 11 imported cases of the Angola genotype in unvaccinated Chinese nationals were reported in China, the first appearance of the disease in Asia in recorded history. Phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to

4888-521: The Americas starting in the 17th century with the European trafficking of enslaved Africans from sub-Saharan Africa. Since the 17th century, several major outbreaks of the disease have occurred in the Americas, Africa, and Europe. In the 18th and 19th centuries, yellow fever was considered one of the most dangerous infectious diseases ; numerous epidemics swept through major cities of the US and in other parts of

4992-431: The DNA polymerase properly binds to the primer-template hybrids and subsequently generates the entire target region during DNA synthesis. Like all enzymes, DNA polymerases are also prone to error, which in turn causes mutations in the PCR fragments that are generated. Another limitation of PCR is that even the smallest amount of contaminating DNA can be amplified, resulting in misleading or ambiguous results. To minimize

5096-523: The Democratic Republic of Congo (2016), Uganda (2016), and more recently in Nigeria and Brazil in 2017 have further increased demand, while straining global vaccine supply. Therefore, to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks, fractional dosing of the vaccine is being considered as a dose-sparing strategy to maximize limited vaccine supplies. Fractional dose yellow fever vaccination refers to administration of

5200-629: The Division of History of Chemistry of the American Chemical Society in 2017. At the core of the PCR method is the use of a suitable DNA polymerase able to withstand the high temperatures of >90 °C (194 °F) required for separation of the two DNA strands in the DNA double helix after each replication cycle. The DNA polymerases initially employed for in vitro experiments presaging PCR were unable to withstand these high temperatures. So

5304-790: The East African genotype, which had remained undetected in the previous 40 years. In South America, two genotypes have been identified (South American genotypes I and II). Based on phylogenetic analysis these two genotypes appear to have originated in West Africa and were first introduced into Brazil. The date of introduction of the predecessor African genotype which gave rise to the South American genotypes appears to be 1822 (95% confidence interval 1701 to 1911). The historical record shows an outbreak of yellow fever occurred in Recife, Brazil, between 1685 and 1690. The disease seems to have disappeared, with

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5408-649: The French troops survived for withdrawal and return to France. Napoleon gave up on the island and his plans for North America, selling the Louisiana Purchase to the US in 1803. In 1804, Haiti proclaimed its independence as the second republic in the Western Hemisphere. Considerable debate exists over whether the number of deaths caused by disease in the Haitian Revolution was exaggerated. Polymerase chain reaction The polymerase chain reaction ( PCR )

5512-643: The Governor, and the Health Officer for the Port of New York. In 1870, the legislature replaced the Board of Health with the Department of Health, with additional responsibilities including street cleaning and sanitary permits. As of December 1894, Charles G. Wilson was serving as President of the Board of Health. As a result of its consolidation with the Department of Mental Health, Mental Retardation and Alcoholism Services, it

5616-466: The PCR and analysis rooms should ever be taken into the PCR preparation room without thorough decontamination. Environmental samples that contain humic acids may inhibit PCR amplification and lead to inaccurate results. The heat-resistant enzymes that are a key component in polymerase chain reaction were discovered in the 1960s as a product of a microbial life form that lived in the superheated waters of Yellowstone 's Mushroom Spring. A 1971 paper in

5720-560: The PCR in 1983, he was working in Emeryville , California for Cetus Corporation , one of the first biotechnology companies, where he was responsible for synthesizing short chains of DNA. Mullis has written that he conceived the idea for PCR while cruising along the Pacific Coast Highway one night in his car. He was playing in his mind with a new way of analyzing changes (mutations) in DNA when he realized that he had instead invented

5824-429: The PCR will assume a prominent place in the clinical laboratory for years to come. One major limitation of PCR is that prior information about the target sequence is necessary in order to generate the primers that will allow its selective amplification. This means that, typically, PCR users must know the precise sequence(s) upstream of the target region on each of the two single-stranded templates in order to ensure that

5928-514: The WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil. In March 2018, Brazil shifted its policy and announced it planned to vaccinate all 77.5 million currently unvaccinated citizens by April 2019. Some countries in Asia are considered to be potentially in danger of yellow fever epidemics, as both mosquitoes with

6032-409: 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. If the vaccination cannot be given for some reason, dispensation may be possible. In this case, an exemption certificate issued by

6136-591: The analysis of rare fetal cells circulating in the mother's bloodstream. PCR analysis is also essential to preimplantation genetic diagnosis , where individual cells of a developing embryo are tested for mutations. PCR allows for rapid and highly specific diagnosis of infectious diseases, including those caused by bacteria or viruses. PCR also permits identification of non-cultivatable or slow-growing microorganisms such as mycobacteria , anaerobic bacteria , or viruses from tissue culture assays and animal models . The basis for PCR diagnostic applications in microbiology

6240-486: The back—and headaches . Symptoms typically improve within five days. In about 15% of people, within a day of improving the fever comes back, abdominal pain occurs, and liver damage begins causing yellow skin . If this occurs, the risk of bleeding and kidney problems is increased. The disease is caused by the yellow fever virus and is spread by the bite of an infected mosquito . It infects humans, other primates , and several types of mosquitoes. In cities, it

6344-407: The capability to transmit yellow fever as well as susceptible monkeys are present. The disease does not yet occur in Asia. To prevent introduction of the virus, some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas. Vaccination has to be proved by a vaccination certificate, which is valid 10 days after the vaccination and lasts for 10 years. Although

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6448-399: The cell surfaces 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

6552-403: The chance of contamination, investigators should reserve separate rooms for reagent preparation, the PCR, and analysis of product. Reagents should be dispensed into single-use aliquots . Pipettors with disposable plungers and extra-long pipette tips should be routinely used. It is moreover recommended to ensure that the lab set-up follows a unidirectional workflow. No materials or reagents used in

6656-472: The detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever. As these tests can cross-react with other flaviviruses, such as dengue virus , these indirect methods cannot conclusively prove yellow fever infection. Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens . Because of the bleeding tendency of yellow fever patients,

6760-577: The device's electric current. Thin-walled reaction tubes permit favorable thermal conductivity to allow for rapid thermal equilibrium. Most thermal cyclers have heated lids to prevent condensation at the top of the reaction tube. Older thermal cyclers lacking a heated lid require a layer of oil on top of the reaction mixture or a ball of wax inside the tube. Typically, PCR consists of a series of 20–40 repeated temperature changes, called thermal cycles, with each cycle commonly consisting of two or three discrete temperature steps (see figure below). The cycling

6864-513: The diagnosis of infectious diseases . PCR amplifies a specific region of a DNA strand (the DNA target). Most PCR methods amplify DNA fragments of between 0.1 and 10 kilo base pairs (kbp) in length, although some techniques allow for amplification of fragments up to 40 kbp. The amount of amplified product is determined by the available substrates in the reaction, which becomes limiting as the reaction progresses. A basic PCR set-up requires several components and reagents, including: The reaction

6968-562: The disease by the name "yellow fever" occurred in 1744. However, Dr. Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weil's disease or hepatitis. 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. Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs. In Colonial times and during

7072-498: The disease can only be confirmed virologically. Since mild cases of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea, and vomiting 6–10 days after leaving the affected area) is treated seriously. If yellow fever is suspected, the virus cannot be confirmed until 6–10 days following the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction , where

7176-467: The disease characterized by recurring fever, this time accompanied by jaundice due to liver damage , as well as abdominal pain . Bleeding in the mouth, nose, eyes, and the gastrointestinal tract cause vomit containing blood , hence one of the names in Spanish for yellow fever, vómito negro ("black vomit"). There may also be kidney failure, hiccups, and delirium. Among those who develop jaundice,

7280-414: The double strands. The second method involves probes that code for specific sequences and are fluorescently labeled. Detection of DNA using these methods can only be seen after the hybridization of probes with its complementary DNA (cDNA) takes place. An interesting technique combination is real-time PCR and reverse transcription. This sophisticated technique, called RT-qPCR, allows for the quantification of

7384-414: The early procedures for DNA replication were very inefficient and time-consuming, and required large amounts of DNA polymerase and continuous handling throughout the process. The discovery in 1976 of Taq polymerase —a DNA polymerase purified from the thermophilic bacterium , Thermus aquaticus , which naturally lives in hot (50 to 80 °C (122 to 176 °F)) environments such as hot springs—paved

7488-493: The emergence of symptoms is probably without effect; ribavirin and other antiviral drugs , as well as treatment with interferons , are ineffective in yellow fever patients. Symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen). However, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided because of an increased risk of gastrointestinal bleeding due to their anticoagulant effects. Yellow fever

7592-480: The employee's geographical area of employment and only while such employee is actually on duty as listed in Chapter 13 subsection (C):. DOHMH Special Officers are prohibited by New York State Law (Criminal Procedure Law) to use or carry a firearm. The New York City Police Department responds to all incidents that occur at New York City Department of Health and Mental Hygiene facilities. The New York City Board of Health

7696-500: The fatality rate is 20 to 50%, while the overall fatality rate is about 3 to 7.5%. Severe cases may have a mortality rate greater than 50%. Surviving the infection provides lifelong immunity , and normally results in no permanent organ damage. Yellow fever can lead to death for 20% to 50% of those who develop severe disease. Jaundice, fatigue, heart rhythm problems, seizures and internal bleeding may also appear as complications of yellow fever during recovery time. Yellow fever

7800-497: The five New York City Health and Mental Hygiene clinics is provided by the New York City Department of Health and Mental Hygiene Police. New York City Health and Mental Hygiene (Police) are employed as Special Officers and who have very limited peace officer authority in connection with special duties of employment pursuant to New York State Criminal Procedure Law § 2.10(40). The exercise of these powers are very limited to

7904-404: The formation of unspecific products. The usage of alternate buffer components or polymerase enzymes can help with amplification of long or otherwise problematic regions of DNA. For instance, Q5 polymerase is said to be ~280 times less error-prone than Taq polymerase. Both the running parameters (e.g. temperature and duration of cycles), or the addition of reagents, such as formamide , may increase

8008-441: The genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma ; this can take 1–4 weeks. 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,

8112-607: The genus Haemagogus , which is indigenous to the Americas, have been known to carry the disease. The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados . 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

8216-778: The insertion of a DNA sequence into a plasmid , phage , or cosmid (depending on size) or the genetic material of another organism. Bacterial colonies (such as E. coli ) can be rapidly screened by PCR for correct DNA vector constructs. PCR may also be used for genetic fingerprinting ; a forensic technique used to identify a person or organism by comparing experimental DNAs through different PCR-based methods. Some PCR fingerprint methods have high discriminative power and can be used to identify genetic relationships between individuals, such as parent-child or between siblings, and are used in paternity testing (Fig. 4). This technique may also be used to determine evolutionary relationships among organisms when certain molecular clocks are used (i.e.

8320-441: 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. Concern exists about yellow fever spreading to southeast Asia, where its vector A. aegypti already occurs. After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in particular. From there, they reach

8424-468: 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. Fatality may occur when cytokine storm , shock , and multiple organ failure follow. Yellow fever is most frequently a clinical diagnosis , based on symptomatology and travel history. Mild cases of

8528-475: 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 General Charles Leclerc 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. Only one-third of

8632-469: The next outbreak occurring in 1849. It was likely introduced with the trafficking of slaves through the slave trade from Africa. Genotype I has been divided into five subclades, A through E. In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvatic or jungle epizootic . Real-time phylogenetic investigations at the epicentre of the outbreak revealed that

8736-481: The only way unvaccinated 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, yellow fever cannot be eradicated except by completely eradicating the mosquitoes that serve as vectors. In Africa, a third infectious cycle known as "savannah cycle" or intermediate cycle, occurs between

8840-478: The outbreak was caused by the introduction of a virus lineage from the Amazon region into the southeast region around July 2016, spreading rapidly across several neotropical monkey species, including brown howler monkeys, which serve as a sentinel species for yellow fever. No cases had been transmitted between humans by the A. aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. In April 2017,

8944-696: The polymerase used was heat-susceptible, it would denature under the high temperatures of the denaturation step. Before the use of Taq polymerase, DNA polymerase had to be manually added every cycle, which was a tedious and costly process. Applications of the technique include DNA cloning for sequencing , gene cloning and manipulation, gene mutagenesis; construction of DNA-based phylogenies , or functional analysis of genes ; diagnosis and monitoring of genetic disorders ; amplification of ancient DNA; analysis of genetic fingerprints for DNA profiling (for example, in forensic science and parentage testing ); and detection of pathogens in nucleic acid tests for

9048-588: The population of the transmitting mosquitoes. In areas where yellow fever is common, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks . Once a person is infected, management is symptomatic; no specific measures are effective against the virus. Death occurs in up to half of those who get severe disease. In 2013, yellow fever was estimated to have caused 130,000 severe infections and 78,000 deaths in Africa. Approximately 90 percent of an estimated 200,000 cases of yellow fever per year occur in Africa. Nearly

9152-464: The reliable quantification of the PCR and RT-qPCR facilitate the implementation of accurate fitting procedures of experimental data in research, medical, diagnostic and infectious disease applications. Prospective parents can be tested for being genetic carriers , or their children might be tested for actually being affected by a disease . DNA samples for prenatal testing can be obtained by amniocentesis , chorionic villus sampling , or even by

9256-450: The specificity and yield of PCR. Computer simulations of theoretical PCR results ( Electronic PCR ) may be performed to assist in primer design. PCR allows isolation of DNA fragments from genomic DNA by selective amplification of a specific region of DNA. This use of PCR augments many ways, such as generating hybridization probes for Southern or northern hybridization and DNA cloning , which require larger amounts of DNA, representing

9360-562: The sylvatic outbreak continued moving toward the Brazilian coast, where most people were unvaccinated. 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. The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March. The CDC issued

9464-466: The technique in 1983. The Taq polymerase enzyme was also covered by patents. There have been several high-profile lawsuits related to the technique, including an unsuccessful lawsuit brought by DuPont . The Swiss pharmaceutical company Hoffmann-La Roche purchased the rights to the patents in 1992. The last of the commercial PCR patents expired in 2017. A related patent battle over the Taq polymerase enzyme

9568-505: The transmission of yellow fever. 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, and had been reported to last for at least 10 years. The World Health Organization (WHO) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease. The attenuated live vaccine stem 17D

9672-516: 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 nonhuman primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently

9776-587: 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 region. West Africa genotype I appears to be especially infectious, as it is often associated with major outbreaks. The three genotypes found outside of Nigeria and Angola occur in areas where outbreaks are rare. Two outbreaks, in Kenya (1992–1993) and Sudan (2003 and 2005), involved

9880-587: The virus is transmitted from mosquitoes to humans or other primates. 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 for an outbreak in Bolivia in 1999, this urban cycle no longer exists in South America. Besides

9984-447: The way for dramatic improvements of the PCR method. The DNA polymerase isolated from T. aquaticus is stable at high temperatures remaining active even after DNA denaturation, thus obviating the need to add new DNA polymerase after each cycle. This allowed an automated thermocycler-based process for DNA amplification. The PCR technique was patented by Kary Mullis and assigned to Cetus Corporation , where Mullis worked when he invented

10088-423: The world. In 1927, yellow fever virus became the first human virus to be isolated. Yellow fever begins after an incubation period of three to six days. Most cases cause only mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting. In these cases, the infection lasts only three to six days. But in 15% of cases, people enter a second, toxic phase of

10192-461: The wound, and the virus reaches the bloodstream of the bitten person. Transovarial transmissionial and transstadial transmission of yellow fever virus within A. aegypti , that is, the transmission from a female mosquito to its 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. Three epidemiologically different infectious cycles occur in which

10296-487: Was about 5 × 10  substitutions/site/year, similar to that of other RNA viruses. The main vector ( A. aegypti ) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, but yellow fever had never occurred there until jet travel introduced 11 cases from the 2016 Angola and DR Congo yellow fever outbreak in Africa. Proposed explanations include: But none is considered satisfactory. Another proposal

10400-411: Was developed in 1937 by Max Theiler . The WHO recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth. Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine-associated viscerotropic disease, which

10504-407: Was endemic in Africa, local populations had developed some immunity to it. When an outbreak of yellow fever would occur in an African community where colonists resided, most Europeans died, while the indigenous Africans usually developed nonlethal symptoms resembling influenza . This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood,

10608-429: Was first used for paternity testing in 1988. Mullis has credited his use of LSD as integral to his development of PCR: "Would I have invented PCR if I hadn't taken LSD? I seriously doubt it. I could sit on a DNA molecule and watch the polymers go by. I learnt that partly on psychedelic drugs." Mullis and biochemist Michael Smith , who had developed other essential ways of manipulating DNA, were jointly awarded

10712-500: Was renamed the Department of Health and Mental Hygiene on July 29, 2002. In 2021, Michelle E. Morse was named the first Chief Medical Officer of the New York City Department of Health and Mental Hygiene. NYC is organized into 30 health districts (sometimes referred to as health center districts), themselves composed of 354 health areas which are sets of census tracts . NYC is also organized into 17 mental health regions . The departmental hierarchy is: On-site security services at

10816-657: 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. Demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes. Recent upsurges in yellow fever outbreaks in Angola (2015),

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