Vaccination

Vaccination is the administration of a vaccine to help the immune system develop protection from a disease. Vaccines contain a microorganism in a weakened or killed state, or proteins or toxins from the organism. In stimulating the body's adaptive immunity, they help prevent sickness from an infectious disease. When a sufficiently large percentage of a population has been vaccinated, herd immunity results. The effectiveness of vaccination has been widely studied and verified.[1][2][3] Vaccination is the most effective method of preventing infectious diseases;[4] widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the elimination of diseases such as polio and tetanus from much of the world.

Smallpox was most likely the first disease people tried to prevent by inoculation and was the first disease for which a vaccine was produced.[5][6] The smallpox vaccine was invented in 1796 by English physician Edward Jenner and, although at least six people had used the same principles years earlier, he was the first to publish evidence that it was effective and to provide advice on its production.[7] Louis Pasteur furthered the concept through his work in microbiology. The immunization was called vaccination because it was derived from a virus affecting cows (Latin: vacca 'cow').[5][7] Smallpox was a contagious and deadly disease, causing the deaths of 20–60% of infected adults and over 80% of infected children.[8] When smallpox was finally eradicated in 1979, it had already killed an estimated 300–500 million people in the 20th century.[9][10][11]

Vaccination and immunization have a similar meaning in everyday language. This is distinct from inoculation, which uses unweakened live pathogens. Vaccination efforts have been met with some controversy on scientific, ethical, political, medical safety, and religious grounds. In the United States, people may receive compensation for those injuries under the National Vaccine Injury Compensation Program. Early success brought widespread acceptance, and mass vaccination campaigns have greatly reduced the incidence of many diseases in numerous geographic regions.

Vaccinations
Vaccination-polio-india
Child receiving an oral polio vaccine
ICD-9-CM99.3-99.5

Mechanism of function

Polio vaccination in Sweden 1957
Polio vaccination started in Sweden in 1957.

Vaccines are a way of artificially activating the immune system to protect against infectious disease. The activation occurs through priming the immune system with an immunogen. Stimulating immune responses with an infectious agent is known as immunization. Vaccination includes various ways of administering immunogens.[12]

Most vaccines are administered before a patient has contracted a disease to help increase future protection. However, some vaccines are administered after the patient already has contracted a disease. Vaccines given after exposure to smallpox are reported to offer some protection from disease or may reduce the severity of disease.[13] The first rabies immunization was given by Louis Pasteur to a child after he was bitten by a rabid dog. Since its discovery, the rabies vaccine have been proven effective in preventing rabies in humans when administered several times over 14 days along with rabies immune globulin and wound care.[14] Other examples include experimental AIDS, cancer and Alzheimer's disease vaccines. Such immunizations aim to trigger an immune response more rapidly and with less harm than natural infection.

Most vaccines are given by injection as they are not absorbed reliably through the intestines. Live attenuated polio, rotavirus, some typhoid, and some cholera vaccines are given orally to produce immunity in the bowel. While vaccination provides a lasting effect, it usually takes several weeks to develop. This differs from passive immunity (the transfer of antibodies, such as in breastfeeding) has immediate effect.[15]

A vaccine failure is when an organism contracts a disease in spite of being vaccinated against it. Primary vaccine failure occurs when an organism's immune system does not produce antibodies when first vaccinated. Vaccines can fail when several series are given and fail to produce an immune response. The term "vaccine failure" does not necessarily imply that the vaccine is defective. Most vaccine failures are simply from individual variations in immune response.

Measles-vaccine-coverage-worldwide-vs-measles-cases-worldwide
Measles infection rate vs vaccination rate, 1980 - 2011. Source: WHO

Vaccination versus inoculation

The term inoculation is often used interchangeably with vaccination. However, some argue that the terms are not synonymous. Dr Byron Plant explains: "Vaccination is the more commonly used term, which actually consists of a 'safe' injection of a sample taken from a cow suffering from cowpox... Inoculation, a practice probably as old as the disease itself, is the injection of the variola virus taken from a pustule or scab of a smallpox sufferer into the superficial layers of the skin, commonly on the upper arm of the subject. Often inoculation was done 'arm-to-arm' or, less effectively, 'scab-to-arm'..." Inoculation oftentimes caused the patient to become infected with smallpox, and in some cases the infection turned into a severe case.[16][17]

Vaccinations began in the 18th century with the work of Edward Jenner and the smallpox vaccine.[18][19][20]

Safety

Vaccine development and approval

Just like any medication or procedure, no vaccine can be 100% safe or effective for everyone because each person's body can react differently.[21][22] While minor side effects, such as soreness or low grade fever, are relatively common, serious side effects are very rare and occur in about 1 out of every 100,000 vaccinations and typically involve allergic reactions that can cause hives or difficulty breathing.[23][24] However, vaccines are the safest they ever have been in history and each vaccine undergoes rigorous clinical trials to ensure their safety and efficacy before FDA approval.[25] Prior to human testing, vaccines are run through computer algorithms to model how they will interact with the immune system and are tested on cells in a culture.[23][25] During the next round of testing, researchers study vaccines in animal, including mice, rabbits, guinea pigs, and monkeys.[23] Vaccines that pass each of these stages of testing are then approved by the FDA to start a three-phase series of human testing, advancing to higher phases only if they are deemed safe and effective at the previous phase. The people in these trials participate voluntarily and are required to prove they understand the purpose of the study and the potential risks.[25] During phase I trials, a vaccine is tested in a group of about 20 people with the primary goal of assessing the vaccine's safety.[23] Phase II trials expand the testing to include 50 to several hundred people. During this stage, the vaccine's safety continues to be evaluated and researchers also gather data on the effectiveness and the ideal dose of the vaccine.[23] Vaccines determined to be safe and efficacious then advance to phase III trials, which focuses on the efficacy of the vaccine in hundreds to thousands of volunteers. This phase can take several years to complete and researchers use this opportunity to compare the vaccinated volunteers to those who have not been vaccinated to highlight any true reactions to the vaccine that occur.[25] If a vaccine passes all of the phases of testing, the manufacturer can then apply for licensure of the vaccine through the FDA. Before the FDA approves use in the general public, they extensively review the results to the clinical trials, safety tests, purity tests, and manufacturing methods and establish that the manufacturer itself is up to government standards in many other areas.[23] However, safety testing of the vaccines never ends even after FDA approval. The FDA continues to monitor the manufacturing protocols, batch purity, and the manufacturing facility itself. Additionally, most vaccines also undergo phase IV trials, which monitors the safe and efficacy of vaccines in tens of thousands of people, or more, across many years.[23] This allows for delayed or very rare reactions to be detected and evaluated.

Safety monitoring

CDC Immunization Safety Office initiatives[26] Government organizations Non-government organizations
Vaccine Adverse Event Reporting System (VAERS)[27] Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER)[28] Immunization Action Coalition (IAC)[29]
Vaccine Safety Datalink (VSD)[30] Health Resources and Service Administration (HRSA)[31] Institute for Safe Medication Practices (ISMP)[32]
Clinical Immunization Safety Assessment (CISA) Project National Institutes of Health (NIH)[33]
Emergency preparedness for vaccine safety National Vaccine Program Office (NVPO)[34]

The administration protocols, efficacy, and adverse events of vaccines are very strictly monitored. Organizations of the federal government, including the CDC and FDA, as well as organizations independent of the government are constantly re-evaluating our vaccine practices. As with all medications, vaccine use is driven by validated data and both the formulations and administration protocols of vaccines are subject to evolve as data continues to be gathered.

Side effects

The Centers for Disease Control and Prevention (CDC) has compiled a list of vaccines and their possible side effects.[24] The risk of side effects varies from one vaccine to the next, but below are examples of side effects and their approximate rate of occurrence with the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine, a common childhood vaccine.[24]

Mild side effects (common)

  • Mild fever (1 in 4)
  • Redness, soreness, swelling at the injection site (1 in 4)
  • Fatigue, poor appetite (1 in 10)
  • Vomiting (1 in 50)

Moderate side effects (uncommon)

  • Seizure (1 in 14,000)
  • High fever (over 105 °F) (1 in 16,000)

Severe side effects (rare)

  • Serious allergic reaction (1 in 1,000,000)
  • Other severe problems including long-term seizure, coma, brain damage have been reported, but are so rare that it is not possible to tell if they are from the vaccine or not

Ingredients commonly of concern

The ingredients of vaccines can vary greatly from one to the next and no two vaccines are the same. The CDC has compiled a list of vaccines and their ingredients that is readily accessible on their website.[35]

Aluminium

Aluminium is an adjuvant ingredient in some vaccines. An adjuvant is a certain type of ingredient that is used to help the body's immune system create a stronger immune response after receiving the vaccination.[36] Aluminium is in a salt form and is used in the following compounds: aluminium hydroxide, aluminium phosphate, and aluminium potassium sulfate. In chemistry, a salt is the ionic version of an element; another example is table salt: Na+
(sodium) and Cl
(chloride). For a given element, the ion form has different properties from the elemental form. Although it is possible to have aluminium toxicity, aluminium salts have been used effectively and safely since the 1930s when they were first used with the diphtheria and tetanus vaccines.[36] Although there is a small increase in the chance of having a local reaction to a vaccine with an aluminium salt (redness, soreness, swelling), there is no increased risk of any serious reactions.[37][38]

Mercury

Certain vaccines contain a compound called thimerosal, which is an organic compound that contains mercury. Mercury is commonly found in two forms that differ by the number of carbon groups in its chemical structure. Methylmercury (one carbon group) is found in fish and is the form that people usually ingest, while ethylmercury (two carbon groups) is the form that is in thimerosal.[39] Although the two have similar chemical compounds, they do not have the same chemical properties and interact with the human body differently. Ethylmercury is cleared from the body faster than methylmercury and is less likely to cause toxic effects.[39]

Thimerosal is used to prevent the growth of bacteria and fungi in vials that contain more than one dose of a vaccine.[39] This helps reduce the risk of potential infections and or serious illness that could occur from contamination of a vaccine vial. Although there is a small increase in risk of injection site redness and swelling with vaccines containing thimerosal, there is no increased risk of serious harm, including autism.[40][41] Even though evidence supports the safety and efficacy of thimerosal in vaccines, thimerosal was removed from childhood vaccines in the United States in 2001 as a precaution.[39]

History

Edward Jenner manuscript
Handwritten draft of Edward Jenner's first vaccination. The document is held at the Royal College of Surgeons in London

It is known that the process of inoculation was used by Chinese physicians in the 10th century.[42] Scholar Ole Lund comments: "The earliest documented examples of vaccination are from India and China in the 17th century, where vaccination with powdered scabs from people infected with smallpox was used to protect against the disease. Smallpox used to be a common disease throughout the world and 20 to 30% of infected persons died from the disease. Smallpox was responsible for 8 to 20% of all deaths in several European countries in the 18th century. The tradition of vaccination may have originated in India in AD 1000."[43] The mention of inoculation in the Sact'eya Grantham, an Ayurvedic text, was noted by the French scholar Henri Marie Husson in the journal Dictionaire des sciences médicales.[44] However, the idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation.[45] Accounts of inoculation against smallpox in China can be found as early as the late 10th century and was reportedly widely practised in China in the reign of the Longqing Emperor (r. 1567–72) during the Ming Dynasty (1368–1644).[46] Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers.[47] According to Voltaire (1742), the Turks derived their use of inoculation to neighbouring Circassia. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years".[48] The Greek physicians Emmanuel Timonis (1669–1720) from the island of Chios and Jacob Pylarinos (1659–1718) from Cephalonia practised smallpox inoculation at Constantinople in the beginning of 18th century[49] and published their work in Philosophical Transactions of the Royal Society in 1714.[50][51] This kind of inoculation and other forms of variolation were introduced into England by Lady Montagu, a famous English letter-writer and wife of the English ambassador at Istanbul between 1716 and 1718, who almost died from smallpox as a young adult and was physically scarred from it. Inoculation was adopted both in England and in America nearly half a century before Jenner's famous smallpox vaccine of 1796[52] but the death rate of about 2% from this method meant that it was mainly used during dangerous outbreaks of the disease and remained controversial.[42] It was noticed during the 18th century that people who had suffered from the less virulent cowpox were immune to smallpox, and the first recorded use of this idea was by a farmer Benjamin Jesty at Yetminster in Dorset, who had suffered the disease and transmitted it to his own family in 1774, his sons subsequently not getting the mild version of smallpox when later inoculated in 1789.

Edward Jenner, testimonial to the efficacy of vaccination. Wellcome L0020705
Jenner's 1802 testimonial to the efficacy of vaccination, signed by 112 members of the Physical Society, London
Jenner phipps 01
Dr Jenner performing his first vaccination on James Phipps, a boy of age 8. May 14th, 1796. Painting by Ernest Board (early 20th century).

It was Edward Jenner, a doctor in Berkeley in Gloucestershire, who established the procedure by introducing material from a cowpox vesicle on Sarah Nelmes, a milkmaid, into the arm of a boy named James Phipps. Two months later he inoculated the boy with smallpox and the disease did not develop. In 1798 Jenner published An Inquiry into the Causes and Effects of the Variolae Vacciniae, which coined the term vaccination and created widespread interest. He distinguished 'true' and 'spurious' cowpox (which did not give the desired effect) and developed an "arm-to-arm" method of propagating the vaccine from the vaccinated individual's pustule. Early attempts at confirmation were confounded by contamination with smallpox, but despite controversy within the medical profession and religious opposition to the use of animal material, by 1801 his report was translated into six languages and over 100,000 people were vaccinated.[42]

Since then vaccination campaigns have spread throughout the globe, sometimes prescribed by law or regulations (See Vaccination Acts). Vaccines are now used against a wide variety of diseases. Louis Pasteur further developed the technique during the 19th century, extending its use to killed agents protecting against anthrax and rabies. The method Pasteur used entailed treating the agents for those diseases so they lost the ability to infect, whereas inoculation was the hopeful selection of a less virulent form of the disease, and Jenner's vaccination entailed the substitution of a different and less dangerous disease. Pasteur adopted the name vaccine as a generic term in honour of Jenner's discovery.

Global-smallpox-cases
Global smallpox cases from 1920 - 2010. Source: WHO (2011)

Maurice Hilleman was the most prolific vaccine inventor, developing successful vaccines for measles, mumps, hepatitis A, hepatitis B, chickenpox, meningitis, pneumonia and Haemophilus influenzae.[53]

In modern times, the first vaccine-preventable disease targeted for eradication was smallpox. The World Health Organization (WHO) coordinated this global eradication effort. The last naturally occurring case of smallpox occurred in Somalia in 1977. In 1988, the governing body of WHO targeted polio for eradication by 2000. Although the target was missed, cases have been reduced by 99.99%.

In 2000, the Global Alliance for Vaccines and Immunization was established to strengthen routine vaccinations and introduce new and under-used vaccines in countries with a per capita GDP of under US $1000.

Society and culture

Poster for vaccination against smallpox
Poster for vaccination against smallpox

To eliminate the risk of outbreaks of some diseases, at various times governments and other institutions have employed policies requiring vaccination for all people. For example, an 1853 law required universal vaccination against smallpox in England and Wales, with fines levied on people who did not comply. Common contemporary U.S. vaccination policies require that children receive recommended vaccinations before entering public school.

Beginning with early vaccination in the nineteenth century, these policies were resisted by a variety of groups, collectively called antivaccinationists, who object on scientific, ethical, political, medical safety, religious, and other grounds. Common objections are that vaccinations do not work, that compulsory vaccination constitutes excessive government intervention in personal matters, or that the proposed vaccinations are not sufficiently safe.[54] Many modern vaccination policies allow exemptions for people who have compromised immune systems, allergies to the components used in vaccinations or strongly held objections.[55]

In countries with limited financial resources, limited vaccination coverage results in greater morbidity and mortality due to infectious disease.[56] More affluent countries are able to subsidize vaccinations for at-risk groups, resulting in more comprehensive and effective coverage. In Australia, for example, the Government subsidizes vaccinations for seniors and indigenous Australians.[57]

Public Health Law Research, an independent US based organization, reported in 2009 that there is insufficient evidence to assess the effectiveness of requiring vaccinations as a condition for specified jobs as a means of reducing incidence of specific diseases among particularly vulnerable populations;[58] that there is sufficient evidence supporting the effectiveness of requiring vaccinations as a condition for attending child care facilities and schools;[59] and that there is strong evidence supporting the effectiveness of standing orders, which allow healthcare workers without prescription authority to administer vaccine as a public health intervention.[60]

Londre wellcome institute boilly vaccinee

La vaccine or Le préjugé vaincu by Louis-Léopold Boilly, 1807

A doctor vaccinating a small girl, other girls with loosened Wellcome V0016682

A doctor vaccinating a small girl, other girls with loosened blouses wait their turn apprehensively by Lance Calkin

'Serum straight from the horse'., inoculation caricature Wellcome L0009827

German caricature showing von Behring extracting the serum with a tap.

The history of vaccination seen from an economic point of vi Wellcome V0011691

Les Malheurs de la Vaccine (The history of vaccination seen from an economic point of view: A pharmacy up for sale; an outmoded inoculist selling his premises; Jenner, to the left, pursues a skeleton with a lancet)

Litigation

Allegations of vaccine injuries in recent decades have appeared in litigation in the U.S. Some families have won substantial awards from sympathetic juries, even though most public health officials have said that the claims of injuries were unfounded.[61] In response, several vaccine makers stopped production, which the US government believed could be a threat to public health, so laws were passed to shield manufacturers from liabilities stemming from vaccine injury claims.[61] The safety and side effects of multiple vaccines have been tested in order to uphold the viability of vaccines as a barrier against disease. The influenza vaccine was tested in controlled trials and proven to have negligible side effects equal to that of a placebo.[62] Some concerns from families might have arisen from social beliefs and norms that cause them to mistrust or refuse vaccinations, contributing to this discrepancy in side effects that were unfounded.[63]

Opposition to vaccination

The cow pock
James Gillray's The Cow-Pock—or—the Wonderful Effects of the New Inoculation!, an 1802 caricature of vaccinated patients who feared it would make them sprout cowlike appendages.

Opposition to vaccination, from a wide array of vaccine critics, has existed since the earliest vaccination campaigns.[54] Although the benefits of preventing serious illness and death from infectious diseases greatly outweigh the risks of rare serious adverse effects following immunization,[64] disputes have arisen over the morality, ethics, effectiveness, and safety of vaccination. Some vaccination critics say that vaccines are ineffective against disease[65] or that vaccine safety studies are inadequate.[65] Some religious groups do not allow vaccination,[66] and some political groups oppose mandatory vaccination on the grounds of individual liberty.[54] In response, concern has been raised that spreading unfounded information about the medical risks of vaccines increases rates of life-threatening infections, not only in the children whose parents refused vaccinations, but also in those who cannot be vaccinated due to age or immunodeficiency, who could contract infections from unvaccinated carriers (see herd immunity).[67] Some parents believe vaccinations cause autism, although there is no scientific evidence to support this idea.[68] In 2011, Andrew Wakefield, a leading proponent of the theory that MMR vaccine causes autism, was found to have been financially motivated to falsify research data and was subsequently stripped of his medical license.[69] In the United States people who refuse vaccines for non-medical reasons have made up a large percentage of the cases of measles, and subsequent cases of permanent hearing loss and death caused by the disease.[70]

Global trend in believing vaccines are not safe
Global survey across 67 countries responding to the question: "Overall I think vaccines are safe". This image depicts the distribution of responses that replied "Strongly disagree" or "Tend to disagree" with the previous statement.[71]

Many parents do not vaccinate their children because they feel that diseases are no longer present due to vaccination.[72] This is a false assumption, since diseases held in check by immunization programs can and do still return if immunization is dropped. These pathogens could possibly infect vaccinated people, due to the pathogen's ability to mutate when it is able to live in unvaccinated hosts. In 2010, California had the worst whooping cough outbreak in 50 years. A possible contributing factor was parents choosing not to vaccinate their children.[73] There was also a case in Texas in 2012 where 21 members of a church contracted measles because they chose not to immunize.[73]

Vaccination and autism

The notion of a connection between vaccines and autism originated in a 1998 paper published in the The Lancet whose lead author was a physician named Andrew Wakefield. His study concluded that eight of the 12 patients (ages 3–10) developed behavioral symptoms consistent with autism following the MMR vaccine (an immunization against measles, mumps, and rubella).[74] The article was widely criticized for lack of scientific rigor and it was proven that Wakefield falsified data in the article.[74] In 2004, 10 of the original 12 co-authors (not including Wakefield) published a retraction of the article and stated the following: "We wish to make it clear that in this paper no causal link was established between MMR vaccine and autism as the data were insufficient."[75] In 2010, The Lancet officially retracted the article stating that several elements of the article were incorrect, including falsified data and protocols. This Lancet article has sparked a much greater anti-vaccination movement, particularly in the United States. Even though the article was fraudulent and was retracted, 1 in 4 parents still believe vaccines can cause autism.[76]

To date, all validated and definitive studies have shown that there is no correlation between vaccines and autism.[77]

Routes of administration

A vaccine administration may be oral, by injection (intramuscular, intradermal, subcutaneous), by puncture, transdermal or intranasal.[78] Several recent clinical trials have aimed to deliver the vaccines via mucosal surfaces to be up-taken by the common mucosal immunity system, thus avoiding the need for injections.[79]

Global trends in vaccination

Share-of-vaccinated-one-year-olds-globally
Global rate of vaccination against DPT (green), polio (yellow), measles (red), and HBV (black) from 1980 - 2015. Source: WHO and UN Populations Division

The World Health Organization (WHO) estimate that vaccination averts 2–3 million deaths per year (in all age groups), and up to 1.5 million children die each year due to diseases that could have been prevented by vaccination.[80] They estimate that 29% of deaths of children under five years old in 2013 were vaccine preventable. In other developing parts of the world, they are faced with the challenge of having a decreased availability of resources and vaccinations. Countries such as those in Sub-Saharan Africa cannot afford to provide the full range of childhood vaccinations.[81]

United States

DTP-Vaccination-rate-by-US-State-and-exemption-status-1
Vaccination rate by state, including exemptions allowed by state. Source: School Vaccination Assessment Report, 2016-2017

Vaccines have led to major decreases in the prevalence of infectious diseases in the United States. In 2007, studies regarding the effectiveness of vaccines on mortality or morbidity rates of those exposed to various diseases have shown almost 100% decreases in death rates, and about a 90% decrease in exposure rates.[82] This has allowed specific organizations and states to adopt standards for recommended early childhood vaccinations. Lower income families who are unable to otherwise afford vaccinations are supported by these organizations and specific government laws. The Vaccine for Children Program and the Social Security Act are two major players in supporting lower socioeconomic groups.

In 2000, the CDC declared that measles had been eliminated in the US (defined as no disease transmission for 12 continuous months).[83] However, with the growing anti-vaccine movement, the US has seen a resurgence of certain vaccine-preventable diseases. The measles virus has now lost its elimination status in the US as the number of measles cases continues to rise in recent years with a total of 17 outbreaks in 2018 and 465 outbreaks in 2019 (as of April 4th, 2019).[84]

Economics of vaccination

Health is often used as one of the metrics for determining the economic prosperity of a country. This is because healthier individuals are generally better suited to contributing to the economic development of a country than the sick.[85] There are many reasons for this. A person who is vaccinated for influenza, not only protects himself from the risk of influenza, but, simultaneously, prevents himself from infecting those around him.[86] This leads to a healthier society, which allows individuals to be more economically productive. Children are consequently able to attend school more often and have been shown to do better academically. Similarly, adults are able to work more often, more efficiently, and more effectively.[85][87]

Costs and benefits

On the whole, vaccinations induce a net benefit to society. Vaccines are often noted for their high return on investment (ROI) values, especially when considering the long-term effects.[88] Some vaccines have much higher ROI values than others. Studies have shown that the ratios of vaccination benefits to costs can differ substantially—from 27:1 for diphtheria/pertussis, to 13.5:1 for measles, 4.76:1 for varicella, and 0.68–1.1 : 1 for pneumococcal conjugate.[86] Some governments choose to subsidize the costs of vaccines, due to some of the high ROI values attributed to vaccinations.The United States subsidizes over half of all vaccines for children, which costs between $400 and $600 each. Although most children do get vaccinated, the adult population of the USA is still below the recommended immunization levels. Many factors can be attributed to this issue. Many adults who have other health conditions are unable to be safely immunized, whereas others opt not to be immunized for the sake of private financial benefits. Many Americans are underinsured, and, as such, are required to pay for vaccines out-of-pocket. Others are responsible for paying high deductibles and co-pays. Although vaccinations usually induce long-term economic benefits, many governments struggle to pay the high short-term costs associated with labor and production. Consequently, many countries neglect to provide such services.[86]

The Coalition for Epidemic Preparedness Innovations published a study in The Lancet in 2018 which estimated the costs of developing vaccines for diseases that could escalate into global humanitarian crises. They focused on 11 diseases which cause relatively few deaths at present and primarily strike the poor which have been highlighted as pandemic risks:

They estimated that it would cost between $2.8 billion and $3.7 billion to develop at least one vaccine for each of them. This should be set against the potential cost of an outbreak. The 2003 SARS outbreak in East Asia cost $54 billion.[89]

See also

References

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Further reading

  • Largent, Mark A. (2012). Vaccine: The Debate in Modern America. Baltimore: Johns Hopkins University Press. ISBN 978-1-4214-0607-7.
  • Carroll, Aaron E.; "Not Up for Debate: The Science Behind Vaccination", New York Times, 17 September 2015
  • Walloch, Karen L.; "The Antivaccine Heresy: Jacobson v. Massachusetts and the Troubled History of Compulsory Vaccination in the United States", University of Rochester Press, 2015, xii

External links

Edward Jenner

Edward Jenner, FRS FRCPE (17 May 1749 – 26 January 1823) was an English physician and scientist who was the pioneer of smallpox vaccine, the world's first vaccine. The terms "vaccine" and "vaccination" are derived from Variolae vaccinae (smallpox of the cow), the term devised by Jenner to denote cowpox. He used it in 1796 in the long title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox.Jenner is often called "the father of immunology", and his work is said to have "saved more lives than the work of any other human". In Jenner's time, smallpox killed around 10 percent of the population, with the number as high as 20 percent in towns and cities where infection spread more easily. In 1821 he was appointed physician extraordinary to King George IV, and was also made mayor of Berkeley and justice of the peace. A member of the Royal Society, in the field of zoology he was the first person to describe the brood parasitism of the cuckoo. In 2002, Jenner was named in the BBC's list of the 100 Greatest Britons.

Feline vaccination

Vaccination plays a vital role in protecting cats from infectious diseases, some of which are potentially fatal. They can be exposed to these diseases from their environment, other pets, or even humans.

HealthforAnimals, the global animal medicines association, summarizes our role in ensuring animals are properly vaccinated: "We also have a moral obligation towards animals in our care, to prevent diseases rather than waiting until the animal gets sick, suffers and requires treatment."

HPV vaccine

Human papilloma virus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus. Available vaccines protect against either two, four, or nine types of HPV. All vaccines protect against at least HPV type 16 and 18 that cause the greatest risk of cervical cancer. It is estimated that they may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and possibly some mouth cancer. They additionally prevent some genital warts with the vaccines against 4 and 9 HPV types providing greater protection.The World Health Organization (WHO) recommends HPV vaccines as part of routine vaccinations in all countries, along with other prevention measures. The vaccines require two or three doses depending on a person's age and immune status. Vaccinating girls around the ages of nine to thirteen is typically recommended. The vaccines provide protection for at least 5 to 10 years. Cervical cancer screening is still required following vaccination. Vaccinating a large portion of the population may also benefit the unvaccinated. In those already infected the vaccines are not effective.HPV vaccines are very safe. Pain at the site of injection occurs in about 80% of people. Redness and swelling at the site and fever may also occur. No link to Guillain–Barré syndrome has been found.The first HPV vaccine became available in 2006. As of 2017, 71 countries include it in their routine vaccinations, at least for girls. They are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$47 a dose as of 2014. In the United States it costs more than US$200. Vaccination may be cost effective in the developing world.

Hepatitis B vaccine

Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended for health-care workers to be vaccinated. In healthy people routine immunization results in more than 95% of people being protected.Blood testing to verify that the vaccine has worked is recommended in those at high risk. Additional doses may be needed in people with poor immune function but are not necessary for most people. In those who have been exposed to the hepatitis B virus but not immunized, hepatitis B immune globulin should be given in addition to the vaccine. The vaccine is given by injection into a muscle.Serious side effects from the hepatitis B vaccine are very uncommon. Pain may occur at the site of injection. It is safe for use during pregnancy or while breastfeeding. It has not been linked to Guillain–Barré syndrome. The current vaccines are produced with recombinant DNA techniques. They are available both by themselves and in combination with other vaccines.The first hepatitis B vaccine was approved in the United States in 1981. A recombinant version came to market in 1986. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. As of 2014, the wholesale cost in the developing world is US$0.58–13.20 per dose. In the United States it costs US$50–100.

Immunization

Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an agent (known as the immunogen).

When this system is exposed to molecules that are foreign to the body, called non-self, it will orchestrate an immune response, and it will also develop the ability to quickly respond to a subsequent encounter because of immunological memory. This is a function of the adaptive immune system. Therefore, by exposing an animal to an immunogen in a controlled way, its body can learn to protect itself: this is called active immunization.

The most important elements of the immune system that are improved by immunization are the T cells, B cells, and the antibodies B cells produce. Memory B cells and memory T cells are responsible for a swift response to a second encounter with a foreign molecule. Passive immunization is direct introduction of these elements into the body, instead of production of these elements by the body itself.

Immunization is done through various techniques, most commonly vaccination. Vaccines against microorganisms that cause diseases can prepare the body's immune system, thus helping to fight or prevent an infection. The fact that mutations can cause cancer cells to produce proteins or other molecules that are known to the body forms the theoretical basis for therapeutic cancer vaccines. Other molecules can be used for immunization as well, for example in experimental vaccines against nicotine (NicVAX) or the hormone ghrelin in experiments to create an obesity vaccine.

Immunizations are often widely stated as less risky and an easier way to become immune to a particular disease than risking a milder form of the disease itself. They are important for both adults and children in that they can protect us from the many diseases out there. Immunization not only protects children against deadly diseases but also helps in developing children's immune systems. Through the use of immunizations, some infections and diseases have almost completely been eradicated throughout the United States and the World. One example is polio. Thanks to dedicated health care professionals and the parents of children who vaccinated on schedule, polio has been eliminated in the U.S. since 1979. Polio is still found in other parts of the world so certain people could still be at risk of getting it. This includes those people who have never had the vaccine, those who didn't receive all doses of the vaccine, or those traveling to areas of the world where polio is still prevalent.

Active immunization/vaccination has been named one of the "Ten Great Public Health Achievements in the 20th Century".

Influenza vaccine

Influenza vaccines, also known as flu shots or flu jabs, are vaccines that protect against infection by influenza viruses. A new version of the vaccine is developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. The United States Centers for Disease Control and Prevention (CDC) estimates that vaccination against influenza reduces sickness, medical visits, hospitalizations, and deaths. When an immunized worker does catch the flu, they are on average back at work a half day sooner. Vaccine effectiveness in those under two years old and over 65 years old remains unknown due to the low quality of the research. Vaccinating children may protect those around them.The World Health Organization (WHO) and the CDC recommend yearly vaccination for nearly all people over the age of six months, especially those at high risk. The European Centre for Disease Prevention and Control also recommends yearly vaccination of high risk groups. These groups include pregnant women, the elderly, children between six months and five years of age, those with other health problems, and those who work in healthcare.The vaccines are generally safe. Fever occurs in five to ten percent of children vaccinated. Temporary muscle pains or feelings of tiredness may occur as well. In certain years, the vaccine has been linked to an increase in Guillain–Barré syndrome among older people at a rate of about one case per million doses. It should not be given to those with severe allergies to previous versions of the vaccine. Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless recommended for people with egg allergies, even if severe. The vaccines come in both inactive and weakened viral forms. The inactive version should be used for those who are pregnant. They come in forms that are injected into a muscle, sprayed into the nose, or injected into the middle layer of the skin.Vaccination against influenza began in the 1930s with large scale availability in the United States beginning in 1945. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale price in the developing world is about $5.25 USD per dose as of 2014. In the United States, it costs less than $25 USD as of 2015.

Inoculation

The terms inoculation, vaccination, and immunization are often used synonymously to refer to artificial induction of immunity against various infectious diseases. However, there are some important historical and current differences. In English medicine, inoculation referred only to the practice of variolation until the very early 1800s. When Edward Jenner introduced smallpox vaccine in 1798, this was initially called cowpox inoculation or vaccine inoculation. Soon, to avoid confusion, smallpox inoculation continued to be referred to as variolation (from Variola = smallpox) and cowpox inoculation was referred to as vaccination (from Jenner's use of variolae vaccinae = smallpox of the cow). Then, in 1891, Louis Pasteur proposed that the terms vaccine and vaccination should be extended to include the new protective procedures being developed. Immunization refers to the use of all vaccines but also extends to the use of antitoxin, which contains preformed antibody such as to diphtheria or tetanus exotoxins. Inoculation is now more or less synonymous in nontechnical usage with injection and the like, and questions along the lines of "Have you had your flu injection/vaccination/inoculation/immunization?" should not cause confusion. The focus is on what is being given and why, not the literal meaning of the technique used.Inoculation also has a specific meaning for procedures done in vitro. These include the transfer of microorganisms into and from laboratory apparatus such as test tubes and petri dishes in research and diagnostic laboratories, and also in commercial applications such as brewing, baking, oenology (wine making), and the production of antibiotics.

In almost all cases the material inoculated is called the Inoculum, or less commonly the inoculant, although the term culture is also used for work done in vitro.

MMR vaccine

The MMR vaccine is a vaccine against measles, mumps, and rubella (German measles). The first dose is generally given to children around 9 to 15 months of age, with a second dose at 15 months to 6 years of age, with at least 4 weeks between the doses. After two doses, 97% of people are protected against measles, 88% against mumps, and at least 97% against rubella. The vaccine is also recommended in those who do not have evidence of immunity, those with well controlled HIV/AIDS, and within 72 hours of exposure to measles among those who are incompletely immunized. It is given by injection.The MMR vaccine is widely used around the world, with over 500 million doses having been given in over 100 countries as of 2001. Measles resulted in 2.6 million deaths per year before immunization became common. This has decreased to 122,000 deaths per year as of 2012, mostly in low income countries. Through vaccination, as of 2018, rates of measles in North and South America are very low. Rates of disease have been seen to increase in populations which go unvaccinated. Between 2000 and 2016, vaccination decreased measles deaths by a further 84%.Side effects of immunization are generally mild and go away without any specific treatment. These may include fever, and pain or redness at the injection site. Severe allergic reactions occur in about one in a million people. The MMR vaccine is not recommended during pregnancy, but may be given while breastfeeding. The vaccine is safe to give at the same time as other vaccines. Being recently immunized does not increase the risk of passing measles, mumps, or rubella on to others. Vaccination does not increase the risk of autism. The MMR vaccine is a mixture of live weakened viruses of the three diseases.The MMR vaccine was developed by Maurice Hilleman. It was licensed for use by Merck in 1971. Stand alone measles, mumps, and rubella vaccines had been previously licensed in 1963, 1967, and 1969 respectively. Recommendations for a second dose were introduced in 1989. The MMRV vaccine which also covers chickenpox may be used instead. An MR vaccine, without coverage for mumps, is also occasionally used.

MMR vaccine and autism

Claims of a link between the MMR vaccine and autism have been extensively investigated and found to be false. The link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud, characterised as "perhaps the most damaging medical hoax of the last 100 years". The fraudulent research paper authored by Andrew Wakefield and published in The Lancet claimed to link the vaccine to colitis and autism spectrum disorders. The paper was retracted in 2010 but is still cited by anti-vaccinationists.The claims in the paper were widely reported, leading to a sharp drop in vaccination rates in the UK and Ireland. Promotion of the claimed link, which continues in anti-vaccination propaganda despite being refuted, has led to an increase in the incidence of measles and mumps, resulting in deaths and serious permanent injuries. Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the Institute of Medicine of the US National Academy of Sciences, the UK National Health Service, and the Cochrane Library all found no link between the MMR vaccine and autism. Physicians, medical journals, and editors have described Wakefield's actions as fraudulent and tied them to epidemics and deaths.An investigation by journalist Brian Deer found that Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest, had manipulated evidence, and had broken other ethical codes. The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet's editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010 and was struck off the Medical Register, meaning he could no longer practise as a physician in the UK. In 2011, Deer provided further information on Wakefield's improper research practices to the British Medical Journal, which in a signed editorial described the original paper as fraudulent. The scientific consensus is that there is no link between the MMR vaccine and autism and that the vaccine's benefits greatly outweigh its potential risks.

Measles

Measles is a highly contagious infectious disease caused by the measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than 40 °C (104 °F), cough, runny nose, and inflamed eyes. Small white spots known as Koplik's spots may form inside the mouth two or three days after the start of symptoms. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms. Common complications include diarrhea (in 8% of cases), middle ear infection (7%), and pneumonia (6%). Less commonly seizures, blindness, or inflammation of the brain may occur. Other names include morbilli, rubeola, red measles, and English measles. Both rubella, which is sometimes called "German measles", and roseola are different diseases caused by unrelated viruses.Measles is an airborne disease which spreads easily through the coughs and sneezes of infected people. It may also be spread through contact with saliva or nasal secretions. Nine out of ten people who are not immune and share living space with an infected person will be infected. People are infectious to others from four days before to four days after the start of the rash. Most people do not get the disease more than once. Testing for the measles virus in suspected cases is important for public health efforts.The measles vaccine is effective at preventing the disease, and is often delivered in combination with other vaccines. Vaccination resulted in a 75% decrease in deaths from measles between 2000 and 2013, with about 85% of children worldwide being vaccinated as of 2014. Once a person has become infected, no specific treatment is available, although supportive care may improve outcomes. Such care may include oral rehydration solution (slightly sweet and salty fluids), healthy food, and medications to control the fever. Antibiotics may be used if a secondary bacterial infection such as bacterial pneumonia occurs. Vitamin A supplementation is also recommended in the developing world.Measles affects about 20 million people a year, primarily in the developing areas of Africa and Asia. While often regarded as a childhood illness, it can affect people of any age. It is one of the leading vaccine-preventable disease causes of death. In 1980, 2.6 million people died of it, and in 1990, 545,000 died; by 2014, global vaccination programs had reduced the number of deaths from measles to 73,000. Rates of disease and deaths, however, increased in 2017 to 2019 due to a decrease in immunization. The risk of death among those infected is about 0.2%, but may be up to 10% in people with malnutrition. Most of those who die from the infection are less than five years old. Measles is not believed to affect other animals.

Measles vaccine

Measles vaccine is a vaccine that prevents measles. Nearly all of those who do not develop immunity after a single dose develop it after a second dose. When rates of vaccination within a population are greater than 92% outbreaks of measles typically no longer occur; however, they may occur again if rates of vaccination decrease. The vaccine's effectiveness lasts many years. It is unclear if it becomes less effective over time. The vaccine may also protect against measles if given within a couple of days after exposure to measles.The vaccine is generally safe, even for those with HIV infections. Side effects are usually mild and short lived. These may include pain at the site of injection or mild fever. Anaphylaxis has been documented in about 3.5–10 cases per million doses. Rates of Guillain–Barré syndrome, autism and inflammatory bowel disease do not appear to be increased by measles vaccination.The vaccine is available both by itself and in combinations such as the MMR vaccine (a combination with the rubella vaccine and mumps vaccine) or the MMRV vaccine (a combination of MMR with the chickenpox vaccine). The measles vaccine is equally effective for preventing measles in all formulations, but side effects vary depending with the combination. The World Health Organization recommends measles vaccine be given at nine months of age in areas of the world where the disease is common, or at twelve months where the disease is not common. Measles vaccine is based on a live but weakened strain of measles. It comes as a dried powder which is mixed with a specific liquid before being injected either just under the skin or into a muscle. Verification that the vaccine was effective can be determined by blood tests.About 85% of children globally have received this vaccine as of 2013. In 2015, at least 160 countries provided two doses in their routine immunization. The measles vaccine was first introduced in 1963. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about 0.70 USD per dose as of 2014. As outbreaks easily occur in under-vaccination populations, the disease is seen as a test of sufficient vaccination within a population.

Polio vaccine

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccines cause about three cases of vaccine-associated paralytic poliomyelitis per million doses given. This compares with 5,000 cases per million who are paralysed following a polio infection. Both are generally safe to give during pregnancy and in those who have HIV/AIDS but are otherwise well.The first polio vaccine was the inactivated polio vaccine. It was developed by Jonas Salk and came into use in 1955. The oral polio vaccine was developed by Albert Sabin and came into commercial use in 1961. They are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.25 per dose for the oral form as of 2014. In the United States, it costs between $25 and $50 for the inactivated form.

Smallpox

Smallpox was an infectious disease caused by one of two virus variants, Variola major and Variola minor. The last naturally occurring case was diagnosed in October 1977 and the World Health Organization (WHO) certified the global eradication of the disease in 1980. The risk of death following contracting the disease was about 30%, with higher rates among babies. Often those who survived had extensive scarring of their skin and some were left blind.The initial symptoms of the disease included fever and vomiting. This was followed by formation of sores in the mouth and a skin rash. Over a number of days the skin rash turned into characteristic fluid filled bumps with a dent in the center. The bumps then scabbed over and fell off leaving scars. The disease used to spread between people or via contaminated objects. Prevention was by the smallpox vaccine. Once the disease had developed, certain antiviral medication may have helped.The origin of smallpox is unknown. The earliest evidence of the disease dates to the 3rd century BCE in Egyptian mummies. The disease historically occurred in outbreaks. In 18th-century Europe, it is estimated 400,000 people per year died from the disease, and one-third of the cases resulted in blindness. These deaths included those of four reigning monarchs and a queen consort. Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. As recently as 1967, 15 million cases occurred a year.Edward Jenner discovered in 1798 that vaccination could prevent smallpox. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. The term "smallpox" was first used in Britain in the 15th century to distinguish the disease from syphilis, which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague.

Smallpox vaccine

Smallpox vaccine, the first successful vaccine to be developed, was introduced by Edward Jenner in 1796. He followed up his observation that milkmaids who had previously caught cowpox did not later catch smallpox by showing that inoculated cowpox protected against inoculated smallpox.

Vaccination policy

Vaccination policy refers to the health policy a government adopts in relation to vaccination. Vaccinations are voluntary in some countries and mandatory in others, as part of their public health system. Some governments pay all or part of the costs of vaccinations in a national vaccination schedule. Vaccination policies are built with the purpose of eradicating disease from, or creating a herd immunity for the population the government aims to protect.

Vaccination schedule

A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence.

A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or reduce the effects of infection by any natural or "wild" pathogen. Many vaccines require multiple doses for maximum effectiveness, either to produce sufficient initial immune response or to boost response that fades over time. For example, tetanus vaccine boosters are often recommended every 10 years. Vaccine schedules are developed by governmental agencies or physicians groups to achieve maximum effectiveness using required and recommended vaccines for a locality while minimizing the number of health care system interactions. Over the past two decades, the recommended vaccination schedule has grown rapidly and become more complicated as many new vaccines have been developed.Some vaccines are recommended only in certain areas (countries, sub national areas, or at-risk populations) where a disease is common. For instance, yellow fever vaccination is on the routine vaccine schedule of French Guiana, is recommended in certain regions of Brazil but in the United States is only given to travelers heading to countries with a history of the disease. In developing countries, vaccine recommendations also take into account the level of health care access, the cost of vaccines and issues with vaccine availability and storage. Sample vaccination schedules discussed by the World Health Organization show a developed country using a schedule which extends over the first five years of a child's life and uses vaccines which cost over $700 including administration costs while a developing country uses a schedule providing vaccines in the first 9 months of life and costing only $25. This difference is due to the lower cost of health care, the lower cost of many vaccines provided to developing nations, and that more expensive vaccines, often for less common diseases, are not utilized.

Vaccine

A vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future. Vaccines can be prophylactic (example: to prevent or ameliorate the effects of a future infection by a natural or "wild" pathogen), or therapeutic (e.g., vaccines against cancer are being investigated).The administration of vaccines is called vaccination. Vaccination is the most effective method of preventing infectious diseases; widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the restriction of diseases such as polio, measles, and tetanus from much of the world. The effectiveness of vaccination has been widely studied and verified; for example, vaccines that have proven effective include the influenza vaccine, the HPV vaccine, and the chicken pox vaccine. The World Health Organization (WHO) reports that licensed vaccines are currently available for twenty-five different preventable infections.The terms vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow), the term devised by Edward Jenner to denote cowpox. He used it in 1798 in the long title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox. In 1881, to honor Jenner, Louis Pasteur proposed that the terms should be extended to cover the new protective inoculations then being developed.

Vaccine hesitancy

Vaccine hesitancy, a reluctance or refusal to be vaccinated or to have one's children vaccinated, is identified by the World Health Organization as one of the top ten global health threats of 2019. Arguments against vaccination are contradicted by overwhelming scientific consensus about the safety and efficacy of vaccines.Hesitancy results from public debates around the medical, ethical and legal issues related to vaccines. It has existed since the invention of vaccination, and pre-dates the coining of the terms "vaccine" and "vaccination" by nearly 80 years. The specific hypotheses raised by anti-vaccination advocates have been found to change over time. Vaccine hesitancy often results in disease outbreaks and deaths from vaccine-preventable diseases.Bills for mandatory vaccination have been considered for legislation, including California Senate Bill 277 and Australia's No Jab No Pay, all of which have been strenuously opposed by anti-vaccination activists. Opposition to mandatory vaccination may be based on anti-vaccine sentiment, or concern that it violates civil liberties or reduces public trust in vaccination.

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 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 also increased.The disease is caused by yellow fever virus and is spread by the bite of an infected female mosquito. It infects only humans, other primates, and several species of mosquitoes. In cities, it 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 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 the population of the transmitting mosquito. In areas where yellow fever is common and vaccination is uncommon, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks. Once infected, management is symptomatic with no specific measures effective against the virus. Death occurs in up to half of those who get severe disease.In 2013, yellow fever resulted in about 127,000 severe infections and 45,000 deaths, with nearly 90% of these occurring in African nations. Nearly 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, from where it spread to South America through the slave trade in the 17th century. 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 seen as one of the most dangerous infectious diseases. In 1927 yellow fever virus became the first human virus to be isolated.

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