Vaccination

Vaccination

Child receiving an oral polio vaccine
ICD-9-CM 99.3-99.5

Vaccination is the administration of antigenic material (a vaccine) to stimulate an individual's immune system to develop adaptive immunity to a pathogen. Vaccines can prevent or ameliorate 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, measles, and tetanus from much of the world. The World Health Organization (WHO) reports that licensed vaccines are currently available for twenty-five different preventable infections.[5]

The active agent of a vaccine may be intact but inactivated (non-infective) or attenuated (with reduced infectivity) forms of the causative pathogens, or purified components of the pathogen that have been found to be highly immunogenic (e.g., outer coat proteins of a virus). Toxoids are produced for immunization against toxin-based diseases, such as the modification of tetanospasmin toxin of tetanus to remove its toxic effect but retain its immunogenic effect.[6]

Smallpox was most likely the first disease people tried to prevent by inoculation.[7][8] and was the first disease for which a vaccine was produced. The smallpox vaccine was invented in 1796 by the British 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.[9] 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').[7][9] Smallpox was a contagious and deadly disease, causing the deaths of 20–60% of infected adults and over 80% of infected children.[10] When smallpox was finally eradicated in 1979, it had already killed an estimated 300–500 million people[11][12][13] in the 20th century.

In common speech, vaccination and immunization have a similar meaning. This distinguishes it from inoculation, which uses unweakened live pathogens, although in common usage either can refer to an immunization. Vaccination efforts have been met with some controversy on scientific, ethical, political, medical safety, and religious grounds. In rare cases, vaccinations can injure people.[14] 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.

Effectiveness

Vaccination has historically been the most effective means to fight and eradicate infectious diseases. Limitations to its effectiveness nevertheless exist.[15] Sometimes, protection fails because the host's immune system simply does not respond adequately or at all. Lack of response commonly results from clinical factors such as diabetes, steroid use, HIV infection or age. It also might fail for genetic reasons if the host's immune system includes no strains of B cells that can generate antibodies suited to reacting effectively and binding to the antigens associated with the pathogen.

Even if the host does develop antibodies, protection might not be adequate; immunity might develop too slowly to be effective in time, the antibodies might not disable the pathogen completely, or there might be multiple strains of the pathogen, not all of which are equally susceptible to the immune reaction. However, even a partial, late, or weak immunity, such as a one resulting from cross-immunity to a strain other than the target strain, may mitigate an infection, resulting in a lower mortality rate, lower morbidity, and faster recovery.

Adjuvants commonly are used to boost immune response, particularly for older people (50–75 years and up), whose immune response to a simple vaccine may have weakened.[16]

Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.[17]

The efficacy or performance of the vaccine is dependent on a number of factors:

If a vaccinated individual does develop the disease vaccinated against (breakthrough infection), the disease is likely to be less virulent than in unvaccinated victims.[19]

The following are important considerations in the effectiveness of a vaccination program:

  1. careful modeling to anticipate the impact that an immunization campaign will have on the epidemiology of the disease in the medium to long term
  2. ongoing surveillance for the relevant disease following introduction of a new vaccine
  3. maintenance of high immunization rates, even when a disease has become rare.

In 1958, there were 763,094 cases of measles in the United States; 552 deaths resulted.[20][21] After the introduction of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56).[21] In early 2008, there were 64 suspected cases of measles. Fifty-four of those infections were associated with importation from another country, although only 13% were actually acquired outside the United States; 63 of the 64 individuals either had never been vaccinated against measles or were uncertain whether they had been vaccinated.[21]

Vaccination has contributed to the eradication of smallpox, one of the most contagious and deadly diseases in humans. Other diseases such as rubella, polio, measles, mumps, chickenpox, and typhoid are nowhere near as common as they were a hundred years ago. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called herd immunity. Polio, which is transmitted only between humans, is targeted by an extensive eradication campaign that has seen endemic polio restricted to only parts of three countries (Afghanistan, Nigeria, and Pakistan).[22] However, the difficulty of reaching all children as well as cultural misunderstandings have caused the anticipated eradication date to be missed several times.

Vaccination also helps prevent the development of antibiotic resistance. For example, by greatly reducing the incidence of pneumonia caused by Streptococcus pneumoniae, vaccination programs have greatly reduced the prevalence of infections resistant to penicillin or other first-line antibiotics.[23][24]

Side effects

The Centers for Disease Control and Prevention (CDC) has compiled a list of vaccines and their possible side effects.[25] 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.[26] 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.[26] 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.[27] 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.[28]

Mechanism of function

Polio vaccination started in Sweden in 1957.

Generically, the process of artificial induction of immunity, in an effort to protect against infectious disease, works by '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.[29]

Some vaccines are administered after the patient already has contracted a disease. Vaccines given after exposure to smallpox, within the first three days, are reported to attenuate the disease considerably, and vaccination up to a week after exposure probably offers some protection from disease or may modify the severity of disease.[30] The first rabies immunization was given by Louis Pasteur to a child after he was bitten by a rabid dog. Since then, it has been found that, in people with healthy immune systems, four doses of rabies vaccine over 14 days, wound care, and treatment of the bite with rabies immune globulin, commenced as soon as possible after exposure, is effective in preventing rabies in humans.[31] 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 hypodermic injection as they are not absorbed reliably through the intestines. Live attenuated polio, 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, while passive immunity (the transfer of antibodies) has immediate effect.[32]

Adjuvants and preservatives

Vaccines typically contain one or more adjuvants, used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum. This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who have an adverse reaction to adsorbed tetanus toxoid may be given the simple vaccine when the time comes for a booster.

In the preparation for the 1990 Persian Gulf campaign, whole cell pertussis vaccine was used as an adjuvant for anthrax vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent.

Vaccines may also contain preservatives to prevent contamination with bacteria or fungi. Until recent years, the preservative thimerosal was used in many vaccines that did not contain live virus. As of 2005, the only childhood vaccine in the U.S. that contains thimerosal in greater than trace amounts is the influenza vaccine,[33] which is currently recommended only for children with certain risk factors.[34] Single-dose influenza vaccines supplied in the UK do not list thiomersal (its UK name) in the ingredients. Preservatives may be used at various stages of production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.[35]

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.[36][37]

Vaccinations began in the 18th century with the work of Edward Jenner and the smallpox vaccine.[38][39][40]

Types

Vaccines work by presenting a foreign antigen to the immune system to evoke an immune response, but there are several ways to do this. Four main types are currently in clinical use:

  1. An inactivated vaccine consists of virus or bacteria that are grown in culture and then killed using a method such as heat or formaldehyde. Although the virus or bacteria particles are destroyed and cannot replicate, the virus capsid proteins or bacterial wall are intact enough to be recognized and remembered by the immune system and evoke a response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles. Since the properly produced vaccine does not reproduce, booster shots are required periodically to reinforce the immune response.
  2. In an attenuated vaccine, live virus or bacteria with very low virulence are administered. They will replicate, but locally or very slowly. Since they do reproduce and continue to present antigen to the immune system beyond the initial vaccination, boosters may be required less often. These vaccines may be produced by passaging, for example, adapting a virus into different host cell cultures, such as in animals, or at suboptimal temperatures, allowing selection of less virulent strains, or by mutagenesis or targeted deletions in genes required for virulence. There is a small risk of reversion to virulence, which is smaller in vaccines with deletions. Attenuated vaccines also cannot be used by immunocompromised individuals. Reversions of virulence were described for a few attenuated viruses of chickens (infectious bursal disease virus, avian infectious bronchitis virus, avian infectious laryngotracheitis virus , avian metapneumovirus )[41]
  3. Virus-like particle vaccines consist of viral protein(s) derived from the structural proteins of a virus. These proteins can self-assemble into particles that resemble the virus from which they were derived but lack viral nucleic acid, meaning that they are not infectious. Because of their highly repetitive, multivalent structure, virus-like particles are typically more immunogenic than subunit vaccines (described below). The human papillomavirus and Hepatitis B virus vaccines are two virus-like particle-based vaccines currently in clinical use.
  4. A subunit vaccine presents an antigen to the immune system without introducing viral particles, whole or otherwise. One method of production involves isolation of a specific protein from a virus or bacterium (such as a bacterial toxin) and administering this by itself. A weakness of this technique is that isolated proteins may have a different three-dimensional structure than the protein in its normal context, and will induce antibodies that may not recognize the infectious organism. In addition, subunit vaccines often elicit weaker antibody responses than the other classes of vaccines.

A number of other vaccine strategies are under experimental investigation. These include DNA vaccination and recombinant viral vectors.

History

Jenner's handwritten draft of the first vaccination

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.[53]

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. But 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.[54]

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 honor of Jenner's discovery.

A doctor performing a typhoid vaccination in Texas, 1943

Maurice Hilleman was the most prolific vaccine inventor, developing successful vaccines for measles, mumps, hepatitis A, hepatitis B, chickenpox, meningitis, pneumonia and 'Haemophilus influenzae'.[55]

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, eradication is very close.

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

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.[56] Many modern vaccination policies allow exemptions for people who have compromised immune systems, allergies to the components used in vaccinations or strongly held objections.[57]

In countries with limited financial resources, limited vaccination coverage results in greater morbidity and mortality due to infectious disease.[58] 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.[59]

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;[60] that there is sufficient evidence supporting the effectiveness of requiring vaccinations as a condition for attending child care facilities and schools;[61] 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.[62]

Vaccination-autism controversy

In the MMR vaccine controversy, a fraudulent 1998 paper by Andrew Wakefield, originally published in The Lancet, presented supposed evidence that the MMR vaccine (an immunization against measles, mumps and rubella that is typically first administered to children shortly after their first birthday) was linked to the onset of autism spectrum disorders.[63] The article was widely criticized for lack of scientific rigour, partially retracted in 2004 by Wakefield's co-authors,[64] and was fully retracted by The Lancet in 2010.[65] Wakefield was struck off the UK's medical registry for the fraud.[66]

This Lancet article has sparked a much greater anti-vaccination movement, primarily in the United States. Even though the article was fraudulent and was retracted, 1 in 4 parents still believe vaccines can cause autism.[67] Many parents do not vaccinate their children because they feel that diseases are no longer present due to vaccination.[68] 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.[69] There was also a case in Texas in 2012 where 21 members of a church contracted measles because they chose not to immunize.[69]

Routes of administration

Air France Vaccinations Centre in the 7th arrondissement of Paris

A vaccine administration may be oral, by injection (intramuscular, intradermal, subcutaneous), by puncture, transdermal or intranasal.[70] 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.[71]

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 which could have been prevented by vaccination.[72] 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.[73] The increasing rates of vaccinations will have lasting effects on future generations; the greater the group of people who become vaccinated can ultimately drive down the spread of infection through herd immunity.{citation needed}}



United States

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.[74] 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.

See also

References

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