Non-specific effect of vaccines

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Women and children in line for a vaccination in Guinea-Bissau. It is estimated that millions of child deaths could be prevented every year if the non-specific effects of vaccines were taken into consideration in immunization programs. Women waiting for consulta.JPG
Women and children in line for a vaccination in Guinea-Bissau. It is estimated that millions of child deaths could be prevented every year if the non-specific effects of vaccines were taken into consideration in immunization programs.

Non-specific effects of vaccines (also called "heterologous effects" or "off-target effects") are effects which go beyond the specific protective effects against the targeted diseases. Non-specific effects can be strongly beneficial by increasing protection against non-targeted infections. [1] This has been shown with two live attenuated vaccines, BCG vaccine and measles vaccine, through multiple randomized controlled trials. [1] Theoretically, non-specific effects of vaccines may be detrimental, increasing overall mortality despite providing protection against the target diseases. Although observational studies suggest that diphtheria-tetanus-pertussis vaccine (DTP) may be highly detrimental, [1] these studies are at high risk of bias and have failed to replicate when conducted by independent groups. [2]

Contents

Ongoing research suggests that non-specific effects of vaccines may depend on the vaccine, the vaccination schedule, and the sex of the infant. [3] For example, one hypothesis suggests that all live attenuated vaccines reduce mortality more than explained by prevention of target infections, while all inactivated vaccines may increase overall mortality despite providing protection against the target disease. These effects may be long-lasting, at least up to the time point where a new type of vaccine is given. The non-specific effects can be very pronounced, with significant effects on overall mortality and morbidity. In a situation with herd immunity to the target disease, the non-specific effects can be more important for overall health than the specific vaccine effects. [3]

The non-specific effects should not be confused with the side effects of vaccines (such as local reactions at the site of vaccination or general reactions such as fever, head ache or rash, which usually resolve within days to weeks – or in rare cases anaphylaxis). Rather, non-specific effects represent a form of general immunomodulation, with important consequences for the immune system's ability to handle subsequent challenges.

It is estimated that millions of child deaths in low income countries could be prevented every year if the non-specific effects of vaccines were taken into consideration in immunization programs. [1]

History

The Bandim Health Project Office built in 2008. Bandim Health Project.JPG
The Bandim Health Project Office built in 2008.

The hypothesis that vaccines have non-specific effects was formulated in the early 1990s by Peter Aaby at the Bandim Health Project in West Africa. [4]

The first indication of the importance of the non-specific effects of vaccines came in a series of randomized controlled trials (RCTs) in the late 1980s. It was tested whether a high-titer (high-dose) measles vaccine (HTMV) given at 4–6 months of age was as effective against measles infection as the standard measles vaccine (MV) given at 9 months of age. Early administration of the HTMV prevented measles infection just as effectively as did the standard MV given at 9 months of age.

However, early administration of the HTMV was associated with twofold higher overall mortality among females (there was no difference in mortality for males). [5] [6] [7] In other words, the girls given HTMV died more often despite having the same protection against measles as the infants given standard MV. The discovery forced WHO to withdraw the HTMV in 1992. [8] It was later discovered that it was not the HTMV, but rather a subsequent inactivated vaccine (DTP or IPV for different children), that caused the increase in female mortality. [9] Although the mechanism was different than initially thought, this finding represents unexpected effects of a change in the vaccine program not attributable to the disease-specific protection provided by the vaccines.

This first observation that vaccines could protect against the target disease but at the same time affect mortality after infection with other pathogens, in a sex-differential manner, led to several further studies showing that other vaccines might also have such nonspecific effects.

Live attenuated versus inactivated vaccines

Numerous observational studies and randomised trials (RCTs) have found that the impact on mortality of live and inactivated vaccines differ markedly. All live vaccines studied so far (BCG, measles vaccine, oral polio vaccine (OPV) and smallpox vaccine) have been shown to reduce mortality more than can be explained by prevention of the targeted infection(s). In contrast, inactivated vaccines (diphtheria-tetanus-pertussis (DTP), hepatitis B, inactivated polio vaccine) may have deleterious effects in spite of providing target disease protection. [10]

BCG vaccine

The live attenuated BCG vaccine developed against tuberculosis has been shown to have strong beneficial effects on the ability to combat non-tuberculosis infections. [3] [11]

Scar after BCG vaccination A scar after received Bacillus Calmette-Guerin.jpg
Scar after BCG vaccination

Several studies have suggested that BCG vaccination may reduce atopy, particularly when given early in life. Furthermore, in multiple observational studies BCG vaccination has been shown to provide beneficial effects on overall mortality. [12] These observations encouraged randomised controlled trials to examine BCG vaccination's beneficial non-specific effects on overall health. [13] [14] [15] [16] Since BCG vaccination is recommended to be given at birth in countries that have a high incidence of tuberculosis it would have been unethical to randomize children into "BCG" vs. "no BCG" groups. However, many low-income countries delay BCG vaccination for low-birth-weight (LBW) infants; this offered the opportunity to directly test the effect of BCG on overall mortality.

In the first two randomised controlled trials receipt of BCG+OPV at birth vs. OPV only ('delayed BCG') was associated with strong reductions in neonatal mortality; these effects were seen as early as 3 days after vaccination. BCG protected against sepsis as well as respiratory infections. [17] [18] Among BCG vaccinated children, those who develop a BCG scar or a positive skin test (TST) are less likely to develop sepsis and exhibit an overall reduction in child mortality of around 50%. [15] [19] [20]

In a recent WHO-commissioned review based on five clinical trials and nine observational studies, it was concluded that "the results indicated a beneficial effect of BCG on overall mortality in the first 6–12 months of life. [17] Relevant follow-up in some of the trials was short, and all of the observational studies were regarded as being at risk of bias, so the confidence in the findings was rated as very low according to the GRADE criteria and "There was a suggestion that BCG vaccination may be more beneficial the earlier it is given". Furthermore, "estimated effects are in the region of a halving of mortality risk" and "any effect of BCG vaccine on all-cause mortality is not likely to be attributable to any great extent to fewer deaths from tuberculosis (i.e. to a specific effect of BCG vaccine against tuberculosis)". [2] Based on the evidence, the WHO's Strategic Group of Experts on Immunization (SAGE) concluded that "the non-specific effects on all-cause mortality warrant further research". [21]

Oral Poliovirus Vaccine

Oral Poliovirus Vaccine (OPV) was developed in the 1950s by Dr. Albert Sabin and is made from live attenuated polioviruses of three serotypes. [22] The first evidence of non-specific effects of OPV was protection by vaccination with OPV of serotype 2 against disease caused by serotype 1 poliovirus without any evidence of cross-neutralization. [23] Vaccination with trivalent OPV helped to stop outbreak of paralytic disease caused by Enterovirus 71 in Bulgaria. [24] In large prospective clinical trials OPV was shown to protect against seasonal influenza and other acute respiratory diseases. [25] [26] Immunization with OPV was also shown to lead to a faster healing of genital herpes lesions. [26] Immunization with OPV was found to reduce all-cause childhood mortality [27] [28] even in the absence of wild poliovirus circulation, hospital admission rate, [29] incidence of bacterial diarrhea, [30] and otitis media. [31] Vaccination with OPV results in Interferon induction that is believed to be the main mediator of the non-specific protective effects of OPV. [26]

Measles vaccine

Standard titer measles vaccine is recommended at 9 months of age in low-income countries where measles infection is endemic and often fatal. Many observational studies have shown that measles-vaccinated children have substantially lower mortality than can be explained by the prevention of measles-related deaths. [32] Many of these observational studies were natural experiments, such as studies comparing the mortality before and after the introduction of measles vaccine and other studies where logistical factors rather than maternal choice determined whether a child was vaccinated or not.

These findings were later supported in randomized trials from 2003 to 2009 in Guinea-Bissau. An intervention group of children given standard titer measles vaccine at 4.5 and 9 month of age had a 30% reduction in all-cause mortality compared to the children in the control group, which were only vaccinated against measles at 9 month of age. [10]

In a recent WHO-commissioned review based on four randomized trials and 18 observational studies, it was concluded that "There was consistent evidence of a beneficial effect of measles vaccine, although all observational studies were assessed as being at risk of bias and the GRADE rating was of low confidence. There was an apparent difference between the effect in girls and boys, with girls benefitting more from measles vaccination", and furthermore "estimated effects are in the region of a halving of mortality risk" and "if these effects are real then they are not fully explained by deaths that were established as due to measles". [2] Based on the evidence, the Strategic Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research". [21] [33]

Diphtheria-tetanus-pertussis vaccine

DTP vaccine against diphtheria, tetanus and pertussis does not seem to have the same beneficial effects as BCG, measles vaccine, OPV and smallpox vaccine, and in fact opposite effects are observed. [34] The negative effects are seen as long as DTP vaccine is the most recent vaccine. BCG or measles vaccine given after DTP reverses the negative effects of DTP. [34] The negative effects are seen mostly in females. [34]

The negative effects are found in several observational studies. However, six WHO-commissioned studies concluded that there were strong beneficial effects of DTP on overall mortality. [35] [36] [37] [38] [39] [40] However, controversy ensued as these studies had important methodological shortcomings. [41] [42] For example, the WHO-commissioned studies had counted "no information about vaccination" as "unvaccinated", and they had retrospectively updated vaccine information from surviving children, while no similar update could be made for dead children, creating a so-called "survival bias" which will always produce highly beneficial effect estimates for the most recent vaccine. [43]

In a recent WHO-commissioned review of DTP based on ten observational studies, it was concluded that, "the findings were inconsistent, with a majority of the studies indicating a detrimental effect of DTP, and two studies indicating a beneficial effect. All of the studies were regarded as being at risk of bias, so the confidence in the findings was rated as very low according to the GRADE criteria."

Furthermore, "three observational studies provided a suggestion that simultaneous administration of BCG and DTP may be preferable to the recommended schedule of BCG before DTP; and there was suggestion that mortality risk may be higher when DTP is given with, or after, measles vaccine compared with when it is given before measles vaccine (from five, and three, observational studies, respectively). These results are consistent with hypotheses that DTP vaccine may have detrimental effects on mortality, although a majority of the evidence was generated by a group centred in Guinea-Bissau who have often written in defence of such a hypothesis." [2]

A large cohort study of over one million Danish children came even to the conclusion that the group of children with fewer DTP vaccinations (without MMR) experienced increased mortality. [44]

Smallpox vaccine

When smallpox vaccine was introduced in the early 19th century, there were anecdotal descriptions of non-specific beneficial effects. In the second half of the 20th century the potential for beneficial non-specific effects of smallpox vaccine was reviewed, and new evidence on "para-immune effects" was added. [45] More recent studies have focused on the phasing out of smallpox vaccine in the 1970s and compared vaccinated and unvaccinated cohorts.

Smallpox vaccine leaves a very characteristic scar. In low-income countries, having a smallpox vaccine scar has been associated with reductions of more than 40% in overall mortality among adults; [46] [47] in high-income countries smallpox vaccination has been associated with a tendency for reduced risk of asthma, [48] and significantly reduced risk of malignant melanoma [49] and infectious disease hospitalizations. [50] There are no studies that contradict these observations. However no randomized trials testing the effect of smallpox vaccine on overall mortality and morbidity have been conducted.

Sex differences

Non-specific effects are frequently different in males and females. There are accumulating data illustrating that males and females may respond differently to vaccination, both in terms of the quality and quantity of the immune response. [5] [6] [7] [34] [51]

Interactions between health interventions

The non-specific effects of vaccines can be boosted or diminished when other immunomodulating health interventions such as other vaccines, or vitamins, are provided. [52]

Influence of pre-existing specific immunity

The beneficial non-specific effects of live vaccines are stronger with earlier vaccination, possibly due to maternal antibodies. [53] Boosting with live vaccines also seems to enhance the beneficial effects.

High-income countries

The non-specific effects were primarily observed in low-income countries with high infectious disease burdens, but they may not be limited to these areas. Recent Danish register-based studies have shown that the live attenuated measles-mumps-rubella vaccine (MMR) protects against hospital admissions with infectious diseases and specifically getting ill by respiratory syncytial virus. [54] [55] [56]

Immunological mechanisms

The findings from the epidemiological studies on the non-specific effects of vaccines pose a challenge to the current understanding of vaccines, and how they affect the immune system, and also question whether boys and girls have identical immune systems and should receive the same treatment.

The mechanisms for these effects are unclear. It is not known how vaccination induces rapid beneficial or harmful changes in the general susceptibility to infectious diseases, but the following mechanisms are likely to be involved.

Heterologous T-cell immunity

It is well known from animal studies that infections, apart from inducing pathogen-specific T-cells, also induce cross-reactive T-cells through epitope sharing, so-called heterologous immunity. [57] [58] Heterologous T-cell immunity can lead to improved clearance of a subsequent cross-reactive challenge, but it may also lead to increased morbidity. [59] This mechanism may explain why DTP could have negative effects.

It would, however, not explain effects occurring shortly after vaccination, as for instance the rapidly occurring beneficial effects of BCG vaccine, [17] as the heterologous effect would only be expected to be present after some weeks, as the adaptive immune response need time to develop. Also, it is difficult to explain why the effect would vanish once a child receives a new vaccine.

Trained innate immunity

The concept that not only plants and insects, but also humans have innate immune memory may provide new clues to why vaccines have non-specific effects. Studies into BCG have recently revealed that BCG induces epigenetic changes in the monocytes in adults, leading to increased pro-inflammatory cytokine production upon challenges with unrelated mitogens and pathogens (trained innate immunity). [60]

In SCID mice that have no adaptive immune system, BCG reduced mortality from an otherwise lethal candida infection. The effects of BCG presented when tested after 2 weeks, but would be expected to occur rapidly after vaccination, and hence might be able to explain the very rapid protection against neonatal septicaemia seen after BCG vaccine. [61]

Trained innate immunity may also explain the generally increased resistance against broad disease categories, such as fevers and lower respiratory tract infections; such effects would be difficult to explain merely by shared epitopes, unless such epitopes were almost universally common on pathogens.

Lastly, it is plausible that the effects are reversible by a different vaccine. Hence, trained innate immunity may provide a biological mechanism for the observed non-specific effects of vaccines. [60]

Controversy

In 2000 Aaby and colleagues presented data from Guinea-Bissau which suggested that DTP vaccination could, under some circumstances (e.g. absence of pertussis) be associated with increases in overall mortality, at least until children received measles vaccine. In response, WHO sponsored the analysis of a variety of data sets in other populations to test the hypothesis. None of these studies replicated the observation of increased mortality associated with DTP vaccination. [35] [36] [37] [38] [39] [40] WHO subsequently concluded, that the evidence was sufficient to reject the hypothesis for an increased nonspecific mortality following DTP vaccination. [62]

However, Aaby and colleagues subsequently pointed out that the studies which failed to show any mortality increase associated with DTP vaccination used methods of analysis that can introduce a bias against finding such an effect. [43]

In these studies, data on childhood vaccinations were typically collected in periodic surveys, and the information on vaccinations, which occurred between successive home visits, was updated at the time of the second visit. The person-time at risk in unvaccinated and vaccinated states was then divided up according to the date of vaccination during the time interval between visits. This method opens up a potential bias, insofar as the updating of person time at risk from unvaccinated to vaccinated is only possible for children who survive to the second follow-up. Those who die between visits typically do not have vaccinations between the first visit and death recorded, and thus they will tend to be allocated as deaths in unvaccinated children – thus incorrectly inflating the mortality rate among unvaccinated children. [43]

This bias has been described before, but in different contexts, as the distinction between "landmark" and "retrospective updating" analysis of cohort data. [63] The retrospective updating method can lead to a considerable bias in vaccine studies, biasing observed mortality rate ratios towards zero (a large effect), whereas the landmark method leads to a non-specific misclassification and biases the mortality rate ratio towards unity(no effect).

An additional problem with the literature on the nonspecific effects of vaccines has been the variety and unexpected nature of the hypotheses which have appeared (in particular relating to sex-specific effects), which has meant that it has not always been clear whether some apparent "effects" were the result of post hoc analyses or whether they were reflections of a priori hypotheses.

This was discussed at length at a review of the work of Aaby and his colleagues in Copenhagen in 2005. [42] The review was convened by the Danish National Research Foundation and the Novo Nordisk Foundation who have sponsored much of the work of Aaby and his colleagues. An outcome of the review was the explicit formulation of a series of testable hypotheses, agreed by the Aaby group. [42] It was hoped that independent investigators would design and conduct studies powered to confirm or refute these hypotheses.

Also, the two foundations sponsored a workshop on the analysis of vaccine effects, which was held in London in 2008. [42] The workshop resulted in three papers. [63] [64] [65] The proceedings were forwarded to WHO which subsequently concluded that "conclusive evidence for or against non-specific effects of vaccines on mortality, including a potential deleterious effect of DTP vaccination on children's survival as has been reported in some studies, was unlikely to be obtained from observational studies. The GACVS will keep a watch on the evidence of nonspecific effects of vaccination.". [66]

In 2013, WHO established a working group tasked with reviewing the evidence for the non-specific effects of BCG, measles and DTP vaccines. Two independent reviews were conducted, an immunological review [67] and an epidemiological review. [2] The results were presented at the April 2014 meeting of WHO's Strategic Group of Experts on Immunization (SAGE). WHO/SAGE "concluded that the findings from the immunological systematic review neither exclude nor confirm the possibility of beneficial or deleterious non-specific immunological effects of the vaccines under study on all-cause mortality. The published literature does not provide confidence in the quality, quantity, or kinetics of impact of any non-specific immunological effects in young children after vaccination. [...] SAGE considered that the non-specific effects on all-cause mortality warrant further research. [...] SAGE considered that additional observational studies with substantial risk of bias would be unlikely to contribute to policy decision making and therefore should not be encouraged." [21]

The Arc of the Swallow

In 2008, Danish crime novel author Sissel-Jo Gazan (author of the Danish crime novel Dinosaur Feather) became interested in the work of the Bandim Health Project and based her science crime novel The Arc of the Swallow (Svalens Graf) on the research into non-specific effects of vaccines.

The novel was published in Danish in 2013; it was on the best-seller list for months and won the Readers' Prize 2014 in Denmark. It was published in English in the UK on November 6, 2014, and in the US on April 7, 2015.

Related Research Articles

<span class="mw-page-title-main">BCG vaccine</span> Vaccine primarily used against tuberculosis

Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recommended in healthy babies as soon after birth as possible. In areas where tuberculosis is not common, only children at high risk are typically immunized, while suspected cases of tuberculosis are individually tested for and treated. Adults who do not have tuberculosis and have not been previously immunized, but are frequently exposed, may be immunized, as well. BCG also has some effectiveness against Buruli ulcer infection and other nontuberculous mycobacterial infections. Additionally, it is sometimes used as part of the treatment of bladder cancer.

<span class="mw-page-title-main">Vaccination</span> Administration of a vaccine to protect against disease

Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live 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. Herd immunity protects those who may be immunocompromised and cannot get a vaccine because even a weakened version would harm them. The effectiveness of vaccination has been widely studied and verified. 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 elimination of diseases such as polio and tetanus from much of the world. However, some diseases, such as measles outbreaks in America, have seen rising cases due to relatively low vaccination rates in the 2010s – attributed, in part, to vaccine hesitancy. According to the World Health Organization, vaccination prevents 3.5–5 million deaths per year.

<span class="mw-page-title-main">Vaccine</span> Pathogen-derived preparation that provides acquired immunity to an infectious disease

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. 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 recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future.

<span class="mw-page-title-main">Measles</span> Viral disease affecting humans

Measles is a highly contagious, vaccine-preventable infectious disease caused by 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, middle ear infection (7%), and pneumonia (6%). These occur in part due to measles-induced immunosuppression. Less commonly seizures, blindness, or inflammation of the brain may occur. Other names include morbilli, rubeola, red measles, and English measles. Both rubella, also known as German measles, and roseola are different diseases caused by unrelated viruses.

<span class="mw-page-title-main">MMR vaccine</span> Any of several combined vaccines against measles, mumps, and rubella

The MMR vaccine is a vaccine against measles, mumps, and rubella, abbreviated as MMR. The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, with at least four 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 for 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.

<span class="mw-page-title-main">Herd immunity</span> Concept in epidemiology

Herd immunity is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become immune to an infection, whether through previous infections or vaccination, thereby reducing the likelihood of infection for individuals who lack immunity.

<span class="mw-page-title-main">Immunization</span> Process by which an individuals immune system becomes fortified against an infectious agent

Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent.

In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.

<span class="mw-page-title-main">DPT vaccine</span> Combination vaccine

The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus. The vaccine components include diphtheria and tetanus toxoids and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself. The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular". In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain any live pathogen, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.

<span class="mw-page-title-main">Vaccine hesitancy</span> Reluctance or refusal to be vaccinated or have ones children vaccinated

Vaccine hesitancy is a delay in acceptance, or refusal, of vaccines despite the availability of vaccine services and supporting evidence. The term covers refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain about their use, or using certain vaccines but not others. The scientific consensus that vaccines are generally safe and effective is overwhelming. Vaccine hesitancy often results in disease outbreaks and deaths from vaccine-preventable diseases. Therefore, the World Health Organization characterizes vaccine hesitancy as one of the top ten global health threats.

Artificial induction of immunity is immunization achieved by human efforts in preventive healthcare, as opposed to natural immunity as produced by organisms' immune systems. It makes people immune to specific diseases by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering, that is, the disease burden, even when eradication of the disease is not possible. Vaccination is the chief type of such immunization, greatly reducing the burden of vaccine-preventable diseases.

Tuberculosis (TB) vaccines are vaccinations intended for the prevention of tuberculosis. Immunotherapy as a defence against TB was first proposed in 1890 by Robert Koch. Today, the only effective tuberculosis vaccine in common use is the Bacillus Calmette-Guérin (BCG) vaccine, first used on humans in 1921. It consists of attenuated (weakened) strains of the cattle tuberculosis bacillus. It is recommended for babys in countries where tuberculosis is common.

In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.

Immunization during pregnancy is the administration of a vaccine to a pregnant individual. This may be done either to protect the individual from disease or to induce an antibody response, such that the antibodies cross the placenta and provide passive immunity to the infant after birth. In many countries, including the US, Canada, UK, Australia and New Zealand, vaccination against influenza, COVID-19 and whooping cough is routinely offered during pregnancy.

<span class="mw-page-title-main">Bandim Health Project</span> West African healh research organization

The Bandim Health Project works with population based health research in one of the world's poorest countries, Guinea-Bissau in West Africa.

The Expanded Program on Immunization(EPI) in the Philippines began in July 1979. And, in 1986, made a response to the Universal Child Immunization goal. The four major strategies include:

  1. sustaining high routine Full Immunized Child (FIC) coverage of at least 90% in all provinces and cities;
  2. sustaining the polio-free country for global certification;
  3. eliminating measles by 2008; and
  4. eliminating neonatal tetanus by 2008.

An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the pathogen.

A vaccination policy is a health policy adopted in order to prevent the spread of infectious disease. These policies are generally put into place by State or local governments, but may also be set by private facilities, such as workplaces or schools. Many policies have been developed and implemented since vaccines were first made widely available.

<span class="mw-page-title-main">Measles vaccine</span> Vaccine used to prevent measles

Measles vaccine protects against becoming infected with measles. Nearly all of those who do not develop immunity after a single dose develop it after a second dose. When rate of vaccination within a population is greater than 92%, outbreaks of measles typically no longer occur; however, they may occur again if the rate 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.

Peter Aaby is trained as an anthropologist but also holds a doctoral degree in medicine. In 1978, Peter Aaby established the Bandim Health Project, a Health and Demographic Surveillance System site in Guinea-Bissau in West Africa, which he has run ever since. In 2000, Peter Aaby was awarded the Novo Nordisk Prize, the most important Danish award within health research.

References

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  2. 1 2 3 4 5 Higgins, Julian PT.; Soares-Weiser, Karla; Reingold, K. (2014-03-13). "Systematic review of the non-specific effects of BCG, DTP and measles containing vaccines" (PDF). WHO/SAGE. Archived (PDF) from the original on 2022-03-01. Retrieved 2023-08-30.
  3. 1 2 3 Benn CS, Netea MG, Selin LK, Aaby P (13 May 2013). "A small jab - a big effect: nonspecific immunomodulation by vaccines". Trends in Immunology. 34 (9): 431–9. doi:10.1016/j.it.2013.04.004. PMID   23680130.
  4. ↑ Aaby, P; Andersen, M; Sodemann, M; Jakobsen, M; Gomes, J; Fernandes, M (20 November 1993). "Reduced childhood mortality after standard measles vaccination at 4-8 months compared with 9-11 months of age". BMJ. 307 (6915): 1308–11. doi:10.1136/bmj.307.6915.1308. PMC   1679462 . PMID   8257884.
  5. 1 2 Holt, EA; Moulton, LH; Siberry, GK; Halsey, NA (November 1993). "Differential mortality by measles vaccine titer and sex". The Journal of Infectious Diseases. 168 (5): 1087–96. doi:10.1093/infdis/168.5.1087. PMID   8228340.
  6. 1 2 Aaby, P; Samb, B; Simondon, F; Knudsen, K; Seck, AM; Bennett, J (1994). "Sex-specific differences in mortality after high-titre measles immunization in rural Senegal". Bull World Health Organ. 72 (5): 761–70. PMC   2486568 . PMID   7955026.
  7. 1 2 Aaby, P; Knudsen, K; Whittle, H; Lisse, IM; Thaarup, J; Poulsen, A (June 1993). "Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate". Journal of Pediatrics. 122 (6): 904–8. doi:10.1016/s0022-3476(09)90015-4. PMID   8501567.
  8. ↑ "Expanded programme on immunization (EPI). Safety of high titre measles vaccines". Wkly Epidemiol Rec. 67 (48): 357–61. 1992. PMID   1449986.
  9. ↑ Aaby, Peter; Jensen, Henrik; Samb, Badara; Cisse, Badara; Sodemann, Morten; Jakobsen, Marianne; Poulsen, Anja; Rodrigues, Amabelia; Lisse, Ida Marie; Simondon, Francois; Whittle, Hilton (28 June 2003). "Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies". The Lancet. 361 (9376): 2183–2188. doi:10.1016/S0140-6736(03)13771-3. PMID   12842371. S2CID   19968745.
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