Vaccination

The vaccination is a process consisting in introducing an external agent (the vaccine ) into a living organism in order to create a positive immune reaction against a Infectious illness. The active ingredient of a vaccine is a Antigène intended to stimulate natural defenses of the organization (the Immune system). There exist four types of vaccines according to their préparation : inactivated infectious agents, attenuated alive agents, sub-units of infectious agents or toxins inactivated.

History of vaccination

As of the 11th century, the Chinese practiced the Variolisation  : it was a question of inoculating a form which one hoped for not very virulent Variole by putting in contact the person to be immunized with the suppurant contents of the substance of the blisters of a patient. The result remained however random and risky, death rate could reach 1 or 2  %. The practice was gradually diffused along the Silk route. It was imported since Constantinople in occident at the beginning of the 18th century. In 1760, Daniel Bernoulli showed that, in spite of the risks, the generalization of this practice would make it possible to gain a little more than three years of life expectancy to the birth.

Itself very favorable to the variolisation, the English doctor Edward Jenner hears of a popular belief according to which to catch the variola of the cows would preserve human form. The May 14th 1796, it inoculated with a child of the pus taken on the hand of farm infected by the Vaccine, or variola of the cows, which was present on worse of the cow. Three months later, it inoculated the Variole with the child who appeared immunized. This practice was spread gradually in all Europe. The word vaccination comes from Latin vacca who means cow .

The principle of action of vaccination was explained by Louis Pasteur and his collaborators Roux and Duclaux, following work of Robert Koch connecting the Microbe S and the diseases. This discovery enabled him to improve the technique. Its first vaccination was the vaccination of a herd of Mouton S against the Choléra the May 5th 1881. The first human vaccination (except vaccination with the original direction of Jenner) was that of a child against the Rage the June 6th 1885.

See also: Chronology of the vaccines

Principle of vaccination

The principal goal of the vaccines is to induce the production by the organization of Anticorps, natural biological agents targeted with the defense of the body with respect to identified pathogenic elements. A vaccine is thus specific to a disease but not to another. This production of antibody decreases gradually within a more or less long time, thus fixing the duration of efficatity of the vaccine. It is measurable and this measurement can be used in certain cases to know if the subject is vaccinated effectively (vaccine anti Hépatite B and anti Tétanos in particular).

The antibodies are produced by lymphocytes B differentiating in Plasmocyte S. the number of lymphocytes B report, not secreting but which react specifically to the presentation of an antigen, does not seem, not to vary to him during time.

However certain vaccines do not cause the formation of antibody but bring into play a reaction of protection known as cellular, it is the case of the BCG (" Bacillus of Calmette and Guérin" , anti-tuberculous vaccine).

The immunizing defenses thus “stimulated” by the vaccine prevent an attack of the disease-causing agent for one length of time which can vary from one vaccine to another. This avoids the development of a Infectious illness on the level of the individual and, in the case of a contagious disease and of a vaccination in mass, on the level of a population.

Ideally, the vaccines should not be inoculated that to the people in good health bus of the more or less severe side effects can be observed with a variable frequency. They can be managed however with people carriers of chronic diseases which are particularly sensitive to certain infections (case of the anti-flu vaccination of the patients carrying respiratory affections).

Types of vaccines

The vaccines are usually inoculated by injection, but they can the being by oral way (what allowed almost élminer the rage of Europe of the 12 by soft foods vaccinating against the Rage distributed to the foxes in nature) and of the tests of vaccines per nasal spray are in the course of test (ex: NasVax anti-flu vaccine in Israel). The vaccine matter itself is classified according to its nature into four catégories :

Vaccines resulting from inactivated infectious agents

Once the identified and isolated infectious agents, they are multiplied in great number before being inactivated (killed) chemically (for example, with the Formaldéhyde) or by heat. In this way of the vaccines are produced for example against the Grippe, the Choléra, the Peste or the Hépatite has.

Vaccines resulting from attenuated alive agents

The infectious agents are multiplied in laboratory until they lose naturally or artificially, by change, their pathogenic character. The stocks obtained are then unable to entirely develop the disease which they caused before, but however preserve their antigens and their capacities to induce immunizing responses. This kind of vaccine is generally more effective and its effect more durable than that which is composed of inactivated infectious agents. But as it consists of micro-organisms of which viability must be maintained to be effective, its conservation is also more difficult. Like examples of this type of vaccine, one can quote the vaccines against the Yellow fever, the Varicelle, the Rubéole, the Oreillons, measles, tuberculosis, the gastroentérites with Rotavirus.

Vaccines made up of sub-units of infectious agents

These vaccines, instead of containing the entirety of the infectious agents, comprise only the components of those necessary to obtaining the immunizing responses. For example, of the vaccines against the viruses of the Hepatitis B or against the Papillomavirus are thus consisted only of proteins which are naturally on the surface of these viruses. One can also quote the vaccine against the whooping-cough, infectious illness due to a bacterium, Bordetella pertussis . Generally, of yeasts modified by genetic Engineering, so that they produce in great quantities proteins of interest, is used in the manufacture of these vaccines.

Vaccines made up of inactivated toxins

When the most serious symptoms of the disease are due to the production of toxins by the infectious agent, it is possible to produce vaccines only starting from these toxins by inactivant them chemically or by heat (a toxin thus made inoffensive then is frequently called a “toxoïde” or more generally a “anatoxine”). The Tetanus or the Diphtérie is two examples of diseases whose symptoms are due to toxins and against which one produces vaccines in this way.

Various additives can reinforce the immune reaction.

Protective inoculation

The protective inoculation is a form of vaccination aiming at stimulating natural defenses in order to prevent the appearance of a disease. It does not cease seeing its field widening.

Diphteria, Tetanus, Whooping-cough, Poliomyelitis, Meningitis due to the germ Haemophilus influenzae of sérotype B , Hepatitis B, seize up, BCG (against the Tuberculose), Measles, Rubella, Mumps and, for the infants in communities (because of its high cost), Pneumococcus. The number of diseases that one seeks to prevent as of more the young age in France ceased lengthening and it will undoubtedly be necessary in the next years to introduce others of them, which forces to simplify it for example by using vaccines “multivalents” (i.e., effective against various diseases at the same time) to avoid delays and abandonments.

Vaccination on broad scale makes it possible to reduce in an important way the incidence of the disease at the vaccinated population, but also (if the transmission of this one is only inter-human) at that which is not it, the human tank of the germ becoming very reduced. The eradication of the Poliomyélite of the type 2 in 1999 is allotted to the vaccination campaigns.

On the other hand, contrary to a spread idea, the role of vaccinations in the eradication of the Variole in 1980 would be minor according to an emanating report/ratio of WHO. It would seem indeed that a strategy of monitoring and damming up installation at the beginning of the year 1970 was more profitable in the eradication of this disease.

Therapeutic vaccination

Also called Immunothérapie activates, this technique consists in stimulating the immune system of the organization to support the production of antibody. It is not thus a question more of preventing the appearance of a disease but of helping the organization of the people already infected to fight against the disease by restoring its immunizing defenses. Contrary to an generally accepted idea, vaccination against the rage is not therapeutic. In fact, in pre-exposure (at the people likely to be reached because of their community activity for example) it is about a usual vaccination (injection of the antigen which will stimulate the manufacture of specific defenses). In post-exposure, i.e. after a bite by an animal likely to be mad, it is about a passive and active immunization. Passivate because there is immunoglobulin injection (antibody) specific against the rage and, at the same time, injection of the anti-rabic vaccine. Contrary to the AIDS or cancer, anti-rabic vaccination is not largely any more at the experimental stage.

These techniques are still at the experimental stage. It is hoped that they will be able to help to fight against of the diseases like the AIDS and the Cancer.

Obligatory vaccines

In Europe

obligatory Vaccines in Europe ( source: Quid 2006)

In France

The obligatory vaccines are refunded by the Social security. The health authorities ensure that the benefit ratio/risk is sufficiently significant. The non-observance of the vaccine regulations exposes to penal sanctions or administrative, in particular with the loss of parental rights, the descolarisation, the reference of an administration, a fine or a sentence of emprisonment. Example for refusal to subject, or to subject those on which one exerts the parental authority or those which one ensures the supervision the obligation of vaccination against tuberculosis Article L. 3112-1 of the Public health code envisages: 3750 euros of fine and 6 months of prison. To want to force rather than to convince is not nevertheless a method which achieves the unanimity at the French citizens since people gathered in association not to quote that the National league for the freedom of vaccinations wait to see the freedom of each and everyone fully devoted to height of the projections of the Charte of the basic rights of the European Union which founds a Clause of conscience. This dispute remains however marginal, at least for the majority of the vaccines.

They are the vaccines suivants :

These 3 last are in general inoculated at the same time as vaccination against the Coqueluche and the Haemophilus influenzae B within a pentavalent vaccine.

Following the total eradication of the Variola within the framework of a world program of WHO, the vaccine against this disease is not necessary any more. Two stocks are however preserved in American and Russian laboratories with an aim of research.

Vaccination against the BCG (Bacillus Calmette Guerin): Tuberculose) is not obligatory any more since 2007.

Since the Health insurance deals with 100  % the vaccine against the influenza at targeted people, mortality related to this disease strongly has chuté : less than 230 deaths per annum (winter 2004-2005), against: 25000 on average in the years 1970.

Other countries

  • against the Cholera: “Vaccination against the cholera is not available any more in France, taking into account its low effectiveness and of the abandonment (justified) of the obligation to vaccinate itself for almost the whole of the countries (in any case for tourism)”.

  • against the Yellow fever: Antiamaril

  • against the typhoid .
Antiamaril vaccination is a complex problem which does not touch only the foreign countries with strong endemicity. In certain French territories of Overseas (Guyana) this vaccination remains obligatory taking into account the high risk of contamination. Certain countries, not-endemic for the yellow fever, require migrants an up to date antiamaril vaccination. That poses the problem of the vaccination of the people immunodéficientes in front of going in these areas. Vaccination against meningitis with méningocoques is strongly advised for the people going to Africa in the countries known as of the " girdle méningitique". It is obligatory for any pilgrim going with Mecque (up to date vaccination dating of more than 15 days and less than three years).

The market of the vaccines

There remains weak compared to the pharmaceutical market (1,7% of the world expenditure in drugs in 2004). For the pharmaceutical group Sanofi Aventis, number 1 European and world number 3 of the drug company, with the consolidated turnover of 25,311 billion euros into 2005 which holds the largest market share world of the vaccines, the profitability of the market remains at the very least considerable.

5 laboratories divide the worldwide market:

  • Sanofi-Pasteur (25% of the market),
  • GlaxoSmithKline (23%),
  • Wyeth (13%),
  • Merck (11%),
  • Chiron (5%).

Vaccines and public health

In 2002, more than 2 million children could have been saved in the world if they had been vaccinated (figure WHO). The two principal diseases which could have profited from a vast campaign of vaccination are the Rougeole and the Viral hepatitis B (close to: 300000 deaths of children for each one of them).

In France, one estimates that vaccinations have, since 1950, contributed to divide by 30 or more mortality due to certain infectious illness, as shows it the following table:

mortality per million people
source: INSERM

The role of vaccination is less clear in other cases: by looking at well the evolution of the regression of the Tuberculosis since the XIXe century (made noted in many countries), one notes objectively that it regressed before the discovery of the antituberculeux one, or of vaccination. The epidemiologists primarily interpret it by the improvement of the conditions of hygiene, the nutritional conditions, etc. On the basis of study made with large scales and organized by the World Health Organization (WHO), some think that the effectiveness of the BCG is low: in a study made on 260.000 people in a country of endémie tubercular patient (in India), the authors did not find a difference significant between the group which had received the BCG and that which had not received it. Another study also made in India on 366.625 people showed that the BCG did not have any preventive action on the forms of pulmonary tuberculoses adult. It should be noted that vaccination against tuberculosis forever have the aim of protecting from the pulmonary forms but from the serious invasive forms from the disease in particular meningitis tubercular patient.

Currently, the effectiveness of the vaccine against the cholera is not yet quite clear: during a clinical trial to test its effectiveness realized on more than 60.000 people in Indonesia, in a context of weak incidence of the cholera, there no was significant protection.

Side effects and risks according to the vaccine

The side effects can be frequent (vaccine fever post) but generally moderate. The accidents, sometimes extremely serious, remain exceptional, even if the history retained some serious facts.

Variola

The Variole is regarded as éradiquée since 1977. Vaccination thus is not practiced any more even if stocks of vaccines are preserved in the event of resurgence. The following complications thus arose rather with the history of medicine:
  • encéphalite postvaccinale (frequency between 1/4704 and 1/40.710 (in Germany), between 1/25.000 and 1/150.000 (in the USA)
  • eczema vaccinatum (frequency 1/26000)
  • occurred of Cancer S (especially Lymphosarcome, cutaneous tumors on the level of the Scarification S)

The BCG

  • Ostéite S (1/21 800 (in Finland), 1/28 270 (in Sweden))
  • Bécégite S: The disseminated bécégite is a very serious complication, sometimes mortal, occurring in a third of the case in children presenting a severe combined immunizing deficit (DICS); the full number of bécégites disseminated is estimated at a dozen of case per annum in France. The bécégite is most frequently observed in children vaccinated before the 6 months age, even of a year.
There exists an abusive use of the " term; bécégite" to indicate awaited post-vaccine reactions: ignition, adenopathies (ganglia), which can abscess even suppuration often leaving an indelible scar. This scar is fundamental to affirm that the person was correctly vaccinated by the BCG. This type of awaited reaction does not require to in no case treatment and cures spontaneously even if the time of cure of the post-vaccine reaction can be long (sometimes several months).

Di-Te-Per (DTCoq in France)

The side effects are especially due to the vaccine anti-whooping-cough (Per)

  • important acute neurological accidents (occurring in 80,5% of the cases in the 24 hours of the injection): convulsions, severe delay intellectual with moderate, Hémiplégie permanent

  • Encephalopathy S acute
  • state of shock, Shock anaphylactic
  • inconsolable persistent cries
The shock anaphylactic is absolutely not specific of coquelucheuse vaccination (PER). It can be observed at likely people as well as with any other vaccine, produced drug or other. It is absolutely unforeseeable as well as a shock anaphylactic occurring after penicillin administration (for example) or after a puncture of hyménoptère.

The vaccine anti-polio

The first vaccination campaign of mass anti Poliomyélite, in the Fifties, was marked by the supply of an important defective batch (virus living not attenuated) outcome with nearly 220.000 contaminations including 70.000 patients, 164 severe paralyzes and 10 deaths

  • transmission risk with the entourage (if vaccine containing alive virus attenuated)
  • unfortunate contamination by the SV40 (simian virus 40 (inoffensive virus for the monkey but oncogene for the man, although to date, no study showed an increase in the cancer risk at those having received the contaminated vaccine))
  • Dermatite S generalized
  • joint pains close to the sites of injection
  • anaphylactic reactions
  • neurological reactions: convulsions, Polynévrite S, myélite transverse, facial paralyzes, Syndrome of Guillain-Barred, subacute Panencephalitis sclerosing
The syndrome of Guillain-Barred is often quoted like " undesirable effect of a vaccination" although no scientific proof has, to date, shown the existence of a cause and effect link.

Measles-Mump-rubella (or vaccine ROR)

  • Purpura thrombocytopenic (thrombocytopenia = falls of the number of the blood plates)

  • complication articular
  • Méningite S

Vaccination anti-hepatitis B

Antiamaril vaccination (vaccination anti yellow fever)

The following reactions were observed:

  • tiny reactions postvaccinales: about the sixth day, there can be a feverish push with cephalgias and dorsalgies which disappear after 1 to 2 days

  • allergic reactions : rash, multiform erythema, urticaria, Angioedème, Asthma (rare cases)
  • reactions of Arthus characterized by an edema and a less Necroses at the point of injection than 24 hours after vaccination
  • risk of particularly high Encéphalite in the young children

Antityphoidic vaccination

  • Nephropathy S early (in the hours which follows vaccination) or late (1 to 2 weeks afterwards)

Anti-flu vaccination

Even notices for this last syndrome that mentioned for the vaccine polio. .

Vaccination against chicken pox

  • shocks anaphylactic

  • transmission risk with the entourage (if vaccine containing alive viruses)

Vaccination antihaemophilus

  • Syndrome of Guillain-Barred (id. that for the vaccine polio).

  • œdémateuses reactions of the lower extremities with cyanosite or will purpura fugacious

Generally

The undesirable reactions are more frequently noted with the vaccines that with the drugs. That is explained by the fact why the vaccines, by definition preventive, are managed on unscathed subjects of the disease from which one protects them. More an great attention is thus paid to the consequences (real or supposed) occurring after administration of the vaccines, because in the absence of the perception of the disease, any unusual reaction felt by the person having received the vaccine is spontaneously allotted to this one. The most obvious example is that of vaccination against hepatitis B (which is the first vaccination which avoids an extremely serious cancer) and its association, contradicted many times by very many studies, with the multiple sclerosis. By supposing that one can vaccinate 100% of the population against a disease X, any post-vaccine undesirable reaction will occur at a vaccinated person. For as much, could one in these circumstances allot the undesirable effect to vaccination, especially if it is about a disease which one knows only imperfectly the natural history?

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