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The pros and cons of immunisation -- Paper two: the importance of immunisation.

Like other medicine, all vaccines have some side effects or complications; in general the incidence and severity of complications is lower than for pharmaceuticals. When considered on a population basis, the incidence of serious complications of vaccination is minute, when compared with the outcome of natural infection. Enlightened governments, which promote immunisation as a means of minimising the impact of infectious diseases in their communities, also accept the responsibility for any adverse events which can be demonstrated to be vaccine related, and provide compensation and care for people who are affected.

Australia↗

An experimental infection with classical swine fever in E2 sub-unit marker-vaccine vaccinated and in non-vaccinated pigs.

The clinical and virological protection induced by an E2 sub-unit marker-vaccine against Classical Swine Fever (CSF) was examined during an experimental infection in vaccinated and non-vaccinated pigs. Forty-five pigs were equally distributed over three adjacent pens of an isolation unit, there was only indirect (airborne) contact between pigs in the different pens. In pen 3 all pigs were vaccinated twice with 4 weeks interval. Pigs in pens 1 and 2 were not vaccinated. Two weeks after booster vaccination, one randomly selected pig in the middle pen was experimentally inoculated with CSF virus. After the initial virus spread in the infected pen, all pigs in the non-vaccinated adjacent pen were infected. In the vaccinated pen, seven out of 14 pigs became infected during the experiment. Survival analysis showed that virus transmission by direct and indirect contact was significantly (p<0.001) delayed in vaccinated pigs as compared to non-vaccinated pigs. In the non-vaccinated pens over 40% of the pigs died and typical clinical signs were noticed. In the vaccinated pen no mortality and no clinical symptoms were observed. Although double vaccination with an E2 sub-unit marker-vaccine was able to prevent the clinical course of the disease it was unable to prevent infection through indirect contact. This finding combined with the slow serological response after vaccination will complicate the possible use of the vaccine in emergency vaccination programmes.

Animals↗

Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in vaccinia and variola viruses. The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-gamma-producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-gamma-producing cells in one donor, 35% in the second donor, and 6% in the third donor. This information will be useful for studies of human T cell memory and for the design and analyses of the immunogenicity of experimental vaccinia vaccines.

CD8-Positive T-Lymphocytes↗

Interpretation and estimation of vaccine efficacy under heterogeneity.

Interpretation and estimation of vaccine efficacy is complicated when the vaccine effect is heterogeneous across vaccinated strata. If a person has a certain susceptibility, or probability of becoming infected conditional on a specified exposure to infection, then one effect of a vaccine would be to reduce that susceptibility, possibly to zero. Vaccine efficacy is a function of the relative susceptibilities in the vaccinated and unvaccinated persons. Under heterogeneity of vaccine effect, a general expression for a summary vaccine efficacy parameter is a function of the vaccine efficacy in the different vaccinated strata weighted by the fraction of the vaccinated subpopulations in each stratum. Interpretation and estimability of the summary vaccine efficacy parameter depends on whether the strata are identifiable, and whether the heterogeneity is host- or vaccine-related. Bounds are derived for the summary vaccine efficacy when the strata are not identifiable for the case of an outbreak of an acute infectious disease. The upper bound assumes that everyone is equally affected by the vaccine, and the lower bound assumes that some are completely protected while others have no protection. The biologic interpretation of the two bounds is different.

Disease Susceptibility↗

[Effectiveness of tuberculosis vaccines].

BCG revaccination in the Sverdlovsk Region is performed thrice: at the age of 5, 10 and 15 years. The percent of children covered by tuberculin diagnosis and BCG vaccination is growing. Complications of BCG vaccination remain at the same level. Tuberculosis morbidity in children rises due to minor forms of tuberculosis. However, it is 2 times less than mean tuberculosis incidence in Russia. Primary infection is registered 4.5 times less frequently.

Adolescent↗

[Smallpox vaccination in a country district (author's transl].

This survey deals with the matter of smallpox vaccination (serum, complications, age, degree of immunity, compulsory vaccination) also with the percentage of first vaccinations, booster vaccinations of children with birth years from 1962 to 1974, as well as the vaccination coverage of 2000 adults within a district. The survey showed a high degree of first vaccination coverage and a satisfactory percentage of booster vaccinations. Of the 2000 adults interviewed 19% had never been vaccinated, 54% ten or more years ago, 17% between the last 3 to 10 years, and only 10% had been vaccinated within the past three years. As a minimum safety measure it is requested that persons who could be exposed to smallpox (public servants, medical officers, flight personnel) be satisfactorily immunized against the disease.

Austria↗

[Parvovirus infections in dogs and cats: problems of immunization].

The general problems of immunization against parvoviroses are only understandable when knowing the basic principles of epidemiology, pathogenesis and immunology of those virus infections. The main difficulties with regard to vaccinations are 1. efficacy of homologous respectively heterologous vaccines, 2. indications for live resp. inactivated vaccines, 3. combination with other vaccines, 4. bridging of the "immunological gap" (refractory phase) of puppies, 5. mode of application and timing of vaccinations (schedule of vaccinations), 6. failure in vaccinated animals, 7. complications originating from vaccinations, 8. passive immunization.

Animals↗

[Convulsions after whooping-cough vaccination].

Convulsions or status epilepticus in 11 infants after pertussis vaccination are reported. In 3 cases grand mal epilepsy persisted and 2 children developed infantile epileptic encephalopathy (Lennox syndrome). On the basis of our own experience, the incidence of seizures approximates 1:4800 infants vaccinated or 1:12 800 vaccinations. According to a recent prospective study from the USA, the incidence of seizures may be closer to 1:600 infants. Since there is a significant difference between the incidence of spontaneous fits in children of the same age group and the incidence after vaccination, a causal relationship between the seizures and vaccination appears to be confirmed. The following conclusions are drawn from these observations: 1. In view of the usually benign course of whooping cough today, current vaccination against pertussis is hardly satisfactory. Improvement of the available vaccines is an urgent necessity. The protection should include the population most at risk, i.e. infants during the first few months of life. 2. Parents should be better informed about the risks involved in pertussis vaccination. 3. Booster inoculations should be abandoned. 4. Health authorities should decide whether the current pertussis vaccination program should be continued. 5. Complications following vaccination should be registered at a national centre.

Adolescent↗

A high incidence of neurological complications following Semple anti-rabies vaccine.

A study was conducted to determine the incidence of neurological complications among a cohort of 6,980 recipients of Semple vaccine administered in Bangkok and 5 nearby provinces in 1984. A review of all patients admitted to public hospitals in these 6 provinces discovered a total of 32 cases, with neurological complications following Semple vaccine. Twenty-two cases (68.8%) were encephalitis or myelitis. The complication rate was 3.6 times higher for males than females and the rate was lowest in the 0-14 year age group. Vaccinees receiving large daily dose of vaccine had a higher rate of complications than those with low dose regimen. One patient died, giving the case-fatality rate of 3.13 per cent. Since the search was limited, the rate of neurological complications to Semple vaccine was a minimum of 4.6 cases per 1,000 vaccinees [1:220]. This complication rate was much higher than most rates reported previously. It is imperative to find economically feasible alternatives to Semple vaccine.

Adolescent↗

Complications of bacille Calmette-Guérin (BCG) vaccination and immunotherapy and their management.

Complications of bacille Calmette-Guérin (BCG) vaccination are uncommon. Fewer than one in 1000 people vaccinated develop significant local reactions, and serious disseminated disease develops in fewer than one in a million. Localised complications--which include hypersensitivity reactions, abscesses at the injection site, and localised lymphadenopathy--are usually self limiting. They usually result from faulty technique, including the accidental intracutaneous injection of the stronger percutaneous vaccine, or poor selection of subjects for vaccination. Abscesses at the injection site usually respond to drainage and chemotherapy with isoniazid or erythromycin. Lymphadenopathy responds poorly to antimicrobial treatment and surgery may be needed for suppurating or discharging lesions to hasten recovery and give a good cosmetic result. Disseminated disease usually occurs in people with impaired immunity, in whom it is often fatal. BCG should never be given to people who are known to be infected with HIV, but the risk of complications in children born to HIV infected mothers is low. Disseminated disease can also result from intravesical instillation of BCG to treat bladder cancer, but this responds to antituberculosis chemotherapy.

Abscess↗

Osteitis after newborn vaccination with three different Bacillus Calmette-Guérin vaccines: twenty-nine years of experience.

Newborns in Finland have been vaccinated with Bacillus Calmette-Guérin (BCG) since the 1950s. Until the end of 1970 the vaccine was made from BCG strain Gothenburg by the Swedish BCG laboratory in Gothenburg and from 1971 on from the same strain in Copenhagen, Denmark. It was replaced by the Glaxo vaccine in 1978. Complications caused by BCG vaccination have been under follow-up, and the data have been collected from nationwide registers. In this study we analyzed the incidence rates of BCG osteitis between the years 1960 and 1988. From 1960 to 1970 the incidence rate was from 2.7 to 13.0/100,000 BCG-vaccinated infants (mean, 7.3; median, 6.9). The incidence increased during the years 1971 to 1978 when it varied between 15.3 and 72.9/100,000 BCG-vaccinated infants (mean, 36.9; median, 30.4). Since 1978 the incidence has varied between 1.7 and 10.1/100,000 BCG-vaccinated infants (mean, 6.4; median, 7.2). In Britain no reports of BCG osteitis have been published despite the use of the same Glaxo vaccine. Our results indicate that the incidence of BCG osteitis in a given population depends on the BCG vaccine used. The follow-up of BCG complications is an essential part of BCG vaccination program.

Animals↗

SMALLPOX CONTROL IN CANADA.

During the period 1961 to 1963 there were 10 separate importations of smallpox cases by aircraft into England and Wales, Germany, Sweden, Poland and Canada. A feature of the resulting outbreaks was the number of cases and deaths of physicians and other health personnel. With the increasing volume of international air traffic there is a risk of importing incubating cases of smallpox into Canada, as occurred in 1962. Millions of Canadians have been protected against smallpox. Some complications of smallpox vaccination have occurred in Canada; such complications can be minimized by proper attention to contraindications to vaccination. The Food and Drug Directorate, Department of National Health and Welfare, has circularized all physicians in Canada to request their co-operation in reporting adverse reactions to drugs. This includes serious, unusual or unsuspected reactions to immunizing agents (vaccines, toxoids and antitoxins). The latter information will be shared with the Epidemiology Division, Department of National Health and Welfare, and the provincial epidemiologist and manufacturer concerned. The importance of maintaining the smallpox immunity of physicians, nurses and other hospital and health personnel in Canada is emphasized.

Biometry↗

Lethal complications of typhoid-cholera-vaccination. (Case report and review of the literature).

Simultaneous parenteral vaccination against typhoid and cholera lead to death through either anaphylactic shock or endotoxic shock in a 36-year-old male. At autopsy the charactertic features of shock as well as chronic interstitial myocarditis were noted. Moreover, fresh histiocytic and lymphocytic nodules were found in the liver, heart and meninges. A review of the literature dealing with lethal complications following parenteral tyhoid vaccinations shows an increased risk in debilitated persons (emaciation, stress, cold). Most of the fatalities occurred in persons who had previous disturbances of the cardiovascular system, as in the case reviewed here. Cardiac failure, Landry's paralysis, renal failure and disturbances of skin, joints and intestines may also follow typhoid vaccinations. However, these latter complications are usually not lethal. The patients presented here had many of the conditions which are known to aggravate the situation and to lead to a lethal culmination. The review of this case and the disucussion following it shows that only healthy persons should receive the parenteral typhoid vaccination. Hopefully, the presentation of this material will help prevent fatalities of this type in the future.

Adult↗

Smallpox: clinical highlights and considerations for vaccination.

Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia) vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.

Humans↗

Comparative trial of live attenuated measles vaccine in Hong Kong by intramuscular and intradermal injection.

Between April and July 1966 a comparative trial of two live attenuated measles vaccines (Schwarz and Beckenham 31), given intramuscularly or intradermally, was conducted in Hong Kong. Some 910 non-immune children completed the trial. The Beckenham 31 vaccine caused significantly more complications than Schwarz vaccine, but it also resulted in a much higher mean antibody titre by both intramuscular and intradermal injection than did Schwarz vaccine. The seroconversion rates were satisfactory for both vaccines given intramuscularly but not for either given intradermally (at one-fifth the recognized intramuscular dose).The authors suggest that either vaccine may usefully be given for measles prophylaxis. The choice between Beckenham 31, with a higher complication rate and higher antibody levels, and Schwarz, with fewer complications but lower antibody levels, would depend on the type of community, the adequacy of the medical services, the severity of measles and an assessment of how either vaccine, with its known complications, might affect other immunization programmes.

Asian People↗

Human immunodeficiency virus infection and routine childhood immunisation.

Current experience with the safety and efficacy of vaccines in infected children and adults is reviewed to examine the basis for decisions about routine immunisations of children infected with the human immunodeficiency virus (HIV). No adverse reactions to inactivated vaccines have been noted, but complications with live vaccines have been recorded with both BCG and smallpox. Limited experience with live poliomyelitis and measles vaccines in HIV-infected children has not yet shown any severe complications from these vaccines. Theoretical concerns that immunisation might accelerate the course of HIV infection are not supported by available data. Serological response to most inactivated and live vaccines is reduced in HIV-infected persons, and is related to the degree of immunosuppression present. Preliminary evidence suggests that the severity of some vaccine-preventable diseases is increased in HIV-infected children. This review finds general support for recommendations on immunisation of HIV-infected children that have been developed by the World Health Organisation.

Acquired Immunodeficiency Syndrome↗