Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Read more here...

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Is there a vaccine which can prevent hepatitis B

For several years a vaccine has been available which is very effective in preventing, although not in treating, hepatitis B. In the U.S., women who receive prenatal care are screened for hepatitis B infection. For women infected with hepatitis B, transmission to their newborns can be prevented by administering hepatitis B vaccine and immune globulin to their infants immediately after birth and continuing the series of three immunizations over the next six months. In infants born to uninfected women, the hepatitis B series is routinely started within the first two months of life. Adults at risk for exposure to hepatitis B may also receive the hepatitis B vaccine series. Once completed, the vaccine provides highly effective, long-term protection that is, direct exposure of a vaccinated individual to the virus through sex or blood will not result in infection.

Case study 2 prevention of influenza through vaccination

Only a small proportion of cases of clinical influenza are caused by the influenza A virus, the target of most vaccines which protect against influenza. This means that in clinical trials of influenza vaccines a large proportion of the cases of clinical influenza would not be prevented even by a totally efficacious vaccine. Also, the proportion of clinical influenza cases unrelated to influenza A fluctuates between trials according to seasonal and geographical variations in other viral infections which cause flu like illnesses. In a systematic review of the efficacy of influenza vaccines20 it was argued that, in this situation, the risk difference is the most appropriate summary statistic if the proportion of participants acquiring influenza A cases is more stable than the proportion acquiring of non-other influenza like viruses across the trials. Inspection of a L'Abb plot (Figure 16.5) and heterogeneity statistics (Table 16.4) indicate that this is the case. However, the statistical...

Lessons from Clinical Cancer Vaccination Trials

Vaccines of different designs have been tested in clinical trials accompanied by extensive moni toring of the immunological in addition to the clinical effects (Whiteside 2000). Despite the different designs, the outcomes of these trials are often very similar the efficient induction of tumor-specific T cell responses is usually reported. In some patients, 20 and more of all circulating CD8+ T cells were found to be specific for the vaccine antigens (Rosenberg et al. 2005 Trefzer et al. 2004). Several cases of clinical responses were reported. However, objective clinical responses, i.e., regression of the tumors by 50 and more, were the exceptions, and comparisons of the immunological and the clinical responses to therapeutic vaccination in cancer patients failed to demonstrate any correlation (Rosenberg et al. 2005 Trefzer et al. 2004). This conclusion can be illustrated with the results of a clinical trial with hybrid cell vaccines for the treatment of malignant melanoma at advanced...

Prospects for Vaccination in Cancer Therapy

Future developments in cancer vaccinology have to take the above-discussed experiences into account. While there is ample room for improvements in vaccine designs and delivery schemes, the basic problem of immune evasion by antigen loss cannot be overcome by vaccination therapy. It needs to be defined, therefore, for which cancers, in which disease states, and possibly in which schemes of combination therapy therapeutic vaccination can best exert its potential against cancer. Nearly all clinical trials for therapeutic cancer vaccine have been conducted with advanced-stage patients. These conditions are expected to be the most difficult to treat, and cure by therapeutic vaccination is bound to remain the exception. However, the extended survival of patients under vaccination therapy suggests its suitability for maintenance therapy where cure is not possible. Adjuvant therapy after surgery may be an important indication for tumor vaccination. A very extensive study with colon carcinoma...

Vaccines and toxin evolution

Despite high vaccination coverage, the once nearly eradicated diseases diphtheria and pertussis have unfortunately reemerged as a health threat in the developed countries (Bass and Stephenson, 1987 Bass and Wittler, 1994 De Serres et al., 1995 Galazka et al., 1995 Wilson, 1995 Andrews et al., 1997 de Melker et al., 1997 Baron et al., 1998). One possible explanation for this reemergence is that the constant selective pressure imposed by immunization might have resulted in increased antigenic divergence in the remaining bacterial population. Consequently, the effects of vaccination on toxin evolution are beginning to be examined (Pappenheimer and Murphy, 1983 Mencarelli et al., 1992 van der Zee et al., 1996b Mooi et al., 1998 Guiso et al., 2001 Weber et al., 2001 von Hunolstein et al., 2003). Comparative genetic analysis of the genes for B. pertussis PT and pertactin (an outer membrane protein) between recent epidemic isolates and the vaccine strains revealed that expansion of strains...

Iibackground Hsppeptide Complexes As Vaccines Against Cancers And Infectious Diseases

The idea that hsps chaperone not only tumor-specific peptides but indeed all peptides generated within a cell, including viral peptides generated during infection, was developed and successfully tested (10 N.E. Blachere and P.K. Srivastava, unpublished results). These results have led to the possibility of development of hsp-peptide complexes as the basis of a new generation of specific vaccines. Hsp-peptide complexes offer unique and unprecedented advantages over other types of vaccines against cancers, infectious and transforming viruses, intracellular bacteria, and protozoa 1. Knowledge of the antigenic epitopes which elicit immunity is a prerequisite for all forms of vaccination. Hsp-peptide based vaccination circumvents this necessity, as hsps are naturally complexed with the repertoire of peptides generated in a cell. For this reason, it is an ideal means for vaccination against infections for which the protective epitopes are yet undefined, or...

Use Of Hsppeptide Complexes As Cancer Vaccines In View Of Existence Of Shared Melanoma Antigens

One of the advantages of hsp-peptide complexes for vaccination against human cancers lies in the possibility that human cancers, like their murine counterparts, are antigenically diverse and individually distinct (see item number 3 in Sec tion II). In that scenario, it would be practically impossible to identify the antigenic epitopes of individual cancer patients. If, however, human tumors are antigenically cross reactive (as outlined in the preceding section), antimelanoma vaccines could be designed simply on the basis of peptide epitopes of known cross reactive melanoma antigens instead of hsp-peptide complexes isolated from individual melanomas. It is the premise of this chapter that hsp-peptide complexes provide a uniquely effective method of vaccination regardless of antigenic individuality or cross reactivity of human tumor antigens. This premise is elaborated as follows. First, the antigenic cross reactivity among human melanomas suggests that once a number of shared melanoma...

Synthetic Multivalent Vaccines

Synthetic vaccines include multivalent molecules that present multiple copies of antigenic determinants tethered to a scaffold. They are designed to mimic the critical parts of antigenic sites and ectodomains found on the surface of pathogenic viruses and bacteria (Figure 2.54). With multiple determinants on its surface, a multivalent molecule is likely to cross-link antigen-specific immunoglobulin receptors on a B-cell and thus stimulate immune responses against specific antigens 3 . 2.9.1 Peptide-Based Anti-influenza Vaccines Kragol et al. 202 reported a peptide-based multivalent vaccine designed to stimulate immune responses against influenza virus (Figure 2.55). This molecule (73) presents four copies of an ectodomain derived from the viral M2 protein, a membrane-bound ion channel, as a B-cell epitope, and two copies of S1 and S2 fragments as T-helper cell epitopes. Targeting B- and T-cells with three such distinct types of cross-linked epitopes makes the synthetic vaccine more...

Superantigens Vaccines and Therapeutic Potential

Mutation of residues in the high-affinity MHC class II binding site reduces the systemic toxicity of the fusion protein while retaining potent anti-tumor activity (83). Similarly, several cell-based vaccines for the stimulation of immunity to metastasic cancers also employ superantigens in order to boost the immune response towards the tumour (88). Third-generation vaccines consisting of tumor cells transfected with MHC class II, CD80, and SEB genes are very effective agents for the treatment of mice with established metastasic disease. The available data for the superantigens highlights their involvement in many diseases through one common mechanism. The production of a vaccine against bacterial superantigens could therefore lead to the abolition of such diseases. At present especially with the number of reported cases of multi-resistant Staphylococcus aureus (MRSA) on the rise, the need for a broad-spectrum vaccine or prophylactic effective against all structurally related bacterial...

Prospects for Vaccines Against Rickettsial Diseases

After recovery from a spotted fever or typhus rickettsiosis, patients and experimental animals develop solid immunity that prevents reinfection. Historically, killed whole rickettsial vaccines have ameliorated the outcome of rickettsial infection. A live attenuated vaccine against epidemic typhus effectively prevented the illness, but unfortunately was prone to reversion to virulence. Thus, past experience indicates that stimulation of protective immunity is entirely feasible. Subunit vaccine development has focused on the major antigens recognized by the humoral immune response, namely OmpA and OmpB (36,37). They stimulate immunity that is usually only partially protective. Recent studies of cross-protective immunity between spotted fever and typhus group rickettsiae have demonstrated that cross-protection is mediated by T-lymphocytes in the absence of cross-reactive antibodies (38). A challenge will be to identify the shared rickettsial proteins that stimulate the components of the...

Example 3 trials of BCG vaccine against tuberculosis

The following table is based on a meta-analysis by Colditz et al.20 which examined the efficacy of BCG vaccine against tuberculosis. 20 Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 1994 271 698-702. 22 Palmer CE, Long MW. Effects of infection with atypical mycobacteria on BCG vaccination and tuberculosis. Am Rev Respir Dis 1966 94 553-68.

Designs of Therapeutic Cancer Vaccines

T cell vaccines have to fulfill the following conditions for induction of CD8+ T cell (Stuhler and Walden 1993, 1994, 2002). First, CD8+ T cell induction is dependent on T cell help. Second, the dependently triggering them via pattern recognition receptors, a group of receptors that binds generic microbial molecules and activates innate immune responses. Among the pattern recognition receptors, the so-called Toll-like receptors (TLR) have been particularly well studied (Hemmi and Akira 2005). Their ligands include CpG motifs of bacterial DNA, double-stranded viral RNA, lipopeptides, and lipoproteins that all have peculiar molecular features only found in microbes or viruses. Engagement of pattern recognition receptors by these molecules leads to activation of antigen-presenting cells involving expression of costimulatory molecules and cyto-kines. T cell vaccines thus should include components that trigger all the above cell types involved in induction of CD8+ cytotoxic effector cells....

Role of Immunological Vaccine Adjuvants

Class I molecules on dendritic cells, which then migrate to the draining lymph nodes where specific T cell activation occurs. Vaccination with TAA-derived peptides alone may be suboptimal to charge and activate dendritic cells, and elicit specific T cell responses it thus requires simultaneous administration of adjuvants. GM-CSF has been used in various vaccine protocols, as it promotes local recruitment and migration of dendritic cells. Enhanced induction of CD8+ peptide-specific T cells and objective tumor responses had initially been reported in three melanoma patients following the addition of GM-CSF to a multipeptide vaccine (Jaeger et al. 1996). In two consecutive small phase I trials performed in tumor-free melanoma patients, no difference in the induction or frequency of peptide-induced T cell responses analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay was observed if tyrosinase peptides were applied alone or in combination with GM-CSF (Scheibenbogen et al. 2003)....


The first vaccine was developed by Weigl in Poland from infected lice from 1920 to 1930. Lice were inoculated intrarectally with viable R. prowazekii. Then, Weigl allowed the lice to feed on himself and his coworkers twice a day, permitting the rickettsiae to multiply in the intestinal cells of the arthropods (97). Many lice were necessary to produce vaccine (100 infected lice for a single dose of vaccine). The Madrid E nonpathogenic strain (98), the Cox vaccine egg (on egg embryonated), and the Durand vaccine (developed in the rat) were also used successfully (97). However, because antibiotic treatment is so efficient, vaccine was not considered a priority. The huge outbreak in Africa in 1997 has resulted in a different opinion as to the potential use of a vaccine.

Drugs and Vaccines

The smallpox virus once was as much of a threat as HIV is today, causing a disease that disfigured or even killed its victims. Because a vaccine was developed in the eighteenth century and was gradually made available to people all over the world, the disease was virtually eliminated. (There have been a few recent reports of cases in India.) The last confirmed outbreak was in 1977 in Somalia. In that year, the World Health Organization declared the disease eradicated. Since then the vaccine has not been given, and few people today are immune to smallpox. The researchers, who were trying to develop an effective contraceptive vaccine, made a simple change in a mousepox virus, inserting a gene that produces a body chemical called interleukin-4 (IL-4). They hoped to stimulate an immune reaction against mouse eggs, which would produce a contraceptive effect. Instead, the gene acted to suppress the part of the immune system that normally fights off viral infection. All the animals given the...

Scrub Typhus Vaccine

Vaccines offer the potential of long-term prevention from morbidity and mortality caused by scrub typhus. They also obviate the difficulties posed by drug resistance, vector control, and preventive chemoprophylaxis. Currently, there is no vaccine in use. During the 1940s, attempts to protect people against scrub typhus by immunization with killed rickettsial vaccines gave uniformly discouraging results under the conditions of field exposure, although animal trials had been successful (120,121). The failure of these vaccines in humans was most likely due to the inability of the killed organisms used to stimulate long-lasting heterologous protection. Other vaccine strategies have included using gamma-irradiated organisms that were metabolically active but incapable of growth, and combined infection and antibiotic prophylaxis (10,122). A DNA vaccine relying on the immunodominant 56-kDa outer membrane protein provided some protection in mice (123). A recombinant 56-kDa protein vaccine...

Therapeutic Vaccines

The discovery that naked DNA could be used as vaccines came about in the early nineties. It was found that plasmid DNA alone (without lipid carrier), when injected into the muscle of animals, was expressed in situ. Studies showed that the gene encoding the influenza virus antigens stimulate both specific humoral (antibodies and B cells) and cellular responses (cytotoxic T cells), accompanied by protection against a live influenza virus infection. DNA-based immunization has since been shown to be effective in inducing protective immunity in various animal models, and may provide a potential alternative to traditional methods of vaccine development. Vaccines are currently developed by the use of live attenuated or killed bacterial and viral preparations. The former group includes vaccines for measles, mumps, and rubella, which stimulate both humoral and cellmediated immune responses. The latter group includes vaccines for influenza, tetanus, hepatitis, which are relatively less potent,...

Acquired immune deficiency syndrome

(AIDS), first identified in 1981, is an infectious disease characterized by failure of the body's immunologic system. Affected individuals become increasingly vulnerable to many normally harmless microorganisms, eventually leading to severe morbidity and high mortality. The infection, spread sexually and through blood, has a high fatality rate, approaching 100 percent. Caused by a human retrovirus known as HIV-1, AIDS can now be found throughout the world -in both industrialized countries and developing nations. Public-health officials throughout the world have focused attention on this pandemic and its potentially catastrophic impact on health, resources, and social structure. Treatments for the disease have been developed, but no cure or vaccine currently exists.

Basic ideas in clinical trial design

Example 1.1 The Salk Polio Vaccine trial One of the largest trials ever conducted took place in the US in 1954 and concerned the evaluation of the Salk Polio Vaccine. The trial has been reported extensively by Meier (1978) and is used by Pocock (1983) in his discussion of the historical development of clinical trials. 1.08 million children from selected schools were included in this first trial. The second graders in those schools were offered the vaccine while the first and third graders would serve as the control group. Parents of the second graders were approached for their consent and it was noted that the consenting parents tended to have higher incomes. Also, this design was not blinded so that both parents and investigators knew which children had received the vaccine and which had not. A further 0.75 million children in other selected schools in grades one to three were to be included in this second trial. All parents were approached for their consent and those children where...

Notes For Organization And Classification

Chapter 4 treats multivalent molecules that inhibit or modulate mammalian cells. The list of tested macromolecular targets is extensive. Selected examples include surface receptors (hepatic asialoglycoprotein receptor, selectins), enzymes (acetylcholine esterase), G-protein-coupled receptors (opioid receptor), and ion channels (cyclicnucleotide-gated channel). Applications in nucleic acid are demonstrated by a daunorubicin dimer acting as a DNA intercalator, and a hairpin-shaped polyamide dimer acting as a minor groove binder. In addition, several types of synthetic vaccines are illustrated, including multivalent globo-H presented on protein carrier as the one mimicking cancer cell surface. Discussion of such diverse cellular targets should help to better understand multi-valent concepts and applications in drug development.

The Unique Role of Heat Shock Proteins in Infections

Memory is another common feature shared by both lymphocyte subsets. Phenotypically immune memory appears as an improved response to repeated contact with the same or a similar antigenic structure. If this structure is expressed by a microbial pathogen, a booster provides the basis for preventive vaccination. On the other hand, if a cross-reactive structure becomes expressed by self, autoimmune responses may arise (6).

Global Epidemiology Of Sexually Transmitted Diseases

As would be expected from the diverse cultures and sexual mores throughout the world, the epidemiology of sexually transmitted disease is highly variable in distribution and changing in different ways in different regions. The factors that influence these differences in prevalence and incidence are the nature of the sexually transmitted disease itself, whether it is curable or incurable by antimicrobials, or is preventable or non-preventable by vaccines. The availability of highly developed health-care networks in western industrialized countries, compared with those of developing countries, influences the epidemiology in a number of ways, through ease of transmission, availability of diagnostic facilities and drugs, transmissibility of behaviour modification messages, and levels of education allowing receptiveness to these messages. The availability of new diagnostic tests has allowed the definition of large reservoirs of asymptomatic infection which have led to marked changes in our...

Methods for estimating a combined effect estimate

While neither of the two models can be said to be correct, a substantial difference in the combined effect calculated by the fixed and random effects models will be seen only if studies are markedly heterogeneous, as in the case of the BCG trials (Table 2.2). Combining trials using a random effects model indicates that BCG vaccination halves the the risk of tuberculosis, whereas fixed effects analysis indicates that the risk is only reduced by 35 . This is essentially explained by the different weight given to the large Madras trial which showed no protective effect of vaccination (41 of the total weight with fixed effects model, 10 with random effects model, Table 2.2). Both analyses are probably misguided. As shown in Figure 2.2, BCG vaccination appears to be effective at higher latitudes but not in warmer regions, possibly because Table 2.2 Meta-analysis of trials of BCG vaccination to prevent tuberculosis using a fixed effects and random effects model. Note the differences in the...

Treatment and Control

The attenuated live yellow fever virus vaccine (17D) has been used for over 50 years in the successful immunization of millions of people. A live attenuated dengue virus vaccine is being tried. A killed Japanese encephalitis virus vaccine is given to millions of people in the Orient. A killed RSSE virus vaccine is used extensively in parts of the former Soviet Union. Killed virus vaccines against EEE, western equine encephalitis, Venezuelan equine encephalitis, and Rift Valley fever virus are used primarily to protect livestock. Laboratory workers studying these viruses are routinely immunized.

The Small Immune System Of The Newborn

Not only has the newborn an immune system oflimited size, but it is also somewhat functionally deficient at birth. Switching through the immunoglobulin isotype genes is inefficient and early antibody responses are mainly composed of IgM antibodies . Immunologic memory is reported to be sparse and several cytokines are only produced in small amounts like IFN-y (interferon-Y and IL-4 (interleukin-4). Phagocytes also have a decreased function. Even if newborns are sensitive to infections they are still apt at protective immune responses quite early. They are not like an immunodeficient individual who cannot respond. For instance newborns can mount a memory TH1 response to BCG-vaccine of a magnitude similar to that in adult6. On the other hand the newborn can only produce 10 of adult levels of IFN- y, known to be important in defense against Mycobacteria.

Argentine Hemorrhagic Fever Junin

Convalescence lasts several weeks after severe illness, and recovery is usually complete. No specific antiviral agents are known but recent reports describe successful treatment with immune plasma. When given before the eighth day of illness, it markedly reduces mortality. Rodent control appears an obvious prevention measure but is impractical given the vast areas of endemicity. A live attenuated vaccine shows promise for preventing the disease in humans. Another possibility being explored utilizes the avirulent Tacaribe virus to induce immunity against Junin.

A tuberculin test does not measure immunity By itself it does not indicate the presence or extent of TB disease it only

The criterion for a significant or positive tuberculin test depends on whether a child has previously had BCG vaccination or not. This is because a reaction to tuberculin is usual after a previous BCG, at least for several years.The reaction is usually weaker (diameter often less than 10 mm) than the reaction to natural infection with M. tuberculosis. A tuberculin test is considered significant or positive when the diameter of skin induration is 10 mm or more. However, if the child is HIV-infected, the tuberculin test is considered positive if the induration is 5 mm or more. A positive tuberculin test is only one piece of evidence in favour of the diagnosis of TB. The younger the child and the greater the diameter of induration, the stronger is that one piece of evidence.

Immunology of Infection

The persistence of PV-induced lesions suggests that the development of an effective cellular immune response against PVs following infection is neither immediate nor universal. Nonetheless, several observations suggest that the host's cell-mediated immune response is responsible for limiting the growth and promoting the regression of PV-induced lesions. First, there is a high prevalence of PV-induced lesions and malignant tumours in hosts with suppressed cellular immunity. Second, the regression of anogenital and skin warts in humans is associated with a pronounced local infiltration of mononuclear cells (activated T lymphocytes, macrophages and, to lesser extents, NK cells and B lymphocytes) invading the epidermis and destroying the neoplastic tissue. On this basis, the cellular immune response in spontaneously regressing warts appears to be consistent with a delayed type hypersensi-tivity (DTH) reaction to foreign antigen. Nonetheless, the presence of specific cytotoxic CD8 + T...

Preface to Third Edition

Human diseases (cholera, anthrax, whooping cough, tetanus, botulism, diptheria, clostridial gas gangrenes, severe diseases caused by superantigenic toxins, Helicobacter pylori-associated peptic ulcers and carcinomas, food poisons, etc.). In this respect, the targeting of immune system cells by various toxins led to a better evaluation of both their beneficial effects (for example as immunomodulators in the case of cholera toxin B subunit) and pathophysiolgical effects in certain diseases in connection with the immune system. Finally, the past years witnessed considerable progress on toxin applications in vaccinology, tumor therapy, and new approaches in the treatment of various diseases. Whether some wild-type toxins can be directly used as therapeutic agents, protein engineering permits us to model more specific and efficient molecules or molecules with a novel activity, or to target a restricted subset of cell population. Novel recombinant toxins are already proposed in the...

Control And Prevention Of Epidemic Typhus

Louse eradication is the most important preventive measure and is essential in the control of epidemic typhus outbreaks. As body lice live only in clothing, where they also lay their eggs, the simplest method of delousing is to remove and destroy all clothing. Thoroughly washing and boiling clothes can also effectively destroy lice. Dusting of all clothing with 10 dichlorodiphenyltrichloroethane, 1 malathion, or 1 permethrine (as in the protocol of the World Health Organisation) is also a rapid and effective method of killing body lice and reduces the risk of reinfestation (55). Although protective vaccines have been developed, they have not been widely used because effective antibiotic treatments are readily available.

HBV and Immunoprophylaxis

The host--cell interactions that allow for the persistence of a virus, and the failure of the immune system to eliminate it in an immunocompetent individual, is a topic of considerable relevance for the DNA tumour virus field. For largely noncytopathic viruses, such as HPV, EBV, KSHV and HBV, they must either overwhelm an effective immune response or adopt mechanisms that allow for avoidance, as suggested by one or more of the hypothesized routes for progression from infection to generation of hepatocellular carcinoma (Figure 18). One approach for EBV therapy, as discussed elsewhere, assumes that the immune system may need to, and can, be stimulated specifically to recognize viral genes that might be expressed in its associated tumours, with beneficial effects. As noted, however, realistically such an approach is aimed at reducing morbidity, rather than effecting cure (Khanna et al., 1999). Such an approach may be even more valid for HBV, which can infect virtually all the hepatocytes...

Structure of the Book

Sample size calculation based on nonparametrics for comparing means with one or two samples is discussed in Chapter 11. Chapter 12 includes sample size calculations in other areas of clinical research such as dose ranging study including the determination of minimum effective dose (MED) and maximum tolerable dose (MTD), analysis of variance with repeated measurements, quality of life assessment, bridging studies, and vaccine clinical trials. In vitro bioequivalence studies are provided to illustrate the derived formulas for sample size calculation.

What Is an Autoimmune Disorder

Vaccines prevent the development of a particular virus, such as polio, for example. Vaccines work like this the vaccine serum contains a small amount of a particular virus in a deadened, noncontagious form an antigen. Essentially, the vaccine shows your body a sample of the virus. This stimulates your immune system to produce a specific antibody to combat the unwanted virus. Later, if you catch the virus, your body will have sufficient specific antibodies, as well as primed lymphocytes ready to make more, to destroy it before it can do any damage. That's why you don't necessarily need to get chicken pox to be protected from it you can be vaccinated against it instead. However, creating a vaccine is a painstaking, complicated process, and it can take years for scientists to develop vaccines to combat specific viruses. Polio struck at epidemic proportions throughout the 1940s and 1950s until a vaccine was discovered.

Preface to First Edition

Disruption of these same central cellular processes in vivo can also be the critical event in the pathogenesis of infectious diseases for man or domestic animals. Many such infectious diseases have major social or economic impacts on man, and such considerations have quickened the pace of the search for therapeutic agents. Currently, a number of physically inactivated bacterial or hybrid engineered toxoids are used as immunogens in vaccination programmes, and there is a major international effort to develop new and more effective vaccines based on our deeper understanding of the molecular events in pathogenesis and the host response to infection. T. Montie (Academic Press) in the early 1970s, most of the books published in the past twenty years have covered the subject by presenting individual toxins or groups of toxins in separate chapters. This is not the main approach followed in this book. Our aim is not to give an exhaustive review of the wide spectrum of the protein toxin...

Confounding and Interaction 211 Confounding

In clinical trials, there are many sources of variation that have an impact on the primary clinical endpoints for clinical evaluation of a test drug under investigation. If some of these variations are not identified and not properly controlled, they can become mixed in with the treatment effect that the trial is designed to demonstrate, in which case the treatment effect is said to be confounded by effects due to these variations. In clinical trials, there are many subtle, unrecognizable, and seemingly innocent confounding factors that can cause ruinous results of clinical trials. Moses (1992) gives the example of the devastating result in the confounder being the personal choice of a patient. The example concerns a polio-vaccine trial that was conducted on two million children worldwide to investigate the effect of Salk poliomyelitis vaccine. This trial reported that the incidence rate of polio was lower in the children whose parents refused injection than whose who received placebo...

Pathogenetic Mechanisms

During development of the initial immune response, the whole repertoire of memory T cells would potentially be attracted to the local inflammatory site. However, certain T-cells subsets may be selectively attracted to particular tissues (57). On the other hand, there is no indication that the homing process is antigen specific. Mycobacterial antigens are potent immunogens, and they are almost ubiquitous. If not presented by infection, most people will be sensitized by naturally occurring mycobacteria in the environment or by the extensively applied BCG vaccine. This would explain why T cells isolated from chronic inflammatory tissues react vigorously to mycobacterial antigens. Furthermore, the wide repertoire of mycobacterial T-cell specificities observed in SF of patients with RA could be interpreted on this background.

The Medical Equivalent of Shock and

There are other factors that often slow work for scientists. Laboratories are exceptionally expensive places to run, and scientists are often in competition with one another to find a new medicine or vaccine that can bring in funds for research. For that reason, research facilities are rarely willing to consolidate or share information, since they view one another as rivals. And because there is no greater achievement for a scientist than discovering a pathogen or its cure, the scientists themselves are often competitors.

Study Area And Population

The area has been under demographic and epidemiological surveillance since the sixties. From 1987 to 1997, information about all births, deaths, migrations and weaning events was collected weekly by highly trained fieldworkers, while bi-monthly rounds were used from 1997 to 1999. Several studies on pertussis vaccines included organization of monthly vaccination sessions according to the Senegalese Expanded Program of Immunization (EPI), from 1989 to 1997.25 A high level of participation (about 80 of infants) was obtained by systematic call of eligible infants during home visits by field workers the week before the session and by transport services. Anthropometric measurements (length measured to the nearest mm and weight measured to the nearest 10 g) were taken routinely.

Breastfeeding And Growth

According to a study of the relationship between nutritional status, growth and mortality risk in a sample ofmore than 5000 children aged 0-5 years, conducted in the Niakhar study area from 1983 to 1985, breastfed children had significantly lower height-for-age and weight-for-height than weaned children from 18 to 36 months of age.7 Traditional midwives, field workers and mothers of underfives in the area consistently stated that this association between malnutrition and breastfeeding did not surprise them, but that it was due to later weaning ofmalnourished children (K. Simondon, unpublished observations). In order to test this statement, a retrospective analysis of factors associated with age at weaning was conducted in a sample of 4515 children, who were born from 1989 to 1995 and had attended vaccination sessions from 1990 to 1996.26 Duration of breastfeeding was analyzed using Cox's proportional hazards models, because about 20 ofthe sample was right-censored, i.e. date of...

Subclinical Mastitis As A Risk Factor For Motherinfant Hiv Transmission

Sectional study of women attending vaccination clinics in the Durban area with their infants (Willumsen et al submitted). We specifically inquired about symptoms of mastitis or problems with breast feeding and we collected milk from each breast separately. Problems ofbreast pain, cracked nipples or other breast feeding difficulties were reported by only 3 of the women and could not explain the high prevalence of raised Na K ratio. Of 269 women with infants 20 weeks old or less, 71 (26 ) had Na Kratio > 0.6 in milk from one breast and 77 (29 ) had raised Na K ratio in both breasts. Unilateral inflammation thus seems common for both subclinical and clinical mastitis, indicating that local inflammation or infection may be an important cause. Although the different sampling methods prevent simple comparisons across studies, raised Na K ratio appeared more common in this population than in those we studied in Bangladesh and Tanzania. One possible reason for this is the high prevalence of...

Future Directions for HSC Transplantation

Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus (HIV) could lead to development of T lymphocytes and monocytic cells resistant to HIV infection after transplantation (thus a form of intracellular vaccination). Transducing autologous HSC138 in AIDS patient to carry protective genes such as anti-sense to HIV-gag, RevM10 and anti HIV-toi,139 has been pursued in early clinical trials.140

Are there other causes of hepatitis

Hepatitis can be caused by many different types of hepatitis viruses. Currently vaccines are only available for hepatitis A and B, the most common forms. Hepatitis C is common among injecting drug users but can probably be transmitted less efficiently through sexual contact. Blood donors are screened for hepatitis C, but there is no vaccine to prevent infection.

Overwhelming Postsplenectomy Infection

Results in the prepneumococcal vaccine group were reported from Boston. In adults, 4 cases of OPSI were observed during 4,837 person-years of follow-up, and in children, 2 cases were found during 717 person-years of follow-up.1 ' A review of 8 reports on postsplenectomy infection in adults found a variation in incidence from 1 case per 137 person-years of follow-up to 1 per 1,190 person-years, with no fatalities.

Historical Perspective

Transmissible agents have a venerable part in the history of cancer research. In 1911, Peyton Rous, often considered to be the father of tumour virology, was the first to demonstrate the acellular transmission of a sarcoma between chickens (the term 'virus' had not yet been coined). The research community was not receptive to the notion that a chronic disease may have an infectious cause and it was to be 55 years before Rous received the Nobel Prize for his seminal discovery. In the 1930s, Shope discovered oncogenic pox viruses and papillomaviruses in rabbits. In 1936, Bittner demonstrated that predisposition to breast cancer in C3H mice was transmitted in breast milk. In 1951, Gross discovered the first murine leukaemia virus and, in 1960, Hilleman identified SV40 virus as a contaminant of polio vaccine grown in monkey kidney cultures. However, the concept that infections might cause chronic diseases, such as cancer, can be traced back even further. For example, in the nineteenth...

Table 1 Cancers attributable to infections these are conservative estimates adapted from Parkin et al 1999

A better understanding of the role of infectious agents in the aetiology of cancer is a public health imperative, because such cancers are theoretically preventable by vaccination or early treatment of infection. Furthermore, cancer-causing infections often cause substantial morbidity and mortality from non-malignant conditions. Therefore, an additional benefit of any scheme to reduce the burden of cancers caused by infections would also involve a reduction in the incidence of other diseases.

Summary and future considerations

In relation to cancer, the identification of novel antigens not only plays a crucial role in the biology and pathology of different types of cancers but also activate both cell-mediated and antibody-mediated immune responses, a more effective immunotherapeutic strategy (i.e. cancer vaccines) for educating our immune system could be developed. In this way, persistent tumour antigens would be recognized and remembered by memory B and T cells already present in the immune system, leading to the prevention of most human cancers (Lollini and Forni, 2003). However, as discussed above, immunization against such persistent tumour antigens should be performed in young people when the immune system is most efficient at recognizing and destroying foreign antigens (Miller, 1996 Abgrall et al., 2002 Davidson et al., 2002 Costello et al., 2003 Lollini and Forni, 2003 Waldman, 2003). Recent advances in this direction may be imminent thanks to advances in tumour immunology, cell and molecular biology...

Human Immunodeficiency Virus HIV

In the absence of an effective vaccine, behavioural change is still the most important method of controlling the spread of HIV. Transmission of the virus in blood and blood products has been largely halted in developed countries, with the introduction of screening and education in combination with needle exchange programmes, which have been shown to be effective in reducing the spread of HIV among intravenous drug users. The bulk of transmission of HIV is sexual, however, and preventive activities include reducing the number of sexual partners, modifying the types of sexual contact and the use of condoms. Several behavioural interventions in high-risk populations have been tried, with variable results, but continued education remains a high priority.

S mansoni S intercalatum

Use of these integrated control measures over many decades has led to the recent eradication of schistosomiasis in Japan, Tunisia and Monserrat (WHO, 1993). In China, 40 years of unremitting control measures have reduced the prevalence of infection by about 90 . Elsewhere in the World, including Brazil, Egypt, Iran, the Philippines and Venezuela, significant reductions in disease prevalence have been achieved. Even in places where the prevalence of infection has remained high, serious manifestations of disease are becoming less common with the use of effective chemotherapy, although declines in cancer incidence are not yet apparent (WHO, 1993). Despite this, the number of cases of schistosomiasis worldwide was estimated to be the same in 1993 as it was in 1984 (WHO, 1993). In endemic areas, populations (and hence the number of susceptible hosts) continue to grow. In addition, developments in water resource management, land use and irrigation have led to a spread of schistosomiasis to...

Genetic Organization and Lipopolysaccharide Biosynthesis

Phase transition of C. burnetii Nine Mile is accompanied with sequential loss of the O-side chain specific sugar -d-virenose or l-dihydroxystreptose and the GalU-a-(1,6)-GlcN disaccha-ride. RFLP pattern comparison from C. burnetii phase I and phase II isolates initially demonstrated a correlation between loss of the O-antigen and a chromosomal deletion within the O-polysaccharide gene cluster (90,113). However, sequence analyses of several isolates revealed no correlation between deletion and LPS chemotype. C. burnetii RSA514 and the Australian strain AUST II display a semirough LPS chemotype, which lacks only the -d-virenose residue in the O-specific chain. Interestingly, the AUST II strain harbors an intact O-antigen cluster similar to RSA514, which has a deletion of approximately 32 kb in this region. Further on, C. burnetii RSA439 and the European vaccine strain M44 express a rough LPS, but only RSA439 has a deletion of approximately 26 kb within the O-antigen cluster (114,115)....

Selection For Gentle Retroviruses And The Mucosal Immune System

Translating this argument to the case of a virus of a metazoan host, the situation that corresponds to preventing a new infection of the multicellular host organism is preventing entry of the STD agent into the tissues of the host's sexual tract. It would appear that the most effective way for this circumstance to be implemented by an infecting pathogen is to stimulate the host to mount both a cellular and humoral (especially IgA) response in the mucosal surfaces against the virus. This need not have any major influence on the pathogen particles already inside other parts of the body, but some minor side effects might well ameliorate or slow down the disease process within the host. Extensive studies of mucosal immune responses have and are being made. While these studies were are largely designed to look for opportunities for future vaccine development, they serve for the present purposes of showing that IgA and T-cell responses are made in mucosal tissues (Mestecky and Russell,...

T Cell Targets on Tumor Cells

Cancer germline antigens, mutated antigens, and viral antigens (reviewed in Renkvist et al. 2001). These TAA have facilitated the development of immunotherapeutic approaches. The characterization of numerous MHC class I-binding epitopes of the TAA recognized by CD8+ T cells simplified the development of synthetic vaccines. MHC class I-binding epitopes consisting of 9-12 amino acids can directly be injected for patient immunization. More recently, epitopes also derived from various TAA presented in association with MHC class II and recognized by CD4+ T cells have been identified.

With Differentiation Antigens and Cancer Testis Antigens

The first trials studying the immunogenicity and toxicity of peptide vaccination have been performed in patients with metastatic melanoma (Marchand et al. 1999 Jaeger et al. 1996 Cormier et al. 1996 Rosenberg et al. 1998 Scheiben-bogen et al. 2000 summarized in Table 18.1). In general, objective tumor remissions were only occasionally seen and were usually restricted to melanoma patients with limited disease. For instance, in a MAGE-3 peptide trial reporting a 30 response rate the 7 patients showing an objective tumor remission all had metastatic disease limited to soft tissue or lymph nodes and 14 patients who were not included in the response evaluation had early progressive disease during vaccination (Marchand et al. 1999). Antigens tested in clinical studies were mostly cancer germline antigens or melanocyte differentiation Table 18.1 Clinical studies of peptide vaccination in patients with metastatic melanoma Table 18.1 Clinical studies of peptide vaccination in patients with...

Reimmunization After HSCT

Most recipients of HSCT will lose their immunity to the vaccinations they have received prior to HSCT. In addition, patients with chronic GVHD are at risk for infections with streptococcus pneumoniae and H. in-fluenzae. Therefore, re-immunization of HSCT recipients is essential. A recent guideline was published detailing the rationale for vaccination schedules 40 . In general, at 12 months post HSCT in patients without chronic GVHD, vaccinations can be given on a schedule similar to that used with normal infants however,the 23-valent pneumococcal polysaccharide vaccine may not result in adequate antibody response, even when administration is delayed to 12months 14 . The 7-valent pneumococcal conjugate vaccine is linked to a protein carrier and may enhance immune response. A recent study showed early immunization with this 7-valent vaccine resulted in protection in most patients. The authors of the study suggest an administration schedule of 3,6 and 12 months 26 .Vaccines that are...

Ralph Crott Introduction

Although there exists a conceptual difference between cost-of-illness (COI) studies and more complete economic evaluations, the problem of estimating the cost of the medical resources used is common to all. One can say the same about whether one is interested in the costing of preventive measures (i.e., vaccination programs or prophylaxis) or interventional measures such as surgery.

Alexandre Emile John Yersin 18631943 Swiss French Microbiologist

The microbiologist Alexandre Yersin is credited with being the first to isolate successfully the bacillus responsible for the bubonic plague and produce a vaccine against it. Yersin was born on the shores of Lake Geneva in Lavaux, Switzerland. Yersin's father predeceased him, and his mother raised him while running a finishing school for girls. Though brought up a Calvinist Christian, Yersin eventually rejected all religion, but he did take up as a hobby the study of insects. As a young man he quitted the Academy of Lausanne, where he had finished a year of pre-medical training, going to Marburg, Germany, in 1884 to study botany. While there he switched his studies to human anatomy and pathology. In 1885 Yersin relocated to Paris, where he worked first in the Hotel Dieu hospital and then in the private bacteriological laboratory of Andre Cornil. While there he met the famed bacteriologist Louis Pasteur, at whose institute Yersin served first as a volunteer in studies of rabies and...

Ruth Freitag Introduction

The modern biotechnology industry has provided the medical community with a new type of pharmaceutical, namely recombinant proteins and peptides. The number of such protein-based drugs is already impressive and expected to increase considerably in the future, as the function and gene sequence of more and more proteins is discovered, for example, as a result of the human genome project and related activities (genomics, proteomics). Soon gene therapy may bring about the next revolution in medical treatment, where for the first time it will be possible to correct the genetic causes of a disease rather than to just counteract the consequences of that genetic defect, i.e., the symptoms of the disease. Gene vaccines present another evolving medical possibility, which has been shown to have some significant advantages over the prophylactic measures taken at present against certain infectious diseases. Biopharmaceuticals, such as proteins and nucleic acids, thus extend the possibilities of...

Tumor Associated Antigens and T cell Epitopes

The first tumor-associated antigens and T cell epitopes were identified by expression cloning of complementary DNA (cDNA) prepared from tumor cells from a melanoma patient into COS cells that had been stably transfected with the genes for an HLA molecule, and probing these double-transfectants with T cells from peripheral blood of the same patient. After repeated sub-cloning, the gene of the tumor-associated antigen was isolated and sequenced for identification (Boon et al. 2006 van der Bruggen et al. 2002). It turned out to be a hitherto unknown protein expressed in tumor cells and testes only, and was dubbed MAGE. It was the first of the extended family of MAGE proteins and the first member of the group cancer-testis antigens. Since testis is an immune-privileged organ, these antigens are relatively tumor-specific and therefore preferred vaccine targets. No function of the tumor testis-associated MAGE proteins has yet been determined. ferent bioinformatic tools. The latter has...

Overview Of Clinical Management

In this regard, adjuvant therapy for melanoma has recently focused on immunoenhancing therapies, such as melanoma vaccines and treatment with proinflammatory mediators, such as interferon-a. Although these approaches have provided encouraging preliminary data in the treatment of clinically advanced melanoma metastases (Murphy et al., 1993), their role as adjuvants to ameliorate the potential for eventual metastatic spread is not as yet fully defined and awaits further experimental validation.

Tumor Specific T cell Responses

Several lines of evidence point at the key role of CD8+ cytotoxic T cells in tumor immunity. A large number of lymphocyte depletion or reconstitution experiments in animal tumor models have proved their capacity to identify and kill tumor cells. Similarly, there are a number of in vitro experiments with human tumor and autologous CD8+ T cells that prove the same point. Immunohistochemical analyses have demonstrated the presence of CD8+ T cells in different tumors and, as in the case of melanoma, have correlated high frequencies of these cells in tumor infiltrates with better prognosis (Parmiani 2005 Rosenberg 2005a, b). Consequently, tumor vaccinology has, in contrast to previous efforts in vaccine development, focused on T cell vaccines. Tumor specificity of the T cells may be tested as follows. The receptor specificity can be directly visualized with fluorochrome-labeled tetramer-ized recombinant MHC molecules loaded with the tumor-associated T cell epitopes of interest, and then...

Clinical Features and Associated Findings

The Advisory Committee on Immunization Practices (ACIP) of the United States Public Health Service has recommended that the United States adopt a sequential poliomyelitis immunization schedule--two doses of inactivated polio vaccine (IPV) followed by two doses of live oral polio vaccine (OPV). y , y At the present time, the World Health Organization recommends only OPV for both routine immunization and to achieve polio eradication. y , y Although OPV is among the safest of vaccines, one case of vaccine-associated polio occurs for every 2.5 million doses of OPV administered. The proposed sequential schedule recommended by the ACIP is a compromise that seeks to retain the advantages of OPV while preventing half of the 8 to 10 vaccine-related cases that occur every year in the United States. y

Bovine Anaplasmosisgallsickness

Of the Anaplasma that infect cattle, A. marginale is the most important, causing almost all clinical outbreaks of bovine anaplasmosis (4). The closely related A. centrale is of limited patho-genicity and seldom causes disease a South African isolate has been used extensively as a live vaccine against A. marginale.

Ligands for Tumour Associated MHC Peptide Complexes

Tumour-specific T cells can be raised in the patients through vaccination, a strategy that so far has had only limited success (Boon et al. 2006). Another possibility is the adoptive transfer of tumour-specific T cells (Blattman and Greenberg 2004). However, the application of cellular reagents for therapy is complicated by a number of factors. The most serious drawback is that the use of a cytotoxic T lymphocyte (CTL) population is limited to the individual patient from whom it is derived otherwise incompatibilities between the MHC types of the CTL preparation and the recipient as well as problems due to MHC restriction will arise. Furthermore, the expansion of CTL ex vivo is a difficult, time-consuming and expensive procedure.

Human TCell Lymphotrophic Virus Type

HAM-TSP spinal cord material, in addition to the upregulation of HLA and cytokine molecules, suggests that an increase in immunological activity in the CNS is the basis of the pathogenesis of HAM-TSP. 1 Immunosuppressive therapy is the only modality available at the present time to treat HAM-TSP. There is no specific antiviral therapy. The best means of treatment may be prevention through an HtLv-1 vaccine, and it has been suggested that the development of vaccination against the HTLV-1 retrovirus would serve as a pathfinder for the development of a vaccine against HIV. y

Autologous Hsct In Recentonset Autoimmune Type 1 Diabetes Mellitus

The benefit-to-risk ratio of autologous HSCT would favor autologous HSCT, however, with the development of gene therapy or successful pre-autoimmune vaccination protocols. If autologous HSCT could correct genetic predisposition to the development of type 1 diabetes, then the potential for long-term disease remission (or cure) would negate the necessity for chronic post-HSCT immuno-suppressive therapies and offset the acute risk of mortality.

Canine Monocytic Ehrlichioses

There are no vaccines available against canine ehrlichioses but a preliminary study has shown killed E. canis stimulate a humoral and cell-mediated immune response and animals may be protected against challenge (34). Chemoprophylaxis is effective (doxycycline 100 mg PO q24 hours) but the best prevention at the moment involves strict control of the tick vectors.

Salmon Poisoning Disease

N. salmincola can be treated with praziquantel (5 mg kg sc) and N. helminthoeca with oxy-tetracycline (7 mg kg q8h for five days) which should be given intravenously because of the vomiting and diarrhea. There are no vaccines, and infections are best controlled by preventing dogs eating uncooked salmonid fish.

Potomac Horse Feverequine Monocytic Neorickettsiosis

Oxytetracycline (6.6mg kg IV q24 hours for five days) is the treatment of choice and a response is usually seen within 12 hours. Inactivated, partially purified, whole-cell vaccines are available but protection is short-lived (around four months) and vaccine failures occur, possibly because of lack of cross-protection between strains of N. risticii (55).

Toxin evolution and transmission in the soil environment

The structural genes encoding the major virulence factors of B. anthracis responsible for anthrax, the anthrax lethal toxin and edema toxin genes (pag, lef, cya) and the poly-D-glutamate capsule biosynthetic genes (capBCA), reside on two large plasmids, pXO1 and pXO2, respectively (Okinaka et al., 1999a Okinaka et al., 1999b). Loss of the pXO2 plasmid resulted in the greatly attenuated Sterne vaccine strain. Although it does not appear that these plasmids are self-transmissible, there are reports that suggest conjugative plas-mids from other Bacillus species might be able to supply the conjugal transfer functions in trans for these two virulence plasmids (Andrup et al., 1996 Pannucci et al., 2002). If this is true, then it is conceivable that

Cell Surface Proteins

Bacterial cell-surface proteins play a role in host-parasite interactions and adaptive response to host defense systems. Cell-surface proteins also represent candidates for vaccine development and serve as useful markers for discrimination of closely related species or strains. As previously described, the Wolbachia surface protein gene exhibits a high level of sequence diversity between species, and has been used as a standard gene for strain identification. Genome sequencing of Wolbachia wMel identified two additional paralogues (named wspB and wspC) in the genome (12). Wu et al. showed that wspB evolves faster than wsp, and proposed that wspB may be an additional marker for discriminating between closely related Wolbachia strains. The A. marginale genome contains two large superfamilies containing immunodominant proteins (56-member msp2 superfamily and 9-member msp1 superfamily). As previously described, recombination between functional genes and pseudogenes contributes to the...

Functional genomics of bacterial pathogens 21 Comparative genomics

In addition, each genome contains genes that are present in only some or none of the other genomes. These strain-specific genes are enriched in genes of unknown function. Together, strain-specific and core genes form the so-called GBS pan-genome. Predictions suggest that the pan-genome is significantly bigger than that of each individual strain and that each newly sequenced genome will add on average 33 new strain-specific genes to the known pan-genome. In addition to the insights on the genetic diversity of S. agalactiae, these studies also provided the foundation for the development of an universal GBS vaccine 12 . For this, computer algorithms were used to identify 598 genes within the GBS pan-genome which are predicted to encode surface-associated and secreted proteins. Of these, 312 were purified and tested for their ability to protect mice from killing by S. agalactiae. Four antigens were identified which, if applied as a combination vaccine, are protective against...

Hepatitis C Virus HCV

HCV is a single-stranded RNA virus which shows marked genetic heterogeneity and at least six major subtypes are known, of which Ib is thought to be the most likely to lead to chronic liver disease. Whilst it is associated with only about one-sixth of all cases of hepatocellular carcinoma world-wide, this proportion is higher and rising in some areas, notably Japan and, to a lesser extent, Spain, Italy and the Middle East (Idilman et al., 1998 Bosch et al., 1999 Colombo, 1999). The infection is usually acquired in adult life via transfusion of blood and blood products or by the use of contaminated instruments and syringes by intravenous drug abusers. Perinatal and sexual transmission are unimportant. The onset of malignancy is preceded by cirrhosis in 90 of cases. The course is long, 20-40 years from infection to tumour, and patients are affected in late middle to old age. Table 3 shows that HCV is definitely associated with hepatocellular carcinoma in case-control and follow-up...

Clostridium Tetani

Some species are naturally resistant to tetanus, although antitoxic antibodies are usually not demonstrated in their tissues.287 Acquired resistance to tetanus is based upon circulating antitoxin, and among susceptible species, widespread vaccination has dramatically lessened the impact of tetanus on animal production. Passive immunity acquired by neonates from the dam (especially in the case of foals and mares) protects for 2-3 months, after which active immunization with toxoid can begin. Boosters, given at 1-5-year intervals, are commonly recommended.

Is Csm An Epidemic Or Sporadic Disease

Serologic differences existed among strains. Four serogroups were identified by the end of World War I. Vaccine therapy remained of limited value but - in the absence of anything else - was frequently tried. In the 1930s, French efforts to protect Africans against serogroup A by vaccination had inconclusive results, and similar British trials in Sudan were unsuccessful. In 1963, sulfa-resistant strains of N. meningitidis were detected, and their spread has halted sulfa prophylaxis. Penicillin therapy is still effective but has no preventive value. Vaccines against serogroups C and A were introduced in the early 1970s, and improved vaccines have been developed since, although protection against serogroup B is still unavailable. Meningitis remains a public-health problem, especially in underdeveloped countries. Death occurs in about 5 percent of all cases, even with prompt treatment.

Rosenbach History Of Tetanus 1886

A fluid toxoid was in use because of its harmlessness and efficacy (although it caused more local reactions than does the modern aluminum phosphate absorbed vaccine). This tox-oid, a combined diphtheria-tetanus toxoid vaccine, was given to infants in parts of France in the late 1920s and, by regulation, to French soldiers in 1931. After World War II, routine use of a combined vaccine of diphtheria and tetanus toxoids (DT) was urged for childhood immunization. Soon the triple vaccine, with pertussis added (DPT), became legally required for school admission in the United States. Childhood immunization

Spirulina Antiviral Studies In Vivo

Negative results with Spirulina either in patients or experimental animals could be the result of an insufficient concentration of the antiviral principle in the anatomical site where the virus is being replicated, or that the virus tested is not sensitive to the antiviral principles produced by Spirulina. For example S. platensis extracts have shown no antiviral activity against viruses like poliovirus and coxsackievirus.12 A similar situation has been found with S. maxima which has no antiviral activity against human adenovirus, poliovirus, rotavirus SA-11, measles vaccine virus, SSPE, and VSV.

Important Findings In The Pediatric Emg Laboratory

Because of the development of the polio vaccine, SMA has become the dominant anterior horn cell disease affecting children in developed countries. The onset of the most common variant, type I (Werdnig-Hoffman disease), is typically in the first 6 mo of life. The infants present with hypotonia, weakness, and delayed motor milestones. Mothers may report decreased fetal movements. Examination is notable for areflexia or hyporeflexia, hypotonia, weakness, and preserved extraocular movements. Tongue fasciculations may sometimes be observed, but are not a reliable finding, especially in young infants, and the lack of tongue fasciculations should never be used to exclude SMA. These children never sit independently and never walk. The majority do not survive the second year of life.

The Immune System And Cancer

Since the incidence of cancer increases rapidly in old age, ageing is another important factor associated with human cancers. Around 65 of all cancers are diagnosed in people over the age of 65 (see Chapter 2). While the increasing accumulation of mutations in genes over time is one factor contributing to the high incidence of cancers in old age, recent evidence suggests that malfunction of the immune system may also contribute (Ginaldi et al., 2001 Burns and Leventhal, 2000 Effros, 2003). It is well established that with increasing age there is deterioration of the immune response (i.e. immunosenescence), which results in increased susceptibility to infection, insufficient responses to vaccines and a high level of autoimmune disorders (Lords et al., 2001 Stacy et al., 2002 Burns, 2004). In particular, one of the common alterations in old age is a decline in T-cell mediated immune responses. The decline in CMI with age is a multifactorial phenomenon and could be due to (i) a decrease...

The First Line Of Body Defence

Vaccine Substances that provoke immune responses (e.g. bacteria, pollen, transplanted tissues) are called antigens. Each antigen may have several components called epitopes, and each epitope provokes the production of a specific antibody or stimulates a specific T-lymphocyte. (Antigen antibody generator.) A modified form of the original antigen that is used in vaccination in order to stimulate the production of memory B-cells and memory T-cells without causing the disease. Antigenic preparations that are used in educating the immune system. As described above, T-lymphocytes are responsible for cell-mediated immunity against foreign antigens. The aim of the majority of cancer vaccines under investigation is to develop antigen-specific T-cell-mediated immune responses against tumour antigens. Adaptive Immune System, Immunological Memory and Vaccination The development of memory B-cells and memory T-cells against the antigen on the infectious agent or cancer cell is the rationale for...

Beneficial Effects of Hsps

Beneficial effects to the host of hsps functioning as immunogen have also been described. Because any kind of microbial pathogen synthesizes hsps (see Table 1), and because hsps are highly conserved among different species, frequent contact with microorganisms of even low virulence could cause a strong immune response to these proteins. Antibody and T-cell responses to hsps have been described using peripheral blood and cord blood cells from healthy individuals (33,50,75,76). High anti-hsp antibody titers were observed in children vaccinated with the trivalent vaccine against tetanus, diphtheria, and pertussis, suggesting immunodominance of hsp antigens (77). Therefore, a more rapid immune response to virulent pathogens displaying hsp cognates may occur in healthy individuals. Consistent with this idea a purified major cytoplasmic membrane protein (a member of the hsp 60 family) of Legionella pneumophila has been shown to be protective in guinea pigs (78). Adoptive transfer of CD4 a p...

Heterogeneity between study results

The thoughtful consideration of heterogeneity between study results is an important aspect of systematic reviews.30,31 As mentioned above, this should start when writing the review protocol, by defining potential sources of heterogeneity and planning appropriate subgroup analyses. Once the data have been assembled, simple inspection of the forest plot is informative. The results from the beta-blocker trials are fairly homogeneous, clustering between a relative risk of 0-5 and 1-0, with widely overlapping confidence intervals (Figure 2.2). In contrast, trials of BCG vaccination for prevention of tuberculosis32 (Figure 2.3) are clearly heterogeneous. The findings of the UK trial, which indicate substantial benefit of BCG vaccination are not compatible with those from the Madras or Puerto Rico trials which suggest little effect or only a modest benefit. There is no overlap in the confidence intervals of the three trials. Other graphical representations, discussed elsewhere, are...

Heat Shock Proteins in the NOD Mouse

Several studies have established that the incidence of IDDM in the NOD mouse can be reduced by exposure to mycobacterial preparations including complete Freund's adjuvant (killed Mycobacterium tuberculosis in oil emulsion) (41-43) and the bacille Calmette-Guerin vaccine (BCG, live attenuated Mycobacterium bovis) (44). The mode of action is unclear, but hypotheses have included nonspecific immune stimulation, activation of suppressor lymphocytes or macrophages (45), alteration of cytokine profiles from TH1 to TH2 (46), or possibly by the common presence of mycobacterial hsp 65 in the administered antigen. In a later paper, Elias et al. repeated a number of elements of the experiments using human hsp 60 in place of the mycobacterial hsp 60 (48). The major difference was that immunization with hsp 60 did not reduce the incidence of IDDM but instead rapidly induced hyperglycaemia. An epitope of human hsp 60 was also identified which stimulated a T-cell response in NOD mouse. This peptide,...

Clostridium Perfringens Type C Enteritis A Backgroundepidemiology

Locally referred to as 'Darmbrand' (or 'fire-bowels') in Germany where outbreaks occurred in the post-World War II period and as 'pigbel' in Papua New Guinea where it was originally associated with ritual pork feasts.81'82 Several lines of evidence have implicated the (3-toxin produced by C. perfringens type C as the primary virulence factor in this disease, including serological studies in surviving patients, ' reproduction of the lesions in guinea pigs, and the clinical efficacy of a toxoid vaccine in an area in which the organism is endemic.85'86 The epidemiology of this disease has been best described in the Highlands of Papua New Guinea where the disease is endemic and affects primarily children under the age of 13 years (see Chapter 12).88 abdominal emergencies requiring surgery and accounted for 23 of all deaths on the pediatric wards at the base hospital in Goroka, Papua New Guinea.88-97 The incidence of disease in nonimmunized children aged 1-15 years in the Chimbu province...

Other Diseases of the Spotted Fever Group

Inapparent infection is common, occurring in as many as half the cases. Rubella has special significance when a woman contracts it in early pregnancy because fetal infection can ensue and result in congenital rubella syndrome (CRS). Rubella is a vaccine-preventable disease, but the vaccine is not yet widely used on a global basis.

Acute Bacterial Meningitis

There are approximately 25,000 cases of bacterial meningitis in the United States each year, but this disease is much more prevalent in developing countries. Group B streptococci and gram- negative enteric bacilli are the etiological organisms of the majority of cases of bacterial meningitis during the neonatal period in developed countries. In underdeveloped countries, gram-negative bacilli, predominantly Escherichia coli, are the most common pathogens. Risk factors that predispose the newborn to bacterial meningitis include maternal infections, particularly of the urinary tract and uterus, obstetrical risk factors, including prolonged rupture of membranes and birth trauma, prematurity, low birth weight (less than 2500 g), congenital anomalies, perinatal hypoxia asphyxia, cardiopulmonary resuscitation and monitoring, prolonged ventilatory support, and intravenous lines. 1 After the neonatal period, Streptococcus pneumoniae and Neisseria meningitidis are...

Precancerous Changes in the Liver Screening and Prevention

The best preventive measure for hepatocellular carcinoma is elimination of the causative agent (primary prevention). Vaccination against HBV is highly effective in reducing chronic infection with this virus and has resulted in a reduction of tumour incidence in countries with nation-wide programmes such as Taiwan. A vaccine against HCV is not yet available but the virus has now been eliminated from blood used for transfusion by screening of donors. It is also possible to reduce exposure to aflatoxin by improving conditions of food storage. However, hundreds of millions of people remain for whom such measures are too late.

Chemotherapy and Biologic Agents

Interleukin-2 does not have direct antitumor effects. Interleukin-2 directly affects T lymphocytes, causing their proliferation. Because of the importance of T lymphocytes in animal models of melanoma rejection, interleukin-2 is widely used in melanoma research for the proliferation of antimelanoma lymphocytes. The use of IL-2 has spread into human trials, and this cytokine is a part of many ongoing immunotherapy trials. Interleukin-2 therapy alone has a 7 complete response rate that is sustained in 3 4 of patients, but use of interleukin-2 is limited by severe systemic toxicity. Biologic agents such as tumor vaccines and cytokines are now being combined. These clinical trials are ongoing and results are too preliminary to make recommendations for therapy.

Diagnosis Of Pulmonary Tuberculosis In Children

In many countries, newborns receive BCG immunization, and yet childhood PTB still occurs.This shows that BCG is not fully effective in protecting against PTB. BCG seems to give better protection against disseminated disease, such as miliary TB or TB meningitis, than it does against PTB. The effectiveness of BCG against PTB is variable between regions, and the reasons for this are not completely understood. One problem is likely to be the timing of the vaccination. In developing countries where TB is common, children will often be exposed to TB early in life and so immunization needs to be given as early as possible, i.e. soon after birth. However, the immune system of a newborn may be too immature to be able to produce an effective immune reaction to the BCG. BCG has been more effective when given to school-aged children. However, in communities where TB is common, this would be too late to protect against most disease. Other factors that reduce the

Ppd As A Carrier Molecule In Animals Sensitized With

Bacille Calmette-Guerin (BCG, attenuated Mycobacterium tuberculosis var. bovis, used as a vaccine against tuberculosis) has been used in the past to non-specifically enhance the immune response to antigens coinjected with it (9). In addition to this, Lachmann and coworkers originally reported (10) that mice first primed with BCG and then immunized in the absence of adjuvants with B-cell The same strategy was applied in our laboratory to investigate whether it was possible to enhance the immunogenicity of defined peptides from antigens of malaria parasites. A few years ago, we had shown that the immunogenicity of a synthetic polypeptide (NANP) , reproducing the entire repetitive sequence of the Plasmodium falciparum circumsporozoite (CS) protein and envisaged as potential malaria vaccine (5), was under strict MHC control, with only mouse haplotype (H-2b) being able to recognize it as both a B- and T-cell epitope (12,13). The MHC-controlled immune response to the (NANP) peptide was...

Assessment Of Immune Response With Antigen Arrays

Prolonged reactivity was monitored in immunized rather than nonimmunized animals, and surviving animals had a higher antibody titer against a wider spectrum of virus antigens. This first successful example of guiding vaccines with antigen microarrays emphasizes the utility of the high-throughput method for similar applications.

Dangerous and Deadly Consequences

Sixty-four percent of all people diagnosed with AIDS, to date, have died. New advancements in the treatment of HIV disease, namely combination therapy, can increase the quality of and prolong life for people with HIV infection, but there remains no cure and no vaccine. Prevention remains our best and most cost-effective tool for saving lives and bringing the epidemic under control.

Using Foods To Convey Medication

There are many sound reasons why intramuscular injection is effective for conveying vaccine antigens to stimulate human immune systems. The Sabin oral vaccine for poliomyelitis is one exception. Now Charles J Arntzen and his colleagues want to produce edible vaccines in fruits, and a high priority has been suggested for hepatitis B vaccine in bananas.32 The justification offered is that local production of the fruit might save the costs of refrigeration and transport presently incurred for conventional vaccines. This is a thoroughly impractical proposition. Trying to get any novel protein produced in sufficient concentration in a fruit would be an uphill battle, because fleshy fruits do not produce much protein except inside their seeds.33 Bananas in any case have no seeds. A calculation similar to that done for the Antarctic fish serum glycoprotein proposal (Chapter 4) demonstrates the utter futility of the exercise. For the foreseeable future, producing vaccines in fruits remains an...

Immunological Considerations

One of the dominant characteristics about EBV is its adaptation to allow for persistence in its host(s), and gene expression, even in the presence of a functional immune system. EBV co-replicates with host DNA, and EBNA-1, required for latent replication, is tolerated, not eliminated, although there are epitopes for class I and class II HLAs in the viral antigen (Khanna et al., 1999). The dominant feature in this protein that allows for its tolerance appears to be the repetitive (IR3) sequence that it harbours. In some cases of BL, where anti-EBNA-1 may be the sole antibody produced, this would allow for viral persistence. In situations where other antigens are expressed, for example in infectious mononucleosis or other EBV-associated malignancies, memory activated T-cells appear to be important in limiting cell expansion and in targeting productively infected cells that express lytically related antigens. Immunological data suggest that vaccines designed to control primary EBV...

Hepatitis B Virus HBV

Those who tested positive for HBV markers at the outset over those who did not, turned out to be nearly 100-fold 10 years later (Beasley, 1988), a much higher figure than the relative risk of lung cancer in smokers over non-smokers. Replicative HBV is not detectable in hepatocellular carcinoma tissue or cell lines but antigenic components such as HBsAg rarely are. The virus is not directly oncogenic in the sense that it does not transform cells in culture. However, it does produce hepatocellular carcinomas when its genome is incorporated in the germ line of mice in transgenic experiments. HBV-like hepadnaviruses also produce the tumour in their respective hosts, particularly the woodchuck. The most important event in hepatic carcinogenesis by HBV is its integration in the DNA of liver cell nuclei. No consistent site exists and it appears to be random and multiple. However, insertion of HBV in the genome leads to its destabilization and chromosomal abnormalities are common, a process...

Adaptive acquired specific immune response

As described above, T lymphocytes are responsible for CMI responses against foreign antigens and the aim of most cancer vaccines under investigation or in development is to create Indeed, the development of memory B and memory T cells against the antigen on the infectious agent or cancer cell is the rationale for successful immunization. The immunization of children against infectious agents is estimated to save the lives of 3 million children a year by helping the body to prevent primary infection (Andre, 2003). However, the development of vaccines against cancer is more challenging because, unlike vaccines against infectious diseases, cancer vaccines are developed for the treatment of disease that is already present in the body and not merely for its prevention (Berd, 1998 Moingeon, 2001).

How can I protect myself from contracting hepatitis B

Not having sex is the most effective way to prevent getting an infection. Monogamy is also safe two people who only have sex with each other are safe if neither partner is infected. People who choose to have sex outside a monogamous relationship but don't know whether their partners carry this virus can protect themselves by receiving the vaccine series. Condoms may also be effective in preventing hepatitis B transmission. Washing the genitals, urinating, or douching after sex does not prevent STDs. For more detailed information on strategies to reduce your risk of acquiring STD HIV see SHARP FafChoosing Safer Options Reduces Risk at

Telomerase Specific Adaptive Immunotherapy 21 Rationale

Telomerase-specific adaptive immunotherapy aims to stimulate a CD8+ cytotoxic T lymphocyte (CTL) response against hTERT overexpression in cancer cells. Clinical approaches to induce CTL responses against tumor neoantigens generally make use of the professional antigen-presenting function of dendritic cells (DC) pulsed with neoantigen mRNA or, in the case of peptide vaccination approaches, with synthetic peptides capable of binding MHC class I molecules (HLA-A, HLA-B, or HLA-C). Pulsed DC prime CTL to lyse target cells displaying endogenously synthesized antigenic peptides in the context of the class I presentation pathway which is present in all nucleated cells (Rock and Goldberg 1999). Although antigen-specific CTL responses can be raised by these methods, clinical efficacy is limited, and the importance of both inhibiting CTL suppressive signals and inducing antigen-specific CD4+ T-helper cell support is now widely recognized (Emens 2006). T helper cells secrete cytokines that both...

Embryonic Stem Cell Opportunities in Developmental Toxicity and Cognitive Disorders

Genetic causes account for approximately 10 of autism cases with multiple candidate target genes identified, such as the serotonin transporter gene, DBH, GABRB3, UBE3A, RAY1 ST7, WNT2, RELN, SPCH1 FOXP2 and GRIK2.40-43 Environmental effects are strongly suggested to contribute to disease etiology. There is substantial evidence from animal models and human epidemiology studies44 that environmental (mercury thimerosal, a preservative used in vaccines and organophoshates) and therapeutic chemicals (thalidomide, valproic acid) exert specific teratogenic effects during neurodevelopment which lead to altered neuronal migration and function and autistic syndrome.39'45 Damaging neuronal and behavioral patterns in autistic children may also result from an indirect rather than direct environmental effect. In mice, repeated exposure to thimerosal leads to neurobehavioral deteriorations, increased oxidative stress and decreased intracellular levels of glutathione, a major antioxidative and...

Spirulina Antiviral Studies In Vitro

Other Spirulina species, such as S. maxima has also shown antiviral activity against human and animal herpesviruses such as HSV-2, HCMV, and suid herpesvirus 1 or pseudorabies virus (SuHV-1). However, this antiviral activity was not observed against other enveloped viruses such as two measles strains (Edmonston-Zagreb vaccine strain and subacute sclerosing panencephalitis Halle strain) and vesicular stomatitis virus (VSV). Similarly to S. platensis the S. maxima extract does not have a virucidal effect on herpesvirus, both extracts inhibit herpesvirus infection by blocking the adsorption and penetration events of t7he viral replication cycle. According to the antiviral results obtained with the extracts from S. maxima using solvents with different polarity, the antiviral effect is related to the presence of highly polar compounds.20

The Role Of The Expanded Programme On Immunization

BCG is not the only immunization in the EPI that may help to protect a child against TB. Measles and whooping cough lower a child's resistance to TB. So whenever you treat a child for TB, check his or her immunization record. If the child has not received scheduled immunisations, encourage the mother to bring him or her for immunizations, once symptoms of TB have resolved. WHO has collaborated with UNICEF in establishing guidelines for immunization. The recommendation is that individuals with known or suspected asymptomatic HIV infection should receive all EPI vaccines, according to national schedules.

Vitamin A In Milk Can Potentially Reduce The Replication Of Enveloped Viruses In Infants

Treatment of HSV-1 infected Vero cells with retinoic acid did not reduce the production of viral glycoproteins, even when the production of infectious virus particles was inhibited by 1,000-fold. Envelope glycoproteins are a constituent of all enveloped viruses and inhibition of their synthesis would have been one possible mechanism for vitamin A dependent reduction in viral infectivity. Studies done using labeled carbohydrates however, suggest that retinoic acid treatment interferes with the processing of carbohydrates attached to enveloped virus proteins. These studies indicate that the maintenance of adequate vitamin A levels in breast milk could help to reduce the severity of enveloped virus infections in infants when a vaccine is not available.

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