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; Continue reading...

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Preerythrocytic Sporozoite Vaccines

The discovery that human volunteers inoculated with irradiated sporozoites were protected for up to 9 months against infectious challenge (Clyde et al., 1973) has led to much effort to develop a pre-erythrocytic vaccine. It is argued that a vaccine that prevents sporozoites entering, or developing in, hepatocytes would eliminate infection before the appearance of clinical disease. Even with less effective vaccines, it may be expected that there would be a reduction in the number or parasites entering the blood from the liver and thereby less risk of severe disease. Pre-erythrocytic vaccine development initially focused on inducing antibodies to the sporozoite surface. Antibodies directed to the circumspor-ozoite protein (CSP) repeat asparagine (N), alanine (A), Proline (P), NANP were shown to neutralize sporozoites in vitro but to give inconsistent protection against P. falciparum infection in vivo (Ballou et al., 1987 Herrington et al., 1987). It is likely that the failure of the...

Transmission Bocking Gametocyte Vaccines

Are carried into the mosquito gut, along with gametocytes. These antibodies then react with sexual stage antigens and interfere with the fertilisation process, thus blocking transmission of malaria (Carter et al., 1984). Experiments in animals suggest that antibodies to a 25 kDa gametocyte antigen block transmission in membrane feeding experiments (Barr et al., 1991) and several other candidates are under consideration. Even though this type of vaccine would confer no direct benefit to the individual, it is hoped that it would reduce the prevalence of malaria in the community and have a significant effect on morbidity and mortality (Kaslow, 1997).

Principles Of Immunity By Vaccination

The provision of safe water and sanitation and the prevention of infectious diseases by immunisation have been the triumph of the twentieth century. This chapter is concerned with specific acquired passive and active immunity in relation to travel and routine vaccines, noting the International Health Regulations adopted by the World Health Organization (WHO). The purpose of these Regulations is to help prevent the international transmission of diseases and, in the context of international travel, to achieve this with the minimum inconvenience to the traveller. The vaccination requirements for international travel are listed conveniently in WHO's International Travel and Health publication, and are considered in greater detail in this and the chapters relating to particular infections.

Killed or Inactivated Vaccines

These are used when live attenuated vaccines are not available or where reversion of an attenuated strain to wild type occurs with relative ease. While killed vaccines are noninfective, they are generally less immunogenic (except toxoids) and several doses and boosters are required. Procedures used for inactivation include formaldehyde, -propriolactone and, more recently, a variety of ethylenimines and psoralens for viruses. Bacteria are killed or inactivated with formaldehyde, phenol acetone or by heating. Both inactivated and live vaccines may be given safely concurrently, although different anatomical sites ofvacci-nation are recommended.

Other Vaccine Components

Components other than antigen in vaccines include suspending fluids, such as sterile water, saline, culture media, adjuvants, stabilisers, preservatives and antibiotics to prevent bacterial contamination. Thiomersal is a preservative that contains mercury and has been used as an additive in vaccines and biological substances for some 70 years because it prevents bacterial and fungal contamination, particularly in multidose containers. In 1999, the American Academy of Paediatrics and the US Public Health Service recommended, as part of the effort to reduce exposure to mercury, that the thiomersal content of vaccines should be reduced or replaced with formulations which do not contain thiomer-sal as a preservative as soon as possible, without unnecessary disruption of the vaccine system. It should be noted that the risk, if any, to infants from exposure to thiomersal is believed to be slight. The demonstrated risks for not vaccinating children far outweigh the theoretical risk for...

Contraindications to Vaccination

A number of general principles must be considered and several factors must be assessed before vaccination, and it is important to distinguish between true contraindi Allergy to protein (e.g. eggs) and to other components of the vaccine (e.g. antibiotics such as streptomycin and neomycin). A definite history of a severe local or a general reaction to a preceding dose of the vaccine.

Travel And Routine Vaccines

All travellers should be advised to undergo a pretravel health risk assessment to determine the potential risks of exposure to infectious disease and other environmental hazards, according to their destination(s), the season in which they are travelling, the circumstances of their stay, i.e. rural or urban, camping or resident in a hotel, mode of transport, and planned activities. Travellers comprise a heterogeneous group whose travel health needs may vary according to their individual requirements, e.g. those of a business traveller may differ considerably from those of a backpacker. The appropriate use of vaccines is to be encouraged, including the use of those that may be optional and those from which travellers may benefit in the future. Achieving immunity against infectious diseases by vaccination often requires that a complete course of immunisation be administered at least 1 month before departure. It is therefore essential that travellers seek travel health advice well in...

Combined Hepatitis A and B Vaccine

Recent advances in combination vaccines have resulted in the availability of two different multivalent vaccines, one containing hepatitis A and hepatitis B antigen (see below, Hepatitis B) and the other being hepatitis A and typhoid antigen (see below and Typhoid). These vaccines may be suitable for those travellers at dual risk of exposure to these diseases. The combined hepatitis A and B vaccine is licensed for both paediatric (0.1 ml 1-15 years) and adult (1.0ml over 16 years) use by the intramuscular route, with the primary course being administered at day 0, 1 month and 6 months. The corresponding levels of antibody protection achieved at each of these time points are 94 , 99 and 100 for hepatitis A, and 34 , 97 and 99 for hepatitis B. Booster doses of the monovalent hepatitis A vaccine should be administered at 10-yearly intervals, with that of the monovalent hepatitis B recommended at 5-yearly intervals at present for those travellers at continued high risk. No serious...

Combined Hepatitis A and Typhoid Vaccine

Another combination vaccine recently licensed in the United Kingdom is that of hepatitis A and typhoid. Licensed currently for those aged 15 years and over, 1.0 ml of vaccine administered intramuscularly will confer protection against hepatitis A and typhoid within 14 days. Booster doses of the monovalent typhoid vaccine must be administered at 3-yearly intervals, while that of the monovalent hepatitis A vaccine must be given at 6-12 months initially, followed by 10-yearly intervals. Again, no serious side-effects have been reported with the use of this vaccine. The future development of routine universal immunisation programmes against hepatitis A, such as those being introduced in the United States and several southern Mediterranean countries, will be of benefit to future generations of travellers, who will be protected well in advance of their travels. It could also be surmised that future universal immunisation programmes will include the use of the combination hepatitis A and B...

Drugs and Vaccinations

Yellow fever vaccination is extremely effective, but cases continue to be imported to Europe and North America from both Africa and South America by travellers who have not been immunised. Active immunisations against hepatitis A and B are both more than 90 effective, whereas currently licensed vaccines against typhoid only have 70 or less protective efficacy. The effectiveness of antimosquito bite measures and antimalarial chemoprophylaxis is variable and highly dependent on adherence by travellers.

Vaccine Preventable Illnesses

Routine immunizations (measles mumps rubella, polio, tetanus toxoid, varicella, if appropriate) should be updated prior to travel. One dose of 23-valent pneumococ-cal vaccine and annual influenza immunization are recommended for healthy adults 65 years and older, and for high-risk individuals below age 65. Age alone is not a contraindication to any vaccine, although seroconversion rates may decrease with age. For the healthy older traveler, general recommendations for both routine and travel vaccines apply. Hepatitis A seropositivity rates are higher in older travelers who have lived in or traveled extensively to endemic areas, or have a prior history of jaundice serologic hepatitis A antibody screening prior to immunization in these individuals may be cost-effective (Castelli et al., 1996 Schwartz and Raveh, 1998). Live vaccines (oral typhoid, oral polio, varicella, yellow fever) should not be given routinely to immunocom-promised travelers. Elderly travelers are at higher risk of...

Antigenspecific vaccines

Antigen-specific vaccines refer to the delivery of recombinant peptides or proteins to a host in order to elicit an antitumor immune response. As previously described, there has been a great deal of interest in the discovery of novel tumor-associated antigens for the use in cancer vaccines. In any immuno-therapy protocol, there are several different means of delivering these antigens to the host (1) DNA-based vaccines (2) peptide- or protein-based vaccines (3) recombinant viral or bacterial vaccines and (4) antigen-pulsed dendritic cell vaccines. DNA vaccines encoding tumor antigens can be delivered as naked DNA or encapsulated by liposomes.92 Despite the possibility of rapid degradation of DNA when given systemically, there has been renewed interest in DNA-based vaccines for both infectious agents as well as neoplastic diseases.93,94 The advantages of administering a cancer vaccine as a peptide or protein would include improved safety compared to other vector-based vaccines. Tumor...

Responses to conjugate vaccines

Polysaccharides on bacterial cells are often poorly immunogenic but represent an important target for immune protection. One approach to overcoming this problem is to attach the polysac-charide to a carrier protein that elicits a strong T-cell immune response. The Hib conjugate vaccine provides an example of a large carbohydrate molecule that cannot elicit the help of thy-mus-processed T cells by itself. When conjugated to diphtheria toxoid, an aggregated glycoprotein, T-cell help can be obtained. Figure 20.13 Processing of a conjugate vaccine between diphtheria toxoid (magenta) and the polyribosyl ribose phosphate of the capsule of Haemophilus influenzae B (green). A B cell with specificity for the capsular polysaccharide binds the conjugate vaccine with its surface Ig (black). The complex is endocytosed and the protein components are broken down to peptides (Figure 20.3). Peptides derived from the diphtheria toxoid are subsequently presented on the B-cell surface in association with...

The Future Vaccination

With CE, some authorities consider that vaccination of livestock, particularly sheep, may be a useful approach where reinfection of livestock is likely to occur from outside the control area (Heath and Lightowlers, 1997). The recent development of an effective recombinant vaccine against ovine echinococcosis (Lightowlers et al., 1996) may thus provide a useful adjunct in control programmes. The vaccine is currently being trialled in a number of geographical areas where CE is endemic, in order to compare efficacy and also to determine whether the vaccine is effective against more than one strain of E. granulosus (Heath and Lightowlers, 1997). The future potential of any immunoprophylactic strategy for echinococcosis may be jeopardised by demonstrated antigenic differences between isolates of Echinococcus (Thompson, 1995). Results to date have demonstrated up to 98 resistance to a challenge infection in sheep (Heath and Holcman, 1997). For the practical benefits of this vaccine to be...

Prevention And Control Pneumococcal Vaccines

There are two types of pneumococcal vaccines a 23-valent pneumococcal polysaccharide vaccine (PPV) and a 7-valent pneumococcal conjugate vaccine (PCV). Pneumococcal Polysaccharide Vaccine This is a polyvalent vaccine containing 25 lg of purified capsular polysaccharide from each of 23 capsular types of pneumococci that together account for about 96 of the pneumococcal isolates causing serious infection in Great Britain (World Health Organization, 1999). Most healthy adults develop a good antibody response to a single dose of the vaccine by the third week following immunisation. Protection is much less reliable in the immunocompromised and in children below the age of 2 years. Pneumococcal Conjugate Vaccine This vaccine contains polysaccharide antigens from seven common serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) conjugated to a protein carrier (currently CRM197 protein). The selected serotypes accounted for 65.6 of pneumococcal invasive infections in England and Wales in 2000 (82.3 in...

Live attenuated Virus Vaccines

These include oral poliomyelitis (Sabin type) vaccine, measles, rubella, mumps and yellow fever vaccine, which have been produced by essentially the random selection Concurrent administration of live vaccines, with the exception of yellow fever, and immunoglobulins should be avoided due to the theoretical possibility of competitive inhibition of the immune response. It is recommended that a 3 month interval should be observed between their administration, although an exception may be made when travel is undertaken at short notice for example, oral polio vaccine may be administered at the same time as human normal immunoglobulin when the risk of exposure to poliomyelitis is considered to be high. With the introduction of more immunogenic active vaccine preparations that have become available, the use of immuno-globulin preparations is expected to decrease significantly in the future. It is still advised that, in circumstances where the administration of more than one live vaccine is...

Route of Administration of Vaccines

The route of administration of vaccines varies according to the type of vaccine. Most vaccines are given by intramuscular injection. 1. By mouth. Oral polio vaccine (OPV) and oral typhoid vaccine are given by mouth. 2. Intramuscular and subcutaneous injection. With the exception of oral vaccines and BCG, all vaccines available currently should be given by intramuscular injection or by deep subcutaneous injection. The site of injection is important the upper arm (the deltoid region) or the anterolateral aspect of the thigh are strongly recommended, and not the buttock. The injection of vaccine into deep fat in the buttocks is likely, particularly with needles shorter than 5 mm, and there is a lack of phagocytic or antigen-presenting cells in layers of fat. Another factor may involve the rapidity with which antigen becomes available to antigen-processing cells from deposition in fat, leading to delay in presentation to T and B cells. An additional factor may be denaturation of antigen...

Yellow Fever and Oral Cholera Vaccines

These vaccines are only indicated for travellers to certain specific destinations in some countries. The consultation should thus ascertain the exact itinerary and the eventual indications. These vaccines are contraindicated in severely immunocompromised individuals. Such travellers to an area for endemic yellow fever should be recommended to change the itinerary or to follow strictly physical mosquito precautions if the trip is unavoidable. When yellow fever vaccine is required to cross a border but no portion of the trip would be in an infected area, a certificate The administration of BCG vaccine to immunocompromised persons is contraindicated because of its potential to cause disseminated disease (USPHS IDSA, 1999).

Vaccines

There is a very large and increasing number of vaccines available worldwide. Although most are safe for im-munocompromised persons, some precautions are necessary with live attenuated vaccines (Tables 3.1 and 3.2). These include the yellow fever vaccine, the Bacille Calmette-Guerin (BCG, against tuberculosis) vaccine, the oral polio (Sabin) vaccine, measles, mumps and rubella (MMR) vaccine, oral typhoid vaccine, oral cholera vaccine and the new varicella vaccine. All inactivated or component vaccines can be offered to immunocom-promised individuals if exposed. Among those, some are recommended strongly for them, such as influenza and pneumococcal vaccines. These vaccines represent no risk for HIV or persons with AIDS. Some severely im-munocompromised individuals may respond poorly to immunisation. Other strategies may thus be needed to protect them, such as passive immunisation with specific immunoglobulins or preventive medication or rapid treatment. All immunisations should be given...

Hepatitis A Vaccine

Several inactivated and attenuated hepatitis A vaccines have been developed and evaluated in human clinical trials and in nonhuman primate models of hepatitis A virus infection (D'Hondt, 1992) however, only inactivated vaccines have been evaluated for efficacy in controlled clinical trials (Innis et al., 1994). The vaccines licensed currently are Havrix (SmithKline Beecham Bio-logicals), Vaqta (Merck and Co., Inc.), Avaxim (Pasteur Merieux Connaught) and Epaxal (Berna Products). All four are inactivated vaccines.

New vaccines

Recent advances in immunology, molecular biology and genetic engineering have stimulated new approaches to the development of vaccines. Scientists are now able to identify more precisely the process by which immunity is acquired to identify the antigenic components which induce protective immunity and to produce relevant biological materials through the cloning of genes or the synthesis of peptides. These developments hold out the prospect of replacing the crude products of < trai ditional vaccines with well-defined antigens. There is also the hope that effective vaccine', can be developed against malaria and other parasitic infection . These biomedical advances have made possible a new generation of vaccines with increased efficacy, safety profile and affordability.

Vaccine Development

Vaccination against P. falciparum is the intervention that is most likely to reduce malaria-associated severe morbidity and mortality in infants and young children in areas with the most intense transmission and to reduce the risk to non-immune travellers to endemic areas. The rationale for developing a malaria vaccine includes prevention of infection (pre-erythrocytic vaccines), prevention of disease (blood-stage vaccines) and reduction of transmission (transmission blocking vaccines) (Miller and Hoffman, 1998).

Bloodstage Vaccines

People in endemic areas develop clinical immunity despite frequent blood-stage infections that are usually asymptomatic, demonstrating that it not necessary (and may not be desirable) to prevent infection in order to prevent disease. Based on the principle of mimicking immunity acquired in an endemic area, a blood-stage vaccine could be designed to reduce or interfere with parasite replication, and numerous animal studies have confirmed that immunisation induces protection that may be more effective than chronic repeated infections. A vaccine could also be designed to prevent pathology, rather than infection. An 'anti-adhesion' vaccine could prevent a key step in pathogenesis, for example, to prevent malaria in pregnancy that appeared to be associated with chondroitin sulphate A binding (Rogerson and Brown, 1997 Reeder et al., 1999). An 'anti-disease' vaccine could neutralise key toxins, such as glycosylphophotidylinositol Many candidate vaccine antigens have been identified and...

Combination Vaccines

In recent years, there has been considerable development in the availability of combination vaccines for both paedi-atric and adult immunisation. Examples include combination vaccines including inactivated antigenic components such as hepatitis A and hepatitis B, and hepatitis A and Vi antigen (S. typhi). Evaluation of the safety and immunogenicity of combination live and inactivated vaccines, e.g. yellow fever, hepatitis A and Vi antigen, are currently being undertaken on a clinical trial basis. Combination vaccines are a useful addition to the portfolio of travel vaccines now available. The benefits include dual protection against disease with a single injection, so aiding compliance and completion of vaccination courses, as well as added convenience for the individual, particularly for those with needle phobia. Combination vaccines also provide an alternative site for administration of other monovalent vaccines that may need to be administered concurrently, which is of particular...

Storage of Vaccines

Refrigerators must contain a maximum-minimum thermometer and refrigerators designed for vaccine storage should be used. Vaccines should not be stored with food and a secure supply of electricity should be used. Vaccines must not be kept at temperatures below 0 C and the maximum-minimum temperatures must be recorded daily. Reconstituted vaccine must be used within the recommended period, usually within 1-4 h, according to the instructions of the manufacturer. Spent or partly used vials and unused vaccine must be disposed of safely, preferably by heat sterilisation or by incineration. The disposal of unused attenuated live vaccines requires special care. The safe disposal of syringes, needles and other sharps without hazard to others and to children is imperative.

Vaccination policy

It is generally agreed that it is no longer desirable to vaccinate populations routinely against smallpox nor is it necessary for governments to require a certificate of smallpox vaccination from international travellers. Vaccine stocks Even though most people are firmly convinced that smallpox has been eradicated, stocks of vaccine are still being held. This is a wise precaution in support of the policy of suspending routine vaccination. Furthermore, there is some concern that because populations are now not immunized, the variola virus may be a tempting candidate for biological warfare.

Vaccination

While prevention with behavioral changes and therapeutic medication use are often challenging in children, vaccines are well accepted and provide effective pretravel intervention that can decrease greatly the risk of many diseases. Attention should be paid to the timing of 'routine' childhood vaccines (Table 23.2) as well as to the use of special travel-related immunizations (Table 23.3). New vaccines are being developed, and expert recommendations change rapidly. Health care providers taking care of traveling children should consult up-to-date sources (such as www.cdc.gov) for current recommendations. 'Routine' Vaccinations Diphtheria (D), tetanus (T), and pertussis (P) vaccines are commonly used in most countries of the world. Diphtheria is an unusual illness in many areas but became more common in Europe and Asia following the restructuring of the former Soviet Union cases in adult travelers were reported. Tetanus is common around the world, and pertussis continues to cause...

Tumor cell vaccines

Active immunization can also be achieved by the administration of autologous or allogenic tumor cells modified to secrete cytokines or other immunostimulatory molecules capable of recruiting antitumor effector cells. Examples include in vitro tumor cell transfection by MHC class II genes,113 transfection of lost MHC class I alleles19 and transfection of the costimulatory molecule B7 to stimulate T cells.114 The strategy of using tumor cell vaccines as a source of tumor antigens eliminates the need to identify and develop immunodominant antigens. As well, engineered tumor cells expressing cytokines may function by providing necessary growth factors to activated CTLs in the absence of helper T cells. Numerous different cytokines have been introduced into tumor cells in vitro including IL-2, IL-4, IL-6, IL-12, TNFa and granulocyte-macrophage colony-stimulating factor (GM-CSF). Many of these preclinical models have shown great success in controlling local tumor outgrowth as well as some...

Cancer Treatment and Research

Kirsch, Matthias, Black, Peter McL. (ed.) Angiogenesis in Brain Tumors. 2003. ISBN 1-4020-7704-1. Keller, E.T., Chung, L.W.K. (eds) The Biology of Skeletal Metastases. 2004. ISBN 1-4020-7749-1. Kumar, Rakesh (ed.) Molecular Targeting and Signal Transduction. 2004. ISBN 1-4020-7822-6. Verweij, J., Pinedo, H.M. (eds) Targeting Treatment of Soft Tissue Sarcomas. 2004. ISBN 1-4020-7808-0. Finn, W.G., Peterson, L.C. (eds) Hematopathology in Oncology. 2004. ISBN 1-4020-7919-2. Farid, N. (ed.) Molecular Basis of Thyroid Cancer. 2004. ISBN 1-4020-8106-5. Khleif, S. (ed.) Tumor Immunology and Cancer Vaccines. 2004. ISBN 1-4020-8119-7. Balducci, L., Extermann, M. (eds) Biological Basis of Geriatric Oncology. 2004. ISBN Abrey, L.E., Chamberlain, M.C., Engelhard, H.H. (eds) Leptomeningeal Metastases. 2005.

Global Burden And Significance Of Infectious Diseases

In industrialised countries, many infectious diseases were controlled successfully during the twentieth century by improvements in hygiene and nutrition as well as by the availability of anti-infective chemotherapy and preventive measures (e.g. vaccines). As a consequence, the importance of infectious diseases has been regarded as becoming very small, and probably vanishing completely, at least in the developed world. However, during the last two decades infectious diseases have regained considerable significance and interest even in high-income countries. The reasons for this are varied

Population Dynamics And Control

The complex dynamics of infectious disease can result in counter-intuitive outcomes to attempts at control inappropriate timing and coverage of a vaccination or community treatment program may make an existing public health problem worse. This unwanted outcome is a result of the complex and inherently non-linear interactions between populations of hosts and the pathogens which infect them (Anderson and May, 1979 Anderson, 1994 Bundy et al., 1995). Such non-linearities lead to intervention outcomes which appear counter-intuitive and are difficult to predict, e.g. partial vaccination coverage may have little effect on infection incidence overall but may make infection more prevalent in different (older) age classes, with potentially disastrous public health consequences if the infection is rubella (Anderson and Grenfell, 1986).

Primary Prevention of Genetic Disorders and Place of Preimplantation Genetic Diagnosis

Environmental programs, (2) discouragement of pregnancy at advanced ages through community education and family planning, (3) periconcep-tion folic acid supplementation or multivitamin fortification of basic foodstuffs, (4) rubella vaccination, (5) avoidance of alcohol consumption and smoking during pregnancy, and (6) prenatal and (7) prepregnancy (preimplantation) diagnosis. The decision to adopt any of the available preventive programmes depends on the differences in health services development, ethnic distribution of congenital disease, and the local attitudes to genetic screening and termination of pregnancy. For example, induced abortions are still not permissible in many countries on eugenic grounds. On the other hand, an increasing number of countries are gradually permitting prenatal diagnosis and termination of pregnancies for medical indications even in some strict religious settings.

The Immunocompromised Traveller

They do so for pleasure, business, family reasons or religious considerations. To tell a severely immunosuppressed person not to travel is unrealistic and does not take into consideration his or her own priorities. Health care providers need to be aware of the most important risks, the preventive measures available and how to inform the potential traveller about risks and options. Preparing an immunocompromised individual for international travel requires attention to a number of important issues that, for the most part, are similar to those faced by any traveller with a chronic condition. These considerations include (1) restrictions on crossing international borders (2) vaccination requirements and their effectiveness and safety (3) susceptibility to infections present at the destination and (4) accessibility of health care overseas and the possible need for medical evacuation home (Health Canada, 1994). Table 3.1 Vaccines generally to be avoided in...

Travel Clinic Operations

Vaccine injections at travel immunization clinics may be administered in multipatient or group clinic settings if necessary, as most vaccines are now administered in the upper arm, and privacy screens or curtains may be used for patients receiving injections of immune globulin in the gluteus muscle. However, a private room is necessary for patient interviews to conduct individual trip risk assessment and patient counseling, as sensitive topics may be discussed. Likewise, physical examinations require privacy, an examination table, the usual medical equipment and supplies, and, often, the help of a medical assistant. Thus, the clinical activities of some travel clinics require the use of dedicated patient examination rooms. Depending on a clinic's location, specific standards for licensure of patient care facilities may govern room dimensions, provisions for patient privacy, presence of a sink in the room for hand-washing, sanitation of medical equipment and linens, hazardous waste...

Patient Information Brochures

One of the challenges of the travel clinic encounter is to impart the large amount of travel health advice and information applicable to a given trip in a way that can be remembered by the patient within the time allocated for the travel clinic encounter (typically 45-60 minutes). Most travel clinics find that the preparation of patient information brochures, preprinted prescriptions, and printed instructions on what to do for vaccine-associated side-effects will save significant time during the travel clinic appointments. The printed materials enable multiple providers to communicate the advice on each relevant topic and provide prescriptions according to the practice standards determined for the given travel clinic. Health topics that have proven useful in the University of Washington travel clinics over the years include

The Changing Epidemiology Of Disease In Travellers

The potential for emergence of new infectious diseases and re-emergence of old ones has increased in recent years. Many factors have contributed to this threat, of which the rapid increase in international travel is one. Other factors are the globalisation of the food industry, and social and environmental changes such as deforestation and rapid urbanisation. In addition, the widespread and inappropriate use of antibiotics has led to the emergence of many resistant infectious diseases. At the same time, successful vaccination programmes and other control measures have brought some diseases close to eradication.

The use of health statistics

At a health centre, for example, each service unit should collect and display statistics on high priority problems. The section of the clinic, which treats sick patients, could, for example, show cases of acute diarrhoea in a simple graph so that comparisons can be made day by day, week by week, and month by month. These statistics may alert the staff of the institution to sudden changes in the number of cases of a particular disease and it could provide some assessment of the performance of the services. The child welfare clinic should display the number of children they have immunized to show both the uptake over time (by comparing vaccination and birth rates) and the proportion completing the course (by indicating the numbers entering and finishing the programme).

Epidemiology Of Phaemolytic Streptococcus Infection

To fully understand the epidemiology of these diseases in terms of how these organisms spread, host and strain characteristics of importance to onward transmission, disease severity and inter- and intraspecies competition for ecological niches, one would need to undertake the most comprehensive of investigations following a large cohort for a substantial period of time. Understanding these factors would allow us to develop effective prevention strategies. An important such measure, discussed in the section Vaccines for P-haemolytic streptococcal disease, is the introduction of a multivalent vaccine. Although existing M-typing data allow us to predict what proportion of disease according to current serotype distribution could be prevented, the possibility of serotype replacement occurring is

Management and Treatment

Passive immunisation with normal human immuno-globulin, or in selected circumstances active immunisation with hepatitis A vaccine, is indicated as soon as possible after exposure and within 2 weeks to all household and sexual contacts, and for those exposed to contaminated food. Immunoglobulin should be given to all classroom contacts in daycare centres (children under 5 years old), and, if there are infants in nappies, immuno-globulin should be given to all potentially exposed children and staff in the centre. Immunoglobulin has been used effectively for controlling outbreaks such as in homes for the mentally handicapped. It is not indicated for contacts in the usual office or factory environment or in schools. Hepatitis A vaccine has, however, been shown to be effective for the control of hepatitis A outbreaks in schools.

Surface Antigen mutants

Production of antibodies to the group antigenic determinant a mediates crossprotection against all subtypes, as has been demonstrated by challenge with a second subtype of the virus following recovery from an initial experimental infection. The epitope a is located in the region of amino acids 124-148 of the major surface protein, and appears to have a double-loop conformation. A monoclonal antibody which recognises a region within this a epitope is capable of neutralising the infectivity of HBV for chimpanzees, and competitive inhibition assays using the same monoclonal antibody demonstrate that equivalent antibodies are present in the sera of subjects immunised with either plasma-derived or recombinant hepatitis B vaccine. During a study of the immunogenicity and efficacy of hepatitis B vaccines in Italy, a number of individuals who had apparently mounted a successful immune response and became anti-surface antibody (anti-HBs)-positive, later became infected with HBV. These cases...

Partial efficacy and partial effectiveness

No single prevention method is 100 effective. Even sexual abstinence, which may be theoretically effective, is imperfectly practised. The most effective prevention technology is the male latex condom, which has an estimated 80-90 level of expected risk reduction with correct and consistent use. Based on the outcomes of the first randomized controlled trial of male circumcision, that intervention appears to have the next highest level of efficacy, at 65-70 for a single procedure (102). Additional methods under study (such as vaccines, microbicides, pre-exposure antiretroviral prophylaxis) are estimated to have only a 25-50 level of effectiveness using current study-design calculations and are methods that require repeated administration (145, 146). This means that researchers, service providers, programme managers, policy-makers and community advocates must not promise too much for any particular method they must be clear about the need to use a combined approach to preventing the...

Active Immunisation

The major humoral antibody response of recipients of hepatitis B vaccine is to the common a epitope, with consequent protection against all subtypes of the virus. First-generation inactivated vaccines were prepared from 22 nm HBsAg particles purified from plasma donations from chronic carriers. These preparations are safe and immunogenic but have been superseded in some countries by recombinant vaccines produced by the expression of HBsAg in yeast cells. The expression plasmid contains only the 3' portion of the HBV surface ORF and only the major surface protein, without pre-S epitopes, is produced. Vaccines containing pre-S2 and pre-S1 as well as the major surface proteins expressed by recombinant DNA technology are undergoing clinical trial. Immunisation against hepatitis B is now recognised as a high priority in preventive medicine in all countries and strategies for immunisation are being revised. Universal vaccination of infants and adolescents is under examination as the...

Nature of the Infectious Agent

The amino acid sequence of the nucleocapsid protein is highly conserved among different isolates of HCV. The next domain in the polyprotein also has a signal sequence at its C-terminus and may be processed in a similar fashion. The product is a glycoprotein, which is probably found in the viral envelope and is variably termed E1 S. The third domain may be cleaved by a protease within the viral polyprotein to yield what is probably a second surface glycoprotein, E2 NS1. These proteins are of considerable interest because of their potential use for tests for the direct detection of viral proteins and for the development of HCV vaccines. Nucleotide sequencing reveals that both domains contain hypervariable regions.

Prevention And Control

The need for effective malaria control remains great as malaria continues to threaten populations in many parts of the world. Obstacles, such as increasing drug resistance among malaria parasites and increasing insecticide resistance among mosquitoes, have made control more difficult and heightened the need for effective vaccines or improved control measures.

Protection of the susceptible host

This may be achieved by active or passive immunization. Protection may also be obtained by the use of antimicrobial drugs, for example chemo-prophylaxis is used for the prevention of malaria, meningococcal meningitis and bacillary dysentery. Mass campaigns are sometimes indicated for dealing with acute epidemics or as a method of controlling or eradicating endemic diseases. Any vaccine or drug used for a mass campaign must be effective, safe, cheap and simple to apply. Following the emergency operation of a mass campaign, the programme should be integrated into the basic health services of the community.

Routine childhood immunization

Assists health authorities to design, implement and evaluate their immunization programmes, train their health personnel and acquire vaccines and other essential supplies. UNICEF has included immunization as an important component of its Child Survival Programme (p. 326). These organizations are also involved in research aimed at solving the problems encountered in running the immunization programmes. For example, live vaccines must be refrigerated to maintain their potency otherwise they would deteriorate. WHO has tackled the problem of ensuring a continuous 'cold chain' from the point of manufacture of the live vaccine to its delivery to children in the most remote rural areas of hot tropical countries. A new initiative, the Global Alliance for Vaccine Initiatives (GAVI) has expanded the base of support for global immunizations by bringing together other stakeholders including the private sector.

Designing Novel Drugs

The chapter on biotechnology drugs enlarges on this subject in more detail, but suffice it to say here that vaccines, antibodies, proteins, peptides, and gene therapies all now exist. These biological drugs bring with them specific, regulatory, clinical trials and manufacturing difficulties. Gene therapy, in particular, carries human safety risks that do not apply to other classes of therapy, e.g. the infective nature of some types of vector that are employed, and the potential for incorporation of the test genetic material into the genome in males, leading to expression of gene products in offspring.

St Louis Encephalitis

The infection is controlled in the USA by vector control, including water drainage and aerial low volume spraying of insecticides in populated areas. Secondary control measures to protect against mosquito bites should be deployed during reported outbreaks. Tick repellents are useful on outer clothes and socks, and the arms, legs and ankles must be covered. Travellers who plan to walk, camp or work in late spring and summer in the heavily forested areas listed above, especially where there is heavy undergrowth, should be immunised with a formalin-inactivated vaccine. Two doses of 0.5ml given intramuscularly 4-12 weeks apart will provide protection for 1 year. An immunoglobulin preparation is also available for postexposure prophylaxis.

Cellmediated Immunity

Studies on y 8 T lymphocyte lines suggested that these cells might be important in modulating the CD4+ T lymphocyte response to Babesia antigens (Brown et al., 1994). Subsequent studies have identified five different antigenic groups of B. bovis merozoite proteins which stimulate proliferation of Th clones. The authors suggest that these antigens are potentially useful for the construction of a vaccine (Brown et al., 1995).

Models of Disease and Therapy

Some people are reluctant to immunize their children because of concerns that vaccines carry unknown risks of poisoning or exotic animal diseases. Others worry that immunizations are wrongfully withheld. The medical community decided that smallpox had been eradicated, and smallpox immunization had no benefit to offset its risks. In 2002, following fear of biological terrorism, the unimmunized population seemed vulnerable. Some asked how we know that smallpox really has been eradicated. There are no definitive scientific answers to such questions because they require proof of a negative. Statistical evidence simply begs the question. Some forms of alternative medicine have no theoretical foundation and no empirical support, and seem to be fraudulent attempts to exploit human suffering. However, the history of medicine includes a number of folk remedies that were discovered and subsequently absorbed by mainstream medicine, with or without scientific proof. Examples include digitalis,...

Posttransplant Coordinators Role

Vaccines Patients must always receive killed virus vaccines after transplantation. 1. Patient must avoid children who have received the live polio vaccine for up to 1 month the child will secrete this vims through the G1 tract. Do not come in contact with child's stools (i.e., changing diapers). 2. Examples of live or weakened vaccines 3. Examples of killed virus vaccines Before discharge, signs and symptoms of rejection, adverse reactions to medications, recommended routine screening, vaccine recommendation, exercise, and healthy living guidelines are reviewed. Tables 6.1 and 6.2 outline a formal, posttransplant medication teaching plan for a renal transplant recipient. Additional reinforcement or new teaching methods can be instituted to avoid complications. Outpatient clinic visits present an excellent opportunity to assess the patient for changing needs. As the patient recovers, new information may be introduced.

Symptomatic treatment

If there is a marked increase in blood requirement, hyper-splenism should be suspected. Any thalassaemic child with an easily palpable spleen probably has some degree of hypersplen-ism. Splenectomy should be carried out as late as is feasible and, if possible, not in the first 5 years because the incidence of post-splenectomy infection seems to be particularly high in early childhood. Apart from increased transfusion requirements, the presence of neutropenia or thrombocytopenia is a useful guide to the presence of hypersplenism. Pneumococcal vaccine should be administered before surgery, and after the operation children should be maintained on prophylactic penicillin indefinitely and the parents warned about the danger of overwhelming infection. Because of this risk it is becoming customary to also immunize these children against Streptococcus pneumoniae and Haemophilus influenzae.

Staphylococcus food poisoning

All meat dishes should be either cooked and eaten immediately or refrigerated until required. Reheating of foodstuffs should be avoided and in New Guinea special precautions should be taken when pig-feasting occurs. A successful vaccine has been developed with a clostridial toxoid prepared from C cultures.

Background and Epidemiology of Hepatitis Viruses in Correctional Settings

Following the implementation of routine hepatitis A vaccination of children, overall hepatitis A rates have declined approximately 75 from 1990-1997 to 2004 (Wasley, Samandari, & Bell, 2005 Fiore et al., 2006). In 2004, the rate of hepatitis A case reports was 1.9 cases per 100,000 population (Fiore et al., 2006). The prevalence of HAV infection among persons aged > 6 years in the United States was estimated to be 31.1 based on data from the National Health and Nutrition Examination Survey III conducted in 1988-1994 (Bell et al., 2005). With the implementation of a comprehensive hepatitis B vaccination strategy since 1991, the incidence of acute hepatitis B has declined 78 during 1990-2005 from 8.5 to 1.9 per 100,000 population (CDC, 2006b). The rate of acute hepatitis B varies by age, sex, and race the highest rates occur among Sexual contact is the predominant mode of HBV transmission among adults (Goldstein et al., 2002). In a sentinel surveillance project including six U.S....

Health Advice And Protective Measures

As shown in Figure 10.2, options for the prevention of travelers' diarrhea include education, vaccination and chemoprophylaxis with either BSS-containing compounds or antibiotics (Ericsson and Rey, 1997). Although vaccination is a promising option, vaccines against all enteropathogens that cause travelers' diarrhea will probably never be possible or cost-effective owing to the large number of strains that cause disease. Promising vaccines against ETEC and Shigella are not available for routine use (Ericsson and Rey, 1997).

Prevention of Viral Hepatitis

Primary prevention of infection with HAV and HBV can be achieved through immunization. For HCV, primary prevention of infection activities includes screening and testing of blood donors, virus inactivation of plasma-derived products, risk reduction counseling and services (e.g., substance abuse treatment) for injection-drug users, and implementation and maintenance of infection control practices to prevent exposure to blood. Identification of persons with chronic HBV and HCV infection provides an opportunity to initiate primary prevention activities including vaccination of household, sex, and needle-sharing contacts of persons with chronic HBV infection and counseling to reduce risks for transmitting HBV and HCV to others. In addition, persons with chronic HBV and HCV infection can be provided medical management that can reduce the progression of chronic liver disease. This section summarizes current information, practices, and recommendations to prevent infection with hepatitis...

Immunological Mechanisms of Immunisation Active Immunisation

Gen-antibody and antigen-T cell interactions, which recognise both surface and internal foreign antigens, and of the induced immunological memory by active immunisation with attenuated live vaccines and killed (inactivated) vaccines. Live vaccines induce a cell-mediated response associated with a vigorous amnestic response, whereas inactivated vaccines initially raise a humoral response that is less efficient in terms of immune protection and often requires the administration of several doses of vaccine as part of the primary course. Consequently, for inactivated vaccines, long-lasting immunity is achieved by stimulation of both the cell-mediated and humoral response by the administration of regular boosters. Immunological or biological memory is dependent on prior selection or priming of lymphocyte clones with specific receptors, so that persistence of the microbial antigen or re-exposure to it maintains, activates and indeed expands the relevant immune functions.

Allergies and Hypersensitivity Reactions

Anaphylactic reactions to a vaccine or to a vaccine constituent are an absolute contraindication to the use of that vaccine or to vaccines containing that constituent. A problem which is encountered frequently is allergy to eggs. Hypersensitivity to egg is a contraindication to influenza vaccine, and an anaphylactic reaction to egg contraindicates influenza and yellow fever vaccines. There is increasing evidence that MMR vaccine can be given safely to children even if they had previously had an anaphylactic reaction after eating food containing egg, but strict caution is advised and day admission to a hospital for the procedure is recommended.

Infection with HIV With or Without Symptoms

Individuals with human immunodeficiency virus (HIV) infection must not receive BCG or yellow fever vaccine. MMR and live attenuated OPV have been given without harmful effects to asymptomatic individuals infected with HIV, who are at an increased risk of infection with these viruses. Note that prolonged excretion of polio virus may occur, and killed (inactivated) Salk-type of polio vaccine may be preferred. In cases of symptomatic HIV infection, the killed polio vaccine should be used and the administration of MMR vaccine must be given with caution and consideration of the risks of vaccination against those of contracting infection. Note that vaccine efficacy may be reduced in individuals with HIV infection and there is often rapid antibody decay and subsequent loss of protection. Other recommended vaccines for this group of individuals include pneumococcal and influenza vaccine, as the risk of infection with either of these respiratory diseases is considerable in terms of morbidity...

Genetic Research and Genetic Counseling in Psychiatric Patients

With the standards regulating clinical experimentation in general, notably in such allied fields as experimentation on vaccines and immunobiological products. They point to the risks of gene therapies being treated entirely separately from biomedical research rather, one should seek to identify the ethical and biosafety dimensions that are specific to these therapies by drawing in extensive interdisciplinary expertise.

Haemophilus Influenza

Immunisation with Hib vaccine has now become a component of the routine childhood immunisation programme in industrialised countries, where it is administered simultaneously with the combination vaccine DTP. As a conjugate polysaccharide vaccine, it provides enhanced immunogenicity which is of particular importance in providing protection for infants under the age of 4 years, the highest risk group. It is also recommended for use in asplenic or immunosuppressed children and adults, in whom a single dose of vaccine will protect against serious respiratory disease. This may well be relevant for such individuals travelling where the risk of exposure may be high in developing countries. Booster doses are not recommended.

Cellular Delivery of Nucleic Acids

Peptoids have also shown great utility in their ability to complex with and deliver nucleic acids to cells, a critical step toward the development of antisense drugs, DNA vaccines, or gene-based therapeutics. Most non-viral nucleic acid delivery systems are based on cationic molecules that can form complexes with the polyan-

Japanese Encephalitis

Vaccination against Japanese encephalitis is recommended for travellers to Southeast Asia and the Indian Subcontinent who will be visiting an endemic rural area, particularly for longer than 1 month during the appropriate season, which varies between countries within the Asian subcontinent. The risk of infection is extremely low and is estimated at approximately < 1 per million travellers, which increases to 1 per 5000 for travellers visiting a rural endemic area. This risk depends upon the season, location and duration of travel as well as the actual activities of the traveller. The vaccine is administered by deep subcutaneous injection at days 0, 7-14 and 28 and is licensed for paediat-ric (0.5ml for those < 3 years) and adult (1.0ml) use. A more rapid schedule may be considered for use, with two doses given at 1-2 weeks apart, and the last dose must be administered at least 10 days prior to travel to enable adequate levels of protection to develop. This schedule will confer...

Meningococcal Meningitis

Protection is afforded by the administration of a single 0.5 ml dose of polysaccharide serogroup A and C vaccine administered intramuscularly, with booster doses recommended between 3 and 5 years. The polysaccharide A and C vaccine is a T-cell independent vaccine with poor im-munogenicity in children under the age of 18 months, so a booster 1 year later is recommended for this age group. In 2000, a specific strain ofNeisseria meningitides, serogroup W135, was identified as the cause of an outbreak of disease during the Hajj. Consequently, a quadrivalent polysaccharide, ACW135Y meningococcal meningitis vaccine has been developed and is now the required men-ingococcal meningitis vaccine for travellers specifically visiting Saudi Arabia for the Hajj. Recently, a new conjugate serogroup C meningococcal meningitis vaccine has been licensed in the United Kingdom for use in all high-risk groups, including infants, children and adolescents. The introduction of this conjugate vaccine has been...

Mumps Measles and Rubella

The risk of travellers' exposure to measles, mumps and rubella is greatest from visits to tropical countries where these diseases remain endemic and routine vaccination programmes are not established, unlike those in industrialised countries. Infants and young children born in industrialised countries, who are going to live for prolonged periods in such areas, should receive their routine childhood immunisations, including MMR, before travel, which may necessitate immunisation at an earlier age than recommended for the national immunisation programme. For those that have defaulted or have not received a complete course of immunisation, the risks of infection should be clearly explained and immunisation strongly recommended and administered before departure. Susceptible adolescents, adults and women of child-bearing age should also be vaccinated with MMR before travel or living abroad. Individuals born before 1957 are generally considered to have natural immunity and are therefore not...

Historical Introduction

Amebas from dust in 1913 and identified them as Amoeba polyphagus. Page (1967) redescribed this ameba as Acanthamoeba polyphaga. Sir Aldo Castellani (1930) also isolated an ameba which was found as a contaminant in his yeast culture, and this ameba was later named as Acanthamoeba castellanii. The pathogenic potential of Acanthamoeba was demonstrated by Culbertson et al. (1958), when they isolated an ameba that occurred as a contaminant in monkey kidney cell cultures during the production of the poliomyelitis vaccine. This isolate is now named as Acanthamoeba culbertsoni. However, it was Fowler and Carter (1965) from Adelaide, Australia, who demonstrated for the first time that these small free-living amebas can cause human disease leading to death. The ameba isolated by them from human brain is now designated Naegleria fowleri. Balamuthia mandrillaris, the third ameba known to cause human disease (Visvesvara et al., 1993), was first isolated in 1986 from the brain of a mandrill baboon...

Pneumococcal Infection

Pneumoccocal infection may occur anywhere in the world but is of particular concern to those at high risk of infection in whom invasive disease may be a serious cause of morbidity and mortality. This group includes those who are over the age of 65 years, are immunocom-promised, have an underlying chronic medical condition, e.g. diabetes mellitus or chronic respiratory or cardiovascular disease or have asplenia or have undergone a sple-nectomy. Asplenic individuals, travelling or otherwise, are advised to receive influenza, meningococcal and Hib vaccine as well as pneumococcal vaccine. Immunisation consists of a single 0.5 ml dose of an inactivated polysaccharide vaccine administered intramuscularly with a booster dose at 5-10 years, which is only recommended for those at significant risk of serious illness. It should be noted that there is an association with rapid decay of antibody levels with polysaccharide vaccines as they are not T-cell dependent, resulting in a poor amnestic...

Tickborne Encephalitis

The vaccine is administered intramuscularly as a primary course of two 0.5 ml injections given 4-12 weeks apart, which will provide protection for 1 year. A third dose is given 9-12 months after the second dose and confers immunity for 3 years. Booster doses are subsequently recommended at 3-yearly intervals for those at continued risk. Serious side-effects are uncommon. A specific immunoglobulin preparation is available for both preexposure and post-exposure use where appropriate. The vaccine is available in the United Kingdom on a named-patient basis only, and additional methods of personal protection should be afforded by the use of insect repellents and appropriate clothing.

Absorption and delivery of macromolecules

Various strategies have been used to target vaccine antigens to the gut-associated lymphoid tissues, such as microspheres prepared from various polymers. Certainly in mice the size of the microspheres has to be less than 5 pm for them to be transported within macrophages through the efferent lymphatics56. Transcytosis through Peyer's patches is most suited for highly potent compounds since there are a limited number of Peyer's patches, hence the overall surface area is relatively small. Patch tissue is rich in lymphocytes, thus substances which interact with lymphocytes are best targeted to Peyer's patches when using the oral route57.

Syndrome Of Acute Anterior Poliomyelitis

In the past, this syndrome was almost invariably due to one of the three types of poliovirus. Vaccines have practically eliminated the disease, but occasional cases still occur in unvaccinated children and in adults exposed to a recently vaccinated child. A similar, though generally Treatment is essentially preventive. The Sabin vaccine, which consists of attenuated live virus, is administered orally to infants in two doses 8 weeks apart, with boosters at 1 year and 4 years of age. Poliomyelitis may follow vaccination (0.02 to 0.04 cases per million doses).

Preparedness and Response Systems Supplies Staff and Space1

To determine the local, state and federal resources that are necessary to respond to disasters, Jonathan L. Burstein has suggested a model defining the preparedness and response problem in terms of systems, supplies, staff, and space (Burstein, 2004). The systems component of the model seeks to address the communications and logistics needed to prepare for and respond to crises. The supply variable addresses the drugs, vaccines, and basic necessities housing, food, and water that victims need, and how to best distribute those resources among affected communities. Staff considerations include training and credentialing adequate numbers of volunteers and ensuring their safety throughout the response effort. The final component of the model, space, takes into account the physical space needed for patient care, isolation, if necessary, and the distribution of community prophylaxis. Upgrading the public health and health care systems by strengthening systems, supplies, staff, and space,...

Future Areas for Research and Evaluation

During 2006, a vaccine for the human papillomavirus (HPV) types most commonly associated with cervical cancer and genital warts was introduced for women (Saslow et al., 2007). It remains to be seen whether recommen dations will be developed to vaccinate young women in youth detention, as there are recommendations for vaccination of adolescents for other infections in this setting.

Immunization strategy

BCG vaccination may be used selectively in tuberculin-negative persons who are at high risk, for example close contacts, doctors, nurses and hospital ward attendants. A strain of BCG that is resistant to isoniazid has been developed this can be used in vaccinating tuberculosis contacts who require immediate protection with isoniazid. BCG may also be used more widely in immunizing tuberculin-negative persons, especially children, in the community. In some developing countries where preliminary tuberculin testing may significantly reduce coverage, BCG may be administered in mass campaigns without tuberculin tests. The disadvantage of this method of 'direct BCG vaccination' is that those who are tuberculin-positive are likely to show more severe local reactions at the site of vaccination. BCG vaccination of the new-born is widely practised in the tropics. Overall, the evidence suggests that it confers considerable protection against tuberculosis in infants and young children. The...

Pneumococcal pneumonia

Vaccination The general measures for the prevention of respiratory infections apply - avoidance of overcrowding, good ventilation and improved personal hygiene with regard to coughing and spitting. Prompt treatment of cases with antibiotics penicillin, cephalosporins, vancomycin would prevent complications. Chemoprophylaxis with penicillin is indicated in cases of outbreaks in institutions. A polyvalent polysaccharide vaccine is available and has been successfully used in children with sickle cell disease. It is not effective in children under 2 years. viral infection (e.g. measles and inlTtieiua vaccination)

Transgenic Plants for Production of Immunotherapeutic Agents

Since the first reports 20 years ago, genetically engineered plants with improved traits, pest and herbicide resistance, etc., have produced significant agricultural revenues. In contrast, the development of plants as bioreactors to produce transgenic proteins for pharmaceutical use is in its infancy. Numerous immunotherapeutic proteins, antibodies, and vaccines have been produced however, a limited number have made their way into clinical trials. The most advanced product in human clinical trials is a secretory immunoglobulin A (IgA) antibody composed of four polypeptide chains that inhibits the binding to teeth of Streptococcus mutans, the major oral pathogen. This chapter will summarize recent work demonstrating the potential of plants to synthesize and assemble complex proteins suitable for human therapeutic use.

Liabilities for Fetal Damage

Given all of the above reasons for including women of child-bearing potential, the issue of the chilling effect of legal liability for fetal damage on firms and institutions is still present, and the necessary addition to the patient's informed consent does not help. The Supreme Court in 1992 rejected an attempt to cap the amount juries could award in damages as 'unconstitutional', i.e., would require a constitutional amendment. This is highly unlikely to occur. The consequence of litigation, particularly in obstetrics, was a dramatic increase in cae-sarean section (18-20 of live births this level was even higher in 1999), resignation from this specialty, and a broader rejection of 'high-risk' or Medicaid patients (O'Reilly et al, 1986 Bello, 1989). A possible solution might be to follow the example of the National Vaccine Injury Act of October 1988, where a trust fund was set up derived from an excise tax imposed on each vaccine. The funds, through an arbitration panel, are used to...

Future Therapeutic Strategies

At present, the treatment of advanced and metastatic medullary thyroid carcinoma is unsatisfactory. Novel alternative therapeutic approaches are under investigation and several experimental studies are already ongoing 173 . Tissue-specific cancer gene therapy has been evaluated for several years. Adenovirus-mediated tumor-specific combined gene therapy using the herpes simplex virus thymidine ganciclovir system and murine interleukin-12 seems very promising. An effective growth suppression of tumor has been observed in rat models affected by medullary thyroid carcinoma and treated with this system 174 . Other interesting approaches are based on immunotherapy, for example stimulation of immune response and vaccination with tumor lysate 175,176 .

Applications in Applied Research

Nuclear receptors function in plants. Agricultural applications of orthogonal li-gand-nuclear receptor pairs include conditional expression of any RNA or protein, including short interfering RNAs to block gene expression, human vaccine proteins, insecticidal proteins and disease resistance genes. Expressing insecticidal proteins and disease resistance genes only at specific times (rather than constitutively) would likely decrease the occurrence of resistance developing in the environment.

David Shapiro and Anthony W

Biological products have a longer and more illustrious history that is generally assumed at one time smallpox accounted for 10 of deaths in some countries, but today this is the only infectious disease ever to have been eradicated from our planet the development of cow pox vaccination was in 1796, while the last case of the disease occurred in 1979 following a laboratory accident. The Vario-cella vaccine may yet not be redundant in combatting bioterrorism. It is beyond the scope of this chapter to discuss all potential applications and all present technologies associated with biological drugs. We merely provide an overview. We shall not cover orthodox vaccines, fermented products (e.g. for antibiotics), blood products, tissue-extracted hormones, diagnostic products (e.g. antibody-based assay systems), and devices utilizing biotechnology products, which are not themselves used therapeutically. These are, technically, biotechnology products, but here we wish to concentrate on the newer...

Reporting Requirements

The reason most often cited for the lack of adverse event reporting is uncertainty about the causality of an adverse reaction. Although confirmation of an ADR is ideal, it is often not feasible. The FDA readily acknowledges this limitation and continues to encourage the reporting of all suspected adverse drug reactions through its MedWatch program. Detailed instructions for reporting adverse events associated with drugs, medical devices, vaccines, and veterinary products is provided online by the FDA (http www.fda.gov medwatch report hcp.htm). The essential components of an ADR report are listed in Table 25.6. The FDA is particularly interested in receiving reports of adverse reactions involving new chemical entities and serious reactions involving any medical product.

Measles MumpsRubella MMR and Measles

Immunity to measles is essential for all travelers. Many young adults require immunization (or reimmunization) for protection. The specific recommendations for the age groups vary depending on the traveler's country of origin and epidemiology of measles in that country. The measles vaccine as well as the MMR (measles, mumps, rubella combination) are live vaccines and contraindicated in pregnancy. Due to the increased incidence of measles in children in developing countries, its communicability, and its potential for causing serious consequences in pregnancy, some health providers would advise delaying travel of a nonimmune woman until after delivery, when the vaccine can be given. If a documented exposure to measles occurs, immune globulin may be given within a 6 day period to a pregnant woman to prevent disease. It is important to remember that the immune globulin may not be available in many high-risk countries.

Tetanus and Diphtheria

To maintain immunity against diphtheria and tetanus a booster dose of tetanus-diphtheria vaccine (Td for adult use) should be given every 10 years. Women traveling to areas where they may deliver under unhygienic circumstances or surroundings should update their immunity to prevent neonatal tetanus. The WHO, the Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists all endorse tetanus toxoid administration during pregnancy. Immunization of pregnant women with tetanus toxoid at least 6 weeks before delivery effectively provides protection of newborns against neonatal tetanus by stimulating the production of specific IgG antibodies that cross the placenta, while also protecting these women against puerperal tetanus. Maternal immunization with tetanus toxoid is practiced worldwide and has resulted in dramatic decreases in the incidence of neonatal tetanus in many regions, with no evidence of adverse effects to mother or fetus...

Meningoccal Meningitis

The bacterial polysaccharide polyvalent meningococcal vaccine may be administered during pregnancy if the woman is entering an area where the disease is epidemic or during an outbreak. The commonly available menin-gococcal vaccine in the United States is a tetravalent vaccine from groups A, C, Y and W135. In a number of other countries only bivalent vaccine from group A and C is commonly used. The safety of the vaccine in pregnancy has not been conclusively demonstrated, although a small study published in 1980 showed no birth defects in infants whose mothers were vaccinated during an epidemic in Brazil.

Beta receptor agonists

As has been mentioned, the pulmonary route has been used to achieve systemic delivery. A product containing ergotamine tartrate is available as an aerosolized dosage inhaler (360 pg per dose) and has the advantage of avoiding the delay in drug absorption due to gastric stasis associated with migraine. In vaccine delivery, aerosol administration of para-influenza Type 2 vaccine has been found to be more effective than subcutaneous injection49). Penicillin reaches the bloodstream in therapeutic quantities after pulmonary delivery, but kanamycin is poorly absorbed from the lung so can only be used for local drug delivery.

New Removalinactivation Technology

Emerging technology promises to complement the currently available methods for virus clearance. Some emerging technologies are nearing commercialization while others require additional development. Ion exchange membrane adsorbers have ligand virus-binding properties similar to those of AEX chromatography, but membranes possess certain practical advantages. For example, ligand target binding to membranes is largely kinetic and not limited by pore diffusion thus, membranes allow very high flow rates, short processing times, and low pressure drops. Membranes are disposable and generally require less floor space and specialized equipment than do columns, while their performance validation is simplified because post-use cleaning is not necessary. Ion exchange membranes have already been used successfully to bind and then release virus particles in vaccine production 23 removing viruses from process intermediates should be even simpler, since the particles are discarded with the disposable...

Congenital Immune Deficiency Due to a Cellular or Humoral Immune Deficiency

Severe combined immune deficiency (SCID) is a rare T-cell disorder, which usually presents within the first months of life. In addition, B-cell function is mostly compromised, leading to both cell-mediated and humoral deficiencies. Life expectancy will generally be short however, if these patients reach travelling age, travel should be discouraged because of disseminated or persistent infection after live attenuated vaccines. This has been described after BCG and oral polio vaccination, but the same can be expected after oral typhoid vaccine and yellow fever vaccine. 2, for the rarely seen X-linked agammaglobulinaemia. Other types do not usually become clinically relevant until the third decade. The presenting infections are predominantly with encapsulated bacteria such as pneumococci, meningococci and Haemophilus influenzae. Common variable immunodeficiency (CVI) and, to a lesser extent, IgA deficiency are a heterogeneous group of diseases that share the features of...

Time after 1st infection weeks

Some microbial antigens - particularly repetitive polysaccharides may activate B cells directly by cross linking multiple immunoglobulin receptors to produce antibody in the absence of T cell help. In the instance of repetitive polysaccharides, primarily mature B cells are activated and although antibody can be synthesized the absence of help, T helper cytokines augment the magnitude of antibody production by these cells. Thus, persons with T cell immunodeficiency (eg HIV infection) tend to have poor responses to immunization with T cell independent polysaccharide vaccines. Cognate T cell help can be provided by conjugating the polysaccharide antigen to an immunogenic peptide. B cell ingestion of the peptide polysaccharide complex results in presentation of the peptide to T helper cells by MHC class II antigens. The cognate T cell help provided by this interaction as outlined above results in an amplified B cell response. Thus, B cell epitopes that are targets for antibody recognition...

Hivrelated Immune Deficiency

Infection with the human immunedoficiency virus (HIV) causes a gradual decrease of CD4 + T lymphocytes. Because of the main role in the human defence system of these cells, not only the cellular but also the humoral defence system is diminished, leading to increased vulnerability to opportunistic infections. A less effective immune response to immunisation and an increased risk of complications after administration of live attenuated vaccines are then seen. In daily practice, the number of CD4 + cells in the peripheral blood is a measure of the level of immune suppression by HIV. In advising HIV-infected travellers several issues are important for consideration the increased vulnerability to infection the decreased efficacy of or contraindications for vaccines interaction of anti-HIV drugs with, most importantly, the antimalarial prophylactic drugs and, lastly, practical problems encountered at the borders of many countries. The availability of treatment in many parts of the world and...

Priority setting for health

Biomedical research to develop new and improved tools - drugs, vaccines, diagnostic methods and vector control measures In situations where more effective control of a disease can be achieved through efficient application of existing technologies, health systems research can provide useful answers. For example, although tetanus neonatorum can be prevented by a simple, affordable measure of toxoid immunization of pregnant women, about a quarter of a million children die each year from this preventable disease. Health services research would help to identify the under-served communities and develop strategies for ensuring that all pregnant women receive this simple and cost-effective intervention. On the other hand, for HIV AIDS, there is an urgent need for biomedical research to discover and develop effective vaccines and new drugs to replace the current technologies that are crude, cumbersome and costly.

Overwhelming postoperative infection

When splenectomy is being planned, the patient should be immunized against pneumococcal pneumonia, H. influenzae type B (HIB) and meningococcal infection. However, while pneu-mococcal vaccine contains antigens to a number of strains of Streptococcus pneumoniae it does not give complete protection because some strains are not covered and antibody response to the different antigens is variable. To obtain the maximum immune response, patients should, if possible, be immunized 2 to 3 months before splenectomy, and a booster dose should be given 5 years later. Most children will have received HIB vaccine but this should be checked booster doses are not necessary for those who received the full course of three injections. Meningococcal vaccines are effective against types A and C but not against type B, the most prevalent in the West. The patient should also receive meningococcal C conjugate vaccine at a 6-month interval as this gives a higher and more lasting immunization against type C...

Novel Therapeutic Delivery Systems In The Treatment Of Prostate Cancer

Tumor cell vaccines are a typical ex vivo gene therapy strategy for cancer and rely on the ability of cancer-specific antigens to elicit an immune response. An approach is to harvest tumor cells from the patient, genetically modify the cells (usually with retroviral transfection) so that they can stimulate the immune system, irradiate the cells so that they are non-tumorigenic, and reinject the cells into the patient. The first tumor vaccine trial for prostate cancer began in 1994 when granulocyte-macrophage colony-stimulating factor (GM-CSF) was transfected using retrovirus into a patient's prostate cancer cells in vitro. The cells were then injected subcutaneously and found to be safe in phase I trials.178 Data from this trial indicate vaccination activated new T-cell and B-cell immune responses against PCA antigens. T-cell responses, evaluated by assessing delayed-type hypersensitivity (DTH) reactions against untransduced autologous tumor cells, were evident in two of eight...

Management of antibody deficiency

Experimental mouse models have clearly demonstrated the importance of IL-12 and IFN-y and their corresponding receptors in protection against infection with intracellular pathogens, particularly mycobacteria. This work led to a search for defects in these proteins in rare cases of infants and young children presenting with chronic mycobacterial disease, including persistent local disseminated BCG infection following vaccination. Families have been reported with autosomal inherited defects involving the IFN-y receptor, STAT-1, which is critical in the signalling pathway for this receptor, and in IL-12 and its receptor. Affected patients usually present with chronic atypical mycobacterial infection at an early age and are also prone to chronic Salmonella infection. A defect in NEMO (NFkB modulator) causes a rare X-linked severe immunodeficiency with ectodermal dysplasia. Defects in IRAK-4 (interleukin-1 receptor-associated kinase 4) have been found in patients prone to recurrent...

Cell Signaling Inhibition

BCL-2 inhibition AKT inhibition Gene therapy Enhancing iodine uptake Demethylating agents Histone deacetylase inhibitors Retinoids Gene therapy Enhanced chemotherapy effects Drug resistance gene inhibitors Combination therapy Immunotherapy Gene therapy Tumor vaccines BCG

Targeted Cytotoxic Agents

Finally, gene therapy using vectors that carry cytotoxic genes (suicide gene therapy) has been utilized to treat thyroid cancer cells in vitro, and,by direct tumor injection,in vivo. The best reported method is to induce thyroid cancer cell expression of thymidine kinase, which will uniquely sensitize the cells to treatment with the antiviral drug ganciclovir 49 . This approach has been used in xenografts as independent therapy, and also in sensitizing the cells to the effects of external irradiation. Gene therapy approaches that combine cytotoxic genes with immunomodulators have also been reported 50-52 . Tumor vaccines offer another immunotherapy model. This group of agents targeted against cell survival therefore represent an attractive option to sensitize cells to the effects of radiation and or chemotherapy.

Advances In Tumor Immunology

Although an exhaustive review of tumor immunology is beyond the scope of this chapter, current concepts, including antigen presentation and the effector arms of the immune system, will be discussed to help understand the immunization strategies undertaken in the many preclinical and clinical vaccine trials for prostate cancer.

Other Emerging Therapies for Thyroid Cancer

Immunotherapy remains a major area of interest for thyroid cancer, and for a number of other malignancies 58,59 . The use of tumor vaccines with or without agents to enhance immune responses, or to induce thyroiditis in patients on chemotherapy using interferons, are avenues of potential treatment for thyroid cancer in the future.

Gene Therapy of Infectious Diseases

With a number of molecular targets for antiviral therapy. The gene manipulation techniques for HIV-1 therapy encompass a variety of gene-transfer based approaches, i.e., antisense oligonucleotides, ribozymes, transdominant negative mutant recombinant HIV-1 proteins, molecular sinks, and suicide gene constructs (46). These technologies can be broadly divided into two groups intracellular immunization and immunotherapy. Intracellular immunization makes the cells resistant to viral replication and inhibits the further spread of the virus, whereas immunotherapeutic approaches block the viral spread by an antiviral cellular response. Immunotherapeutic approaches involve the use of vaccines and adoptive transfer of CD8+ T-cell clones. The human immune system provides the major defense against the spread of infections within the host. The mechanism involves either the recognition of extracellular pathogens by the antibodies or the generation of cytotoxic T-cells (CTLs) that eliminate the...

Detection of tumorassociated antigens

The concept behind active immunotherapy is based on the theory that tumors possess specific antigens that can be recognized by the immune system, identified as being foreign and then destroyed. Indeed, numerous gene therapy studies have confirmed the hypothesis that most theoretically 'non-immunogenic' tumors are indeed immunogenic.63,64 Although few truly 'foreign' antigens have been identified, the term tumor-associated antigen (TAA) describes antigens that are found on human tumors but are also expressed in varying degrees by normal cells. Since the first convincing demonstration of their existence,65 there has been a great deal of interest in identifying these TAAs for therapeutic use in human cancers. Although most advances in this field have come from work with melanoma cells (probably the most immunogenic human tumor), prostate cancer TAAs are beginning to become identified, further stimulating the investigations toward an effective prostate cancer vaccine. There are various...

Epidemiology Clinical Features and Geographical Distribution

A rotavirus vaccine, a rhesus-based rotavirus vaccine-tetravelent (RRV-TV), has been licensed in the USA and elsewhere. RRV-TV is a live attenuated oral vaccine which incorporates a rhesus monkey rotavirus strain (with human serotype G3 specificity) and three singlegene human-rhesus reassortants. Immunisation early in life, which mimics the child's first natural infection, will not prevent all subsequent disease but should prevent most cases of severe rotavirus diarrhoea including hospital admission for treatment. The US Advisory Committee on Immunization Practices (1999a) recommends routine immunisation with three oral doses of RRV-TV for infants at the age of 2, 4 and 6 months. This vaccine can be administered together with DPT, Hib vaccine, oral polio vaccine, inactivated polio vaccine and hepatitis B vaccine. RRV-TV is effective but has now been withdrawn owing to a number of adverse events. Vaccines against other viruses causing gastroenteritis are not available.

Malaria And Other Insectborne Diseases

No single intervention is 100 protective, and a multi-faceted approach to the prevention of insect-borne diseases is needed. Vaccination and chemoprophylaxis are not available for many diseases transmitted by insects thus, the avoidance of bites by mosquitoes and other insects should be a primary focus. Malaria Vaccines The initial optimism for the usefulness of a South American malaria vaccine has waned, as studies in other populations showed very limited efficacy in children. New DNA vaccines offering a combination of antigens in a prime-boost technique now hold great promise. Vaccines could be ready for clinical trials in children during the first few years of the twenty-first century.

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