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; More here...

The Revised Authoritative Guide To Vaccine Legal Exemptions Overview

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Vaccines Block Disease

Vaccines represent an alternative way to combat microbes and viruses. Vaccines are preparations of attenuated pathogen or noninfectious parts of pathogens. When eaten or injected, vaccines create a protective immune response against a particular pathogen. Some vaccines are so effective that they eliminate a disease, as was the case with smallpox. The absence of disease means no resistance problem. Unfortunately, we have been unable to make effective vaccines for many pathogens, most notably HIV, tuberculosis, and malaria. Moreover, pathogen diversity can generate resistance to a vaccine (see Box 1-4).

Administration Of Vaccines

The route of administration depends on the vaccine. Live polio vaccine is always given by mouth. Injectable vaccines are usually administered intramuscularly or deep subcutaneously, although an equally effective but smaller dose can sometimes be given intradermally and this may be relevant with expensive vaccines (e.g. rabies). Since vaccination usually requires attendance at a clinic it is often worthwhile giving more than one vaccine at a visit. Individuals can respond to multiple antigens administered simultaneously, although between 4 and 14 days after one vaccine individuals may respond poorly to another. Therefore vaccines should either be given simultaneously, preferably at different sites, or after an interval of at least 3 weeks. If multiple doses are required the optimum interval will depend on which type of vaccine (live or killed) is used. It is 1 month between doses of polio vaccine and 1 and 4 months, respectively, between the first and second and the second and third...

Epidemiological Consequences Of Mass Vaccination

If an individual benefits from being immunized it is often assumed that the overall effect on society at large will be equally beneficial. This may not, however, always be the case. The reason for this is that we are changing aspects of herd immunity and it may not be possible to precisely anticipate the shift of susceptible cohorts. Deferring childhood diseases to older age groups may consequently increase the frequency of complications if the vaccine coverage is too low (e.g. measles). A special case is the use of rubella vaccine if only a low but still significant fraction of children and teenagers is immunized, there is a possibility, through the consequent reduced spread of wild-type virus in the community, of accumulating more susceptible women at childbearing age, and thus possibly increasing the incidence of congenital rubella syndrome. Another special case is the selective use of influenza vaccines among risk groups aimed at reducing morbidity and mortality among these...

Need for a Pediatric Vaccine Against Prevalent Serotypes

Malnutrition and impairs childhood development, in endemic areas (Petri et al. 2008 Moore et al. 2010). The infection originates through contacts with Shigella, a Gram-negative enteroinvasive bacterium. The species Shigella is divided into four groups, namely, S.flexneri (SF), S. sonnei, S. dysenteriae (SD) and S. boydii, which are subdivided into some 50 serotypes and subserotypes according to the structure of their O-Ag RU (Simmons and Romanowska 1987 Liu et al. 2008). Several serotypes trigger infection, and the prevalence of antibiotic-resistant strains is markedly on the rise (Kosek et al. 2010). Of utmost concern, SD1 sets off devastating epidemics, whereas S. sonnei and SF - most of the 15 known serotypes - account for endemic infections. While SF is prevalent in developing countries, S. sonnei causes occasional outbreaks in developed countries and tends to gain importance in emerging countries. Despite the persisting need for a vaccine and the breadth of candidate vaccines...

DLPS Conjugates as Advanced Investigational Shigella Vaccines

The strong indication that Shigella O-Ags are major targets of the host's humoral protective immune response against bacillary dysentery (Cohen et al. 1991) has been exploited advantageously (Levine et al. 2007 Kweon 2008 Kaminski and Oaks 2009). Prime investigations on dLPS conjugates capable of inducing anti-LPS IgG-mediated protection (Robbins et al. 1992) focused on the most prevalent serotypes, namely SD1, SF serotype 2a (SF2a), and S. sonnei. Candidate vaccines against SF2a and S. sonnei were shown to have excellent safety records and to be immunogenic in adults. Subsequently, immunogenicity in 1 to 4-year-old children, the age group at greatest risk for shigellosis, was also demonstrated (Passwell et al. 2003). Of particular merit is the finding that a S. sonnei conjugate provided protection in young adult volunteers (Cohen et al. 1997) and more importantly, in the 3 to 4 years old (Passwell et al. 2010). A further support to the concept resides in the evidence that anti-LPS...

Cancer Vaccines That Elicit

The consensus that cytotoxic T lymphocytes play a major role in tumor control led to efforts to design vaccines that specifically induce or amplify tumor-specific CTL. Key to production of such vaccines is the identification of tumor antigens recognized by CTL. In humans in particular, the vast majority of tumors arise sporadically, and the associated antigens are highly variable and difficult to predict. Early attempts to define tumor antigens based on antibody reactivity to tumor surface structures seemed of limited use, particularly once it was realized that CTL do not recognize native antigen at cell surfaces. Using these and other approaches, a large number of tumor-associated peptides have been identified (80-82). Some are derived from proteins normally expressed at low levels in a limited number of cells, but over-expressed in tumor cells. Some represent proteins (differentiation antigens) normally present only at restricted stages of development, but expressed -again, often at...

Monitoring vaccination studies

Assays to quantitate antigen-specific T cells are crucial for the development of cancer immunotherapy. A major issue in vaccine development is the correlation of clinical efficacy with T cell responses as surrogate markers. There is increasing evidence now from various clinical cancer vaccination trials for a relation between the detection of vaccine-induced T cells by cytokine-based assays and clinical responses (reviewed in 14). Standardization and validation of T cell assays to monitor the induction of specific T cells responses is crucial to reliable monitoring of clinical trials. Several expert workshops have been performed within the EORTC melanoma group and the International Society of Biological Therapy of Cancer (ISBTC) on T cell assay methodology and standardization (15, 16). The simultaneous use of two ex vivo T cell assays including a functional assay for T cell monitoring has been proposed (16). Controls for the quality of the samples as well as for the accuracy and...

On the Road Towards a SF Glycovaccine in the Context of Multivalency

As already stated, the number and highly variable geographical distribution of SF serotypes causing shigellosis may hamper the development of a broadly efficient vaccine (Levine et al. 2007). Based on type and group antigenic determinants (Fig. 1.6), SF3a, which also predominates in several countries, is an attractive serotype to include in a broad serotype coverage vaccine comprised of a limited number of serotypes. In this context, it was included as a major component of several cocktail vaccine candidates (Levine et al. 2007). In particular, a bivalent attenuated construct combining SF3a and SF2a provided a high level of cross-protection among other SF serotypes (Noriega et al. 1999). In line with the above mentioned studies, investigations on the immunodominant epitopes on SF3a O-Ag was initiated recently (Boutet and Mulard 2008 Boutet et al. 2009). Another serotype of interest is SF6, the only serotype whose O-Ag is not built from the A2B2C2D2 tetrasaccharide backbone (Fig. 1.6)....

Conclusion and Perspectives OSBased Enteric Vaccines Dream or Reality

Polysaccharide vaccines have found widespread use in preventing infections caused by capsulated bacteria either in the form of purified polysaccharides or conjugates thereof. Its proven track record has encouraged broader developments to include conjugate vaccine candidates based on dLPSs instead of capsular polysaccharides. Some dLPS-based conjugates have been shown to be safe and immunogenic in healthy volunteers including young children. With regards to enteric infections, the protective efficacy of a S. sonnei vaccine candidate has been demonstrated. Complying with the quality control and safety standards requested by the Health Authorities is a complex challenge, especially if using dLPS antigens of natural source. However, as illustrated in this chapter, recent advances in glycochemistry have paved the way to promising well-characterized conjugates derived from synthetic OS haptens, acting as functional mimics of the natural polysaccharide antigen. Towards this aim, numerous...

Anti Parasite Vaccines

The success of vaccination against viruses and bacteria that induced sterile immunity (i.e., the protection is explained by an anti-microbial effect) led scientists to search for parasite vaccines that would induce anti-parasite immunity. A number of conventional live vaccines were developed against coccidiosis, babesiosis, theileriosis, and toxoplasmosis, that showed a clear anti-parasite effect (e.g., the reduction in oocyst output in chickens vaccinated with live Eimeria parasites was typically > 90 22 ). However, not all live vaccines were considered safe. Against a number of parasites, it appeared impossible to design an effective vaccine, because these parasites showed antigenic diversity (differences between different clones of parasites) and antigenic variation (differences within a cloned parasite population), that allowed them to escape the established immune response 23 . It appeared very difficult to replace effective live vaccines with non-live vaccines for a variety of...

C difficile toxoid vaccine

Vaccines have also been studied as a method of prophylaxis for CDAD. A parenteral C. difficile formalin-inactivated toxoid A and B vaccine has been shown to be highly immunogenic in clinical studies in 30 healthy adults when given as 4 intramuscular inoculations on days 1, 8, 30, and 60 62 . The vaccine elicited fourfold increase in neutralizing antibodies to toxins A and B in all but two of the subjects, and serum antitoxin A IgA and IgG antibody responses were seen in all but one subject. A pilot study on the C. difficile toxoid vaccine in recurrent CDAD was conducted 63 . The study concluded that a C. difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C. difficile and its toxins in high-risk individuals. This result was later validated in a larger, randomized, double-blind, and placebo-controlled trial.

Available Vaccines Live Vaccines

Vaccination with live organisms has a long tradition, and was practiced as a traditional Chinese medicine long before the discovery of vaccination against smallpox by Jenner 32 . This strategy does not aim to specifically orchestrate the innate and adaptive immune response rather, it relies on the natural sequence of host-responses that follows infection with a low or controlled dose of pathogen. These vaccines protect against disease by inhibiting parasite proliferation in the vaccinated host when it becomes infected. Several approaches have been taken to ensure that, upon vaccination, the infection does not induce unacceptable clinical symptoms however, it should be noted that, depending on secondary factors, there is an inherent risk that an overt clinical disease may occur. As a consequence, although live vaccines are still being used, their replacement by inactivated vaccines is a continuous pursuit.

Avian influenza vaccine

Traditionally, vaccination has been the principal approach to protecting individuals against influenza. Currently, no influenza A H5N1 vaccine is available although several candidate vaccines are being developed. Preliminary data suggest that either higher concentrations of antigens than used in seasonal influenza vaccines and or addition of adjuvants to these vaccines will be necessary to induce protective responses 8 . Gearing production, to rapidly make necessary quantities, of such a vaccine in the event of pandemic spread will be a great challenge to the vaccine industry.

Ist To Monitor T Cell Directed Vaccine Trials In Cancer Patients

IST is a useful tool to evaluate the induction, localization, and phenotype of antigen specific CD8+ T cells in tissues after T cell directed vaccination of cancer patients. Schrama et al. characterized the inoculation site of dendritic cell (DC) vaccination in patients with melanoma. They determined that antigen pulsed DC, but not unpulsed DC recruited and induced the local expansion of melanoma specific T cells at the inoculation site. They used MHC-multimers loaded with melanoma antigens MART, MAGE3, and gp100 and stained skin biopsies from vaccinated patients to demonstrate the specificity of the recruited and expanded T cells at the inoculation site.

Seasonal Influenza Virus Is Controlled by Vaccines

Seasonal influenza, which moves around the world every year, is blocked by vaccines. Seasonal flu is thought to begin in wild waterfowl in Asia. From there, it spreads through domestic poultry and eventually reaches pigs. Viral reassortment occurring in pig tissues infected with both bird flu virus and human flu virus can produce a new version of influenza that is highly infectious to humans. (The viral genetic material comes as eight separate segments when a cell is infected with two virus variants, progeny viruses acquire their eight genetic segments as a mixture, some derived from one parental virus and some from the other.) After the virus starts to spread among humans, it is isolated and used to prepare vaccine that is administered in the fall. Because the majority of infections occur months later in late winter (February and March in the Northern Hemisphere), there is time to prepare and distribute the vaccine. Unfortunately, new vaccines need to be prepared each year because...

Peptide Vaccine Induced Anaphylaxis in the NOD Mouse

The identification of autoantigens in autoimmune diseases such as type 1 diabetes or multiple sclerosis has made peptide immunotherapy possible. In fact, peptide vaccine trials are currently underway in type 1 diabetes for an altered peptide ligand of insulin peptide B 9-23 (20), for GAD peptides, and for heat shock protein 60 (HSP60) (p277) (21). However, in mouse studies of peptide vaccination, anaphylaxis has been reported in diabetes experiments using the B 9-23 peptide (22) and GAD peptides (23) and in multiple sclerosis studies (experimental autoimmune encephalitis) using proteolipid protein (PLP) (139-151) and myelin oligodendrocyte glycoprotein (MOG) (35-55) peptides (24). Even more concerning is the report of systemic hypersensitivity reactions in humans during phase II trials with an altered peptide ligand for myelin basic protein (MBP) (83-99) (25,26), which led to the premature discontinuation of therapy in some patients. More research into peptide-induced anaphylaxis,...

Clinical Box 52 Phytol and Vaccines

In immunology, an adjuvant is a substance that enhances the ability of a vaccine to stimulate an individual's specific and nonspecific immune responses. Adjuvants can increase the efficacy of a vaccine by a variety of actions, including (1) retaining the vaccine in the body or at the site of injection, (2) reducing degradation of the vaccine, and (3) recruiting macrophages and other cells to augment immune responses to a pathogen or associated antigens. Many adjuvants that are presently available can enhance the efficacy of a vaccine, but the adjuvants may also cause severe adverse inflammatory reactions. Consequently, the only adjuvant currently accepted by the Food and Drug Administration (FDA) for use in humans is aluminum hydroxide (alum). Recently, Lim and colleagues at Indiana State University have discovered that the hydrophobic phytol tail of chlorophyll and other phytol derivatives are effective and relatively safe adjuvants. This is an exciting discovery because it has the...

Vaccines A Cost Effective Strategy to Contain Antimicrobial Resistance

The immune system in the human body is responsible for protection against disease. Once vaccines are introduced into the body they mimic natural infection and stimulate immune responses, which are directed to act against invading organisms. The protection thus conferred is often long lasting. Most vaccines act in this way against acute infections. Advanced molecular techniques can also be used to produce vaccines against pathogens causing chronic infections. The success of the smallpox vaccine has been a history-making event and the World Health Organization's Expanded Programme of Immunization (EPI) has become a hallmark of disease containment with a bare minimum cost of 2 per person against six major infectious diseases. There is evidence from an US study that a savings of 53.2 billion can be met by immunizing children of a specific year birth cohort while the expenditure for the vaccination programme will only be 5.1 billion in terms of direct and indirect (societal) costs. Success...

Vaccines and Infectious Disease

They are produced from micro-organisms that can inflict a disease and are typically prepared from the pathogen or are versions of the pathogen that are weakened or attenuated through laboratory techniques. Once the vaccine is inside the human body, the defence system is activated against the particular disease. Vaccines induce immune responses directed at containing and eliminating the causative agent of the disease. The emergence of antibiotic resistance and the attendant escalating costs of treatment have most probably pushed public health researchers to look for more cost-effective disease-control interventions, vaccines being the most favourable option.

Vaccines Against Viral Infections and Their Cost Effectiveness

Infections with signs that do not clearly point to bacterial origin are often thought to be viral. Since specific anti-viral treatments are often not available, vaccines that mimic closely to the natural infections are the principal means for control. Vaccines have been proved to be effective against acute, self-limiting infections and can confer long-lasting immunity. The same may not be true for chronic viral infections but with the advent of molecular biology there is a strong possibility of developing vaccines against chronic viral infections like hepatitis C virus (HCV), human papilloma virus (HPV) and HIV (Berzofsky et al. 2004). The major viral vaccination success story is the eradication of smallpox by the year 1977. The WHO spent more than 300 million in 11 years, an amount that has been repaid many times over - probably each year - in human lives saved (Ehreth 2003). Polio vaccines were discovered by Salk (1947) and then by Sabin (1957). The polio vaccines were made widely...

Vaccine for the Expanded Programme of Immunization

Until recently, early vaccines were mainly used by affluent countries. In the early- and mid-20th century there was rapid development of vaccine production following which World Health Organization (WHO) in the year 1974 undertook a massive program to control six major childhood diseases namely tetanus, diphtheria, pertussis, tuberculosis, poliomyelitis and measles through effective vaccination using EPI. During the early 1990s, hepatitis B was incorporated into the EPI while yellow fever was recommended for the countries where it is endemic. WHO is now periodically setting time-bound targets to control each of these diseases. EPI became the trademark in vaccine dosing, safety, efficacy, coverage and cost-effectiveness (Le Gonidec 1985). EPI was successful in combating disease that caused enormous suffering to the human being at a very marginal cost. The common EPI protocol adopted by the member countries of WHO does not cost more than 2 per individual as opposed to the treatment that...

Vaccine for the Future

In age group under 5 (Wiedermann and Kollaritsch 2006). Most industrialized countries have been able to contain these infections through improvement of water supply and sanitation, whereas the people living in the underdeveloped countries and those travelling to these areas still suffer from these infections (Bloom and Canning 2000 Reiff et al. 1996). Majority of the enteric diseases are caused by bacteria but in very young children diarrhoea is mainly due to rotavirus and highly affected by seasonality. Early studies in rotavirus vaccination showed cost saving promises (Carlin et al. 1999 Takala et al. 1998). There are difficulties with inducing immunity against a wide range of pathogens causing enteric infections but there are some effective vaccines available and research is underway to have clearer definition of the aetiology and epidemiology of enteric infections with a view to finding newer and more appropriate vaccines that can prevent diarrhoea due to viral or bacterial...

Vaccines A Renewed Hope

The EPI has ushered a new era in preventive medicine. Without the EPI, most preventable diseases will re-emerge and continue to sicken the children and increase mortality, health problems and chronic disability. But EPI has its drawbacks with the reporting of adverse events, cold chain requirements and less than optimal implementation in many countries. Renewed efforts are being made through global donor programmes such as the Advanced Market Commitment and the plan of Global Alliance for Vaccines and Immunization to make new and possibly expensive vaccines available to those who would not have otherwise had access to them in developing countries. The future appears even more promising more and more countries are incorporating newer vaccines or rescheduling programmes in order to achieve a wide range of coverage against some of the most deadly diseases. The immediate costs of the vaccine seem to be high but vaccination costs should not be taken in isolation but must be seen in the...

What is the vaccine for MS

There seems to be a great deal of confusion in the minds of many MS patients and their families about a vaccine for MS. Some seem to think of any injectable drug as a vaccine, but this is not a correct concept. All of the medications currently approved by the FDA for chronic (long-term) use in MS are drugs but are not considered to be vaccines, although their use is to prevent periods of ill health. Interferon-beta-1b (Betaseron) and interferon-beta-la (Avonex and Rebif) and glatiramer acetate (Copaxone) are injectable drugs but are not vaccines. In contrast, a vaccine, which is generally injected, stimulates the immune system, resulting in antibody formation or a direct effect of lymphocytes against proteins or cells that have specific proteins on their surface. Several vaccines against cells in the immune system have been used in research trials.

Is there going to be a vaccine for MS

There is ongoing research into T-cell vaccines for MS. The original experiments in Europe attracted great interest. They involved injecting crude preparations of blood lymphocytes into patients in an attempt to eliminate or reduce the number of activated lymphocytes in MS patients. Ongoing studies involve a more sophisticated selection of cells to be targeted for removal by immune action. They appear to be tolerable and effective to a degree. They do not result in a long-lasting benefit. Other stalled studies attempted to induce immune tolerance without provoking a direct attack on existing cells only preliminary data on their safety have been published. No studies of this third generation type of vaccine are continuing.

Pseudolymphomas at sites of vaccination

Rarely, a florid inflammatory reaction develops at sites of vaccinations. Clinically, lesions may show either superficial papules or nodules, or subcutaneous tumours 70 . The histopathological pattern may be lichenoid, simulating that seen in mycosis fungoides, or nodular with the formation of germinal centres, simulating a follicle centre cell lymphoma (Fig. 20.37). It is believed that pseudolymphomas after vaccination represent a form of local reactive hyperplasia or a persisting delayed hypersensitivity reaction to a vaccine constituent. Lesions may arise after injection of different vaccines including those used for allergen hyposensitization 78 . We have observed the onset of bilateral lesions of lymphocytoma cutis at the skin sites of different injections of early summer meningoencephalitis (fr h Sommer Meningoencephalitis FSME) vaccinations performed after an interval of over 1 year.

Box 14 Vaccine Resistant Pathogens

Vaccines typically instruct the human immune system to recognize a pathogen and destroy it. In some circumstances, the pathogen can alter its surface properties to make it less responsive to the immune system. For example, the malaria parasite frequently changes its surface consequently, the human immune system is always a step behind the parasite. In other cases, the pathogen species exists in many varieties. Shortly after the U.S. anthrax scare of 2001, considerable concern arose because the bacterial strain used in the attacks, the Ames strain, was relatively resistant to the available vaccines. Vaccines for Streptococcus pneumoniae (also known as pneumococ-cus) illustrate the principle of replacement.29 This organism, which causes pneumonia, otitis media (middle ear infection), sinusitis, and meningitis, colonizes the nasopharynx of 50 of children and about 2.5 of adults. Two types of vaccine are available, one prepared against polysaccharides of 23 pneumococcal strains and the...

Antiviral vaccines

Almost everyone has heard the term vaccination and, in fact, has been given a vaccine, whether it be for poliovirus, measles virus, or mumps virus. Just what is a vaccine How is it prepared and administered And is it possible to create one for every viral infection of significance

Vaccines

As with early diagnostic tests for HIV-1, initial vaccine candidates were primarily based on subtype B (168). However, the expanding knowledge of HIV genetic diversity coupled with the urgent need to develop vaccines for subtypes other than B in developing countries where the majority of infections occur has led to a number of new vaccine candidates which are described elsewhere in this book (Progress in the development and testing of HIV vaccines). To the extent that vaccine efficacy is strain- or subtype-speciSc, the ability to evaluate them in areas of highest HIV incidence, where multiple HIV strains may be present, and the later applicability of the vaccine may pose considerable challenges. Currently, it is unclear to what extent the various HIV-1 subtypes or clades represent different immunotypes for host humoral and cellular responses (168). Ongoing assessment of vaccine candidates will clearly depend on continued surveillance and characterization of viral variants as well as...

Vaccination

When considering immunity, it is important to realize that there is often a difference between natural immunity that arises after repeated infections with the parasite, and vaccine-induced immunity in which the immune system of the host is trained to produce a protective immunological response that may not occur with natural infection. In the past, vaccinologists have used the principles of natural immunity for the development of live vaccines (see Anti-Parasite Vaccines below) however, with a better understanding of immunology, it appears possible to more specifically direct the immune system to generate the protective response by using antigens and adjuvants (Signals 0 and 1 Figure 4.2). Recently, more sophisticated strategies have beenused (see Adjuvants below), in which the immune response is guided by certain cytokines and other regulatory molecules (Signals 2 and 3 Figure 4.2). Based on the protective principle, it is possible to recognize three different groups of vaccine,...

Anti Disease Vaccines

With an increasing knowledge concerning the pathogenesis of a parasitic infection, the way was opened to develop vaccines that specifically aimed to prevent clinical signs, without affecting parasite proliferation per se. The existence of anti-disease immunity is already evident in malaria children first develop anti-disease immunity that does not protect them from subsequent reinfection however, during adolescence an additional protective immunity is developed with a clear anti-parasite characteristic 24 . Subsequently, it was discovered that P. falciparum produces molecules that are pathogenic in themselves and behave as toxins by stimulating PRRs on myeloid cells that trigger the production of inflammatory cytokines through TLR1 2 (see Activation of Nonspecific Cellular Systems above). This finding culminated in the identification and synthetic production of the active moiety, glycosylphosphatidyl inositol (GPI) anchors, that function to bind the surface proteins to the parasite...

Therapeutic Vaccines

Similar to the therapeutic use of drugs for infected subjects, it is possible to use vaccines as therapeutics. The earliest example of therapeutic vaccination was in 1885, when Louis Pasteur treated a boy who had been bitten by a rabid dog with an attenuated rabies vaccine 30 . In Leishmania infection in dogs, the vaccination of parasite-positive dogs was shown to reduce the parasite burden moreover, when combined with a chemotherapeutic drug, the effect was greater 31 . In particular, for apicomplexan parasites that survive in the immune host (carrier status), a therapeutic vaccination could be used to reduce the parasite density in certain environments. At present, however, no such vaccines have been developed for the Apicomplexa.

Tuberculosis vaccine

Currently, BCG (Bacille Calmette-Guerin) is the only licensed tuberculosis vaccine. It has a number of shortcomings, among which is a relatively short period of protection, and poor antibody stimulation response beyond childhood. Since there are clearly many problems with treating TB at this point, a lot of effort and money has been focused on creation of a vaccine, as a means of preventing future infections in those at highest risk and putting a cap on the ever increasing TB epidemic. Unfortunately, it appears the obstacles in the development of such a vaccine are no less challenging than those hindering drug development. It is well know that BCG varies in effectiveness among those who receive it. This has previously been attributed to different environmental factors or differences in the BCG strains used to create the vaccine. However, a recent gene analysis has found that M. tuberculosis is genetically distinct in different parts of the world and has evolved into 6 different...

Non Live Vaccines

In order to improve the safety of vaccines, recent investigations have been focused on the use of killed vaccines. Although some inactivated bacterial vaccines may be administered without an adjuvant (most likely due to the fact that some of the bacterial components have inherent adjuvant activity), inactivated parasite vaccines require an adjuvant to induce protective immunity. During the early twentieth century, when bacterial vaccine cocktails were first developed, oils were used as an adjuvant, the rationale being that the oil would prevent the instantaneous release of bacterial toxins into the host, which would lead to serious adverse effects 52 . Although, in this case, the adjuvant was used to increase the safety of the vaccine, it later became apparent that these compounds would also affect the innate and adaptive immune system 53 . Although the mode of action of most adjuvants is unknown (see Mode of Action below), it is generally assumed that they affect the cytokine context...

Killed Vaccines

Different methods of inactivation are used, of which chemical treatment is the preferred approach this might involve treatment with formaldehyde, beta-propiolactone (BPL), and or bromoethylamine (BEA). Alternative methods include inactivation by ultrasonic treatment, heating, ultraviolet-light irradiation, and gamma-irradiation. Some examples exist of parasitic vaccines produced along these principles, notably a vaccine against Neospora caninum-induced abortion in cattle, and against B. divergens in Austria. The N. caninum vaccine contains tachyzoites derived from in-vitro cultures that are inactivated with BEA 39 , while the adjuvant is a depot-forming preparation containing a polymer of acrylic acid crosslinked with polyallylsucrose. The B. divergens vaccine contains formalinized, infected red blood cells, adjuvanted with aluminum hydroxide and saponin 40 .

Subunit Vaccines

A vaccine that does not contain whole organisms is referred to as a subunit vaccine. In general, subunit vaccines contain (partially) purified antigens from whole, killed organisms. Purification may be necessary to remove any putative toxic antigens that might compromise the safety of the vaccine, or to remove immunodominant antigens that might jeopardize the immunogenicity of the protective antigen. Currently, a subunit vaccine against coccidiosis in broilers is available commercially that contains antigens from the gametocytes (sexual forms) of Eimeria maxima in an oil adjuvant. The vaccine functions indirectly by inducing a maternal immunity in broiler breeders, in order to protect the progeny against coccidiosis. The effector mechanism is anti-parasitic 43 . Some subunit vaccines do not contain antigen from the parasite's cell itself, but rather contain the excreted secreted antigens of the parasite. Examples of this include the vaccines against Babesia canis and Babesia rossi in...

DNA Vaccines

Vaccines that do not contain the protective antigen, but instead contain the DNA that encodes for the vaccine antigen, are termed DNA vaccines 55 . These may be live viral vectors, but non-live DNA fragments may also be injected into the host under circumstances that maximize the chance of DNA entering a nucleated cell. In this way, the parasite protein is produced and expressed by the host cell, and can be recognized by the cells of the immune system. The feasibility of messenger RNA to induce protective immunity has also been evidenced 56 . Whilst these approaches appear to show much promise in the field of virology, such vaccines have not yet become available in the areas of bacteriology and parasitology. Improved responses can be obtained when subjects are primed with a DNA vaccine and boosted with the (recombinant) protein or viral vectors encoding the vaccine antigen 57, 58 . However, whilst this technique holds much promise, such combinations are presently not commercially...

Why Choose Vaccines

Emergencies are always unpredictable and it often becomes difficult to plan for health emergencies to ensure adequate and timely response. Diseases that kill millions each year require immediate resolution, which may be conferred through antibiotics, as well as lasting measures to prevent recurrence, and here vaccines would certainly fulfil the charge. Introduction of an effective vaccine helped in the eradication of smallpox others have been contained over the period while research is still underway aimed at controlling or eradicating other dreadful viral diseases. It is evident from the WHO (2006) that affluent countries are well ahead on the vaccine coverage but it is also reassuring to see that developing countries of Southeast Asia and sub-Saharan Africa are also catching up (Table 27.2). Along with this, the industrialized countries took initiative to introduce vaccines against some diseases that caused outbreaks with a high mortality with overwhelming success. Presently, HIV...

Vaccines The Cost

A true cost-effectiveness study for vaccines is probably not possible as it will require a non-vaccinated or placebo-receiving comparison group, which is unethical. Most of cost-effectiveness studies are based on epidemiological models or simulations of the disease in question but all of these clearly showed the benefit of vaccination in terms of both direct and indirect costs (Table 27.3) (Hudeakova et al. 2004). The cost-effectiveness of a vaccine depends on the combined information on the incidence of the disease, its sequelae if not treated, the safety and efficacy of the vaccine, and its cost from production to program administration and the alternative intervention available for the disease in question. Cost-effectiveness for any intervention has become an important issue in national health budgeting. When the intervention is able to give the maximum benefit at an acceptable cost, the effectiveness is attained. But there is no clear margin of the cost of an effective...

Allergen Vaccines

Licensing of allergen vaccines for clinical use in the United States is regulated by the US Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Allergenic Products and Parasitology. Many of the common vaccines used in clinical allergy practice are available as standardized products or are pending standardization. This means that allergen vaccines, as provided by commercial manufacturers, meet standards that assure that the appropriate allergens are included in a given vaccine. However, many allergen vaccines derived from natural sources are not yet standardized, and it is probably not economically feasible or practical to standardize all of those currently available for diagnosis and treatment. Currently, unstandardized allergenic vaccines are labeled on the basis of relative concentration (weight by volume or protein nitrogen units per milliliter) of the respective allergen source.

Hp and Vaccination

Louagie et al. investigated the Hp polymorphism and the immune response after a recombinant hepatitis B vaccination. In comparison with Hp 1-1 and 2-1, the Hp 2-2 phenotype was associated with a significantly lower hepatitis B antibody titer. The magnitude and the kinetics of the anti-HBs response were determined by the Hp polymorphism. The Hp concentration and immune response to the vaccine behaved independently 130 . In accordance, an inferior immune response of Hp 2-2 subjects has also been observed following influenza vaccination 131 . However, Hp 2-2 individuals display a more vigorous immune response to typhoid vaccination 132, 133 .

Newer Vaccines

Approximately 2.0 of the 10.6 million deaths that occur in young children each year are due to pneumonia (Wardlaw et al. 2006). About half of these deaths occur among children in sub-Saharan Africa and another 30 occur in the countries of south Asia (Bryce et al. 2005). In developing countries 11-20 million children with severe pneumonia are known to require hospital admission (Rudan et al. 2004). Streptococcus pneumoniae has been identified as a main bacterial cause of pneumonia (Shann 1986) and other pneumococcal diseases particularly in very young children where a polysaccharide vaccine is not very effective. Recent estimates from WHO indicate that pneumococcal infections are responsible for 1.6 million deaths each year, half of them in the age group under 5 and the highest risk is among the children less than 2 years old and in elderly person (WHO, 2007). Emergence of penicillin- and multiple drug-resistant pneumococci has compounded the problems of managing children with...

Present status of the basic features of artificial cells of macro micron nano and molecular dimensions

The general principles of artificial cells can form the basis of a large number of artificial systems (Fig. 2.1). In addition to being of cellular dimensions in the micron range, they can also be in the macro range, nano range or molecular range. Furthermore, the membrane material includes polymer, biodegradable polymer, lipid, crosslinked protein, lipid-polymer complex, lipid-protein complex and membrane with transport carriers. Artificial cells can contain an unlimited variety of material individually or in combinations (Fig. 2.1). These include cells, stem cells, enzymes, multienzyme systems, hemoglobin, magnetic materials, microorganisms, vaccines, genes for gene therapy, genetically engineered cells, adsorbents, drugs, hormones, peptides, proteins and others.

African horse plague virus Synonym for

Transmitted by nocturnal biting flies of the genus Culicoides. Experimentally goats are slightly susceptible but ferrets and dogs are infected more readily. Mice, rats and guinea pigs can be infected i.c. A mouse brain passage virus vaccine is effective. Virion is 75-80nm in diameter, icosahedral and similar to Bluetongue virus. Infectivity is ether-resistant but acid-sensitive, being inactivated below pH 6. Horse erythro-cytes are agglutinated. Virus contains double-stranded RNA in 10 segments. Multiplies in eggs in yolk-sac, and in cell cultures of many species. Although originally confined to Africa, the virus was inadvertently introduced into Spain, and is now endemic around Madrid and other areas to the south. Synonyms African horse plague virus perdesiekte virus pestis equorum virus.

African Rift Valley fever virus See Rift Valley fever virus

200nm envelope is acquired as it buds through the plasma membrane. Survives dry at room temperature for years. Resists inactivation by some disinfectants but inactivated by 1 formaldehyde in 6 days, 2 sodium hydroxide in 24 days. Chloroform- and ether-resistant. Replicates in the chick embryo yolk-sac killing the embryo, and in cell cultures of swine macrophages, such as pig bone marrow. Hemadsorption of pig erythro-cytes is seen after 24 h and CPE later. After 100 passes the virus loses virulence for pigs but does not give protection from infection with virulent virus. Antibodies do not provide immunity. Originally observed in East, South and West Africa, the virus reached Portugal and Spain in 1957, France in 1964, Italy in 1967 and Cuba in 1971. Outbreaks occurred in Malta, Sardinia and Brazil in 1978, and Haiti in 1979. In 1982 a severe outbreak occurred for the first time in West Africa. The disease is believed to have been eradicated from Europe (except Sardinia) since 1995. In...

Experimental Autoimmune Encephalomyelitis As A Model For Ms

While the priming of T cells in active EAE seems to be similar in all rodent EAE models, the effector phase in the target organ and the modes of chronification of the disease process seem to depend on strain- and species-specific properties. The Lewis rat, for instance, shows a mono-phasic disease with massive inflammation, but only a minor degree of demyelination. Several murine EAE models, mostly using the myelin basic protein (MBP) as inducing myelin protein, also show a monophasic but highly demyelinating EAE course (Nogai et al., 2005) which resembles the human disease ''acute disseminated encephalomyelitis'' (ADEM), which has been shown to be associated with recent infections or vaccinations (although no controlled study exists for novel recombinant vaccines).

Classification Of Biologic Agents Based On Hazard

Biosafety Level 2 agents are those most commonly being sought in clinical specimens, and they include all the common agents of infectious disease, as well as HIV and several more unusual pathogens. For handling dinical specimens suspected of harboring any of these pathogens, Biosafety Level 2 precautions are sufficient. This level of safety includes the principles outlined previously plus limiting access to the laboratory during working procedures, training laboratory personnel in handling pathogenic agents, direction by competent supervisors, and performing aerosol-generating procedures in a BSC. Employers must offer hepatitis B vaccine to all employees determined to be at risk of exposure. Bacillus anthracis and Yersinia pestis, two organisms mentioned as possible bioterrorism agents, are actually listed as BSL-2 organisms.

Amplified reverse transcriptase AmpRT

Anatid herpesvirus 1 (AnHV-1) An unas-signed species in the family Herpesviridae. Differs from other her-pesviruses with respect to its structure and maturation. Mature virus particles are seen accumulated in long extensions of the endoplasmic reticulum their size varies between 160 and 380nm, and they are embedded in an osmiophilic matrix. In addition, capsids (about 80nm in diameter) and developmental stages of the viral nucleoid (about 40nm in diameter) are encountered in the nuclei of infected cells. A natural infection in domestic ducks, and possibly of mallard, Anas platyrhynchos, in the UK. There is nasal and ocular discharge, and diarrhea, with up to 97 mortality. At post-mortem examination petechial bleedings in mucosal membranes and many organs are prevalent. In less acute cases hemorrhagic or pseudomembra-nous pharyngitis, esophagitis and cloacitis are frequently observed. Typical herpesvirus particles are observed by electron microscopy in the nucleus and the cytoplasm of...

Physiology The Study of Function

Physiology7 uses the methods of experimental science discussed later. It has many subdisciplines such as neurophysiology (physiology of the nervous system), endocrinology (physiology of hormones), and pathophys-iology (mechanisms of disease). Partly because of limitations on experimentation with humans, much of what we know about bodily function has been gained through comparative physiology, the study of how different species have solved problems of life such as water balance, respiration, and reproduction. Comparative physiology is also the basis for the development of new drugs and medical procedures. For example, a cardiac surgeon cannot practice on humans without first succeeding in animal surgery, and a vaccine cannot be used on human subjects until it has been demonstrated through animal research that it confers significant benefits without unacceptable risks.

Antibiotic Resistance Is Divided into Three Types

A third type of resistance involves pathogen species unaffected by particular antibiotics. They are said to be intrinsically resistant. Little can be done about this type of resistance except to develop vaccines and use good infection control practices that keep the pathogens away from us. Most viruses fall in this category.

Background And Context

The HIV pandemic is arguably the most compelling public health crisis of the post-World War II generation. In the post-World War II era, infectious diseases were on the wane. Common bacterial infections were readily treated with available antibiotics ubiquitous childhood diseases (e.g. polio, measles, mumps) were preventable with vaccination even the scourge of smallpox was eradicated worldwide. The epidemiology and clinical management of chronic diseases such as heart disease and cancers and an emerging interest in environmental health were ascendant public health priorities. Despite the warning signs of fertile ground for an infectious disease epidemic, HIV continues to confound medical and public health practitioners worldwide. As yet, there is no cure, and no vaccine. The ability to mount effective prevention and control efforts is complicated by social taboos, fear and prejudice. In the U.S., because HIV is spread principally through sex and sharing of drug-injection...

Therapy And Prophylaxis

Vaccines are now available against a number of virus infections. The vaccines are composed of either live attenuated virus (e.g. rubella, mumps, measles), inactivated whole virus (e.g. rabies, influenza) or viral components (e.g. influenza, hepatitis B). Second- and third-generation vaccines are recombinant DNA vaccines (hepatitis B) and synthetic peptide vaccines, respectively.

When Should Virological Testing Be Ordered

In all clinical work the benefit of a precise diagnosis is indisputable. The consequences for the treatment of individual patients are obvious, and preventive measures can be taken to reduce the risk of transmitting the infection to others. In epidemics the laboratory diagnosis of a few early cases also benefits the doctor in that it allows confident aetiological diagnosis to be made for subsequent similar clinical cases. National and global epidemiological surveillance and control programmes will also require data from diagnostic laboratories. Decision as to the current composition of an influenza vaccine is one such example. The most common clinical situations requiring virological laboratory examinations are Mumps. In sporadic or doubtful cases, and in cases of orchitis, meningoencephalitis or pancreatitis when the clinical diagnosis of mumps is not certain. Immunity status screening for vaccination of adult or prepubertal males. Hepatitis. All cases of hepatitis should be examined...

Attachment interference See interference

Attenuated virus strains Mutant strains with low virulence or which are avirulent for their natural host species, and in which they can thus be used as a vaccine. Often obtained by passage in cell culture or in a host different from the one in which they usually cause disease.

Biodegradable polymeric artificial cells nanoparticles nanocapsules

Biodegradable membrane artificial cells have been prepared to contain enzymes, hormones, vaccines, and other biologicals (Chang, 1976a). The polylactide polymer can degrade in the body into lactic acid and finally into water and carbon dioxide. In the same study, variations in preparation can result in artificial cells that release insulin at different rates (Chang, 1976a). Biodegradable drug delivery systems are now used widely in different forms, ranging from microscopic to nanodimensions (LaVan et al., 2002). They are also known as nanoparticles, nanocapsules, polymersomes, nanotubules, etc.

Big Pharma Has Walked Away and Is Slow to Return

Of the major companies who have been in the field, Johnson & Johnson is still investing in antibiotic development, while Novartis and GSK are still putting money into vaccine studies. It appears that it will take some significant changes at the regulatory, federal, and medical practice levels to encourage Big Pharma to get its feet wet again.

Generation Of Tumor Antigen Epitopes

Several recent studies have focused on identifying candidate T cell epitopes that can be efficiently processed by the proteasome. In one study, long peptides that encompassed candidate HLA-A2 restricted T cell epitopes derived from PRAME were incubated with purified proteasomes (92). The analysis of the peptide digests revealed that the appropriate carboxy terminal residue was generated from only 4 out of the 19 high affinity peptides that were subjected to degradation using this procedure. The T cells that were generated following in vitro sensitization with peptides that were identified using this approach appeared to efficiently recognize tumor cells that expressed PRAME and HLA-A2, indicating that this process might facilitate the identification of relevant peptide vaccine target epitopes. An epitope of the SSX-2 antigen that was initially identified by SEREX analysis was identified by incubation of long peptides with purified proteasomes (16).

The Nature Of Virus Reservoirs

While many human viral diseases are maintained in the human population itself, some important pathogens are maintained primarily in other vertebrates. A disease that is transmissible from other vertebrates to humans is termed a zoonosis. Rabies is a classic example of a zoonosis that affects humans only sporadically. Because humans rarely transmit the virus to other animals or other humans, infection of a human is essentially a dead end for the virus. The rabies virus, which is transmitted in saliva via a bite, is maintained in populations of wild animals, most generally carnivores. The long incubation period and other characteristics of the pathogenesis of rabies mean that an infected animal can move great distances and carry out many normal behavioral patterns prior to the onset of disease symptoms. These symptoms may include hypersensitivity to sound and light, and finally, hyperexcitability and frenzy. Except in rare instances of inhalation of aerosols, humans only acquire the...

Kochs Postulates Help Establish That a Pathogen Causes Disease

The importance of the postulates is emphasized by a controversy over the viral nature of AIDS. An animal model was not available to establish that the human immunodeficiency virus (HIV) actually causes AIDS, as prescribed by Koch's postulates. In the late 1980s, Peter Duesberg challenged the prevailing idea that HIV causes AIDS (see Box 2-2).38 If Duesberg were correct, the money being spent to find antiviral agents and vaccines was being wasted. Moreover, the cure for the disease would be changes in behavior and nutrition, not antivirals. Indeed, antivirals used to interrupt the transmission of HIV from mother to a new-born child were said by Duesberg to cause AIDS. Duesberg's ideas were immediately dismissed by the scientific community, sometimes with strong language, and NIH funding for his work was stopped. However, having a well-known scientist cast doubt on the link between HIV and AIDS provided impetus for South Africa to delay treatment of the virus. Delay is thought to have...

How Are Antivirals Used In Clinical Practice

Who are infected, in much the same way as most vaccines are used. Prophylactic protection with a chemical antiviral is more rapid in onset than that induced by vaccines, since some antiviral protection would be anticipated within 30 minutes of drug administration. Most antivirals are administered by mouth and rapid adsorption of drug and spread to all tissues of the body is often achieved. To maintain active levels of drug in the target organ redosing is required, perhaps twice daily. Clinical use is less convenient if oral absorption is poor, and if the drug has to be given by intravenous infusion or, in the case of respiratory infections, by aerosol or nasal spray. However, it could be argued that with respiratory infection direct application of a drug to the nose and airways could have medical advantages.

Patients Are Media Scared and Ill Informed

The increasing incidence or prevalence of antibiotic resistance is now an issue of major public concern. Newspaper headlines frequently carry feature stories of the impact on individuals as the doomsday scenario of widespread and untreatable drug-resistant infections in our hospitals. The extent and significance of antibiotic-resistant bacteria is clearly becoming increasingly apparent. Reports of antibiotic resistance and concerns highlighted by ID specialists over the last half century were generally unheeded until partway through the last decade (mid-1990s) when the importance of the issue finally achieved political recognition. In 1995, the American Society for Microbiology and three years later the U.K. Select Committee of the House of Lords published reports that were influential in developing national strategies. Soon after these initiatives the European Union and the WHO presented their approaches to this global problem. The latter currently has a six-part strategy for...

Resistance Containment

It has recently been suggested that integrated interventions be applied to address the infectious disease burden of the poor (Ehrenberg and Ault 2005). In view of the inseparability of the problem of resistance from mitigating factors like poverty, which also impact the overall infectious disease burden, it makes sense to pursue resistance containment as part of an overall health package for the poor. Many interventions including national disease control and management programs and vaccination, which improve health care in general, also assist in containing resistance (Okeke et al. 2005). One reason why the poor bear more of the burden from resistance is because interventions designed to contain resistance, or to improve health, are not necessarily accessible to the people who need them most. For example, the Integrated Management of Childhood Illnesses (IMCI) program has been implemented in many poor countries, but poor people in these countries are least likely to benefit from it...

Modern Biology Has Refined Kochs Postulates

Many advances have occurred in molecular and cell biology since Koch's paper. We now have clinical interventions (antibiotics and vaccines) that remove pathogens, and pathogens are known to acquire resistance that overcomes the antibiotics. Both events can correlate with changes in disease, thereby providing evidence that a particular pathogen causes a particular disease. Genomic nucleotide sequence analysis enables molecular ecology and microbial population genetics to contribute to causality arguments that are becoming increasingly complex. Thus, we now have a variety of ways to examine causality (see Box 2-3). At the same time, we are faced with political limitations on use of animals to establish causality (postulates 3 and 4) when a large body

Factors affecting the control of viral disease in populations

The generation of lasting immunity provides an effective means of controlling and even eradicating certain viral diseases. The antigenic stability of the smallpox virus and effective immunity against it allowed effective vaccination programs to eradicate the disease from the population. Polio and measles are current candidates for partial or total elimination from the population due to availability of effective vaccines. In addition, currently a program is underway to try to vaccinate wild populations of raccoons and other small carnivores against rabies with use of vaccine-laced bait. It is hoped that such an approach will reduce or eliminate the growing incidence of rabies in United States wild animal populations. Of course, the reason for this solicitude has little to do with the animals involved rather, it is to afford protection to domestic animals, and ultimately to humans. Despite our considerable abilities, not all viral diseases can be readily controlled even under the most...

Clinical Applications

Simultaneous measurement of antibodies to 23 pneumococcal capsular polysaccharides (PnPs) was developed recently (Biagini et al., 2003), which showed results similar to another xMAP assay developed for antibodies to PnPs (Pickering et al., 2002a). The assay simultaneously determines serum IgG concentrations to 14 PnPs serotypes. The multiplexed assay showed good overall agreement with a well-established ELISA that is currently recommended for evaluation of pneumo-coccal vaccine immunogenicity.

Amantadine An M2 Channel Blocker Of Influenza A Virus

Recommendations from a WHO expert group are that the anti-influenza compounds should be used prophylactically where epidemiological investigations show the presence of influenza A in the community. Prophylactic use should continue daily for up to 4-5 weeks until the epidemic has passed. Chemoprophylaxis is recommended for 'special-risk' groups, such as over-65s, some diabetics, and persons with chronic heart or chest diseases who have either not been immunized or who wish to receive additional protection to that of immunization, or those being potentially exposed to virus infection before vaccination has become effective (2-3 weeks). These members of the community are at much higher risk of serious complications and death following influenza than others. Clinicians now appreciate that amantadine dosage must be carefully adjusted for elderly and frail individuals and particularly those with kidney disease or urinary retention, in whom the drug could accumulate. A reduced dose of 100 mg...

LPSs as the Targets of Protection

V. cholerae is the causative agent of cholera, a highly contagious diarrhoeal disease, often occurring as devastating outbreaks (Sack et al. 2004). O-Ag composition allowed the classification of vibrios into some 200 serogroups (Chatterjee and Chaudhuri 2003), two of which - serogroup O1 and the emergent serogroup O139 - account for the vast majority of epidemic cholera. Recovery from disease confers serogroup-specific immunity against subsequent infections, and the presence of anti-V. cholerae LPS Abs is generally considered to be a marker for immunity to cholera (Provenzano et al. 2006). Two whole-cell vaccines are in use today, although their efficacy varies among recipients. In the search for an improved vaccine that would induce long-term immunity for those at risk, better defined immunogens could emerge from the use of glycoconjugates encompassing multiple copies of dLPS (Boutonnier et al. 2001 Paulovicova et al. 2006 Grandjean et al. 2009) or synthetic O-Ag fragments thereof...

The Glorious Pastand The New Challenges

The global eradication of smallpox stands as a landmark in the history of immunization. An intense combined international effort, The Smallpox Eradication Programme of 1967 organized through the World Health Organization (WHO), led to the complete elimination in 1977 of one of mankind's great scourges. A long time had passed since Jenner in l796 successfully inoculated a farmer's boy with pustule material from a dairymaid suffering from cowpox (see illustration to Chapter 41). Additional achievements during the 20th century have been the introduction of many new virus vaccines, e.g. polio, measles, rubella, mumps, rabies, yellow fever, influenza, varicella and hepatitis A and B. Vaccines against e.g. adenovirus, cytomega-lovirus, herpes simplex virus and rotavirus are currently being developed or are under clinical trials. Great optimism followed the successful smallpox programme, but not all infectious diseases of viral aetiology may be so amenable to control. In particular, a...

Immune Modulation of APL

Further work showed that DNA vaccines could be effective in treatment of mouse models of APL. DNA vaccination is a process in which plasmids that express potential antigens are injected intramuscularly (Wolff et al. 1990). The injected plasmids are taken up by some of the cells and begin to express the encoded antigens. This process can lead to both cell-mediated and humoral immune responses to these antigens. In one study, DNA vaccines encoded either full-length PML-RARa or a fusion of 33 amino acids surrounding the junction of PML and RARa to an immunogenic fragment of tetanus toxin (Padua et al. 2003). Vaccination with either of these plasmids extended survival of mice that had been injected with leukemic cells from MRP8 PML-RARA transgenic mice. Interestingly, the survival benefit was present not only in mice treated with the vaccine alone, but also in mice treated with a combination of DNA vaccination and ATRA. In another study of DNA vaccination, vaccines encoded PML-RARa,...

Reducing Infectious Disease Burden

Immunizations are clearly the most effective way to reduce infectious disease burden. Although there have been some notable disappointments in vaccine development (the lack of an effective HIV vaccine for instance), there remain vaccines effective against common bacterial infections that are underutilized in developing countries - including Haemophilus influenzae and pneumococcal vaccines. Increased use of these vaccines, and continued improvement of the current vaccines, would clearly diminish the need for antimicrobials and reduce (especially with Streptococcus pneumoniae) one of the most troubling organisms in terms of current resistance patterns (Cherian, 2007 Morris et al., 2008). The lack of a vaccine for sexually transmitted diseases (with the exception of human papilloma virus) is also a concern, as Neisseria gonorrhea remains both an important public health problem and an organism for which resistance has been an ongoing problem (Rupp et al., 2005).

Epidemiologic Evidence That Influenza Increases the Risk of Bacterial CAP

Several types of evidence support an epidemiologic relationship between influenza infection and subsequent bacterial CAP. First, an ecologic relationship between influenza and CAP has been recognized for many years, with hospitalizations and deaths related to both diseases peaking simultaneously 51 . More direct evidence at the individual patient level was provided by a retrospective case-control study conducted in the context of an outbreak of severe pneumococcal disease among children. In that study, the investigators demonstrated a 12-fold increased risk of an influenza-like illness in the 7-28 days before hospitalization for pneumococcal pneumonia and a nearly 4-fold increased risk of a positive influenza A convalescent serology among patients with pneumococcal disease 52 . A more novel approach to the question of causality was taken in the context of a randomized, double-blind, placebo-controlled clinical trial of a protein-polysaccharide conjugate pneumococcal vaccine in South...

Border disease virus X818 An isolate of

Produced in sheep, cattle and probably deer. Experimental infection of rabbits produces a similar disease. Sporadic cases of natural infection have been reported in donkeys, mules and llamas. Guinea pigs, rats and mice can be infected experimentally. Human infection has been suggested by the reported detection of virus-related sequences in peripheral blood leukocytes of some patients with psychiatric disorders. These results require confirmation. The disease in horses has been detected mainly in Saxony but also in other parts of Germany, the Principality of Liechtenstein, Poland, Rumania, Russia, Syria and Egypt. A virus causing staggers in horses in Nigeria may be the same. The virus has been isolated from ticks of several genera and from the brains of herons and other wild birds. Transmission by oral and nasal secretions is possible. A virus vaccine has been used with success. Replicates on the CAM and in cultures of lamb testis and monkey kidney cells with CPE.

Sideeffects And Complications

It is important to remember that trivial side-effects are quite common with viral vaccines. These are most often local pain, redness and induration at the injection site. Less frequent are systemic effects such as fever, malaise, headache, arthralgia and nausea. With some live virus vaccines such as measles and rubella mild symptoms and signs resembling the natural disease may occur. Serious complications are extremely rare, but they do occur for example, paralytic poliomyelitis following the use of live attenuated polio vaccine, and encephalitis following yellow fever vaccination in infants. Note that it is important to adhere to the manufacturer's health authority's list of contraindications cited for each vaccine in question so that the risk of allergic reactions or other preventable complications can be minimized. Immunosuppression is a contraindication for use of live vaccines. However, different countries are adapting different strategies for the immunization of HIV-positive...

Bovine hemadsorbing enteric virus

Bovine herpesvirus 1 (BoHV-1) A species in the genus Varicellovirus. A natural worldwide infection in cattle, but antibodies can also be found in mule deer, Odocoileus hemionus, and ferrets are susceptible to disease in the USA. Wild ruminants in Africa are probably the original host. The virus has also been isolated from soft-shelled ticks, Ornithodorus coriaceus, collected from mule deer in western USA, but it is not clear whether ticks are a reservoir host. May cause a silent, mild infection, or acute disease of the whole respiratory tract. Mortality can be as high as 75 . In Europe it has been known to cause conjunctivitis and, notably, disease of the genital tract when lesions appear on the external genitalia. There is no evidence of antigenic difference between the respiratory and genital strains. Young goats infected experimentally develop fever in rabbits there is meningoencephalitis with paralysis of the hind legs. Transmission of the virus is by contact, especially under...

Ishmael Kasvosve Marijn M Speeckaertt Reinhart Speeckaertt Gwinyai Masukume and Joris R Delanghet J

Hp and populations, three major haptoglobin phenotypes Hp 1-1, Hp 2-1, and Hp 2-2 are present, but additional phenotypes have been identified. Hapto-globin polymorphism has important biological and clinical significance. In this review, we examine the putative role of haptoglobin polymorphism in parasitic, bacterial, and viral infections. Despite many striking effects of haptoglobin polymorphism in infectious conditions, the effects of haptoglo-bin genetic variation upon infections are not always predictable due to the multifunctional character of the plasma protein (e.g., antibody-like properties, immunomodulation, iron metabolism). More studies on the interplay of haptoglobin polymorphism, vaccination, and susceptibility or resistance to common infections seem warranted.

Prevention and Control

Prevention and control of drug resistance primarily involves promoting appropriate use of antimicrobial drugs to extend their useful life and preventing infection transmission (e.g., through appropriate infection control and vaccine use). Appropriate antimicrobial drug use is defined as use that maximizes therapeutic impact while minimizing toxicity and the development of resistance. In practice, this means prescribing antimicrobial therapy when, and only when, beneficial to a patient targeting therapy to the desired pathogens and using the appropriate drug, dose, and duration. Prevention and control programs do not obviate the need for a constantly flowing pipeline of new drugs, as current drugs will inevitably become less effective with time because of resistance. CDC has been working with a variety of partners to promote appropriate antimicrobial use in the community (outpatient prescribing), in health care settings, and in agriculture (12). Preventing transmission of infections...

Antimicrobial Resistance in Resource Constrained Settings

In an era of increasing global migration, infectious diseases represent major national and international public health threats affecting resource-rich and resource-poor countries. The main strategies to prevent and control infectious diseases include public health improvements in sanitation and hygiene, safe water initiatives, as well as vaccines and the use of antimicrobial agents (WHO 2001). Regrettably, a potential outcome of antimicrobial use to control the clinical impact of these infections is the emergence of antimicrobial resistance as an evolutionary response of microbial pathogens (Livermore 2007 Moellering 1998 Rhem and Weber 2007).

Mechanisms For Protection Of Immune Cells And Prevention Of Tumor Escape

Immune escape mechanisms utilized by malignant cells represent major obstacles in the outcome of immunotherapy in patients with malignant disease because of their multifaceted nature. Therefore, there is a need to develop strategies to counteract the immune escape mechanisms utilized by malignant cells in order to enhance the efficacy of T-cell based immunotherapies. At present, various vaccination strategies are being evaluated in phase I clinical trials. In this regard, polyvalent vaccines may be preferable to monovalent vaccines, in order to counteract the selective loss of the target antigens. Moreover, polyvalent vaccines may lead to the activation of CD4+ T lymphocytes, which appear to be an important immune component in the eradication of tumor cells (148). The choice of multivalent vaccines is also supported by the reports of beneficial effects on the clinical course of the disease in the trials conducted in patients immunized with polyvalent vaccines (149-153). However,...

Bovine viral diarrhea virus 1 BVDV1 A

The virus may cross the placenta, causing abortion or fetal abnormalities. Infection of the fetus with a non-cytopathic strain before development of immunological competence (110 days' gestation) can result in the animal being persistently infected with BDV for life. It is these animals that maintain the virus in the population, and that may develop severe mucosal disease which develops in such persistently infected cattle when they become infected with a second cytopathic strain of BDV. The disease is often mild and antibodies may be present in most members of a herd. Antibodies not found in humans or horses. A related virus occurs in sheep in southern Germany and pigs in Australia. Serial passage in rabbits leads to attenuation of virulence for cattle and this virus may be used as a vaccine. There are probably at least seven antigenically distinguishable types of the virus. It is spherical, 57nm in diameter with a 24nm wide core, and envelope without projections. Infectivity...

On the Quality of the AntiLPS Ab Response

As a whole, the above results suggest that selected antigenicity data, possibly supported by X-ray analysis, may provide important knowledge of the minimal structural elements required for the design of efficient V. cholerae O1 glycoconjugate immunogens. In this perspective, delineating the exact molecular features of antigenic motifs C and A, as well as the protective capacity of Abs directed against the latter, may contribute to a better understanding of the available immunogenicity data and improve vaccine design. However, in the Ogawa context, data also underline that although informative and contributive to vaccine design, fine knowledge of the structural characteristics of LPS Ab recognition may not be predictive of the immu-nogenic potency of the ensuing glycoconjugates. As stated in the introduction to this chapter, besides the carbohydrate hapten component and carrier, numerous factors govern the quality of the induced immune response and as such, require optimization....

Infection of an accidental target tissue leading to permanent damage despite efficient clearing

It should be noted that paralysis resulting from neuronal infection does not aid the virus's spread among individuals this paralytic outcome is a dead end. Perhaps ironically, the paralytic complications of poliovirus infections have had negative selective advantages, since if such a dramatic outcome did not occur, there would have been no interest in developing a vaccine against poliovirus infection A variation on the theme of accidental destruction of neuronal targets by an otherwise relatively benign course of acute virus infection can be seen in rubella. This disease (also called German measles), which is caused by an RNA virus, is a mild (often asymptomatic) infection resulting in a slight rash. Although infection is mild in an immunocompetent individual, the virus has a strong tropism for replicating and differentiating neural tissue. Therefore, women in the first trimester of pregnancy who are infected with rubella have a very high probability of having an infant with severe...

Strategies for Reducing Secondary Pneumonia Caused by Resistant Bacteria during a Pandemic

Several strategies might reduce the burden of antimicrobial resistant secondary bacterial pneumonia during a pandemic. Strategies aimed at reducing the incidence of influenza infection could markedly reduce episodes of secondary bacterial pneumonia. These include use of antiviral agents, influenza vaccines and social distancing measures. There is also some evidence to support strategies that could limit unnecessary antibiotic use even when prior influenza infection is suspected. Previous pandemics suggest that patients who appear relatively well and do not have significant findings on chest radiographs will not benefit from antibiotics 71 . Although clinicians over-prescribe antibiotics for patients with clinical signs of pneumonia 100 , results of radiographs, when provided to clinicians, can reduce antibiotic use among patients suspected of having pneumonia from 43 to 17 101 . The role of antibacterial vaccines for the prevention of secondary bacterial pneumonia is also a critical...

Canine adenoviruses 1 and 2 CAdV1 and

-2) Two serotypes of Canine adenovirus, a species in the genus Mastadenovirus. A natural infection of dogs, often silent, but in puppies there is often fever, vomiting and diarrhea with up to 25 mortality. There is cutaneous edema, ascites, hemorrhages into the viscera and hepatitis. Also a cause of laryngotracheitis (kennel cough). In foxes there is acute encephalitis and hemorrhage into the brain. Spread of infection is from the respiratory tract and urine. Experimentally, dogs and foxes may be infected by any route. Bears, coyotes, wolves and raccoons are susceptible. Virus replication with CPE occurs in cultures of dog, ferret, raccoon and pig cells. Hemagglutination is reported. A modified live vaccine, attenuated by passage in pig kidney cell cultures, produces solid immunity following a single dose in dogs of any age. The complete DNA sequence of canine adenovirus 1 has been determined. There was little identity to human adenoviruses in the early region genes, more in the late...

Capping See capped terminus

Although a common disease of goats (in most countries surveyed, 80 of goats are infected), the virus has also been isolated from sheep with progressive pneumonia. Arthritic disease is seen frequently in adult goats, and is progressive with gradual swelling of the knee joints. Goat kids are more likely to develop encephalomyelitis with posterior paresis, occasionally leading to limb paralysis. When affected kids recover they go on to develop severe arthritis as adults. In dairy goats mastitis is also common. Control is by separating kids from animals immediately after birth to prevent colostrum transmission. No vaccines are available.

Viral infections of the liver viral hepatitis

It is spread by contaminated water or food, and causes a potentially severe but controllable loss of liver function and general malaise. Proper medical care will generally result in full recovery of liver function and full clearance of virus from the host, with effective immunity against reinfection. A relatively effective hepatitis A vaccine is available for individuals at risk of infection.

Understanding senescence and the maintenance of proliferative capacity

Understanding protective immunity is the gateway to vaccine development. Long term immunological protection is likely to depend on both the quantity and the quality of the antigen specific CD4+ and CD8+ T-cells that are generated. The level of antigen provided and the manner of presentation do certainly impact on both these parameters. However what defines exactly these parameters and how to govern them are not known yet. Although we are becoming better at inducing antigen specific T-cell responses in vivo using various vaccine strategies (e.g. antigen with adjuvants, antigen presenting dendritic cells, recombinants viral vectors, DNA), interrogation and controversy still remain as regards which are the most relevant T-cell phenotypic subpopulations or functional characteristics (i.e. effector functions as well as T-cell receptor usage and affinity - avidity) to generate. The path is still long before we reach a complete understanding of all T-cell mediated immunity mysteries the...

Chum salmon reovirus Psr Psrv A

Contagious disease which only affects pigs. Causes fever, apathy, vomiting, eye discharge, diarrhea and cutaneous hemorrhages, and is frequently fatal. Secondary bacterial infection often occurs. Strains vary in virulence some are mild, others neurotropic and some are poorly neutralized by antiserum. Disease first reported in the Mid-western USA in about 1810, then in the UK in 1862, and has since spread worldwide. The pathological lesion consists of degeneration of small blood vessels causing hemorrhage. There is leukopenia, atrophy of the thymus and lymphocytic depletion of peripheral lymphoid tissues. Infection of sows 10 to 50 days pregnant may result in infection of the fetuses, abortion or congenital tremor due to cerebellar hyperplasia. Hyperimmune serum can provide passive immunity, and there are several vaccines available, attenuated in rabbits or in cell culture, that provide active immunity. However, the European Union has adopted a non-vaccination policy, and control in...

Databases and Methods

Following a basic genome analysis (Tables 2.1 and 2.2), specific knowledge and database material (Table 2.3) are added for the detailed analysis of (i) apicomplexan genomes (ii) transmission vectors and (iii) the human host. Notably, the api-complexan biology reveals interesting basic differences from the human host, including different organelles and membranes. These represent clear advantages for drug development, such as the specific trans-splicing that occurs in trypano-somes. Moreover, some organelles do not occur in the human host, such as the glycosome 16 . On the other hand, the apicomplexans have also evolved specific strategies for host immune escape, an example being the well-known surface antigen turncoat strategy in trypanosomes. Although this active immune evasion by api-complexans comes in different flavors, it provides real challenges for a number of therapeutic strategies, such as vaccine development.

Common cold virus See human rhinoviruses

Comvax A combination vaccine containing Hemophilus B conjugate (meningococcal protein conjugate) and hepatitis B (recombinant vaccine). congenital rubella syndrome Although rubella is usually a trivial childhood exanthem, if infection occurs in utero during the first 3 months of pregnancy, 20 of infected infants are born with one or more multiple severe congenital abnormalities, including neurosensory deafness, total or partial blindness, congenital heart disease and microcephaly with mental retardation. There may also be bone translucency, retardation of growth, hepatosplenomegaly and throm-bocytopenic purpura. Vaccination of girls age 15 months against rubella as part of the MMR vaccine has resulted in a dramatic fall in congenital rubella syndrome cases since the vaccine was licensed in 1969 in the USA and 1970 in the UK.

Potential for Inducing Cross Protective Abs Insights Gained from Molecular Dynamics Simulations

Although the absence of cross-reactivity between species has been documented (Mel et al. 1965 Formal et al. 1966, 1991 Rasolofo-Razanamparany et al. 2001). An interesting outcome of a recent clinical trial was the cross-protection against non-vaccine SF types found to be stimulated in 1 to 4 year-old children receiving a SF2a dLPS-rEPA conjugate (Passwell et al. 2010). Although the modest number of events impaired any statistical significance, this first hint on the ability of dLPS conjugates at inducing SF cross-protective sera in young children is a step forward to a conjugate vaccine, which would provide multiple serotype coverage in the targeted population by use of few LPSs. In a previous study, it was postulated that immunizing with type 2a, 3a and 6 SF O-Ags could protect against almost every SF serotypes (Noriega et al. 1999). A recent report on the preferred conformations adopted by 12 SF O-Ags, as predicted by NMR-supported molecular dynamics simulations, revealed the...

Prevention Of Hiv Infection In Children

The use of HIV vaccines in the perinatal period and later in infancy to protect against breast feeding transmission of HIV is theoretically appealing if an effective and immuno-genic product could be developed. Studies using passive antibody have so far been inconclusive (107). Phase 1 studies of perinatal HIV vaccine candidates are currently underway (108,109). A model of peripartum antiretrovirals paired with an infant HIV vaccine series is a promising approach which requires further study for use in developing countries where many HIV-infected women breastfeed into the second year.

Delgadito virus See Cao Delgadito virus

Dengue virus (DENV) A species in the genus Flavivirus. Causes an acute febrile illness in humans with symptoms ranging from clinically inapparent to severe fatal hemorrhagic disease. There is an incubation period of 5-8 days, and the symptoms last about 10 days with severe headaches, retro-ocular pain, and back and limb pains. Often there is a scar-letiniform or maculopapular rash. The most severe symptoms, hemorrhagic fever with shock, probably result from infection with one dengue virus serotype in persons immune to another (See dengue viruses 1-4). The natural hosts for the virus are Aedes mosquitoes, humans, and non-human primates. Aedes aegypti is the principal vector worldwide, but other important vectors are Aedes albopictus in Asia and the Americas, Aedes scutellaris in the Pacific, and Aedes africanus and Aedes luteocephalus in Africa. The virus is only transmitted by the bite of an infective mosquito vector. Following infection, humans and nonhuman primates usually develop a...

Historical Overview of Pneumococcal Antibiotic Resistance

The worldwide spread of nonsusceptible strains of pneumococci has been related to the dissemination of certain highly resistant pneumococcal clones (serotypes 6A, 6B, 9V, 14,19F, and 23F) (Davies et al., 1999 McDougal et al., 1992). All have been associated with infections in humans and are represented in the currently available pneumococcal vaccines. In contrast, serotypes 1, 3, 4, 5, 7, 11, 15, and 18, rarely carry resistance genes (Chenoweth et al., 2000 Musher, 2000).

Alexander N Zakhartchouk Qiaohua Wu and Suresh K Tikoo

Adenoviruses have become a popular vehicle for gene transfer into animal and human cells. However, wide prevalence of preexisting immunity to human adenovirus (HAdV) and the promiscuous nature of the virus have made the use of nonhuman adenoviruses an attractive alternative. Moreover, readministration of viral vectors is often required to maintain therapeutic levels of transgene expression, resulting in vector-specific immune responses. Although a number of features of bovine adenovirus (BAdV)-3 make it attractive for use as a vector in human vaccination, BAdV-3 transduces nonbovine cells, including human cells, poorly. However, genetic modification of capsid proteins (e.g., fiber, pIX) has helped in increasing the utility of BAdV-3 as a vector for transducing nonbovine cells. Here, we will describe the methods used to construct recombinant BAdV-3 expressing chimeric fiber or chimeric pIX proteins. Key Words Bovine adenovirus (BAdV)-3 pIX fiber tropism gene therapy vaccination EYFP...

Concentration from Sewage Water

Maini and Piva tested a series of different concentration methods for measuring adenoviruses in sewage water (10). They found no advantage in using dextran sulfate-polyethylene glycol systems, compared to alumina adsorption, for that purpose (10). Quite the opposite was found with a similar system for porcine enteroviruses by Hazlett (12), who obtained about 100-fold concentration with from 37 to full recovery. In the latter study, the concentration or adsorption, obtained with cobalt chloride, polyethylene glycol precipitation, or adsorption to aluminium hydroxide or calcium hydroxyphosphate were not satisfactory (12). Poyry used a dextran-polyethylene glycol system for the concentration of polioviruses with successful results in a study on polio vaccination in Finland (11). This method is described in Subheading 3.1.

Adult immunisation programmes

Vaccination campaigns against infectious diseases are a key part of community health initiatives. In the community setting, pharmacist-led adult immunisation programmes for pneumococcal and influenza vaccination have long been advocated by ASHP (1993). Within both community and hospital settings, pharmacists can facilitate identification of patients and staff to be targeted for vaccination, provide relevant education, and supply the vaccine. In addition, in select instances, pharmacists may be in the best position to administer the vaccine (Grabenstein and Bonasso, 1999 Sanchez et al., 2003).

Preparation of Purified Virus Material

The aqueous polymer extraction method has been utilized for the preparation of a Foot-and-Mouth disease virus vaccine (13,14). It was used for purification of Venezuelan equine encephalitis virus (VEE) and the material used to establish an enzyme-linked immunosorbent assay (ELISA) for detection of VEE antibodies in human and animal sera (15,16). The high purity was obtained by a three-step extraction procedure in which the virus was alternatively partitioned to the bottom and top phase. A similar procedure has been discussed by Philipson et al. (17) and Norrby and Albertsson (18).

DsRNA adenosine deaminase activity See DRADA

Duck adenovirus 1 (DAdV-1) An unas-signed virus in the family Adenoviridae, causing egg drop syndrome (EDS). First described in 1976 as a disease of laying hens and referred to as EDS 76 virus in many publications. A widespread natural infection of ducks and geese, which show little evidence of disease. In chickens the virus replicates in nasal mucosa and subsequently in lymphoid tissues and in the pouch shell gland, resulting in eggs with abnormal thin shells and a general loss in egg production. The virus is transmitted vertically in chicken flocks, and may remain silent until the birds approach peak egg production. Isolated from chickens worldwide, which probably became infected through a contaminated vaccine. Infection also occurs in some flocks by direct contact with wild or domestic ducks or geese. Control is by eradication through slaughter of antibody-positive birds or by immunization with an oil adjuvant-inactivated vaccine applied at 3-4 months of age. Sequencing of the...

Duck hepatitis virus 1 and 3 DHV1 and

-3) Unassigned viruses in the family Picornaviridae, often referred to as 'enteroviruses' there are two serotypes, 1 and 3. Cause a widespread infection of ducks with disease in ducklings. There is hemorrhagic necrosis of the liver and high mortality. Older birds are immune. Virus is present in the excreta. Birds hatched from the eggs of immune birds resist infection. Virus replicates in hens' eggs, killing the embryo, but becomes attenuated on passage and may be used as a vaccine for ducklings. Multiplies without CPE in chick cell cultures, but with CPE in duck cell cultures. Experimentally, other birds and mammals are resistant. Type 1 virus was isolated from an outbreak of

Drug Resistance in African Trypanosomiasis

Abstract African trypanosomes include the causative agents of sleeping sickness in humans and those affecting live stock. Vaccination being jeopardized by the ever-changing surface coats of bloodstream-form trypanosomes, chemotherapy is the mainstay in the control of infections. However, the drugs in use are old, cause severe side effects, and their efficacy is undermined by the emergence of drug-resistant trypanosomes. Reliable supply of drugs for the human disease is difficult to maintain since patients are unable to meet treatment costs. Fortunately the prospects for the control of trypanosomiasis have improved recently by drug donations from Sanofi-Aventis to the WHO and through support from the Bill and Melinda Gates Foundation. Here we review the current drugs against African trypanosomes, discuss the mechanisms of drug resistance, and address key issues for the control of trypanosomiasis in face of the limited options for chemotherapy.

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