Poliomyelitis

The acetylcholinesterase inhibitor tacrine (64) was approved for the treatment of mild-to-moderate SDAT in the United States in 1993 followed by several other countries. The acetylcholinesterase inhibitor galanthamine (65), which has long been in clinical use in Austria for the treatment of indications such as facial neuralgia and residual poliomyelitis paralysis, has also been approved for use in... 

Poliomyelitis. Two vaccines are Hcensed for the control of poliomyelitis in the United States. The Hve, attenuated oral polio vims (OPV) vaccine can be used for the immunization of normal children. The killed or inactivated vaccine is recommended for immunization of adults at increased... 

In the area of medicinal chemistry, Haemers and coworkers synthesized a series of 4 -hydroxy-3-methoxyflavones that exhibited antiviral activity against poliomyelitis and rhinoviruses. A representative number of compounds is shown below. First, O-hydroxyacetophenones 61 were converted to the corresponding flavones 64 using standard conditions in yields of 74-92%. Cleavage of the benzyloxy groups of 64 was then achieved under acidic conditions to deliver the requisite flavones 65. 

Vaccine diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus combined Pediarix Active immunization against diphtheria, tetanus, pertussis and all known subtypes of hepatitis B virus, and poliomyelitis immunization Sfee adverse reactions against individual vaccines. Primary immunization series 3 doses of 0.5 mLat 6-to 8-week intervals IM (first dose is 2 months of age, but may be given as early as 6 weeks of age)... 

There is a dark side to receptor-mediated endocyto-sis in that viruses which cause such diseases as hepatitis (affecting liver cells), poliomyelitis (affecting motor neurons), and AIDS (affecting T cells) initiate their damage by this mechanism. Iron toxicity also begins with excessive uptake due to endocytosis. 

Picomaviruses Poliovirus Naked icosahedral particles 28 nm in diameter One of a group of enteroviruses common in the gut of humans. The primary site of multiplication is the lymphoid tissue of the alimentary tract. Only rarely do they cause systemic infections or serious neurological conditions like encephalitis or poliomyelitis... 

Cell cultures provide infeeted fluids that eontain little debris and can generally be satisfactorily clarified by filtration. Beeause most viral vaccines made fiom cell cultures consist of live attenuated vims, there is no inaetivation stage in their manufacture. There are, however, two important exeeptions inaetivated poliomyelitis vims vaccine is inactivated with dilute formalin or /3-propiolaotone and rabies vaccine is inactivated with /3-propiolactone. The preparation of these inaetivated vaccines also involves a concentration stage, by adsorption and elution of the vims in the case of poliomyelitis vaccine and by ultrafiltration in the case of rabies vaceine. When processing is complete the bulk materials may be stored until needed for blending into final vaccine. Because of the lability of many vimses, however, it is necessary to store most purified materials at temperatures of-70°C. 

Poliomyelitis (inactivated)t (Salktype) Human diploid cell cultures infected with each of the three serotypes of poliovirus 1 Clarification 2 Inactivation with formalin 3 Concentration 4 Blending of virus of each serotype Induction of antibodies to polioviruses in chicks or guinea-pigs Inoculation of cell cultures and monkey spinal cords to exclude live virus... 

Poliomyelitis (live or oral) (Sabin type) Cell cultures infected with attenuated poliovirus of each of the three serotypes 1 Clarification 2 Blending of virus of three serotypes in stabilizing medium Infectivity titration of each of three virus serotypes Test for attenuation by Inoculation of spinal cords of monkeys and comparison of lesions with those produced by a reference vaccine... 

An example fiom virus vaeeine manufaeture is the titration, prior to inactivation, of the infectivity of the pools of live poliovims used to make inactivated poliomyelitis vaccine. Adequate infectivity of the virus from the tissue cultures is an indicator of the adequate virus content of the starting material and, sinee infectivity is destroyed in the inactivation process, there is no possibility of performing such an estimation after formolization. 

Viral vaccines present problems of safety testing far more complex than those experienced with bacterial vaccines. With killed viral vaccines the potential hazards are those due to incomplete virus inactivation and the consequent presence of residual live virus in the preparation. The tests used to detect such live virus consist of the inoculation of susceptible tissue cultures and of susceptible animals. The cultures are examined for cytopathic effects and the animals for symptoms of disease and histological evidence of infection at autopsy. This test is of particular importance in inactivated poliomyelitis vaccine, the vaccine being injected intraspinally into monkeys. At autopsy, sections of brain and spinal cord are examined microscopically for the histological lesions indicative of proliferating poliovirus. 

With attenuated viral vaccines the potential hazards are those associated with reversion of the virus during production to a degree of virulence capable of causing disease in vaccinees. To a large extent this possibility is controlled by very careful selection of a stable seed but, especially with live attenuated poliomyelitis vaccine, it is usual to compare the neurovirulence of the vaccine with that of a vaccine known to be safe in field use. The technique involves the intraspinal inoculation of monkeys with a reference vaccine and with the test vaccine and a comparison ofthe neurological lesions and symptoms, if any, that are caused. If the vaccine causes abnormalities in excess of those caused by the reference it fails the test. 

Fig. 16.1 Reported incidence of paralytic poliomyelitis in England and Wales during the 1950s and 1960s. After introduction of vaccination programmes the incidence of disease dropped from an endemic incidence of ca. 5000 cases per year to fewer than 10.

No medical or therapeutic procedure comes without some risk to the patient. All possible steps are taken to ensure safely, quahty and efficacy of vaccines and immunological products (Chapter 15). The risks associated with immunization procedures must be constantly reviewed and balanced against the risks of, and associated with, contracting the disease, hi this respect, smallpox vaccination in the UK was abandoned in the mid 1970s as the risks associated with vaccination then exceeded the predicted number of deaths that would follow importation of the disease. Shortly after this, in 1980, The World Health Assembly pronounced the world to be free of smallpox. Similarly, the incidence of paralytic poliomyelitis in the USA and UK in 1996 was low but the majority of cases related to vaccine use. As the worldwide elimination of poliomyelitis approaches, there is much debate as to the value of the vaccine outside of an endemic area. 

Two major advantages stem from the use of live vaccines. Firstly, the immunization mimics a natural infection such that only a single exposure is required to render an individual immune. Secondly, the exposure may be mediated through the natural route of infection (e.g. oral) thereby stimulating an immime response that is appropriate to a particular disease (e.g. secretory antibody as primary defence against poliomyelitis virus in the gut). 

Disadvantages associated with the use of live vaccines are also apparent. Live attenuated vaccines, administered through the natural route of infection, will be replicated in the patient and could be transmitted to others, ff attenuation is lost during this replicative process then irrfectiorrs rrtight result (see poliomyelitis, below). A second, major disadvantage of live vaccines is that the course of their action might be affected by the infeetion and immunological status of the patient. 

Polio is the only disease, at present, for which both hve and killed vaccines compete. Since the introduction of the killed vims (Salk) in 1956 and the live attenuated virus (Sabin) in 1962 there has been a remaikable decline in the incidence of poliomyelitis (Fig. 16.1). The inactivated polio vaccine (TPV) contains formalin-killed poliovirus of all three serotypes. On injection, the vaccine stimulates the production of antibodies of the IgM and IgG class which neutrahze the vims in the second stage of infection. A course of three injections at monthly intervals produces long-lasting immunity to all three poliovirus types. 

Faecal excretion of vaeeine virus will oeeur and may last for up to 6 weeks. Such released virus will spread to elose eontaets and infect/(re)immunize them. Since the introduction of OPV, notifications of paralytic poliomyelitis in the UK have dropped speetacularly. From 1985-95, 19 of the 28 notified cases of paralytic poliomyelitis were associated with vaeeine strains (14 reeipients, 5 contacts). Vaccine-associated poliomyelitis may occur through reversion of the attenuated strains to the virulent wild-... 

DTP and HiB Poliomyelitis 1st dose 2 months 2nd dose 3 months 3rd dose 4 months Primary course... 

Booster DT Poliomyelitis MMR booster 3-5 years 3 years after primary course... 

Poliomyelitis is a highly contagious disease that is often asymptomatic however, approximately 1 in every 100 to 1000 cases will develop a rapidly progressive paralytic disease. Polio is caused by poliovirus which has three serotypes type 1 is most frequently associated with paralytic disease. Poliovirus replicates in the oropharynx and intestinal tract and is excreted in oral secretions and feces, which can infect others. As a result, more than 90% of unvaccinated individuals will become infected with poliovirus following household exposure to wild-type poliovirus. Since the introduction of the first poliovirus vaccine, there has been a significant reduction in the number of polio cases. Today, polio caused by wild-type poliovirus has been eradicated from the Western Hemisphere with the goal of eradicating it from the world.11... 

The first inactivated poliovirus vaccine was introduced in the 1950s in an injectable formulation, and replaced in the 1960s by a live oral poliovirus vaccine. The oral poliovirus vaccine not only elicits systemic immunogenicity but also a localized immune response in the intestinal tract. Unfortunately, the oral poliovirus vaccine has the risk of vaccine-associated paralytic poliomyelitis occurring in approximately 1 case of every 2.4 million doses distributed. The risk with the first dose of oral poliovirus vaccine is 1 case in 750,000 doses.11... 

The last reported case of indigenous wild-type poliovirus in the United States was in 1979 subsequent cases were all vaccine-associated. In 1997, a transition period to the inactivated poliovirus vaccine was begun to reduce the risk of vac-cine-associated paralytic poliomyelitis. By January 2000, the oral vaccine was no longer recommended for routine use. Currently, the inactivated poliovirus vaccine is recommended for routine use in the United States. The oral poliovirus vaccine is still widely used in some countries where poliovirus eradication has been more difficult. 

Kojic acid is not, so far as is yet known, active against viruses. It was tested, with negative results, against one strain of poliomyelitis virus and one strain of St. Louis encephalitis virus in mice,128 and also against sixty races of bacteriophage.124... 

Signs and Symptoms Disease is biphasic. Initial symptoms are flu-like and include fever, headache, pain behind the eyes, and a vague feeling of bodily discomfort (malaise). Initial phase does not appear to involve the central nervous system. However, 4-10 days after apparent recover, there is a return of fever with meningoencephalitis or symptoms resembling paralytic poliomyelitis. Convalescence may be prolonged. 

Suggested Alternatives for Differential Diagnosis Other tick-borne encephalitis, influenza, poliomyelitis. 

Suggested Alternatives for Differential Diagnosis Encephalitis, Herpes Simplex, tetanus, Guillain-Barre syndrome, poliomyelitis, transverse myelitis, cerebrovascular accident, psychosis, intracranial mass, epilepsy, atropine poisoning, and Creutzfeldt-Jacob disease. 

College of Veterinary Medicine. "Enterovirus Encephalomyelitis Teschen Disease, Talfan Disease, Poliomyelitis Suum, Benign Enzootic Paresis." Iowa State University, August 5, 2005. 

Formaldehyde-killed Yersinia pestis Mixture of purified surface polysaccharide antigens obtained from differing serotypes of Streptococcus pneumoniae Live attenuated strains of poliomyelitis virus... 

Poliomyelitis vaccine (Salk Inactivated poliomyelitis virus vaccine parenteral)... 

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