Smallpox prevention

A vaccine is a preparation used to prevent a specific infectious disease by inducing immunity in the host against the pathogenic microorganism. The practice is also called immunization. The first human immunization was performed in 1796 by Edward Jenner in England which led to the discovery of smallpox vaccine. However, classical vaccinology developed 100 years later, after the work by Louis Pasteur demonstrated that microorganisms are causes of diseases. 

Preventive medicine through vaccination continues to be the most cost-effective pubHc health practice, even with the drastic advance in modern medicine. Mass vaccination programs have eradicated smallpox from the earth. The World Health Organization (WHO) has a major campaign underway to eradicate poHo by the year 2000. The development of vaccines has saved millions of Hves and prevented many more from suffering. However, there are stiU many diseases without effective vaccines, such as malaria. With the recent emergence of antibiotic-resistance strains and exotic vimses, an effective vaccine development program becomes a top priority of pubHc health poHcy. 

Thiosemicarba2ones have long been used as antiviral agents, principally against pox vimses of the vaccinia family. One compound of this series, the isatin derivative (6) C HgN OS, has been used prophylacticaHy to prevent outbreaks of smallpox in humans (10) and to inhibit the protein synthesis in poxvims-infected cells. The molecular mechanics relating to this property are still not known (11), though the binding of a metal ion may be a key factor... 

Methisa2one [1910-68-5] C qH qN OS (l-methyl-3-thiosemicarba2one of 2-oxoindole, (7), one of the more active in the isatin-3-thiosernicarba2one [487-16-1] series, has been used in the treatment and prevention of smallpox and vaccinia infections that develop as complications of smallpox vaccination... 

The development and widespread use of vaccines is one of the greatest public health achievements of the twentieth century. Other than safe drinking water, no other modality has had a greater impact on reducing mortality from infectious diseases. The first accounts of deliberate inoculation to prevent disease date back as far as the tenth century. However it wasn t until 1798 that Edward Jenner published his work on inoculation of natural cowpox as a means to prevent infection with smallpox. This was the first scientific attempt to prevent infection by inoculation. Since 1900, vaccines have been developed against more than 20 diseases, with half of these recommended for... 

The application of vaccine technology forms a core element of modern medicinal endeavour. It plays a central role in both human and veterinary medicine and represents the only commonly employed prophylactic (i.e. preventative) approach undertaken to control many infectious diseases. The current (annual) global vaccine market stands at in excess of US 3 billion. Immunization programmes, particularly those undertaken on a multinational scale, have served to reduce dramatically the incidence of many killer/disabling diseases, such as smallpox, polio and tuberculosis. 

There is no proven treatment for smallpox, but in persons exposed to smallpox who do not show symptoms as yet, the vaccine — if given within four days after exposure — can lessen the severity of or even prevent illness. However, once a patient shows symptom, treatment is limited to supportive therapy and antibiotics to treat bacterial infections. Patients with smallpox can benefit from supportive therapy such as intravenous fluids, and medicines to control fever or pain. 

If the vaccine is given within 4 days after exposure to smallpox, it can lessen the severity of illness or even prevent it. 

Vaccination is not recommended at this time, and the vaccine is not available to healthcare providers or to the public. In the absence of a confirmed case of smallpox anywhere in the world, there is no need to be vaccinated against smallpox. CDC has clear guidelines for providing vaccine to people exposed to smallpox if a case did occur. Healthcare workers and close contacts of the person or persons with confirmed smallpox disease would receive the vaccine. Through CDC, healthcare workers would have access to the vaccine if it were needed to prevent the disease. 

How many people would have to get smallpox before it is considered an outbreak One suspected case of smallpox is considered a public health emergency. Smallpox surveillance in the United States includes detecting a suspected case or cases, making a definitive diagnosis with rapid laboratory confirmation at CDC, and preventing further smallpox transmission. A suspected smallpox case should be reported immediately by telephone to state or local health officials. They should immediately obtain advice regarding isolation of the patient or patients, and on laboratory specimen collection. State or local health officials should notify CDC immediately at (404) 639-2184 or (404) 639-0385 if a suspected case of smallpox is reported. 

Although personnel who have been vaccinated recently and who have a demonstrated immune response should be fully protected against infection with smallpox virus, they should continue to observe standard contact precautions including using protective clothing and shoe covers when in contact with smallpox patients or contaminated materials to prevent inadvertent spread of variola virus to susceptible persons and potential self-contact with other infectious agents. 

Nonhospital isolation of confirmed or suspected smallpox patients should be of a sufficient degree to prevent the spread of disease to nonimmune persons during the time the patient is considered potentially infectious, which includes from the onset of symptoms until all scabs have separated. 

If a vaccinated or unvaccinated contact experiences a fever >101° F (38° C) during the 17-day period after his or her last exposure to a smallpox patient, the contact should be isolated immediately to prevent contact with nonvaccinated or nonimmune persons until smallpox can be ruled out by clinical or laboratory examination. 

The word vaccination comes from vaccinia, the name of the virus now known to cause cowpox vaca is the Latin word for cow ). The term vaccination is now broadly used to describe the process of causing a mild disease in order to protect a person from a more dangerous disease. Vaccination is one form of immunization, exposing the body to a material to stimulate a protective response from the immune system. Vaccination is routinely used to prevent many illnesses, including measles, rnmnps, German measles (rubella), chicken pox, and polio. Many of these illnesses have disappeared or become very rare in developed countries that provide widespread vaccinations. Smallpox has been eradicated worldwide, thanks to... 

Three basic approaches are used to control viral diseases vaccination, antiviral chemotherapy, and stimulation of host resistance mechanisms. Vaccination has been used successfully to prevent measles, rubella, mumps, poliomyelitis, yellow fever, smallpox, chickenpox, and hepatitis B. Unfortunately, the usefulness of vaccines appears to be limited when many stereotypes are involved (e.g., rhinoviruses, HIV). Furthermore, vaccines have little or no use once the infection has been established because they cannot prevent the spread of active infections within the host. Passive immunization with human immune globulin, equine antiserum, or antiserum from vaccinated humans can be used to assist the body s own defense mechanisms. Intramuscular preparations of immune globulin may be used to prevent infection following viral exposure and as replacement therapy in individuals with antibody deficiencies. Peak plasma concentrations of intramuscular immune globulins occur in about 2 days. In contrast, intravenously administered immune globulin provides immediate passive immunity. 

Respiratory, skin, and soft-tissue infections UTIs pelvic inflammatory disease (PID) brucellosis trachoma Rocky Mountain spotted fever typhus Q fever lickettsia severe acne (Adoxa) smallpox psittacosis ornithosis granuloma inguinale lymphogranuloma venereum intestinal amebiasis (adjunctive treatment) prevention of rheumatic fever ... 

Unfortunately, inoculation not only prevented virulent cases of smallpox, it also caused them. The mild cases of smallpox triggered by inoculation were contagious and could spread the natural, deadly, form of the disease. As a result, the entire community could be affected by inoculation. Practiced under conditions of strict isolation and quarantine, it could reduce the number of people who would become sick and thereby infectious without such precautions, it could trigger an epidemic. 

The aromatic and heteroaromatic thiosemicarbazones (39) are powerful chelating agents which have been rather neglected in the mainstream of chelation chemistry. Perrin and Stiinzi43) have reviewed their role as antiviral agents and noted their use in 1950 to reduce the severity of vaccinia infections of chick embryos and mice. The thiosemicarbazones have been used prophylactically to prevent outbreaks of smallpox in persons who had been in contact with the disease295). Pfauz96) has reviewed the pharmaceutical applications of thiosemicarbazones. 

There are just a few studies of the use of caspase inhibitors to prevent apoptosis. Most studies concentrate on the expression of proteins of the IAP family (XIAP being the most noticeable) and the viral components p35 and CrmA (Vives et al., 2003a). CrmA, encoded by the smallpox virus, is a pseudo-substrate for serine and cysteine proteases. It inhibits caspases 1, 8, and 10 in several cell types (Sauerwald et al., 2003). p35 is a wide-spectrum caspase inhibitor encoded by baculoviruses, and it also behaves as a pseudo-substrate, inhibiting caspases 1, 3, 6, 7, 8, and 10 (Zhou et al., 1998). XIAP is the most potent member of the IAP family. It is found in the mammalian genome and is responsible for the inhibition of caspases 3, 7, and 9 (Sauerwald et al., 2002). An increased protective effect is found in CHO and HEK-293 cells expressing a XIAP mutant resistant to degradation (XIAP-BIR123) when compared with the wild-type protein (Sauerwald et al., 2002). 

Other types of replication-deficient viral vectors that have been used in the gene therapy field include Herpes simplex viral (HSV) vectors that (1) are able to transduce nondividing cells and (2) are highly infective for neurologic tissue and vaccinia vectors. Vaccinia vectors in turn (1) are able to transduce nondividing cells and (2) have the ability to efficiently infect many types of cells. The primary safety concerns for HSV vectors are the potential for tropism to the CNS and the potential for latency and reactivation. Vaccinia vectors contain the same backbone as the smallpox vaccine, thus the available safety databases for vaccinia administration in humans consist primarily of preventive vaccination in a healthy population. Principal safety concerns with the use of vaccinia vectors include (1) their ability to replicate in humans and possibly... 

The discovery of vaccines for smallpox, cholera, and typhoid and the variety of vaccines now available have led to a significant reduction in the mortality and morbidity due to many diseases, with smallpox being the first to have been completely eradicated and poliomyelitis targeted to be the next. At present, the World Health Organization is working toward the complete elimination of poliomyelitis throughout the world [188,189], However, since Jenner discovered the vaccine for smallpox more than two centuries ago [190], only some 50 vaccines have been approved for use, and few additional vaccines have been discovered. Most of those in current use are administered parenterally they can induce only a systemic immune response, not mucosal immunity. Obviously the latter is very important in the prevention and treatment of infectious diseases, be they due to viral, bacterial, or parasitic pathogens that attack via the mucosal surfaces [190],... 

The existence of an immune system in mammals, highly effective in protecting against disease after recovery from an initial infection, also has not prevented periodic catastrophic epidemics and epizootics. However, an astute English country doctor, Edward Jenner, noted immunological cross protection against deadly smallpox in English milkmaids who had recovered from mild cowpox. Despite skepticism, ridicule and even hostility of many of his peers, Jenner developed vaccination as one of the safest and most effective mammalian disease preventive measures known. We hope and believe that the same can be accomplished for plants. 

Centers for Disease Control and Prevention. (March 25, 2003a). Temporary deferral recommended for heart patients volunteering for smallpox vaccination. Retrieved March 11, 2007 from http //www.bt.cdc.gov/agent/smallpox/vaccination/ heartproblems. asp... 

There is also heightened concern that a bioterrorist could release smallpox, a disease that has been eradicated from the globe since at least 1980. Officially, only two places on Earth still maintain viable smallpox virus in cold storage Novosibirsk, Russia and Atlanta, Georgia, at the Centers for Disease Control and Prevention (CDC). Some unconfirmed reports allege that other countries, however, including North Korea and perhaps others, still hold on to smallpox virus specimens. Could a terrorist release smallpox, and how would it affect a mostly immunologically naive population ... 

Centers for Disease Control and Prevention. (2003). Update Cardiac related events during the civilian smallpox vaccination program—United States, 2003. MMWR Morbidity and Mortality Weekly Report, 52, 492-496. 

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