Smallpox

Smallpox is a serious, contagious, and sometimes fatal infectious disease. There is no specific treatment for smallpox disease, and the only prevention is vaccination. The name smallpox is derived from the Latin word for spotted and refers to the raised bumps that appear on the face and body of an infected person. 

There are two clinical forms of smallpox. Variola major is the severe and most common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox ordinary (the most frequent type, accounting for 90% or more of cases) modified (mild and occurring in previously vaccinated persons) flat and hemorrhagic (both rare and very severe). Historically, variola major has an overall fatality rate of about 30% however, flat and hemorrhagic smallpox usually are fatal. Variola minor is a less common presentation of smallpox, and a much less severe disease, with death rates historically of 1 % or le.ss. 

Smallpox outbreaks have occurred from time to time for thousands of years, but the disease is now eradicated after a successful worldwide vaccination program. The last case of smallpox in the United States was in 1949. The last naturally occurring case in the world was in Somalia in 1977. After the disease was eliminated from the world, routine vaccination against smallpox among the general public was stopped because it was no longer necessary for prevention. 

Generally, direct and fairly prolonged face-to-face contact is required to spread smallpox from one person to another. Smallpox also can be spread through direct contact with infected bodily fluids or contaminated objects such as bedding or clothing. Rarely, smallpox has been spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. Humans are the only natural hosts of variola. Smallpox is not known to be transmitted by insects or animals. 

A person with smallpox is sometimes contagious with onset of fever (prodrome phase), but the person becomes most contagious with the onset of rash. At this stage the infected person is usually very sick and not able to move around in the community. The infected person is contagious until the last smallpox scab falls off. 

The rest of this chapter will show how the most successful treatment modalities have developed. These include vaccination (for smallpox, polio, measles, etc.), and chemotherapy using anti-viral drugs. A large number of viral diseases still lack an effective means of treatment, and the chapter will also cover the attempts to treat the common cold and influenza the struggles with HIV and the emergence of viruses (Marburg, Ebola, Lassa) that cause haemorrhagic fever. 

An early example of biological warfare is also alleged to have occurred when Sir Jeffrey Amherst, who was commander of the English forces in North America, ordered that smallpox-contaminated blankets be distributed to the local native people. The effects on a population that had never been exposed to this virus were devastating. 

The situation in Europe changed towards the end of the 17th century. Improvements in sanitation produced a dramatic decline in the incidence of bubonic plague, whilst a mutation of the variola virus (the causative agent of smallpox) appears to have produced a more virulent strain. During the 18th century, most Europeans contracted smallpox and around one in five of the population (a total in excess of 50 million people) died from the disease. Localised epidemics could be even more devastating like the one of 1707 in Iceland, when 36% of the population died, or the one of 1719 in Paris, when 14000 of the population died. 

Smallpox is the most terrible of all the ministers of death...leaving on those whose lives it spared the hideous traces of its power, turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the betrothed maiden objects of horror to the lover. 

Such was the fate that befell Lady Mary Wortley Montagu, a woman of considerable beauty whose face was scarred by the effects of smallpox in 1715. In 1716, she accompanied her husband when he took up the post of Ambassador to Turkey in Istanbul. Here, she took a close interest in the Turkish method of inoculation that was used as a preventative measure against smallpox. In her now justly famous letter to her friend Mary Chiswell in 1717, she gave a graphic description of the technique  

MEDICAL MANAGEMENT Active Immunoprophylaxis Passive Immunoprophylaxis Chemoprophylaxis and Chemotherapy 

Research Medical Officer, Division of Virology, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011 

The poxviruses (of the family Poxviridae) are a family of large, enveloped deoxyribonucleic acid (DNA) viruses.1 The most notorious poxvirus is variola, the causative agent of smallpox. Smallpox was an important cause of morbidity and mortality in the developing world until recent times. Since the host range of the variola virus is confined to humans, aggressive case identification and contact 

Since 1983, there have existed two WHO-ap-proved and -inspected repositories of variola virus the CDC in the United States and Vector Laboratories in Russia. WHO continues to debate whether, given the completion of sequencing of several reference strains, all stocks of variola virus should be destroyed. Proponents of retaining these smallpox stocks argue that military or terrorist use of variola 

Those who advocate eradication of the official variola virus repositories cite the possibility of accidental or intentional release of the virus as a threat to international public health political instability 

Viral implantation into oropharynx/respiratory tract spreads to regional lymph nodes viremia with virus multiplication in spleen, bone marrow, lymph nodes locates in leukocytes, small dermal blood vessels, and submucosal oral and pharyngeal cells 

Source Humans prior to global eradication pres- 

Populations All distribution probably similar to general popu- 

mucosa - petechiae Mouth, mucosa - pustules [21] 

Skin - rash, macular/papular [3, 9, 12, 14, 17] Skin - rash, petechiae [h] 

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Smallpox vaccine Smalt Smaltite SMA resins SMART Smart catalysts Smart gels Smart hydrogels Smart material Smart materials... 

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... 

Blattergift, n. smallpox toxin, smallpox virus. Blattergips, m. selenite, blatterigi u. leafy, foliated, laminated. Blatter kies, rw. lamellar pyrites, -kohle, /. 

Menschen-alter, n. generation, -blut, n. human blood, -fett, n. human fat. -freund, m. philanthropist, -geschlecht, n. mankind, humanity, -kdrper, m. human body, -lehre, /. anthropology human teaching, -pocken, /.pi. smallpox. 

Pocken-gift, n. smallpox virus, -holz, n. = Pockholz. -impfimg,/. vaccination, -lymphe, /. vaccine lymph, -narbe,/. pit. -wurzel,/. chinaroot. 

Do not take live virus vaccinations (eg, smallpox) because of the risk of a lack of antibody response This does not include patients receiving the corticosteroids as replacement therapy. 

DNA viruses Poxviruses Variola Vaccinia Large particles 200 x 250nm complex symmetry Variola is the smallpox virus. It produces a systemic infection with a characteristic vesicular rash affecting the face, arms and legs, and has a high mortality rate. Vaccinia has been derived from the cowpox virus and is used to immunize against smallpox... 

Methisazone (Fig. 5.2IB) inhibits DNA viruses (particularly vaccinia and variola) but not RNA viruses, and has been used in the prophylaxis of smallpox. It is now little used, especially as, according to the World Health Organization, smallpox has now been eradicated. 

In 1801, Jenner prophesied the eradication of smallpox by the practice of vaccirrahon. hr 1967 the disease infected 10 milhon people. The World Health Orgarrizahon (WHO) initiated a programme of confinement and vaccirration with the object of eradicating the disease. In Somalia in 1977 the last case of rraturally acquired smallpox occurred, and in 1979 the WHO announced the total eradication of smallpox, thus firUrlling Jenner s prophecy. 

Viruses replicate only in living cells so the first viral vaccines were necessarily made in animals smallpox vaccine in the dermis of calves and sheep and rabies vaccines in the spinal cords of rabbits and the brains of mice. Such methods are no longer used in advanced vaccine production and the only intact animal hosts that are used are embryonated hens eggs. Almost all of the vims that is needed for viral vaccine production is obtained from cell cultures infected with vims of the appropriate strain. 

Viral vaccines less generally available than those listed in die table include Congo Crimean haemorrhagic fever vaccine, dengue fever vaccine, Japanese encephalitis B vaccine, smallpox vaccine, tick borne encephalitis vaccine, and Venezuelan encephalitis vaccine. 

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. 

A live vaccine strain of measles (Chapter 15) was introduced in the USA in 1962 and to the UK in 1968. A single injection produces high-level immunity in over 95% of recipients. Moreover, since the vaccine induces immunity more rapidly than the natural infection, it may be used to control the impact of measles outbreaks. The measles virus cannot survive outside ofan infected host. Widespread use ofthe vaccine therefore has the potential, as with smallpox, of eliminating the disease worldwide. Mass immunization has reduced the incidence of measles to almost nil, although a 15-fold increase in the incidence was noted in the USA between 1989 and 1991 because of poor compliance. 

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... 

Slow-acting, contagious Variola major (smallpox) Flu-like symptoms 12 to 14 days... 

In particular, I am indebted to Donald A. Henderson, MD, MPH, who directed the World Health Organization s eradication of smallpox, for his private e-mail communication, Nov. 23, 1999, explaining the effect of refrigeration on vaccination and smallpox. 

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