Smallpox pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Infection
Smallpox is highly contagious, although less so than other infectious diseases. Smallpox is not notably infectious in the prodromal period—viral shedding is usually delayed until the appearance of the rash. Smallpox is transmitted primarily through prolonged social contact or direct contact with infected body fluids or contaminated objects (fomites) such as bedding or clothes. Infection in the natural disease will be via the lungs. The fact that there has been no recurrence of wild smallpox since its elimination thirty years ago makes the assumptions made at the start of the elimination campaign - that human smallpox carriers do not exist, and that the virus does not exist outside humans - some of the most certain facts in medical science.
Smallpox is a member of the family poxviridae, subfamily chordopoxvirinae. The lifecycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. It is a large virus, with a double stranded DNA genome of about 200 kilobases, making it more complicated than many bacteria.
The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers. The initial or prodromal symptoms are similar to other viral diseases such as influenza and the common cold: fevers, muscle pain, stomach aches, etc. The digestive tract is commonly involved, leading to vomiting. Most people become prostrated at this stage.
Smallpox virus preferentially attacks skin cells, and by days 12–15, smallpox infection becomes obvious. The attack on skin cells causes the characteristic pimples associated with the disease. The pimples tend to erupt first in the mouth, then on the arms and the hands, and later on the rest of the body. At this point the pimples, called macules, are usually still fairly small. This is the stage at which the victim is most contagious.
By days 15–16 the condition worsens, and at this point the disease can take two very different courses, depending on whether it is ordinary or hemorrhagic smallpox. The most common type is classic ordinary smallpox, in which the pimples grow into vesicles and then fill up with pus, turning them into pustules. Ordinary smallpox generally takes one of two basic courses. In discrete ordinary smallpox, the pustules stand out on the skin separately. There is a greater chance of surviving this form. In confluent ordinary smallpox, the blisters merge together into sheets which begin to detach the outer layers of skin from the underlying flesh. This form is usually fatal. If the patient survives the course of the disease, the pustules deflate in time (the duration is variable), and start to dry up, usually beginning on day 28. Eventually the pustules completely dry and start to flake off. Once all of the pustules flake off, the patient is considered cured, and is no longer contagious.
Chickenpox and smallpox can be distinguished in the field via several methods. An examination of the patient's palms and soles is necessary: unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly the same size since the viral effect progresses more uniformly.
Inoculation
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By that time, a preventive treatment for smallpox had finally arrived. It was a process called inoculation, also known as insufflation or variolation. Inoculation was not a sudden innovation, as it is known to have been practiced in India as early as 1000 BC.[1] The Indians rubbed pus into the skin lesions. The Chinese blew powdered smallpox scabs up the noses of the healthy after discovery, by a Buddhist nun, that this inoculated non-immune people. The patients would then develop a mild case of the disease and from then on were immune to it. This technique is known as variolation and although variolation had a 0.5-2% mortality rate, this was considerably less than the 20-30% mortality rate of the disease itself. The process spread to Turkey where Lady Mary Wortley Montagu, wife of the British ambassador, learned of it from Emmanuel Timoni (ca. 1670–1718), a doctor affiliated with the British Embassy in Istanbul.[2] She had the procedure performed on her son and daughter, aged 5 and 4 respectively. They both recovered quickly and the procedure was hailed as a success and reported to the Royal Society in England. Timoni, from the University of Padova, Italy and a member of the Royal Society of London since 1703, published “an account, or history, of the procuring the smallpox by incision” in December 1713 in the Philosophical Transactions. His work was published again in 1714 in Leipzig and was followed by those of Pylarino (1715), Leduc (1722), and Maitland (1722).
In 1721, an epidemic of smallpox hit London and left the British Royal Family in fear.[2] Reading of Lady Wortley Montagu’s efforts, they wanted to use inoculation on themselves. Doctors told them that it was a dangerous procedure, so they decided to try it on other people first. The test subjects they used were condemned prisoners. The doctors inoculated the prisoners and all of them recovered in a couple of weeks. So assured, the British royal family inoculated themselves and reassured the English people that it was safe.
But inoculation still had its critics. Prominent among them were religious preachers who claimed that smallpox was God’s way of punishing people and that inoculation was a tool of Satan. This resistance only encouraged Montagu and the others to work even harder. By 1723 inoculations were extremely common in England, but even scientific opposition (such as the Fellow of the Royal College of Physicians Pierce Dod) continued for some time.
In 1721, Onesimus was the slave of a Boston preacher when smallpox came to Boston via a ship arriving from Barbados.[3] His owner, Cotton Mather asked his slave if he ever had smallpox. Onesimus said, “Yes and no,” and explained a technique from his homeland in Africa, thought to be in Sudan. He explained that pus from an infected person was deliberately rubbed into a scratch or cut of a non-infected person, and when successful, the person had immunity. This remedy from an African slave was the precursor to inoculations. Cotton Mather, the son of a former Harvard University dean, was waging a campaign of his own to promote the process, although religious resistance to inoculation was very strong. At one point, Cotton Mather was in danger from a crowd that wanted to hang him. After six patients died from the procedure, he was called a murderer. But, when the population of Boston returned after the end of a smallpox epidemic in 1722, he was an instant hero. Out of the population of Boston, 7% had died from smallpox. Out of the 300 people that chose to inoculate themselves, only 2% died. In 1750, the English magazine, Gentleman's Magazine, reprinted a 1725 pamphlet that argued in support of smallpox inoculations. By 1774, it was considered odd not to choose inoculation. Onesimus was later freed by Mather, not for his knowledge and help in combating smallpox, but because Mather considered him to be disobedient.
Even though inoculation was a powerful method of controlling smallpox, it was far from perfect. Inoculation caused a mild case of smallpox which resulted in death in about 2% of the cases. It was also difficult to administer. Sick patients had to be locked away to prevent them from transmitting the disease to others. Thus George Washington initially hesitated to have his Revolutionary War troops inoculated during a smallpox outbreak in February 1777, writing, “should We inoculate generally, the Enemy, knowing it, will certainly take Advantage of our Situation;” but the virulence of the outbreak soon prompted him to order inoculation for all troops and recruits who had not had the disease.[4]
In 1796, a young boy in England was inoculated by Edward Jenner. The boy suffered from the disease for an entire month and recovered completely.
References
- ↑ Bourzac K (2002). "Smallpox: Historical Review of a Potential Bioterrorist Tool". Journal of Young Investigators. 6 (3): –.
- ↑ 2.0 2.1
- ↑ "BLACK HISTORY MONTH II: Why Wasn't I Taught That? (B. Willoughby)". Tolerance in the News. Retrieved 2006-09-23.
- ↑ Grizzard FE, Washington G, Chase PD, Twohig D (1985). George Washington to Major General Horatio Gates, 5–6 February 1777. In: The papers of George Washington. 8. Charlottesville: University Press of Virginia. ISBN 0-8139-1787-5.