Target Health Blog

Small Pox, Deadlier Than Any Bomb. & Still Not Completely Destroyed

April 2, 2018


A child showing rash due to ordinary-type smallpox (variola major). Photo credit: CDC - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #4728.  Public Domain,

In 2017, Bill Gates stated that bioterrorism with smallpox could be more dangerous than a nuclear weapon.

Smallpox is an infectious 1) ___ caused by one of two virus variants, Variola major and Variola minor. The last naturally occurring case was diagnosed in October 1977 and the World Health Organization certified the global eradication of the disease in 1980. The risk of death following contracting the disease was about 30%, with higher rates among babies. Often those who survive have extensive scarring of their skin and some are left blind. The initial symptoms of the disease include fever and vomiting. This is then followed by formation of sores in the mouth and a skin rash. Over a number of days the skin 2) ___ turns into characteristic fluid filled bumps with a dent in the center. The bumps then scab over and fall off leaving scars. The disease used to spread between people or via contaminated objects. Prevention is by the smallpox vaccine. Once the disease has developed certain antiviral medication may help. 

There were two clinical forms of smallpox. Variola major was the severe and most common form, with a more extensive rash and higher 3) ___. Variola minor was a less common presentation, and a much less severe disease, with historical death rates of 1% or less. Subclinical (asymptomatic) infections with variola virus were noted, but were not common. In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by virus isolation. 

The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. Once inhaled, variola major virus invades the oropharyngeal (mouth and throat) or the respiratory mucosa, migrates to regional lymph 4) ___, and begins to multiply. In the initial growth phase the virus seems to move from cell to 5)___, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers (this is called viremia), and a second wave of multiplication occurs in the spleen, bone marrow, and lymph nodes. The initial symptoms are similar to other viral diseases such as influenza and the common 6) ___: fever of at least 38.3 oC (101 oF), muscle pain, malaise, headache and prostration. As the digestive tract is commonly involved, nausea and vomiting and backache often occur. The prodrome, or pre-eruptive stage, usually lasts 2-4 days. By days 12-15 the first visible lesions - small reddish spots called enanthem - appear on mucous membranes of the mouth, tongue, palate, and throat, and temperature falls to near normal. These lesions rapidly enlarge and rupture, releasing large amounts of virus into the saliva. Smallpox virus preferentially attacks skin cells, causing the characteristic pimples (called macules) associated with the disease. A rash develops on the skin 24 to 48 hours after lesions on the mucous membranes appear. Typically, the macules first appear on the forehead, then rapidly spread to the whole 7) ___, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process takes no more than 24 to 36 hours, after which no new lesions appear. At this point variola major infection can take several very different courses, resulting in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic. Historically, smallpox has an overall fatality rate of about 30%; the malignant and hemorrhagic forms are usually fatal.

The last cases of smallpox in the world occurred in an outbreak of two cases (one of which was fatal) in Birmingham, United Kingdom, in 1978. A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978, after which Professor Henry Bedson, the scientist responsible for smallpox research at the university, killed himself. All known stocks of smallpox were subsequently destroyed or transferred to two WHO-designated reference laboratories with BSL-4 facilities - the United States' Centers for Disease Control and Prevention and Russia's State Research Center of Virology and Biotechnology VECTOR. WHO first recommended destruction of the 8) ___ in 1986 and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1999. Due to resistance from the U.S. and Russia, in 2002 the World Health Assembly agreed to permit the temporary retention of the virus stocks for specific research purposes. Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. Some scientists have argued that the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests; a 2010 review by a team of public health experts appointed by WHO concluded that no essential public health purpose is served by the U.S. and Russia continuing to retain virus stocks. The latter view is frequently supported in the scientific community, particularly among veterans of the WHO Smallpox Eradication Program.

In March 2004, smallpox scabs were found inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. The envelope was labeled as containing 9) ___ from a vaccination and gave scientists at the Centers for Disease Control and Prevention an opportunity to study the history of smallpox vaccination in the United States. On July 1, 2014, six sealed glass vials of smallpox dated 1954, along with sample vials of other pathogens, were discovered in a cold storage room in an FDA laboratory at the National Institutes of Health location in Bethesda, Maryland. The smallpox vials were subsequently transferred to the custody of the CDC in Atlanta, where virus taken from at least two vials proved viable in culture. After studies were conducted, the CDC destroyed the virus under WHO observation on February 24, 2015.

In 2017, Canadian scientists recreated an extinct horse pox virus to demonstrate that the 10) ___ virus can be recreated in a small lab at a cost of about $100,000, by a team of scientists without specialist knowledge. This makes the retention controversy moot since the virus can be easily recreated even if all samples are destroyed. Although the scientists performed the research to help development of new vaccines as well as trace smallpox's history, the possibility of the techniques being used for nefarious purposes was immediately recognized, leading to new regulation questions. Sources:; Wikipedia

ANSWERS: 1) disease; 2) rash; 3) fever; 4) nodes; 5) cell; 6) cold; 7) face; 8) virus; 9) scabs; 10) smallpox

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