POXVIRIDAE


A Story of Viral Eradication

 

 

 

 

 

 

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Katie Hagey                                      Humans & Viruses                         Professor Robert Siegel               Stanford University

 

 "I hope that one day the practice of producing cowpox in human beings will spread all over the world - when that day comes, there will be no more smallpox"                

- Edward Jenner

Introduction to Poxviruses

Poxviridae, which serves as an umbrella for the largest human viruses, can credit its name to the Anglo-Saxon word 'pokkes', or pouch, referring to the characteristic vesicular lesions of the family.  Variola is Latin for spot, while 'smallpox' was introduced during the 1500s to differentiate the disease from syphilis, the 'great pox'.  Evidence suggests that poxviruses have persisted in human populations for millenia - the mummy of Pharaoh Ramses V shows lesions indicative of smallpox infection.  Further, smallpox is the prototype of successful fights against infectious disease; it represents both the first vaccine and the first disease to be eradicated worldwide by immunization.  In the current era, there are some worries that poxviruses, particularly smallpox, may be used as possible agents of bioterrorism.

Timeline: Punctuated events in the history of poxviruses 

1157 B.C.: Pharoah Ramses V dies of smallpox 

1520: Hernando Cortez brings smallpox with him to America, effectively killing 3.5 million Aztecs who lacked immunity

1700: It is believed that the practice of inoculating healthy people with material from smallpox lesions in order to prevent disease originated in China.  In 1700, Joseph Lister sent an account of the practice of variolation to The Royal Society.

1717: In 1717, Lady Mary Wortley Montague, wife of the British Ambassador, decided to inoculate her own son against smallpox because she was so convinced of variolation's safety and efficacy after witnessing the practice in Turkey. Upon returning to England, she worked tirelessly to have variolation generally accepted. 

 1798: In 1798, Edward Jenner published 'An inquiry into the causes and effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire, and known by the name of the cow-pox', which reported how, over a period of years, he had noticed the immunity provided by cowpox, and how he decided deliberately to introduce the disease into a patient to see if the effect could be artificially produced.

 

1949: After a successful worldwide vaccination program, the last case of smallpox in the United States was in 1949.  

 

 

 

 1950: The first hemisphere-wide effort to eradicate smallpox was made in 1950 by the Pan American Health Organization; the campaign was successful in eliminating smallpox from all American countries except Argentina, Brazil, Colombia, and Ecuador.

1958: Monkeypox was first discovered in laboratory monkeys in 1958, though later blood tests of animals in Africa later found evidence of monkeypox infection in a number of African rodents. Ultimately, the monkeypox virus was isolated from an African squirrel.

 

 

1966: By 1966, vaccination was widely practiced, but regional differences in uptake ensured the fact that the disease would continue to flare up in epidemic proportions. To deal with this reality, the WHO voted to spend $2.5 million for an immunization campaign designed to eradicate smallpox completely within 10 years.

1970: Monkeypox was reported in humans for the first time in 1970.

1972: Routine smallpox vaccination among the American public stopped in 1972 after the disease was eradicated in the United States. Until recently, the U.S. government provided the vaccine only to a few hundred scientists and medical professionals working with smallpox and similar viruses in a research setting.

 1977: The last naturally occurring case of smallpox 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.

*The last case of smallpox was reported in this Somalian man 

 

 January 1986: Can infectious smallpox persist in preserved cadavers? In 1986, Italian scientists claimed to have serological and electron microscope evidence of smallpox in a Neapolitan mummy from the 16th century.

January 1996: In 1996, the World Health Assembly recommended that all the remaining stocks of variola virus be destroyed by June 1999. This has still not happened.

September 2000: A 4-year-old girl from a small farm in eastern Finland was hospitalized in September 2000 because of umbilicated vesicopapules, which developed over the previous 5 days and unresponsiveness to cephalexin. She had a past history of moderate atopic dermatitis. Animals at her home farm included a horse, three dogs, and a rabbit, but she had no contact with cats because of allergy. On examination, most lesions were located on her swollen red extremities, a few were found on the side of her body, and 3-mm lesions were found on the face and vulva. All lesions were at the same stage of development. She was febrile with 38°C temperature and feeling unwell. A biopsy sample from a papule was sent to a virology laboratory, where orthopoxvirus particles 230 ´ 300 nm in size were demonstrated by electron microscopy with negative staining. Cowpox virus (orthopoxvirus) infection was diagnosed by electron microscopy, PCR, virus isolation, and serologic testing (positive IgM or low avidity of IgG antibodies).

August 2002: A Boer goat herd outbreak of skin lesions characterized by scabby, papillomatous dermatitis on the lips and extending into the buccal cavity was investigated in August of 2002. Members of the herd presented with acute submandibular edema, swollen mandibular lymph nodes, necrotic areas on the buccal mucosa, and lesions characteristic of orf on the muzzle.

September 2002: After September 11, the U.S. government took further actions to improve its level of preparedness against terrorism. One of many such measures—designed specifically to prepare for an intentional release of the smallpox virus—included updating and releasing a smallpox response plan. Currently, the U.S. government has enough vaccine to vaccinate every person in the United States in the event of a smallpox emergency.

June 2003: In June 2003, there was an outbreak of monkeypox in many of the north-eastern states. Monkeypox was found in both prairie dogs and humans, though it didn't cause any deaths. The main clinical features were rash, fever, respiratory symptoms, and lymphadenopathy.