Small Pox Research Paper

Small pox was a deadly killer that has plagued mankind from as early as 1570B.C where signs of small pox scarring have been found on Egyptian mummies (1). Although, crowding of the poor in cities led to more outbreaks of this airborne virus, small pox was not a picky virus as it infected both the rich and poor alike. Those whom contracted small pox were very likely to die and if they did survive they suffered from disfigured scarring and blindness. By the 18th century people were looking for a cure to this terrible virus but there was great difficulty because no one knew what caused small pox.

Edward Jenner was from Berkeley, Gloucestershire, and named the father of immunology pioneered and founded a vaccination for small pox (1). When Jenner was eight years old he was treated with what was thought to be the medical gold standard inoculation or variolation against small pox. Jenner’s doctor originally treated him by introducing variola of a recent smallpox victim into his hand (1). This was done because it was thought if the patient developed the pox and lived

they would build up an immunity against small pox. Unfortunately, not everybody inoculated lived but it gave the others better odds of survival rather than taking their chances on spontaneously getting small pox. Fortunately, Jenner did survive his inoculation and grew up to be a doctor, where he moved back to his hometown, Gloucestershire, to work on different experiments.
Once Jenner moved back home he had more contact with cows and their milk maids. It was rumored that milk maids were actually immune to the small pox virus. Milk maids commonly became infected with cowpox because it could be transferred from the infected cows utters to the milk maids hands during the milking process. Although cowpox looks like small pox it is actually a relatively mild disease. Jenner came upon the idea of deliberately infecting a young patient with cowpox in order to set up an immunity from the smallpox infection. If Jenner was right then there would no longer be a need to take the risk of variolation. Jenner carried out his experiment on May 14th, 1796; he took a sample of pus from Sarah Nelmes, a milk maid, who had been infected by cowpox and introduced into a small cut on a healthy eight year old boy James Phipps (1). James did end up coming down with the cowpox infection but fortunately recovered quickly. Two months later Jenner introduced different quantities of the small pox infection to James but he did not fall ill instead he showed immunity to the disease. Jenner wrote up his findings in an article to be published but the publication was refused because of his methods. He then decided to self-publish a paper but was mocked not only because of his methods but the public thought they may have the risk of becoming cow-like.
Jenner termed the word “Vaccination” from the Latin word vacca which means cow (1). An inescapable connotation for the squeamish public about introducing a cow disease to themselves. Gradually vaccination became popular, but Jenner never received fame or wealth, except 10,000 pounds on his work (1). He continued to do vaccinations until he died in 1823. By 1840 variolation was banned and in 1853 vaccination became compulsory in England (1). In 1967 the world health organization started the mass vaccination program, and by 1980 small pox was declared eradicated (1). Edward Jenner’s work was said to have saved more lives than the work of any other man.

Ebola virus (EBOV) belongs to the family Filoviridae. They are enveloped, filamentous, negative-sense RNA viruses that may be associated with severe zoonotic disease in humans (3). Currently, there are 5 species of the Ebola virus, and of the five, four species of EBOV have caused fatal disease in humans with mortality rates of 25%–90% depending on virus strain (3). In contrast, the Reston Ebola virus (REBOV) has never been identified to cause disease in humans. Several instances of humans seroconverting to REBOV have been documented; however, these were not associated with illness or death, suggesting that REBOV may be avirulent in humans (3).
REBOV was first identified during the investigation of fatal hemorrhagic fever involving cynomolgus macaques in a research facility in Reston, Virgina, which had been imported from the Philippines.

Macaques showed sudden onset of illness with signs of anorexia, cough, nasal exudates, swollen eyelids, and enlarged spleens and kidneys (3). Macaques were determined to be co-infected with REBOV and simian hemorrhagic fever virus (SHFV). Through testing REBOV was demonstrated to be less pathogenic than ZEBOV and SEBOV, with only 7 of 7 African green monkeys and 4 of 8 cynomolgus macaques surviving challenge (3). REBOV could not be recovered from survivors 20–600 days after challenge. Following this initial outbreak in Reston, several other cases of REBOV have occurred in both the United States and Italy, all attributed to animals imported from the Philippines and all from the same monkey breeding facility

(3).
From September 2007 to May 2008, disease outbreaks were reported on several pig farms in the Philippines. Pigs of all ages were affected, with a wide variety of clinical signs of disease including fever, coughing, and skin lesions (3). In addition to evidence of infection in swine, 141 people were also tested for the presence of antibodies to REBOV. Six individuals tested positive for immunoglobulin G (IgG), all of whom worked on pig farms or with swine products, suggesting the potential transmission from pigs to humans (3).
The isolation of REBOV from swine may indicate emergence of a filovirus in a new mammalian host. REBOV infection of swine raises important biosecurity concerns about the potential for disease emergence in humans and other livestock animals. In previous outbreaks of REBOV in monkey facilities, there have been no incidences of disease in humans despite several people seroconverting to the virus (3).
With an understanding of how REBOV came to be and how it affects both primates and now swine it is uncertain how humans will react to the Reston Virus. This is important because it could act like the other members in its family and mutate to become a lethal virus for humans. Also the patients that tested positive for REBOV could be reacting to this virus like a similar infection. Take tuberculosis for example some people who are infected have latent TB who have fought off an infection before it could turn into active TB. If someone has a compromised immune system TB can become active within hours and show symptoms. This is important because although these patients who have REBOV are not sick does not mean that REBOV cannot go to an active form and create similar symptoms as ZEBOV or SEBOV. Now seeing how REBOV came to be, we need to assess if this virus could be used as a gateway vaccine for the other strands in its family.
For starters a vaccine would save roughly 12,000 people a year from Ebola related deaths, and another 20,000 people from being infected (see table 1.). We know from the Reston Virus that to this day there has not been any illness related to the virus, so if it could be used as a vaccine, we in theory could immunize the human population of the Ebola Virus. Also if we could infect individuals with a non lethal Ebola virus, we have seen that human bodies have built antibodies to that specific virus for up to 12 years (4).

Countries with Former Widespread Transmission and Current, Established Control
Country Total Cases Laboratory-Confirmed Cases Total Deaths
Guinea2 3804 3351 2536
Sierra Leone 3 14124 8707 3956
Liberia4 10675 3160 4809
Total 28603 15217 11301

Previously Affected Countries5
Country Total Cases Laboratory-Confirmed Cases Total Deaths
Nigeria 20 19 8
Senegal 1 1 0
Spain 1 1 0
United States 4 4 1
Mali 8 7 6
United Kingdom 1 1 0
Italy 1 1 0
Total 36 34 15

Table 1: Ebola Total cases and affected countries

On the other hand there may be more cons to creating a vaccine using the Reston virus than would actually be beneficial for mankind. Creating a vaccine helps mankind survive but it does not eradicate the virus from the planet. Until we find the true host; bats, primates, or pigs and understand how to purge it from all species on earth, the Ebola virus will continue to grow and evolve into a more potent and virulent virus. From the very few individuals that were infected by the REBOV we do see there is no illness however that is but a very small percentage of the human population on earth. We do not understand the entire genome of REBOV and what if through testing we find out that the Reston Virus shows mortality rate for 1%. If we do the math and vaccinate just the population of where the Ebola virus is prevalent in Guinea and Nigeria ~200 million people then we would kill almost 2 million people which is roughly 150 times more than what Ebola kills per year. Also this is stating that different Ebola strands show antibody cross-reactivity. There is some self-reactivity to the different strands of Ebola with the IgM and IgG proteins of Ebola viruses however it shows that there is not enough cross reactivity for immunity (5).
We have seen patients who have been infected and survived an Ebola infection create enough antibodies for up to 12 years, however that was only for that specific strand of Ebola. So if they were to become infected by another strand of Ebola then they would become sick because the antibodies would not be able to fight off the other strand (4). This then tells us that although Reston may be have small traces of antibody reactivity you would need to supplement the virus to specifically attack one of the 4 deadly strands. This means you need to make 4 different vaccines for the Ebola virus. Last but not least the utter thought of using humans as test subjects by infecting them with either the reston virus, or using the few that survived the reston virus outbreak and infect them with another deadly strand of Ebola is hugely unethical. Using humans as a primary source of testing is a big no no, take for example the experiments at Tuskegee. Needless to say we cannot move forward with the Reston Virus until we learn more about it and its genome.
In the aspect of feasibility it would be near impossible because as of today there are only 6 individuals you have been documented with becoming infected with the Reston virus. This shows that very few people get the virus and we have yet to know in detail the damage Reston does to the human body. So other than those 6 individuals who you would need to willing volunteer and become re-infected with another strand of Ebola, you would have to find new volunteers to infect with multiple Ebola viruses . Also if things did not work out the likelihood of surviving the 4 strands of Ebola that effect humans is average 50% depending on the outbreak and can be anywhere from 25% to 90% fatality. So a large increase of death would come with this vaccination and it would be significantly higher than the amount of lives Ebola takes naturally per year. The only appropriate call is to join with World health organization to offer early treatment efforts. Through their work they have been able to prevent the death rate from 10% to 47% on this current outbreak.
Edward Jenner may have lucked out when finding a vaccine for small pox. Not knowing that cowpox and small pox were of the same family; he just heard that if you had cowpox you couldn’t get small pox and that unfortunately that does not hold true to all viruses. For example MMR vaccine is used for treatment of both measles and mumps that are part of the Paramyxoviridae family, but they do not cross protect. Also the MMR vaccine cannot protect from other Paramyxoviridae viruses like the Nipah Virus. As you can see each disease reacts in the human body differently and until we have enough research on how the Reston virus would affect the majority of the population it would be wiser to not do a vaccination at this point but work on improving early treatment methods of the Ebola viruses.