Josh Pritchard

Name of the Disease: Ebola Virus Disease
Ebola, previously known as Ebola hemorrhagic fever, is a disease effecting human and non-human primates caused by the infection of one of the Ebola virus strains. The Ebola virus is one of the two filamentous viral members of the Filoviridae family of the order Mononegavirales. Filovirus virions are 14,000nm in length and a uniformly 80nm diameter. Virion are enveloped in a lipid membrane and contain one molecule of single-stranded negative-sense RNA. The Ebola virus genome consists of seven genes encoding for single structural proteins except the glycoprotein gene that encodes for two trans-membrane surface proteins glycoprotein 1 and glycoprotein 2.

Root cause of the Disease: New virion are spread by budding off of the host cell. Factors regarding replication of filoviruses remains to be understood. Ebola hemorrhagic fever is believed to be a zoonotic disease transmitted to humans through direct contact with infected living or dead animal bodily fluids. Although the reservoir host species remains unknown, a great deal of supporting evidence indicates that bats are likely to be the reservoir. The existence of Marburg and Ebola viruses in bats, as well as the frequency of outbreak near bat inhabited caves taken together indicate the bat as the reservoir. The other member of the Filovirdae is the Marburg virus which was first discovered in 1967 when a group of German and Yugoslavian scientists handled green monkey tissues and contracted hemorrhagic fever.The Ebola virus is represented in Figures 1. and Figures 2. below.

Poster «The Ebola Virus»
Poster «The Ebola Virus»

Figure 1. A computer generated image of the Ebola virus exhibiting virion structural an protenaceous features. Retrieved from:
http://visualscience.ru/en/projects/ebola/poster/


File:Ebola virus em.jpg
File:Ebola virus em.jpg

Figure 2. A transmission electron micrograph of Ebola virus virion. Retrieved From:
http://phil.cdc.gov/phil/details.asp?pid=1833

Affected cell types/tissues/organs/systems: The virus spreads after an incubation period of 2-21 days from the infected site to lymph nodes, liver, and spleen. Upon contact with the virus monocytes, macrophages, and dendritic cells are colonized. The infected monocytes and macrophages secrete soluble factors such as tissue factors and cytokines and chemokines. The release of tissue factor induces affects resulting in fibrin formation and eventual coagulation in the vascular system. Cytokines and chemokines cause the upregulation of pro-apoptotic genes causing lymphocyte apoptosis. Dendritic cells then become impaired and can no longer signal T cells dysregulating the host immune response system. Soluble factors released from target cells also contribute to the impairment of the vascular system leading to vascular leakage.The blood coagulation defects cause petechiae, ecchymoses, and uncontrolled bleeding. The spreading of the virus dysregulates the host immune response, causing coagulation abnormalities,vascular system obstruction and leakage, causing hypotension shock and multi-organ failure ultimately leading to succumbence. The pathogenesis in primates is dispalyed in Figure 3.


Pathology Flow Charts and Explanations

external image S1462399404008300sup007.gif
Figure 3. Ebola virus pathogenesis. Retrieved From:
https://microbewiki.kenyon.edu/index.php/Infection_Mechanism_of_Genus_Ebolavirus.

Historical Background: The Ebola virus was first discovered in 1976 with two virtually simultaneous outbreaks of two different subtypes. Ebola Sudan was contracted in a population in Sudan between July and November, while between August and November of the same year a second subtype, Ebola Zaire was contracted in a population in the Democratic Republic of Congo. In 1989 Ebola Reston was described after an introduction into quarantine facilities in Virginia and Pennsylvania through monkey importation from the Phillipines. Another Ebola strain was discovered in 1994 when a researcher performing an autopsy on an infected chimpanzee in the Tai Forest was exposed to Ebola Ivory Coast. The researcher was treated in Switzerland and survived, and is the only known case of the strain causing human infection. Alarmingly, yet another subtype of Ebola has emerged in December 2007 known as Ebola Bundibugyo, named after the district in Uganda of the first reported occurrence. Historically, Ebola has appeared infrequently yet infection frequency appears to be on the rise since 2000. With the exception of Ebola Reston found in the Philippines, the Ebola virus is endemic to the continent of Africa. It is likely that a similar host is acting as a reservoir in the Philippines. Due to remoteness of outbreaks, it is highly probable that historically, more outbreaks have occurred than are currently known.
A list of known Ebola cases is given in Table 1.


Known Cases and Outbreaks of Ebola Virus Disease, in Reverse Chronological Order:


Year(s)
Country
Ebola subtype
Reported number of human cases
Reported number (%) of deaths among cases
Situation
March 2014-Present
Multiple countries
Ebola virus
4655*
2431 (52%)*
Ongoing outbreak across multiple countries in West Africa. Number of patients is constantly evolving due to the ongoing investigation. 32
November 2012-January 2013
Uganda
Sudan virus
6*
3* (50%)
Outbreak occurred in the Luwero District. CDC assisted the Ministry of Health in the epidemiologic and diagnostic aspects of the outbreak. Testing of samples by CDC's Viral Special Pathogens Branch occurred at UVRI in Entebbe. 31
June-November 2012
Democratic Republic of the Congo
Bundibugyo virus
36*
13* (36.1%)
Outbreak occurred in DRC’s Province Orientale. Laboratory support was provided through CDC and the Public Health Agency of Canada (PHAC)’s field laboratory in Isiro, and through the CDC/UVRI lab in Uganda. The outbreak in DRC has no epidemiologic link to the near contemporaneous Ebola outbreak in the Kibaale district of Uganda. 31
June-October 2012
Uganda
Sudan virus
11*
4* (36.4%)
Outbreak occurred in the Kibaale District of Uganda. Laboratory tests of blood samples were conducted by the UVRI and the U.S. Centers for Disease Control and Prevention (CDC). 31
May 2011
Uganda
Sudan virus
1
1 (100%)
The Ugandan Ministry of Health informed the public that a patient with suspected Ebola Hemorrhagic fever died on May 6, 2011 in the Luwero district, Uganda. The quick diagnosis from a blood sample of Ebola virus was provided by the new CDC Viral Hemorrhagic Fever laboratory installed at the Uganda Viral Research Institute (UVRI). 30
December 2008-February 2009
Democratic Republic of the Congo
Ebola virus
32
15 (47%)
Outbreak occurred in the Mweka and luebo health zones of the Province of Kasai Occidental. 29
November 2008
Philippines
Reston virus
6 (asymptomatic)
0
First known occurrence of Ebola-Reston in pigs. Strain closely similar to earlier strains. Six workers from the pig farm and slaughterhouse developed antibodies but did not become sick. 27 28
December 2007-January 2008
Uganda
Bundibugyo virus
149
37 (25%)
Outbreak occurred in Bundibugyo District in western Uganda. First reported occurance of a new strain. 26
2007
Democratic Republic of Congo
Ebola virus
264
187 (71%)
Outbreak occurred in Kasai Occidental Province. The outbreak was declared over November 20. Last confirmed case on October 4 and last death on October 10. 24 25
2004
Russia
Ebola virus
1
1 (100%)
Laboratory contamination. 23
2004
Sudan (South Sudan)
Sudan virus
17
7 (41%)
Outbreak occurred in Yambio county of southern Sudan. This outbreak was concurrent with an outbreak of measles in the same area, and several suspected EHF cases were later reclassified as measeles cases. 22
November-December 2003
Republic of Congo
Ebola virus
35
29 (83%)
Outbreak occured in Mbomo and Mbandza villages located in Mbomo distric, Cuvette Ouest Département. 21
December 2002-April 2003
Republic of Congo
Ebola virus
143
128 (89%)
Outbreak occurred in the districts of Mbomo and Kéllé in Cuvette Ouest Département. 20
October 2001-March 2002
Republic of Congo
Ebola virus
57
43 (75%)
Outbreak occurred over the border of Gabon and the Republic of the Congo. This was the first time that Ebola hemorrhagic fever was reported in the Republic of the Congo. 19
October 2001-March 2002
Gabon
Ebola virus
65
53 (82%)
Outbreak occured over the border of Gabon and the Republic of the Congo. 19
2000-2001
Uganda
Sudan virus
425
224 (53%)
Occurred in Gulu, Masindi, and Mbarara districts of Uganda. The three most important risks associated with Ebola virus infection were attending funerals of Ebola hemorrhagic fever case-patients, having contact with case-patients in one's family, and providing medical care to Ebola case-patients without using adequate personal protective measures. 18
1996
Russia
Ebola virus
1
1 (100%)
Laboratory contamination 17
1996
Philippines
Reston virus
0
0
Ebola-Reston virus was identified in a mokey export facility in the Philippines. No human infections were identified. 16
1996
USA
Reston virus
0
0
Ebola-Reston virus was introduced into a quarantine facility in Texas by monkeys imported from the Philippines. No human infections were identified. 15
1996
South Africa
Ebola virus
2
1 (50%)
A medical professional traveled from Gabon to Johannesburg, South Africa, after having treated Ebola virus-infected patients and thus having been exposed to the virus. He was hospitalized, and a nurse who took care of him became infected and died. 14
1996-1997 (July-January)
Gabon
Ebola virus
60
45 (74%)
Occurred in Booué area with transport of patients to Libreville. Index case-patient was a hunter who lived in a forest camp. Disease was spread by close contact with infected persons. A dead chimpanzee found in the forest at the time was determined to be infected. 11
1996 (January-April)
Gabon
Ebola virus
37
21 (57%)
Occured in Mayibout area. A chimpanzee found dead in the forest was eaten by people hunting for food. Nineteen people who were involved in the butchery of the animal became ill; other cases occured in family members. 11
1995
Democratic Republic of the Congo (formerly Zaire)
Ebola virus
315
250 (81%)
Occured in Kikwit and surrounding area. Traced to index case-patient who worked in forest adjoining the city. Epidemic spread through families and hospitals. 13
1994
Côte d'Ivoire (Ivory Coast)
Taï Forest virus
1
0
Scientist became ill after conducting an autopsy on a wild chimpanzee in the Tai Forest. The patient was treated in Switzerland. 12
1994
Gabon
Ebola virus
52
31 (60%)
Occured in Mékouka and other gold-mining camps deep in the rain forest. Initially thought to be yellow fever; identified as Ebola hemorrhagic fever in 1995. 11
1992
Italy
Reston virus
0
0
Ebola-Reston virus was introduced into quarantine facilities in Sienna by monkeys imported from the same export facility in the Philippines that was involved in the episodes in the United States. No humans were infected. 10
1989-1990
Philippines
Reston virus
3 (asymptomatic)
0
High mortality among cynomolgus macaques in a primate facility responsible for exporting animals in the USA. 8
Three workers in the animal facility developed antibodies but did not get sick. 9
1990
USA
Reston virus
4 (asymptomatic)
0
Ebola-Reston virus was introduced once again into quarantine facilities in Virginia, and Texas by monkeys imported from the Philippines. Four humans developed antibodies but did not get sick. 7
1989
USA
Reston virus
0
0
Ebola-Reston virus was introduced into quarantine facilities in Virginia and Pennsylvania by monkeys imported from the Philippines. 6
1979
Sudan (South Sudan)
Sudan virus
34
22 (65%)
Occured in Nzara, Maridi. Recurrent outbreak at the same site as the 1976 Sudan epidemic. 5
1977
Zaire
Ebola virus
1
1 (100%)
Noted retrospectively in the village of Tandala. 4
1976
England
Sudan virus
1
0
Laboratory infection by accidental stick of contaminated needle. 3
1976
Sudan (South Sudan)
Sudan virus
284
151 (53%)
Occurred in Nzara, Maridi and the surrounding area. Disease was spread mainly through close personal contact within hospitals. Many medical care personnel were infected. 2
1976
Zaire (Democratic Republic of the Congo - DRC)
Ebola virus
318
280 (88%)
Occurred in Yambuku and surrounding area. Disease was spread by close personal contact and by use of contaminated needles and syringes in hospitals/clinics. This outbreak was the first recognition of the disease. 1

*Numbers reflect laboratory confirmed cases only.

(UPDATED) Table 1. A reported case count and location list for Ebola hemorrhagic fever. Retrieved From:
http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html.

Common Symptoms: The Ebola virus may manifest several severe symptoms including high fever, headaches, joint and muscle pain, sore throat, weakness, diarrhea, vomiting, abdominal pain, and unexplained hemorrhage. These symptoms can occur anywhere from two to twenty-one days after exposure to the virus. Progression of Ebola hemorrhagic fever may cause multi-organ failure and shock, resulting in death. Due to the potential use as a biological weapon, increasing frequency, and alarmingly high mortality rates of the Ebola infected populations, (up to of 90% in cases of Ebola Zaire) much investigative attention has been focused on the ecology, pathology, treatment, and potential vaccination of the Ebola virus.

Standard Treatments: Individual cases of Ebola should be cared for using barrier nursing procedures, and isolating patients. Barrier layers such as gloves and protective clothing are an effective means of preventing additional spread of the virus.The currently implemented treatment strategies have been based around treating symptoms and providing supportive measures. The regulation of a patients fluids and electrolytes should be monitored, integrating proper administration of intravenous treatment with sterilized utensils. Possible antibiotic administration may be necessary to fight off secondary infections that may cause complications. Upon patient organ failure, treatment should be specific to the organ that failed. For example if kidneys failed, dialysis may be necessary.

Vaccination Potential: Most of the research conducted so far involving potential vaccinations and treatments have revolved around the E. Zaire virus in order to develop a functional vaccine. Some potential seems to exist for the use of RNA interference based vaccination strategies. Experimental vaccines are underway, but have yet to be tested for safety and effectiveness.

Current Research: Current research shows that the most recent Ebola outbreak began in Guniea, West Africa in February 2014 and spread to Liberia in March. It then spread to Sierra Leone in May, followed by Nigeria in July. Genetic similarity throughout the samples indicate that there was a single transmission from a natural reservior, followed by human-to-human transmission. Research suggests that the spread of the virus into Sierra Leone occurred due to two genetically distinct viruses being introduced at the same time (http://www.sciencemag.org/content/345/6202/1369.full).
There are no treatments or methods of prevention for the Ebola virus, but the FDA has performed research on the use of Selective Estrogen Receptor Modulators in order to inhibit the Ebola virus infection. Research shows that among the strongest in inhibiting the Ebola virus are: clomiphene, toremifene, tamoxifen, and raloxifene. Clomiphene and toremifene inhibit the Ebola virus in vitro, in vivo, and also inhibits EBOV entry at a step after internalization (http://stm.sciencemag.org/content/scitransmed/5/190/190ra79.full.html).
There has also been researched performed on the use of melatonin in the treatment of those who are already infected with the Ebola virus. There are similarities between the Ebola virus and septic shock. Melatonin has previously been shown to effectively treat sepsis in previous experiments. The purpose of the use of melatonin is to slow down the body's immuno-inflammatory response that occurs when infected with the Ebola virus. This can suppress the risk of DIC and hemmorhage, in order to provide additional survival time for those infected with Ebola (http://www.pbraunmd.org/pbraunmd/melatonin_and_ebola_jpi12186.pdf).



References:
Arpit, S., Shraddha, A. J., Verma, A. P. S. K., Kumar, A. (2012) Immuno-Infrmatic speculation and computational modeling of novel MHC-IILiterature Cited
human leukocyte antigenic alleles to elicit vaccine for Ebola virus. Vaccines and Vaccination, 3 (4), 1-3

Gire, S,Goba, A., Anderson, K., Sealfon, R., & Park, D. (2014). "Genomic surveillance elucidates Ebola Virus origin and transmission during the 2014 outbreak." Journal of Science. Volume 345, Issue 6202. Pages 1369-1372.

Johansen, L., Brannen, J., & Delos, S. (2013). "FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection." Journal of Science Translational Medicine. Volume 5, Issue 90. Pages 179-190.

Tan, D., Reiter, R.,& Manchester, L. (2014). "Ebola virus disease: Potential use of melatonin as a treatment." Journal of Cellular and Structural Biology. Volume, Issue, and Pages not available from PDF.