Disease Research Assignment- By Chelsea Landwehr 2014

What is the cause of Ebola HF?

Ebola Hemorrhagic fever (EHF) or Ebola virus disease (EVD) is one of numerous viral hemorrhagic fevers. It is a severe, often fatal disease in humans and non-human primates (for example; monkeys, gorillas and chimpanzees). Ebola HF is caused by infection with a virus of the family, Filoviridae, genus Ebolavirus. The first Ebolavirus species was discovered in 1976, after two simultaneous outbreaks occurred in Nzara, Sudan and in Yambuky, Democratic Republic of Congo. The latter was found in a village near the Ebola River after which the disease takes its name.

There are five identified subspecies of Ebolavirus, four of which, have caused disease in humans: Ebola virus (Zaire Ebolavirus), Sudan virus (Sudan Ebolavirus), Taï Forest virus (Taï Forest Ebolavirus, formerly Côte d’Ivoire Ebolavirus) and Bundibugyo virus (Bundibugyo Ebolavirus). The fifth virus; Reston virus (Reston Ebolavirus), has only caused disease in non-human primates.

The natural reservoir host of ebolaviruses is unknown. Researchers, however, on the basis of available evidence and knowledge similar viruses, believe that the virus is ‘zoonotic’ or animal-borne with bats and non-human primates being the most likely reservoir. Four of the five subtypes of Ebolavirus occur in an animal host native to Africa. It is unknown if the cause of Ebola HF has any correlation to the environmental conditions of the infected area and if their are any vectors which carry the disease.1 - 10 aerosolized organisms of Ebolavirus are sufficient to cause infection in humans.

How is Ebola HF SPread?

Because the natural reservoir of Ebolavirus has not yet been identified, researchers are only able to hypothesize that Ebola HF is transmitted to humans from animals. Humans contract Ebola if they are in close contact with the blood, secretions, organs and other bodily fluids of infected animals. Animals that have been found carrying Ebola include various monkey species, chimpanzees, gorillas, baboons and duikers (all primates). The virus was also recently been discovered in two species of rodents and one species of shrew, raising the possibility that these animals may be intermediary hosts (they harbour the virus for a short period before passing it to different hosts).

Ebola HF spreads throughout communities via direct contact through broken skin or mucous membranes with the body fluids of infected people or indirect contact with the environments contaminated with such body fluids (for example a syringe). The viruses which cause Ebola HF are usually passed through family and friends, as they are in close contact with secretions when caring for ill patients and can also be transmitted if mourners have direct contact with the deceased’s body at a burial ceremony. During outbreaks of Ebola HF, health care settings like clinics and hospitals can spread the disease quickly if hospital staff are not wearing protective equipment like gloves, masks and  gowns appropriately or if instruments such as syringes are not cleaned and sterilized or disposed of properly.

Ebola HF is communicable as long as blood, secretions, organs, or semen contain the virus. Ebola HF has been isolated from semen 61 days after the onset of illness, and transmission through semen can still occur 7 weeks after clinical recovery. The virus can survive in liquid or dried material for a number of days and its infectivity is found to be stable at room temperature or at 4°C for several days. It is unknown if the spread of Ebola HF is impacted by environmental conditions.

Is Ebola HF a Widespread Disease or Endemic to Particular locations in the World?

Four of the five subtypes of Ebolavirus have been found to occur in an animal host native to Africa which means that African countries and communities are the most vulnerable and highly susceptible to the disease. Ebola HF occurs mainly in areas surrounding rainforests in central Africa with the exception of Reston virus which occurs in the Phillipines. Ebola HF is a highly contagious disease, however its ability to spread efficiently enough to cause a pandemic is limited, because transmission of these viruses requires close contact with the infected patient, and the patient only has a short time before death or serious illness. In small African communities the disease can be easily spread, however if a tourist or animal were to travel or be exported/imported internationally with the disease, the short time between the person becoming infectious and the onset of symptoms allows medical professionals to quickly quarantine the source, and prevent transmission of the pathogen elsewhere minimising the death and case toll.

According to Figure 1, countries reported with Ebola Virus Disease outbreaks include Guinea, Liberia, Ivory Coast, Philippines, Gabon and Democratic Republic of Congo among others. Furthermore, countries who have reported Ebola Reston outbreaks in imported monkeys from the Philippines include USA and Italy.

Figure 1.2 describes the ongoing distribution of Ebola HF in West Africa as of 29 June 2014. The map isolates ongoing Ebola transmission in parts of Sierra Leone, Guinea and Liberia.


Is Ebola HF a Rare or Common Disease?

Ebola HF is rare but deadly disease. The likelihood of contracting the disease if you are not within a place where there has been a recent outbreak or in contact with a person or animal with Ebola HF are extremely low. Outbreaks of Ebola HF have occurred sparingly throughout time as they strike with a high death toll (90%) but only do so not regularly.

Figure 2 shows the outbreaks of Ebola virus since its discovery in 1976.c Select the graph for an in depth analysis and timeline of all reported Ebola HF cases since 1976.

Figure 2

This year (2014) there has been an Ebola HF epidemic across West Africa. According to the World Health Organisation Africa who published an article on the 25th July 2014, “The World Health Organisation (WHO) continues to monitor the evolution of the Ebola virus disease (EVD) outbreak in Sierra Leone, Liberia, and Guinea. The Ebola epidemic trend remains precarious, with community and health-facility transmissions of infection still taking place”. As of 31 July 2014, the death toll has reached 729 with 1,300 cases across Guinea, Sierra Leone and Liberia. It has been recorded as the worst outbreak in West Africa and the first time that three countries have been involved as well as the first time that there has been outbreaks in capital cities.

Below is a news report published on 31 July 2014 about the Ebola HF epidemic and how the World Health Organization has announced a plan to help those hardest hit by the outbreak.

What are the symptoms of Ebola HF?

The Ebola virions enter the host cells through endocytosis (the transport of solid matter or  liquid into a cell by means of a coated vacuole or vesicle) and replication occurs in the cytoplasm. Upon infection, the virus targets the host's blood coagulative and immune defence system and leads to severe immunosuppression (the inhibition of the normal immune response because of a disease). Early signs of infection are non-specific and flu-like, and may include sudden onset of;

  • Fever
  • Asthenia (lack of strength; weakness)
  • Diarrhoea
  • Headach
  • Myalgia (pain in muscles)
  • Arthralgia (pain in joints)
  • Vomiting
  • Abdominal pains
  • Loss of Appetite

Less common early symptoms can include;

  • Conjunctival injection
  • Sore throat
  • Rashes
  • Bleeding

Upon the onset of the infection several illnesses may occur;

  • Shock
  • Cerebral Oedema (when the brain's water content rises, causing the pressure to rise in the skull)
  • Coagulation disorders
  • Secondary bacterial infections

Approximately 4-5 days after this, haemorrhaging (bleeding) symptoms begin:

  • Haemorrhagic conjunctivitis (bleeding from conjunctiva (in eye)
  • Pharyngitis
  • Bleeding gums
  • Oral/lip ulceration
  • Haematemesis (vomiting of blood)
  • Melena (the production of dark sticky faeces containing partly digested blood, as a result of internal bleeding or the swallowing of blood)
  • Haematuria (blood in urine)
  • Epistaxis (nose bleeding)
  • Vaginal bleeding
  • Hepatocellular damage (damaged hepatocyte cells in the liver)
  • Marrow depression [such as thrombocytopenia (platelet deficiency) and leucopenia (reduction of WBC in blood)]
  • Serum transaminase elevation (elevation of liver enzymes)
  • Proteinuria (the presence of abnormal quantities of protein in the urine, which may indicate damage to the kidneys)

Persons that are terminally ill typically present with obtundation (altered level of consciousness), anuria (failure of the kidneys to produce urine), shock, tachypnea (abnormally rapid breathing), normothermia (normal body temperature), arthralgia, and ocular diseases. Haemorrhagic diathesis (excessive bleeding) is often accompanied by hepatic (liver) damage and renal (kidney) failure, central nervous system involvement, and terminal shock with multi-organ failure. Pregnant women with Ebola HF will usually abort their fetuses and experience copious bleeding.

What is the Incubation period for Ebola HF?

The incubation period for Ebola HF is between 2 and 21 days with 4-9 days being most common interval.

What Treatments are used for Ebola HF?

When diagnosing Ebola HF, other diseases such as malaria, typhoid fever, cholera, plague, relapsing fever, meningitis, hepatitis and other viral haemorrhagic fevers can me made to be ruled out. Ebola HF can be diagnosed definitively in a laboratory through several types of tests:

  • antibody-capture enzyme-linked immunosorbent assay (ELISA)
  • antigen detection tests
  • serum neutralization test
  • reverse transcriptase polymerase chain reaction (RT-PCR) assay
  • electron microscopy
  • virus isolation by cell culture.

Samples from patients are an extreme biohazard risk; testing should be conducted under maximum biological containment conditions.

There is no effective antiviral treatment for Ebola HF nor is there an available licensed vaccine. Instead, treatment is supportive, and is directed at

  • balancing the patient’s fluids and electrolytes
  • maintaining their oxygen status and blood pressure
  • treating them for any complicating infections

Developing a treatment for Ebola HF is challenging since the disease is difficult to diagnose clinically in the early stages of infection and because early symptoms such as headache and fever are nonspecific to ebolaviruses and may be initially misdiagnosed. Any patients suspected of having Ebola HF should be isolated, and caregivers should wear protective garments (refer below).

Experimental treatments have been tested and proven effective in animal models but are not available for clinical use by humans.

The drug susceptibility of Ebola HF is unknown, however S-adenosylhomocysteine hydrolase inhibitors have been found to have complete mortality protection in mice infected with a lethal dose of Ebolavirus. Ebolavirus is also susceptible to various disinfectants. Ebolavirus are moderately thermolabile (readily destroyed or deactivated by heat). Ebolavirus can undergo inactivation by 30- 60 minutes of heat treatment, 5 minutes of boiling, gamma radiation (1.2 x106 rads to 1.27 x106 rads) and/or UV radiation.

On June 13 2012, encouraging findings were published in the ‘Science Translational Medicine’ Journal. According to the Disease Daily in an article published on 31 June 2012;

“Researchers from the National Microbiology Laboratory in Winnipeg, Manitoba identified a number of antibodies that corresponded to proteins on the shell of the Ebola virus. They combined the antibodies into a specific cocktail and administered it to four macaques within 24 hours of infection. All four macaques survived. When the cocktail was administered within 48 hours of infection, two of four macaques survived.”

This article presented promising findings but whether any further investigations into this experiment have been conducted, are unknown.

Refer to: http://healthmap.org/site/diseasedaily/article/did...for further detail.

In article posted by Vox on 3 August 2014, it is revealed that over the past few years, a Canadian Pharmaceutical company called ‘Tekmira’ have been working on an Ebola treatment (not vaccine), called TKM-Ebola. It has been noted as amongst the most advanced attempts at a drug that could protect against and treat Ebola HF but has recently encountered a setback by the Food and Drug Administration. The Defence department awarded the project a $140 million contract in 2010 after the vaccine proved effective in treating non-human primates (chimps). The government’s decision to award the contract has stemmed from a movement in trying to prevent bioterrorist attacks, where ebolavirus could be used as the weapon. The FDA halted the phase one trials at the beginning of July this year, on request the Tekmira provide further informations about how their drug works, before the company begins giving trial subjects larger doses which is done in phase one experiments to test how much the human body can handle. The article states; “Still, both of these treatments are early in the research and development project. After phase one testing comes phases two and three, which typically involve running trials on hundreds and then thousands of subjects, respectively.”

Refer to http://www.vox.com/2014/8/3/5962381/ebola-outbreak...for further detail.

In relation to the current Ebola outbreak in West Africa, two American aid workers- Dr. Kent Brantly and Ms. Nancy Writebol have contracted the disease in Liberia and Dr. Brantly has been transported to a special isolation facility in Atlanta, meanwhile Ms. Writebol is expected to arrive in the coming days. According to their respected charities, both workers were given supportive care from the onset of them being diagnosed and Dr. Brantly has received a blood transfusion from a 14-year-old boy who survived Ebola under his care, in the hope that antibodies would help him fight the virus. Both Dr. Brantly and Ms. Writebol received an experimental serum (Ms. Writebol's was different), though their respective charities didn't specify what the treatment was.

Refer to http://online.wsj.com/articles/cdc-chief-seeks-to-... for full details.

What is the Prognosis of an Ebola Infected Patient With and Without Treatment?

As a result of there being no specific treatment for Ebola HF, and treatment is only limited to maintaining a person’s body functions (for example, hydration and blood pressure levels), the prognosis for a patient with Ebola HF is poor. Fatality rates for this disease range between 50 and 100%, with most dying of dehydration caused by gastric problems. Those who do survive are likely to experience complications like:

  • Weakness
  • Fatigue
  • Headaches
  • Hair Loss
  • Hepatitis
  • Sensory changes
  • Inflammation of organs (for example, the testicles and the eyes)

It is unclear why some patients will survive and others won’t from the disease, however it is most likely as a result of the patients who have died, having a poor immune response to the virus.

Whilst the current outbreak of Ebola HF is occurring in Africa, of the two American aid workers who have been infected with the virus, Dr. Kent Brantly has received a blood transfusion from a patient who survived Ebola HF and Ms. Writebol has received an unidentified experimental serum. According to a Fox News article posted on 4 August 2014; “though there are conflicting reports, and no one is saying exactly what the experimental serum is, its likely that both of the reported methods contained antibodies to the Ebola virus, said Dr. William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center in Nashville, Tennessee. Delivering antibodies to a patient could slow the virus's replication, and give the immune system time to recover”.

With an Ebola HF outbreak currently spreading across Africa, scientist could be lead to new possibilities and further develop their findings from previous experiments (refer to previous question). As technology advances and time passes, we will soon be able learn whether either experimental treatments on the two Americans currently being isolated in Emory University Hospital in Atlanta will work- this possibly leading to scientist developing a treatment and possibly a vaccine for this deadly virus by further advancing their findings or being deterred by the results and following down a new path.

Refer to http://www.foxnews.com/health/2014/08/04/ebola-ser...for all information on the experimental serums being used on Dr Brantly and Ms. Writebol and the speculations surrounding them. Also refer to the information provided on antibody based methods of vaccination and the difficulties associated with  gauging a treatment's effectiveness.


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