Will Ebola ever be eradicated

Mubarak Abdi

Abstract

The Ebola virus is very well-known, especially having been popularized during the 2014 West African epidemic. It has claimed thousands of lives throughout West Africa, as well as ruined many countries’ economies, agriculture, society and overall stability Since its first appearance in 1976, the Ebola Virus has appeared and disappeared, causing over 20 serious outbreaks that have had a great impact. Billions of dollars have been spent on healthcare, food, and research to stop the virus, only for it to come back and cause more turmoil.  The question scientists across the world ask the question that the victims of this virus ask, and the question I am going to explore in this article: Will the Ebola Virus ever be eradicated?

Section 1: What is Ebola?

Ebola is a viral hemorrhagic fever that can cause illness in humans. The genus Ebolavirus belongs to the family Filoviridae, a group of viruses that cause hemorrhagic fevers, high fevers,and bleeding. Ebola has two sibling viruses, Marburg and Cuevavirus, which are also part of the Filoviridae. Ebolavirus contains several species, Zaire, Sudan, Tai Forest, Bundibugyo, Reston and Bombali, Zaire, Sudan, and Tai. 

Figure 1 – Colourised transmission electron micrograph of the Ebola Virus taken by Forest and Bundibugyo all cause some type of illness to humans, Zaire being the most deadly having caused the most deaths[1].

The Zaire strain is most just referred to as Ebola Virus or EBOV.  Reston affects other mammals like monkeys and pigs, whilst Bombali is a recent strain found in only bats[2]. The virus is transmitted through direct contact with any bodily fluids from an infected person or animal, including saliva, vomit, urine and sweat. Ebola can also survive as fluids on dry surfaces. Once transmitted, the symptoms develop after 2-21 days[3]. People can only spread the virus after they develop symptoms; however, some symptoms aren’t as noticeable, so there still need to be cautious. Symptoms begin as ‘dry’ symptoms which mimic those of influenza such as fevers, aches and fatigue. Then they progress into ‘wet’ symptoms: diarrhoea and vomiting. As the virus continues to harm the body, more symptoms occur like rashes, red eyes, haemorrhaging and internal bleeding. This internal bleeding becomes external as victims begin vomiting and urinating blood. If proper treatment is not received, it will lead to death through organ failure, shock from fluid loss, or blood loss. The virus is caused by a a worm-like structure about 80nm in diameter and can be up to 1000nm long[4]. It usually appears in a long, filamentous form, but can be circular or irregularly shaped. On the surface, it has several glycoproteins projecting at 7-10 nm. These are used to attach to its target host cells, allowing the virus to insert its genetic material. It then has an outer envelope and an inner envelope that allow the movement of the genetic material. Next, there is a small matrix containing a few proteins such as VP (virion protein) 24 and 40. Finally, there is a nucleocapsid that contains RNA (ribonucleic acid) and several proteins. The genetic material is a linear, single-stranded, negative-sense RNA that is 18–19 kb in size. It contains almost 19,000 base pairs. The proteins are called NP (nucleoprotein), VP35, VP30, and L (the enzyme RNA polymerase). NP is used to encapsulate the viral genome and L is used to replicate the RNA genome when transferred into the host cell. ^[5]

The virus is so deadly because it attacks the immune system, the body’s main defense. It usually attacks monocytes, macrophages, and dendritic cells, which are all types of white blood cells. The monocytes and macrophages help destroy pathogens through phagocytosis, swallowing the entire pathogen and breaking it down from within using enzymes. Dendritic cells place the antigens, substances that induce an immune response found on the surface of pathogens, on their surface to activate T-Cells. This is the first line of defence, so when Ebola attacks these cells, it entirely removes the immune system’s attack.

When the macrophages try engulfing the virus, they become infected and release proteins that create blood clots in the blood vessels. They also damage the vessels’ linings using nitric oxide and inflammatory proteins. This creates haemorrhaging which is observed as bleeding from the eyes and nose. The damaged blood vessels lower blood pressure and eventually cause many organ failures that lead to death.^[6]

The virus kills other cells by attaching to them using the glycoproteins on its surface. Once attached, it breaks down the barriers and inserts its genetic material and protein inside. Using the cell’s resources and organelles, it replicates itself several times, until the cell bursts open and releases all the viral particles. As the cell is killed in the process the cycle continues with new cells.

The virus spreads through the initial infection site to regional lymph nodes^[7]. These are nodes in the body that contain a lot of white blood cells and therefore are very susceptible to Ebola. The virus then enters the lymphatic system, a system connecting all lymph nodes in the body. There it can enter the bloodstream, and then travel to other parts of the body; the liver and the adrenal gland are its main targets. This eventually leads to the same symptoms as with the macrophages, causing internal bleeding, fluid loss and organ failures,  which all lead to death.

Section 2: History of Ebola

The Ebola virus (Zaire strain) was first heard of in August 1976. A Belgian nun fell ill in Yambuku, Zaire (Democratic Republic of Congo). A sample of her blood was sent off to Belgium to be investigated. They found a worm-like virus inside, which had similar properties to the Marburg virus. They later found out the nun had died, and the people who attended her funeral had also become infected and died. The Belgium scientist investigating this virus, Peter Piol, personally went to Zaire to investigate what was going on. He also found that the person washing a deceased victim of the virus would also become infected. So, Peter and his team tried to help the village using quarantining and cleanliness. By the end of the outbreak in November 1976, there were 318 cases and 280 deaths. The virus was named after a nearby river, Ebola. It was later believed that it was transmitted from a bat, making Ebola a zoonotic virus, meaning it was transmitted from an animal^[8][9]

In June of the same year, the first outbreak of the Sudan strain occurred. On 27th June, in Nzara, Sudan, a shopkeeper of a cotton factory fell ill and died two weeks later. Slowly, co-workers and families of the shopkeeper began getting ill and dying from the virus. There were 48 cases and 27 deaths traced back to the original infection site. Once infected people began travelling outside of Nzara, the virus spread to different cities: Maridi, Tembura and Juba. By the last reported case on the 25th of November, there were a total of 284 cases, with 151 deaths. Another outbreak occurred in the same initial infection area, from the 31st of July to the 6th of October 1979, there were 34 cases and 22 deaths in Nzara, Sudan.^[10]

After these two initial outbreaks, Ebola made a small name for itself amongst the scientific community. The two strains acted very similarly, both transmitted through the direct contact of an infected person and the unsanitary conditions in Sudan and the DRC, it spread very fast. The fatality rate was quite different though 88% for the Zaire strain while the Sudan strain had 53%, so it was clear which one was the more deadly species.

In 1989, a different strain of Ebola was found. The Reston strain was found in Cynomolgus monkeys also known as crab-eating macaques. The monkeys were shipped from the Philippines and arrived in Reston, Virginia where the virus was discovered. The virus is not harmful to humans, although humans can carry the virus and spread it. This was the first strain found in non-humans and it was found in pigs later in 2008, so it is known to be not exclusive to monkeys.^[11]

Figure 2 – Map of Africa, red countries are countries that have had Ebola Outbreaks up until 2010. [31]

In 1995, the second Ebola outbreak in the Democratic Republic of Congo occurred in Kiewit and then spread to neighbouring villages. It was able to be traced back to a forest worker, who is thought to have transmitted the virus from an animal, presumably a bat. The outbreak lasted from May to July, causing 315 cases and 254 deaths. In Gabon, there were 3 notable outbreaks from  1994 to 1997, accumulating almost 100 deaths. ^[12]

On the 8th of October 2000, the first case of the Sudan strain outside of Sudan was reported in the Gulu district of Uganda. The virus spread to other districts including Masindi and Mbarara. The main cause of the spread was due to funeral attendance, where the families would meet the dead bodies. By the end of the outbreak, there were 425 cases and 224 dead, giving it the highest case rate of all outbreaks up until the 2014 outbreak. Throughout the 2000s, there were several outbreaks across West Africa. The majority were small, only causing a couple of deaths except for a couple who had deaths in the hundreds. The main countries affected were previous victims, including Uganda, DRC, Sudan and Gabon, and now the Republic of Congo.^[13

On 26th December 2013, a two-year-old boy named Emile Ouamouno from Meliandou in the Guéckédou Prefecture, Guinea got sick after playing near a hollow tree that was inhabited by infected bats. He later died, starting the spread of the 2014 West African epidemic, the largest Ebola outbreak to date. The spread was slow at first; it wasn’t until 23rd March 2014 that it was publicly announced as an outbreak by the World Health Organization (WHO) at 49 cases and 29 deaths. This small number quickly changed as the virus began to rapidly spread. ^[14]

On 30th March, the first Ebola case was recorded in Lofa County in Liberia. This was the first case recorded outside of Guinea, so the spread was increasing. Then Sierra Leone recorded their first Ebola case on 24th May from a doctor who was treating patients across the border of Guinea. On 23 July 2014, Nigeria followed as they claimed their first Ebola case as well, and by 8th August, the WHO was forced to declare the outbreak as a “public health emergency of international concern” as a total of 1,711 cases and 932 deaths had been reported.

On September 30th, 2014, the first human-human transmission of the virus outside of Africa occurred in Madrid, Spain. A nurse had just treated two Ebola patients, Manuel Garcia Viejo and Miguel Pujaris, who had come back from Liberia and Sierra Leone. She became the first person to contract the virus outside of Africa. There had been other cases in the UK and USA, but those were from people who had contracted the virus in Africa and were treated in the respective countries. She survived and no more cases occurred in Spain. ^[15]

By the end of 2014, 20,171 cases and 7,890 deaths were reported. Several cases have been reported in Senegal, Mali and Nigeria but nothing major, along with one or two cases in Spain, UK and USA. By the end of 2015, 28,601 cases and 11,300 deaths were reported. One new case in Italy was reported in May 2015. However, this was similar to the cases in the UK and USA as the patient was a health worker who worked in Africa but was treated in Italy. In 2015, only 8000 new cases were reported, showing that the spread of the virus slowed, demonstrating the effectiveness of the treatment.

Figure 3 – Map of the distribution of the Ebola virus epidemic in Guinea, Liberia, and Sierra Leone. [32]

In 2016, the epidemic had completely slowed down and Sierra Leone declared the end of the epidemic on March 17, Guinea following on June 1. Finally, Liberia had its last reported case on 29 April but had to wait 42 days, which is two incubation periods, to make sure that was the last case. It ended on June 9th, which officially declared the end of the 2014 West African epidemic after 28,646 cases and 11,323 deaths.

On 25 July 2018, in Mangina, North Kivu in the Democratic Republic of Congo, the burial of a 65-year-old woman caused the spread of yet another Ebola outbreak in the DRC. This outbreak occurred almost 2000 km away from the previous outbreak, which killed 33 people. It is possible there was a connection between the two. On 1 August, the Ministry of Health declared the start of the outbreak and on 25 June 2020, it ended with 3,470 cases and 2,280 deaths.^[16]

On 7th February 2021, another outbreak was declared in Butembo, North Kivu Province. The first case was found in a 42-year-old woman who was submitted to the health centre for hemorrhagic fever. There have been 12 cases and 6 deaths. It was declared over on the 3rd of May, making it the 12th outbreak in the DRC.^[17] The only ongoing outbreak is in Guinea. On 14th February 2021, Guinea’s health minister declared an outbreak in the N’Zérékoré prefecture. The first reports of Ebola were after the burial of a nurse in Gouécké on the 1st of February. As of April 7th, there have been 23 confirmed cases and 12 deaths.^[18]

Section 3: Vaccines

Since Ebola directly attacks the immune system first, it is hard for the body to fight against the virus. If the white blood cells are killed before the T-cells are activated, then the T-cells cannot divide into helper T-cells through mitosis or cell division. These helper T-cells go on to stimulate the white blood cells to work faster, activating cytotoxic cells which kill the pathogens by making holes in their membrane, letting water inside, which bursts the cell and activate B-cells, which then divide into plasma cells that produce antibodies. The antibodies are specific proteins that bind to the antigens on the pathogens, rendering them useless and making it easy for the white blood cells to kill them. Ebola is very hard for the body to handle alone, which prompted the need for a vaccine to be developed.

Figure 4 – Image showing the filling of a needle with the vaccine. [33]

On December 19th, 2019, The United States Food and Drug Administration (FDA), approved the first Ebola Vaccine, rVSV-ZEBOV, also known as Ervebo. The Ervebo vaccine was made by the NLM (National Microbiology Laboratory), a branch of the Public Health Agency of Canada. They partnered with the BPSC (Bio Protection Systems Corp), the subsidiary owned by NewLink Genetics Corp, in the 2000s. The vaccine is manufactured by Merck. It is only for adults older than 18 and the vaccine is given as a single 1-mL dose injection into the muscle around the shoulder or thigh. The vaccine should be kept at −80°C to −60°C but can be at 2°C–8°C for two weeks or 25°C for two hours. It must be protected from light, so it is stored in a cupboard or anywhere that shades it from light.^[19]

The work on the vaccine started back in 1980, after the first Ebola outbreak, as scientists examined Ebola genetic material to try and figure out a vaccine. They took the backbone of a vesicular stomatitis virus (VSV) and inserted the proteins from the virus with one from the Ebola virus.^[20] The Ebola virus proteins were separated from the rest of the virus by centrifugation, a method of separating particles from a solution by spinning it in a centrifuge tube. Since the proteins have different masses from each other, they can be separated by spinning at a certain speed, rotation, and density.

The VSV backbone was first cloned into pATX-MCS. This is a modified version of the backbone, so the backbone would accept deletion and addition of genes. Then,“ Mlu I” and “Avr II” restriction enzymes were used to delete the VSV-G gene. Restriction enzymes are enzymes taken from bacteria that can delete genes, so they were used to manually delete the genes safely, as other methods would destroy other parts of the DNA. Then the same enzymes insert the Ebola Glycoprotein to replace the gene.^[21] So, the VSV backbone now has the Ebola virus attachment protein on its surface, which will be used to convince the body that they are being attacked by the virus without causing any harm. This will cause the body to react and create specific antibodies for that glycoprotein. After the false attack, the body stores this information as memory cells. The body can become immune to the virus because when the real attack occurs, the body recognizes the glycoprotein and will divide the antibodies rapidly, fast enough to kill the virus before it can critically damage the body.

Then, the restriction enzymes Xho I and Nhe I were used to open a new insertion in the genome, inserting one other Ebola gene: NP, VP40, or VP24. This is so the VSV is more likely to be recognised as the Ebola virus by the body. Different vaccines were made for different strains e.g., rVSV-CI-GP is used for CIEBOV. This is because different strains have different glycoproteins, so multiple vaccines will be needed for each glycoprotein. This leads to pATX-VSVDG-XN2, the molecule used as the vaccine host. ^[21]

Throughout the 2000s, testing was done to make sure the vaccine worked. For animal testing, mice and guinea pigs were used. 1×104 plaque-forming units of the vaccine were given to mice and 2×105 to guinea pigs. After the original dose, they would receive another after 21 days. Then the animals were given 1000 median lethal doses of MA-ZEBOV (Mice Adapted version of the Zaire Ebola Virus) for mice, GPA-ZEBOV (Guinea Pig Adapted version of the Zaire Ebola Virus) for guinea pigs. The most effective vaccines in mice were rVSV-CI-GP (22/22), rVSV-R-GP (20/20) and rVSV-Z Mayinga-GP (20/20). In guinea pigs, rVSV-Z-GP (8/8) was the most effective. So, these results were used to finalize which vaccines will be forwarded for more testing.^[21]

In October 2014, the vaccine was approved to enter several different types of official testing.^[22] To test for efficiency, two groups of participants, who were exposed to the virus, were given the vaccine, immediately after exposure and 21 days after. They found the Ervebo vaccine had 100% efficiency. To test the effect of the vaccine on pregnancy, two groups of pregnant women were observed, vaccinated and non-vaccinated. They found 45% of vaccinated women lost their pregnancy vs. 33% of non-vaccinated women. During these trials, they decided on the 1ml dose. Finally, on December 19th, 2019, the Ervebo vaccine was approved by the FDA for use.^[23]

On February 14th, 2020 the vaccine was approved by DRC, Burundi, Ghana and Zambia. More than 290,000 people in the DRC were vaccinated by August of the same year.^[24] The vaccine was rolled out efficiently and was being used well. Even in the outbreaks of 2021, the vaccine was used to slow the spread of the virus down, which worked very well. The goal was to get as many people vaccinated as possible to form herd immunity. If the majority are vaccinated, it makes a virus less likely to be transmitted to any unvaccinated being.

Section 4: World Reaction to Ebola

The main organization that was at the forefront of all the outbreak responses was the World Health Organization (WHO). They are a specialised agency working for the United Nations since 1948. This organization has helped control many viruses, especially Ebola. Since the first outbreak in 1976, it has helped create plans and roadmaps for countries to follow to overcome outbreak after outbreak. The organization raised more than $450 million for the 2014 epidemic, gathering 60 donors, the majority of which were from countries^[25].

On 19 September 2014, the UN established the first-ever emergency health mission to battle Ebola.^[26] This helped tremendously with funding and gathering health workers to beat Ebola. In 2015, it was closed as the Ebola cases dropped enough for it to not be seen as a threat anymore. Their World Food Programme also helped raise money to be spent solely on food. The United Nations Children’s Fund or UNICEF is another subsidy of the UN. Other ways they helped were through arranging meetings between UN members to discuss Ebola and also spreading correct information so that the fear of Ebola would be reduced.

Other organizations that helped included the African Development Bank, which donated $223 million for everything Ebola-related including, food shelter, treatment and research.^[27] The African Union sent out over 2000 health workers to help treat Ebola patients.^[28] The World Bank Group donated $230 million to Sierra Leone, Guinea and Liberia during the 2014 epidemic.^[29]

So overall, it can be established that organizations across the world have contributed a lot to helping underdeveloped African countries with fighting Ebola. However, it could always have been more as some countries like the DRC are still struggling economically due to how much research and resources were spent on Ebola. The response from the rest of the world was quick and very efficient, as the many outbreaks, especially the 2014 epidemic, could have turned out worse.

Section 5: Conclusion – Will Ebola ever become eradicated?

In conclusion, the answer to “Will Ebola ever become eradicated?” is simply yes. It has only been a few years since the Ervebo vaccine was released. There hasn’t been too much time for many people to become vaccinated. Smallpox is a very famous virus that has been eradicated. The first case of smallpox could be dated back to ancient Egypt, and the vaccine was only made in 1796. Then it took almost 200 years for the virus to become eradicated in 1980. Although this is a long time, this deadly virus that everyone thought would never go, eventually was eradicated. So, the same can be said for Ebola.

Viruses like influenza are hard to combat as there are new strains every year; however, Ebola has only 6 known strains, 2 of which do not harm humans. Furthermore, the same Zaire strain is the cause of almost all outbreaks, so Ebola is not shown to mutate. The most recent outbreaks ended in just a few months, with the help of the vaccine. As more people become vaccinated, there is less chance of the virus spreading. If this keeps up, likely, the virus will only stay a threat for a few more decades.

Ebola is a deadly virus, with limited treatment that can kill it in a matter of weeks. Through perseverance in science and health departments, there is a high chance that Ebola will become eradicated.

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