Monday, 4 August 2014

Why is Ebola virus so deadly?

In December 2013 Guinea saw the first death from an outbreak of Ebola virus. This, still on going, Ebola epidemic is now the largest in recorded history. I’ve therefore put together this blog post that will tell you about the virus species and what can make it so deadly.

The first recorded outbreaks of Ebola virus were in 1976 in Zaire and Sudan, with the name being derived from the Ebola River in Zaire (now the Democratic Republic of Congo). These outbreaks were caused by two different species of the Ebola virus family, with the Zaire strain being more deadly. In Sudan, there were a total of 151 deaths from 284 confirmed cases, whereas Zaire had 280 deaths from 318 cases.

The Ebola virus structure - false colouring of an electron microscope image
Zaire is still the most deadly of the five currently defined Ebola species. However, its case fatality rate is often misconstrued in my opinion. There have been a total of 14 ‘outbreaks’ of Zaire Ebola virus with case fatality ranging from 44-100%. But two of those ‘outbreaks’ have been of a single person, who died, giving two 100% case fatality ‘outbreaks.’ If you remove those two, the average case fatality from all recorded Zaire Ebola virus outbreaks is 75%. It’s still very high, but not the often-reported 90%.

With that said, Ebola viruses are undoubtedly extremely deadly. For a point of comparison, the worst influenza outbreak, 1918 Spanish Flu, had a case fatality rate of around 2.5%. But what is it that can make Ebola virus deadly?

Like all other viruses, Ebola virus must enter and infect cells. Different viruses have different cells they infect. For example, influenza preferentially infects lung cells, while HIV preferentially infects white blood cells. Ebola targets a lot of cells, but it is thought the earliest to be infected are white blood cells. Similarly to HIV, Ebola infection kills these cells that constitute our immune system. However, while HIV takes years, Ebola can kill in a matter of weeks.

As Ebola viruses infect cells of the immune system, our bodies try to fight back by releasing chemicals known as cytokines. Cytokines attract immune cells to the sites of infection and help to activate the immune response – they are essential to combating infection. Cytokine release causes the general symptoms associated with viral infections such as headaches, fever, nausea and inflammation. In addition to infection triggering release of cytokines, cell death is also a major cause. With Ebola killing cells and the immune response, there is a huge release of cytokines.

While the cytokine response is essential to fighting infection, it is a response balanced on a knife-edge. Cytokines act through a positive feedback mechanism; infected cells release cytokines to activate immune cells, these activated cells then release more cytokines and so on. If this isn’t regulated, there can be an uncontrolled release of cytokines throughout the body, known as a cytokine storm. Ebola infection can cause this uncontrolled release of cytokines resulting in a massively exaggerated response and extreme fever and vomiting, to name just two symptoms.

So Ebola viruses can cause cytokine storm, while also, somewhat paradoxically, decimating the immune system. But it doesn’t stop there; Ebola can also damage and infect endothelial cells that line the blood vessels through our bodies, producing holes in these vessels and allowing fluids to escape. Combine this with the dilation of blood vessels caused by the inflammatory response from cytokines and you have a situation where Ebola virus causes huge fluid loss and drop in blood pressure (potentially resulting in shock).

Leaky blood vessels, combined with the cytokine-induced fever, give the symptoms Ebola is best known for, ‘haemorrhagic fever’. The haemorrhaging causes massive blood blisters around the body and release of blood from the gums and into the eyes (causing them to turn red). This is just the striking exterior; there is also internal bleeding to exacerbate the situation.

With all the fluids lost due to leaking of blood vessels through the body, combined with further loss from vomiting and diarrhoea, hydration becomes one of the biggest issues for patients infected with Ebola. Indeed, rehydration therapy is one of the few treatments available to patients with Ebola, but needs to be given early, before the late stages of haemorrhaging and fever.

With all of these different symptoms combined, hopefully it’s clear why Ebola virus can cause such a deadly infection.

Ebola virus is spread through close contact with bodily fluids from an infected person (or animal); hence the vomiting and diarrhoea are highly advantageous to the virus. This tends to put close family members and medical staff at the highest risk of contracting the virus. However, there can also be sexual spread for weeks after a patient has apparently recovered from infection.

The current West Africa outbreak is suspected to have killed 826 people from 1440 cases (as of 4th August 2014 – this site is regularly updated). This gives the current outbreak of the Zaire species of Ebola a case fatality rate of around 57%, much lower than the average for this species. The reasons for why some outbreaks of the same Ebola species are so deadly compared to others are unclear, but I’d speculate one major factor is the work of health care personnel. Limiting spread by isolation of patients, giving rapid rehydration therapy and tracking spread as much as possible are unboundedly having a huge impact in controlling this outbreak. In the past, outbreaks had occurred in areas of huge diplomatic unrest and poverty making the necessary responses much harder. The current outbreak is in areas of huge poverty, but the international response is undoubtedly having a major impact on limiting deaths. 
A health care worked in an isolation unit

While Ebola virus is unquestionably a dangerous and deadly virus, the need for close contact spread would suggest to me that it will never really take off as a pandemic. I would speculate that developed parts of the world would see nowhere near as much death from the virus, even if an outbreak were to occur, because of being able to limit spread with isolation measures and the speed with which this could be done in richer parts of the world. Hopefully with the continued work of health care professionals in West Africa, this current outbreak will soon be curtailed. 

Clearly my hope that the Ebola outbreak would "soon be curtailed" hasn't come to fruition. It is now a little over a year since the first death from this Ebola outbreak and the death toll has reached 8,414 (15th Jan 2015) from 21,261 cases (13,427 being laboratory confirmed). However, it has been reported today that the number of new cases may be declining. Hopefully this trend will continue and 2015 will see the end of this Ebola epidemic. 

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