Understanding Ebola Virus Disease (EVD)

               Ebola is a filovirus that causes Ebola virus disease (EVD), the deadliest of a dozen hemorrhagic fever diseases. Mortality rates in previous Ebola epidemics ranged between sixty and ninety percent.   

            The natural reservoir of Ebola virus is the African fruit bat. Occasionally the virus passes from bats to other forest mammals that are killed for bush meat. Touching or skinning infected animals during hunting or food preparation and bat feces can transmit the virus to humans. Transmission is rare but frequent enough to cause periodic outbreaks that can spread. The 2014-2015 epidemic in West Africa began with patient zero – a two-year-old boy in Gueckedou, Guinea infected while playing in bat feces-infested soil below a hollow tree where a colony of bats nested. Perhaps he picked up a dead bat.

            With an incubation period of up to twenty-one days, in 2015 Ebola not only threatened Guinea, Liberia and Sierra Leone, potentially it could have spread globally. This highlights the urgency of reacting swiftly to epidemics when they arise and the need for concerted international efforts to bring them under control before they spread. This requires technical and financial support for all reasonable efforts by governments and NGOs to limit the virus to the countries already affected. It requires innovative thinking including designing small, rapid, simple clinical trials of existing antiviral drugs to determine what might be effective in counteracting this and other emerging viruses.

            Responders need to consider how Ebola causes hemorrhagic fever. If health authorities understand how the virus causes the disease, they should gain greater insight into how to treat it. Currently we do not have a 100% effective regimen. Even if there is no “cure”, based on our knowledge of viral genetics and immunology health workers should strive to improve the current inadequate standard of care. They should implement a more effective strategy to save many lives that are now lost. The desire for a perfect solution should not prevent using currently proven therapies, even if they do not achieve a 100% cure rate. National medical services must be ready to implement innovative solutions to reduce death and the spread of this disease each time it crosses the species barrier.

            One of the oldest maxims of war is, “Know your enemy.” To wage war against Ebola we need to understand how is it different from other viruses and how it causes hemorrhagic fever? The answer is simple. Ebola drains selenium from the body faster than any other known virus. As it drains selenium, blood clots form in the circulatory system due to the part selenium plays in clotting and in improving blood circulation. Simultaneously, hyperoxidation shoots blood vessels full of holes so they hemorrhage. The dilemma is how to treat a disease that causes both clotting and hemorrhaging.       

Ebola genes encode instructions to assemble selenium containing viral proteins - selenoproteins. Proteins are biology’s basic building blocks. Just like human cells, viruses are made of proteins. Most viruses include selenoproteins because selenium is a universally protective element. Incorporating selenium helps viruses evade immune defenses and may help them infect cells. Having selenium as part of their outer envelope makes them more attractive for cells to accept since cells need selenium. An envelope made of selenium provides a desirable “chocolate coating” to entice cells to incorporate viruses. Just as the immune system and human cells need selenium to protect and maintain our health, bacteria and viruses need to highjack selenium - our selenium – to help protect them from destruction by the immune system. The biggest selenium thief of all is the Ebola virus. Ebola primarily targets Selenium-rich immune cells and organs including the liver and kidneys.  

Scientist Will Taylor determined that just one of Ebola’s selenoproteins requires fifteen atoms of selenium. That may not sound like much. But when you consider that Ebola is one of the fastest replicating viruses, making billions of copies a day, a person’s reserves can be depleted rapidly. That is precisely what happens. Ebola drains the body of selenium. Since selenium is the cornerstone, most important element for the immune system, selenium depletion directly affects numerous immune processes. Selenium deficiency switches on several negative immune system pathways. This is what kills Ebola patients – the misdirected, out of control, over-response of their own immune system caused by acute selenium deficiency.

Slowly draining selenium from the body as HIV does causes AIDS. Ebola drains as much selenium in ten days as it takes HIV ten years to do. When total selenium in the body falls below 70% of normal, a person dies.

            How does Ebola cause massive blood clotting – known as disseminated intravascular coagulation (DIC)? It does this by rapidly draining selenium. Acute or chronic severe selenium deficiency causes blood clotting in all mammals because selenium affects platelet aggregation – one of its many effects. While severe selenium deficiency causes blood clotting, supplementing patients with selenium helps prevent dangerous clots from forming. It also reduces the disastrous hyper-peroxidative damage to blood vessels by basophils. How does Ebola cause hemorrhage?       

Wall sign in Monrovia, Liberia, 2014

            Ebola infection sets off a violent reaction in the immune system. Macrophage cells call up specialist immune chemical warfare cells called basophils. Filled with oxidizing chemical agents, basophils spray their toxic agents trying to kill off the viral intruders resulting in blood vessels sustaining severe collateral damage. Along with destroying some virus, the hyper-oxidative chemicals blow tiny holes in the membrane of blood vessels and organs causing hemorrhage. Chock full of holes, blood vessels and capillaries are severely damaged by this immune overreaction. Most patients eventually hemorrhage to death internally. The selenium-rich liver virtually melts.

Ironically however, some scientists claim the main problem in EVD may not be hemorrhaging since hemorrhaging is observed outwardly in only about three per cent of cases and occurs only at a late stage of EVD.

How can medical science overcome the immunological contradictions Ebola poses?

            Pharmaceutical companies have spent over ten years and billions of dollars trying to develop an effective treatment against Ebola with little to show. They have developed a somewhat effective vaccine but that will not help those who do get infected. National governments affected by Ebola have a choice. They can wait and hope drug companies eventually develop a drug against Ebola. But how effective will it be and how much will it cost? How many years will that take? Or is there is a faster, cheaper approach that may work? Health ministries should test other currently approved existing antivirals against Ebola. With minimal planning, small simple trials could start up each time Ebola reemerges from the biome.

            During the 2014-2015 Ebola outbreak in Liberia survival rates generally did not surpass 45% based on accepted best medical practices as provided by the Médecins Sans Frontières (MSF) - World Health Organization (WHO) treatment guidelines. The Liberian Ministry of Health sponsored a quick, informal clinical trial of selenium on forty patients at ELWA-2 Ebola treatment unit (ETU) in Monrovia. In that trial the survival rate increased from 44% to 68% almost immediately after adding 1.2mg of selenium AAC to the standard therapy regimen recommended in the MSG/WHO treatment guideline. 2.0mg of selenium should have been used. That optimal dose of 2.0mg should have increased survival to the 75% range. This is important since lower mortality rates attract infected patients to ETUs for treatment while higher death rates scare them away helping to spread the epidemic.

            During the 2014 crisis the BBC reported that at a rural Liberian ETU, Dr. Gobee Logan used the HIV reverse transcriptase inhibitor lamivudine (Heptavir 150mg) on eighteen Ebola patients. Sixteen survived - a survival rate of 89%. This self-reported trial was not independently monitored so it is anecdotal. But if Ebola is a retrovirus, such an outcome might be expected. However, this report could represent a fluke, or even be a hoax.

            With so many antiviral drugs currently available – thirty years ago there was only one – one must ask why governments do not act to test them against Ebola and Zika. Do they expect pharmaceutical companies to ride to the rescue with a magic bullet cure every time a novel emerging virus like Zika or Ebola appears? It is probable some currently available antiviral medications are more broad-spectrum than we realize. If lamivudine actually has an effect against EVD, then Truvada must be many times as potent. No one can say because it has not been tested. Selenium is certainly a broad-spectrum antiviral. It works by at least four different antiviral mechanisms against HIV and has a significant impact against many other viral diseases as well.  

            Early in the HIV epidemic the failure to test medications with known antiviral properties such as selenium and nuclear-factor kappa-binding inhibitors (NF-kBIs) like aspirin was a major mistake. That cost thousands even millions of lives. Ignoring this fact still does. Selenium has proved both effective in slowing down HIV becoming AIDS, increasing CD4 count, and reducing opportunistic infections. Aspirin (ASA)/Asacol (5-ASA) proved 75% as effective as AZT in lowering HIV viral load, and twice as effective as AZT in increasing CD4 count. It is too bad that those who died early in the HIV epidemic did not know this. Selenium and aspirin were ignored because there was no profit motive. Inferior, toxic, yet immensely profitable drugs like AZT were tested and promoted instead.          

            In 2014 I asked why authorities should not test every available antiviral drug against Ebola – and later Zika – to determine which ones may be effective. It is exceedingly odd that the WHO/MSF guidelines for treating Ebola include antibacterial drugs but no antivirals. That guideline is outdated and inadequate because it does not include selenium. The idea that a new drug needs to be developed for every new disease is a disastrous ideology for anyone who gets infected. New specific drugs are certainly needed, but to paraphrase George Orwell’s Animal Farm, New drugs are not always good - AZT a prime example - and old drugs are not always bad. There can be new uses for old drugs. We should be ready to test them when emergencies arise. It is not that difficult.

            Science can be counterintuitive. Using anti-coagulative drugs to try to resolve the disseminated intravascular coagulation, plus antioxidants to tame toxic blasts from basophiles might help tame Ebola. Maybe not. But thinking inside the box solves few scientific riddles. Selenium already has proved effective. It holds huge promise in treating Ebola and probably Zika as well. It is well established that higher levels of selenium reduce viral damage to DNA, the cause during pregnancy of most birth defects and many lifelong chronic diseases.

            What is the way forward for Africa’s response to emerging viruses? Should we expect the WHO and western drug companies to deliver magic bullet solutions years down the road for each new virus? Or should we rise to the challenge, think innovatively, and test currently available antivirals to determine what works and what does not?                         

References

Inhibitory Effect of Selenite and Other Antioxidants on Complement-Mediated Tissue Injury in Patients with         Epidemic Hemorrhagic Fever.  Jian-Cun Hou, Biological Trace Element Research 1997;56:125-130

Computational Genomic Analysis of Hemorrhagic Fever Viruses. Chandra Sekar Ramanthan and Ethan Will Taylor, Biological Trace Element Research 1997;56:93-105

Genomic Structures of Viral Agents in Relation to the Biosynthesis of Selenoproteins. Ethan Will Taylor et.al., Biological Trace Element Research,1997;56:63-91

Selenium and Viral Diseases: Facts and Hypotheses. Ethan Will Taylor, Journal of Orthomolecular Medicine, 1997;12:227-239

Aspirin Inhibits Both Lipid Peroxides and Thromboxane in Preeclamptic Placentas. Yuping Wang and Scott W. Walsh, Free Radical Biology & Medicine,1995;18:3:585-591                                                                                                                                                              revised 11/16/2022