Trial and Error with Ebola

The Ebola virus has engulfed three countries in West Africa frightening societies and wrecking economies. This epidemic and those that are certain to come more often in the future threaten the entire world. While Ebola is not contagious – it is not spread through the air – it is highly infectious. Even touching the body of someone who has died from Ebola can infect a person. Between 20% and 50% of all cases have been traced to contact with the bodies of deceased Ebola victims, often at funeral ceremonies. If medicines can be found that reduce the mortality rate in Ebola virus disease (EVD) this will have a knock-on effect reducing postmortem transmissions and significantly slow the spread of the epidemic. It will also encourage people to seek medical attention at Ebola treatment units (ETUs) sooner. That will reduce transmissions too.

After Ebola struck, international health organizations eventually descended en mass to fight the virus with the best weapons they knew – mostly rehydration with electrolytes (sports drinks), antibiotics and drugs that reduce diarrhea and vomiting. Like a Greek chorus the CDC, NIH, WHO and MSF chanted, “There is no effective treatment and there is no cure.” Unfortunately for the infected, those organizations had not done their homework, or perhaps the scientific facts simply did not fit their medical paradigm.

As an independent Aids researcher since 1989, years ago I read about an outbreak of Marburg virus – Ebola’s closest viral cousin – in Angola that German doctors treated with selenium tablets. They reduced an expected almost 100% mortality rate to only 40%. Likewise, Chinese doctors treated an epidemic hemorrhagic fever virus outbreak with selenium supplements and saw a 60% reduction in deaths. With this information in mind in early August I took 60 bottles of selenium tablets to Liberia. After a trial was quickly approved at the highest level of the ministry of health, I presented them with sixty bottles in order to conduct an informal clinical trial. Dr Jerry Brown used most of that to treat forty-seven Ebola patients at ELWA Hospital Ebola treatment unit, just outside Monrovia. The survival rate of the forty-seven patients who received the supplement increased to 68% compared to the previous average survival at ELWA of 44%. That 54.4% improvement in survival was achieved even though the 1.2mg per day dose of selenium used on the patients was only 60% of the 2.0mg daily I had recommended based on all the scientific evidence. When asked why they had used a lower dose than planned the doctor said the nurses had seen how strongly it was working so they insisted that all the patients receive the selenium. That reduced the amount available for each patient in the trial.     

Despite the outstanding success of this quick, informal clinical trial against Ebola the Greek chorus chimed, “We cannot use selenium against Ebola – there are no peer reviewed medical journal articles of selenium against Ebola.” So disregarding this successful test of the selenium against Ebola-Zaire, MSF refused to use it in their Ebola treatment units (ETUs). At a major protocol meeting at the Corina Hotel the WHO and a consortium of US health agencies tried to shut down further testing or use of selenium in the current epidemic. What was their motivation in trying to suppress the first treatment that has proved truly effective in treating Ebola?

Science and medicine have come a long way since Aristotle and Hippocrates. Today, trial and error in the form of controlled clinical trials remains the cornerstone of scientific medicine. But who decides what gets tested and what gets published? An old adage suggests the Golden Rule decides – those with the gold decide. Today that is the pharmaceutical industry.

How curious it is that in the 21^st Century physicians treat an aggressively infectious virus that potentially threatens the entire world primarily with a sports drink, saline IV drips and antibiotics. Especially since antibiotics have zero effect against the virus itself. Is this some kind of remedial medicine that ignores published science? Why would doctors not use or at least try one of an array of antiviral drugs instead of antibiotics? If this was a newly discovered bacteria instead of a virus physicians would reach to their shelf of dozens of different antibacterial drugs to see which one might work. When the culprit is a virus, why does the medical community totally ignore twenty or more established antiviral drugs that already have been proven safe and effective against other viruses? Viruses do share many characteristics. Instead of following this rational approach the medical community flounders about trying to find any other way except testing long-approved, affordable antiviral drugs to treat Ebola. This defies logic. Basically IV-ing sports drinks? Sure they help with rehydration, but this is not a football game. And Ebola is not cholera.  

Although antibiotic drugs were developed and rapidly expanded from the 1940s through the 1980s, the first officially recognized antiviral drug was not discovered until 1983 – acyclovir against herpes. In truth, the very first antiviral drug was developed in 1898 - aspirin. For over one hundred years the little white tablet once called the miracle drug has been used to treat symptoms of viral diseases like colds and influenza, even though doctors did not understand its underlying mechanism of action. Acetyl-salacylic acid (aspirin or ASA) inhibits a human protein called nuclear-factor kappa-binding (NF-kB). “NF-kappaB” plays a critical role both in cellular reproduction and maintenance functions and the immune system; in inflammation, fever and numerous other critical immunological processes. It also plays a key role in stimulating viral replication. NF-kappaB is so potent it has to be very carefully controlled within the cell because it packs such a powerful punch when the cell needs to create new proteins, as when cells divide. Cells must keep NF-kB carefully locked away in a cellular closet in the cytoplasm when not needed, least protein production get out of control. However viruses like HIV and Ebola have the ability to unlock this cellular closet and flood the nucleus of the cell with NF-kappaB in order to make the cell produce an avalanche of the viral proteins needed to assemble new viruses. When viruses release the NF-kB protein it becomes the fuel that feeds the viral replication machinery. Thus anything like aspirin, asacol, ibuprofen or selenium that inhibits NF-kB will reduce viral replication and diminish the impact of viral disease and illness. However since NF-kB was not discovered until 1986, for almost a century scientists could not accurately explain how aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) exerted their multiple salutatory effects on the immune system.   

The Aids crisis of the 1980s unleashed billions of dollars of viral research money and even more billions of profits for the pharmaceutical industry. Today there are more than twenty approved, widely used, well characterized antiviral drugs to treat herpes, HIV and hepatitis. Like antibacterial drugs, some antivirals are broad spectrum and work to treat many viral diseases. Certainly selenium and NSAID drugs are broad spectrum because they inhibit NF-kB, the primary stimulant to viral replication in the nucleus of infected cells. Because most viruses including HIV and Ebola genetically encode selenium proteins, selenium supplements also help replace the selenium viruses drain from our cells and organs. They help repair the damage viruses do in causing the loss of the body’s selenium reserves that are so essential to health.

 It is no surprise that the personnel of international medical organizations working on the frontline of the Ebola crisis reel in horror at the very mention of aspirin as a possible treatment for Ebola. It would be sheer folly and highly dangerous to use an anti-coagulative drug on a hemorrhagic disease. Oddly enough, the name Ebola “hemorhaggic” fever is a misnomer, even an oxymoron. Based on the latest research published in the New England Journal of Medicine only about one percent of Ebola-Zaire patients demonstrate symptoms of hemorrhaging, and those symptoms appear very late in the disease, just before death when the benefits of treatment already have been exhausted. However almost all symptoms of EVD reflect the rapid loss of selenium that the virus causes.

That loss of selenium causes massive blood clotting referred to as disseminated intravascular coagulation (DIC). Selenium supplementation, aspirin and NSAIDs all help to correct that. As strong antioxidants, selenium, aspirin and other NSAID drugs also help prevent the oxidative damage to blood vessels that causes the late stage haemorrhaging observed in a tiny minority of cases. Regardless, aspirin and NSAIDs would be quite beneficial in the early and mid-stages of EVD. The aspirin analogue drug asacol (5-ASA), which doesn’t prevent platelet aggregation, could be used in the later phase of EVD if necessary in consideration of the 1% who do suffer haemorrhaging. As NF-kB inhibitors, aspirin, asacol, NSAIDs and selenium all reduce viral replication, reduce pain and fever, and reduce the hyperoxidation that damages blood vessels and leads to haemorrhage in the first place. Their use would be superior to the current accepted protocol that utilizes the pain killer acetaminophen (Panadol, Tylenol) that does not inhibit NF-kappaB. That analgesic may damage the liver, a particularly dangerous side effect in EVD which itself attacks the liver.  

In late September 2014, the BBC reported that Liberian Dr Gabriel Logan who supervises a small rural ETU in the interior of Liberia had tried a first generation HIV anti-retroviral drug (ARV) called lamivudine against Ebola. Dr Logan claimed remarkable success since thirteen of fifteen patients in his ETU survived. Even though a doctor made this anecdotal report it should be viewed cautiously since no one has duplicated it yet. However a high official in the ministry of health confirmed to me personally that those patients had all tested positive for Ebola. Still, a documented anecdote of this nature should be followed up as quickly as possible since it would be cheap, quick and easy to verify this result in a small pilot study. Surprisingly, this news report was enough to incite an official from the World Health Organization (WHO) in Geneva to phone Liberia to demand to know where that ETU physician had gotten lamivudine. Is it really such a surprise that a doctor in Africa might have an HIV drug that has been on the market for twenty-five years on his clinic pharmacy shelf? What must have frightened the WHO is that someone was imaginative enough to try an approved antiviral drug against Ebola. While Anthony Fauci, Director of the National Institute of Allergy and Infectious Disease at the National Institutes of Health publicly gives Dr Logan a thumbs up for his research finding lamivudine helpful against Ebola in a television interview, behind the scenes NIH staffers in Liberia try to shut down any testing or use of lamivudine on Ebola patients. This is the very definition of hypocrisy. 

How dare doctors use their ingenuity and personal initiative! Are African doctors completely out of control? On the contrary, this dramatically points to the immediate need to systematically test all approved antiviral drugs against Ebola as soon as possible. After I saw that BBC report I immediately fired off a letter to the health authorities in Monrovia suggesting they test the much more advanced ARV, Truvada, against Ebola. Truvada is approximately ten times as effective against HIV as lamivudine. It should be equally more potent against Ebola. It is a combination of three powerful antiviral drugs including lamivudine. Of all the ARVs used to treat HIV, Truvada is the one most likely to be effective against Ebola. Nine months into this epidemic we have still not adopted the most sensible approach to discovering effective treatments against Ebola. That would be lining up and testing all the various existing and experimental antiviral drugs and potential immune boosting medications, just the editorial in The Economist magazine dated 18 October 2014 proposed.

The above episode also raises the question of what role the WHO plays in promoting and protecting world health. If the WHO hears that some particular medication is working in an epidemic situation should not they call for more of that effective medicine to be used, or at least try to make sure it is promptly tested to confirm its efficacy? In this case they appeared to be acting as guardians of the health of the pharmaceutical industry instead of the health of the sick and poor people of the world.

Nevertheless, with half a dozen different classes of antiviral drugs that have proved safe and effective against HIV, herpes and hepatitis; should not some of them be tested against Ebola? Not testing them threatens the health systems of the countries involved. More than three hundred and forty health workers have already died, and not having effective therapies increases the chance that this virus will spread globally. The CDC, NIH, WHO and MSF chorus still chimes, “There is no treatment and there is no cure for Ebola.” How do they know if they refuse to even try the antivirals that currently are sitting on the shelf? This choral chant echoes both Animal Farm by George Orwell and too many Greek dramas that end in tragedySo what solution do the World Health Organization and American health authorities propose?

These international health organizations subscribe to the same questionable ideology. “Existing drugs are no good. A new disease, requires brand new specific medications to be developed.” They refuse to consider what drugs already have been proven safe, effective and affordable against other viruses and they hasten to build barriers to their testing and use. Not only do they disregard the decades of science and the billions of dollars already spent to develop existing drugs, they also disregard what has been used successfully to reduce the mortality rate in other hemorrhagic fever virus epidemics in Angola and China. Since this virus is “new” and this virus is different, they suggest we need new, different medications that will eventually be sold to governments at premium prices. It may take years to develop these new drugs. Even if they have to turn all Ebola patients into Guinea pigs and Ebola spreads around the world while they conduct new drug development, they are determined to find that unique drug to treat this unique disease, come what may. Could any ideology be so wrong at the onset of an epic health emergency?

 Yes novel, untested, unproven, potentially dangerous drugs should be tested against EVD. Maybe the “silver bullet” drug against Ebola will be found among them. But these experimental pharmaceuticals should only be tested after drugs that already have been proven safe for human consumption and effective against other viral diseases have been tested. Even these proven antivirals should only be tested on top of a standard of care that should include two milligrams of sodium selenite (selenium) per day. If 1.2 milligrams of selenium has proven to reduce the mortality rate by 43.6%, then certainly using the correct dosage of 2.0 mg per day should reduce the mortality rate by at least 50% and bring the EVD survival rate to between 70-75%. Then it is just a matter of making marginal improvements on that success by testing and finding additional drugs that can provide an additive effect. Gradually improving a combination of therapies is the pathway to success in treating this disease. This is how researchers gradually tamed HIV disease. However it will always be difficult to achieve much higher than a 90% survival rate with Ebola since some patients arrive  at the ETU on death’s door and cannot be saved no matter how successful the intervention. This approach does not stand in the way of new drug development. It just prevents turning patients suffering with Ebola into mere Guinea pigs in pursuit of that worthy goal, or just letting them die with no effective treatment at all when effective therapies are currently available to use. That would be the most immoral decision of all.  The rapid testing and use of current antiviral drugs will slow down the spread of this disease and reduce deaths.

So let the comparative trials begin! The current use of “supportive care” plus selenium increases the survival rate of EVD to the range of 70-75%. Now line up all the other antiviral medications on top of that enhanced standard of care and see what can raise survival rates to 80%, 85% and eventually 90%. Will the NSAIDs aspirin, asacol, and ibuprofen add 5% or 10% to the survival rate? Will Truvada add another 10% or 15%? No one knows until these drugs are tested. We do not need the gold standard of double-blind placebo-controlled trials. Doctors can use across the board comparative trials to quickly determine what works and what does not. In this situation using placebos is synonymous with condemning patients to death.

So, trial and error is already working. The doctors at the ELWA hospital ETU tried selenium and it worked. There was no error. Now authorities need to quickly test everything in the antiviral armamentarium and see what else works. Stop the dithering. Stop the obfuscation and obstruction. End the inertia. Eliminate the “it’s a new disease, therefore we need a new drug” mentality. West Africans should not be the world’s Guinea pigs, and the world should not be endangered by a corrupt paradigm that mitigates against quickly finding an effective combination therapy for Ebola. Failing to do so endangers the world.