written by reader Ebola, Vaccination, Flu, Viral Transmission: The Links and the Kinks

Doc Gumshoe's take on Ebola

By Michael Jorrin, "Doc Gumshoe", November 17, 2014

[ed. note: Michael Jorrin, who we like to call “Doc Gumshoe”, is a longtime medical writer who shares his thoughts with us a couple times a month. He is not a doctor, and his articles are not typically focused on investment ideas]

This post will neither spook you nor cheer you up. In adding Doc Gumshoe’s voice to the multitudes who have been speaking and writing (some with passion and eloquence and wisdom, some hysterically and focusing attention on themselves) I hope to avoid redundancy and approach this exceedingly difficult and painful subject with a degree of calm and, yes, my habitual skepticism.

Here are some assertions, which I put forward with considerable confidence.

  • One, there will be nothing even remotely resembling an Ebola epidemic in the US or any other developed country.
  • Two, the course of the epidemic in West Africa is uncertain. But even if the current Ebola epidemic diminishes, the virus is here to stay, resulting in future outbreaks and epidemics.
  • Three, combating Ebola in Africa must rely more on containment than on treatment.

What’s the basis for my confidence in making these assertions?

First, regarding the unlikelihood of an epidemic in developed countries: to date, in the developed world, a total of three patients with Ebola have died – the priest, who died in Spain, a Sudanese health-care worker who died in a German hospital, and the visitor from Liberia, who died in Dallas after the management of his infection was disgracefully botched. In contrast, several aid workers who have returned from Africa to their home countries infected with Ebola have recovered, and both of the nurses who were infected by the African visitor have recovered, as well as the nurse in Spain who was infected by the priest. And as I write this, all the possible Ebola contacts in Texas have been cleared. The American physician, Dr Craig Spencer, who returned from Africa, was diagnosed with Ebola in New York City (after having spent several days unconcernedly going about town) was released from Bellevue Hospital on November 11th. It is certainly likely that as health-care workers return to their home countries, some of them will be infected with Ebola. It is also likely that there may be some transmission of Ebola from those infected individuals. But in developed nations all real or suspected cases of Ebola will be managed with the utmost care (the Dallas lesson having been taken to heart), and treated with supportive therapies plus whatever active treatment options may be available. The disease will not spread.

Second, regarding the future of Ebola beyond the current epidemic in West Africa: it may wane, or it may spread at an accelerating rate. Previous Ebola outbreaks in various regions in Africa have remitted more or less spontaneously, and it is within the limits of possibility that the current West African epidemic might do the same. When I say “spontaneously,” I mean that the previous outbreaks ended due to a combination of circumstances that included individual patient care, public health measures, and also, perhaps, changes in the activity of the virus. By that vague phrase – what does “the activity of the virus” mean? – I am pointing to a number of possibilities that can affect the course of an epidemic. Here are some: the disease initially affects the most susceptible persons, and kills a great number of them; the remaining population, which is either physically or genetically more resistant, survives, and develops Ebola antibodies. Here’s another: the virus itself changes, becoming less virulent and/or less transmissible. Viruses do this; we’ll discuss the “why” later.

However – and this is the real point of my assertion – even if the current Ebola epidemic diminishes, the virus will persist in animal reservoirs, and as long as this is the case, there is likely to be transmission to humans. And considering conditions in Africa, epidemics are likely.

Third, regarding combating Ebola in Africa through containment: providing humane treatment to persons infected with Ebola is an ethical absolute, but it won’t do much to prevent the spread of the epidemic. In fact, unless treatment is conducted according to standards that are attained only at the most advanced medical facilities, the possibility exists that efforts at treatment may even contribute to the spread of the disease. I will say more about containment, but consider the following scenario:

A possible, but dreadful, sequence of events

As we very well know, Ebola is a terrifying disease, and people all over the world are, by now, frightened of it. In parts of West Africa, we have learned that people initially mistrusted health-care workers, and were reluctant to seek medical care in hospitals, because they thought that most people who went to hospitals didn‘t come out alive. That may have changed; people are indeed seeking medical care when they suspect they might have Ebola.

But what happens then? At the moment, in Africa, tests for the Ebola virus must be conducted in laboratories (of which there are only a few) and this requires transporting blood samples for long distances. In rural areas, this can take a full day or longer. The blood tests currently being used take several hours, and the labs are swamped, so getting results can take several days.

In the meantime, the person with suspected Ebola is kept in facilities with other persons who also may have Ebola. For a person who did not have Ebola at the time of presentation to the medical facility, the risk of being infected with Ebola during this period (while waiting for test results) is considerable.

So, the test results come back, and person A is found to be Ebola-free. However, the blood sample was taken several days ago, and in the meantime person A has become infected by contact with person B, who does indeed have Ebola.

Person A is then discharged from the hospital, or, if he or she continues to have suspicious symptoms, moved to another ward for observation or treatment of whatever non-Ebola disease may be the culprit. But by now person A does have Ebola, and may transmit Ebola to other people in this non-Ebola ward, including to health-care workers.

A similar scenario would unfold in the case of a false negative result, or if at the time person A’s blood was drawn his/her viral load was not enough to generate a correct result.

A major need in the effort to control Ebola is, therefore, a rapid and accurate test that can be conducted quickly and relatively inexpensively and, perhaps most important, does not require transportation of blood samples over long distances to a laboratory, but can be done where potential Ebola patients present for care.

And (from the selfish point of view of those of us who live in the US and other developed nations), it would be a huge advantage if such a test could be conducted at points of entry. The ideal would be a thumb-prick test, such as is used to test blood sugar in diabetics.

The current gold standard for testing Ebola is reverse transcription polymerase chain reaction (RT-PCR), which is able to detect really small quantities of a virus. An accelerated version of this test, the FilmArray, is a device made by an outfit called BioFire; it reportedly yields equally accurate results in about one hour . Many hospitals in the US have acquired the FilmArray. So far, they are scarce to nonexistent in Africa, probably because they are very expensive.

A company in Colorado called Corgenix (CONX) is working on a device that produces results in 10 to 15 minutes (I posted a comment mentioning the Corgenix test to Dr KSS’s superb Ebola piece for the Irregulars). It does not employ the RT-PCR method; instead it tests for antibodies to the virus. The advantage of a much faster, and much cheaper testing method might be seriously offset by the diminished accuracy of the method. In particular, antibody tests would not likely detect the presence of the virus as early as the RT-PCR method, because antibodies do not appear immediately, and also might not appear until the viral load is much higher. However, in terms of containing Ebola in Africa, a quick, cheap test could work wonders. And the Corgenix method could be valuable in airports, if it became necessary to screen arriving passengers more thoroughly than is done currently.

What else is necessary to contain the Ebola virus?

Better diagnostic tools are only part of the strategy – essential, but not the whole thing. At the top of the list of other essentials is hygiene and sanitation. It’s obvious that the strictest hygiene needs to be practiced whenever there is possible contact with an Ebola patient, whether in a medical facility, at home, or anywhere in between. It’s obvious, yes, but violations of hygiene occur even in the best hospitals in the most advanced nations – otherwise, why would we in the US have such a high rate of hospital-acquired infections? (I know, we can’t blame all hospital-acquired infections on poor hygiene. Infections due to antibiotic-resistant pathogens would happen even with the strictest hygiene, because we’re already colonized by those pathogens, and when we’re treated with some antibiotics, the balance of systemic microbes is affected in such a way that the evil bugs thrive and make us sick.) It wasn’t poor hygiene that made those Dallas nurses get sick, but unfamiliarity with the protocol. But more than 200 health-workers in Africa have sickened and died from contact with Ebola patients, and who knows how many other people they infected.

Sanitation is a colossal concern. The amount of medical waste that a single Ebola patient generates in a hospital is huge, and it needs to be disposed of properly, which means incineration or steaming to about 260⁰ F for 20 minutes. Disposal of an Ebola patient’s bodily wastes – bloody diarrhea, vomit, urine, etc – needs to be managed scrupulously, so that there no contamination of the water supply. Needless to say, this is difficult anywhere and nearly impossible under the present circumstances in the affected regions.

Another issue is burial or cremation of the dead. Thomas Eric Duncan, the Liberian visitor, was cremated. This has not been happening in Africa. It is not precisely known how long the virus survives in a dead body, but the fact that the human host is no longer living does not mean that the cells in the host’s body do not survive for a time, and as long as they do, the virus survives with them. In dealing with Ebola, it is instructive to consider the practices in controlling an epidemic of cholera, where maintaining the integrity of the water supply is an imperative. Burying the dead too close to rivers and streams is highly dangerous.

How long the virus survives when not carried in host cells is a crucial question. We are told that it is present only in fluids produced by infected individuals, and the usual list of fluids includes blood, feces, urine, sweat, saliva, and mucus. The doctrine is that the contagious phase is when the infected individual is secreting these fluids in abundance – this is sometimes called “wet” Ebola, in contrast with “dry” Ebola, which is thought to be less contagious, not because the patient is not infected with the virus, but because the virus is only transmitted by those fluids, and if we don’t come into contact with those fluids, we’re safe. However, it is not usually mentioned that Ebola virus is present in semen and breast milk for up to 50 days after a patient has recovered.

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So containment of the disease means that contact with all those fluids must absolutely be prevented, certainly while the patient is experiencing symptoms, and probably for a period of time after the patient’s recovery, which, in the case of certain bodily fluids, may be seven weeks or longer.

What’s our best shot at containing and ultimately subduing Ebola?

In a word, vaccination. Vaccines are the weapon of choice against any infectious disease, and vaccination programs have been almost totally effective against devastating diseases such as polio and smallpox. And vaccination (despite the empowered opposition of certain factions) has also been immensely effective in lowering the incidence of a number of childhood diseases.

Vaccination has two great benefits. (If you already know this, skip ahead.) The obvious one is that it protects the individual against the disease, by eliciting the production of antibodies – it’s not the vaccine that kills the germs, it’s our own antibodies that do the job. The vaccine “teaches” the organism to recognize the invading pathogen, so when the pathogen does invade, the organism already “knows” that it’s a dangerous invader and mobilizes any of a very large number of possible tactics to combat the invader. The organism doesn’t first have to figure out that the particular invading pathogen is harmful – it “remembers” and reacts accordingly.

But the second benefit is much less widely-understood. It’s known as herd immunity. What that means is that when all, or nearly all of the individuals in a community are vaccinated, some pathogens that need human hosts just die out. They can’t find a person to infect. This type of immunity is highly important, especially in infectious diseases in which the vaccine is not 100% effective, and in fact, many vaccines are not 100% effective. But if a child is in a school where almost all the kids have had their routine inoculations, that child is highly unlikely to get the measles, even if that particular child has NOT received the measles vaccine! And why is this? Because very few of the other kids are going to be infected with measles, and will not pass it on to the unvaccinated child.

But what if the unvaccinated child does get the measles? Then even the vaccinated kids are at some risk – probably fairly low, but at risk nonetheless. There have been precisely such instances, where a relatively small minority of children whose parents had opted out of the DPT vaccine (diphtheria/tetanus/pertussis) became conduits for the transmission of pertussis (whooping cough) to children who had actually received the vaccination, so that the incidence of pertussis in that community soared.

The moral of that story is that herd immunity protects everybody. We can think of vaccination as something like insurance – it protects the individual policyholder, but it also protects the community.

What does this have to do with Ebola?

Let’s for a moment consider flu vaccinations. The vaccination rates in the US are shockingly low, considering that the vaccine is largely effective, and that somewhere around 30,000 people die each year from influenza. In fact, only about 40% of adults and 60% of children get their annual flu shots. But even that unsatisfactory rate of vaccination has had a powerful effect on the flu virus itself.

How can that be? I know this is difficult, but what we need to do is put ourselves in the shoes of the flu virus itself. What does it want? Like all life, it “wants” to survive. (Yes, there are debates about whether a virus is really a life form, and pretty obviously, using words like “wants” when we talk about viruses is highly dubious, but let’s give Doc Gumshoe a bit of leeway here, please.)

In order to survive, all viruses need living hosts. A virus that killed its host really quickly, like a deadly poison, in just a few hours, would simply not survive to infect other hosts. One of the great survival advantages of the human immunodeficiency virus (HIV) is that infected humans live for a really long time – many years, sometimes – before developing any symptoms, and during that time they are perfectly capable of infecting other humans with HIV. This is to some degree offset, in the case of HIV, by the fact that it’s actually not terribly contagious. A very large quantity of the virus needs to be passed from the infected person to another person to pass on the infection – that’s why HIV is not transmitted by casual contact.

Therefore, the virus doesn’t really “want” to make the human host dreadfully sick. Now, the flu vaccine, as we all know, is reformulated every year. The experts at the CDC try to predict which strains are going to be the prevalent flu strains in the coming season, and they pick the three strains that they think will be the most virulent – i.e., cause the most severe disease – and manufacture the vaccine against those strains.

So, even though there are lots of unvaccinated people in the US for those strains to infect, there are even more people, unvaccinated and vaccinated that will be susceptible to strains that were not included in that year’s flu vaccine. Therefore, the less virulent strains have better survival odds than the more virulent strains. And this has been going on for many years, in the US and other developed countries. The result is that, by and large, influenza is less virulent now that it was 25 years ago, and certainly, much less virulent than it was back in 1918 to 1919, when it killed more people worldwide than World War I.

Because, remember, what the virus wants is NOT to kill people, but to keep them alive and transmitting the virus, so that it, too, can survive.

Ebola’s survival advantage is that a tiny amount of the virus, perhaps just a few individual particles, can result in an infection. On the other hand, the fact that hosts do not transmit the virus until they demonstrate symptoms is not a survival advantage – it’s a survival drawback, because it makes it easier for humans to avoid exposure.

When (I’m being optimistic here!) an Ebola vaccine is developed and employed, one of the effects may be that the vaccine selects for the more virulent strains of Ebola, so that the viral strains that preferentially survive are the less virulent strains. In time it’s possible that widespread Ebola vaccination will tend to select for strains that are less lethal, perhaps something like the current flu strains – at least, those that are most prevalent.

Is there any progress in Ebola vaccines?

There is guarded optimism in some quarters, including the World Health Organization. At least two vaccine candidates are reasonably far along, one developed by GlaxoSmithKline (GSK) and the other by the Canadian Health Agency, being tested by a small US outfit called NewLink Genetics (NLNK). Johnson and Johnson (JNJ) also has a vaccine in the works, and supposedly the Russians are working on a vaccine.

Reasons for optimism: medical science has a reasonably good record in creating vaccines against a range of viruses, and, as viruses go, the Ebola virus is simple. A fundamental principle of creating a vaccine against a virus is to start with an entirely harmless virus, and add to it enough of the genetic characteristics of the target virus so that when the bioengineered harmless virus is introduced into the body of a person, the person’s immune system learns to recognize enough of the characteristics of the target virus (in this case, Ebola) so that if the real Ebola virus should invade, the immune system is ready to attack, and (we hope!) kill the invading Ebola before it has a chance to do any damage.

Reasons for pessimism: several, including the failure, despite enormous efforts, to develop an effective vaccine against HIV, and the unfortunate mutability of viruses like Ebola, which encode their genetic information in RNA. This means that today’s vaccine might not work against tomorrow’s virus.

Nonetheless, a vaccine is the best and possibly the only shot against Ebola, at least in Africa. Containment in the affected African regions would likely rely on a technique known as “ring vaccination.” That means concentrating the vaccination program around the specific areas where the outbreak is most prevalent, with the intention, first and foremost, of preventing spread. This is fundamentally different from a vaccination program that seeks to immunize the entire population. The objective is certainly to protect the individuals, but the more important objective is to deny the virus a pathway to transmission. Ring vaccination has been highly effective in stopping the spread of epidemics like smallpox.

A great advantage of ring vaccinations is that they maximize the effective use of the available supply of vaccine. Even after a vaccine is developed and demonstrated to be safe and effective, initially there will be only a limited number of doses available, since it will take many months to produce anywhere near the number of doses of vaccine needed to immunize the entire at-risk populations. Therefore, it will be vital to deploy the vaccine initially available in such a way as to prevent the creation of new human hosts for the virus.

What are the biggest risks that Ebola poses to the planet?

The risk that has been talked about as scariest is the risk that the Ebola virus will mutate and become airborne. The scientists at the Broad Institute at MIT, at the laboratory where Ebola was sequenced, believe that this possibility is miniscule. Dr Eric Lander, director of the Broad Institute, points out that although the Ebola virus mutates constantly, all of the mutations are basically consistent with the inherent life-cycle of the virus, which has enabled it to survive for thousands of years. A mutation that would permit it to survive in a dry state, and be able to be carried on dust particles, would be tantamount to turning into a different species altogether.

This is not to say that the Ebola virus cannot be transmitted in very small droplets of fluid, but these do not travel in the air for more than a very short distance – a few feet at most. Yes, health workers need to wear protective gear when they are in close proximity to a person with active Ebola, and it is possible that if someone with Ebola sneezed on you in the subway, you might be infected. But it’s nowhere near as transmissible as the flu.

Most knowledgeable people agree that the biggest and most frightening risks are if Ebola is transmitted to crowded population centers with limited infrastructure, poor sanitation, and inadequate medical facilities. The government of Nigeria has been especially watchful, and they have proudly proclaimed that Nigeria is “Ebola free.” Whether this is true or not, I cannot say. (Note, this is the same government that has announced that the girls who were kidnapped by Boko Haram would soon be returned.) However, if there were an Ebola outbtreak in Lagos, it would be a nightmare. This is a city with a population of 21 million living an area one-tenth the size of metropolitan New York City, most of them in slum conditions.

If Ebola were to emerge in India it would similarly be a nightmare. It would be aggravated – aggravated is far too mild a word! – by the prevalence in India of public defecation: it is estimated that about 600 million persons in India do not have access to toilets and consequently relieve themselves outdoors. In the countryside this takes place, if possible, in wooded areas – away from farmed fields. But in the teeming city slums, it takes place anywhere and everywhere. Ebola would thrive in such an environment, and the measures necessary to contain it are difficult to conceive.

What about drug treatment for Ebola?

The drug that has received most attention is ZMapp. It has been used in a few people with Ebola, and they have recovered. Whether this is due to the beneficial activity of the drug or not is difficult to say. What is certainly true is that at this point it is exceedingly scarce. By no stretch of the imagination will enough ZMapp be available to treat patients in West Africa soon enough to make a dent in the epidemic.

ZMapp is a mixture of several bioengineered monoclonal antibodies (mAbs). It is grown in a tobacco plant by Kentucky Bioprocessing, which is a subsidiary of Reynolds American. There have been no actual clinicial trials of ZMapp, and ramping up production, particularly in the absence of real data, seems to be a dubious strategy. However, if results in even a few patients continue to be positive, even limited amounts of ZMapp could make a difference in combating Ebola. It could mean that health workers who went to Africa to take part in the effort would know that if they contracted Ebola, an effective drug was available to treat them. This might result in an increase in the number of health workers who were willing to expose themselves to the risk of Ebola, beyond the risk-takers and the “heroes.”

Doctors Without Borders (MSF) has announced clinical trials in Africa of three Ebola treatments. One is Avigan (faripiravir), a drug manufactured by Toyama Chemical of Japan, a division of Fujifilm. Avigan is active against a number of viruses, including some flu strains. It has been used in Europe in a few Ebola patients, all of whom have survivied. The trial is being conducted in Guinea by the French National Institute of Health and Medical Research. Another is brincidofovir, from Chimerix (CMRX), an old drug that got FDA approval in 1996 for treatment of cytomegalovirus (a frequent comorbidity with HIV). The brincidovir trial is funded by the Wellcome Trust and will be run by Oxford University. The third treatment consists of transfusions from Ebola survivors, who presumably have developed Ebola antibodies (Dr Craig Spencer received such a transfusion). None of these will be randomized controlled trials. There will be no placebo arm. Trial results will be based on a comparison of outcomes between patients in the trial who received one of the three treatments and patients not in the trial, but otherwise receiving the same care.

I need to add here that I am skeptical about extrapolating successful treatment results in the US or Europe to the African epidemic zones. Most patients treated for Ebola in the US or Europe have recovered, and there is no way of knowing how much any of the drug interventions contributed to their recovery. It would indeed be excellent news if the trial subjects in Africa recovered at a significantly higher rate than the other patients, but we shouldn’t count on it.

A practical consideration: who pays for vaccine and drug development?

The pharmaceutical and medical establishments of the developed world have been faulted for paying insufficient attention to Ebola since it was first identified in 1976. I’ll stay out of that controversy, other than to point out that after the first couple of outbreaks, Ebola essentially dropped out of sight. However, it is certainly the case that there have been no incentives for pharma to develop Ebola drugs or vaccines, at least up to the present time. The current African epidemic has likely changed that. If an Ebola vaccine were developed, governments would likely support a vaccination program in Africa and would also likely stockpile the vaccine in their home countries in the event of need. The same calculation would apply to an effective Ebola drug. Ebola does not represent an opportunity for pharma in the same class as diseases and conditions that affect vast numbers in the developed world. But when it comes to combating an adversary in Ebola’s class, the developed world will take all possible precautions, no matter what the cost.

Late news: Ebola spreads to Mali

The details of this case are complex, not only medically, but circumstantially, It concerns an iman who apparently was infected across the border in Guinea, and then travelled to Mali for treatment. He was not diagnosed with Ebola in the hospital in Mali, and was thought to have died of kidney failure unconnected with Ebola. Ebola was identified as the culprit only when a nurse who treated the iman fell ill and died. A number of the iman’s connections have also become infected and died; the hospital is now sealed off, several health workers in the hospital have become infected, and it is not known to what extent Ebola will spread among the hospital patients. Another factor that may contribute to the spread is that the iman’s body was returned to his home mosque in Guinea, where his body was washed; it is not known how many people came into contact with his body.

This latest incursion of Ebola is an example of how this virus can cross Africa’s porous borders, and how an infection that starts in a single individual can spread exponentially. A key factor in the Mali outbreak is the puzzling failure of the health workers there to identify the infection as Ebola; thus, the iman was not isolated and the health workers that treated him did not take the essential precautions. This is a recipe for transforming a single infection into an epidemic. My confidence in asserting that Ebola will not become a serious threat in developed nations is that our health workers and hospitals will not make similar errors.

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Thanks in advance for your comments – blessings or curses, all welcome either way. Also, please let me know what topics you’re interested in for future posts. Best to all, Michael Jorrin (aka Doc Gumshoe).

This is a discussion topic or guest posting submitted by a Stock Gumshoe reader. The content has not been edited or reviewed by Stock Gumshoe, and any opinions expressed are those of the author alone.