Could the Ebola virus epidemic have been prevented?

Ebola is comingThe cover of this week’s issue of Businessweek declares that ‘Ebola is coming’ in letters colored like blood, with the subtitle ‘The US had a chance to stop the virus in its tracks. It missed’. Although the article presents a good analysis of the hurdles in developing antibody therapy for Ebola virus infection, the cover is overstated. Why does Businessweek think that Ebola virus is coming to the US? (there is no mention of this topic in the article). Are we sure that antibody therapy would have stopped the outbreak? (no, as stated in the article).

How the U.S. Screwed Up in the Fight Against Ebola is an analysis of why ZMapp, the cocktail of monoclonal antibodies that block infection with Ebola virus, has not yet been approved for use in humans. ZMapp was given to two American workers who had become infected with the virus while working in Africa. The two workers recovered, but the role of ZMapp in their recovery is unknown – as the authors of the article note. Although ZMapp can prevent lethal infection of nonhuman primates with Ebola virus, it is not known if it would work in humans. Answering that question requires a clinical trial, and the article explores why this phase was not done years ago. Only after the large Ebola virus outbreak in west Africa did the US provide funds to conduct a phase I trial of the drug.

The article discusses how development of ZMapp languished for years, because the US government did not consider the Ebolaviruses to be a pressing problem. In hindsight they were wrong, and now anyone can seem smart by saying we should have pushed development of Ebola virus vaccines and therapeutics.

The real question is whether we will learn from this experience, and be better prepared for the next viral outbreak. Just because infections are rare or geographically localized should not lessen their importance, as these features can change. Knowing the animal source of a viral infection may also lead to developing ways to prevent infections. For example, because people acquire Hendra virus from horses, immunization of these animals should prevent human infections.

What other antiviral vaccines and drugs should we be developing? This question is difficult to answer because we discover new viruses regularly and making therapeutics for all of them is not possible. Testing an antiviral drug or vaccine against rare viruses is difficult because identifying populations that are at risk for infection may be a hit or miss proposition.

Influenza viruses are at the top of the list for vaccine and drug development, because nearly everyone gets infected. Other viruses we should be ready for include SARS and MERS coronaviruses, dengue virus, chikungunya virus, Lassa virus, Nipah and Hendra viruses. I’m sure you can think of other viruses that belong on this list.

Developing antiviral vaccines and drugs is expensive. For some of the viruses on my list (dengue, chikungunya) there are currently large enough markets that permit involvement of for-profit pharmaceutical companies. Development of therapeutics against viruses that cause rare infections must be supported largely by governments.

The US does not spend enough money on basic life sciences research. We do spend a great deal of money on the military. President Obama recently declared Ebola virus to be a top national security priority. Why not view all infectious diseases in this way, to ensure that they receive the funding for research that they deserve?

While the Businessweek cover is misleading, intended to stimulate sales, the article does make us think about the problems we confront when dealing with rare but lethal diseases. No one should conclude that Ebola virus outbreak in Africa could have been prevented, because antiviral therapies have not yet been tested in humans. But we won’t know if we never do the research.

TWiV 304: Given X, solve for EBOV

On episode #304 of the science show This Week in Virology, the TWiV team consults an epidemiologist to forecast the future scope of the Ebola virus epidemic in West Africa.

You can find TWiV #304 at

Transmission of Ebola virus

jet nebulizerAs the West African epidemic of Ebola virus grows, so does misinformation about the virus, particularly how it is transmitted from person to person. Ebola virus is transmitted from human to human by close contact with infected patients and virus-containing body fluids. It does not spread among humans by respiratory aerosols, the route of transmission  of many other human viruses such as influenza virus, measles virus, or rhinovirus. Furthermore, the mode of human to human transmission of Ebola virus is not likely to change.

What is aerosol transmission? Here is a definition from Medscape:

Aerosol transmission has been defined as person-to-person transmission of pathogens through the air by means of inhalation of infectious particles. Particles up to 100 μm in size are considered inhalable (inspirable). These aerosolized particles are small enough to be inhaled into the oronasopharynx, with the smaller, respirable size ranges (eg, < 10 μm) penetrating deeper into the trachea and lung.

All of us emit aerosols when we speak, breathe, sneeze, or cough. If we are infected with a respiratory virus such as influenza virus, the aerosols contain virus particles. Depending on their size, aerosols may travel long distances, and when inhaled they lodge on mucosal surfaces of the respiratory tract, initiating an infection.

Viral transmission can also occur when virus-containing respiratory droplets travel from the respiratory tract of an infected person to mucosal surfaces of another person. Because these droplets are larger, they cannot travel long distances as do aerosols, and are considered a form of contact transmission. Ebola virus can certainly be transmitted from person to person by droplets.

Medical procedures, like intubation, can also generate aerosols. It is possible that a health care worker could be infected by performing these procedures on a patient with Ebola virus disease. But the health care worker will not transmit the virus by aerosol to another person. In other words, there is no chain of respiratory aerosol transmission among infected people, as there is with influenza virus.

In the laboratory, machines called nebulizers (which are used to administer medications to humans by inhalation) can be used to produce virus-containing aerosols for studies in animals. A human would likely be infected with an Ebola virus-containing aerosol generated by a nebulizer (theoretically; such an experiment would be unethical).

A variety of laboratory animals have been infected with Ebola virus (Zaire ebolavirus) using aerosols. In one study rhesus macaques were infected with aerosolized Ebola virus using a chamber placed over the animals’ heads. This procedure resulted in replication of the virus in the respiratory tract followed by death. Virus particles were detected in the respiratory tract, but no attempts were made to transmit infection from one animal to another by aerosol. In another study, cynomolgous macaques, rhesus macaques, and African Green monkeys could be infected with Ebola virus aerosols using a head-only chamber. Virus replicated in the respiratory tract, and moved from regional lymph nodes to the blood and then to other organs. Virus titers in the respiratory tract appeared to be lower than in the previous study. No animal to animal transmission experiments were done.

When rhesus macaques were inoculated intramuscularly with Ebola virus,  virus could be detected in oral and nasal swabs; however infection was not transmitted to animals housed in separate cages. The authors conclude that ‘Airborne transmission of EBOV between non-human primates does not occur readily’.

Pigs can also be infected with Ebola virus. In one study, after dripping virus into the nose, eyes, and mouth, replication to high titers was detected in the respiratory tract, accompanied by severe lung pathology. The infected pigs can transmit infection to uninfected pigs in the same cage, but this experimental setup does not allow distinguishing between aerosol, droplet, or contact spread.

In another porcine transmission experiment, animals were infected oronasally as above, and placed in a room with cynomolgous macaques. The pigs were allowed to roam the floor, while the macaques were housed in cages. All of the macaques became infected, but their lungs had minimal damage. However it is not known how the virus was transmitted from pigs to macaques. The authors write: ‘The design and size of the animal cubicle did not allow to distinguish whether the transmission was by aerosol, small or large droplets in the air, or droplets created during floor cleaning which landed inside the NHP cages’. The authors also indicate that transmission between macaques in similar housing conditions was never observed.

While these experimental findings show that animals can be infected with Ebola virus by aerosol, they do not provide definitive evidence for animal to animal transmission via this route. It is clear is that the virus does not transmit via respiratory aerosols among nonhuman primates.

We do not know why, in humans or non-human primates, Ebola virus does not transmit by respiratory aerosols. The virus might not reach sufficiently high titers in the respiratory tract, or be stable in respiratory secretions, to be efficiently transmitted by this route. There are many other possibilities. A careful study of Ebola virus titers in the human respiratory tract, and in respiratory secretions, would be valuable. However during Ebola virus outbreaks the main concern is to save people, not conduct experiments.

These experiments reveal the large gaps in our understanding about virus transmission in general, and specifically why Ebola virus is not transmitted among primates by respiratory aerosols.

TWiV 302: The sky is falling

On episode #302 of the science show This Week in Virology, the TWiVers discuss the growing Ebola virus outbreak in West Africa, and an epidemic of respiratory disease in the US caused by enterovirus D68.

You can find TWiV #302 at

An outbreak of enterovirus 68


EV-A71 by Jason Roberts

During the winter of 1962 in California, a new virus was isolated from the oropharynx of 4 children who had been hospitalized with respiratory disease that included pneumonia and bronchiolitis. On the basis of its physical, chemical, and biological properties, the virus was classified as an enterovirus in the picornavirus family. Subsequently named enterovirus D68, it has been rarely reported in the United States (there were 79 isolations from 2009-2013). Towards the end of August 2014, an outbreak of severe respiratory disease associated with EV-D68 emerged in Kansas and Illinois.

Hospitals in Kansas City, Missouri, and Chicago, Illinois reported to the CDC an increase in the number of patients hospitalized with severe respiratory illness. EV-D68 was subsequently identified by polymerase chain reaction and nucleotide sequencing in 19/22 and 11/14 nasopharyngeal specimens from Kansas City and Chicago, respectively. Median ages of the patients were 4 and 5 years in the two cities, and most were admitted to the pediatric intensive care units due to respiratory distress. Other states have reported increases in cases of severe respiratory illness, and these are being investigated at CDC to determine if they are also associated with EV-D68.

There is no vaccine to prevent EV-D68 infection, nor is antiviral therapy available to treat infected patients. Current treatment is supportive to assist breathing; in a healthy individual the infection will resolve within a week. In the current outbreak no fatalities have been reported.

EV-D68 has been previously associated with mild to severe respiratory illness and is known to cause clusters of infections. It is not clear why there has been a sudden increase in the number of cases in the US. According to Mark Pallansch, Director of the Division of Viral Diseases at CDC, “our ability to find and detect the virus has improved to the point where we may now be recognizing more frequently what has always occurred in the past. So a lot of these techniques are now being applied more routinely both at the CDC but also at state health departments.” (Source: NPR).

I am sure that the nucleotide sequence of the EV-D68 virus isolated from these patients will reveal differences with previous strains. However whether or not those changes have anything to do with the increased number of isolations in the US will be very difficult to determine, especially as there is no animal model for EV-D68 respiratory disease.

Although how EV-D68 is transmitted has not been well studied, the virus can be detected in respiratory secretions (saliva, nasal mucus, sputum) and is therefore likely to spread from person to person by coughing, sneezing, or touching contaminated surfaces. The virus has been isolated from some of the children in California with acute flaccid paralysis, and there is at least one report of its association with central nervous system disease. In this case viral nucleic acids were detected in the cerebrospinal fluid. EV-D68 probably does not replicate in the human intestinal tract because the virus is inactivated by low pH.

Readers might wonder why a virus that causes respiratory illness is called an enterovirus. This nomenclature is largely historical: poliovirus, which replicates in the enteric tract, was the prototype member of this genus. Other viruses, including Coxsackieviruses and echoviruses, were added to the genus based on their physical and chemical properties. However soon it became apparent that many of these viruses could also replicate in the respiratory tract. Years later the rhinoviruses, which do not replicate in the enteric tract, were added to the enterovirus genus based on nucleotide sequence comparisons. While it was decided to keep the name ‘enterovirus’ for this group of viruses, it is certainly confusing and I would argue that it should be replaced by a more descriptive name.

Zaire ebolavirus in West Africa

Dr. Tom Solomon is Director of the Institute for Infection and Global Health at the University of Liverpool. Here he speaks with Vincent Racaniello about the 2014 outbreak of Zaire ebolavirus in West Africa. Dr. Solomon discusses why the epidemic has spread, how it might be curtailed, the return of two infected health workers back to the United States for treatment, and the possibility that he might be traveling to the affected region to assist with medical care.


TWiV 283: No Reston for the weary

On episode #283 of the science show This Week in Virology, Jens Kuhn speaks with the TWiV team about filoviruses, including the recent Ebola virus outbreak in Guinea.

You can find TWiV #283 at

Mumps in college

Morbidity and Mortality Weekly Report summarizes a mumps outbreak that occurred in 2011 on a university campus in California:

On September 29, 2011, the California Department of Public Health (CDPH) confirmed by polymerase chain reaction (PCR) three cases of mumps among students recently evaluated at their university’s student health services with symptoms suggestive of mumps. An investigation by CDPH, student health services, and the local health department identified 29 mumps cases. The presumed source patient was an unvaccinated student with a history of recent travel to Western Europe, where mumps is circulating. The student had mumps symptoms >28 days before the onset of symptoms among the patients confirmed on September 29. Recognizing that at least two generations of transmission had occurred before public health authorities were alerted, measles, mumps, and rubella (MMR) vaccine was provided as a control measure. This outbreak demonstrates the potential value of requiring MMR vaccination (including documentation of immunization or other evidence of immunity) before college enrollment, heightened clinical awareness, and timely reporting of suspected mumps patients to public health authorities.

All 29 cases were epidemiologically linked to the university. One of the cases was the source patient’s roommate who had received two doses of MMR (measles, mumps, rubella) vaccine. Other outbreaks of mumps have occurred in populations in which many individuals had received 2 doses of MMR.

Data collected during previous mumps outbreaks on college campuses indicate that extended person-to-person contact, in combination with waning vaccine-induced immunity, might make colleges and universities high-risk settings for outbreaks, even when 2-dose MMR vaccination coverage is high

CDC suggests that all colleges and universities consider requiring documentation that students have received 2 doses of MMR vaccine before matriculation.

The mumps vaccine was licensed in the US in 1967, resulting in a significant decline in the number of cases. However outbreaks continue to occur, even in immunized populations, when the virus is introduced by overseas travelers. The vaccine is included in national health programs of only 62% of countries, and immunization rates have declined in many European countries, leading to outbreaks of measles and mumps.

Spillover and science communication

Spillover by David QuammenDavid Quammen, whose book Spillover was recently published, has been the recipient of a good deal of publicity in the past week. Last Wednesday he participated in a New York Academy of Sciences Symposium called ‘Wrath Goes Viral‘; on Saturday he was profiled in the New York Times (The Subject is Science, the Style is Faulkner), and yesterday Spillover was reviewed in the Sunday Book Review by Sonia Shah. Publicity for science is always good, but Shah identifies a key shortcoming of the book.

Shah notes that Spillover describes the “unfolding convergence between veterinary science and human medicine, and how veterinary-­minded medical experts discover and track diseases that spread across species”, detailing “Quammen’s prodigious, globe-trotting adventures with microbe hunters in the field, trapping bats in southern China and hysterical monkeys in Bangladesh”. But Quammen shies away from explanation, saying that he “would rather dazzle us with the difficulty of the science than help us comprehend it”:

He practically apologizes for having to describe fundamental concepts like the basic reproduction rate, or “R0” (the number of new infections caused by an initial case), critical community size (the number of susceptible individuals required to sustain transmission of an infectious disease) and the high mutation rate of RNA viruses. C’mon. Kate Winslet explained R0 in Steven Soderbergh’s film “Contagion” in 20 seconds. As “Spillover” so richly details, we’re talking about the potential end of the human race here. We can take it.

On page 305, before presenting an equation for R0, Quammen writes “There will be no math questions in the quiz at the end of this book, but I thought you might like to cast your eyes upon it. Ready? Don’t flinch, don’t worry, don’t blink”. I’m not fond of this approach. If you have read this blog or listened to any of my science podcasts, you know that I don’t believe that science needs to be dumbed down for a lay audience.

I’m not sure why Quammen shies away from the details. Perhaps he doesn’t feel qualified to explain science (he was an English major in college), or did not believe it was within the scope of the book (Walter Isaacson calls it a ‘masterpiece of science reporting’.) Fortunately, there are many other places online where you can learn the details of virology (see the sidebar of this blog for some examples), or for that matter, any type of science. Sadly, Quammen does not appear to be aware of any of these sources of good science.

I have a copy of Spillover on my desk and when I’m finished reading I’ll have more to say here, and perhaps also on TWiV. The good news is that he had a number of scientists read over the manuscript. At least Quammen doesn’t shy away from fact checking.

TWiV 199: Of mice, ticks, and pigs

On episode #199 of the science show This Week in Virology, Vincent, Alan, Rich, and Kathy discuss recent outbreaks of hantavirus pulmonary syndrome in Yosemite National Park and novel swine-origin influenza in the US midwest, and isolation of the Heartland virus from two patients in Missouri with severe febrile illness.

You can find TWiV #199 at