virology blog
About viruses and viral disease
On episode #307 of the science show This Week in Virology, Tara Smith joins the TWiEBOVsters to discuss the Ebola virus outbreak in west Africa, spread of the disease to and within the US, transmission of the virus, and much more.
You can find TWiV #307 at www.microbe.tv/twiv.
On episode #306 of the science show This Week in Virology, the Grand Masters of the TWiVÂ discuss Ebola virus transmission, air travel from West Africa, Ebola virus infectivity on surfaces, the Dallas Ebola virus patient, and Ebola virus in dogs.
You can find TWiV #306 at www.microbe.tv/twiv.
The 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.
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 www.microbe.tv/twiv.
As 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.
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 www.microbe.tv/twiv.