TWiV 312: She sells B cells

On episode #312 of the science show This Week in Virology, the TWiVbolans discuss the finding that human noroviruses, major causes of gastroenteritis, can for the first time be propagated in B cell cultures, with the help of enteric bacteria.

You can find TWiV #312 at www.microbe.tv/twiv.

TWiV 309: Ebola email

On episode #309 of the science show This Week in Virology, the TWiVocytes answer questions about Ebola virus, including mode of transmission, quarantine, incubation period, immunity, and much more.

You can find TWiV #309 at www.microbe.tv/twiv.

Can Ebola virus infect via the skin?

SkinI received this question about Ebola virus infection via email:

Can you become infected if infected droplet lands on your skin even if there is no abrasion on the skin? I am now hearing this, which surprises me. The virus can enter through the actual skin and does not need mucus membrane to enter?

The skin of most animals is an effective barrier against viral infections. The outer layer of human skin, called the stratum corneum, consists of a layer of dead, keratinized cells (illustrated). Viruses cannot replicate in, or be transported across, dead cells. Therefore any virus that lands on the skin cannot simply replicate in the outer layer or be transported to the underlying living cells.

However, viruses can pass through the dead layer of the skin through cuts or abrasions. Many activities, such as shaving, or even scratching, lead to microabrasions. It is relatively easy to breach the dead layer of cells with a fingernail, and such abrasions cannot be seen.

A patient in the late stages of Ebola virus infection (such as the Dallas patient) is shedding high amounts of virus particles in body fluids. If virus-laden droplets land on the skin, the virus can readily enter via cuts or abrasions. Even if the skin is intact, the droplets could be inadvertently transferred to mucous membranes of the eye, nose, or mouth, initiating infection. For this reason it is important that the skin be entirely covered when caring for Ebola virus infected patients.

TWiV 307: Ebola aetiology

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.

TWiV 306: This Week in Ebolavirus

On episode #306 of the science show This Week in Virology, the Grand Masters of the TWiV 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 incubation period of a viral infection

Incubation periodThe time before the symptoms of a viral infection appear is called the incubation period. During this time, viral genomes are replicating and the host is responding, producing cytokines such as interferon that can have global effects, leading to the classical symptoms of an acute infection (e.g., fever, malaise, aches, pains, and nausea). These symptoms are called the prodrome, to distinguish them from those characteristic of infection (e.g. paralysis for poliovirus, hemorrhagic fever for Ebolaviruses, rash for measles virus).

Whether or not an infected person is contagious (i.e. is shedding virus) during the incubation period depends on the virus. For example, Ebola virus infected patients do not pass the virus on to others during the incubation period. This fact explains why Tom Frieden said there was ‘zero chance’ that the passenger from Liberia who was diagnosed with Ebola virus infection in Dallas would have infected others while on an airplane. He had no symptoms of infection because he was still in the incubation period of the disease.

In contrast to Ebolaviruses, poliovirus and norovirus are shed during the incubation period – in the feces, where they can infect others.

Remarkably, viral incubation periods can vary from 1 or 2 days to years (Table; click to magnify). Short incubation times usually indicate that actions at the primary site of infection produce the characteristic symptoms of the disease. Longer incubation times indicate that the host response, or the tissue damage required to reveal the symptoms of infection, take place away from the primary site of infection.

The table was taken from the third edition of Principles of Virology. Missing from the table (which will be corrected in the next edition) is the incubation period of Ebola virus, which is 2 to 21 days. I would also argue that the incubation period of HIV is not 1-10 years, but 2-4 weeks, the time until the prodromal symptoms occur. The characteristic symptom of HIV-1 infection, immunosuppression, occurs much later.

WHO on Ebola virus transmission

The World Health Organization has issued a situation assessment entitled ‘What we know about transmission of the Ebola virus among humans‘. WHO is rather late entering the transmission discussion which began on 12 September 2014 with the suggestion that Ebola virus transmission could go airborne. WHO is a big organization and moves slowly; nevertheless their voice may reassure those who are not convinced by what virologists have to say. Here are the salient points (voiced here and by many others in the past few weeks).

The Ebola virus is transmitted among humans through close and direct physical contact with infected bodily fluids, the most infectious being blood, faeces and vomit.

Ebola virus disease is not an airborne infection. Airborne spread among humans implies inhalation of an infectious dose of virus from a suspended cloud of small dried droplets.

This mode of transmission has not been observed during extensive studies of the Ebola virus over several decades.

Moreover, scientists are unaware of any virus that has dramatically changed its mode of transmission*. For example, the H5N1 avian influenza virus, which has caused sporadic human cases since 1997, is now endemic in chickens and ducks in large parts of Asia.

That virus has probably circulated through many billions of birds for at least two decades. Its mode of transmission remains basically unchanged.

Speculation that Ebola virus disease might mutate into a form that could easily spread among humans through the air is just that: speculation, unsubstantiated by any evidence.

The last sentence is the key point:

To stop this outbreak, more needs to be done to implement – on a much larger scale – well-known protective and preventive measures. Abundant evidence has documented their effectiveness

*Sounds familiar?

TWiV 305: Rhymes with shinola

On episode #305 of the science show This Week in Virology, Vincent, Alan, and Kathy continue their coverage of the Ebola virus outbreak in West Africa, with a discussion of case fatality ratio, reproductive index, a conspiracy theory, and spread of the virus to the United States.

You can find TWiV #305 at www.microbe.tv/twiv.

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 www.microbe.tv/twiv.

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.