Ebola has mutated. Asymptomatic carriers.

From the BBC, January 29, 2015

Scientists tracking the Ebola outbreak in Guinea say the virus has mutated.

Researchers at the Institut Pasteur in France, which first identified the outbreak last March, are investigating whether it could have become more contagious.

[snip]

“We’ve now seen several cases that don’t have any symptoms at all, asymptomatic cases,” said Anavaj Sakuntabhai.

“These people may be the people who can spread the virus better, but we still don’t know that yet. A virus can change itself to less deadly, but more contagious and that’s something we are afraid of.”

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New Ebola – Evolution of a Virus

Recently, a paper describing the sequencing of many samples from patients in Sierra Leone with Ebola was published in Science by Gire et al.:

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

There have been many headlines referring to this paper with variants of this phrase: “Ebola rapidly mutating!” The meaning and implications of such statements is not always clear due to an incomplete understanding of evolution. Therefore, I think it is worth defining some terms and explaining how viruses evolve generally and how Ebola may be evolving specifically.

First, I should like to clarify the difference between the rate at which mutations occur and the rate at which mutations are observed. Mutations are changes in the genetic sequence. They can occur for several reasons including mistakes which occur during replication of viruses. The rates at which these mutations occur thus depend in part on how accurately enzymes copy genetic sequence. This mutation rate is unlikely to change for a given species unless there is a change in the enzymes involved in copying genetic material. This is a very rare occurence. However, changes in the rate at which mutations are observed is much more common because another important force, selection, affects this process.

Many mutations occur but are never observed. How can this be? If a mutation occurs which is deleterious, it will decrease the likelihood that an organism will survive. Such mutations are common in viruses. However, although unfavorable mutations have always been occuring in Ebola, they were unlikely to be observed because the individual viruses which possesed them did not produce many additional viruses. We say that such viruses were selected against.

One of the key concepts of evolution is that selection can change. If the environment of an organism changes, then what constitutes a “bad” mutation, from the viewpoint of the organism, can also change. For a virus, the host is the environment. If the host for Ebola changes from, say, a fruitbat, to a human, then the environment has changed and the effect of a mutation on the ability of the virus to survive and replicate may change. In fact, a mutation which was selected against in fruitbats may be selected for in humans if it helps the virus survive in its new environment – humans. This will lead to a change in observed mutations in viruses which have colonised a new host even if the rate at which mutations actually occur has not changed.

Thus far, this has been a relatively academic discussion.  But now we come to the public health implications of the Science paper.  One interpretation of these results is that Ebola is adapting to its new host, humans, by acquiring new genetic sequences which allow it to replicate and spread person to person more effectively. Indeed, given that the virus has apparently been spreading human to human since December 2013, it would be surprising if this were not occuring.

In the past, Ebola would spread from its animal host to humans, pass human to human a few times, and then die out.  It never had a chance to adapt to humans.  The current outbreak is different. Because Ebola now has had many “passages” through the novel human environment, it has had many more opportunities to adapt to humans.  This may be reflected in some of the changes in genetic sequence observed in the Science paper.  It may also be reflected in changes in the ability of the virus to replicate and spread in humans.  People who expect Ebola to remain unchanging in its new human host are ignoring evolution.  If mutations can occur which will allow the virus to spread more efficiently in humans, then, given enough time, such mutations will occur.

Ebola was an animal virus.

It is becoming a human virus.

Cluster of deaths related to influenza in Maryland family

[hat-tip, Ree, Dr. Niman and Pixie for many articles on this story]

From WUSA9, March 6, 2012

Calvert County Department of Health officials have not confirmed that “Influenza A” killed three people in a Lusby home, but say it was a contributing factor.

[snip]

“The first case of illness occurred in an 81-year-old woman who presented symptoms at her home beginning on or about February 23, 2012. She was cared for at home by three of her children, a son and two daughters. The caregivers developed similar upper respiratory symptoms on or about February 28, 2012. All were hospitalized and became critically ill. The elderly woman, a 58-year-old son and a 56-year-old daughter subsequently died. A third family member and caregiver is currently hospitalized at the Washington Hospital Center,” CCHD officials said.

Although we don’t know for sure that flu killed all of these people, according to the Maryland Department of Health and Mental Hygeine, at least two of the patients tested positive for influenza A. The reports indicate possible human to human spread of an influenza strain with unusual properties. Both the attack rate and the case fatality rate would appear to be very high. Indeed, this pattern is more similar to what we have seen with H5N1 in Asia than H3N2 or H1N1 in the US.

From KGOAM, March 6, 2012

“The first thing that comes to mind is influenza. It can be devastating and make people very ill,” said Dr. William Schaffner, chair of preventive medicine at Vanderbilt University Medical Center in Nashville. “But when they’re a cluster like this, we have to wonder if it may be a mutant strain of flu virus. There’s been some concern about a swine flu variant.”

It is obviously essential that we get the sequence of all 8 genomic segments as soon as possible. With existing technology, it should be possible to have this within 24 hours. Lets hope the CDC is better equipped to handle this outbreak than it was for the 2009 pandemic.

[Update, March 7, 2011

From The Maryland Department of Health and Mental Hygeine [hat-tip, Dr. Niman]

Testing by the DHMH Laboratories Administration has confirmed that two of the cases had Influenza H3, a strain of Influenza A that has been circulating this season.

]

Mutation in Shenzhen H5N1 virus

Reports in Chinese language news sources indicate that Shenzhen health authorities have discovered a mutation in the H5N1 virus that recently killed a bus driver in that city. The nature of the mutation or its effects are unclear, but may make the virus more pathogenic and difficult to treat. The Chinese public is being reassured that the virus cannot transmit human to human, easily.

Immediate deposit of sequences in GenBank is necessary for evaluation of this virus.

The bird flu death man virus has the sudden change (Sina.com)

Shenzhen bird flu death man virus gene mutation (881903.com)

 

The Black Swan Lands in Japan – Part 2 – Biological effects of radiation

The leakage of radiation from nuclear power plants in Japan has prompted attempts to minimise the dangers of radiation. These efforts are, at best, misguided and at worst, intended to mislead.

One of the errors that I have frequently seen in the media is the confusion between acute and long term effects of radiation. “Radiation sickness” is an acute illness that requires high levels of radiation to manifest itself. However, long term effects of radiation such as cancer and genetic mutations can occur at relatively low levels of radiation. So, just because people are not dropping dead of radiation sickness does *not* mean that no ill effects are occuring.

Radiation can damage DNA in cells. During the repair process, a mistake may be made in reconstituting it. This can result in cancer that may not manifest itself for many years. If radiation damages germ cells (sperm or eggs) the children of the person exposed may have genetic mutations. Fetuses are also highly susceptible to radiation damage at certain stages of development. Exposure to radiation in the womb can result in many birth defects, including mental retardation, and predispose the child to cancer later in life.

Some pundits and public officials have suggested that low levels of radiation are like getting some extra X-rays. They should know that X-rays are considered carcinogens. Although the risk from a single X-ray is low, getting a lot of unnecessary X-rays is not a good idea. When large numbers of people are exposed to low, but above background, radiation, the odds that some of them will get cancer goes up.

Some have argued that background radiation can be relatively high in some areas and that therefore there is no risk to low levels of radiation. Those people should know that people exposed to relatively high “background” radiation are at increased risk of cancer. That is why homes with high levels of naturally occuring radon in their basements are urged to mitigate it.

Some pundits who apparently received good educations in the physical sciences have revealed a striking ignorance of biological processes. They appear to only be aware of the effects of external radiation. In fact, radiation can also be ingested in many forms. Fallout that may be at relatively low levels on the grass can be concentrated in the milk of cows who must eat large amounts of grass every day. Children who drink this milk will receive much more concentrated radiation than would be expected based on environmental sampling.

Low levels of radiation can cause long term health effects. They are hard to study because they involve stochastic processes (DNA damage and repair), variability in susceptibility (based on individual genetics) and a long lag time before the health effects are seen. However, there is substantial evidence that, on a population basis, even low levels of radiation can have health effects. Pretending they don’t exist won’t make them go away.

References

Radiation Protection – Health Effects
EPA

Radiation and Pregnancy: A Fact Sheet for the Public
CDC

Radioactive I-131 from Fallout
National Cancer Institute

Radon and Cancer: Questions and Answers
National Cancer Institute

Imperial College London task force investigates mutations in UK strain of pandemic H1N1

A research team at Imperial College London has reactivated the MOSAIC study to investigate mutations in the pandemic H1N1 virus.

From the Daily Mail, January 9, 2011 [hat-tip BeWell]:

Professor Peter Openshaw, director of the Centre for Respiratory Infection at Imperial, said: ‘We have paid particular attention to whether the mutations are affecting how well the vaccine works and whether the slight mutations have led to it becoming more severe.’

[snip]

Asthma specialist nurse Katy Odeadra, who works in the Chest and Allergy Clinic at St Mary’s Hospital, said: ‘All the talk among doctors and nurses dealing with swine flu cases is of a mutated form of the virus.’

The suspicion that the pandemic H1N1 virus has mutated in a functionally significant way is likely due to the strain on critical care resources. Many more people, especially middle-aged adults, have required heroic efforts to keep them alive this year as opposed to the last wave of the pandemic. There are a number of possible explanations for this phenomenon. But I believe that the most likely is that the virus circulating in the United Kingdom has changed such that it can now readily infect middle-aged adults. Previously, most of the outbreaks were among children. This is no longer true.

The case fatality rate (CFR) was higher among middle-aged adults last year. So, even if the virus has not become any more lethal, infection of a larger proportion of middle-aged adults will naturally lead to more severe and lethal cases.

As to whether the current flu vaccine protects against pandemic H1N1 virus currently circulating in the UK, we don’t know for sure because so few people there have been vaccinated. Thus far, we have not seen a similar pattern of infection in countries with relatively high levels of vaccination like Canada or the United States. However, it seems unlikely that the new virus will remain confined to the UK. Once the new strain reaches North America, the efficacy of the current vaccine (or lack thereof) should be readily apparent.

Fatal cluster in Texas

A 42 year old woman who worked at the University of Texas in Austin died of the new H1N1 virus on September 27, 2009 (abcNews).  Her 35 year old sister died of the new H1N1 virus October 7, 2009 (KXAN). Although we don’t know for certain that the virus was transmitted from one sister to another, the timing of the deaths is consistent with this possibility. Although it is possible that one or both sisters had underlying conditions that may have contributed to their deaths, any fatal cluster should be vigorously investigated as it may indicate that a more lethal virus has developed. Viral samples from each patient should be completely sequenced. This would allow investigators to determine whether the two sisters were infected with the same strain of virus. Live virus should also be used to infect ferrets to determine if the strain that killed these two women is more lethal than other new H1N1 strains.

If it sounds like you’ve read a blog like this before, it’s because you have.  I wrote a blog describing a similar fatal cluster in Indiana. I recommended the same experiments be done. As far as I know, no reports of any such experiments have been made public. This is a mistake, imo. There was a report suggesting a lethal mutation in American cases, but which Americans were involved was never disclosed.

The overall incidence of death in Texas is not disproportionate to that state’s population. However, there have been anecdotal reports of much more severe strains in outbreaks in Texas. Is there something going on in Texas? Hard to know, at this point.

I just hope I don’t have to write any more blogs about fatal clusters.