Saturday 28 February 2015

Editor's Note #21 Far better resting place I go to than I have ever known...

I've spent all day analysing why the death of a person I never knew makes me sad. And as the day draws to a close, I've settled on the fact that it is what he represented to me, so many years ago, and for so many years since, that makes me sad that he has left the world. So I've devoted my day to remembering Star Trek and Spock - Leonard Nimoy's most iconic of characters, and to being grateful Mr Nimoy put so much of himself into that role so many years ago.

In the passing of Spock I'm revisiting so many things he inadvertently taught me as a younger version of myself; things that have some part in making me who I am today.

Top of the list is science. Spock got to look for stuff, understand stuff, deal calmly and logically (I fail greatly here) with things, and was a valued and integral member of his crew. Of course I'd have loved to be on an Enterprise, seeking, learning and finding stuff in space, too! I can't quantify how much Spock and Star Trek have shaped my drive to search and find some more earthly things - seek new viruses, learn new knowledge and find out how infectious diseases are caused.

From here.
Spock was Mr Nimoy. But more than that-all Vulcans must now have elements of Mr Nimoy's portrayal of this one character or for many, they are not Vulcan at all. That's quite an acting legacy. You can't just write "be logical" down on a script-you have to have seen a Vulcan. A part of Nimoy was given to Spock. Other actors achieve this too of course - to my mind all Klingons are represented by Michael Dorn, Rangers by Viggo Mortensen, Wolverine is Hugh Jackman, Tony Stark is Robert Downey Jr, Batman is Christian Bale...and so on.

As Bones said in Star Trek II: The Wrath of Khan (from which the image above is borrowed): "He's really not dead, as long as we remember him". 

Of course we will remember him. How could we forget the person, the character, the message of hope, tolerance and that use of logic? And the accidental humour. Spock was a perfect foil used so well to look both at, and into, ourselves.

Today I still very much respect and admire the ideals that represent the many iterations of earlier Star Trek voyages - care, knowledge, teamwork and a sense of shared goals chosen for the betterment of us all. 

In a world  that can so often be filled with hate, pettiness, self-interest, fractured communities, an absence of care, a disrespect of knowledge and lack of desire to work together, Trek still contains hope that others who share the mission and vision will eventually rise high enough in their roles, often enough, to make the world a better place. Many already do. Star Trek's creators and those who brought its many stories to us, are owed much.

We should always strive to continue the ongoing mission to explore, seek and boldly go where no-one has gone before, in whatever it is that we choose to do. 

Spock understood the need to work for everyone's benefit. He voiced it so well when he reminded Kirk that he has no ego to bruise and that "The needs of the many outweigh the needs of the few". We should try and stow our own egos more often, and work towards the bigger needs. We should do that as part of the same cree more often too - that of the spaceship Earth.

The ship is not yet out of danger Spock, but you gave us a lot to help make it work better. 


Wednesday 25 February 2015

A new Middle East respiratory syndrome coronavirus (MERS-CoV) table of graphs stacks up...

My new favourite graphic. 

This shows MERS-CoV detection by month since the virus was identified in 2012. Detections are further broken down by each region of the Kingdom of Saudi Arabia (KSA) in which they were reported  by the KSA Ministry of Health website here.

At the moment its highlights that the KSA has a real problem in the Eastern region (Ash Sharqiyah) and growing issue in Ar Riyad (as always with MERS-CoV detections) but that Al Quassim region is also of growing concern.

This table of graphs is part of my MERS-CoV static page to be found at...

I try and update these data as often as possible - at the moment detection are rising and February is currently the 4th largest month for new detections - updates occur every day or two.

  1. Kingdom of Saudi Arabia Ministry of Helath MERS-CoV data

Monday 23 February 2015

Transmission of Ebola viruses: What we know and jumping the black swan

Last week a review was released entitled Transmission of Ebola Viruses: What We Know and What We Do Not Know. The review, which is listed in the Opinion / Hypothesis section of mBio, was penned by by Michael T Osterholm and a large team of Ebola experts. You may know him from such articles as What We’re Afraid to Say About Ebola and What we should — and shouldn't — be worried about regarding Ebola or his entertaining seminar at the Johns Hopkins Bloomberg School of Public Health Ebola forum.

First up a few random points from me...
  • This is basically a good review of the historical literature on transmission of Ebola virus and some other ebolaviruses. By the way, this literature is based on real experience, observation and experimentation, defining our understanding of how Ebola virus has transmitted among humans.
    It's worth noting that there have been no concerns made public, nor any new transmission data from the epidemic in West Africa, which indicate changes in the way Ebola virus spreads from person to person
  • This review is an opinion/hypothesis piece so it has a lot of room to move. The language fairly clearly defines where the thinking strays into areas without any actual data to support them. Look for phrases with words like "possible", "could", "postulated", "may", "suggesting" and "can"
A quote from the new review by Osterholm
and experts. Highlighting is mine.
  • Does anyone actually care whether we use words like aerosol, airborne, droplet, droplet nuclei, wet droplets or propelled to mean "not by touch"? I'm not sure any more, but I think they should. Words have meaning and slightly different words carry subtley, yet importantly different meanings. It's important to keep in mind who the messages relating to public health should ultimately try and reach - that would be the public. Experts, comparatively few in number, already have an innate sense of the differences between the words above, right? Right?! Well, many do anyway. Trying to change language or redefine a target in the midst of an epidemic, is at best bad timing and at worst it seems self-serving (although to what end I cannot guess). 
Suggested ways in which an ebolavirus can spread from a known EVD case to a new person. The most likely route is suggested by the thickest arrows with solid outlines while the least likely or most improbable route is indicated by the thinnest arrow with a dashed outline.
Click on image to enlarge.

  • Ebolaviruses are not just blood-borne viruses in humans like HIV is for example; they are not just gastrointestinal viruses like norovirus (although droplets play a role here too); they are not considered by anyone to be airborne viruses like influenza virus
    What they are, in a transmission sense, is a hybrid of the first two - reaching high loads in the blood and the gastrointestinal system. To me, these shared features make it more clear why a different level of personal protective equipment (PPE) is needed than would be considered essential for caring with patients with just one or other type of virus
  • One distinct viral group may remain infectious for a longer period, shorter period, or not at all compared to another distinct viral group, in droplet nuclei - the air-dried (gel-like mix of proteins and salts..and infectious or non-infectious virus) form of droplets that have not yet hit an object or the ground.
  • The figure of just 1-10 viruses being required for an infection to take hold has generously been bandied about during the Zaire ebolavirus (the EBOV|Mak variant) epidemic of 2014/2015. But some overlook a simple component of this apparently easy infection process; 1-10 viruses landing on a cell is not the same as 1-10 intact infectious viruses being emitted from an infected host, travelling out of the host's infected cells in a drop of blood, semen, urine, sweat, saliva, diarrhoea or vomit, retaining infectivity while passing through various environmental conditions, onto a new host's mucosal surface, perhaps indirectly via a hard surface, getting past that body's innate immune defences and eventually attaching onto and gaining entry into that new host's cell, successfully replicating within it and then infecting neighbouring cells to establish a new infection. It may take thousands or hundreds of thousands of viruses in that initial drop of infection material to get those 1-10 infectious virus particles to start a productive, symptomatic human infection.
    We know little about this part of the story outside of the laboratory
  • On that theme, there is much in general we still do not know about the ebolaviruses and Ebola virus disease (EVD). Direct contact with virus-laden fluids or a needle-stick injury are still considered to be major routes for acquiring an ebolavirus infection but direct mucosal contact with propelled droplets may occur at distance further away than the old 3ft/1m rule.(6)
    Truly airborne dried or semi-dried droplets that contain sufficient infectious Ebola virus, can be inspired and can result in an upper or lower respiratory tract infection that progresses to become systemic EVD in humans....have yet to be found. They may contribute to infections, but it will be very hard to prove that this is a transmission pathway that exists as a thing separate from droplet transmission. The authors sort of note this difficulty too; both droplets and droplet nuclei result from coughs, sneezes and explosive vomiting and diarrhoea.
    The suggestion that droplets are produced from the respiratory tract and then inhaled by another person (6) resulting in EVD is really straining the use of "improbable"
  • I've written about some of this stuff before - on the distinct issue of Ebola virus and pigs here, on droplets and droplet nuclei here, the complexities of contact here, on seeking some better words here and on previous versions of this theme by some authors of this latest review here and here and I'm not going to rehash all of that here! I invite you to read those posts
Mixed messages..

A problems I have with this review is this line in the abstract..
We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.
While Osterholm and expert colleagues round off the review by clearly stating that airborne ebolavirus transmission is an "improbable scenario", and that droplet transmission is plausible (I don't disagree with the latter statement), parts of the rest of the review struggle to tow that line quite so clearly. The media seemed to have struggled to find that message too..

It is 'very likely' that the Ebola virus will spread through airborne particles, experts say
Daly Mail

Limited airborne transmission of Ebola is ‘very likely,’ new analysis says
Washington Post

..although one bright light in the gloom managed extremely well..

No, A New Scientific Report Does Not Say That Ebola Is Now Airborne
Vice News

Prof Vincent Racaniello noted in his blog post about the review that we understand what viruses do now, by what we have observed them to be capable of doing in the past

Do ebolaviruses actually have the potential to shift to a primary method of spread that occurs via droplets or droplet nuclei and spread like a rhinovirus, influenza virus or the name a few? If no virus which we humans have ever watched has changed its method of spread so dramatically before, why would this particular one do it now? Well, why wouldn't it, you may well ask? Because it takes more than some genomic mutations and drift to do this. At some point we need to remember that each virus comes with its own toolset and it doesn't usually have a lot of replacement parts or upgrades in a satchel over its capsid. It can only tweak its component parts so much and so far before it reaches the limit of what it "is". Could one virus become another virus? Maybe it could. I look forward to becoming Superman myself. What would it take to overcome whatever biological throttles have existed on the ebolaviruses prior to so much human spread, for a virus to stop spreading primarily by fluids resulting from certain host disease processes, to being spread mostly by inspiration of respirable droplets? Certainly something we've never seen before and something in need of a utility belt and  can of bat EBOla repellent. Again, we're not just talking about some "genotypic changes"; the ebolaviruses would need to accumulate a plethora of stable genetic changes to make that sort of transition, possibly in combination with changes in the disease processes within its

An opinion by any other title...

Despite the review being an opinion piece, it seems to have some trouble owning up to its own real opinion; that Ebola viruses can spread by a new route and cause new disease. The title really should have reflected the content better in this regard. In approximate number 5,800 words included 440 (8%) on animal transmission studies which are mostly about aerosol spread; 925 (16%) devoted to defining aerosols and droplets and trying to change the paradigm; 670 (12%) about what we need to learn, which includes some content on aerosol transmission; 670 (12%) on a respiratory transmission hypothesis. So a sizable chunk, nearly half of the content, is heavily focussed on educating us abut Ebola and aerosol transmission. The topic is additionally reinforced within every other section as well. So why hide what the article was really focussed on; not the general transmission of ebolaviruses, but transmission via an as yet unproven-route? The authors note that an "aerosol" contains all the different droplet sizes and degrees of droplet wetness and that this entire range is propelled out of us via cough, vomit, diarrhoea and by  aerosol generating mechanical procedures. We agree on that bit. But once the bigger wetter droplets fall away and one is not standing unprotected within their range, is there an infectious virus left in the drier smaller droplet nuclei which are held aloft by air currents until they impact with something or someone? 

Have we ever seen Ebola virus infections caught by people walking into a room after an infected case has left is the case for measles or rhinovirus, truly airborne transmissible viruses? Or is droplet spread only occurring in close proximity to the source? This is another point the authors raise-that being close to someone who just vomited may result in breathing in larger droplets that are infectious but have not yet fallen to the ground. How will we ever know that this is not a propelled droplet instead? Explosively coughed or vomited material can travel a sizable distance as well? So we still await some evidence to support the musing that inhaled droplets carry infectious ebolavirus in them, and that they are distinct from the more likely impacting of propelled droplets. Propelled droplets are likely a key reason that updated PPE guidelines recommend against any exposed skin and the use of eye protection, gloves, boots and a respirator; the yellow suits that will forever be linked to EVD in West Africa. But even those suits don't support that Ebola virus has been, or is showing new signs of, spreading primarily via a respiratory route?

What I could not find in this new review was a more thorough discussion - and some hypothesis and opinion - of the risk associated with how healthcare workers acquired their infections when outside of Ebola treatment units or in western hospitals. Also absent was opinion on the practical risks of semen remaining infectious, or harbouring viral RNA as was found in 2014 in a returning asymptomatic convalescent man [3] (sexual transmission has not been documented [11]). I would very much have liked to read some hypotheses on the role infectious urine might play in urban settings lacking no sewers and with densely co-located populations, since urine has been shown to remain infectious for longer than blood, in a detailed case study from Germany in 2014.[3]

Wrap up...

So to summarize, coming into contact with virus-laden body fluids either by touch, perhaps via an intermediate surface (a fomite; unproven) or by having these fluids propelled onto you (as yet unproven), are considered the main risk factors that comprise the overwhelming majority of human-acquired ebolavirus infections. Current PPE guidelines are designed to combat these and if western hospitals are any guide, they work well - although it's a tough comparison given the different carer-to-patient ratios in western hospitals compared to outbreak conditions in west Africa. 

What role "respirable droplets" or droplet nuclei play in transmitting ebolaviruses between humans awaits evidence but nothing points to a role for an airborne route of infection in west Africa.[6] Hopefully some studies will be looking very hard at this question. Nothing hints at any changes in  EBOV/Mak that could result in it becoming a "respiratory pathogen with primary respiratory spread" capability.

I recommend reading a few other recent reviews and articles to get a more rounded view [7,8,10,12] and if you want to see droplet, aerosol and airborne get smooshed together into an undifferentiated mess, that's in print too.[9]

  1. Transmission of Ebola Viruses: What We Know and What We Do Not Know
  2. Experts suspect Ebola virus sometimes spreads by air
  3. A Case of Severe Ebola Virus Infection Complicated by Gram-Negative Septicemia.
    Kreuels B, Wichmann D, Emmerich P et al.  N Engl J Med. 2014 Dec 18;371(25):2394-401
  4. Ethical issues in isolating people treated for Ebola
  5. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings
  6. Ebola virus disease in Africa: epidemiology and nosocomial transmission
  7. Understanding Ebola Virus Transmission
  8. Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in 2014: an observational study
  9. Ebola, through air or not through air: that is the question
  10. Review of Human-to-Human Transmission of Ebola Virus from the US CDC
  11. Sexual transmission of the Ebola Virus : evidence and knowledge gaps
  12. What we know about transmission of the Ebola virus among humans from the WHO

Sunday 22 February 2015

Two tales of the same review...

Could these articles about a recent review on Ebola virus transmission be any more different?

Which do you "believe"?

Limited airborne transmission of Ebola is ‘very likely,’ new analysis says Post
From the Washington Post

No, A New Scientific Report Does Not Say That Ebola Is Now Airborne
From Vice News

The article being referred to is from a team of "Ebola experts" and is entitled: 
Transmission of Ebola Viruses: What We Know and What We Do Not Know.

At this juncture might I just add that I do not consider myself a real Ebola virus disease (EVD) expert. I'm just an interested scientist who blogs about Ebola virus and the most recent outbreaks and epidemic. To be an expert, at least in my opinion, one would have to have one or more of the following under one's belt:
  • to have conducted experiments on the Ebola virus and written those up in the scientific literature
  • to have generated data from other derivative works with parts of the virus, such as in vaccine works, and written those up
  • to have treated or cared for patients with Ebola virus disease (EVD)
  • to have worked in a public health capacity managing an outbreak of EVD
The rest of us are interested parties but will likely always miss some aspect of understanding the virus and its disease having not been in close contact with it, its hosts or the response to it.

Saturday 21 February 2015

Ebola virus disease: obliterating a variant and stalled case decline...

We've seen the words vigilant and vigilance used widely in recent weeks, ever since we entered a "new phase" of the Ebola virus disease (EVD) battle/fight/war.

The reason for vigilance in all things to do with this campaign has become obvious as the weeks have passed; the reduction in cases has stalled.

I've very crudely drawn in some trends below. Whether you agree with them or not, it is clear that since the fast fall in confirmed cases reported between November-January, it seems to have become very difficult to stamp out the last fires of EVD. 

The phases.
(Very) rough trends in the number of EVD cases over time.
Date from World Health Organization situation reports (SitReps)
and situation summaries (SitSumms).
Click on image to enlarge.
Liberia has come the closest to completing this goal of obliterating the Makona variant of the Zaire ebolavirus (EBOV|Makona) with just 3-9 confirmed cases between World Health Organization (WHO) Situation Report (SitReps) during any of the past 7 weeks. It seems that recent cases can be traced to known transmission chains too and that means no surprise outbreaks. 

However, the people of Guinea and Sierra Leone have not quite got the messages that those in Liberia seem to have embraced (without touching!) so admirably. 

In the last WHO SitRep [1] it was noted that 39-45 unsafe burials (probably not all that occurred) occurred in a week and >40 EVD cases were identified post-mortem. This last observation means exposure of the community to the virus, not getting help and treatment for ill people, and unnecessarily requiring contact tracers to play catch-up. Bad for the infected people their friends and families and the response to EVD. It doesn't have to be that way.

This paints a picture of problems with Ebola outreach and education, communication and cooperation. Those things will keep the latest EVD "phase" chugging along. 

We do need to destroy this variant of Ebola virus by isolating it in the last human cases in each of Guinea, Liberia and Sierra Leone. Once those people recover or regrettably die, EBOV|Makona will be gone, except for what's in lab freezers around the world and in sequence databases thanks to the efforts of a few expert research teams. Once gone from "the wild", the evolutionary clock resets back to the EBOV variants in the animals of the forest.

EBOV|Makona knows too much; it has seen too much; it has learned too much, to be allowed to "live". It has been passed through humans too many times and while there is a vanishingly small chance it will sprout wings, it is still a virus that spreads relatively easily under the right conditions and circumstances. Explosive loss of 8 litres of fluids a day provides many ways to pass along this blood/gastro virus. EBOV|Makona may also have adapted, and continues to adapt, in other ways that would mean its stay among humans becomes lengthy and its dissemination more widespread.

More bad news from an unsuccessful obliteration of EBOV|Makona-smouldering EVD in Sierra Leone and Guinea may release new case embers that drift across borders and set new fires in other countries. We don't need hundreds of cases a day for that to happen.[3] We know cases also fly with the aid of planes (not wings). And the cycle could renew. I don't think we'll see such big outbreaks of EBOV|Makona again, for reasons I laid out here, but chasing new fires is more work than stamping out the remnants of old ones. Vigilance and action. 

I think vaccines still have an important role to play in the final phase of this epidemic, even if only 3 new healthcare worker cases were noted in the past SitRep week. Vaccine given to more than just healthcare workers could be useful here if others will accept the needle.

  • Ebola outreach
  • Education
  • Communication
  • Cooperation

Oh, and vigilance.



Thursday 19 February 2015

Avian influenza H7N9 human infection emerged 2 years ago...

Seems like only 365 days ago I wrote about H7N9 being 1 year old.

Now - it's another year later.

While we have studied, written, read and learned much, much more about this emerging respiratory virus than we have about the Middle East respiratory syndrome coronavirus - even after its 3 years among us - we are still watching a new outbreak of human H7N9 cases spread across China. 

Each year more provinces are added to the list to report human infections - more infections likely go unnoticed, unrecorded and/or unreported. Gaps in the reporting is not unexpected and not unusual. 

Each outbreak with its accompanying economic damage, financial losses, human illness and death is because of the desire to maintain a tradition, namely the consumption of freshly extinguished poultry.

We're really good at getting ourselves into pickles. And we seem to be doomed to repeat the patterns, playing catchup and never getting in front of our new and emerging infectious diseases problems. And each time we seem amazed at what we learn, but really, we learn the same thing over, and over and over again. Eventually we'll run out of infectious threats I guess. 

Or they'll run out of hosts in which to incubate in and spread from.

Happy Lunar New Year.

Gung hei fat choi! & Gong Xi Fa Cai! the Cantonese and Mandarin speaking readers who may stumble across this blog, as well as everyone else who visits!

May all who read this have a happy, healthy and prosperous Lunar New Year, an enjoyable Spring Festival and much luck in the Chinese Year of the goat (mounrain sheep)!

Wednesday 18 February 2015

Guangdong sees sense among the feathers...

Guangdong province in southern China is suspending its poultry markets. All of them. From 15-Feb to 28-Feb.[1] While the closures are only for 2-weeks, this will be very important for stopping human cases of avian influenza, particularity of the H7N9 subtype, during the bustling spring period in China. 

Live poultry market closures also remove a traditional dish of fresh cooked chicken. One can be certain that no-one will die because of the substitution of frozen or factory prepared chicken for a fresh chicken, even if chefs don't succumb to the tantrums of last year and refuse to prepare dishes made from anything but fresh market-selected poultry. One can be equally certain that if the markets remain operating during the peak season for influenza virus circulation as they have been, that human infections, and deaths, due to H7N9 infections, will also continue 

Guangdong province has been a major
source of human H7N9 cases in 2015.
Some restrictions were put in place back in December 2014 [2], but that did not stop human cases of infection or deaths.

Why does this closure in Guangdong matter? 

Guangdong province has been a major source of human H7N9 cases this year, as it was in 2014. If we look at the activity under the outbreak curves, we can see the brown line of Guangdong cases has been prominent in both years, only brought under control last year after the closure of the poultry markets...although their temporary closure may have been the reason for the long tail on Outbreak #2's epidemic curve compared to Outbreak #1. Will that tailing happen again in 2015 because Guangdong's markets are only being closed for a short period? Time will tell. 

Occurring at a similar time is the change in seasons. Seasonal change towards summer, makes the survival of influenza viruses in the environment more difficult. It's hard to tease out any one main cause of the precipitous case decline; the market closures or the seasons changing or both. Because most H7N9 human cases have exposure to poultry listed among their details when they are passed along and posted by the World Health Organization, live poultry markets clearly are one major factor for human acquisition of infection. There is literature that agrees.[3,4,5]

The activity under the epidemic curves for each of the three outbreaks. Guangdong province-acquired human cases are indicated by the brown line and features in 2014 and 2015.
Having these markets close is a great achievement for stopping these unnecessary and preventable infections and deaths die to H7N9. Its a big step, a sacrifice and its social change in action. But shutting them permanently would be better.



Thursday 5 February 2015

Cases of Ebola virus infection can be exported any old time...

I'm adding my two cents on the issues around remaining vigilant about Ebola virus disease (EVD) cases. 

There are far fewer weekly EVD cases than there used to be but it remains absolutely essential to "kill off" this particular highly-passaged Zaire ebolavirus variant. In other words, push new cases down to zero per day in all three countries, keep it there for 42-days, and thus declare all three nations free of Ebola virus transmission.

Apart from the obvious desire to see these countries rid of this horrible and deadly pestilence, another, less likely thing to consider is that more spillovers to other countries can still happen at any time. And apart from the costs, the reaction from a certain country to its first imported case, just does not bear living through again.

Whether human cases were just kicking off, or after they began accruing at an exponential rate of hundreds per day, the hotspot countries have been the source of export of a case to another country. 

That said, in my opinion we are in a much better global position today than we were six to twelve months ago. We can much more effectively engage and thwart the spread of infection from an EVD case that appears on our doorstep because we now know Ebola virus is out there and can hop on a plane, and many countries and regions within countries have done something to prepare for that rare arrival. Some countries were already in a better position than others, simply because they have (relatively) huge healthcare 
processes in place and are now aware of how to help, and how quickly to respond, should a foreign neighbour acquire a case. 

None of that is to say zero spread in other countries is a given in the near future; humans being humans, accidents and mistakes will always happen. But we are just very unlikely to see EVD spread in a new country to the extent that we saw last year. Hopefully I'm not being too naive on that call.

If we look at the images below, it's plain to see that EVD cases were exported from these countries both early on and late in the outbreaks and later epidemic. Guinea being slightly more of a culprit than the other two countries of intense and widespread transmission (Liberia and Sierra Leone).

Guinea's Ebola virus disease experience. The approximate time at which 
another country receives a person infected by Ebola virus, most likely acquired
from within Liberia, are indicated by an arrow.
Click on graph to enlarge.
Sierra Leone's Ebola virus disease experience. The approximate time at which 
another country receives a person infected by Ebola virus, most likely acquired
from within Liberia, are indicated by an arrow.
Click on graph to enlarge.

Liberia's Ebola virus disease experience. The approximate time at which
another country receives a person infected by Ebola virus, most likely acquired
from within Liberia, are indicated by an arrow.
Click on graph to enlarge.