Sunday, 29 March 2015

Where did the MERS-CoV comorbidity and animal contact fields go...? [UPDATED]

Is this the work of the US CDC and other visitors helping the Kingdom of Saudi Arabia (KSA) Ministry of Health (MOH) resolve their Middle East respiratory syndrome coronavirus (MERS-CoV) problem? Is it an arbitrary reporting change by the Command and Control Center (CCC)? Is it someone forgetting to unhide the relevant columns in their spreadsheet?
Changes to the KSA MOH MERS-CoV public 
reporting detail after 17-March-2015.
1. The MERS-CoV graph changed scale and caught up.
2. Three fields disappeared: pre-existing disease, 
animal exposure and contact with a known cases 
within a hospital setting
3. The promise of weekly updates was dangled-
without reference to a host site.
Click on image to enlarge.

I don't know why, but since 17th March, the KSA MOH MERS-CoV reports have stopped posting information about whether each newly announced MERS case had a comorbidity and whether they had animal contact. Granted, the last field was almost always "No" or "Under Investigation" - and thus of little use (we rely almost exclusively on the World Health Organization reports to provide useful animal data) - but I wonder why the MOH has chosen to stop posting even the heading this month? 

The much more epidemiologically significant description of whether the case was an "expat" or a "Saudi" citizen remains - whew! 

And the MOH has continued to do away with all of that pesky detail that might allow an observer to link a death to a previously announced case. Thank goodness we don't have that clutter to deal with - or the details from the found113 which I presume are now completely lost in the sands of time. 

I guess the removal of these latest 2 data fields is just all part of providing the world with more of that full transparency and up-to-date information about this emerging pathogen - like the MOH "News" page - all the latest info you could want from August and earlier is to be found there. 

Oh well, at least you can get the latest from the weekly updates...if Google Translate's efforts can be understood.

It really isn't as hard as it is being made to look to get the reporting aspects right.

Friday, 27 March 2015

Editor's Note #22: Two years old today..

On March 27 2013, around the time of Easter and the school holidays, I gave in to the urgings of my wife, to try this blogging thing. 

And today it's two years later and now very clear to me that writing for fun, but based around what I know in science, will be something I do for many years to come. 

At times it's been tough - or maybe other pressures made it feel tougher than it was - and I've considered stopping and have at times paused. As hard as it was though, I found myself wanting to chime in on stuff and could not stay away. I still find that weird, but it must have been a part of me all along - I just hadn't noticed it until after I turned 40'ish. I'm a bit slow sometimes. 

Turns out that I enjoy writing and I needed a hobby that I enjoy and that helped inform and generated such unexpected positive feedback. Everyone needs that I think. Bit of a shame that the typos don't get fewer but such is life. 

It also turns out that blogging made me resign from my job of 23 years - which just so happens to co-occur with this very date. No, of course my resignation was not for such a simplistic reason, but blogging was one of a few major factors that set the process in motion. In particular, blogging about outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV), avian influenza A(H7N9) virus and the Ebola virus disease epidemic in West Africa. It was that last one that really had the greatest impact on me though. 

From blogging has come more interactions with the media (something I am now a firm believer in more scientists needing to do-communicate what we do to our stakeholders), new collaborations, papers, strange discussions with affiliate Institutes about why they'd rather me not link them in print or press to this press or these papers since I had no research funding for these viruses, friendly discussions with very high ranking Health officials, advice to documentary makers and then an invited role helping out my State's public health team. That one was the kicker. The feeling that the virology information and patterns I'd spent years accruing and piecing together in my head, and now blogging about and drawing graphs and graphics to describe, could be used for the greater good completely ruined me. But in a good way. It triggered many realisations about my current role, some were familiar to me as I had been living with them daily for years, others I had felt in the corners of my mind but they were too intangible and just wouldn't coalesce into anything that would describe itself to me and yet others that were patterns I simply didn't see. Told you I was a bit slow sometimes.

You could of course dismiss all of this as the rantings of a failed scientist who - despite an h-index of 32, 80 papers (15 with >100 citations), >400 citations per year for the past 9 years, 14 book chapters, roles as an Associate Editor at the Journal of Clinical Virology, a Section Editor at Biomolecular Detection and Quantification and an Editorial board for Viruses as well as having continuous competitive research grant funding since he was awarded his PhD in 2003 until 2014 - had missed out on achieving most of his recent grant applications. Go right ahead.

I wanted to use what I'd learned for the greater good. Yeah - as a comic nerd that makes even me cringe a little. But that's where I've been heading, knowingly or not, for some years now. Well, soon I'll be a part of a team that cam help me to do that. 

So I wish you a Happy 2nd birthday little VDU. You've helped me to grow and to learn at the rate of a human two year old. And in doing so, I've met and made friends with a lot of great people around the world. For such tiny things, viruses can have such an impact on us. Quite the hobby.

Monday, 23 March 2015

Useful Ebola virus disease graphics...

Good graphics can be really helpful to convey information quickly - and no-one has time to read words anymore right?


The one above came from CNN [1] and presents the number of cases that have been treated in the United States prior to the 11 or so contacts/associates of the last unidentified case being evacuated.

The second one, above, came form the European Centre for Disease Control and Prevention (ECDC).[2] These guys make excellent plane travel/infectious disease maps. This one shows that the UK has kept pace with the US in medical evacuations or repatriations of EVD cases, or suspected cases, from the hotzone in west Africa.

References..

  1. http://edition.cnn.com/2015/03/16/us/new-day-five-things/index.html
  2. http://ecdc.europa.eu/en/healthtopics/ebola_marburg_fevers/Pages/medical-evacuations.aspx

Saturday, 21 March 2015

Liberia enters the next phase of Ebola virus disease (EVD) eradication with a new case...

version 2

What a heartbreaking disappointment this is for the people of Liberia, with a reported new case of EVD in a 44-year old woman who showed signs of disease 15th March and tested positive for Ebola virus on Friday 20th in Monrovia, Liberia.[2,7,8] after more then 3-weeks (28 days or more[6]) with zero new cases and no ongoing, known, transmission of Ebola virus in any county in the country.[5] The previous final case in Liberia tested negative around the 3rd of March (about 17-days ago), when the 42-day clock was started.[5] 

Now it has been stopped. 

Starting it again will await this new case returning a negative test as well as all their contacts (who will be monitored for 21-days) being declared infection- (actually disease-, but I say infection intentionally) free.

And thus we enter the next phase – that of a different type of frustration and heartbreak as countries within the tri-nation hotzone come tantalisingly close to being declared free of known cases of Ebola virus disease (EVD; see how those seemingly pedantic words [1] have added meaning now?) or virus transmission, or in fact succeed only to have a random case pop up from somewhere unexpected or travel across a border causing disappointment for the people of the country, the aid workers and the family and friends of the new case. 

A random case will also trigger all new contact tracing efforts to try and find the source and lock down further spread as quickly as possible. 

There is noise on twitter (see Tweet below) and in the media quoting authorities [6] noting that the case may have been from a sexual contact with a previously infected male. Infectious virus has been found in semen in the past in which it can linger for more than a month [3,4], but this has not been a factor in the timing of release of convalescent males in the recent epidemic. If this is the route of acquisition, then the ensuing costs, scope of the response, risk to a country that had nearly cleared the virus and to the stamina of an Ebola-ravaged country may serve to justify additional testing the future.
The route of acquisition in this latest case remains totally unconfirmed at writing.[7] I'll update this post as I find more details.

My thoughts are with you Liberians – stay strong – it’s a setback to be sure, but you were very close this time and will get there. 

References...
  1. http://unfoundationblog.org/mali-42-days-free-of-ebola-transmission/ 
  2. http://www.bbc.com/news/world-africa-31991748?ocid=socialflow_twitter
  3. http://www.ncbi.nlm.nih.gov/pubmed/25467652
  4. http://virologydownunder.blogspot.com.au/2014/08/ebola-virus-in-semen-is-real-deal.html
  5. http://apps.who.int/ebola/current-situation/ebola-situation-report-18-march-2015
  6. http://www.aljazeera.com/news/2015/03/ebola-case-ends-liberia-countdown-virus-free-150321003004879.html
  7. http://time.com/3753233/ebola-liberia-new-patient/
  8. http://www.nytimes.com/2015/03/21/world/africa/liberia-reports-first-ebola-case-in-weeks.html

Wednesday, 18 March 2015

Catching Ebola: mistakes, messages and madness [amended]

Written by Dr. Ian M. Mackay and Dr. Katherine E. Arden

Despite obvious community and media fear, speculation and exclamation that Ebola virus would enter and spread widely within countries outside the hotzone, such an event did not come to pass in 2014. The early public health messaging on Ebola virus and disease were, for the most part, spot on. 

In 2014 and 2015, thousands of cases of Ebola virus disease (EVD) ravaged Guinea, Sierra Leone and Liberia in 2014 (the "hotzone"). A smaller outbreak was defeated in Nigeria [8] and another distinct Ebola virus variant drove an outbreak of EVD in the Democratic Republic of the Congo[7] - they too controlled spread of the virus. Ebola virus travelled from the hotzone to other countries including Senegal, Nigeria, the United States of America (USA), Mali and most recently, the United Kingdom. It did this by hitching a ride in a usually unknowingly infected human host. 


Over 40 people have been intentionally evacuated or repatriated for observation or more aggressive supportive care - and perhaps the use of experimental therapies - to France, the USA, Spain, Sweden, Norway, Denmark, Germany, Netherlands, Italy, Switzerland and the United Kingdom.[1,18] 


Recently, the last country outside of Africa to have unintentionally acquired a case of EVD, the United Kingdom, passed a milestone; 42 days since the last ill patient tested negative for Ebola virus. They were declared free of known virus transmission.[17]


Containing the spread of each imported case has relied upon stringent infection prevention and control measures and the identification and monitoring of each and every contact of an Ebola virus infected person. And these have been used with great success. No country, apart from the three in which transmission has been widespread and intense, has seen the appearance of multiple and continuing rounds of new EVD cases. A rough calculation of the numbers of contacts falling ill from each EVD index case who travelled outside the hotzone is shown in the table. It only includes those with data available publicly.


On average, fewer than 1 in 100 contacts (0.8%) came down with EVD. Not the easiest virus to catch? If you compare that to measles, 9 in 10 non-immune people close to an infectious measles case will acquire disease (90%).[19]


Table 1. Index cases and the proportion of contacts they infected
a-man travelled overland from Guinea while infected; b-man with EVD repatriated from Liberia; c-man who flew while symptomatic to Lagos, Nigeria with a stopover in Lome, Togo; d-man flew from Liberia while infected; e-male healthcare worker returned from Guinea; f-a 2 year old girl travelling overland while infected; g-male travelled by car to a clinic in Bamako, Mali from Guinea (assumed Ebola case); h-female healthcare worker returning from deployment in Sierra Leone; i-this figure may indicate all contacts for  both Mali cases
The extent of the fear inspired by the first imported EVD case was especially clear from the massive spike in social media content from the United States which followed the arrival from Liberia of an individual with EVD; far more social media activity than had been seen in the United States to that point, or since.[14,10] This month, even though 11 contacts/associates are being flown back to the United States for observation; on the heels of the index case, social media activity has barely responded – in fact Twitter is possibly more positive/neutral about Ebola in the US in March 2015 than in August 2014, rather than excessively fearful, mean or just plain hysterical.[10] 

Some of the heat may have been taken out of the emotional response to Ebola outside Africa because it is now clear that a catastrophic pandemic is not going to happen. Kinda like we were told. I know; it;s so uncool to be reminded that you were told something by a grown up - and it was right! 


Well...THEY TOLD YOU SO!!! 


Nations with better (some!) healthcare infrastructure, preparedness, healthcare to patient ratios and those who got advice and help quickly, curtailed the spread of EVD. Kicked it out. Stomped on it. Terminated it. This was true even when contacts had been classified as at high risk of getting sick.[15] 


Public health messaging made some big calls early on. Some examples include tweets by Head of Public Relations for the WHO, Gregory Härtl, and later by the Centers for Disease Control and Prevention’s Director, Dr Tom Freiden.[11] They made it clear that Ebola virus was not easy to catch and that measures to stop an outbreak were known.[16] At the time, this didn't jibe with other voices and the unprecedented number of EVD cases and deaths, especially from August onwards, that were tallying up at an exponential rate in west Africa. But those messages, while technically correct, probably didn't convey enough of some of the biggest factors in a disease outbreak - fear, ignorance (meant only in the sense of no specific knowledge of Ebola virus and EVD), tradition and history - the human factors rather than the viral ones. Some comments about transmission suggested essentially no chance of even a single new case happening on the home soil of richer countries - they were overly enthusiastic. They were unjustifiable and when some hospital workers in non-African countries became infected, they were ultimately seen for the mistake in message crafting that they were.


Much of the science of the Ebola epidemic is yet to be written, but what we know today is that it is unlikely that Ebola transmission is any different from what was observed decades ago. Direct, physical contact with a very ill person’s fluids is the overwhelmingly biggest risk factor to target in reducing disease spread. And even then there's no guarantee that disease will result from all instances of contact. We still have much to learn.


What has changed since the bad old days? We’ve learned how to better manage and support EVD cases. EVD is a disease that caught us a little unawares in its combination of "skills" - it spreads by care and through direct contact, accrues a lot of virus in the blood but also vast quantities in explosively propelled fluids produced from "both ends"; virus that remains infectious for even longer in urine and semen than in blood. Quite the mix of issues to deal with.


EVD is no longer a death sentence, and this needs to become part of the new messaging paradigm. It's a message that may still be highly relevant to those in Guinea and Sierra Leone who seemingly would still rather risk death than seek care at a treatment unit. Post-mortem detection of EVD cases is ongoing, although may be on the decrease but also nearly a third of cases in Guinea and Sierra Leone are arising from unknown human sources.[21] Contextual communication is needed from within each country and region. That aspect cannot be allowed to wane. 

With early care, and active care, rather than the palliative model that seemed to occur when the ratio of EVD cases to healthcare workers was too high, patients mostly surviveThe EVD treatment center at the Hastings Police Training School near Freetown, Sierra Leone stands as a model for successful life saving and is the best described example of this from the west Africa epidemic to date.[20]

Ebola virus infection is not easy to catch, it can be survived much more often than was generally accepted and its spread can indeed be stopped. Stopping an Ebola outbreak quickly seems to be helped mostly by prior education, ongoing communication, forewarning and preparation but also needs ongoing surveillance, functional healthcare infrastructure, a range of experienced workers and all of that must all be under-written by money.

But even with all that help in place, mistakes will be made and lessons will be learned, by everyone, all the time. Embrace that. We're all human.


References 

  1. http://www.nytimes.com/interactive/2014/07/31/world/africa/ebola-virus-outbreak-qa.html
  2. http://apps.who.int/iris/bitstream/10665/137510/1/roadmapsitrep_5Nov14_eng.pdf 
  3. http://www.who.int/mediacentre/news/ebola/20-november-2014-mali/en/ 
  4. http://www.who.int/mediacentre/news/ebola/17-october-2014/en/ 
  5. http://www.nyc.gov/html/doh/html/pr/press-statements.shtml 
  6. http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html 
  7. http://www.nejm.org/doi/full/10.1056/NEJMoa1411099 
  8. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20920 
  9. http://apps.who.int/ebola/en/status-outbreak/situation-reports/ebola-situation-report-14-january-2015 
  10. http://www.symplur.com/blog/the-life-cycle-of-ebola-on-twitter/ 
  11. http://www.foxnews.com/opinion/2014/08/09/truth-about-ebola-us-risks-and-how-to-stop-it/ 
  12. http://www.nytimes.com/interactive/2014/10/20/us/cascade-of-contacts-from-ebola-case.html 
  13. https://www.gov.uk/government/news/ebola-contact-tracing-underway
  14. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)62016-X.pdf
  15. http://www.who.int/mediacentre/news/ebola/3-september-2014/en/ 
  16. http://www.bloomberg.com/news/videos/b/4a798222-3666-446d-81ff-f21412a3f068?cmpid=yhoo
  17. http://www.euro.who.int/en/health-topics/emergencies/pages/news/news/2015/03/united-kingdom-is-declared-free-of-ebola-virus-disease/_recache
  18. http://ecdc.europa.eu/en/healthtopics/ebola_marburg_fevers/Pages/medical-evacuations.aspx
  19. http://www.cdc.gov/measles/about/transmission.html
  20. http://www.nejm.org/doi/full/10.1056/NEJMc1413685
  21. http://apps.who.int/iris/bitstream/10665/156273/1/roadmapsitrep_18Mar2015_eng.pdf?ua=1&ua=1

Monday, 9 March 2015

Last country outside the hotzone to pass 42-day period-awaits official announcement...

The United Kingdom (UK) reached the 42-day mark, during which no new known cases resulted from the index case, on the 6th March 2015. 

The UK's accidentally imported Ebola virus disease (EVD) case, a female healthcare worker returning from deployment in Sierra Leone [1], last tested negative for Ebola virus on 23rd of January. She was discharged from hospital on 24th of January.[2]


Timeline of the UK EVD case. 
Green=onset; pink=hospitalization; blue=date of final NEG test on which the 42-day clock started; grey box=country considered, if not yet declared, free of known ongoing Ebola virus transmission.
Click on image to enlarge

All that remains now is for an official announcement...from someone (else) official, singing this achievement from the rooftops. 

A Public Health England report (below), posted on the UK government website has already acknowledged the 42 day mark. 

A bit understated even for the mother country!


From here
Click on image to enlarge.
References...

  1. World Health Organization Disease Outbreak News (DON)
    http://www.who.int/csr/don/30-december-2014-ebola/en/
  2. Ebola Situation Report - 4 March 2015
    http://apps.who.int/ebola/current-situation/ebola-situation-report-4-march-2015

MERS in the UAE...

Over my weekend, the Robert Koch Institute (RKI) in Germany reported that they had a Middle East respiratory syndrome case (65 year old returning German) under their care, imported from the United Arab Emirates (UAE).[1,2]

There have been two other MERS cases hospitalized in Germany - 1 from Qatar and the other originating from the UAE, where infections are presumed to have been acquired.

This latest case is nothing astonishing but it does act as a warning that there most likely are other MERS cases circulating in the UAE. Alternatively, this person may have visited the Kingdom of Saudi Arabia (KSA) before travelling to Germany, acquiring an infection there. 

When cases emerge in other countries they can be very telling. They speak of what might be happening in the host country. The UAE has only reported (this is the important word for any outbreak observation) a single case since July last year. Was RKI just "lucky" to pick up the only other MERS-CoV case in the UAE over the past 8 months? Highly doubtful. In the absence of other information (WHO detailed data will surely follow soon), it is much more likely that MERS-CoV is circulating in the UAE, as it is in the KSA and possibly neighbouring countries, but that cases are going either undetected or unreported.


When animals were described alongside human cases.
Click on graph to enlarge.
Taken from MERS number page.
Current MERS-CoV circulation would be in keeping with the popular theory that MERS is a seasonal zoonosis (animal infection that spills over to humans causing disease on occasion), and that more primary human cases, although still relatively rare, emerge during periods when more infections are occurring in camels - which seems to occur around this time of year. That seasonality in camels has not really been established yet and still it is one popular theory among those who do not completely deny any involvement of camels in MERS whatsoever. Also worth repeating is that MERS-CoV appears to be inefficient at transmitting between people - at least so far as the testing done to date has revealed.

From the rare spillover cases acquired by humans from camels, humans proceed to do the lion's share of the work in continuing to spread MERS-CoV among humans. Yay us. 

In recent WHO disease outbreak news reports [3,4], the detailed information reveals multiple instances of cases having shared wards with laboratory-confirmed MERS-CoV cases - and despite assurances that the same healthcare workers did not attend both people, some form of contact has apparently occurred somewhere, somehow. The precise details of what that contact was, still seem to be beyond the capacity of the Saudi disease detectives to capture. But in that detail lies some important hospital (or community) transmission clues - even if those clues are as simple as revealing that the wring question are being asked, too few contacts are being tested, healthcare workers movements are not being tracked sufficiently, or finding that people (patients, contacts and healthcare workers) do not answer the question fully. 

A little thing called infection prevention and control is apparently still not being adequately adhered to in some parts of the region. 

In other words, MERS is a rare but preventable disease.

References...

  1. Flutrackers post
    https://flutrackers.com/forum/forum/novel-coronavirus-ncov-mers-2012-2014/germany-coronavirus/726247-germany-reports-3rd-imported-mers-cov-case?_=1425773133137
  2. Robert Koch Institute [German]
    http://www.rki.de/DE/Content/InfAZ/M/MERS_Coronavirus/MERS-CoV.html
  3. WHO MERS DON 06MAR
    http://www.who.int/csr/don/6-march-2015-mers-saudi-arabia/en/
  4. WHOMERS DON 23FEB
    http://www.who.int/csr/don/23-february-2015-mers-saudi-arabia/en/


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. 

LLAP

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... http://virologydownunder.blogspot.com.au/2014/08/mers-cov-daily-monthly-and-cumulative.html

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.



References...
  1. Kingdom of Saudi Arabia Ministry of Helath MERS-CoV data http://www.moh.gov.sa/en/CCC/pressreleases/pages/default.aspx

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 measles..to 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 host...us.

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 it...as 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]

References...
  1. Transmission of Ebola Viruses: What We Know and What We Do Not Knowhttp://mbio.asm.org/content/6/2/e00137-15
  2. Experts suspect Ebola virus sometimes spreads by air
    http://www.cidrap.umn.edu/news-perspective/2015/02/experts-suspect-ebola-virus-sometimes-spreads-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
    http://www.nejm.org/doi/full/10.1056/NEJMoa1411677
  4. Ethical issues in isolating people treated for Ebola
    http://www.ncbi.nlm.nih.gov/pubmed/25588871
  5. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settingshttp://www.ajicjournal.org/article/S0196-6553(07)00740-7/pdf
  6. Ebola virus disease in Africa: epidemiology and nosocomial transmissionhttp://www.ncbi.nlm.nih.gov/pubmed/25655197
  7. Understanding Ebola Virus Transmission
    http://www.mdpi.com/1999-4915/7/2/511
  8. Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in 2014: an observational study
    http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(14)71075-8/abstract
  9. Ebola, through air or not through air: that is the question
    http://www.ncbi.nlm.nih.gov/pubmed/25646157
  10. Review of Human-to-Human Transmission of Ebola Virus from the US CDC
    http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html
  11. Sexual transmission of the Ebola Virus : evidence and knowledge gaps
    http://www.who.int/reproductivehealth/topics/rtis/ebola-virus-semen/en/
  12. What we know about transmission of the Ebola virus among humans from the WHO
    http://www.who.int/mediacentre/news/ebola/06-october-2014/en/