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Showing posts with label transmission. Show all posts
Showing posts with label transmission. Show all posts
Wednesday, 16 August 2017
Wednesday, 27 July 2016
Public Zika virus data can be volatile Zika virus data...
So it turns out I hadn't had a stroke or started losing my mind.
....10 hours earlier....
I received an answer to my questions tweeted at the Colombian National Institute of Health asking why Colombia's Zika virus (ZIKV) data had been revised downward. Was it simply data cleaning? How did it happen? Why now? As you can see from the drop in weekly figures (that last red bar), it was a quite a cleanup if so - a drop in 5,000 cases!
Dr Fernando Ruiz, the Deputy Minister of Public Health and Service Delivery Colombia kindly engaged me on Twitter, telling me that each week their data get adjusted to account for current and former week's lags. I sent him Graph 1 above to try and reiterate that this past epidemiological week had been a bit different than any other this year. When he bounced some numbers at me something seemed weird - these were different from what I'd recorded.
Sure enough, my spreadsheet no longer matched up with the numbers I'd harvested on Sunday morning (my time, AEST) from the Week No.28 Colombian Epidemiological Bulletin.
Weird. My usual first reaction - it's all my fault. Had I been daydreaming when I copied the numbers across? Had my Excel formulae betrayed me (never!)? Had the kids edited my blog? Had the cat sneakily deleted and typed a few figures. Had I had a small cerebral incident? Am I having one now?
Am I doomed to never know the answer?
Thankfully, @FluTrackers had a post from @thelonevirologi including charts and numbers from the Colombian data and sure enough a key figure was there that was common to both our datasets - but no longer anywhere to be found on the Colombian bulletin - 7 166 confirmed laboratory cases. And, coming to the rescue of my sanity, @thelonevirologi still had the original PDF - the data had indeed been released wrongly and then corrected and re-released by the National Institute of Health. Phew.
Public data are volatile
This really is a stark reminder that public data are volatile and can change.
Sometimes that change may not be identified by the publisher - no version numbering and no note to say what changed and why. Simple stuff to add, but sometimes completely absent.
We bloggers, who live in the 'grey literature' world (and rarely attract citations from the scientific literature), may be better at understanding the need to own our changes and mistakes. We often try to correct them in a way that is obvious to those who use or even rely on our information. This is just good practice.
And what about Colombia's ZIKV numbers this week?
As to the updated ZIKV figures from Colombia, the revised versions show that clinically suspect ZIKV disease cases do in fact continue to rise (+933) and that there were 22 more confirmed cases among pregnant women added this past week. No general ZIKV disease confirmations were reported after the 176 from last week and no new cases of ZIKV-associated microcephaly were added this week after 4 consecutive weeks of growth. Perhaps this is one of those laboratory 'off weeks'.
Colombia notes that it expects ZIKV-related microcephaly cases to increase in September and October 2016 as more pregnant women come to term.[2] A nearly 8% increase in (known) miscarriages has already been reported in Colombia but no rise in the use of abortion clinics which might otherwise "hide" the congenital impact of ZIKV infection not registered as microcephaly.[3]
Given these ZIKV infections are still being suspected and detected, it seems very strange that Colombia picked now to declare it's epidemic over.[2] For certain, numbers have been slowing each week for at least 6 weeks but they are still being reported (perhaps just lagging older results?).
A quick summary: sexual events play a role in ZIKV transmission, persistence of virus is real at several sites, we have not yet examined all possible transmission avenues (oral and respiratory epithelium, eyes, ingestion) and we still don't know whether the 80% of cases that are asymptomatic play any role in human-to-mosquito or human-to-human transmission nor whether that 80% figure still holds today.
Perhaps the Colombians simply mean that the ZIKV numbers per week have fallen below some arbitrary internal epidemic threshold value now. Maybe cases are still being identified, just not at epidemic levels or rates. I'd have thought a threshold would take more than a year and a bit to determine for a new disease with so much still unknown, but perhaps not.
....10 hours earlier....
I received an answer to my questions tweeted at the Colombian National Institute of Health asking why Colombia's Zika virus (ZIKV) data had been revised downward. Was it simply data cleaning? How did it happen? Why now? As you can see from the drop in weekly figures (that last red bar), it was a quite a cleanup if so - a drop in 5,000 cases!
 |
| Graph No. 1. The cumulative curve of suspected ZVD cases (pink circles, left-hand axis) and the change in suspected ZVD case numbers when compared to the preceding week's total (red bars, right-hand axis) including the original epidemiological week No. 28 data. Data from [1]. Click on graph to enlarge. |
 |
Graph No.2. The cumulative curve of confirmed ZIKV infections
(lilac circles, left-hand axis) and the change in confirmed ZIKV infection
numbers when compared to the preceding week's total
(purple bars, right-hand axis). Now added the reported umber of microcephaly cases
confirmed as ZIKV infected (yellow bars, right-hand axis) including the original
epidemiological week No. 28 data. To account for adjustments
that take cases away when there is no weekly case growth, a negative
value - the y-axes now allow for negative values. Data from [1].
Click on graph to enlarge.
|
Dr Fernando Ruiz, the Deputy Minister of Public Health and Service Delivery Colombia kindly engaged me on Twitter, telling me that each week their data get adjusted to account for current and former week's lags. I sent him Graph 1 above to try and reiterate that this past epidemiological week had been a bit different than any other this year. When he bounced some numbers at me something seemed weird - these were different from what I'd recorded.
Sure enough, my spreadsheet no longer matched up with the numbers I'd harvested on Sunday morning (my time, AEST) from the Week No.28 Colombian Epidemiological Bulletin.
Weird. My usual first reaction - it's all my fault. Had I been daydreaming when I copied the numbers across? Had my Excel formulae betrayed me (never!)? Had the kids edited my blog? Had the cat sneakily deleted and typed a few figures. Had I had a small cerebral incident? Am I having one now?
Am I doomed to never know the answer?
Thankfully, @FluTrackers had a post from @thelonevirologi including charts and numbers from the Colombian data and sure enough a key figure was there that was common to both our datasets - but no longer anywhere to be found on the Colombian bulletin - 7 166 confirmed laboratory cases. And, coming to the rescue of my sanity, @thelonevirologi still had the original PDF - the data had indeed been released wrongly and then corrected and re-released by the National Institute of Health. Phew.
Public data are volatile
This really is a stark reminder that public data are volatile and can change.
Sometimes that change may not be identified by the publisher - no version numbering and no note to say what changed and why. Simple stuff to add, but sometimes completely absent.
We bloggers, who live in the 'grey literature' world (and rarely attract citations from the scientific literature), may be better at understanding the need to own our changes and mistakes. We often try to correct them in a way that is obvious to those who use or even rely on our information. This is just good practice.
And what about Colombia's ZIKV numbers this week?
As to the updated ZIKV figures from Colombia, the revised versions show that clinically suspect ZIKV disease cases do in fact continue to rise (+933) and that there were 22 more confirmed cases among pregnant women added this past week. No general ZIKV disease confirmations were reported after the 176 from last week and no new cases of ZIKV-associated microcephaly were added this week after 4 consecutive weeks of growth. Perhaps this is one of those laboratory 'off weeks'.
Colombia notes that it expects ZIKV-related microcephaly cases to increase in September and October 2016 as more pregnant women come to term.[2] A nearly 8% increase in (known) miscarriages has already been reported in Colombia but no rise in the use of abortion clinics which might otherwise "hide" the congenital impact of ZIKV infection not registered as microcephaly.[3]
Given these ZIKV infections are still being suspected and detected, it seems very strange that Colombia picked now to declare it's epidemic over.[2] For certain, numbers have been slowing each week for at least 6 weeks but they are still being reported (perhaps just lagging older results?).
A quick summary: sexual events play a role in ZIKV transmission, persistence of virus is real at several sites, we have not yet examined all possible transmission avenues (oral and respiratory epithelium, eyes, ingestion) and we still don't know whether the 80% of cases that are asymptomatic play any role in human-to-mosquito or human-to-human transmission nor whether that 80% figure still holds today.
Perhaps the Colombians simply mean that the ZIKV numbers per week have fallen below some arbitrary internal epidemic threshold value now. Maybe cases are still being identified, just not at epidemic levels or rates. I'd have thought a threshold would take more than a year and a bit to determine for a new disease with so much still unknown, but perhaps not.
 |
Graph No. 3. The corrected cumulative curve of suspected ZVD cases (pink circles, left-hand axis) and the change in suspected ZVD case numbers when compared to the preceding week's total (red bars, right-hand axis) including the updated epidemiological week No. 28 data. Data from [1]. Click on graph to enlarge. |
 |
| Graph No.4. The cumulative curve of confirmed ZIKV infections (lilac circles, left-hand axis) and the change in confirmed ZIKV infection numbers when compared to the preceding week's total (purple bars, right-hand axis). Now added the reported umber of microcephaly cases confirmed as ZIKV infected (yellow bars, right-hand axis) including the updated epidemiological week No. 28 data. To account for adjustments that take cases away when there is no weekly case growth, a negative value - the y-axes now allow for negative values. Data from [1]. Click on graph to enlarge. |
References...
- http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/Forms/public.aspx
- http://www.nytimes.com/2016/07/26/world/americas/colombia-zika-epidemic-end.html?partner=rss&emc=rss&smid=tw-nytimes&smtyp=cur&_r=0
- https://www.washingtonpost.com/world/the_americas/colombia-offers-the-possibility-that-the-zika-epidemic-may-not-be-as-bad-as-feared/2016/07/12/d8c91e60-3d78-11e6-9e16-4cf01a41decb_story.html?postshare=8051469159730881&tid=ss_tw
Thursday, 14 January 2016
Ebola virus disease is not known to be occurring in humans anywhere in the world right now...but the virus is probably everywhere it was before..
"Ebola" is not "extinct"
Ebola virus is not kicked out of West Africa.
West Africa is not "Ebola free".
It is just wrong to say there is no more Ebola virus in Liberia, Guinea or Sierra Leone.
But - as of right now - there are no known human cases of Ebola virus disease (EVD) in Guinea, Liberia, Sierra Leone, or anywhere else in the world for that matter.
That does not mean there are not cases we don't know about. It certainly does not mean that Ebola virus is not still to be found in one or more species of animal reservoir in the forests throughout Africa.
Of course we still don't know every way in which Ebola virus can re-occur in and from humans. We hardly know all the details of what it has done during the past 2 years thanks to slow and old fashioned ideas about publishing important clicnial data during times of wide need.
Do we have reliable antivirals to use after this epidemic? We do not. We have a pretty good looking vaccine - and lots of other potential things. We did show what the world can do when it works together in trying to get a vaccine to people. But we started much too late, in every aspect of the response. Everyone did. Except those on the ground already.
Is Ebola virus persisting in an unknown number of EVD survivors? Undoubtedly. Sorry - but stigmatisation aside - that is a fact. Sticking our heads in the sand and not looking closely enough at events are two of the many reasons EVD was able to sow the destruction it did in West Africa.
Let's face the facts. Not hide from them or fail to fully explore them.
For the 900 health workers, of whom >500 died; for the >28,000 EVD case and >11,000 deaths; for the many families and friends, villages and communities who lost someone dear to them - we are all so glad it is nearly over. There will be more challenges in the coming month and years, but the constant Ebola-driven fear, sickness and death is behind you now.
One way or another.
For the rest of us, it is our responsibility to do honour to those who have and still are suffering by never again being so slow, so arrogant and so limited in our imagination as to let this happen - to any country - again.
But of course, we will.
We do.
We are.
Ebola virus is not kicked out of West Africa.
West Africa is not "Ebola free".
It is just wrong to say there is no more Ebola virus in Liberia, Guinea or Sierra Leone.
But - as of right now - there are no known human cases of Ebola virus disease (EVD) in Guinea, Liberia, Sierra Leone, or anywhere else in the world for that matter.
That does not mean there are not cases we don't know about. It certainly does not mean that Ebola virus is not still to be found in one or more species of animal reservoir in the forests throughout Africa.
Of course we still don't know every way in which Ebola virus can re-occur in and from humans. We hardly know all the details of what it has done during the past 2 years thanks to slow and old fashioned ideas about publishing important clicnial data during times of wide need.
Do we have reliable antivirals to use after this epidemic? We do not. We have a pretty good looking vaccine - and lots of other potential things. We did show what the world can do when it works together in trying to get a vaccine to people. But we started much too late, in every aspect of the response. Everyone did. Except those on the ground already.
Is Ebola virus persisting in an unknown number of EVD survivors? Undoubtedly. Sorry - but stigmatisation aside - that is a fact. Sticking our heads in the sand and not looking closely enough at events are two of the many reasons EVD was able to sow the destruction it did in West Africa.
Let's face the facts. Not hide from them or fail to fully explore them.
For the 900 health workers, of whom >500 died; for the >28,000 EVD case and >11,000 deaths; for the many families and friends, villages and communities who lost someone dear to them - we are all so glad it is nearly over. There will be more challenges in the coming month and years, but the constant Ebola-driven fear, sickness and death is behind you now.
One way or another.
For the rest of us, it is our responsibility to do honour to those who have and still are suffering by never again being so slow, so arrogant and so limited in our imagination as to let this happen - to any country - again.
But of course, we will.
We do.
We are.
Tuesday, 29 December 2015
Congratulations to Guinea for defeating its Ebola virus disease epidemic!
CONGRATULATIONS!!!
After a very long and painful battle with many, many losses, Guinea has stopped the Ebola virus epidemic that began there in December 2013; two years ago.[1]
For those of us that have been watching this tragedy unfold from the sidelines since the numbers started rolling out 23 March 2014, much more so for those citizens of Guinea and Liberia and Sierra Leone who have lived and died through this, for those who went to their aid, for those who facilitated that aid and for those in countries all around the world who received and treated cases - we are happy today in a way we have not been for nearly two years. Longer for some who were involved in caring for and trying to understand and diagnose the disease in the suspected index case, a small child from Meliandou village, Guéckédou in Guinea who became ill 26 December 2013.
After a very long and painful battle with many, many losses, Guinea has stopped the Ebola virus epidemic that began there in December 2013; two years ago.[1]
From Guinea, the Makona variant of a Zaire ebolavirus spread to and throughout Liberia and Sierra Leone. For Liberia, the wait for its third declaration of freedom from any new acute human cases, must continue until 14 January.[2] Two weeks and a bit.
Sierra Leone has remained free any human cases since early November.[3]
My family and I were out having lunch when the clock ticked over and my 10-year old boy (10M) said "Dad, no-one at any of these other tables will know how good it is to hear this news". My family has talked a lot about Ebola virus and Ebola virus disease in the past year and a half. And we've all learned a lot by talking and sharing and generally communicating. We've also been frequently reminded of all that we have. But 10M was likely very right.
 |
| From http://virologydownunder.blogspot.com.au/2014/07/ebola-virus-disease-evd-2014-west.html |
While cases and clusters may yet flare up in Guinea and elsewhere in West Africa there remain many thousands of survivors who are still suffering the consequences of infection and of viral persistence.
Good luck Guinea on your 90-day period of vigilance - and beyond. You have earned some dancing!
References...
Saturday, 7 November 2015
Congratulations to Sierra Leone for defeating its Ebola virus disease epidemic!
Edited by Katherine Arden, PhD.
Note to Correspondents
Subject: Ebola transmission in Sierra Leone over.
Nation enters 90-day enhanced surveillance period
On 7 November 2015, if no new case of Ebola virus disease is recorded, Sierra Leone will have met the criteria set by the World Health Organization (WHO) for declaring the end of Ebola transmission. If Sierra Leone meets that milestone, on that day, the WHO will declare the end of Ebola transmission in Sierra Leone, at an event organised by the Government of Sierra Leone through the National Ebola Response Centre (NERC)."
Within the next 90 day enhanced surveillance period and in the months and months to come, we may see a case or cases pop up and clusters may result. But Sierra Leone knows what Ebola virus disease is and how to deal with it. It won't be caught out the same way again.
Nation enters 90-day enhanced surveillance period On 7 November 2015, if no new case of Ebola virus disease is recorded, Sierra Leone will have met the criteria set by the World Health Organization (WHO) for declaring the end of Ebola transmission. If Sierra Leone meets that milestone, on that day, the WHO will declare the end of Ebola transmission in Sierra Leone, at an event organised by the Government of Sierra Leone through the National Ebola Response Centre (NERC)."
This is the message that greets you on the NERC website today. Ebola virus transmission has finally been kicked out of Sierra Leone after a 42 period with no cases confirmed. Getting to zero is now, Got to zero!
CONGRATULATIONS!!!
It has been a hard fought battle with many, many losses. Battling the Ebola virus has also provided many teaching moments for the nation...as it has been for Liberia and still is for Guinea...and the world.
Within the next 90 day enhanced surveillance period and in the months and months to come, we may see a case or cases pop up and clusters may result. But Sierra Leone knows what Ebola virus disease is and how to deal with it. It won't be caught out the same way again.
Many more teaching moments undoubtedly remain. But each will surely be faced with the same strength and passion that drove the nation to defeat an epidemic the likes of which the world had never before seen.
The people of Sierra Leone made many new friends during this tragedy and hopefully they will always be but a call or a text or an email away. Far too many of those incredibly brave local and international health workers, burial teams, laboratory specialists and ambulance drivers paid for their efforts with their lives. So to them, to those who survived, to all the contact tracers, the social anthropologists, the psychosocial experts, the survivor clinics, the organizers, the facilitators, the doers and the thinkers from within and outside Sierra Leone, we give our heartfelt thanks for your work and your many sacrifices. You together with the people of Sierra Leone all contained and defeated Ebola virus disease and you did it in the face of often overwhelming odds.
Enjoy the parties. Remember the lessons. Be vigilant.
References...
Thursday, 5 November 2015
Updating the very model of a modern mammal-camel....
The new findings from the case-control study out of the Kingdom of Saudi Arabia (and US CDC) deserve an update of my old model of how one might become infected with MERS-CoV after exposure to an infected camel.[1,2]
The major change is the removal of the ingestion options. As readers of this blog will know, I've never been a "believer" in that route of infection, and the new study would seem to support that gut feeling with some facts.
As ever, the distinction between direct contact and being close enough to be exposed to droplets that are inhaled, has not been possible and wasn't attempted. The word "droplet" does not appear anywhere in the paper. In fact, animal contact and droplet-producing processes are all rolled together in the new study under the direct contact banner - so I have retained droplets among the possible risks shown in the figure.
References...
 |
| Some of the possible ways in which MERS-CoV may be spread from an infected camel to a human in direct or close contact with the camel or with surfaces onto which MERS-CoV-laden camel excretions or secretions have been deposited. |
As ever, the distinction between direct contact and being close enough to be exposed to droplets that are inhaled, has not been possible and wasn't attempted. The word "droplet" does not appear anywhere in the paper. In fact, animal contact and droplet-producing processes are all rolled together in the new study under the direct contact banner - so I have retained droplets among the possible risks shown in the figure.
References...
Friday, 23 October 2015
Markets that deal in camels may help spread MERS-CoV variants..
This camel/MERS-CoV study from Farag and colleagues, serves as follow-up of sorts to my last post. The paper, which was published in July 2015's Infection, Ecology and Epidemiology, is entitled High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014.[1]
The authors remind us in the background that the routes of direct or indirect zoonotic transmission are still unknown but that a "large proportion of MERS cases" are suspected to have resulted from zoonotic transmission.
105 dromedary camels (DCs) either from a market sale or directly from Qatar or the Kingdom of Saudi Arabia (KSA) were sampled in February (n=53) and March (n=52), 2014. Samples included nasal, oral, rectal and bronchial swabs and lymph nodes from animals grouped into age 3 groups: 0 to 6 months (n=41), 7 to 12 months (n=35) or greater than 12 months (n=29) of age. Testing for virus was by Corman et al's UpE and N gene real-time RT-PCRs.[2] Testing for antibodies was via the detection of a reaction to the MERS-CoV, severe acute respiratory syndrome (SARS)-CoV and human CoV (HCoV)-OC43 spike domain S1 antigen using the protein-microarray method described previously by this group.[4]
Findings...
References...
The authors remind us in the background that the routes of direct or indirect zoonotic transmission are still unknown but that a "large proportion of MERS cases" are suspected to have resulted from zoonotic transmission.
105 dromedary camels (DCs) either from a market sale or directly from Qatar or the Kingdom of Saudi Arabia (KSA) were sampled in February (n=53) and March (n=52), 2014. Samples included nasal, oral, rectal and bronchial swabs and lymph nodes from animals grouped into age 3 groups: 0 to 6 months (n=41), 7 to 12 months (n=35) or greater than 12 months (n=29) of age. Testing for virus was by Corman et al's UpE and N gene real-time RT-PCRs.[2] Testing for antibodies was via the detection of a reaction to the MERS-CoV, severe acute respiratory syndrome (SARS)-CoV and human CoV (HCoV)-OC43 spike domain S1 antigen using the protein-microarray method described previously by this group.[4]
Findings...
- 59% of DCs had at least one MERS-CoV RNA positive sample but no significant difference in viral load was apparent between sample types or ages
- 61/101 (60.3%) of DC's nasal samples had RNA detected
- 23/102 (22.5%) of DC's saliva samples had RNA detected
- 15/103 (14.6%) of DC's rectal samples had RNA detected
- 7/101 (6.9%) of DC's bronchial samples had RNA detected
- 5/53 (9.4%) of DC's lymph nodes had RNA detected
- 5 different MERS-CoV variants (subtly different versions of MERS-CoV) were circulating in Qatar among the sampled animals at this time according to RT-PCR/sequencing method that targets a fragment of the S2 domain of the MERS-CoV Spike gene.[3]
- 100/103 (97%) animals were reactive for IgG, and most of 53 animals tested, had antibodies capable of specifically neutralizing cellular infection by MERS-CoV as determined by a 90% plaque reduction neutralization test (PRNT90; [5])
- Antibody levels and viral load did not correlate suggesting - based on this subset of the immune response - that reinfection may be possible since protection may be limited, as it is among humans with the 4 known HCoVs. The authors note that this may prove a challenge for any future DC vaccine which would need to produce a protective effect to meets its need
- No age-specific differences were found in MERS-CoV RNA shedding - usually younger DCs are distinctly more likely to be shedding viral RNA than older DCs
Discussion...
The authors noted here that discrepancies do exist between their study and those of some others - specifically, that others have not found viral RNA in faeces - but those studies also tested fewer animals. It is important, when percentages are not high, to test enough animals to see the full extent of MERS-CoV shedding and potential transmission routes.
DCs from different regions within Qatar and outside Qatar, may be shedding MERS-CoV while in DC markets and holding pens, sometimes for weeks, awaiting slaughter.
Camel markets are thus a likely high risk area for acquiring a MERS-CoV infection - and multiple variants can be circulating here.
In previous Qatari investigations, human cases have been linked with visits to the areas studied here and have also included DC slaughterer cases, supporting the notion that humans with DC exposures (presumably when they are infected with MERS-CoV) are at risk of becoming infected themselves.
Yet this study did not manage to capture the process of transmission in action. It is that process that holds such importance for this chapter on MERS-CoV and especially for those who disbelieve the role of DCs in human MERS cases.
In the next post, we will re-visit a study that did seem to capture DC>human infection.
- High proportion of MERS-CoV shedding dromedaries at slaughterhouse
with a potential epidemiological link to human cases, Qatar 2014.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505336/ - http://www.ncbi.nlm.nih.gov/pubmed/23041020
- http://www.ncbi.nlm.nih.gov/pubmed/25728084
- http://virologydownunder.blogspot.com.au/2015/10/if-you-are-often-in-contact-with-camels.html
- http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70164-6/abstract
Thursday, 10 September 2015
Ignore mild and asymptomatic cases at your peril...
Infected but apparently well people may be key points along the transmission chain - not just in spreading infectious virus, but also in contaminating surfaces.
Or they may have no role in transmission at all.
When you have problems that weren't solved by the easy answers - look harder.
Or they may have no role in transmission at all.
When you have problems that weren't solved by the easy answers - look harder.
Study. Test. Find out. Communicate.
 |
| Knowing the full story of how a virus spreads is hard work. But transmission is not necessarily a simple process. Like everything biological, it may be more complex than we care to acknowledge. Such a complex scenario is shown here. Completely fictitious. Or maybe not. Testing can answer questions. Communication can provide answers.Click on image to enlarge. |
Monday, 8 June 2015
MERS-CoV and opportunity to spread...
1,500 people were exposed via direct or indirect contact, to one Doctor who was already ill and later tested positive for the Middle East respiratory syndrome coronavirus (MERS-CoV).[1]
So what?
If this were measles virus - that sort of exposure could spell disaster for infection control and measles containment. In measles, every infected person can infect about 18 other people...but that's an average of course and on an individual basis, the number of new cases can move around that value depending on the number of contacts each person has...and the type of contact...and how much virus the index case sheds... and everyone's their immune function...etc, etc, etc.
But MERS-CoV ain't no measles virus.
Time and again we've seen that MERS-CoV does not pass easily to new people. Around 4% of household contacts were deemed infected, across 26 households, in a study from 2014.[2] About 2-3% in some other analyses.[3] And by 'easily' I mean lots and lots of contact becoming ill from each case they are exposed too. If 4% of those 1,500 hundred contacts of the South Koran Doctor had been exposed to an infectious dose of MERS-CoV from this Doctor - who really does get around - and the incubation period is as short as the 3 or 4 days it has been in some cases in South Korea...then any minute now, we'll expect to see 60 more cases in the community and in hospitals, all with links to this health professional.
I'm not holding my breath (pardon the pun) for this though, because I doubt the contact was often very close. I also won't go into the fact that there maybe no actual testing of contacts happening - we have no idea of that aspect of the South Korean incident. I really hope the South Koreans are testing. It would be a great study producing some valuable transmission data outside of Saudi Arabia. And not just PCR testing but collecting blood for serology (antibody studies) testing later too.
Google tells me that South Korea has a population of 50,220,000 in 2013. So there have been 87 cases of MERS since May...about 0.0002% of the population are infected. At this point, perhaps we should start assembling a list of how many people went through the hospitals with the most cases, that did not acquire MERS-CoV...just to provide some added context to the cluster. In other words - the past few days have seen case numbers growing day on day - but infections are still contained within the hospital setting. Close contact. No community spread. No camels infected in zoos.
Tomorrow is another day and we'll see what is added to the tally resulting from the arrival of a single infected traveller.
References..
So what?
If this were measles virus - that sort of exposure could spell disaster for infection control and measles containment. In measles, every infected person can infect about 18 other people...but that's an average of course and on an individual basis, the number of new cases can move around that value depending on the number of contacts each person has...and the type of contact...and how much virus the index case sheds... and everyone's their immune function...etc, etc, etc.
But MERS-CoV ain't no measles virus.
Time and again we've seen that MERS-CoV does not pass easily to new people. Around 4% of household contacts were deemed infected, across 26 households, in a study from 2014.[2] About 2-3% in some other analyses.[3] And by 'easily' I mean lots and lots of contact becoming ill from each case they are exposed too. If 4% of those 1,500 hundred contacts of the South Koran Doctor had been exposed to an infectious dose of MERS-CoV from this Doctor - who really does get around - and the incubation period is as short as the 3 or 4 days it has been in some cases in South Korea...then any minute now, we'll expect to see 60 more cases in the community and in hospitals, all with links to this health professional.
I'm not holding my breath (pardon the pun) for this though, because I doubt the contact was often very close. I also won't go into the fact that there maybe no actual testing of contacts happening - we have no idea of that aspect of the South Korean incident. I really hope the South Koreans are testing. It would be a great study producing some valuable transmission data outside of Saudi Arabia. And not just PCR testing but collecting blood for serology (antibody studies) testing later too.
Google tells me that South Korea has a population of 50,220,000 in 2013. So there have been 87 cases of MERS since May...about 0.0002% of the population are infected. At this point, perhaps we should start assembling a list of how many people went through the hospitals with the most cases, that did not acquire MERS-CoV...just to provide some added context to the cluster. In other words - the past few days have seen case numbers growing day on day - but infections are still contained within the hospital setting. Close contact. No community spread. No camels infected in zoos.
Tomorrow is another day and we'll see what is added to the tally resulting from the arrival of a single infected traveller.
References..
- http://www.koreaherald.com/view.php?ud=20150604001315
- MERS-CoV around the house-yes, it does transmit at home
http://virologydownunder.blogspot.com.au/2014/08/mers-cov-around-house-yes-it-doers.html - If this is what MERS-CoV detections look like with more testing...what is the "normal" community level of virus?? [UPDATED]
http://virologydownunder.blogspot.com.au/2014/04/if-this-is-what-mers-cov-detections.html
Saturday, 4 April 2015
Ebola - the lesser transmission risks are still risks...
The United Nations (UN) Foundation blog has used some pretty strong language in their latest post of the 5 Things to Know on Ebola This Week.
Number 2 on their list stated (by highlighting)...
Perhaps the results are known behind closed doors and perhaps that testing has firmly pointed to a sexual transmission route. The UN post above certainly seems very sure and it also seems that this event has triggered an update to recommendations. There is solid literature about the presence of infectious Ebola virus in seminal fluids so the possibility shouldn't be far beyond belief.[4]
Another possible, albeit also unproven, transmission route is urine. This fluid seems to me to be a far more likely source of trouble. One cannot abstain from urination. So why worry about urine as a risk for transmission of Ebola virus? An EVD case study last year showed very nicely that infectious Ebola virus could be cultured from urine for about 12 days longer than it could be from blood.[1] Viral RNA has also been found in urine for four weeks.[1,2]
Perhaps urine should be a more noteworthy concern for its potential to remain infectious after blood test become negative. This concern might be greater wherever toilet and hand-washing facilities and sewers, are minimal or poorly maintained.
Urine and seminal fluids are not considered to be major transmission routes for Ebola virus. But let's not forget that it was probably an unlikely transmission event, and route - a single jump from an animal to a human - that triggered >25,000 EVD cases in this epidemic. Even a rare risk must be given serious consideration when such a large public health impact can realistically result.
References...
Number 2 on their list stated (by highlighting)...
First detected case of Ebola transmitted through sexual intercourseWhile there is reported to be ongoing testing (and presumably virus genotyping), I've yet to hear publicly the outcome of such testing.
Earlier research suggested that three months of abstinence or condom use among male survivors would suffice to prevent the transmission of Ebola through intercourse. But an Ebola patient in Liberia who died last week had just one known risk factor: her boyfriend was an Ebola survivor, treated last September. This is the first case detected of the Ebola virus being transmitted through sexual intercourse, which has necessitated updated recommendations. Read the full story here: http://unfoundationblog.org/ebola/5-things-to-know-on-ebola-this-week-10/#sthash.2HkUbbYT.dpuf
Perhaps the results are known behind closed doors and perhaps that testing has firmly pointed to a sexual transmission route. The UN post above certainly seems very sure and it also seems that this event has triggered an update to recommendations. There is solid literature about the presence of infectious Ebola virus in seminal fluids so the possibility shouldn't be far beyond belief.[4]
Another possible, albeit also unproven, transmission route is urine. This fluid seems to me to be a far more likely source of trouble. One cannot abstain from urination. So why worry about urine as a risk for transmission of Ebola virus? An EVD case study last year showed very nicely that infectious Ebola virus could be cultured from urine for about 12 days longer than it could be from blood.[1] Viral RNA has also been found in urine for four weeks.[1,2]
Perhaps urine should be a more noteworthy concern for its potential to remain infectious after blood test become negative. This concern might be greater wherever toilet and hand-washing facilities and sewers, are minimal or poorly maintained.
Urine and seminal fluids are not considered to be major transmission routes for Ebola virus. But let's not forget that it was probably an unlikely transmission event, and route - a single jump from an animal to a human - that triggered >25,000 EVD cases in this epidemic. Even a rare risk must be given serious consideration when such a large public health impact can realistically result.
References...
- Kreuels B, Wichmann D, Emmerich P et al. A Case of Severe Ebola Virus Infection Complicated by Gram-Negative Septicemia. N Engl J Med. 2014 Oct 22. 371:2394-2401
- Lyon GM, Mehta AK, Varkey JB et al. Clinical Care of Two Patients with Ebola Virus Disease in the United States. N Engl J Med. 2014 Nov 12. 371:2401-2409
- Ebola Virus Disease (EVD). Key questions and answers concerning water, sanitation and hygiene. World Health Organization. http://apps.who.int/iris/bitstream/10665/137181/1/WHO_EVD_WSH_14_eng.pdf?ua=1
- Mackay IM, Arden KE. Ebola virus in the semen of convalescent men. Lancet Infect Dis. 2015 Feb;15(2):149-50.
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
|
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 survive. The 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
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
- http://www.nytimes.com/interactive/2014/07/31/world/africa/ebola-virus-outbreak-qa.html
- http://apps.who.int/iris/bitstream/10665/137510/1/roadmapsitrep_5Nov14_eng.pdf
- http://www.who.int/mediacentre/news/ebola/20-november-2014-mali/en/
- http://www.who.int/mediacentre/news/ebola/17-october-2014/en/
- http://www.nyc.gov/html/doh/html/pr/press-statements.shtml
- http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html
- http://www.nejm.org/doi/full/10.1056/NEJMoa1411099
- http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20920
- http://apps.who.int/ebola/en/status-outbreak/situation-reports/ebola-situation-report-14-january-2015
- http://www.symplur.com/blog/the-life-cycle-of-ebola-on-twitter/
- http://www.foxnews.com/opinion/2014/08/09/truth-about-ebola-us-risks-and-how-to-stop-it/
- http://www.nytimes.com/interactive/2014/10/20/us/cascade-of-contacts-from-ebola-case.html
- https://www.gov.uk/government/news/ebola-contact-tracing-underway
- http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)62016-X.pdf
- http://www.who.int/mediacentre/news/ebola/3-september-2014/en/
- http://www.bloomberg.com/news/videos/b/4a798222-3666-446d-81ff-f21412a3f068?cmpid=yhoo
- http://www.euro.who.int/en/health-topics/emergencies/pages/news/news/2015/03/united-kingdom-is-declared-free-of-ebola-virus-disease/_recache
- http://ecdc.europa.eu/en/healthtopics/ebola_marburg_fevers/Pages/medical-evacuations.aspx
- http://www.cdc.gov/measles/about/transmission.html
- http://www.nejm.org/doi/full/10.1056/NEJMc1413685
- http://apps.who.int/iris/bitstream/10665/156273/1/roadmapsitrep_18Mar2015_eng.pdf?ua=1&ua=1
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...
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...
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..
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...
- Transmission of Ebola Viruses: What We Know and What We Do Not Knowhttp://mbio.asm.org/content/6/2/e00137-15
- Experts suspect Ebola virus sometimes spreads by air
http://www.cidrap.umn.edu/news-perspective/2015/02/experts-suspect-ebola-virus-sometimes-spreads-air - 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 - Ethical issues in isolating people treated for Ebola
http://www.ncbi.nlm.nih.gov/pubmed/25588871 - 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settingshttp://www.ajicjournal.org/article/S0196-6553(07)00740-7/pdf
- Ebola virus disease in Africa: epidemiology and nosocomial transmissionhttp://www.ncbi.nlm.nih.gov/pubmed/25655197
- Understanding Ebola Virus Transmission
http://www.mdpi.com/1999-4915/7/2/511 - 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 - Ebola, through air or not through air: that is the question
http://www.ncbi.nlm.nih.gov/pubmed/25646157 - Review of Human-to-Human Transmission of Ebola Virus from the US CDC
http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html - Sexual transmission of the Ebola Virus : evidence and knowledge gaps
http://www.who.int/reproductivehealth/topics/rtis/ebola-virus-semen/en/ - 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/
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