The race to contain West Africa's Ebola outbreak(wired.co.uk)
wired.co.uk
The race to contain West Africa's Ebola outbreak
http://www.wired.co.uk/news/archive/2014-04/11/ebola-open-street-map
38 comments
Please use caution when interpreting preclinical drug results. Yes, Tekmira saw great efficacy in non-human primates, but that doesn't necessarily translate into human efficacy.
Tekmira focuses on RNAi therapeutics (a field in which I spent time on the research side in industry). Many RNAi companies have fallen from grace in recent years due to liver toxicity associated with lipid nanoparticle (LNP) siRNA delivery vehicles. Tekmira was a pioneer in lipid delivery, and they use an LNP vehicle in their TKM-Ebola therapy.
I'm sure the siRNA they use is wonderful, with great knockdown and durability, but in this space it is the delivery vehicle forming the bottleneck.
Disclaimers aside, Tekmira initiated a PhI trial of Ebola-TKM this past January and it will be interesting to see how the toxicity plays out.
I know very little about LNP delivery -- what's the cause of the toxicity?
As I understand it, the toxicity is caused by the implementation of the LNP delivery system, rather than a factor inherent to LNP delivery in general. As there are LNP systems that have proven to effectively deliver to target.
Basically, this LNP delivery system is for encapsulating a desired portion of RNA within a 'shell'[+], so that it may be delivered to a biological target.
The shell is necessary because siRNA is anionic and hydrophilic (negatively charged and water loving/binding.) Which makes it difficult to deliver to targets. It is also unstable in serum (component of blood) and can have unintended side effects if delivered to the wrong target.
There have been attempts to engineer custom siRNA directly. These attempts have resulted in siRNA that cause fewer unintended side effects and have higher stability. However, this method still requires high dosage in vivo and the effects are limited to the liver.
The more promising approach involves wrapping the siRNA in a lipid 'shell'. The 'shell' is inserted into the biological system and travels through the bloodstream to the target area.
The two underlying causes of toxicity (in some LNP delivery implementations) seem to be: the charge of the LNP system and the 'dosage' of the LNP delivery system.
Recent research has shown that it is possible to engineer these 'shells' in such a fashion that they can carry the siRNA safely to target, mitigate the undesirable surface charge, and require relatively low dosage.
Specifically, they have developed ionizable cationic lipids with pKa below 7 to encapsulate the 'package' at a low pH, while maintaining a relatively neutral surface charge at physiological pH. Also, the delivery 'package' itself is made much smaller.
([+] Lipid Nanoparticle delivery is a means of biological/in-solution transport for small matter in general, in this case it is specifically a means of delivering small interface RNA, siRNA, within a biological system.)
Disclaimer: I'm not an expert, but I do have experience in a somewhat related field. This is a high level explanation and it's possible that my explanation handwaves or is mistaken in some aspect.
These papers do a better job of explaining it than I can:
http://www.ncbi.nlm.nih.gov/pubmed/21179008
http://www.liposomes.ca/publications/311%20Wan%20et%20al%202...
Basically, this LNP delivery system is for encapsulating a desired portion of RNA within a 'shell'[+], so that it may be delivered to a biological target.
The shell is necessary because siRNA is anionic and hydrophilic (negatively charged and water loving/binding.) Which makes it difficult to deliver to targets. It is also unstable in serum (component of blood) and can have unintended side effects if delivered to the wrong target.
There have been attempts to engineer custom siRNA directly. These attempts have resulted in siRNA that cause fewer unintended side effects and have higher stability. However, this method still requires high dosage in vivo and the effects are limited to the liver.
The more promising approach involves wrapping the siRNA in a lipid 'shell'. The 'shell' is inserted into the biological system and travels through the bloodstream to the target area.
The two underlying causes of toxicity (in some LNP delivery implementations) seem to be: the charge of the LNP system and the 'dosage' of the LNP delivery system.
Recent research has shown that it is possible to engineer these 'shells' in such a fashion that they can carry the siRNA safely to target, mitigate the undesirable surface charge, and require relatively low dosage.
Specifically, they have developed ionizable cationic lipids with pKa below 7 to encapsulate the 'package' at a low pH, while maintaining a relatively neutral surface charge at physiological pH. Also, the delivery 'package' itself is made much smaller.
([+] Lipid Nanoparticle delivery is a means of biological/in-solution transport for small matter in general, in this case it is specifically a means of delivering small interface RNA, siRNA, within a biological system.)
Disclaimer: I'm not an expert, but I do have experience in a somewhat related field. This is a high level explanation and it's possible that my explanation handwaves or is mistaken in some aspect.
These papers do a better job of explaining it than I can:
http://www.ncbi.nlm.nih.gov/pubmed/21179008
http://www.liposomes.ca/publications/311%20Wan%20et%20al%202...
So if the US DoD doesn't fund medical research, not a single other organization or country does? If that is the case, then turning DoD funding back on does not seem like a sustainable plan.
What is the response from the EU's member states (who's medical systems are often touted as superior)? After all, they're much closer to this than we are.
What is the response from the EU's member states (who's medical systems are often touted as superior)? After all, they're much closer to this than we are.
I don't know the answer to your question of whether other countries fund development of Marburg or Ebola treatments.
I believe at the time the DoD funded it out of pure national self-interest: regardless of geographic proximity, just one infected person on the wrong flight could present a massive national security risk.
To be fair the DoD did continue funding Ebola cures with Tekmira, and Tekmira earlier this year began dosing of the first human patient. That patient is healthy and the dosing is to test the safety profile of the drug. Reportedly the WHO has not requested any emergency supplies of Tekmira's drug yet.
I believe at the time the DoD funded it out of pure national self-interest: regardless of geographic proximity, just one infected person on the wrong flight could present a massive national security risk.
To be fair the DoD did continue funding Ebola cures with Tekmira, and Tekmira earlier this year began dosing of the first human patient. That patient is healthy and the dosing is to test the safety profile of the drug. Reportedly the WHO has not requested any emergency supplies of Tekmira's drug yet.
The DoD funded it because they're worried about weaponized Ebola and Marburg. Given that the DoD is in the middle of a budget crunch, it's believable that they'd cut funding for defense programs against less-likely military threats.
Superior medical systems != superior medical research
When you talk about sustainable plans here, it's all about relative stability. Sure the DOD might not be a completely sustainable way to fund this research, but I would certainly vote to turn it back on given the alternative being zero funding. You could make the argument that something like the Gates Foundation might be better, but I don't think it's obviously better in all areas than the DOD.
When you talk about sustainable plans here, it's all about relative stability. Sure the DOD might not be a completely sustainable way to fund this research, but I would certainly vote to turn it back on given the alternative being zero funding. You could make the argument that something like the Gates Foundation might be better, but I don't think it's obviously better in all areas than the DOD.
The DoD is by far the largest, wealthiest, and most powerful institution on the planet when it comes to the broad range of things it's involved in.
Saying DoD attention and funding for something is 'unsustainable' is sort of like saying the efforts of our planet to solve some problem are not sustainable.
Saying DoD attention and funding for something is 'unsustainable' is sort of like saying the efforts of our planet to solve some problem are not sustainable.
The US is solely responsible for, to my understanding, most of the breakthrough pathology research in the past hundred years or so. No indication that is going to change. At least it's a hell of a legacy to leave.
Please do correct me if I am wrong. I am no expert in pathology.
Please do correct me if I am wrong. I am no expert in pathology.
We have a lot of other medical research entities in the US (NIH, CDC, a bunch of top universities, private pharma...), and I think the DOD is probably responsible for very few of the breakthroughs of the past 100 years.
I'm not sure about the record of foreign governments, universities, companies, and other researchers, but I suspect the US is by far the biggest, but not the only. Just in the commercial world there are a lot of really excellent pharma and biotech companies outside the US - GSK, Roche, Bayer, Novartis, ...
I'm not sure about the record of foreign governments, universities, companies, and other researchers, but I suspect the US is by far the biggest, but not the only. Just in the commercial world there are a lot of really excellent pharma and biotech companies outside the US - GSK, Roche, Bayer, Novartis, ...
More information in the OpenStreetMap Wiki: http://wiki.openstreetmap.org/wiki/2014_West_Africa_Ebola_Re...
Here is also a great visualization of the development after satelite images were available: https://wiki.openstreetmap.org/w/images/a/a8/Gueckedou-mappi...
And the changesets: https://wiki.openstreetmap.org/w/images/f/fe/Gueckedou-chang...
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http://www.newscientist.com/article/mg22229644.400-online-ar...
http://redcrosschat.org/2014/04/10/digital-mapping-volunteer...
Here is also a great visualization of the development after satelite images were available: https://wiki.openstreetmap.org/w/images/a/a8/Gueckedou-mappi...
And the changesets: https://wiki.openstreetmap.org/w/images/f/fe/Gueckedou-chang...
---
http://www.newscientist.com/article/mg22229644.400-online-ar...
http://redcrosschat.org/2014/04/10/digital-mapping-volunteer...
This outbreak is scary because it's finally hit a major city in Africa.
All you need is for one case to hop on an international flight, and things get much harder to control.
All you need is for one case to hop on an international flight, and things get much harder to control.
One of the factors that keeps Ebola from causing massive epidemics and pandemics is it's rapid mortality rate. It kills people relatively fast and consistently, so outbreaks often burn themselves out.
https://en.wikipedia.org/wiki/Ebola_virus_disease#Epidemiolo...
If you're curious, The Coming Plague is a very interesting book that covers many hemorrhagic fevers like Ebola: http://www.amazon.com/The-Coming-Plague-Emerging-Diseases/dp...
https://en.wikipedia.org/wiki/Ebola_virus_disease#Epidemiolo...
If you're curious, The Coming Plague is a very interesting book that covers many hemorrhagic fevers like Ebola: http://www.amazon.com/The-Coming-Plague-Emerging-Diseases/dp...
Most previous outbreaks have been in rural areas, though. So depending mainly on the mortality for containment doesn't sound like the most prudent strategy.
The incubation period of Ebola virus can be quite long (more than two weeks) which is more than enough time to spread the disease geographically far. EVD/EHF is also contagious during the incubation period when no symptoms are present.
The incubation period of Ebola virus can be quite long (more than two weeks) which is more than enough time to spread the disease geographically far. EVD/EHF is also contagious during the incubation period when no symptoms are present.
It doesn't kill people faster than a flight to a major international airport. That's all that matters.
The doctors in Minnesota are still saying that the virus that this person was infected with was “Lassa fever” a different form of Hemorrhagic fever than Ebola, but given the area of the country that the passenger traveled from, many believe that this is a case of Ebola.
The latest reports are saying that there are a number of unverified infections in the nations surrounding Guinea and Liberia. Nobody knows until the testing is done.
The big problem is that it's in a city. It's easier to control when it hits isolated villages.
The big problem is that it's in a city. It's easier to control when it hits isolated villages.
Does Ebola present a threat to modern industrialized countries?
My understanding is that it is spread through contact with bodily fluids of an infected person, so in order to be safe you can basically just drink sealed bottled water and eat food that you prepared yourself (canned only, if people handling fresh food might be infected?).
HIV is also transmitted by fluids (though nowhere near as easily) but HIV has a longer incubation period which makes it more difficult for industrialized nations to deal with.
My understanding is that it is spread through contact with bodily fluids of an infected person, so in order to be safe you can basically just drink sealed bottled water and eat food that you prepared yourself (canned only, if people handling fresh food might be infected?).
HIV is also transmitted by fluids (though nowhere near as easily) but HIV has a longer incubation period which makes it more difficult for industrialized nations to deal with.
Yes, it's highly contagious. HIV is actually remarkably difficult to transmit (on the order of single-digit percentage seroconversion for sexual acts), but Ebola routinely transfers between patients and caregivers.
That's why doctors treating Ebola have to wear serious containment gear, but doctors treating HIV patients have to wear gloves and maybe eye protection.
That's why doctors treating Ebola have to wear serious containment gear, but doctors treating HIV patients have to wear gloves and maybe eye protection.
i think part of it has to do with the high fatality rate along with no specific treatment plan
Aye, it's certainly dangerous. I'm mostly wondering what likely outcome of Ebola infected passengers on a plane to NYC would be. I am inclined to think that Ebola would not spread particularly well in a city like that, and would be quickly contained/isolated.
Hard to say. Most hospitals are not prepared for (and don't expect) a disease like Ebola to walk through the door. So while we have much better standards of cleanliness and isolation than a hospital in sub-saharan Africa, we're still likely to be taken by surprise by a patient who presents with a bad fever.
The worst case is that someone gets infected and flies to a major city before they get really sick. You could have a huge network of transmission before it ever hits a hospital.
The worst case is that someone gets infected and flies to a major city before they get really sick. You could have a huge network of transmission before it ever hits a hospital.
I would say the worst case is a working class African immigrant heads back home to see their ailing parents, contracts Ebola, and flies back to Paris or London while suffering from a head cold or the flu that makes them cough & sneeze. After the flight, they go back to their job as a line cook. They tough out the sinus infection, because their job requires them to. A week later, major symptoms start to develop and finally they seek a progression of primary care doctor, urgent care, hospital ER, and finally hospital isolation ward when they approach the end and the symptoms are identified for what they are. In this time they've not only hit the plane passengers, they've used packed mass transit a dozen times and infected thousands through food.
Bodily fluids can be a moderate danger or they can be a very severe danger, based largely on the circumstances of the infected.
Bodily fluids can be a moderate danger or they can be a very severe danger, based largely on the circumstances of the infected.
Can you elaborate on ebola's ability to survive / transmit via something like food? How long can it continue to be contagious in that type of scenario? Would some foods be more friendly as a transport?
As someone currently in Paris: god damn it!
Yes, it's not considered as large a risk for that exact reason - in the most severe case you simply shut down all transport and wait 15 days
What's worse in guinea right now, is that anyone that is showing any symptoms even remotely related to the disease is quarantined with others with it. It sucks because what is the other thing to do?
The panic is spreading and people don't know what to do, hence why violence is now breaking.
The panic is spreading and people don't know what to do, hence why violence is now breaking.
>It sucks because what is the other thing to do?
Quarantine them in separate spaces?
I mean, DUH!
Quarantine them in separate spaces?
I mean, DUH!
Warning, rampant speculation:
Say ten people come in with similar symptoms but no certainty of Ebola. You quarantine them all as 'maybe'. It later turns out one actually has Ebola. The other 'maybe' cases are now likely at a very similar level of risk to that which they would have been at had they been quarantined with definite cases.
Yes, quarantining them separately is better, but probably not much better, and in many cases probably not sufficently better to consume considerably limited resources.
Summary: I don't think this warrants 'DUH!'.
Say ten people come in with similar symptoms but no certainty of Ebola. You quarantine them all as 'maybe'. It later turns out one actually has Ebola. The other 'maybe' cases are now likely at a very similar level of risk to that which they would have been at had they been quarantined with definite cases.
Yes, quarantining them separately is better, but probably not much better, and in many cases probably not sufficently better to consume considerably limited resources.
Summary: I don't think this warrants 'DUH!'.
Ebola has a startlingly high fatality rate, but most cases of it are in developing nations. Does anybody know what fatality rate you could expect from advanced medicine and techniques in a developed nation?
The fatality rate would be the same. We do not have any treatments available for any of the Ebola strains, as such our only option is to limit the spread. Whether developed nations are better able to do so, I'm not sure.
Governments in the West are stronger, so might be more able to rapidly contain outbreaks as a result, perhaps?
The title currently reads:
"OpenStreetMap and The race to contain West Africa's Ebola outbreak"
It should be "OpenStreetMap and The Red Cross / MSF ..."
It should be "OpenStreetMap and The Red Cross / MSF ..."
This article is so poorly written/researched that it makes me doubt its content. If you know anything about Africa, how can you confuse Gaddafi's Libya with Tunisia? And, according to wikipedia, Ebola has a mortality rate of 68%; where does the 90% come from?
> They had experimented after the fall of Gaddafi in Tunisia, with a sole employee mapping a refugee camp for internal use.
During and after the fall of Gaddafi, tens if not hundreds of thousands of people left Libya, most of them going to neighbouring countries. That comment refers to one of the refugee camps set up by the Red Cross in Tunisia, for Libyan refugees.
During and after the fall of Gaddafi, tens if not hundreds of thousands of people left Libya, most of them going to neighbouring countries. That comment refers to one of the refugee camps set up by the Red Cross in Tunisia, for Libyan refugees.
The 90% refers to this specific strain of Ebola, the Zaire strain. The article does make some mistakes, though: for example, the cases in Sierra Leone are not yet confirmed to be Ebola.
Some information from the CDC:
http://www.cdc.gov/vhf/ebola/outbreaks/guinea/
http://www.cdc.gov/vhf/ebola/outbreaks/guinea/
Unfortunately a portion of this research was funded by the DoD, which decided to cut funding in 2012 at least for the Sarepta Marburg cure, which significantly slowed down progress and prevented any stockpiling of the medicine.