I questioned your claim regarding epithelial infection because the ZMAPP drug began as an effort to transport modified alleles to treat cystic fibrosis. The researcher used Ebola glycoproteins due to the virus' efficient transduction of lung tissue. Your claim doesn't jibe with the ZMAPP work.
On the epithelial issue:
Intracellular Events and Cell Fate in Filovirus Infection Viruses 2011 (PDF pg 4)Indeed, MARV or ZEBOV can be isolated from any organ or tissue. Besides the typical target cells for ZEBOV and MARV infection in non-human primates, additional target cells were occasionally found in individual animals. These cells included alveolar epithelial cells, bronchial epithelial cells and the cells of endocardial layer.
Ebola haemorrhagic fever Lancet March 2011Target cells and tissues
Ebola virus has a broad cell tropism, infecting a wide range of cell types. In-situ hybridisation and electron microscopic analyses of tissues from patients with fatal disease or from experimentally infected non-human primates show that monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and several types of epithelial cells all lend support to replication of these viruses.
Regarding the transmission vector issue:
Ebola Hemorrhagic Fever, Kikwit, Democratic Republic of the Congo, 1995: Risk Factors for Patients without a Reported Exposure JID 1999In 1995, 316 people became ill with Ebola hemorrhagic fever (EHF) in Kikwit, Democratic Republic of the Congo. The exposure source was not reported for 55 patients (17%) at the start of this investigation, and it remained unknown for 12 patients after extensive epidemiologic evaluation. Both admission to a hospital and visiting a person with fever and bleeding were risk factors associated with infection. Nineteen patients appeared to have been exposed while visiting someone with suspected EHF, although they did not provide care. Fourteen of the 19 reported touching the patient with suspected EHF; 5 reported that they had no physical contact. Although close contact while caring for an infected person was probably the major route of transmission in this and previous EHF outbreaks, the virus may have been transmitted by touch, droplet, airborne particle, or fomite; thus, expansion of the use of barrier techniques to include casual contacts might prevent or mitigate future epidemics.
If you go back to my first post to you in this thread, I agreed that it's unlikely that Ebola will mutate into the epidemiological definition of an airborne disease. Nor must it undergo such mutation. Fomite, contact, droplet and aerosol are more than sufficient to spread it far and wide, as we're seeing now in West Africa. Much will be learned from this outbreak and much previous work will be upended.
You seem to think that no one should be the least bit concerned about the spread of Ebola to the western hemisphere. That is your right, of course, but your continued insistence that you know all possible epidemiological factors is odd given that the researchers engaged with this virus will not say the same. Every statement I've heard and read regarding vectors is predicated with a statement that much is unknown regarding transmission and pathogenesis.
I suspect continued efforts to communicate with you will not prove fruitful. You appear hell-bent on sticking to your opinion and position, and cannot abide a hint of disagreement, divergence or doubt.
I plan to revisit this thread when this outbreak is over and compare events to predictions. It will be interesting to see how it ends.
I work with PPE every day. One of my favorite observations is "for VRE, nobody does it right. For meningococcal meningitis, everybody does it right".
Even given the catastrophic conditions in West Africa, the attack rate among HCWs with access to PPE is extraordinary. I think this is most consistent with transcutaneous (intact skin) infection with an extremely low ID50.
Scary stuff.
I picked this up via the PANDEMIC FLU INFORMATION FORUM.
Short form, Lancet documented in June 2000 that asymptomatic Ebola Hell exists and it is Coming for Breakfast.
“This study showed that asymptomatic, replicative Ebola infection can and does occur in human beings. The lack of genetic differences between symptomatic and asymptomatic individuals suggest that asymptomatic Ebola infection did not result from viral mutations.”
http://www.ncbi.nlm.nih.gov/pubmed/10881895
The abstract, in full:
Quote:
Lancet. 2000 Jun 24;355(9222):2210-5.
Human asymptomatic Ebola infection and strong inflammatory response.
Leroy EM1, Baize S, Volchkov VE, Fisher-Hoch SP, Georges-Courbot MC, Lansoud-Soukate J, Capron M, Debré P, McCormick JB, Georges AJ.
Author information
Abstract
BACKGROUND:
Ebola virus is one of the most virulent pathogens, killing a very high proportion of patients within 5-7 days. Two outbreaks of fulminating haemorrhagic fever occurred in northern Gabon in 1996, with a 70% case-fatality rate. During both outbreaks we identified some individuals in direct contact with sick patients who never developed symptoms. We aimed to determine whether these individuals were indeed infected with Ebola virus, and how they maintained asymptomatic status.
METHODS:
Blood was collected from 24 close contacts of symptomatic patients. These asymptomatic individuals were sampled 2, 3, or 4 times during a 1-month period after the first exposure to symptomatic patients. Serum samples were analysed for the presence of Ebola antigens, virus-specific IgM and IgG (by ELISA and western blot), and different cytokines and chemokines. RNA was extracted from peripheral blood mononuclear cells, and reverse transcriptase-PCR assays were done to amplify RNA of Ebola virus. PCR products were then sequenced.
FINDINGS:
11 of 24 asymptomatic individuals developed both IgM and IgG responses to Ebola antigens, indicating viral infection. Western-blot analysis showed that IgG responses were directed to nucleoprotein and viral protein of 40 kDa. The glycoprotein and viral protein of 24 kDa genes showed no nucleotide differences between symptomatic and asymptomatic individuals. Asymptomatic individuals had a strong inflammatory response characterised by high circulating concentrations of cytokines and chemokines.
INTERPRETATION:
This study showed that asymptomatic, replicative Ebola infection can and does occur in human beings. The lack of genetic differences between symptomatic and asymptomatic individuals suggest that asymptomatic Ebola infection did not result from viral mutations. Elucidation of the factors related to the genesis of the strong inflammatory response occurring early during the infectious process in these asymptomatic individuals could increase our understanding of the disease.
I think that all knowledgeable people are fully aware that droplet transmission is possible. I have never said otherwise. What I say, and what all of the published data supports is that Ebola is not airborne. As any PhD trained microbiologist will tell you, there are very important differences between droplet and airborne transmission, (or between droplets and droplet nuclei). And the infection control measures are different for each kind of transmission.
I questioned your claim regarding epithelial infection because the ZMAPP drug began as an effort to transport modified alleles to treat cystic fibrosis. The researcher used Ebola glycoproteins due to the virus' efficient transduction of lung tissue. Your claim doesn't jibe with the ZMAPP work.
Hmm, it looks like you have ZMapp confused with some kind of gene therapy. ZMapp is a cocktail of monoclonal antibodies, and those antibodies are specific for Ebola virus proteins. Those antibodies cannot attach to epithelial cells, or any other cells. They are injected into the blood, where they look for and attach to Ebola viruses. They then act as a signal to the immune system to get to work to destroy the viruses. There is no Ebola protein in the ZMapp.
I notice that you didn't bother putting any kind of reference to your claim that Ebola glycoprotein was investigated for treatment of cystic fibrosis. Despite your garbled description of this work, it did not take long for me to find some references in PubMed. The first thing I notice is that there are few references to this work, none of them recent. The second thing I notice is that this work involved a modified Ebola glycoprotein inserted into an FIV-type virus. By modifying it, they changed its behavior. This means that whatever biological properties either Ebola virus or FIV virus have in their native forms are not applicable. The fact that a modified Ebola glycoprotein can bind with some affinity to epithelial cells says nothing about the binding affinities of the native protein. (Perhaps your failure to include a reference was not an oversight?)
Intracellular Events and Cell Fate in Filovirus Infection Viruses 2011 (PDF pg 4)
Indeed, MARV or ZEBOV can be isolated from any organ or tissue. Besides the typical target cells for ZEBOV and MARV infection in non-human primates, additional target cells were occasionally found in individual animals. These cells included alveolar epithelial cells, bronchial epithelial cells and the cells of endocardial layer.
In other words, finding virus in these non-target cells was a sporadic event--it did not happen in every animal observed, and was rare even when it was observed. That review only had one reference for these observations of virus in non-target cells, meaning that there is little corroboration for this observation. I will also point out that during the course of Ebola infection, the viremia can be extremely high, 10 million virions/milliliter of blood. All cell types undergo a process called "endocytosis", where they engulf molecules from outside of the cell and bring them inside the cell in a tiny vacuole. Although viruses use cell-surface receptor mediated endocytosis to gain entry into the cell, when the viremia is that high, it is quite possible for the cell to randomly endocytose a viral particle or two when it undergoes non-specific endocytosis. So, it is not surprising that an occasional non-target cell might contain some virus. That does not mean, however, that the non-target tissue is teeming with virus, or that the virus can replicate in or bud from the non-target cell.
I should also point out that monkeys are not people; the virus can and does have different tropisms in different animal species.
Ebola haemorrhagic fever Lancet March 2011
You mislabeled this link; it was not a Lancet article, but was the International Journal of Experimental Pathology.
I notice that, although you make a big deal of the researchers finding virus near epithelial cells in Rhesis monkeys--which are not humans, and which show a different pathology--you failed to quote the following from the same article: "Epidemiology studies of human disease out-breaks in sub-Saharan Africa did not suggest that aerosol transmission of filoviruses was likely in that setting. Virus did not spread easily from person to person during the Ebola virus epidemics in Africa, and attack rates were highest in individuals who were in direct physical contact with a primary case (Bres 1978). The rates were 3.5 times higher in people who provided nursing care than in those who were in casual contact with a primary case; no cases occurred in children whose only known exposure to the virus was sleeping in the huts occupied by their fatally ill parents. Although coughing was common among the human Ebola haemorrhagic fever cases in Africa, there was no direct evidence for aerogenic spread of Ebola virus in human populations. (Emphasis mine.) So, back in 1995, Ebola researchers noted what Ebola researchers said previously and what they continue to say now: Ebola is not an airborne disease.
Your problem is that you want desperately to believe that it is transmissible by aerosols, and you are looking for straws to support that belief. You have no independent evidence of aerosol transmission, and (unfortunately for you) no Ebola researcher has ever experimentally or epidemiologically established an aerosol route of transmission.
agreed that it's unlikely that Ebola will mutate into the epidemiological definition of an airborne disease. Nor must it undergo such mutation. Fomite, contact, droplet and aerosol are more than sufficient to spread it far and wide, as we're seeing now in West Africa.
Airborne transmission = aerosol transmission (unless you are speaking of artificially created aerosols)
Droplets can be propelled through the air, but are not airborne.
Ebola can be spread by droplets, but not through aerosols.
You seem to think that no one should be the least bit concerned about the spread of Ebola to the western hemisphere. That is your right, of course, but your continued insistence that you know all possible epidemiological factors is odd given that the researchers engaged with this virus will not say the same. Every statement I've heard and read regarding vectors is predicated with a statement that much is unknown regarding transmission and pathogenesis.
When did I ever say that the potential of Ebola disease introduction into the US is not a concern? I don't recall saying that at all. What I have done is point out that it is extremely unlikely for Ebola to cause an outbreak like that in Africa. It is certainly quite appropriate to alert clinicians to the potential of such a disease so that they can recognize it if a case *does* come into their facility. I have certainly implied, if not said, that Ebola won't be a problem as long as we are prepared for it and stay vigilant--that is not at all the same thing as saying that there is nothing to worry about, and we can be complacent. I was pretty much the same way before Y2K--I figured that people were busy remediating the potential problems ahead of time, so that Y2K would not end up being the end of civilization--and I was right. No reason to get all worked up when proper preparations are in place.
Marburg, another filovirus disease that is almost identical to Ebola, *has* entered the US. No one even knew about it; our normal infection control measures were sufficient to prevent any secondary cases.
I have pointed out many times that there is a LOT of unknown surrounding Ebola. I think that you mistake my confidence in the things that I know are true as somehow my being convinced that I know everything. Go back and reread some of my previous posts. You will see that I am actually very clear about where knowledge is limited. I have said that Ebola spreads through direct contact with infected liquids or sick patients--this is well-established. I have also said that Ebola could spread through fomites--this has not been definitely established or ruled out. I have also said that there is no evidence that Ebola spreads through a natural aerosol route--a study to address this matter has not, to my knowledge, been carried out, but there is enough epi evidence and some collateral experimental animal evidence to be able to discount this mode of transmission.
I suspect continued efforts to communicate with you will not prove fruitful.
That's because you haven't really been communicating. You've been trying to make a claim that simply is not true, and I have taken a considerable amount of time to explain to you why it is not true, and to try to get you to understand the nuances of the issue. You do not have to respond to this post, but I will continue to try to educate people on the various aspects of this disease.
Except for the terrorism aspects of it, I will not talk about that.