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1. I have an idea that may help stop the international spread of Ebola Virus. Currently, Ebola virus disease is diagnosed first clinically (by symptoms), namely fever, headache, pain, vomiting and more. Then it is diagnosed in laboratory testing for the actual virus chemical. However, there is a gap in time between the moment of human exposure to the virus and the appearance of symptoms. This is the notorious 2-21 day incubation period. During that time the person is not infectious, ie, they do not transmit virus, but it is in their body. The reason for the time lag is that the virus grows from probably a tiny inoculum to high enough levels of virus to cause disease. Think about if someone sneezes on you, you don’t get symptoms right away: it takes a few days before you feel sick.
2. During those incubation days, when the virus is reproducing, there is an unseen battle between the virus and your Immune System taking place. You are not aware of the battle. Then, if your immune system wins, you never even know it happened. If the virus wins, and your immune system fails, you feel symptoms. For most infectious diseases, there is no test for the incubation period. We are now in an international crisis, so taking temperatures at departure and arrivals is important, but as has been seen, it will not prevent importing virus during the incubation period.
3. I suggest INDIRECT testing for virus growth BEFORE symptoms appear. At the moment is it technically too challenging to find and detect the low and dispersed amounts of virus. However, during the aforementioned battle between the virus and the immune system, there are changes in the body and the immune system that may be detectable before symptoms appear. Something called “Type 1 Interferons” are among the first proteins induced as part of the innate immune response in the beginning of a virus infection. These proteins are well-known and well-studied and human diagnostic kits are commercially available. Just like any other detective work, we should be able to find clues; remnants of battles that may be helpful in the current crisis.
4. There are many other proteins, called pro-inflammatory cytokines, chemokines, pattern recognition receptors and others that change in the early stages of a clinical infection. There are published scientific reports about human proteins that change, either increase or decrease in abundance in the human body during Ebola virus infection, possibly early in the process, possibly even before symptoms appear.
5. Many of these tests are already commercially available. For example: C-reactive protein (CRP) is used as a flag indicating the body’s response to acute and chronic inflammation, myocardial infarction, bacterial infections and other events. A blood test for gamma interferon is used to predict development of active from latent tuberculosis.
6. I suggest making these tests available on an investigative, situational, off-label and provisional basis. Such a test could be part of a panel of tests, which now includes country of origin and temperature before entry or departure at international airports. Even if the tests are not FDA approved for CLINICAL human treatment, it might be useful as a preliminary airport screening. Before objections are raised about cost and practicality, this is a simple idea and if it works, would go far towards mitigating the unbridled, unsubstantiated frenzy surrounding an already difficult situation. It is probably relatively inexpensive, considering the costs that are either current or anticipated.
Here is a (certainly incomplete) list of company selling these products. These are simply from web searches, I have no interest in any of these companies or their products.
| COMPANY | PRODUCT |
| http://www.randox.com/inflammatory-markers.php | C-reactive protein (CRP) |
| http://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection
| Predict development of active tuberculosis from latent tb.
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| http://www.abdserotec.com/pattern-recognition-receptor-antibodies.html | pattern recognition receptors |
| http://www.qiagen.com/products/genes%20and%20pathways/complete%20biology%20list/innate%20immunity/ | Nyumerous kets for testing innate immunity |
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3.
Expert Rev Clin Immunol. 2014 Jun;10(6):781-90. doi: 10.1586/1744666X.2014.908705. Epub 2014 Apr 18.
Characterization of host immune responses in Ebola virus infections.
Wong G1, Kobinger GP, Qiu X.
Author information
- 1Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street Winnipeg, MB, R3E 3R2 Canada.
Abstract
Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.
Cell Host Microbe. 2013 Jul 17;14(1):5-6. doi: 10.1016/j.chom.2013.07.004.
Balance of power in host-virus arms races.
Kok KH1, Jin DY.
Author information
- 1Department of Biochemistry and State Key Laboratory for Liver Research, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Abstract
The sensing of viral RNA by the host innate immune system is mediated by RIG-I and its partner PACT. In this issue of Cell Host & Microbe, Luthra et al. (2013) show that the Ebola virus VP35 protein counteracts the action of PACT at the cost of compromising its own function in viral replication.
Copyright © 2013 Elsevier Inc. All rights reserved.
Comment on
- Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. [Cell Host Microbe. 2013]
8.
J Interferon Cytokine Res.2014 Feb;34(2):79-89. doi: 10.1089/jir.2013.0035. Epub 2013 Oct 8.
Ebola virus-like particles stimulate type I interferons and proinflammatory cytokine expression through the toll-like receptor and interferon signaling pathways.
Ayithan N1, Bradfute SB, Anthony SM, Stuthman KS, Dye JM, Bavari S, Bray M, Ozato K.
Author information
- 11 Program in Genomics of Differentiation, National Institute of Child Health and Human Development , National Institutes of Health, Bethesda, Maryland.
Abstract
Ebola viruses (EBOV) can cause severe hemorrhagic disease with high case fatality rates. Currently, no vaccines or therapeutics are approved for use in humans. Ebola virus-like particles (eVLP) comprising of virus protein (VP40), glycoprotein, and nucleoprotein protect rodents and nonhuman primates from lethal EBOV infection, representing as a candidate vaccine for EBOV infection. Previous reports have shown that eVLP stimulate the expression of proinflammatory cytokines in dendritic cells (DCs) and macrophages (MΦs) in vitro. However, the molecular mechanisms and signaling pathways through which eVLP induce innate immune responses remain obscure. In this study, we show that eVLP stimulate not only the expression of proinflammatory cytokines but also the expression of type I interferons (IFNs) and IFN-stimulated genes (ISGs) in murine bone marrow-derived DCs (BMDCs) and MΦs. Our data indicate that eVLP trigger host responses through toll-like receptor (TLR) pathway utilizing 2 distinct adaptors, MyD88 and TRIF. More interestingly, eVLP activated the IFN signaling pathway by inducing a set of potent antiviral ISGs. Last, eVLP and synthetic adjuvants, Poly I:C and CpG DNA, cooperatively increased the expression of cytokines and ISGs. Further supporting this synergy, eVLP when administered together with Poly I:C conferred mice enhanced protection against EBOV infection. These results indicate that eVLP stimulate early innate immune responses through TLR and type I IFN signaling pathways to protect the host from EBOV infection.
PMID:
24102579
[PubMed - indexed for MEDLINE]
PMCID:
PMC3924795
[Available on 2015/2/1]
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