If there was a safe vaccine against Ebola virus would you
take it? I think most people would say yes. Yet why do so many Americans refuse
flu vaccination, when thousands of American lives would be saved every year by
flu vaccination? I find this contrast noteworthy.
Another interesting revelation for me during this Ebola
virus scare is the high level of scientific illiteracy in this country.People are faulting public officials for not
knowing every detail about Ebola virus disease, not realizing that the scientific
method is based on developing theories after gathering evidence.Lack of scientific information can only be
corrected by experimentation, which takes time, money, commitment at high
levels and ethical practices (there are guidelines for experimentation in
humans).Theories may change, based on new
evidence.I believe that the level of
irrational panic would be greatly reduced if Americans placed much higher value
on science education and literacy.
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.
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.
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.
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.
